A randomised, open-label, phase 2 study of the IDO1 inhibitor epacadostat (INCB024360) versus tamoxifen as therapy for biochemically recurrent (CA-125 relapse)-only epithelial ovarian cancer, primary peritoneal carcinoma, or fallopian tube cancer.

PubMed

Kristeleit, Rebecca; Davidenko, Irina; Shirinkin, Vadim; El-Khouly, Fatima; Bondarenko, Igor; Goodheart, Michael J; Gorbunova, Vera; Penning, Carol A; Shi, Jack G; Liu, Xiangdong; Newton, Robert C; Zhao, Yufan; Maleski, Janet; Leopold, Lance; Schilder, Russell J

2017-09-01

Indoleamine 2,3-dioxygenase-1 (IDO1) is a key regulator of immune tolerance in ovarian cancer. This study investigated efficacy and safety of the IDO1 enzyme inhibitor epacadostat versus tamoxifen in patients with biochemical-only recurrence (CA-125 elevation) following complete remission after first-line chemotherapy for advanced epithelial ovarian, primary peritoneal, or fallopian tube cancer. In this open-label, phase 2 study (NCT01685255), patients were randomised 1:1 to epacadostat 600mg or tamoxifen 20mg twice daily for successive 28-day cycles and stratified by time since completion of first-line chemotherapy to first CA-125 elevation (3 to <12 or ≥12months). The primary endpoint was investigator-assessed progression-free survival (PFS; RECIST v1.1). Secondary endpoints included CA-125 response (Gynecologic Cancer InterGroup criteria), overall survival, safety, and tolerability. The study was terminated primarily due to slow accrual and lack of evidence of superiority. Median PFS was 3.75months for epacadostat (n=22) versus 5.56months for tamoxifen (n=20; HR, 1.34 [95% CI, 0.58-3.14]; P=0.54). Of evaluable patients, 1 (5.0%) epacadostat and 3 (15.8%) tamoxifen patients had confirmed CA-125 responses. The most common treatment-emergent adverse event was fatigue (epacadostat, 36.4%; tamoxifen, 40.0%). Immune-related adverse events, observed with epacadostat only, were primarily rash (18.2%) and pruritus (9.1%). Epacadostat pharmacokinetics/pharmacodynamics were consistent with its known mechanism of action. IDO1 expression was observed in 94% of archival tumour samples. This first report of immunotherapy evaluation in biochemical-only relapse ovarian cancer and of IDO1 inhibitor monotherapy in ovarian cancer found no significant difference in efficacy between epacadostat and tamoxifen. Epacadostat was generally well tolerated. Copyright © 2017 Elsevier Inc. All rights reserved.

Serum CA125 predicts extrauterine disease and survival in uterine carcinosarcoma

PubMed Central

Huang, Gloria S.; Chiu, Lydia G.; Gebb, Juliana S.; Gunter, Marc J.; Sukumvanich, Paniti; Goldberg, Gary L.; Einstein, Mark H.

2009-01-01

Objective The purpose of this study was to determine the clinical utility of CA125 measurement in patients with uterine carcinosarcoma (CS). Methods Ninety-five consecutive patients treated for CS at a single institution were identified. All 54 patients who underwent preoperative CA125 measurement were included in the study. Data were abstracted from the medical records. Tests of association between preoperative CA125 and previously identified clinicopathologic prognostic factors were performed using Fisher’s exact test and Pearson chi-square test. To evaluate relationship of CA125 elevation and survival, a Cox proportional hazard model was used for multivariate analysis, incorporating all of prognostic factors identified by univariate analysis. Results Preoperative CA125 was significantly associated with the presence of extrauterine disease (P<0.001), deep myometrial invasion (P<0.001), and serous histology of the epithelial component (P=0.005). Using univariate survival analysis, stage (HR=1.808, P=0.004), postoperative CA125 level (HR=9.855, P<0.001), and estrogen receptor positivity (HR=0.314, P=0.029) were significantly associated with survival. In the multivariate model, only postoperative CA125 level remained significantly associated with poor survival (HR=5.725, P=0.009). Conclusion Preoperative CA125 elevation is a marker of extrauterine disease and deep myometrial invasion in patients with uterine CS. Postoperative CA125 elevation is an independent prognostic factor for poor survival. These findings indicate that CA125 may be a clinically useful serum marker in the management of patients with CS. PMID:17935762

Ultrasound molecular imaging of ovarian cancer with CA-125 targeted nanobubble contrast agents.

PubMed

Gao, Yong; Hernandez, Christopher; Yuan, Hai-Xia; Lilly, Jacob; Kota, Pavan; Zhou, Haoyan; Wu, Hanping; Exner, Agata A

2017-10-01

Ultrasound is frequently utilized in diagnosis of gynecologic malignancies such as ovarian cancer. Because epithelial ovarian cancer (EOC) is often characterized by overexpression of cancer antigen 125 (CA-125), ultrasound contrast agents able to target this molecular signature could be a promising complementary strategy. In this work, we demonstrate application of CA-125-targeted echogenic lipid and surfactant-stabilized nanobubbles imaged with standard clinical contrast harmonic ultrasound for imaging of CA-125 positive OVCAR-3 tumors in mice. Surface functionalization of the nanobubbles with a CA-125 antibody achieved rapid significantly (P < 0.05) enhanced tumor accumulation, higher peak ultrasound signal intensity and slower wash out rates in OVCAR-3 tumors compared to CA-125 negative SKOV-3 tumors. Targeted nanobubbles also exhibited increased tumor retention and prolonged echogenicity compared to untargeted nanobubbles. Data suggest that ultrasound molecular imaging using CA-125 antibody-conjugated nanobubbles may contribute to improved diagnosis of EOC. Copyright © 2017 Elsevier Inc. All rights reserved.

Deregulation of miRNAs Contributes to Development and Progression of Prostate Cancer

DTIC Science & Technology

2012-09-01

p14ARF gene were co-transfected with miR-125b into LNCaP cells. Cotransfection resulted in approximately 50% reduction of the enzyme activity (Fig...Figure3. Downregulation of miR-125b activity induces apoptosis in p53-null CaP cells. A) Western blot analysis of p14ARF and...miR-124-mediated downregulation of the AR affects the AR activity , both AR- positive LNCaP and C4-2B were treated with miR-124 mimic. Western blot

Dialysate cancer antigen 125 concentration as marker of peritoneal membrane status in patients treated with chronic peritoneal dialysis.

PubMed

Krediet, R T

2001-01-01

This study reviews publications on the history of cancer antigen 125 (CA125), the background of its use as a marker of mesothelial cell mass, determination in peritoneal effluent, and its practical use in both the follow-up of peritoneal dialysis (PD) patients and as a marker of in vivo biocompatibility of dialysis solutions. Review article. CA125 is a high molecular weight glycoprotein. Previous studies in ascites suggested its release by mesothelial cells. In vitro studies with cultured mesothelial cells showed constitutive production, the majority of which was dependent on mesothelial cell mass. Serum CA125 is normal in PD patients, but its concentration in peritoneal dialysate suggests local release, probably from mesothelial cells. Effluent CA125 can be considered a marker of mesothelial cell mass in stable PD patients, but large amounts are found during peritonitis, due probably to necrosis of mesothelial cells. The majority of studies found no relationship between dialysate CA125 and peritoneal transport parameters. Some cross-sectional studies reported a relationship with duration of PD, but others were unable to confirm this, due probably to the large interindividual variability. Longitudinal follow-up has shown a decrease in dialysate CA125, indicating loss of mesothelial cell mass. Application of theoretically more-biocompatible PD solutions causes an increase in dialysate CA125. Dialysate CA125 is a mesothelial cell mass marker. The concentration of CA125 should be determined after a standardized dwell. A single low value is not informative. A decrease with time on PD suggests loss of mesothelial cell mass. Dialysate CA125 is a marker of in vivo biocompatibility of (new) dialysis solutions. More research is necessary on the best methodology for measuring low concentrations and establishing normal values and a significant change.

Correlation between ovarian chocolate cyst and serum carbohydrate antigen 125 level and the effect of ultrasound-guided interventional sclerotherapy on serum carbohydrate antigen 125 level.

PubMed

Wang, Si-Ming; Cai, Huai-Qiu; Dong, Xiao-Qiu; Fan, Qiu-Lan; Wang, Lu-Lu; Shao, Xiao-Hui; Zhang, Li-Wei

2015-01-01

This study was to investigate the correlation between ovarian chocolate cysts and serum carbohydrate antigen (CA)-125 levels and to demonstrate the effect of ultrasound-guided interventional sclerotherapy (UGIS) on serum CA-125 levels. Based on the serum CA-125 level, as determined by chemiluminescence detection prior to UGIS, 105 patients with ovarian chocolate cysts were divided into the normal group (CA-125 ≤ 35 U/mL, 45 patients) and the abnormal group (35 U/mL < CA-125 ≤ 200 U/mL, 60 patients). There were six clinical indicators including age, disease duration, dysmenorrhea history, child-bearing history, abortion history and surgical history. The ultrasonography characteristics were cyst diameter, cyst wall thickness and the side on which the cyst occurred. The correlations between serum CA-125 levels pretreatment and the clinical indicators and ultrasonography characteristics was analyzed. The serum CA-125 levels pretreatment, 3 months post-treatment and 6 months post-treatment were compared. The pretreatment serum CA-125 levels of the 105 patients positively correlated with disease duration (r = 0.3932, P = 0.0040), dysmenorrhea history (r = 0.2351, P = 0.0111), cyst diameter (r = 0.3415, P < 0.0001) and cyst wall thickness (r = 0.4263, P < 0.0001). Compared with the pretreatment level, the mean serum CA-125 level in the abnormal group at 3 months post-treatment was significantly lower (P < 0.01), and at 6 months post-treatment, the mean serum CA-125 level had decreased to a normal level (P < 0.01). UGIS significantly decreased abnormal serum CA-125 levels in patients with ovarian chocolate cysts. © 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.

Lower numbers of circulating natural killer T (NK T) cells in individuals with human T lymphotropic virus type 1 (HTLV-1) associated neurological disease

PubMed Central

Ndhlovu, L C; Snyder-Cappione, J E; Carvalho, K I; Leal, F E; Loo, C P; bruno, F R; Jha, A R; Devita, D; Hasenkrug, A M; Barbosa, H M R; Segurado, A C; Nixon, D F; Murphy, E L; Kallas, E G

2009-01-01

Human T lymphotropic virus type 1 (HTLV-1) infects 10–20 million people worldwide. The majority of infected individuals are asymptomatic; however, approximately 3% develop the debilitating neurological disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). There is also currently no cure, vaccine or effective therapy for HTLV-1 infection, and the mechanisms for progression to HAM/TSP remain unclear. NK T cells are an immunoregulatory T cell subset whose frequencies and effector functions are associated critically with immunity against infectious diseases. We hypothesized that NK T cells are associated with HAM/TSP progression. We measured NK T cell frequencies and absolute numbers in individuals with HAM/TSP infection from two cohorts on two continents: São Paulo, Brazil and San Francisco, CA, USA, and found significantly lower levels when compared with healthy subjects and/or asymptomatic carriers. Also, the circulating NK T cell compartment in HAM/TSP subjects is comprised of significantly more CD4+ and fewer CD8+ cells than healthy controls. These findings suggest that lower numbers of circulating NK T cells and enrichment of the CD4+ NK T subset are associated with HTLV-1 disease progression. PMID:19778295

Comparison of plasma amino acid profile-based index and CA125 in the diagnosis of epithelial ovarian cancers and borderline malignant tumors.

PubMed

Miyagi, Etsuko; Maruyama, Yasuyo; Mogami, Tae; Numazaki, Reiko; Ikeda, Atsuko; Yamamoto, Hiroshi; Hirahara, Fumiki

2017-02-01

We previously developed a new plasma amino acid profile-based index (API) to detect ovarian, cervical, and endometrial cancers. Here, we compared API to serum cancer antigen 125 (CA125) for distinguishing epithelial ovarian malignant tumors from benign growths. API and CA125 were measured preoperatively in patients with ovarian tumors, which were later classified into 59 epithelial ovarian cancers, 21 epithelial borderline malignant tumors, and 97 benign tumors including 40 endometriotic cysts. The diagnostic accuracy and cutoff points of API were evaluated using receiver operating characteristic (ROC) curves. The area under the ROC curves showed the equivalent performance of API and CA125 to discriminate between malignant/borderline malignant and benign tumors (both 0.77), and API was superior to CA125 for discrimination between malignant/borderline malignant lesions and endometriotic cysts (API, 0.75 vs. CA125, 0.59; p < 0.05). At the API cutoff level of 6.0, API and CA125 had equal positive rates of detecting cancers and borderline malignancies (API, 0.71 vs. CA125, 0.74; p = 0.84) or cancers alone (API, 0.73 vs. CA125, 0.85; p = 0.12). However, API had a significantly lower detection rate of benign endometriotic cysts (0.35; 95 % CI, 0.21-0.52) compared with that of CA125 (0.65; 95 % CI, 0.48-0.79) (p < 0.05). API is an effective new tumor marker to detect ovarian cancers and borderline malignancies with a low false-positive rate for endometriosis. A large-scale prospective clinical study using the cutoff value of API determined in this study is warranted to validate API for practical clinical use.

The Value of Serum CA125 in the Diagnosis of Borderline Tumors of the Ovary: A Subanalysis of the Prospective Multicenter ROBOT Study.

PubMed

Fotopoulou, Christina; Sehouli, Jalid; Ewald-Riegler, Nina; de Gregorio, Nikolaus; Reuss, Alexander; Richter, Rolf; Mahner, Sven; Kommoss, Friedrich; Schmalfeldt, Barbara; Fehm, Tanja; Hanker, Lars; Wimberger, Pauline; Canzler, Ulrich; Pfisterer, Jacobus; Kommoss, Stefan; Hauptmann, Steffen; du Bois, Andreas

2015-09-01

The value of the serum tumor marker CA125 in borderline tumors of the ovary (BOTs) is not well defined, with unclear benefit in both diagnosis and follow-up. The aim of the present project was to identify the predictive value of CA125 for stage and relapse. CA125 data were extracted from the ROBOT multicenter study of patients with BOT treated between 1998 and 2008 in 24 German centers. While patients' data were retrieved retrospectively from hospital records and clinical tumor registries, follow-up and independent central pathology review were performed prospectively. We identified 127 patients from the ROBOT database fulfilling the eligibility criterion of available CA125 at initial diagnosis. Eighty-three (65.3%) patients had increased CA125 levels (>35 U/L). Of the patients, 85.0% presented with serous and 13.4% with mucinous BOT histology, whereas 29.9% had stage I disease. Fifteen (11.8%) patients experienced a relapse. Multivariate analysis identified raised CA125, young age, and serous histology as independent predictors of peritoneal implants of any type at initial presentation. Raised CA125 at initial diagnosis was, however, not an independent predictor of future relapse. Elevated CA125 seems to be associated with the presence of peritoneal implants of any type at initial diagnosis of serous BOT, but failed to have any independent predictive value on future relapse. Prospective multicenter studies are warranted to evaluate CA125 measurements in the follow-up management of BOT.

Amniotic fluid and maternal serum levels of CA125 in pregnancies affected by Down syndrome: a re-evaluation of the role of CA125 in Down syndrome screening.

PubMed

Spencer, K; Muller, F; Aitken, D A

1997-08-01

In a study of amniotic fluid from 91 Down syndrome cases and 240 controls, we have shown that the median value of CA125 in pregnancies affected by Down syndrome on the whole reflects those observed in the maternal serum from 106 affected cases and 238 controls. The median MOM for CA125 in amniotic fluid from Down syndrome pregnancies was 1.04 and in maternal serum 1.06, neither value being significantly different from that for the control population. We confirm our previous observation that CA125 is not a marker of Down syndrome and conclude that CA125 has no role to play in Down syndrome screening.

Comparison of tumor markers and clinicopathological features in serous and mucinous borderline ovarian tumors.

PubMed

Alanbay, I; Aktürk, E; Coksuer, H; Ercan, C M; Karaşahin, E; Dede, M; Yenen, M C; Ozan, H; Dilek, S

2012-01-01

The aim of this study was to assess tumor markers and clinicopathological findings of patients with serous and mucinous borderline ovarian tumor (BOT) features. The study consisted of 50 patients that were diagnosed with and treated for BOT between 2005-2010 in three centers. CA125, CA19-9, and CA125+CA19-9 levels and clinicopathological features were compared in serous and mucinous histotypes. In serous and mucinous BOTs, correlations between tumor markers and demographics such as age, menopausal status, parity, clinical findings (stage, relapse, adjuvant chemotherapy, cytology, lymph node involvement and tumoral morphology (cystic-solid content, papilla, septation) were evaluated. There were no significant differences between serous and mucinous tumors in the clinicopathological features such as stage, tumor markers, age, menopausal status, or cytology. In serous BOTs we found a significant relation between elevated CA125+ CA19-9, CA19-9 and recurrence (p < 0.05). Also there was a significant relation between elevated CA125+ CA19-9, CA19-9 and cytology positivity (p < 0.05). We found a significant relation in serous BOTs between elevated CA125+CA19-9, adjuvant chemotherapy and lymph node metastases (p < 0.05). Also In mucinous BOTs with papilla formation we found a significant relation between elevated CA125 and CA125+ CA19-9 (p < 0.05). There was significant relation between cytology positivity and elevated CA19-9 in mucinous BOTs (p < 0.05). Serum tumor markers of serous and mucinous BOTs were different in relation to their clinicopathological features. This may reflect differences of serous and mucinous BOTs.

High-Grade Serous Ovarian Cancer: Use of Machine Learning to Predict Abdominopelvic Recurrence on CT on the Basis of Serial Cancer Antigen 125 Levels.

PubMed

Shinagare, Atul B; Balthazar, Patricia; Ip, Ivan K; Lacson, Ronilda; Liu, Joyce; Ramaiya, Nikhil; Khorasani, Ramin

2018-05-19

The aim of this study was to use machine learning to predict abdominal recurrence on CT on the basis of serial cancer antigen 125 (CA125) levels in patients with advanced high-grade serous ovarian cancer on surveillance. This institutional review board-approved, HIPAA-compliant, retrospective, hypothesis-generating study included all 57 patients (mean age, 61 ± 11.2 years) with advanced high-grade serous ovarian cancer who underwent cytoreductive surgery from January to December 2012, followed by surveillance abdominopelvic CT and corresponding CA125 levels. A blinded radiologist reviewed abdominopelvic CT studies until recurrence was noted. Four measures of CA125 were assessed: actual CA125 levels at the time of CT, absolute change since prior CT, relative change since prior CT, and rate of change since prior CT. Using machine learning, support vector machine models were optimized and evaluated using 10-fold cross-validation to determine the CA125 measure most predictive of abdominal recurrence. The association of the most accurate CA125 measure was further analyzed using Cox proportional-hazards model along with age, tumor size, stage, and degree of cytoreduction. Rate of change in CA125 was most predictive of abdominal recurrence in a linear kernel support vector machine model and was significantly higher preceding CT studies showing abdominal recurrence (median 13.2 versus 0.6 units/month; P = .007). On multivariate analysis, a higher rate of CA125 increase was significantly associated with recurrence (hazard ratio, 1.02 per 10 units change; 95% confidence interval, 1.0006-1.04; P = .04). A higher rate of CA125 increase is associated with abdominal recurrence. The rate of increase of CA125 may help in the selection of patients who are most likely to benefit from abdominopelvic CT in surveillance of ovarian cancer. Copyright © 2018 American College of Radiology. Published by Elsevier Inc. All rights reserved.

46 CFR 7.125 - Point Vincente, CA to Point Conception, CA.

Code of Federal Regulations, 2010 CFR

2010-10-01

... BOUNDARY LINES Pacific Coast § 7.125 Point Vincente, CA to Point Conception, CA. (a) A line drawn from Redondo Beach East Jetty Light “2” to Redondo Beach West Jetty Light “3”. (b) A line drawn from Marina Del... 46 Shipping 1 2010-10-01 2010-10-01 false Point Vincente, CA to Point Conception, CA. 7.125...

46 CFR 7.125 - Point Vincente, CA to Point Conception, CA.

Code of Federal Regulations, 2012 CFR

2012-10-01

... BOUNDARY LINES Pacific Coast § 7.125 Point Vincente, CA to Point Conception, CA. (a) A line drawn from Redondo Beach East Jetty Light “2” to Redondo Beach West Jetty Light “3”. (b) A line drawn from Marina Del... 46 Shipping 1 2012-10-01 2012-10-01 false Point Vincente, CA to Point Conception, CA. 7.125...

46 CFR 7.125 - Point Vincente, CA to Point Conception, CA.

Code of Federal Regulations, 2013 CFR

2013-10-01

... BOUNDARY LINES Pacific Coast § 7.125 Point Vincente, CA to Point Conception, CA. (a) A line drawn from Redondo Beach East Jetty Light “2” to Redondo Beach West Jetty Light “3”. (b) A line drawn from Marina Del... 46 Shipping 1 2013-10-01 2013-10-01 false Point Vincente, CA to Point Conception, CA. 7.125...

46 CFR 7.125 - Point Vincente, CA to Point Conception, CA.

Code of Federal Regulations, 2014 CFR

2014-10-01

... BOUNDARY LINES Pacific Coast § 7.125 Point Vincente, CA to Point Conception, CA. (a) A line drawn from Redondo Beach East Jetty Light “2” to Redondo Beach West Jetty Light “3”. (b) A line drawn from Marina Del... 46 Shipping 1 2014-10-01 2014-10-01 false Point Vincente, CA to Point Conception, CA. 7.125...

46 CFR 7.125 - Point Vincente, CA to Point Conception, CA.

Code of Federal Regulations, 2011 CFR

2011-10-01

... BOUNDARY LINES Pacific Coast § 7.125 Point Vincente, CA to Point Conception, CA. (a) A line drawn from Redondo Beach East Jetty Light “2” to Redondo Beach West Jetty Light “3”. (b) A line drawn from Marina Del... 46 Shipping 1 2011-10-01 2011-10-01 false Point Vincente, CA to Point Conception, CA. 7.125...

Heart failure in patients with aortic stenosis: clinical and prognostic significance of carbohydrate antigen 125 and brain natriuretic peptide measurement.

PubMed

Antonini-Canterin, Francesco; Popescu, Bogdan A; Popescu, Andreea C; Beladan, Carmen C; Korcova, Renata; Piazza, Rita; Cappelletti, Piero; Rubin, Daniela; Cassin, Matteo; Faggiano, Pompilio; Nicolosi, Gian Luigi

2008-08-29

Brain natriuretic peptide (BNP) is related to symptomatic status and outcome in aortic stenosis (AS) patients. Carbohydrate antigen 125 (CA125) demonstrated recently a BNP-like behaviour in patients with congestive heart failure (CHF) but has never been studied in AS patients. We aimed to assess the role of CA125 and BNP in AS patients. CA125 and BNP blood levels, transthoracic echocardiography and independent evaluation of CHF symptoms were obtained in 64 consecutive patients (76+/-9 years; 35 males) with AS (valve area 0.9+/-0.3 cm(2)). A pre-specified combined end-point consisting of cardiac mortality, urgent aortic valve replacement and hospitalization for CHF was considered. The median follow-up was 8 months (interquartile range 4.5-10 months). Both CA125 and BNP have accurately identified patients with III-IV NYHA class: area under the ROC curve was 0.85 for CA125 and 0.78 for BNP (best cut-offs of 10.3 U/mL and 254.64 pg/mL respectively) and were independently correlated to left ventricular ejection fraction. Fifty-two percent of patients with CA125>or=10.3 U/mL vs. 13% with CA125<10.3 U/mL (p<0.01) and 65% patients with BNP>or=254 pg/mL vs. 7% with BNP<254 pg/mL (p<0.001) have reached the end-point. Both CA125 and BNP levels are significantly correlated with NYHA class and outcome in patients with AS. CA125 blood level assessment (less expensive) may improve the clinical management in this setting.

The selective conservative management of small traumatic pneumothoraces following stab injuries is safe: experience from a high-volume trauma service in South Africa.

PubMed

Kong, V Y; Oosthuizen, G V; Clarke, D L

2015-02-01

The selective conservative management of small pneumothoraces (PTXs) following stab injuries is controversial. We reviewed a cohort of patients managed conservatively in a high volume trauma service in South Africa. A retrospective review over a 2-year period identified 125 asymptomatic patients with small PTXs measuring <2 cm on chest radiograph who were managed conservatively. Of the 125 patients included in the study, 92% were male (115/125), and the median age for all patients was 21 years (19-24). Ninety-seven per cent (121/125) of the weapons involved were knives, and 3% (4/125) were screwdrivers. Sixty-one per cent of all injuries were on the left side. Eighty-two per cent (102/125) sustained a single stab, and 18% (23/125) had multiple stabs. Thirty-nine per cent (49/125) had a PTX <0.5 cm (Group A), 26% (32/125) were ≥ 0.5 to <1 cm (Group B), 19% (24/125) were ≥ 1 to <1.5 cm (Group C) and 15% (20/125) were ≥ 1.5 to <2 cm (Group D). Three per cent of all patients (4/125) eventually required ICDs (one in Group C, three in Group D). All four patients had ICDs in situ for 24 h. The remaining 97% (121/125) were all managed successfully by active clinical observation alone. There were no subsequent readmissions, morbidity or mortality as a direct result of our conservative approach. The selective conservative management of asymptomatic small PTXs from stab injuries is safe if undertaken in the appropriate setting.

Saliva CA125 and TPS levels in patients with oral squamous cell carcinoma.

PubMed

Geng, Xue-fei; Du, Meng; Han, Jing-xiu; Zhang, Min; Tang, Xiao-fei; Xing, Ru-dong

2013-01-01

To determine the levels of carbohydrate antigen 125 (CA125) and tissue polypeptide-specific antigen (TPS) in saliva of patients with oral squamous cell carcinoma (OSCC) and patients with nonneoplastic disease of the oral cavity, and to investigate their diagnostic value and their relationship with pathological grade and clinical stage. A total of 97 hospitalized patients with OSCC, 36 patients with nonneoplastic disease of the oral cavity and 50 healthy individuals were included in this investigation. Mixed saliva was collected from these patients and the healthy controls before treatment. Saliva samples were analyzed by enzyme-linked immunosorbent assay (ELISA). The saliva CA125 and TPS concentrations were significantly higher in patients with OSCC than in patients with nonneoplastic disease and healthy controls, but not significantly different between patients with nonneoplastic disease and controls. Neither the saliva CA125 nor the TPS level was correlated with pathological grade and clinical stage. The sensitivity, specificity and accuracy of saliva CA125 and TPS for the diagnosis of OSCC were 80.0%, 66.0%, 75.7%, and 82.1%, 74.0%, 79.3%, respectively. When CA125 and TPS were analyzed independently, there was no significant difference in sensitivity, specificity and accuracy between the two markers. When CA125 and TPS were analyzed in combination, there was no significant difference in sensitivity, specificity and accuracy between independent detection and combined detection. The saliva CA125 and TPS concentrations were elevated in patients with OSCC. CA125 and TPS may prove to be useful tumor markers in OSCC.

CA 125 and other tumor markers in uterine leiomyomas and their association with lesion characteristics

PubMed Central

Babacan, Ali; Kizilaslan, Cem; Gun, Ismet; Muhcu, Murat; Mungen, Ercument; Atay, Vedat

2014-01-01

The aim of this study was to investigate the factors associated with serum levels of several tumor markers in a group of patients operated for uterine myoma. One hundred thirty-seven female patients operated for uterine myoma were included. Serum samples were examined for CA 125, CA 19-9, CA 15-3, carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP) levels as part of routine workup. Pathological and morphological characteristics of the patients were retrieved from medical records. The mean age was 46.7 ± 8.8 years (range, 22-85 y). Abnormally high levels of CA 125, CA 19-9, CA 15-3, CEA, and AFP were found in 19.7%, 6.6%, 5.1%, 3.7%, and 1.5% of the patients, respectively. Patients with additional adenomyosis and patients with at least one large myoma (≥ 5 cm diameter) had significantly higher levels of CA 125. Multivariate analysis identified coexistence of adenomyosis (OR 7.7 [95% CI, 2.6-23.0], p < 0.001) and presence of at least one large myoma (OR 5.6 [1.4-22.8], p = 0.016) as independent predictors of abnormally high CA 125 levels. CA 125 levels are affected by the tumor size and coexistence of adenomyosis in uterine leiomyomas. Indirect mechanisms caused by large myoma size such as peritoneal irritation may be responsible for CA 125 elevations. PMID:24955185

Combining serum microRNA and CA-125 as prognostic indicators of preoperative surgical outcome in women with high-grade serous ovarian cancer.

PubMed

Shah, Jaynish S; Gard, Gregory B; Yang, Jean; Maidens, Jayne; Valmadre, Susan; Soon, Patsy S; Marsh, Deborah J

2018-01-01

The most widely used approach for the clinical management of women with high-grade serous ovarian cancer (HGSOC) is surgery, followed by platinum and taxane based chemotherapy. The degree of macroscopic disease remaining at the conclusion of surgery is a key prognostic factor determining progression free and overall survival. We sought to develop a non-invasive test to assist surgeons to determine the likelihood of achieving complete surgical resection. This knowledge could be used to plan surgical approaches for optimal clinical management. We profiled 170 serum microRNAs (miRNAs) using the Serum/Plasma Focus miRNA PCR panel containing locked nucleic acid (LNA) primers (Exiqon) in women with HGSOC (N=56) and age-matched healthy volunteers (N=30). Additionally, we measured serum CA-125 levels in the same samples. The HGSOC cohort was further classified based on the degree of macroscopic disease at the conclusion of surgery. Stepwise logistic regression was used to identify predictive markers. We identified a combination of miR-375 and CA-125 as the strongest discriminator of healthy versus HGSOC serum, with an area under the curve (AUC) of 0.956. The inclusion of miR-210 increased the AUC to 0.984; however, miR-210 was affected by hemolysis. The combination of miR-34a-5p and CA-125 was the strongest predictor of completeness of surgical resection with an AUC of 0.818. A molecular test incorporating circulating miRNA to predict completeness of surgical resection for women with HGSOC has the potential to contribute to planning for optimal patient management, ultimately improving patient outcome. Copyright © 2017 Elsevier Inc. All rights reserved.

Effluent CA 125 concentration in chronic peritoneal dialysis patients: influence of PD duration, peritoneal transport and PD regimen.

PubMed

Fusshöller, Andreas; Grabensee, Bernd; Plum, Jörg

2003-01-01

In terms of the integrity of the peritoneal membrane in peritoneal dialysis (PD), the peritoneal mesothelial cells play a pivotal role since its monolayer constitutes the first line of the peritoneal membrane. Cancer antigen 125 (CA 125) is released by peritoneal mesothelial cells and correlates with the mesothelial cell mass in PD. Since its effluent concentration is easy to determine in chronic PD patients, CA 125 serves as an in vivo marker of biocompatibility. We performed a cross-sectional study to investigate the relation between PD duration, peritoneal transport and the PD regimen (CAPD/CCPD) on effluent CA 125 concentration in 22 chronic PD patients. We compared long-term (>6 months) with short-term PD treatment, patients with high small solute transport properties (MTAC >11 ml/min, d/p ratio of creatinine >0.72) to patients with low small solute transport and CAPD with APD patients. A peritoneal equilibration test was performed with 1.36% glucose. Dialysate/plasma (D/P) ratio and mass transfer area coefficient (MTAC) of creatinine were calculated and the 4-hour effluent concentration of CA 125 was determined. CA 125 tended to be lower in the long-term PD patients and also in APD patients, but statistical significance was missing. Effluent CA 125 was significantly increased in patients with an MTAC of creatinine >11 ml/min (40.2 +/- 11.2 vs. 20.7 +/- 1.2 U/ml) and in patients with a d/p ratio of creatinine >0.72 (48.2 +/- 11.0 vs. 21.6 +/- 1.6 U/ml). CA 125 and the d/p ratio of creatinine were positively correlated (r = 0.68). The positive correlation of CA 125 with peritoneal small solute transport especially in the early phase of PD treatment indicates an initial correlation of the mesothelial cell mass with the peritoneal surface area. A direct relation between the CA 125 concentration and peritoneal transport is unlikely. In our study the CA 125 effluent concentration tended to be lower in long-term PD patients and also in APD patients, possibly indicating a cell depletory influence of the conventional PD fluid. Copyright 2003 S. Karger AG, Basel

Evaluation of CA125 and NT-proBNP values in patients undergoing transcatheter aortic valve implantation

PubMed Central

Ayhan, Hüseyin; Kasapkara, Hacı Ahmet; Durmaz, Tahir; Keleş, Telat; Sarı, Cenk; Baştuğ, Serdal; Erdoğan, Kemal Eşref; Bayram, Nihal Akar; Bilen, Emine; Akçay, Murat; Bozkurt, Engin

2015-01-01

Background Transcatheter aortic valve implantation (TAVI) is a minimally invasive, emerging therapy in surgically high risk, or inoperable patients. Parameters used for risk classification have some deficiencies in the selection of patients. The objective of this study is to evaluate the impact of TAVI on carbohydrate antigen 125 (CA125) and N-Terminal pro Brain-type Natriuretic Peptide (NT-proBNP) as biomarkers that have been used frequently in recent years, and also the relationship of these biomarkers to prognosis. Methods & Results Transcatheter aortic valve implantation was practiced on 31 patients in this study. Then, CA125 and NT-proBNP levels studied in patients prior to and after the TAVI were evaluated. The patients were also grouped in accordance with their left ventricular ejection fraction (LVEF) and CA125 levels (LVEF ≥ 40% and < 40%; CA125 ≤ 35 U/L and > 35 U/L). The TAVI operation was successfully performed in all patients. There was no in-hospital mortality and substantial improvement in functional capacity was detected at follow ups. In addition, a statistically significant decrease was detected in post-TAVI CA125 and NT-proBNP levels of all patients (CA125 83.8 ± 18.1 U/L vs. 64.3 ± 14.2 U/L, P = 0.008; NT-proBNP: 4633.6 ± 627.6 pg/mL vs. 2866.3 ± 536.8 pg/mL, P < 0.001). In groups divided according to the CA125 levels, there was also statistically significant post-TAVI decline in CA125 levels. Within CA125 > 35 U/L and LVEF < 40% groups, the permanent need for a pacemaker was required in one (3.2%) patient and mortality was observed in two (6.4%) patients after TAVI at follow up. Conclusions The results show that TAVI can be performed effectively and reliably in patients with high baseline levels of CA125 and NT-proBNP. These biomarkers are reduced substantially with TAVI, while high biomarker levels are associated with undesired events, and certainly, these biomarkers can be used for risk classifications in patient selection for TAVI. PMID:25870611

Effects of interleukin 10 polymorphisms on the development of hepatitis B virus infection: a systemic review and meta-analysis

PubMed Central

Shu, Chi; Wang, Jiarong; He, Yazhou; Song, Tiange; Chen, Zhiyuan; Tang, Siqi; Tang, Xueyang

2015-01-01

Current opinion varies in the roles of the IL-10 polymorphisms in the process of hepatitis B virus (HBV) infection. We have performed a systemic review and up-dated meta-analysis including 37 eligible case-control studies to summarize all the available data on the association between IL-10 polymorphisms and development of HBV infection. In the present study, we found that the IL-10-1082 G/A, -592 C/A polymorphisms were associated with a significantly decreased risk of chronic HBV infection (AA + GA vs. GG: P = 0.003, OR = 0.55, 95% CI = 0.37-0.82; AA vs. CA + CC: P = 0.03, OR = 0.83, 95% CI = 0.71-0.98). While the -819 C/T TT carriers were associated with a borderline significantly decreased risk of chronic HBV infection (TT vs. CT + CC: P = 0.05, OR = 0.82, 95% CI = 0.68-1.00). Significant result was observed in the association between IL-10-1082 G/A polymorphism and HBV clearance (AA vs. GG: P = 0.04, OR = 1.33, 95% CI = 1.01-1.75). In addition, significant association was found between the -1082 G/A, -819 C/T polymorphisms and an increased risk of progression of HBV infection from asymptomatic carrier to chronic hepatitis B (AA + GA vs. GG: P = 0.0003, OR = 2.13, 95% CI = 1.41-3.22; TT + CT vs. CC: P = 0.005, OR = 1.53, 95% CI = 1.13-2.07), whereas the -592 C/A polymorphism was associated with a significantly decreased risk of progression from asymptomatic carrier to hepatocellular carcinoma (AA vs. CC: P = 0.02, OR = 0.63, 95% CI = 0.43-0.92). Our meta-analysis suggested that the IL-10 polymorphisms might be associated with a decreased risk of chronic HBV infection, while the -1082 AA carriers might be more likely to clear HBV following acute infection. In addition, these three polymorphisms might cast in roles of the progression of HBV infection. PMID:26550115

Economic Impact of Increased Utilization of Multivariate Assay Testing to Guide the Treatment of Ovarian Cancer: Implications for Payers.

PubMed

Brodsky, Burton S; Owens, Gary M; Scotti, Dennis J; Needham, Keith A; Cool, Christina L

2017-10-01

Ovarian cancer is the eighth most common cancer among women, but ranks fifth in cancer-related causes of death, the majority of which are detected in late stages, after the cancer has metastasized. The CA125 test is the standard of care for assessing suspicious pelvic masses. However, the primary use of CA125 is to monitor treatment progress rather than to screen for disease, and its sensitivity is exceedingly low, unlike the multivariate assay OVA1. A cost-effective treatment of ovarian cancer requires early and accurate diagnosis of pelvic masses and reduced referrals of patients with benign tumors to a gynecologic oncologist. To analyze the economic impact of increased utilization of a multivariate assay, such as OVA1, to guide the treatment of ovarian cancer. The study population was drawn from Medicare and commercial health plan claims data. A budget impact model was constructed to estimate the economic consequences of substituting the multivariate assay OVA1 to replace the single biomarker assay CA125 to assess the likelihood of pelvic mass malignancy in premenopausal and/or postmenopausal women. All patients selected for the analysis had CA125 testing before surgical intervention. A total of 92,843 health plan members were included for analysis, comprising 48,113 commercially insured members and 44,730 Medicare beneficiaries. Estimates of future health plan expenditures, which were calculated from base-case assumptions, projected overall savings of $0.05 per-member per-month (PMPM) for commercially insured members and $0.01 PMPM for Medicare beneficiaries as a result of increased utilization of OVA1. Sensitivity analysis revealed potential savings of up to $0.17 PMPM for commercially insured patients and up to $0.05 for Medicare beneficiaries. The results of the budget impact model support the use of OVA1 instead of CA125 by indicating that modest cost-savings can be achieved, while reaping the clinical benefits of improved diagnostic accuracy, early disease detection, and reductions in multiple, and possibly unnecessary, referrals to gynecologic oncologists.

An ultra-sensitive impedimetric immunosensor for detection of the serum oncomarker CA-125 in ovarian cancer patients

NASA Astrophysics Data System (ADS)

Johari-Ahar, M.; Rashidi, M. R.; Barar, J.; Aghaie, M.; Mohammadnejad, D.; Ramazani, A.; Karami, P.; Coukos, G.; Omidi, Y.

2015-02-01

Effective treatment of ovarian cancer depends upon the early detection of the malignancy. Here, we report on the development of a new nanostructured immunosensor for early detection of cancer antigen 125 (CA-125). A gold electrode was modified with mercaptopropionic acid (MPA), and then consecutively conjugated with silica coated gold nanoparticles (AuNP@SiO2), CdSe quantum dots (QDs) and anti-CA-125 monoclonal antibody (mAb). The engineered MPA|AuNP@SiO2|QD|mAb immunosensor was characterised using transmission electron microscopy (TEM), atomic force microscopy (AFM), cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). Successive conjugation of AuNP@SiO2, CdSe QD and anti-CA-125 mAb onto the gold electrode resulted in sensitive detection of CA-125 with a limit of detection (LOD) of 0.0016 U mL-1 and a linear detection range (LDR) of 0-0.1 U mL-1. Based on the high sensitivity and specificity of the immunosensor, we propose this highly stable and reproducible biosensor for the early detection of CA-125.Effective treatment of ovarian cancer depends upon the early detection of the malignancy. Here, we report on the development of a new nanostructured immunosensor for early detection of cancer antigen 125 (CA-125). A gold electrode was modified with mercaptopropionic acid (MPA), and then consecutively conjugated with silica coated gold nanoparticles (AuNP@SiO2), CdSe quantum dots (QDs) and anti-CA-125 monoclonal antibody (mAb). The engineered MPA|AuNP@SiO2|QD|mAb immunosensor was characterised using transmission electron microscopy (TEM), atomic force microscopy (AFM), cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). Successive conjugation of AuNP@SiO2, CdSe QD and anti-CA-125 mAb onto the gold electrode resulted in sensitive detection of CA-125 with a limit of detection (LOD) of 0.0016 U mL-1 and a linear detection range (LDR) of 0-0.1 U mL-1. Based on the high sensitivity and specificity of the immunosensor, we propose this highly stable and reproducible biosensor for the early detection of CA-125. Electronic supplementary information (ESI) available: Additional materials including Figures and discussion as described in the text. See DOI: 10.1039/c4nr06687a

Ovarian Cancer, Stem Cells, and Bioreactors

DTIC Science & Technology

2009-10-01

also indirectly assessed by measuring CEA and CA125 levels in the circulating medium. CEA and CA125, belonging to the CEA antigen family, are...with OVC#6 could not be detected. The low level of CA125 may be due to a dilution of the protein in the circulating medium as protein concentrations...lower than 8.7U/ml are below the assay sensitivity. Unfortunately, we have been unable to obtain the CA125 circulating level for either patient so

Surface modification of alignment layer by ultraviolet irradiation to dramatically improve the detection limit of liquid-crystal-based immunoassay for the cancer biomarker CA125.

PubMed

Su, Hui-Wen; Lee, Mon-Juan; Lee, Wei

2015-05-01

Liquid crystal (LC)-based biosensing has attracted much attention in recent years. We focus on improving the detection limit of LC-based immunoassay techniques by surface modification of the surfactant alignment layer consisting of dimethyloctadecyl[3-(trimethoxysilyl)propyl]ammonium chloride (DMOAP). The cancer biomarker CA125 was detected with an array of anti-CA125 antibodies immobilized on the ultraviolet (UV)-modified DMOAP monolayer. Compared with a pristine counterpart, UV irradiation enhanced the binding affinity of the CA125 antibody and reproducibility of immunodetection in which a detection limit of 0.01 ng∕ml for the cancer biomarker CA125 was achieved. Additionally, the optical texture observed under a crossed polarized microscope was correlated with the analyte concentration. In a proof-of-concept experiment using CA125-spiked human serum as the analyte, specific binding between the CA125 antigen and the anti-CA125 antibody resulted in a distinct and concentration-dependent optical response despite the high background caused by nonspecific binding of other biomolecules in the human serum. Results from this study indicate that UVmodification of the alignment layer, as well as detection with LCs of large birefringence, contributes to the enhanced performance of the label-free LC-based immunodetection, which may be considered a promising alternative to conventional label-based methods.

Comparison of risk of malignancy index (RMI), CA125, CA 19-9, ultrasound score, and menopausal status in borderline ovarian tumor.

PubMed

Alanbay, Ibrahim; Akturk, Erhan; Coksuer, Hakan; Ercan, Mutlu; Karaşahin, Emre; Dede, Murat; Yenen, Mufit Cemal; Ozan, Hakan; Baser, Iskender

2012-06-01

The aim of this study was to assess the prognostic values of risk of malignancy index (RMI IV), ultrasound score, menopausal status, and serum CA125 and CA19-9 level in patients with borderline ovarian tumor (BOT). Fifty women having borderline ovarian tumor (BOT) and 5O individuals with benign adnexal mass were enrolled in this retrospective study. The sensitivity, specificity, positive predictive values, negative predictive values and diagnostic accuracy of preoperative serum levels of the CA125 and CA19-9, ultrasound findings and menopausal status, and RMI IV were calculated for prediction of discrimination between BOTs and benign adnexal masses and the results were compared. The RMI IV was the best method for discrimination between BOTs and benign adnexal masses and was more accurate than the other parameters. When Receiver Operator Characteristic area under the curves for menopausal status was analyzed, serum CA 125 and CA19-9 level, ultrasound score, RMI IV(CA125), and RMI IV(CA19-9) were, 0.580, 0.625, 0.548, 0.694, 0.734 and 0.711, respectively. The best RMI IV cut-off was found to be 200 for discrimination of benign and BOT lesions. In the RMI formulation, replacing CA125 with CA19-9 didn't affect RMI IV sensitivity and specificity for discrimination. Compared to ultrasound, menopausal status, CA-125, CA19-9, the RMI IV was found to be the best predictive method for differentiation of BOTs from benign adnexal masses. RMI IV cut-off value of 200 is suitable for differentiation of benign and BOT's.

Leiomyoma of broad ligament mimicking ovarian malignancy- report of a unique case.

PubMed

Mallick, D; Saha, M; Chakrabarti, S; Chakraborty, J

2014-01-01

Tumors of the broad ligament are uncommon. Leiomyoma, which is the commonest female genital neoplasm, is also the most common solid tumor of the broad ligament. Leiomyomas affect 30% of all women of reproductive age but the incidence of broad-ligament leiomyoma is <1%. These benign tumors are usually asymptomatic. A case is being described where a 52 year old presented with gradual abdominal swelling which was clinically and radiologically diagnosed as ovarian malignancy. On abdominal and bimanual palpation a soft cystic mass was noted in the right pelvic region. CA 125 was mildly raised. CEA, CA 19.9 levels were within normal limit. The radiological diagnosis was ovarian cyst with possibility of malignant changes. Staging laparotomy and histopathological examination of the resected specimen revealed a right sided broad ligament leiomyoma with cystic changes. The degenerative changes in the leiomyoma lead to the clinical and radiological diagnostic confusion. Thus, though uncommon, broad ligament leiomyoma should be considered during evaluation of adnexal masses for optimal patient management. The above description of leiomyoma in the broad ligament is a highly unique case and thus deserves appropriate attention.

Two-marker combinations for preoperative discrimination of benign and malignant ovarian masses.

PubMed

Freydanck, Maj Kristin; Laubender, Ruediger Paul; Rack, Brigitte; Schuhmacher, Lan; Jeschke, Udo; Scholz, Christoph

2012-05-01

When caring for patients with ovarian neoplasms, correct preoperative discrimination of benign and malignant disease is deemed vital. In this study, we tested serum biomarkers' alone and in combination, to achieve this aim. We measured the concentrations of Cancer Antigen (CA)-125, CA15-3, CA27-29, Carcinoembryonic Antigen (CEA), CA19-9, human chorionic gonadotropin (hCG), Placental Protein (PP)1490, CA72-4, galectin-3, galectin-1 and Human epididymis protein (HE)4 in sera of 133 patients with pelvic masses by ELISA and correlated the results to subsequent histology. We used the area under the curve (AUC) of biomarkers and their combinations and calculated the 95% confidence intervals by using casewise resampling. The best single biomarkers were CA-125 (sensitivity and AUC) and HE4 (specificity). Combinations with HE4 and CA19-9 improved the predictive power of CA-125. The best discrimination was achieved by the combination of CA-125 and HE4, with an AUC of 0.961. A combination of CA-125 with HE4 could facilitate the identification of women at risk for ovarian cancer.

High level of CA 125 due to large endometrioma.

PubMed

Phupong, Vorapong; Chen, Orawan; Ultchaswadi, Pornthip

2004-09-01

CA 125 is a tumor-associated antigen. Its high levels are usually associated with ovarian malignancies, whereas smaller increases in the levels were associated with benign gynecologic conditions. The authors report a high level of CA 125 in a case of large ovarian endometrioma. A 45-year-old nulliparous Thai woman, presented with an increase of her abdominal girth for 7 months. Transabdominal ultrasonogram demonstrated a large ovarian cyst and multiple small leiomyoma uteri, and serum CA 125 level was 1,006 U/ml. The preoperative diagnosis was ovarian cancer with leiomyoma uteri. Exploratory laparotomy was performed. There were a large right ovarian endometrioma, small left ovarian endometrioma and multiple small leiomyoma. Total abdominal hysterectomy and bilateral salpingo-oophorectomy was performed and histopathology confirmed the diagnosis of endometrioma and leiomyoma. The serum CA 125 level declined to non-detectable at the 4th week. She was well at discharge and throughout her 4th week follow-up period Although a very high level of CA 125 is associated with a malignant process, it can also be found in benign conditions such as a large endometrioma. The case emphasizes the association of high levels of CA 125 with benign gynecologic conditions.

CO2 sensing of La0.875Ca0.125FeO3 in wet vapor: a comparison of experimental results and first-principles calculations.

PubMed

Wang, Xiaofeng; Chen, Yanping; Qin, Hongwei; Li, Ling; Shi, Changmin; Liu, Liang; Hu, Jifan

2015-05-28

Experimental results show that with an increase of relative humidity, the resistance of La0.875Ca0.125FeO3 decreases at room temperature but increases at higher temperatures (140-360 °C). The humid effect at room temperature is due to the movement of H(+) or H3O(+) inside of the condensed water layer on the surface of La0.875Ca0.125FeO3. Regarding the humid effect at high temperatures, the density functional theory (DFT) calculations show that H2O can be adsorbed onto the La0.875Ca0.125FeO3 surface in the molecular and dissociative adsorption configurations, where the La0.875Ca0.125FeO3 surface gains some electrons from H2O or its dissociative products, consistent with our observation. Experimental results also show that CO2 sensing response at high temperatures decreases with an increase of room-temperature relative humidity. DFT calculations indicate that CO2 adsorbed onto the La0.875Ca0.125FeO3(010) surface, where high concentration oxygen adsorption occurs without water adsorption nearby, releases some electrons into the semiconductor surface, playing the role of a donor. The interaction between CO2 and the local La0.875Ca0.125FeO3(010) surface with pre-adsorption of H2O nearby results in some electron transfer from the La0.875Ca0.125FeO3 surface to CO2, which is responsible for the weakening of CO2 response at high temperatures for La0.875Ca0.125FeO3 with an increase of room-temperature relative humidity.

The utility of serum CA-125 in predicting extra-uterine disease in apparent early-stage endometrial cancer.

PubMed

Nicklin, James; Janda, Monika; Gebski, Val; Jobling, Thomas; Land, Russell; Manolitsas, Tom; McCartney, Anthony; Nascimento, Marcelo; Perrin, Lewis; Baker, Jannah F; Obermair, Andreas

2012-08-15

Surgical staging in early-stage uterine cancer is controversial. Preoperative serum CA-125 may be of clinical value in predicting the presence of extra-uterine disease in patients with apparent early-stage endometrial cancer. Between October 6, 2005, and June 17, 2010, 760 patients were enrolled in an international, multicentre, prospective randomized trial (LACE) comparing laparotomy with laparoscopy in the management of endometrial cancer apparently confined to the uterus. Of these, 657 patients with endometrial adenocarcinoma had a preoperative serum CA-125 value recorded. Multiple cross-validation analysis was undertaken to correlate preoperative serum CA-125 with stage of disease (Stage I vs. Stage II+) after surgery. Patients' median preoperative serum CA-125 was 14 U/ml. A cutoff point of 30 U/ml was associated with the smallest misclassification error, and using this cutoff, 98 patients (14.9%) had elevated CA-125 levels. Of those, 36 (36.7%) had evidence of extra-uterine disease. Of the 116 patients (17.7%) with evidence of extra-uterine disease, 31.0% had an elevated CA-125 level. On univariate and multivariable logistic regression analysis, only preoperative CA-125 level, but no other preoperative clinical characteristics were found to be associated with extra-uterine spread of disease. Utilizing a cutoff point of 30 U/ml achieved a sensitivity, specificity, positive predictive value and negative predictive value of 31.0, 88.5, 36.7 and 85.7%, respectively. Elevated CA-125 above 30 U/ml in patients with apparent early-stage disease is a risk factor for the presence of extra-uterine disease and may assist clinicians in the management of patients with clinical Stage I endometrial cancer. Copyright © 2011 UICC.

Prognostic Value of the Interaction between Galectin-3 and Antigen Carbohydrate 125 in Acute Heart Failure

PubMed Central

Núñez, Julio; Rabinovich, Gabriel A.; Sandino, Justo; Mainar, Luis; Palau, Patricia; Santas, Enrique; Villanueva, Maria Pilar; Núñez, Eduardo; Bodí, Vicent; Chorro, Francisco J.; Miñana, Gema; Sanchis, Juan

2015-01-01

Aims Galectin-3 (Gal-3) and carbohydrate antigen 125 (CA125) have emerged as robust prognostic biomarkers in heart failure. Experimental data have also suggested a potential molecular interaction between CA125 and Gal-3; however, the biological and clinical relevance of this interaction is still uncertain. We sought to evaluate, in patients admitted for acute heart failure, the association between plasma Gal-3 with all-cause mortality and the risk for rehospitalizations among high and low levels of CA125. Methods and Results We included 264 consecutive patients admitted for acute heart failure to the Cardiology Department in a third-level center. Both biomarkers were measured on admission. Negative binomial and Cox regression models were used to evaluate the prognostic effect of the interaction between Gal-3 and CA125 (dichotomized by its median) with hospital readmission and all-cause mortality, respectively. During a median follow-up of 2 years (IQR = 1-2.8), 108 (40.9%) patients deaths and 365 rehospitalizations in 171 (69.5%) patients were registered. In a multivariable setting, the effect of Gal-3 on mortality and rehospitalization was differentially mediated by CA125 (p = 0.007 and p<0.001, respectively). Indeed, in patients with CA125 above median (>67 U/ml), values across the continuum of Gal-3 showed a positive and almost linear relationship with either the risk of death or rehospitalization. Conversely, when CA125 was below median (≤67 U/ml), Gal-3 lacked any prognostic effect on both endpoints. Conclusion In patients with acute heart failure, Gal-3 was strongly associated with higher risk of long-term mortality and repeated rehospitalizations, but only in those patients exhibiting higher values of CA125 (above 67 U/ml). PMID:25875367

Long-term effects of low calcium dialysates on the serum calcium levels during maintenance hemodialysis treatments: A systematic review and meta-analysis.

PubMed

Yoshikawa, Masahiro; Takase, Osamu; Tsujimura, Taro; Sano, Etsuko; Hayashi, Matsuhiko; Takato, Tsuyoshi; Hishikawa, Keiichi

2018-03-28

Hypercalcemia and hyperparathyroidism in patients receiving maintenance hemodialysis (MHD) can cause the progression of cardiovascular diseases (CVD) and mineral bone disorders (MBD). The KDIGO recommends the dialysates with a calcium (Ca) concentration of 1.25-1.5 mmol/L for MHD treatments, but the optimal concentration remains controversial. Here, we conducted a systematic review and a meta-analysis of seven randomized controlled trials examining a total of 622 patients to investigate the optimal concentration for MHD for 6 months or longer. The dialysates with a low Ca concentration (1.125 or 1.25 mmol/L) significantly lowered the serum Ca and raised the intact parathyroid hormone levels by 0.52 mg/dL (95% confidence interval, 0.20-0.85) and 39.59 pg/mL (14.80-64.38), respectively, compared with a high Ca concentration (1.50 or 1.75 mmol/L). Three studies showed that a low concentration was preferred for lowering arterial calcifications or atherosclerosis in different arteries, but one study showed that coronary arterial calcifications increased with a low concentration. Two studies showed contradictory outcomes in terms of MBD. Our meta-analysis showed that a dialysate with a low Ca concentration lowered the serum Ca levels in patients receiving long-term MHD, but further studies are needed to determine the optimal Ca concentration in terms of CVD and MBD.

Evaluation of the importance of the serum levels of CA-125, CA15-3, CA-19-9, carcinoembryonic antigen and alpha fetoprotein for distinguishing benign and malignant adnexal masses and contribution of different test combinations to diagnostic accuracy.

PubMed

Bozkurt, M; Yumru, A E; Aral, I

2013-01-01

The aim of this study was to investigate the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPPV) of the serum levels of CA-125, CA15-3, CA19-9, carcinoembryonic antigen (CEA), and alpha-fetoprotein (AFP) in the differentiation of benign and malignant ovarian tumors histopathologically diagnosed in patients and to determine the effects of the different test combinations on diagnostic accuracy. One-hundred sixty-eight patients that had their preoperative CA-125, CA15-3, CA19-9, CEA, AFP levels assessed and that were subsequently surgically treated for adnexal masses, were included in the study. For each tumor markers in these patients with histopathologically-confirmed diagnosis, the sensitivity, specificity, PPV and NPV, and diagnostic accuracy, and odds ratio were calculated. The sensitivity, specificity, PPV, NPV of CA125 with cut-off 35 U/ml, were found to be 78.9%, 86.9%, 63.8%, and 93.3%, respectively. The diagnostic odds ratio of CA-125 with cut-off of 35 U/ml, was found to be 25. With cut-off65 U/ml, the sensitivity, specificity, PPV, NPV values were 65.7%, 95.3%, 80.6%, and 90.5%, respectively. The sensitivity, specificity, PPV, and NPV of CEA were 16%, 93%, 37%, and 83%, respectively. For AFP, the sensitivity, specificity, PPV and NPV were to be 2.6%, 98%, 33.3%, and 77.5%, respectively. For CA 15-3, the sensitivity, specificity, PPV and NPV were found to be 26.3% 96.1%, 66.6%, and 81.6%, respectively. Likelihood ratio tests: positive (LR+) = 6.83 and negative (LR-) = 0.76, with an odds ratio: 8.9. The risk of malignancy for adnexal masses with higher CA15-3 increased by approximately nine times. For CA19-9, the sensitivity, specificity, PPV and NPV value were found to be 18.4%, 93%, 43.7%, and 79.6%, respectively. CA19-9 was not statistically significant in the differentiation of benign and malignant of adnexal masses. Even the combinations of CA125 + CEA + CA19-9 and CA125 + CEA + CA19-9 +AFP and CA125 + CA15-3 made a small contribution (one, two, and four cases, respectively), but was not statistically significant. The levels of CA-125 and CA15-3 were found to be significant in order to distinguish benign and malign; CA 19-9, CEA, and AFP were not found to be significant. The different test combinations did not have contribution for diagnostic accuracy.

Calcium metabolism in cows receiving an intramuscular injection of 1,25-dihydroxyvitamin D3 combined with prostaglandin F(2alpha) closely before parturition.

PubMed

Yamagishi, Norio; Ayukawa, Yu; Lee, Inhyung; Oboshi, Kenji; Naito, Yoshihisa

2005-06-01

To determine the effect of exogenous 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] combined with induced parturition on calcium (Ca) metabolism, cows received a single intramuscular injection of 1,25(OH)2D3 and prostaglandin F(2alpha) (PGF(2alpha)) closely before calving. Ten late-pregnant, multiparous Holstein cows were assigned to 1,25(OH)2D3 group (five treated with both 1,25(OH)2D3 and PGF(2alpha)) and control group (five treated with PGF(2alpha)). 1,25(OH)2D3 group showed an increase in plasma Ca concentration around parturition, whereas control group revealed a decrease in plasma Ca level. Plasma Ca concentration in 1,25(OH)2D3 group were significantly higher than that in control group during -0.5 to 3 days after parturition.

Prognostic value of repeated serum CA 125 measurements in first trimester pregnancy.

PubMed

Schmidt, T; Rein, D T; Foth, D; Eibach, H W; Kurbacher, C M; Mallmann, P; Römer, T

2001-08-01

To assess the diagnostic value of maternal CA 125 in patients with symptomatic first trimester pregnancy and to evaluate the prognostic significance of CA 125 versus beta-hCG in early pregnancies with intact fetal heartbeat, complicated by vaginal bleeding. Two prospective open-label studies with longitudinal follow-up in the second trial. Academic Department of Obstetrics and Gynecology, University of Cologne. Study 1: 168 patients presenting between gestational weeks 6 and 12 with: extrauterine pregnancy, 29; missed abortion, 50; incomplete spontaneous abortion, 38; imminent abortion, 33; and normal pregnancy (no history of endometriosis or ovarian mass), 18. Study 2: Fifty consecutive patients with vaginal bleeding during gestational weeks 6-12 all of whom having demostrable fetal heartbeat. Eighteen patients finally aborted whereas the remainder had normally continuing pregnancy until term. Study 1: Single serum determinations of CA 125 and beta-hCG were correlated with the different disorders observed. Study 2: Two sequential measurements of serum CA 125 and beta-hCG performed within a 5-7 days interval were related to the outcome of pregnancy as indicated by changes of the ultrasound presentation, miscarriage, future hospitalization, or delivery. Study 1: Patients with vaginal bleeding generally had higher median CA 125 values (38 IU/ml; range 1.3-540) compared to non-bleeding patients (17.8 IU/ml; range 1.0-157). No statistically significant differences in regard to median serum CA 125 levels between symptomatic and normal pregnancies occurred: normal pregnancy, 25.5 IU/ml (range 3.2-97); ectopic pregnancy, 26 IU/ml (range 1.3-157); missed abortion, 19.1IU/ml (range 1-242); threatened abortion, 48 IU/ml (range 5.2-540); spontaneous abortion, 40 IU/ml (range 5.4-442). Study 2: Initial CA 125 levels did not differ significantly between both groups of patients with 27/32 non-aborters and 13/18 aborters showing concentrations below 65 IU/ml. After 5-7 days, CA 125 in all patients who eventually aborted remained high or increased whereas non-aborters all had constantly low or steeply declining CA 125 measures. beta-hCG increased in all non-aborters but also in 13/18 aborters during the 5-7 day interval. Single serum measurements of CA 125 in symptomatic first trimester pregnant patients failed to discriminate spontaneous abortion, ectopic or normal pregnancies. However, sequential determinations of maternal CA 125 measurements appear to be a highly sensitive prognostic marker in patients with viable pregnancy at risk for abortion.

Imperforate hymen with elevated serum CA 125 and CA 19-9 levels.

PubMed

Sak, Muhammet Erdal; Evsen, Mehmet Siddik; Soydinc, Hatice Ender; Sak, Sibel; Yalinkaya, Ahmet

2013-01-01

To report the clinical characteristics of 14 patients with imperforate hymen and their levels of tumor markers (CA 19-9 and CA 125). Fourteen patients with imperforate hymen who followed-up between September 2006 and September 2010 in the Department of Obstetrics and Gynecology, Dicle University School of Medicine, Diyarbakir, Turkey, were evaluated retrospectively. The clinical features and the management of the patients are discussed. The mean age of the patients was 13.8 years. All patients had primary amenorrhea and pelvic pain. The most common clinical symptoms were cryptomenorrhea in 14 patients, pelvic pain in 11, palpable abdominal mass in 6, voiding difficulties in 7, and defecation problems in 2. In 6 patients with palpable pelvic mass, the mean + standard deviation values of tumor markers were as follows: CA 125, 84.0 +/- 23.7 and CA 19-9, 162 +/- 189. One week after surgery we measured CA 125 and CA 19-9 levels once again. The postoperative mean CA 125 level was 13.8 +/- 3.6, and the mean postoperative CA 19-9 level was 17.5 +/- 3.5. Preoperative levels of CA 125 and CA 19-9 were significantly higher than those of the postoperative period (p < 0.001 for both comparisons). Six patients were treated by T-shaped incision and 8 patients by a central surgical incision through the hymenal membrane. Diagnosis of imperforate hymen is very important before undergoing surgery in a different clinic. Many patients have seen several doctors before receiving a clear diagnosis and have had tumor markers evaluated because the presence of pelvic mass in patients suggests the possibility of a gynecologic malignancy. Imperforate hymen is one of the benign conditions that increase serum CA 125 and CA 19-9 levels and which is not listed in the classical medical textbooks. These markers are not needed for the diagnosis.

Serum expression level of squamous cell carcinoma antigen, highly sensitive C-reactive protein, and CA-125 as potential biomarkers for recurrence of cervical cancer.

PubMed

Guo, Suyang; Yang, Bo; Liu, Hongli; Li, Yuzhi; Li, Shengze; Ma, Ling; Liu, Jian; Guo, Wei

2017-01-01

The aim of this study was to evaluate the serum expression levels of squamous cell carcinoma antigen (SCC-Ag), highly sensitive C-reactive protein (hs-CRP), and CA-125 as potential serum biomarkers for recurrence of cervical cancer. Eighty-six cervical cancer patients who received radical treatment were retrospectively included in this study from February 2011 to January 2014. Of the included 86 cases, 23 were recurred within the 36 months (recurrence group [RG]) and other 63 patients did not (non-RG [NRG]). The serum levels of SCC-Ag, hs-CRP, and CA-125 were examined and compared between the two groups. The prediction recurrence sensitivity, specificity area under the receiver operating characteristic curve were calculated by STATA11.0 software (http://www.stata.com). The correlation among SCC-Ag, hs-CRP, and CA-125 were analyzed by Pearson correlation test. The serum levels of SCC-Ag, hs-CRP, and CA-125 were 1.29 (0.21-33.20) mg/mL, 4.78 (0.22-175.20) mg/mL, and 11.56 (2.028-123.66) IU/mL for NRG and 5.64 (0.50-136.80) mg/mL, 22.41 (0.56-588.90) mg/mL, and 25.41 (3.658-3687.00) IU/mL for RG, respectively. The serum levels of SCC-Ag, hs-CRP, and CA-125 in NG group were significant higher than those of NRG group (P < 0.05). The recurrence prediction sensitivity was 0.74, 0.65, and 0.74; specificity was 0.65, 0.63, and 0.58; area under the curve was 0.75, 0.66, and 0.67, respectively, for serum SCC-Ag, hs-CRP, and CA-125. Significant positive correlation between SCC-Ag and hs-CRP (rpearson = 0.20, P = 0.04), SCC-Ag and CA-125 (rpearson = 0.64, P < 0.001), hs-CRP and CA-125 (rpearson= -0.13, P = 0.56) was found in the RG patients. Serum SCC-Ag, hs-CRP, and CA-125 were higher in recurrence cervical patients which could be potential biomarkers for predicting cervical cancer recurrence risk.

Combined panel of serum human tissue kallikreins and CA-125 for the detection of epithelial ovarian cancer.

PubMed

Koh, Stephen Chee Liang; Huak, Chan Yiong; Lutan, Delfi; Marpuang, Johny; Ketut, Suwiyoga; Budiana, Nyoma Gede; Saleh, Agustria Zainu; Aziz, Mohamad Farid; Winarto, Hariyono; Pradjatmo, Heru; Hoan, Nguyen Khac Han; Thanh, Pham Viet; Choolani, Mahesh

2012-07-01

To determine the predictive accuracy of the combined panels of serum human tissue kallikreins (hKs) and CA-125 for the detection of epithelial ovarian cancer. Serum specimens collected from 5 Indonesian centers and 1 Vietnamese center were analyzed for CA-125, hK6, and hK10 levels. A total of 375 specimens from patients presenting with ovarian tumors, which include 156 benign cysts, 172 epithelial ovarian cancers (stage I/II, n=72; stage III/IV, n=100), 36 germ cell tumors and 11 borderline tumors, were included in the study analysis. Receiver operating characteristic analysis were performed to determine the cutoffs for age, CA-125, hK6, and hK10. Sensitivity, specificity, negative, and positive predictive values were determined for various combinations of the biomarkers. The levels of hK6 and hK10 were significantly elevated in ovarian cancer cases compared to benign cysts. Combination of 3 markers, age/CA-125/hk6 or CA-125/hk6/hk10, showed improved specificity (100%) and positive predictive value (100%) for prediction of ovarian cancer, when compared to the performance of single markers having 80-92% specificity and 74-87% positive predictive value. Four-marker combination, age/CA-125/hK6/hK10 also showed 100% specificity and 100% positive predictive value, although it demonstrated low sensitivity (11.9%) and negative predictive value (52.8%). The combination of human tissue kallikreins and CA-125 showed potential for improving prediction of epithelial ovarian cancer in patients presenting with ovarian tumors.

CA-125 blood test

MedlinePlus

... above 35 U/mL is considered abnormal. Normal value ranges may vary slightly among different laboratories. Some ... 125 usually does not mean ovarian cancer is present. Most healthy women with an elevated CA-125 ...

Impaired Compensation for Salt-Induced Urinary Calcium Loss in a Space Flight Model

NASA Technical Reports Server (NTRS)

Navidi, Meena; Harper, J. S.; Evans, J.; Fung, P.; Wolinsky, I.; Arnaud, S. B.; Wade, Charles E. (Technical Monitor)

1994-01-01

The loss of urinary calcium (UCa) induced by high sodium (HiNa) diets is compensated for by an increase in net intestinal Ca absorption (abs.). To determine the capacity of the intestine to absorb Ca in a space flight model in which the formation of 1,25-dihydroxyvitamin D (1,25-D) is suppressed, we induced Ca loss with HiNa diets (8%) and restricted dietary Ca (0.2%). In 200 g rats with hind limbs unloaded by tail suspension (S), we examined intestinal Ca abs. by direct measurement in the duodenum (everted gut sac or S/M), vitamin D receptors (VDR) and Ca balance. We also measured serum ionized calcium (ICa), pH, parathyroid hormone (PTH) and 1,25D. PTH was related to ICa (r = -0.44, p is less than 0.02), pH (r = -0.47, p is less than 0.02) and %Ca abs. (r = -0.40, p is less than 0.05). 1,25-D was related to %Ca abs. (r = 0.60, p is less than 0.001) but not VDR or S/M. Effects of the model were lower serum 1,25-D (110 +/- 59 vs. 199 +/- 80 pg/ml, p is less than 0.005), %Ca abs. (83 +/- 6.9 vs. 93 +/- 3.2, p is less than 0.03) and Ca balance (27 +/- 0.2 vs. 30 +/- 0.3 mg/d, p is less than 0.001) in S than controls (C). The HiNa diet increased UCa excretion from 2 to 13% of dietary Ca. Responses to HiNa diets, compared to normal Na, revealed no differences in 1,25-D, Ca abs. or VDR. Ca balances were lower in HiNa (27 +/- 0.3 vs. 30 +/- 0.4 mg/d, p is less than 0.001) in spite of higher Ca intakes. The failure of S rats fed HiNa diets to increase Ca abs. in response to Na-induced Ca loss appears to be related to suppressed 1,25-D in the space flight model, the cause of which remains obscure.

Validation of a novel biomarker panel for the detection of ovarian cancer

PubMed Central

Leung, Felix; Bernardini, Marcus Q.; Brown, Marshall D.; Zheng, Yingye; Molina, Rafael; Bast, Robert C.; Davis, Gerard; Serra, Stefano; Diamandis, Eleftherios P.; Kulasingam, Vathany

2016-01-01

Background Ovarian cancer (OvCa) is the most lethal gynecological malignancy. Our integrated -omics approach to OvCa biomarker discovery has identified kallikrein 6 (KLK6) and folate-receptor 1 (FOLR1) as promising candidates but these markers require further validation. Methods KLK6, FOLR1 CA125 and HE4 were investigated in three independent serum cohorts with a total of 20 healthy controls, 150 benign controls and 216 OvCa patients. The serum biomarker levels were determined by ELISA or automated immunoassay. Results All biomarkers demonstrated elevations in the sera of OvCa patients compared to controls (p<0.01). Overall, CA125 and HE4 displayed the strongest ability (AUC 0.80 and 0.82, respectively) to identify OvCa patients and the addition of HE4 to CA125 improved the sensitivity from 36% to 67% at a set specificity of 95%. As well, the combination of HE4 and FOLR1 was a strong predictor of OvCa diagnosis, displaying comparable sensitivity (65%) to the best performing CA125-based models (67%) at a set specificity of 95%. Conclusions The markers identified through our integrated –omics approach performed similarly to the clinically-approved markers CA125 and HE4. Furthermore, HE4 represents a powerful diagnostic marker for OvCa and should be used more routinely in a clinical setting. Impact The implications of our study are two-fold: (1) we have demonstrated the strengths of HE4 alone and in combination with CA125, lending credence to increasing its usage in the clinic; and (2) we have demonstrated the clinical utility of our integrated –omics approach to identifying novel serum markers with comparable performance to clinical markers. PMID:27448593

Measurement of serum CA-125 concentrations does not improve the value of Chlamydia trachomatis antibody in predicting tubal pathology at laparoscopy.

PubMed

Ng, E H; Tang, O S; Ho, P C

2001-04-01

Chlamydia antibody testing (CAT) has been used to predict tubal pathology associated with Chlamydia infection, the leading cause of pelvic inflammatory disease (PID). Tubal pathology not related to C. trachomatis is unlikely to be identified by CAT alone. A correlation between serum CA-125 concentrations and the severity of adnexal inflammation during acute PID was demonstrated. The objectives of this study were to determine the prevalence of C. trachomatis infection in an Asian infertile population and to assess the role of a combination of serum CA-125 and CAT in the prediction of tubal pathology as shown by laparoscopy. A total of 110 consecutive women attending an infertility clinic for work-up were recruited. Blood was taken for CAT and CA-125 on the day of hospital admission and an endocervical swab was taken for culture of C. trachomatis prior to laparoscopy. Two (1.8%) women had C. trachomatis found in the endocervix and 28 (25.5%) women had CAT of > or = 1:32. Serum CA-125 concentrations were > 35 IU/ml in 11 (10%) women. The discriminative capacity of CAT in the diagnosis of tubal pathology including both proximal and distal obstruction was not improved by measuring serum CA-125, regardless of the threshold values of serum CA-125 concentration.

Clinical value of preoperative serum CA 19-9 and CA 125 levels in predicting the resectability of hilar cholangiocarcinoma.

PubMed

Hu, Hai-Jie; Mao, Hui; Tan, Yong-Qiong; Shrestha, Anuj; Ma, Wen-Jie; Yang, Qin; Wang, Jun-Ke; Cheng, Nan-Sheng; Li, Fu-Yu

2016-01-01

To examine the predictive value of tumor markers for evaluating tumor resectability in patients with hilar cholangiocarcinoma and to explore the prognostic effect of various preoperative factors on resectability in patients with potentially resectable tumors. Patients with potentially resectable tumors judged by radiologic examination were included. The receiver operating characteristic (ROC) analysis was conducted to evaluate serum carbohydrate antigenic determinant 19-9 (CA 19-9), carbohydrate antigen 125 (CA 125) and carcino embryonie antigen levels on tumor resectability. Univariate and multivariate logistic regression models were also conducted to analysis the correlation of preoperative factors with resectability. In patients with normal bilirubin levels, ROC curve analysis calculated the ideal CA 19-9 cut-off value of 203.96 U/ml in prediction of resectability, with a sensitivity of 83.7 %, specificity of 80 %, positive predictive value of 91.1 % and negative predictive value of 66.7 %. Meanwhile, the optimal cut-off value for CA 125 to predict resectability was 25.905 U/ml (sensitivity, 78.6 %; specificity, 67.5 %). In a multivariate logistic regression model, tumor size ≤3 cm (OR 4.149, 95 % CI 1.326-12.981, P = 0.015), preoperative CA 19-9 level ≤200 U/ml (OR 20.324, 95 % CI 6.509-63.467, P < 0.001), preoperative CA 125 levels ≤26 U/ml (OR 8.209, 95 % CI 2.624-25.677, P < 0.001) were independent determinants of resectability in patients diagnosed as hilar cholangiocarcinoma. Preoperative CA 19-9 and CA 125 levels predict resectability in patients with radiological resectable hilar cholangiocarcinoma. Increased preoperative CA 19-9 levels and CA 125 levels are associated with poor resectability rate.

Aptamer and 5-fluorouracil dual-loading Ag2S quantum dots used as a sensitive label-free probe for near-infrared photoluminescence turn-on detection of CA125 antigen.

PubMed

Jin, Hui; Gui, Rijun; Gong, Jun; Huang, Wenxue

2017-06-15

In this article, Ag 2 S quantum dots (QDs) were prepared by a facile aqueous synthesis method, using thiourea as a new sulfur precursor. Based on electrostatic interactions, 5-fluorouracil (5-Fu) was combined with the aptamer of CA125 antigen to fabricate aptamer/5-Fu complex. The surface of as-prepared Ag 2 S QDs was modified with polyethylenimine, followed by combination with the aptamer/5-Fu complex to form Ag 2 S QDs/aptamer/5-Fu hybrids. During the combination of Ag 2 S QDs with aptamer/5-Fu complex, near-infrared (NIR) photoluminescence (PL) of QDs (peaked at 850nm) was markedly reduced under excitation at 625nm, attributed to photo-induced electron transfer from QDs to 5-Fu. However, the addition of CA125 induced obvious NIR PL recovery, which was ascribed to the strong binding affinity of CA125 with its aptamer, and the separation of aptamer/5-Fu complex from the surface of QDs. Hence, the Ag 2 S QDs/aptamer/5-Fu hybrids were developed as a novel NIR PL turn-on probe of CA125. In the concentration range of [CA125] from 0.1 to 10 6 ngmL -1 , there were a good linear relationship between NIR PL intensities of Ag 2 S QDs and Log[CA125], and a low limit of detection of 0.07ngmL -1 . Experimental results revealed the highly selective and sensitive NIR PL responses of this probe to CA125, over other potential interferences. In real human body fluids, this probe also exhibited superior analytical performance, together with high detection recoveries. Copyright © 2016 Elsevier B.V. All rights reserved.

Effect of 1,25-dihydroxyvitamin D3 on plasma concentrations of calcium-binding protein in normal and rachitic (vitamin D-dependent rickets type I) pigs.

PubMed

Maunder, E M; Pillay, A V; Care, A D

1987-10-01

An i.v. injection of calcitriol (1,25-(OH)2D3) had no effect within 2.5 h on plasma concentrations of calbindin-D9K (vitamin D-induced calcium-binding protein; CaBP) in hypocalcaemic pigs with inherited vitamin D-dependent rickets type I or in their normocalcaemic siblings or half-siblings. Three days later the plasma concentration of CaBP had doubled in the hypocalcaemic pigs, but was unaltered in the normocalcaemic siblings and half-siblings. Following daily i.v. injections of 1,25-(OH)2D3 for a further 5 days (days 4-8) plasma concentrations of CaBP increased in both the hypocalcaemic (days 4-8) and normocalcaemic (day 8) pigs, the effect being more rapid and greater in the hypocalcaemic 1,25-(OH)2D3-deficient animals. An i.v. injection of 1,25-(OH)2D3 to pure Yucatan pigs also had no effect on plasma concentrations of CaBP within 1.5 h, but in the following 1 h there was some indication of an increase in plasma CaBP levels. In contrast to the normal pigs, insulin-induced hypoglycaemia did not lead to a peak in plasma CaBP concentrations in the hypocalcaemic pigs. There was also no change in the plasma concentrations of 1,25-(OH)2D3 associated with the peak in plasma CaBP following insulin-induced hypoglycaemia in normocalcaemic pigs. These results suggest that changes in plasma concentrations of 1,25-(OH)2D3 are not directly involved in mediating the increase in plasma CaBP which follows hypoglycaemia induced by insulin in normal pigs, although 1,25-(OH)2D3 probably plays a permissive role.

Elevation of serum CA 125 and D-dimer levels associated with rupture of ovarian endometrioma.

PubMed

Uharcek, P; Mlyncek, M; Ravinger, J

2007-01-01

Patients with endometriosis rarely have a serum CA 125 concentration >100 IU/mL. A raised plasma level of D-dimer indicates active fibrinolysis, either secondary to clot formation or primarily activated. This condition is seldom diagnosed in patients with endometriosis. A 53-year-old woman was referred to our institution for acute abdominal pain. Laparoscopic surgery revealed a large ovarian cyst with rupture on the left side. Preoperative laboratory tests detected high serum CA 125 and D-dimer levels. Adnexectomy was performed, resulting in a sharp decrease in serum CA 125 and D-dimer concentration. We describe the clinical course of the patient. Rupture of a large ovarian endometrioma can lead to a high serum concentration of CA 125, a condition which, in addition to the detected pelvic mass, may mimic a malignant process. The increased D-dimer plasma level indicated that a ruptured endometriotic cyst can induce coagulation reactions.

Three-dimensional power doppler ultrasound is useful to monitor the response to treatment in a patient with primary papillary serous carcinoma of the peritoneum.

PubMed

Su, Jen-Min; Huang, Yu-Fang; Chen, Helen H W; Cheng, Ya-Min; Chou, Cheng-Yang

2006-05-01

To date, this is the first report to monitor changes of intratumor vascularization and the response to radiation and Cyberknife therapy in a patient with recurrent primary papillary serous carcinoma of the peritoneum by three dimensional (3D) power Doppler ultrasonography (PDUS). Transvaginal 3D PDUS detected a recurrent presacral tumor with abundant intratumor vascularity. Serial examinations of the tumor volume and serum CA-125 level were studied before, during, and 6 mo after therapy. Meanwhile, the intratumor blood flow was measured and expressed as vascularity indices. All of the tumor volume, intratumor vascularity indices and serum CA-125 level decreased progressively following therapy. A remaining lesion with nearly absent intratumor power Doppler signals suggested a scarring lesion posttreatment. Indeed, CT-guided tissue biopsy confirmed fibrotic change. 3D PDUS is useful to monitor the response to treatments and to differentiate residual tumors from lesions of scarring change posttreatment. It provides more accurate posttreatment information than pelvic computed tomography.

Chronic High Fructose Intake Reduces Serum 1,25 (OH)2D3 Levels in Calcium-Sufficient Rodents

PubMed Central

Douard, Veronique; Patel, Chirag; Lee, Jacklyn; Tharabenjasin, Phuntila; Williams, Edek; Fritton, J. Christopher; Sabbagh, Yves; Ferraris, Ronaldo P.

2014-01-01

Excessive fructose consumption inhibits adaptive increases in intestinal Ca2+ transport in lactating and weanling rats with increased Ca2+ requirements by preventing the increase in serum levels of 1,25(OH)2D3. Here we tested the hypothesis that chronic fructose intake decreases 1,25(OH)2D3 levels independent of increases in Ca2+ requirements. Adult mice fed for five wk a high glucose-low Ca2+ diet displayed expected compensatory increases in intestinal and renal Ca2+ transporter expression and activity, in renal CYP27B1 (coding for 1α-hydroxylase) expression as well as in serum 1,25(OH)2D3 levels, compared with mice fed isocaloric glucose- or fructose-normal Ca2+ diets. Replacing glucose with fructose prevented these increases in Ca2+ transporter, CYP27B1, and 1,25(OH)2D3 levels induced by a low Ca2+ diet. In adult mice fed for three mo a normal Ca2+ diet, renal expression of CYP27B1 and of CYP24A1 (24-hydroxylase) decreased and increased, respectively, when the carbohydrate source was fructose instead of glucose or starch. Intestinal and renal Ca2+ transporter activity and expression did not vary with dietary carbohydrate. To determine the time course of fructose effects, a high fructose or glucose diet with normal Ca2+ levels was fed to adult rats for three mo. Serum levels of 1,25(OH)2D3 decreased and of FGF23 increased significantly over time. Renal expression of CYP27B1 and serum levels of 1,25(OH)2D3 still decreased in fructose- compared to those in glucose-fed rats after three mo. Serum parathyroid hormone, Ca2+ and phosphate levels were normal and independent of dietary sugar as well as time of feeding. Thus, chronically high fructose intakes can decrease serum levels of 1,25(OH)2D3 in adult rodents experiencing no Ca2+ stress and fed sufficient levels of dietary Ca2+. This finding is highly significant because fructose constitutes a substantial portion of the average diet of Americans already deficient in vitamin D. PMID:24718641

miR-125b inhibits keratinocyte proliferation and promotes keratinocyte apoptosis in oral lichen planus by targeting MMP-2 expression through PI3K/Akt/mTOR pathway.

PubMed

Wang, Jing; Luo, Hong; Xiao, Yan; Wang, Luyao

2016-05-01

Oral lichen planus (OLP) is a chronic inflammatory mucosal disease that involves the degeneration of keratinocytes. However, the etiology and mechanisms of OLP pathogenesis have not been fully elucidated. In this study, we used keratinocytes HaCaT stimulated with lipopolysaccharide (LPS) to mimic a local OLP immune environment, and investigated the regulatory role of miR-125b in keratinocyte proliferation and apoptosis under OLP conditions. Immunohistochemical analysis and quantitative real-time PCR (qRT-PCR) assay showed that MMP-2 expression was up-regulated and miR-125b expression was down-regulated in both OLP mucosa tissues and LPS-incubated HaCaT cells. Western blot analysis indicated that miR-125b overexpression suppressed LPS-induced MMP-2 expression in HaCaT cells. Molecularly, our results confirmed that MMP-2 is a target gene of miR-125b in HaCaT cells. The effect of miR-125b on cell proliferation was revealed by CCK-8 assay, BrdU assay and cell cycle analysis, which illustrated that miR-125b overexpression impeded LPS-induced HaCaT cell proliferation. Flow cytometry analysis further demonstrated that miR-125b overexpression promoted HaCaT cell apoptosis. Moreover, these effects were involved in PI3K/Akt/mTOR activation, as miR-125b overexpression inhibited LPS-enhanced expression of p-Akt and p-mTOR proteins. Taken together, these data confirm that miR-125b might inhibit keratinocyte proliferation and promote keratinocyte apoptosis in OLP pathogenesis by targeting MMP-2 through PI3K/Akt/mTOR pathway. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

M-CSF in a new biomarker panel with HE4 and CA 125 in the diagnostics of epithelial ovarian cancer patients.

PubMed

Będkowska, Grażyna Ewa; Ławicki, Sławomir; Gacuta, Ewa; Pawłowski, Przemysław; Szmitkowski, Maciej

2015-05-03

We investigated plasma levels of M-CSF and conventional tumor markers (HE4 and CA 125) in epithelial ovarian cancer patients as compared to control groups: benign ovarian tumor patients (cysts) and healthy subjects. M-CSF levels were determined by ELISA, HE4 and CA 125 levels - by CMIA method. Our results have demonstrated significant differences in the concentration levels of M-CSF, CA 125 and HE4 between the groups of ovarian cancer patients, cysts patients and the healthy controls. In the groups tested M-CSF demonstrated equal to or higher values than both CA 125 and HE4 in diagnostic sensitivity (SE), positive and negative predictive values (PPV, NPV), and in the area under the ROC curve (AUC), particularly in the group with the serous epithelial sub-type of OC. Moreover, CA 125 showed better results of the aforementioned diagnostic criteria than HE4. The combined use of the parameters studied resulted in a further, significant increase in the value of the diagnostic indicators and in the value of the diagnostic power (AUC), especially in the early stages of ovarian cancer. These findings suggest a high usefulness of M-CSF in diagnosing the serous sub-type of epithelial ovarian cancer and in discriminating between cancer and non-carcinoma lesions, particularly in new diagnostic panels in combination with CA 125 and HE4 for the detection of EOC in the early stages.

Modifications of the mouse bone marrow microenvironment favor angiogenesis and correlate with disease progression from asymptomatic to symptomatic multiple myeloma

PubMed Central

Calcinotto, Arianna; Ponzoni, Maurilio; Ria, Roberto; Grioni, Matteo; Cattaneo, Elena; Villa, Isabella; Sabrina Bertilaccio, Maria Teresa; Chesi, Marta; Rubinacci, Alessandro; Tonon, Giovanni; Bergsagel, P Leif; Vacca, Angelo; Bellone, Matteo

2015-01-01

While multiple myeloma (MM) is almost invariably preceded by asymptomatic monoclonal gammopathy of undetermined significance (MGUS) and/or smoldering MM (SMM), the alterations of the bone marrow (BM) microenvironment that establish progression to symptomatic disease are circumstantial. Here we show that in Vk*MYC mice harboring oncogene-driven plasma cell proliferative disorder, disease appearance associated with substantial modifications of the BM microenvironment, including a progressive accumulation of both CD8+ and CD4+ T cells with a dominant T helper type 1 (Th1) response. Progression from asymptomatic to symptomatic MM was characterized by further BM accrual of T cells with reduced Th1 and persistently increased Th2 cytokine production, which associated with accumulation of CD206+Tie2+ macrophages, and increased pro-angiogenic cytokines and microvessel density (MVD). Notably, MVD was also increased at diagnosis in the BM of MGUS and SMM patients that subsequently progressed to MM when compared with MGUS and SMM that remained quiescent. These findings suggest a multistep pathogenic process in MM, in which the immune system may contribute to angiogenesis and disease progression. They also suggest initiating a large multicenter study to investigate MVD in asymptomatic patients as prognostic factor for the progression and outcome of this disease. PMID:26155424

Low-calcium diets increase both production and clearance of 1,25-dihydroxyvitamin D3 in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fox, J.; Bunker, J.E.; Kamimura, M.

1990-02-01

Administration of large doses of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) to animals induces 1,25(OH)2D3 side-chain oxidative pathways. This study determined if the elevated plasma 1,25(OH)2D3 seen in rats fed low-Ca diets is associated not only with an increased production rate (PR) but also with an increased metabolic clearance rate (MCR) of the hormone. In vitamin D-replete rats fed a Ca-deficient diet for 3-4 wk, the PR increased 21-fold, plasma levels 15-fold, and the MCR by 37%. The increased MCR in Ca-deficient rats was associated with a 48% increase in hepatic microsomal UDP glucuronyl transferase enzyme activity, whereas 1,25(OH)2D3 catabolism by homogenates ofmore » liver and small intestinal mucosa was unchanged. In contrast to the effects of low-Ca diets, acute (7 h) pharmacological elevation of plasma 1,25(OH)2D3 to 1.5 ng/ml in normal rats did not influence the MCR. Thus chronically elevated 1,25(OH)2D3 levels are necessary to stimulate clearance. In conclusion, 1,25(OH)2D3 clearance in rats can be stimulated not only by chronic pharmacological doses of 1,25(OH)2D3 but also by the physiological stimulus of a low-Ca diet. Hence, plasma 1,25(OH)2D3 levels can be regulated by changes in both PR and MCR.« less

Does serum CA125 have clinical value for follow-up monitoring of postoperative patients with epithelial ovarian cancer? Results of a 12-year study.

PubMed

Guo, Na; Peng, Zhilan

2017-03-11

The detection of CA125 has been used in the follow up of ovarian cancer. At present, some scholars believe that serum CA125 has no clinical value for the follow-up monitoring the recurrence for postoperative patients with epithelial ovarian cancer, but in our clinical follow-up found that when the serum CA125 value is <35 U/ml, postoperative patients of epithelial ovarian carcinoma had already showed recurrent lesions in some ecological and imaging examinations or in laparotomy exploration and biopsy, and we given the patients timely treatment, the prognosis were improved. Retrospective analysis the values of serum CA125 of 342 postoperative patients of epithelial ovarian carcinoma, consisting of 296 non-recurrent and 46 recurrent cases, as well as 3175 cases of menopausal women and 603 cases of postoperative patients of gynecological malignant tumor for the follow-up from January 2005 to December 2016. The median value of CA125 for non-recurrent patients of epithelial ovarian carcinoma is 8.9 U/ml, the median value of CA125 for non-recurrent patients of epithelial ovarian carcinoma is 29.7 U/ml; for menopausal women, 8.1 U/ml; and for postoperative patients of gynecological malignant tumor, 7.2 U/ml, whereas the mean ± standard deviation is 9.0 ± 1.9 U/ml, 31.3 ± 16.2U/ml, 8.0 ± 1.1 U/ml, and 6.8 ± 2.1 U/ml, respectively. If the value of the CA125 for postoperative patients of epithelial ovarian carcinoma between 10 and 35 U/ml indicates a relative risk of recurrence. When the value of CA125 is higher than 10 U/ml and continuously increased, need to be vigilant and should be combined with imaging examination (PET-CT). This result may improve the prognosis for recurrent patients because of the early detection of recurrent lesions and early retreatment.

Highly accurate detection of ovarian cancer using CA125 but limited improvement with serum matrix-assisted laser desorption/ionization time-of-flight mass spectrometry profiling.

PubMed

Tiss, Ali; Timms, John F; Smith, Celia; Devetyarov, Dmitry; Gentry-Maharaj, Aleksandra; Camuzeaux, Stephane; Burford, Brian; Nouretdinov, Ilia; Ford, Jeremy; Luo, Zhiyuan; Jacobs, Ian; Menon, Usha; Gammerman, Alex; Cramer, Rainer

2010-12-01

Our objective was to test the performance of CA125 in classifying serum samples from a cohort of malignant and benign ovarian cancers and age-matched healthy controls and to assess whether combining information from matrix-assisted laser desorption/ionization (MALDI) time-of-flight profiling could improve diagnostic performance. Serum samples from women with ovarian neoplasms and healthy volunteers were subjected to CA125 assay and MALDI time-of-flight mass spectrometry (MS) profiling. Models were built from training data sets using discriminatory MALDI MS peaks in combination with CA125 values and tested their ability to classify blinded test samples. These were compared with models using CA125 threshold levels from 193 patients with ovarian cancer, 290 with benign neoplasm, and 2236 postmenopausal healthy controls. Using a CA125 cutoff of 30 U/mL, an overall sensitivity of 94.8% (96.6% specificity) was obtained when comparing malignancies versus healthy postmenopausal controls, whereas a cutoff of 65 U/mL provided a sensitivity of 83.9% (99.6% specificity). High classification accuracies were obtained for early-stage cancers (93.5% sensitivity). Reasons for high accuracies include recruitment bias, restriction to postmenopausal women, and inclusion of only primary invasive epithelial ovarian cancer cases. The combination of MS profiling information with CA125 did not significantly improve the specificity/accuracy compared with classifications on the basis of CA125 alone. We report unexpectedly good performance of serum CA125 using threshold classification in discriminating healthy controls and women with benign masses from those with invasive ovarian cancer. This highlights the dependence of diagnostic tests on the characteristics of the study population and the crucial need for authors to provide sufficient relevant details to allow comparison. Our study also shows that MS profiling information adds little to diagnostic accuracy. This finding is in contrast with other reports and shows the limitations of serum MS profiling for biomarker discovery and as a diagnostic tool.

Clinical utility of circulating matrix metalloproteinase-7 (MMP-7), CC chemokine ligand 18 (CCL18) and CC chemokine ligand 11 (CCL11) as markers for diagnosis of epithelial ovarian cancer.

PubMed

Zohny, Samir F; Fayed, Salah T

2010-12-01

Ovarian cancer remains a highly lethal disease. The aim of the present study was to evaluate the usefulness of measuring serum matrix metalloproteinase-7 (MMP-7), CC chemokine ligand 18 (CCL18) and CC chemokine ligand 11 (CCL11) in comparison with serum cancer antigen 125 (CA 125) for diagnosis of epithelial ovarian cancer (EOC). This study included 51 patients with EOC, 27 patients with benign ovarian lesions and 29 healthy volunteers. Serum CA 125 was determined by microparticle enzyme immunoassay, while serum MMP-7, CCL18 and CCL11 were measured using enzyme-linked immunosorbent assay. The sensitivity and specificity were 86.3% and 92.9% for CA 125, 80.4% and 87.5% for MMP-7, 84.3% and 91.1% for CCL18 and, 68.6% and 62.5% for CCL11. Combination of CA 125, MMP-7, CCL18 and CCL11 gave a promising sensitivity of 100%, but specificity was decreased to 60.7%. The combined use of serum CA 125, MMP-7, CCL18 and CCL11 effectively detected early stages EOC with high sensitivity of 94.4%. Our data indicate that serum MMP-7, CCL18 and CCL11, in combination with CA 125 could be useful in diagnosis of EOC.

Effects of ranolazine in a model of doxorubicin-induced left ventricle diastolic dysfunction.

PubMed

Cappetta, Donato; Esposito, Grazia; Coppini, Raffaele; Piegari, Elena; Russo, Rosa; Ciuffreda, Loreta Pia; Rivellino, Alessia; Santini, Lorenzo; Rafaniello, Concetta; Scavone, Cristina; Rossi, Francesco; Berrino, Liberato; Urbanek, Konrad; De Angelis, Antonella

2017-11-01

Doxorubicin is a highly effective anticancer drug, but its clinical application is hampered by cardiotoxicity. Asymptomatic diastolic dysfunction can be the earliest manifestation of doxorubicin cardiotoxicity. Therefore, a search for therapeutic intervention that can interfere with early manifestations and possibly prevent later development of cardiotoxicity is warranted. Increased doxorubicin-dependent ROS may explain, in part, Ca 2+ and Na + overload that contributes to diastolic dysfunction and development of heart failure. Therefore, we tested whether the administration of ranolazine, a selective blocker of late Na + current, immediately after completing doxorubicin therapy, could affect diastolic dysfunction and interfere with the progression of functional decline. Fischer 344 rats received a cumulative dose of doxorubicin of 15 mg·kg -1 over a period of 2 weeks. After the assessment of diastolic dysfunction, the animals were treated with ranolazine (80 mg·kg -1 , daily) for the following 4 weeks. While diastolic and systolic function progressively deteriorated in doxorubicin-treated animals, treatment with ranolazine relieved diastolic dysfunction and prevented worsening of systolic function, decreasing mortality. Ranolazine lowered myocardial NADPH oxidase 2 expression and oxidative/nitrative stress. Expression of the Na + /Ca 2+ exchanger 1 and Na v 1.5 channels was reduced and of the sarcoplasmic/endoplasmic reticulum Ca 2+ -ATPase 2 protein was increased. In addition, ranolazine lowered doxorubicin-induced hyper-phosphorylation and oxidation of Ca 2+ /calmodulin-dependent protein kinase II, and decreased myocardial fibrosis. Ranolazine, by the increased Na + influx, induced by doxorubicin, altered cardiac Ca 2+ and Na + handling and attenuated diastolic dysfunction induced by doxorubicin, thus preventing the progression of cardiomyopathy. This article is part of a themed section on New Insights into Cardiotoxicity Caused by Chemotherapeutic Agents. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.21/issuetoc. © 2017 The British Pharmacological Society.

How to Use CA-125 More Effectively in the Diagnosis of Deep Endometriosis

PubMed Central

Raymundo, Thiers Soares; Soares, Leila Cristina; Pereira, Thiago Rodrigues Dantas; Demôro, Alessandra Viviane Evangelista

2017-01-01

Deep infiltrative endometriosis (DIE) is a severe form of the disease. The median time interval from the onset of symptoms to diagnosis of endometriosis is around 8 years. In this prospective study patients were divided into two groups: cases (34 DIE patients) and control (20 tubal ligation patients). The main objective of this study was to evaluate the performance of CA-125 measurement in the menstrual and midcycle phases of the cycle, as well as the difference in its levels between the two phases, for the early diagnosis of DIE. Area Under the Curve (AUC) of CA-125 in menstrual phase and of the difference between menstrual and midcycle phases had the best performance (both with AUC = 0.96), followed by CA-125 in the midcycle (AUC = 0.89). The ratio between menstrual and midcycle phases had the worst performance. CA-125 may be useful for the diagnosis of deep endometriosis, especially when both are collected during menstruation and in midcycle. These may help to decrease the long interval until the definitive diagnosis of DIE. Multicentric studies with larger samples should be performed to better evaluate the cost-effectiveness of measuring CA-125 in two different phases of the menstrual cycle. PMID:28660213

Excessive fructose intake causes 1,25-(OH)2D3-dependent inhibition of intestinal and renal calcium transport in growing rats

PubMed Central

Douard, Veronique; Sabbagh, Yves; Lee, Jacklyn; Patel, Chirag; Kemp, Francis W.; Bogden, John D.; Lin, Sheldon

2013-01-01

We recently discovered that chronic high fructose intake by lactating rats prevented adaptive increases in rates of active intestinal Ca2+ transport and in levels of 1,25-(OH)2D3, the active form of vitamin D. Since sufficient Ca2+ absorption is essential for skeletal growth, our discovery may explain findings that excessive consumption of sweeteners compromises bone integrity in children. We tested the hypothesis that 1,25-(OH)2D3 mediates the inhibitory effect of excessive fructose intake on active Ca2+ transport. First, compared with those fed glucose or starch, growing rats fed fructose for 4 wk had a marked reduction in intestinal Ca2+ transport rate as well as in expression of intestinal and renal Ca2+ transporters that was tightly associated with decreases in circulating levels of 1,25-(OH)2D3, bone length, and total bone ash weight but not with serum parathyroid hormone (PTH). Dietary fructose increased the expression of 24-hydroxylase (CYP24A1) and decreased that of 1α-hydroxylase (CYP27B1), suggesting that fructose might enhance the renal catabolism and impair the synthesis, respectively, of 1,25-(OH)2D3. Serum FGF23, which is secreted by osteocytes and inhibits CYP27B1 expression, was upregulated, suggesting a potential role of bone in mediating the fructose effects on 1,25-(OH)2D3 synthesis. Second, 1,25-(OH)2D3 treatment rescued the fructose effect and normalized intestinal and renal Ca2+ transporter expression. The mechanism underlying the deleterious effect of excessive fructose intake on intestinal and renal Ca2+ transporters is a reduction in serum levels of 1,25-(OH)2D3. This finding is significant because of the large amounts of fructose now consumed by Americans increasingly vulnerable to Ca2+ and vitamin D deficiency. PMID:23571713

Self-Test Kit: Rapid Diagnosis of Urogenital Infections in Military Women

DTIC Science & Technology

1999-09-01

in women with other infections and it was not clear whether they had symptomatic urinary tract infections or asymptomatic bacteriuria and symptoms from...CA), and bacterial vaginosis (BV) by PCR or standard methods. A asymptomatic pregnant women (n=1 57) were also screened for TV and bacterial...were less likely to respond to the survey.6 In another study of 476 asymptomatic active duty army women presenting for routine pap smears, 39(8.2

EDRN Breast and Ovary Cancer CVC, Study 3: Phase 3 Validation of screening decision rules in preclinical UKCTOCS serial samples — EDRN Public Portal

Cancer.gov

We will collaborate with investigators from University College London to test a screening decision rule in preclinical serial samples from the U.K. Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) to learn if the panel can do better than CA125 alone. The UKCTOCS is an ideal setting for retrospective validation of an early detection marker panel and decision rule because it offers serial samples collected annually and use of imaging in women with rising CA125. Multi-modal strategies using serum markers HE4, MSLN, MMP7, and CA125 will be compared to strategies relying exclusively on CA125 and transvaginal sonography (TVS).

Molecular Characterization of Human MUC16 (CA125) in Breast Cancer

DTIC Science & Technology

2015-04-01

and O-linked glycosylation takes place as it progresses through the cis-medial-trans Golgi apparatus . In addition, the juxta-membrane ectodomain...swapping experiment. Further, the cleavage of MUC16 was found to take place in the Golgi /post- Golgi compartments and is dependent on the acidic pH in the...therapeutic interventions based on MUC16. 15. SUBJECT TERMS Mucin 16 (MUC16), MUC16-Cter, Golgi /post- Golgi , nuclear localization 16. SECURITY

The diagnostic value of serum tumor markers CEA, CA19-9, CA125, CA15-3, and TPS in metastatic breast cancer.

PubMed

Wang, Weigang; Xu, Xiaoqin; Tian, Baoguo; Wang, Yan; Du, Lili; Sun, Ting; Shi, Yanchun; Zhao, Xianwen; Jing, Jiexian

2017-07-01

This study aims to understand the diagnostic value of serum tumor markers carcinoembryonic antigen (CEA), cancer antigen 19-9 (CA19-9), cancer antigen 125 (CA125), cancer antigen 15-3 (CA15-3), and tissue polypeptide-specific antigen (TPS) in metastatic breast cancer (MBC). A total of 164 metastatic breast cancer patients in Shanxi Cancer Hospital were recruited between February 2016 and July 2016. 200 breast cancer patients without metastasis in the same period were randomly selected as the control group. The general characteristics, immunohistochemical, and pathological results were investigated between the two groups, and tumor markers were determined. There were statistical differences in the concentration and the positive rates of CEA, CA19-9, CA125, CA15-3, and TPS between the MBC and control group (P<0.05). The highest sensitivity was in CEA and the highest specificity was in CA125 for the diagnosis of MBC when using a single tumor marker at 56.7% and 97.0%, respectively. In addition, two tumor markers were used for the diagnosis of MBC and the CEA and TPS combination had the highest diagnostic sensitivity with 78.7%, while the CA15-3 and CA125 combination had the highest specificity of 91.5%. Analysis of tumor markers of 164 MBC found that there were statistical differences in the positive rates of CEA and CA15-3 between bone metastases and other metastases (χ 2 =6.00, P=0.014; χ 2 =7.32, P=0.007, respectively). The sensitivity and specificity values of the CEA and CA15-3 combination in the diagnosis of bone metastases were 77.1% and 45.8%, respectively. The positive rate of TPS in the lung metastases group was lower than in other metastases (χ 2 =8.06, P=0.005).There were significant differences in the positive rates of CA15-3 and TPS between liver metastases and other metastases (χ 2 =15.42, P<0.001; χ 2 =9.72, P=0.002, respectively). The sensitivity and specificity of the CA15-3 and TPS combination in the diagnosis of liver metastases were 92.3% and 45.6%, respectively, and the positive rate of CEA in triple-negative metastatic breast cancer is lower than in other subtypes (χ 2 =4.80, P=0.028). Therefore, serum CEA, CA19-9, CA125, CA15-3, and TPS can be used in the diagnosis of MBC, and different combinations of tumor markers have varying diagnostic value. Copyright © 2017 Elsevier B.V. All rights reserved.

Differentiation between borderline and benign ovarian tumors: combined analysis of MRI with tumor markers for large cystic masses (≥5 cm).

PubMed

Park, Sung Yoon; Oh, Young Taik; Jung, Dae Chul

2016-05-01

There is overlap in imaging features between borderline and benign ovarian tumors. To analyze diagnostic performance of magnetic resonance imaging (MRI) combined with tumor markers for differentiating borderline from benign ovarian tumor. Ninety-nine patient with MRI and surgically confirmed ovarian tumors 5 cm or larger (borderline, n = 37; benign, n = 62) were included. On MRI, tumor size, septal number (0; 1-4; 5 or more), and presence of solid portion such as papillary projection or septal thickening 0.5 cm or larger were investigated. Serum tumor markers (carbohydrate antigen 125 [CA 125] and CA 19-9) were recorded. Multivariate analysis was conducted for assessing whether combined MRI with tumor markers could differentiate borderline from benign tumor. The diagnostic performance was also analyzed. Incidence of solid portion was 67.6% (25/37) in borderline and 3.2% (2/62) in benign tumors (P < 0.05). In all patients, without combined analysis of MRI with tumor markers, multivariate analysis revealed solid portion (P < 0.001) and CA 125 (P = 0.039) were significant for predicting borderline tumors. When combined analysis of MRI with CA 125 ((i) the presence of solid portion or (ii) CA 125 > 44.1 U/mL with septal number ≥5 for borderline tumor) is incorporated to multivariate analysis, it was only significant (P = 0.001). The sensitivity, specificity, PPV, NPV, and accuracy of combined analysis of MRI with CA 125 were 89.1%, 91.9%, 86.8%, 93.4, and 90.9%, respectively. Combined analysis of MRI with CA 125 may allow better differentiation between borderline and benign ovarian tumor compared with MRI alone. © The Foundation Acta Radiologica 2015.

Prognostic value of preoperative Ca125 and Tag72 serum levels and their correlation to disease relapse and survival in endometrial cancer.

PubMed

Myriokefalitaki, Eva; Vorgias, George; Vlahos, George; Rodolakis, Alexandros

2015-09-01

To evaluate preoperative serum levels of Ca125 and Tag72-4 tumour markers and investigate if abnormal levels correlate to mortality and disease-free survival. Retrospective observational study of a cohort of 282 women (mean age 62.3, SD 10.5 years) with primary endometrial cancer included all consecutive cases treated in a tertiary Gynaecological oncology Center. Excluded cases with other cancer or previous cancer treatment, major abdominal pathology or inflammation, endometriosis. Preoperative serum Tag72 and Ca125 levels were determined and evaluated in relation to disease-free survival (DFS) and disease-specific overall survival (DOS). Raised Ca125 correlates to worse overall disease-specific survival (66.1 vs 87.8 months, p = 0.021) and Tag72 correlates to shorter disease-free survival (69.2 vs 67.3 months, p = 0.021) and higher recurrence rate (13.5 vs 6 %, p = 0.021). When both Ca125 and Tag72 are abnormal DFS and DOS are worse. 93.3 % (72.3 months) vs 82.4 %, (61.3 months) p = 0.018 and 96.3 % (74.8 months) vs 88.2 %, (65.9 months) p = 0.021, respectively. This study enhances the value of preoperative tumour markers and their prognostic value. Ca125 and Tag72 appear to be good predictors of poor prognosis in patients with endometrial cancer.

Role of ascitic fluid adenosine deaminase (ADA) and serum CA-125 in the diagnosis of tuberculous peritonitis.

PubMed

Ali, N; Nath, N C; Parvin, R; Rahman, A; Bhuiyan, T M; Rahman, M; Mohsin M N

2014-12-01

This cross sectional study was carried out in the department of gastroenterology, BIRDEM, Dhaka from January 2010 to May 2011 to determine the role of ascitic fluid ADA and serum CA-125 in the diagnosis of clinically suspected tubercular peritonitis. Total 30 patients (age 39.69 ± 21.26, 18M/12F) with clinical suspicion of tuberculosis peritonitis were included in this study after analyzing selection criteria. Laparoscopic peritoneal biopsy with 'histopathological diagnosis' was considered gold standard against which accuracics of two biomarkers (ADA & CA-125) were compared. Cut off value of ADA and CA-125 are 24 u/l, 35 U/ml respectively. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of ADA as a diagnostic modality in tuberculos peritonitis were 87.5%, 83.33%, 95.45%, 62.5% and 86.67% respectively where as CA-125 was found to have 83.33% sensitivity, 50% specificity, 86.9% positive predictive value, 42.85% negative predictive value and 76.6% accuracy. Both biomarkers are simple, non-invasive, rapid and relatively cheap diagnostic test where as laparoscopy is an invasive procedure, costly & requires trained staff and not without risk and also not feasible in all the centre in our country. So ascitic fluid ADA and serum CA-125 are important diagnostic test for peritoneal tuberculosis.

Significance of serum and bile tumor markers in the diagnostic approach of patients with malignant pancreatobiliary disease.

PubMed

Natsios, Athanasios; Vezakis, Antonios; Kaparos, Georgios; Fragulidis, Georgios; Karakostas, Nikolaos; Kouskouni, Evangelia; Logothetis, Emmanouil; Polydorou, Andreas

2015-01-01

Serum and bile tumor markers are under intense scrutiny for the diagnosis of malignant disease. The purpose of our study was to report the usefulness of serum and bile tumor markers for the discrimination between benign and malignant pancreatobiliary diseases. Between March 2010 and May 2013, 95 patients with obstructive jaundice or history of biliary obstruction, were included in the study. During ERCP, bile samples were obtained for measurement of tumor markers CEA, CA19- 9, CA125, CA72-4 and CA242. Serum samples were taken before ERCP for the same measurements. The patients were divided into two groups: patients with malignant disease and patients with benign disease. Serum tumor marker levels were significantly higher in patients with malignant disease. Serum CA242 and CA19-9 exhibited the highest diagnostic accuracy (76.8% and 73.7%, respectively). CA125 and CA72-4 levels in bile samples were significantly higher in patients with malignant disease. Bile CA125, CEA and CA72-4 achieved the best diagnostic accuracy (69, 65 and 65), respectively). The combined detection of CA19-9, CA242 in serum and CA125, CA72-4 in bile along with total bilirubin levels, showed the best diagnostic accuracy (81%). Serum and bile tumor markers, when studied alone, lack the diagnostic yield to discriminate benign from malignant pancreatobiliary diseases. In cases of diagnostic dilemmas the combination of serum and bile markers might be helpful.

Diuretic Strategies in Acute Heart Failure and Renal Dysfunction: Conventional vs Carbohydrate Antigen 125-guided Strategy. Clinical Trial Design.

PubMed

García-Blas, Sergio; Bonanad, Clara; Llàcer, Pau; Ventura, Silvia; Núñez, José María; Sánchez, Ruth; Chamorro, Carlos; Fácila, Lorenzo; de la Espriella, Rafael; Vaquer, Juana María; Cordero, Alberto; Roqué, Mercè; Ortiz, Víctor; Racugno, Paolo; Bodí, Vicent; Valero, Ernesto; Santas, Enrique; Moreno, María Del Carmen; Miñana, Gema; Carratalá, Arturo; Bondanza, Lourdes; Payá, Ana; Cardells, Ingrid; Heredia, Raquel; Pellicer, Mauricio; Valls, Guillermo; Palau, Patricia; Bosch, María José; Raso, Rafael; Sánchez, Andrés; Bertomeu-González, Vicente; Bertomeu-Martínez, Vicente; Montagud-Balaguer, Vicente; Albiach-Montañana, Cristina; Pendás-Meneau, Jezabel; Marcaida, Goitzane; Cervantes-García, Sonia; San Antonio, Rodolfo; de Mingo, Elisabet; Chorro, Francisco J; Sanchis, Juan; Núñez, Julio

2017-12-01

The optimal treatment of patients with acute heart failure (AHF) and cardiorenal syndrome type 1 (CRS-1) is far from being well-defined. Arterial hypoperfusion in concert with venous congestion plays a crucial role in the pathophysiology of CRS-I. Plasma carbohydrate antigen 125 (CA125) has emerged as a surrogate of fluid overload in AHF. The aim of this study was to evaluate the clinical usefulness of CA125 for tailoring the intensity of diuretic therapy in patients with CRS-1. Multicenter, open-label, parallel clinical trial, in which patients with AHF and serum creatinine ≥ 1.4mg/dL on admission will be randomized to: a) standard diuretic strategy: titration-based on conventional clinical and biochemical evaluation, or b) diuretic strategy based on CA125: high dose if CA125 > 35 U/mL, and low doses otherwise. The main endpoint will be renal function changes at 24 and 72hours after therapy initiation. Secondary endpoints will include: a) clinical and biochemical changes at 24 and 72hours, and b) renal function changes and major clinical events at 30 days. The results of this study will add important knowledge on the usefulness of CA125 for guiding diuretic treatment in CRS-1. In addition, it will pave the way toward a better knowledge of the pathophysiology of this challenging situation. We hypothesize that higher levels of CA125 will identify a patient population with CRS-1 who could benefit from the use of a more intense diuretic strategy. Conversely, low levels of this glycoprotein could select those patients who would be harmed by high diuretic doses. Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

[Serum levels of CA-125 antigen during the first trimester of pregnancy complications and the risk of miscarriage].

PubMed

Fiegler, Patrycja; Kamiński, Kazimierz; Wegrzyn, Piotr

2003-05-01

The ultrasound, serum beta-HCG and progesterone titres are widely used to assess the risk of miscarriage at the early stages of pregnancy. Though very useful, they are not considered as satisfactorily accurate predictors of imminent abortion during the first three months of pregnancy. Prospective evaluation of clinical usefulness of serum CA125 from 4-12th week of pregnancy in a group of women with symptoms of imminent abortion. A study group were 250 consecutive women with symptoms of imminent abortion. Inclusion criteria were: abdominal pain, spotting, ultrasound picture of the embryo in the uterus, monovular pregnancy, normal ultrasound picture of ovaries, gestational age ranging from 4-12 weeks (assessed on a last menstrual period basis with ultrasound corroboration). 55 women with physiological course of pregnancy made up a control group. CA125 levels was evaluated with Roche Cobas Core CA125 II EIA. In patients with symptoms of imminent abortion, serum CA125 titration in 4 to 12 weeks' gestation seems to be valuable only in woman with vaginal spotting or bleeding.

A new mutation in the calcium-sensing receptor gene causing hypocalcaemia: case report of a father and two sons.

PubMed

Schoutteten, M K; Bravenboer, B; Seneca, S; Stouffs, K; Velkeniers, B

2017-07-01

Regulation of calcium is mediated by parathyroid hormone (PTH) and 1.25-dihydroxyvitamine D3. The calcium-sensing receptor (CaSR) regulates PTH release by a negative feedback system. Gain-of-function mutations in the CaSR gene reset the calcium-PTH axis, leading to hypocalcaemia. We analysed a family with hypocalcaemia. The proband was a 47-year-old man (index, patient I1), who presented with paraesthesias in both limbs. He has two sons (patient II1 a nd I I2). The probands' lab results showed: serum calcium of 1.95 mmol/l, albumin 41 g/l, phosphate 0.81 mmol/l and PTH 6.6 ng/l (normal 15-65 ng/l). Based on this analysis, we suspected a hereditary form of hypocalcaemia and performed genetic testing by polymerase chain reaction and Sanger sequencing of the coding regions and intron boundaries of the CaSR gene. Genetic analysis revealed a new heterozygous mutation: c.2195A>G, p.(Asn732Ser) in exon 7. The lab results of patient II1 showed: serum calcium of 1.93 mmol/l, phosphate 1.31 mmol/l, albumin 41 g/l, and PTH 24.3 ng/l. His genotype revealed the same activating mutation and, like his father, he also lost his scalp hair at an early adolescent age. Patient II2 is asymptomatic, and has neither biochemical abnormalities, nor the familial CaSR gene mutation. He still has all his scalp hair. 1) The c.2195A>G, p.(Asn732Ser) mutation in exon 7 of the CaSR gene leads to hypocalcaemia, and has not been reported before in the medical literature. 2) Possibly, this mutation is linked to premature baldness.

Calcium balance in mature male rats with unloaded hindlimbs

NASA Technical Reports Server (NTRS)

Navidi, Meena; Evans, Juliann; Wolinsky, Ira; Arnaud, Sara B.

2004-01-01

BACKGROUND: Calcium balances, regulated by the calcium endocrine system, are negative during spaceflight but have not been reported in flight simulation models using fully mature small animals. METHODS: We conducted two calcium (Ca) balance studies in 6-mo-old male rats exposed to a model that unloads the hindlimbs (HU) for 4 wk. Control (C) and HU rats were fed diets with 0.5% Ca in the first and 0.1% Ca in the second study. Housing in metabolic cages enabled daily food and water intake measurements as well as collections of urine and fecal specimens. At necropsy, blood was obtained for measures of Ca-regulating hormones. RESULTS: Both C and HU rats adjusted to housing and diets with decreases in body weight and negative Ca balances during the first week of each experiment. Thereafter, averages of Ca balances were more negative in the unloaded rats than controls: -8.1 vs. -1.6 mg x d(-1) in rats fed 0.5% (p < 0.05). This difference was not due to urinary Ca excretion since it was lower in HU than C rats (1.27 +/- 0.51 mg x d(-1) vs. 2.35 +/- 0.82 mg x d(-1), p < 0.05). Fecal Ca in HU rats exceeded dietary Ca by 4-7%, Restricting dietary Ca to 0.1% was followed by an increase in serum 1,25-dihydroxyvitamin D (1,25-D) and greater intestinal Ca absorption than in rats fed 0.5% Ca. Ca balances in rats fed 0.1% Ca were also more negative in HU than C rats (-2.4 vs. -0.03 mg x d(-1), p < 0.05). Parathyroid hormone (PTH) was suppressed and 1,25-D increased in HU rats fed 0.5% Ca. C rats fed 0.1% Ca had increased PTH and 1,25-D was the same as in the HU group. CONCLUSION: After adaptation, Ca balances were more negative in mature male rats with unloaded hindlimbs than controls, an effect from increased secretion and loss of endogenous fecal Ca associated with increased 1,25-D in Ca-replete and Ca-restricted rats.

Smartphone-based immunosensor for CA125 detection.

PubMed

Hosu, Oana; Ravalli, Andrea; Lo Piccolo, Giuseppe Mattia; Cristea, Cecilia; Sandulescu, Robert; Marrazza, Giovanna

2017-05-01

In this work, we report the design, the development and the characterization of the analytical performances of a colorimetric smartphone-based immunosensor for the detection of cancer antigen 125 (CA125). The immunosensor was based on a sandwich strategy in which the primary antibody was immobilized by spotting onto the 3D nitrocellulose membrane. The immunospots were subsequently incubated with CA125 solutions, followed by the affinity reaction with a secondary antibody labeled with gold nanoparticles (AuNPs). The antibody-AuNPs captured onto immunospots induced the silver deposition from a silver enhancer solution leading to the formation of gold-silver nanoparticles of different grey color spots depending on CA125 concentration. The 8 megapixels smartphone camera was integrated in a home-made dark box and used as transducer of color image acquisition and data handling. The pixel intensity of the captured images was determined by an image processing algorithm. The experimental parameters involved in each step of the immunosensor design were studied and optimized, obtaining a limit of detection of 30U/mL CA125. The selectivity of the immunoassay was proven against different concentration solutions of Vascular Endothelial Growth Factor (VEGF) antigen as an unspecific protein when a blank signal was obtained for all tested solutions. Finally, preliminary experiments in human serum samples spiked with CA125 protein were also performed. Therefore, the proposed system could represent a powerful point-of-care tool for the next generation technology for detecting and monitoring cancer biomarkers at early stages by taking advantage of nowadays gadgets with enhanced features such as smartphones. Copyright © 2017 Elsevier B.V. All rights reserved.

Ca 125 and Ca 19-9: two cancer-associated sialylsaccharide antigens on a mucus glycoprotein from human milk.

PubMed

Hanisch, F G; Uhlenbruck, G; Dienst, C; Stottrop, M; Hippauf, E

1985-06-03

The cancer-associated antigens Ca 125 and Ca 19-9 were demonstrated by radioimmunoassay to form structural units of a mucus glycoprotein in human milk taken from healthy women four days after parturition. The glycoprotein precipitated with the casein fraction at pH 4.6 and was completely absent in the whey as judged from Ca 19-9 assay. It could be effectively enriched by phenol-saline extraction from soluble milk proteins and further purified by gel filtration on Sephacryl S300 and Sephacryl S400. The active component with a bouyant density of 1.41 g/ml in isopycnic density gradient centrifugation (CsCl) shared common physico-chemical and chemical characteristics of mucus glycoproteins. Carbohydrates representing about 68% by weight were conjugated to protein by alkali-labile linkages, exclusively and were essentially free of D-mannose. Activities of Ca 125 and Ca 19-9 were both destroyed by treatment with periodate, mild alkali or neuraminidase suggesting the antigens are sialylated saccharides bound to protein by alkali-labile linkages. The fraction of monosialylated saccharide alditols isolated after reductive beta-elimination from the mucus glycoprotein was shown to inhibit monoclonal antibodies anti-(Ca 125) and anti-(Ca 19-9) in radioimmunoassay.

Endoplasmic reticulum and lysosomal Ca²⁺ stores are remodelled in GBA1-linked Parkinson disease patient fibroblasts.

PubMed

Kilpatrick, Bethan S; Magalhaes, Joana; Beavan, Michelle S; McNeill, Alisdair; Gegg, Matthew E; Cleeter, Michael W J; Bloor-Young, Duncan; Churchill, Grant C; Duchen, Michael R; Schapira, Anthony H; Patel, Sandip

2016-01-01

Mutations in β-glucocerebrosidase (encoded by GBA1) cause Gaucher disease (GD), a lysosomal storage disorder, and increase the risk of developing Parkinson disease (PD). The pathogenetic relationship between the two disorders is unclear. Here, we characterised Ca(2+) release in fibroblasts from type I GD and PD patients together with age-matched, asymptomatic carriers, all with the common N370S mutation in β-glucocerebrosidase. We show that endoplasmic reticulum (ER) Ca(2+) release was potentiated in GD and PD patient fibroblasts but not in cells from asymptomatic carriers. ER Ca(2+) signalling was also potentiated in fibroblasts from aged healthy subjects relative to younger individuals but not further increased in aged PD patient cells. Chemical or molecular inhibition of β-glucocerebrosidase in fibroblasts and a neuronal cell line did not affect ER Ca(2+) signalling suggesting defects are independent of enzymatic activity loss. Conversely, lysosomal Ca(2+) store content was reduced in PD fibroblasts and associated with age-dependent alterations in lysosomal morphology. Accelerated remodelling of Ca(2+) stores by pathogenic GBA1 mutations may therefore feature in PD. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Struma Ovarii with Elevated Ca-125 Levels and Ascites Mimicking Advanced Ca Ovary

PubMed Central

Sinha, Navin Kumar

2014-01-01

Struma ovarii is uncommon tumor of ovary which can mimic as advanced carcinoma of ovary. Thyroid tissue is relatively frequent constituent of mature ovarian teratoma. Case of struma ovarii masquerading as cancer of ovary in a female aged 63 yrs showing complex large unilateral multilocular adnexal mass with elevated CA 125 (more than 1721 IU/L) and massive ascites mislead treating surgeons for long time. Clinicians were virtually clueless about preoperative diagnosis. Combination of ascites has been seen in one third cases but association with raised CA 125 is rare(only 8-10 cases so far). This case developed hypothyroidism one week after surgery. PMID:24783110

Normocalcemia without hyperparathyroidism in vitamin D-deficient rats.

PubMed

Kollenkirchen, U; Fox, J; Walters, M R

1991-03-01

Despite numerous attempts, no reliable dietary regimen exists to achieve vitamin D deficiency (-D) in rats without attendant changes in plasma parathyroid hormone (PTH), Ca, or phosphate. This represents an important obstacle to proper investigations of the physiologic role(s) of vitamin D metabolites in the function of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] target tissues. This paper describes the successful development of such a diet, which uses a combination of high Ca content, properly controlled Ca/P ratio, and lactose. Normal weanling rats were fed diets containing A, 0.8% Ca, 0.5% P, +D3, or -D diets containing B, 0.8% Ca and 0.5% P; C, 2.0% Ca and 1.25% P; or D, 2.0% Ca, 1.25% P, and 20% lactose. After 6 diet weeks group D rats remained normocalcemic and normophosphatemic, but diet groups B and C became hypocalcemic (6.9 +/- 0.8 and 7.2 +/- 0.4 mg/dl, respectively). Thus high dietary Ca and P was incapable of maintaining normal plasma Ca levels in the absence of dietary lactose. The normocalcemia in group D was not maintained by elevated PTH secretion because N-terminal PTH levels were also normal (14 +/- 3 versus 20 +/- 5 pg/ml). In contrast, PTH levels were markedly elevated in hypocalcemic groups B and C (47 +/- 7 and 48 +/- 10 pg/ml, respectively). Plasma 25-OHD3 and 1,25-(OH)2D3 levels were reduced to less than 120 and less than 12 pg/ml, respectively, in all -D groups. Thus the high-Ca diet and the use of normal weanlings did not impede the development of vitamin D deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

Peritoneal tuberculosis with elevated serum Ca-125 level mimicking advanced stage ovarian cancer: a case report.

PubMed

Tan, Orkun; Luchansky, Edward; Rosenman, Stephen; Pua, Tarah; Azodi, Masoud

2009-08-01

Tuberculosis is still a common problem in immigrant population with peritoneal tuberculosis as the most common presentation of extrapulmonary disease. A 36-year-old woman presented with abdominal distention, night sweats and weight loss. Physical examination and radiologic studies revealed ascites, omental caking and bilateral enlarged ovaries with an elevated serum Ca-125 of 353 U/mL. Acid-fast stain and culture were negative for Mycobacterium tuberculosis. Diagnostic laparoscopy and biopsy revealed multiple granulomas with epithelioid cells and caseification necrosis confirming tuberculosis. Treatment with anti-tuberculin drugs resulted in resolution of symptoms with a reduction in Ca-125 to normal. Laparoscopic biopsy with frozen section evaluation would spare patients with peritoneal tuberculosis from unnecessary extensive surgery. Serum Ca-125 level may be useful in monitoring treatment response.

The role of 1,25-dihydroxyvitamin D in the inhibition of bone formation induced by skeletal unloading

NASA Technical Reports Server (NTRS)

Halloran, B. P.; Bikle, D. D.; Wronski, T. J.; GLOBUS. R.; Levens, M. J.; Morey-Holton, E.

1983-01-01

Skeletal unloading results in osteopenia. To examine the involvement of vitamin D in this process, the rear limbs of growing rats were unloaded and alterations in bone calcium and bone histology were related to changes in serum calcium (Ca), inorganic phosphorus (P sub i), 25-hydroxyvitamin D (25-OH-D), 24,25-dihydroxyvitamin D (24,25(OH)2D and 1,25-dihydroxyvitamin D (1,25(OH)2D. Acute skeletal unloading induced a transitory inhibition of Ca accumulation in unloaded bones. This was accompanied by a transitory rise in serum Ca, a 21% decrease in longitudinal bone growth (P 0.01), a 32% decrease in bone surface lined with osteoblasts (P .05), no change in bone surface lined with osteoclasts and a decrease in circulating (1,25(OH)2D. No significant changes in the serum concentrations of P sub i, 25-OH-D or 24,25(OH)2D were observed. After 2 weeks of unloading, bone Ca stabilized at approximately 70% of control and serum Ca and 1,25(OH)2D returned to control values. Maintenance of a constant serum 1,25(OH)2D concentration by chronic infusion of 1,25(OH)2D (Alza osmotic minipump) throughout the study period did not prevent the bone changes induced by acute unloading. These results suggest that acute skeletal unloading in the growing rat produces a transitory inhibition of bone formation which in turn produces a transitory hypercalcemia.

Ultrasonographic markers and preoperative CA-125 to distinguish between borderline ovarian tumors and stage I ovarian cancer.

PubMed

Zacharakis, Dimitrios; Thomakos, Nikolaos; Biliatis, Ioannis; Rodolakis, Alexandros; Simou, Maria; Daskalakis, Georgios; Bamias, Aris; Antsaklis, Aris

2013-03-01

Preoperative evaluation of ovarian masses has become increasingly important for optimal planning of treatment. The aim of this study was to assess the role of preoperative serum cancer antigen 125 (CA-125) levels in correlation with ultrasonographic features in order to distinguish between borderline ovarian tumors (BOTs) and stage I epithelial ovarian carcinoma (EOC). Retrospective study. Tertiary University Hospital. We reviewed all women with BOTs and stage I EOC from January 2000 to December 2010. Data from 165 women (66 BOTs and 99 stage I EOC) were analyzed. Multivariable logistic regression with stepwise selection of variables was used to determine which clinical variables, ultrasound features and CA-125 level were independently associated with invasiveness. Utility of ultrasonographic markers and CA-125 in the preoperative differential diagnosis between BOTs and stage I EOC. Women with CA-125 > 100 IU mL(-1) had almost three times greater likelihood of belonging in the EOC group [odds ratio (OR) 3.02; confidence interval (CI) 95%: 1.13-8.12]. Furthermore, the presence of large solid component (≥20% of the tumor comprised of solid components) was associated with 4.25 times greater odds of it to representing ovarian cancer rather than a BOT (OR 4.25; 95% CI: 2.05-8.82). In contrast, the presence of papillary projections was associated with a 73% lower likelihood of EOC (OR 0.27; 95% CI: 0.13-0.58). Preoperative CA-125 > 100 IU mL(-1) combined with the presence of a large solid component and the absence of papillary projections seems to improve the discriminative ability in favor of stage I EOC. © 2012 The Authors Acta Obstetricia et Gynecologica Scandinavica © 2012 Nordic Federation of Societies of Obstetrics and Gynecology.

Assessing the Risk of Progression From Asymptomatic Left Ventricular Dysfunction to Overt Heart Failure: A Systematic Overview and Meta-Analysis.

PubMed

Echouffo-Tcheugui, Justin B; Erqou, Sebhat; Butler, Javed; Yancy, Clyde W; Fonarow, Gregg C

2016-04-01

This study sought to provide estimates of the risk of progression to overt heart failure (HF) from systolic or diastolic asymptomatic left ventricular dysfunction through a systematic review and meta-analysis. Precise population-based estimates on the progression from asymptomatic left ventricular dysfunction (or stage B HF) to clinical HF (stage C HF) remain limited, despite its prognostic and clinical implications. Pre-emptive intervention with neurohormonal modulation may attenuate disease progression. MEDLINE and EMBASE were systematically searched (until March 2015). Cohort studies reporting on the progression from asymptomatic left ventricular systolic dysfunction (ALVSD) or asymptomatic left ventricular diastolic dysfunction (ALVDD) to overt HF were included. Effect estimates (prevalence, incidence, and relative risk) were pooled using a random-effects model meta-analysis, separately for systolic and diastolic dysfunction, with heterogeneity assessed with the I(2) statistic. Thirteen reports based on 11 distinct studies of progression of ALVSD were included in the meta-analysis assessing a total of 25,369 participants followed for 7.9 years on average. The absolute risks of progression to HF were 8.4 per 100 person-years (95% confidence interval [CI]: 4.0 to 12.8 per 100 person-years) for those with ALVSD, 2.8 per 100 person-years (95% CI: 1.9 to 3.7 per 100 person-years) for those with ALVDD, and 1.04 per 100 person-years (95% CI: 0.0 to 2.2 per 100 person-years) without any ventricular dysfunction evident. The combined maximally adjusted relative risk of HF for ALVSD was 4.6 (95% CI: 2.2 to 9.8), and that of ALVDD was 1.7 (95% CI: 1.3 to 2.2). ALVSD and ALVDD are each associated with a substantial risk for incident HF indicating an imperative to develop effective intervention at these stages. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Significance of serum CA125 and TPS antigen levels for determination of overall survival after three chemotherapy courses in ovarian cancer patients during long-term follow-up.

PubMed

van Dalen, A; Favier, J; Hallensleben, E; Burges, A; Stieber, P; de Bruijn, H W A; Fink, D; Ferrero, A; McGing, P; Harlozinska, A; Kainz, Ch; Markowska, J; Molina, R; Sturgeon, C; Bowman, A; Einarsson, R; Goike, H

2009-01-01

To evaluate the prognostic significance for overall survival rate for the marker combination TPS and CA125 in ovarian cancer patients after three chemotherapy courses during long-term clinical follow-up. The overall survival of 212 (out of 213) ovarian cancer patients (FIGO Stages I-IV) was analyzed in a prospective multicenter study during a 10-year clinical follow-up by univariate and multivariate analysis. In patients with ovarian cancer FIGO Stage I (34 patients) or FIGO Stage II (30 patients) disease, the univariate and multivariate analysis of the 10-year overall survival data showed that CA125 and TPS serum levels were not independent prognostic factors. In the FIGO Stage III group (112 patients), the 10-year overall survival was 15.2%; while in the FIGO Stage IV group (36 patients) a 10-year overall survival of 5.6% was seen. Here, the tumor markers CA125 and TPS levels were significant prognostic factors in both univariate and multivariate analysis (p < 0.0001). In a combined FIGO Stage III + FIGO Stage IV group (60 patients with optimal debulking surgery), multivariate analysis demonstrated that CA125 and TPS levels were independent prognostic factors. For patients in this combined FIGO Stage III + IV group having both markers below respective discrimination level, 35.3% survived for more than ten years, as opposed to patients having one marker above the discrimination level where the 10-year survival was reduced to 10% of the patients. For patients showing both markers above the respective discrimination level, none of the patients survived for the 10-year follow-up time. In FIGO III and IV ovarian cancer patients, only patients with CA 125 and TPS markers below the discrimination level after three chemotherapy courses indicated a favorable prognosis. Patients with an elevated level of CA 125 or TPS or both markers after three chemotherapy courses showed unfavorable prognosis.

Serum concentrations of soluble (s)L- and (s)P-selectins in women with ovarian cancer.

PubMed

Majchrzak-Baczmańska, Dominika B; Głowacka, Ewa; Wilczyński, Miłosz; Malinowski, Andrzej

2018-03-01

The aim of the study was to compare serum concentration of soluble L- and P-selectins in women with ovarian cancer (OC) and healthy controls, and to investigate sL- and sP-selectin levels with regard to clinical and pathological parameters. Correlation analysis was used to measure the following: sL- and sP-selectin concentration and Ca125; sP-selectin and platelet concentrations; and sL-selectin and serum leukocyte levels in women with OC. The study included 29 patients with OC and 23 healthy controls. Serum concentrations of sL- and sP-selectins were measured in all subjects. Routine diagnostic tests: CBC and USG (both groups) and Ca125 (study group) were performed. Significantly higher serum concentrations of sL- and sP-selectins were found in the study group as compared to controls. Lower levels of serum sL-selectin were observed in women with poorly-differentiated OC (G3) and advanced stages of the disease (FIGO III, IV), but the results were statistically insignificant. No statistically significant relationship was detected between sP-selectin serum concentration in women with OC and tumour differentiation, histological type, and stage of the disease. No significant correlation was found between sL- and sP-selectins and Ca125 levels. A weak correlation was found between serum concentration of sP-selectin in women with OC and platelet count. No statistically significant correlation was observed between sL-selectin concentration and serum leukocyte levels in women with OC. The analysis of sL- and sP-selectin concentrations may be a useful tool in the diagnosis of OC. The levels of sL-selectin decrease with disease progression.

76 FR 59410 - Government-Owned Inventions; Availability for Licensing

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-26

... tumors. The experimental results (average of 91.4% true positive volume fraction and 4.0% of false... test for the tumor marker CA-125. The CA-125 test only returns a true positive result for about 50% of...

Nanoparticle-based sandwich electrochemical immunoassay for carbohydrate antigen 125 with signal enhancement using enzyme-coated nanometer-sized enzyme-doped silica beads.

PubMed

Tang, Dianping; Su, Biling; Tang, Juan; Ren, Jingjing; Chen, Guonan

2010-02-15

A novel nanoparticle-based electrochemical immunoassay of carbohydrate antigen 125 (CA125) as a model was designed to couple with a microfluidic strategy using anti-CA125-functionalized magnetic beads as immunosensing probes. To construct the immunoassay, thionine-horseradish peroxidase conjugation (TH-HRP) was initially doped into nanosilica particles using the reverse micelle method, and then HRP-labeled anti-CA125 antibodies (HRP-anti-CA125) were bound onto the surface of the synthesized nanoparticles, which were used as recognition elements. Different from conventional nanoparticle-based electrochemical immunoassays, the recognition elements of the immunoassay simultaneously contained electron mediator and enzyme labels and simplified the electrochemical measurement process. The sandwich-type immunoassay format was used for the online formation of the immunocomplex in an incubation cell and captured in the detection cell with an external magnet. The electrochemical signals derived from the carried HRP toward the reduction of H(2)O(2) using the doped thionine as electron mediator. Under optimal conditions, the electrochemical immunoassay exhibited a wide working range from 0.1 to 450 U/mL with a detection limit of 0.1 U/mL CA125. The precision, reproducibility, and stability of the immunoassay were acceptable. The assay was evaluated for clinical serum samples, receiving in excellent accordance with results obtained from the standard enzyme-linked immunosorbent assay (ELISA) method. Concluding, the nanoparticle-based assay format provides a promising approach in clinical application and thus represents a versatile detection method.

Selenium Binding Protein 1 (SBP1) autoantibodies in ovarian disorders and ovarian cancer

PubMed Central

Yu-Rice, Yi; Edassery, Seby L.; Urban, Nicole; Hellstrom, Ingegerd; Hellstrom, Karl Erik; Deng, Youping; Li, Yan; Luborsky, Judith L.

2016-01-01

Infertility is a risk factor for ovarian cancer (OvCa). The goal was to determine if antibodies to Selenium Binding Protein 1 (SBP1), an autoantibody we identified in patients with premature ovarian failure (POF), occurs in both infertility and OvCa patients, and thus could be associated with preneoplasia. Anti-SBP1 was measured by immunoassay against recombinant SBP1, in sera from OvCa (n=41), infertility (n=92) and control (n=87) patients. Infertility causes were POF, unexplained, irregular ovulation or endometriosis. The percent of anti-SBP1 positive sera was higher in POF (p=0.02), irregular ovulation (p=0.001), unexplained causes (p=0.02), late (III–IV) stage OvCa (p=0.02) but was not significant in endometriosis, benign ovarian tumors/cysts, early stage (I–II) OvCa or uterine cancer compared to healthy controls. Anti-SBP1 was significantly higher in women with serous (p=0.04) but not non-serous (p=0.33) OvCa compared to controls. Also, we determined if anti-SBP1 was associated with CA125 or anti-p53, markers often studied in OvCa. Anti-p53 and CA125 were measured by established immunoassays. The ability of anti-SBP1 alone to discriminate infertility or OvCa from controls, or when combined with anti-p53 and CA125, to identify OvCa was evaluated by comparing the Area Under the Curve (AUC) in ROC analysis. Anti-SBP1 alone discriminated infertility (AUC=0.7; p=0.001) or OvCa (AUC=0.67; p=0.03) from controls. The sensitivity and specificity of OvCa identification was increased by combining CA125, anti-p53 and anti-SBP1 (AUC=0.96). Therefore, anti-SBP1 occurs in infertile women with POF, ovulatory disturbances or unexplained infertility and in serous OvCa. This suggests an autoimmune process is associated with development of serous OvCa. PMID:27965399

Outcome of treatment of respiratory tract infections due to Streptococcus pneumoniae, including drug-resistant strains, with pharmacokinetically enhanced amoxycillin/clavulanate.

PubMed

File, Thomas M; Jacobs, Michael R; Poole, Michael D; Wynne, Brian

2002-10-01

The efficacy of a new pharmacokinetically enhanced formulation of amoxycillin/clavulanate (AMX/CA) 2000/125 mg, twice daily, designed to provide adequate levels of amoxycillin over the 12-h dosing interval to eradicate penicillin-resistant Streptococcus pneumoniae (PRSP) with amoxycillin (+/-clavulanic acid) MICs of /=4 mg/l. In the pooled comparator group, the success rate at follow-up was 86.5% (45/52). For PRSP (AMX/CA MICs of 0.5-8 mg/l), the overall success rate was 98.2% (55/56) at follow-up for AMX/CA 2000/125 mg and 50.0% (2/4) for comparators. AMX/CA 2000/125 mg shows efficacy comparable to that of the comparators evaluated against S. pneumoniae infections. Due to its favorable pharmacokinetic/pharmacodynamic profile and promising clinical success, the new AMX/CA 2000/125 mg formulation should be considered for the empirical treatment of respiratory tract infections in regions with a high prevalence of antimicrobial-resistant S. pneumoniae and in patients at high risk of antimicrobial-resistant S. pneumoniae infection as this formulation covers many PRSP that are non-susceptible to amoxycillin (+/-clavulanic acid) (MICs of >/=4 mg/l) as well as common beta-lactamase-producing respiratory pathogens.

Calcium Balance in Mature Rats Exposed to a Space Flight Model

NASA Technical Reports Server (NTRS)

Navidi, Meena; Evans, J.; Looft-Wilson, R.; Wolinsky, I.; Arnaud, S. B.; Hargens, Alan R. (Technical Monitor)

1996-01-01

Depressed intestinal calcium absorption (Ca abs.) and lower circulating 1,25-dihydroxyvitamin D (1,25-D) are associated with less positive calcium balance in young 200 g rats exposed to skeletal unloading by hind-limb suspension than controls (C) . To determine the effect of the space flight model on calcium balance in mature rats, we exposed 6 mo. old males weighing 492 +/- 12g to the model for 4 weeks (S) and compared Ca in the diet, urine, feces and 1,25-D in S and C. Rats were fed diets containing sufficient Ca to satisfy metabolic needs, but not to cause deficiency (0.1%). At the end of 4 weeks, there was a 5 percent weight loss in S, but not in C; and no differences in dietary, urine (UCa) or fecal Ca (FCa) in S and C. Net Ca abs. (0.1 vs 2.7 %), 1,25-D (50 +/- 16 vs 47 +/- 14 pg/ml) and Ca balances (-1.8 +/- 4 vs -1.0 +/- 2.9 mg/d) were similar in C and S. UCa loss was added to the model by inducing calciuria with 8% salt diets (HiNa). A 4-fold increase in UCa in C and S was transiently higher in S than C after 1 week. After 4 weeks, loss in BW was greater in S than C, Ca abs was higher in C than S (32 +/- 10 vs 3.5 +/- 16%, p less than .05), 1,25-D greater in S than C (98 +/- 15 vs 79 +/- 14 pg/ml p less than .05) and Ca balance less in S than C (-5.2 +/- 4 vs -1.7 +/- 2 mg/d, p less than .05). Ca balance in the mature rat is unaffected by the space flight model unless calciuria intervenes and reveals the failure of the intestine to enhance Ca abs. and compensate for UCa loss.

Cancer Antigen 125 as a Biomarker in Peritoneal Dialysis: Mesothelial Cell Health or Death?

PubMed Central

Cheema, Harpaul; Bargman, Joanne M.

2013-01-01

The concentration or appearance rate of cancer antigen 125 (CA125) in peritoneal dialysis (PD) effluent has been used for many years as a biomarker for mesothelial cell mass in patients on PD. However, this marker has limitations, and emerging evidence has raised doubts as to its significance. This review explores our current understanding of CA125, its prominent role in studies of “biocompatible” PD solutions, and the ongoing uncertainty concerning its interpretation as a measure of mesothelial cell health. PMID:23843586

Escherichia coli isolates causing asymptomatic bacteriuria in catheterized and noncatheterized individuals possess similar virulence properties.

PubMed

Watts, Rebecca E; Hancock, Viktoria; Ong, Cheryl-Lynn Y; Vejborg, Rebecca Munk; Mabbett, Amanda N; Totsika, Makrina; Looke, David F; Nimmo, Graeme R; Klemm, Per; Schembri, Mark A

2010-07-01

Urinary tract infections (UTIs) are among the most common infectious diseases of humans, with Escherichia coli being responsible for >80% of all cases. Asymptomatic bacteriuria (ABU) occurs when bacteria colonize the urinary tract without causing clinical symptoms and can affect both catheterized patients (catheter-associated ABU [CA-ABU]) and noncatheterized patients. Here, we compared the virulence properties of a collection of ABU and CA-ABU nosocomial E. coli isolates in terms of antibiotic resistance, phylogenetic grouping, specific UTI-associated virulence genes, hemagglutination characteristics, and biofilm formation. CA-ABU isolates were similar to ABU isolates with regard to the majority of these characteristics; exceptions were that CA-ABU isolates had a higher prevalence of the polysaccharide capsule marker genes kpsMT II and kpsMT K1, while more ABU strains were capable of mannose-resistant hemagglutination. To examine biofilm growth in detail, we performed a global gene expression analysis with two CA-ABU strains that formed a strong biofilm and that possessed a limited adhesin repertoire. The gene expression profile of the CA-ABU strains during biofilm growth showed considerable overlap with that previously described for the prototype ABU E. coli strain, 83972. This is the first global gene expression analysis of E. coli CA-ABU strains. Overall, our data suggest that nosocomial ABU and CA-ABU E. coli isolates possess similar virulence profiles.

Blood Plasma-Derived Anti-Glycan Antibodies to Sialylated and Sulfated Glycans Identify Ovarian Cancer Patients

PubMed Central

Pochechueva, Tatiana; Chinarev, Alexander; Schoetzau, Andreas; Fedier, André; Bovin, Nicolai V.; Hacker, Neville F.; Jacob, Francis; Heinzelmann-Schwarz, Viola

2016-01-01

Altered levels of naturally occurring anti-glycan antibodies (AGA) circulating in human blood plasma are found in different pathologies including cancer. Here the levels of AGA directed against 22 negatively charged (sialylated and sulfated) glycans were assessed in high-grade serous ovarian cancer (HGSOC, n = 22) patients and benign controls (n = 31) using our previously developed suspension glycan array (SGA). Specifically, the ability of AGA to differentiate between controls and HGSOC, the most common and aggressive type of ovarian cancer with a poor outcome was determined. Results were compared to CA125, the commonly used ovarian cancer biomarker. AGA to seven glycans that significantly (P<0.05) differentiated between HGSOC and control were identified: AGA to top candidates SiaTn and 6-OSulfo-TF (both IgM) differentiated comparably to CA125. The area under the curve (AUC) of a panel of AGA to 5 glycans (SiaTn, 6-OSulfo-TF, 6-OSulfo-LN, SiaLea, and GM2) (0.878) was comparable to CA125 (0.864), but it markedly increased (0.985) when combined with CA125. AGA to SiaTn and 6-OSulfo-TF were also valuable predictors for HGSOC when CA125 values appeared inconclusive, i.e. were below a certain threshold. AGA-glycan binding was in some cases isotype-dependent and sensitive to glycosidic linkage switch (α2–6 vs. α2–3), to sialylation, and to sulfation of the glycans. In conclusion, plasma-derived AGA to sialylated and sulfated glycans including SiaTn and 6-OSulfo-TF detected by SGA present a valuable alternative to CA125 for differentiating controls from HGSOC patients and for predicting the likelihood of HGSOC, and may be potential HGSOC tumor markers. PMID:27764122

Blood Plasma-Derived Anti-Glycan Antibodies to Sialylated and Sulfated Glycans Identify Ovarian Cancer Patients.

PubMed

Pochechueva, Tatiana; Chinarev, Alexander; Schoetzau, Andreas; Fedier, André; Bovin, Nicolai V; Hacker, Neville F; Jacob, Francis; Heinzelmann-Schwarz, Viola

2016-01-01

Altered levels of naturally occurring anti-glycan antibodies (AGA) circulating in human blood plasma are found in different pathologies including cancer. Here the levels of AGA directed against 22 negatively charged (sialylated and sulfated) glycans were assessed in high-grade serous ovarian cancer (HGSOC, n = 22) patients and benign controls (n = 31) using our previously developed suspension glycan array (SGA). Specifically, the ability of AGA to differentiate between controls and HGSOC, the most common and aggressive type of ovarian cancer with a poor outcome was determined. Results were compared to CA125, the commonly used ovarian cancer biomarker. AGA to seven glycans that significantly (P<0.05) differentiated between HGSOC and control were identified: AGA to top candidates SiaTn and 6-OSulfo-TF (both IgM) differentiated comparably to CA125. The area under the curve (AUC) of a panel of AGA to 5 glycans (SiaTn, 6-OSulfo-TF, 6-OSulfo-LN, SiaLea, and GM2) (0.878) was comparable to CA125 (0.864), but it markedly increased (0.985) when combined with CA125. AGA to SiaTn and 6-OSulfo-TF were also valuable predictors for HGSOC when CA125 values appeared inconclusive, i.e. were below a certain threshold. AGA-glycan binding was in some cases isotype-dependent and sensitive to glycosidic linkage switch (α2-6 vs. α2-3), to sialylation, and to sulfation of the glycans. In conclusion, plasma-derived AGA to sialylated and sulfated glycans including SiaTn and 6-OSulfo-TF detected by SGA present a valuable alternative to CA125 for differentiating controls from HGSOC patients and for predicting the likelihood of HGSOC, and may be potential HGSOC tumor markers.

Preoperative HE4 and ROMA values do not improve the CA125 diagnostic value for borderline tumors of the ovary (BOT) - a study of the TOC Consortium.

PubMed

Braicu, Elena Ioana; Van Gorp, Toon; Nassir, Mani; Richter, Rolf; Chekerov, Radoslav; Gasimli, Khayal; Timmerman, Dirk; Vergote, Ignace; Sehouli, Jalid

2014-01-01

Borderline tumors of the ovary (BOT) are a distinct entity of ovarian tumors, characterized by lack of stromal invasion. Recent studies postulated that the presence of invasive implants, incomplete staging, fertility sparing surgery and residual tumor after surgery are major prognostic factors for BOT. There are no biomarkers that can predict BOT or the presence of invasive implants. The aim of our study was to assess the value of CA125 and HE4 alone, or within ROMA score for detecting BOT, and for predicting the presence of invasive implants. Retrospective, monocentric study on 167 women diagnosed with BOT or benign ovarian masses. Serum HE4, CA125 levels and ROMA were assessed preoperatively. Due to low number of BOT with invasive implants, we performed an unmatched analysis (consecutive patients) and a matched analysis (according to age and histology) to compare BOT with invasive implants, BOT without invasive implants and benign disease. There were no significant differences in the HE4 and CA125 expressions in the three groups of patients (p = 0.984 and p = 0.141, respectively). The ROC analysis showed that CA125 alone is superior to ROMA and HE4 in discriminating patients with BOT with invasive implants from patients with benign diseases and BOT without invasive implants. A newly established score, ROMABOT, did not perform better than ROMA. The analysis of the matched groups revealed similar results as the analysis of all samples. Both HE4 and CA125 are not reliable biomarkers for the diagnosis of BOT or for predicting the presence of invasive implants.

Effect of simulated weightlessness and chronic 1,25-dihydroxyvitamin D administration on bone metabolism

NASA Technical Reports Server (NTRS)

Halloran, B. P.; Bikle, D. D.; Globus, R. K.; Levens, M. J.; Wronski, T. J.; Morey-Holton, E.

1985-01-01

Weightlessness, as experienced during space flight, and simulated weightlessness induce osteopenia. Using the suspended rat model to simulate weightlessness, a reduction in total tibia Ca and bone formation rate at the tibiofibular junction as well as an inhibition of Ca-45 and H-3-proline uptake by bone within 5-7 days of skeletal unloading was observed. Between days 7 and 15 of unloading, uptake of Ca-45 and H-3-proline, and bone formation rate return to normal, although total bone Ca remains abnormally low. To examine the relationship between these characteristic changes in bone metabolism induced by skeletal unloading and vitamin D metabolism, the serum concentrations of 25-hydroxyvitamin D (25-OH-D), 24, 25-dihydroxyvitamin D (24,25(OH)2D) and 1,25-dihydroxyvitamin D (1,25(OH)2D) at various times after skeletal unloading were measured. The effect of chronic infusion of 1,25(OH)2D3 on the bone changes associated with unloading was also determined.

Prediction of pelvic pathology in subfertile women with combined Chlamydia antibody and CA-125 tests.

PubMed

Penninx, Josien; Brandes, Monique; de Bruin, Jan Peter; Schneeberger, Peter M; Hamilton, Carl J C M

2009-12-01

Chlamydia antibody test (CAT) has been proposed to predict tubal disease. A correlation between CA-125 and the extent of endometriosis has been found by others. In this study we explored whether a combination of the two tests adds to the predictive value of the individual tests for predicting tubal disease or endometriosis. We also used the combination of tests as a new index test to screen for severe pelvic pathology. This retrospective study compares the findings of 240 laparoscopies with the serological test results. Findings were classified according to the existing ASRM scoring systems for adnexal adhesions, distal tubal occlusion and endometriosis. Severe pelvic pathology was defined as the presence of ASRM classes III and IV tubal disease or ASRM classes III and IV endometriosis. The predictive value was calculated for both tests separately and for the combined test. The combined test was positive if at least one test result was abnormal (CAT positive and/or CA-125 > or =35 IU/ml). 67/240 women had tubal disease, 81/240 had some degree of endometriosis. The odds ratios (ORs) of the CAT and the combined test to diagnose severe tubal disease were 6.6 (2.6-17.0) and 7.3 (2.9-19.3), respectively. The ORs of the CA-125 and the combined test to diagnose severe endometriosis were 15.6 (6.2-40.2) and 3.0 (1.2-8.0), respectively. Severe pelvic pathology was present in 65/240 women (27%). The ORs for severe pelvic pathology of the CAT, CA-125 and the combined test were 2.5 (1.4-5.3), 4.9 (1.9-9.6) and 6.6 (3.3-13.4), respectively. If the combined test was normal 15 out 131 women (11%) were shown to have severe pelvic pathology. The combined test adds hardly anything to the predictive value of CAT alone to diagnose severe tubal disease. The combined test is better than the CAT to predict severe pelvic pathology, but is not significantly better than the CA-125. If both the CAT and CA-125 are normal one could consider not performing a laparoscopy.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hefferan, T.E.; Sherman, S.S.; Sinha, R.

Eighty female Sprague-Dawley 8 week old rats were pair-fed for 2 months a semi-purified egg white diet containing 0.2% Ca and Zn at 4.5, 10, 100 or 200ppm. The vitamin D source was D/sub 3/ or 1,25(OH)/sub 2/D. Serum 1,25(OH)/sub 2/D, Ca and femur densities were determined. Femur densities were shown to regress significantly (p<0.01) with increasing dietary Zn when D/sub 3/ was in the diet. In addition, feeding D/sub 3/ resulted in a significant negative correlation of serum Ca with increased dietary Zn (p<0.05). There was a trend for 1,25(OH)/sub 2/D to increase with increasing Zn intake. However, serummore » values in rats consuming 1,25(OH)/sub 2/D were lower compared to rats consuming D/sub 3/ (25.9+/-3.6 vs 53.0+/-5.9 pg/ml). A second study was conducted to determine if non-fasted rats had elevated 1,25(OH)/sub 2/D serum levels. The rats were fed a similar semi-purified diet containing 0.2% Ca, 10ppm Zn and D/sub 3/ or 1,25(OH)/sub 2/D. No significant difference in 1,25(OH)/sub 2/D values was found between D/sub 3/ and 1,25(OH)/sub 2/D fed groups in the full fed state (80.8+/-11.4 vs 81.0+/-14.3 pg/ml). These results indicate high Zn intakes antagonize normal calcification and may interfere with normal function of the vitamin D endocrine system.« less

Evidence that low plasma 1,25-dihydroxyvitamin D causes intestinal malabsorption of calcium and phosphate in juvenile X-linked hypophosphatemic mice.

PubMed

Meyer, R A; Meyer, M H; Gray, R W; Bruns, M E

1987-02-01

X-linked hypophosphatemic (Hyp) mice are a model for human sex-linked vitamin D-resistant rickets. We have reported intestinal malabsorption of calcium in young Hyp mice, and in this report we have explored the mechanism for it. To test for resistance of the intestine to 1,25(OH)2 vitamin D3, this hormone was continually infused via osmotic minipumps into 4-week-old normal and Hyp mice at 0, 17, 50 or 150 ng/kg/day. After 3 days, 45Ca and inorganic 32P were administered by gavage, and the mice were sacrificed on the fifth day. The Hyp mice showed responses to the hormone equivalent to the normal mice in terms of increased intestinal absorption of both 45Ca and 32P, increased plasma isotope levels, increased femoral isotope content, and increased duodenal and renal 9 kD vitamin D-dependent calcium-binding protein (calbindin-D9K; CaBP). Plasma 1,25(OH)2D was measured in these mice. There were significant correlations of plasma 1,25(OH)2D to the intestinal absorption of 45Ca and 32P and to duodenal and renal CaBP. Plasma 1,25(OH)2D was also measured in stock normal and Hyp mice and was found to be lower in 4-week-old Hyp mice than in 4-week-old normal mice (113 +/- 10 pM (n = 18) vs. 67 +/- 10 (n = 20), normal vs. Hyp, p less than .01), but unchanged at 13 weeks of age (77 +/- 13 (n = 13) vs. 70 +/- 15 (n = 15), NS). This observed difference in plasma 1,25(OH)2D between normal and Hyp mice at 4 weeks of age was sufficient to explain the observed normal-to-Hyp differences in intestinal absorption of 45Ca and duodenal and renal CaBP. It also explained 72 +/- 18% of the observed difference in 32P absorption. We conclude that Hyp mouse intestine is not resistant to 1,25(OH)2D and that the lower plasma 1,25(OH)2D of 4-week-old Hyp mice causes intestinal malabsorption of calcium and phosphate.

Application of multiplex nested methylated specific PCR in early diagnosis of epithelial ovarian cancer.

PubMed

Wang, Bi; Yu, Lei; Yang, Guo-Zhen; Luo, Xin; Huang, Lin

2015-01-01

To explore the application of multiplex nested methylated specific polymerase chain reaction (PCR) in the early diagnosis of epithelial ovarian carcinoma (EOC). Serum and fresh tissue samples were collected from 114 EOC patients. RUNX3, TFPI2 and OPCML served as target genes. Methylation levels of tissues were assessed by multiplex nested methylated specific PCR, the results being compared with those for carcinoma antigen 125 (CA125). The serum free deoxyribose nucleic acid (DNA) methylation spectrum of EOC patients was completely contained in the DNA spectrum of cancer tissues, providing an accurate reflection of tumor DNA methylation conditions. Serum levels of CA125 and free DNA methylation in the EOC group were evidently higher than those in benign lesion and control groups (p<0.05). Patients with early EOC had markedly lower serum CA125 than those with advanced EOC (p<0.05), but there was no significant difference in free DNA methylation (p>0.05). The sensitivity, specificity and positive predicative value (PPV) of multiplex nested methylated specific PCR were significantly higher for detection of all patients and those with early EOC than those for CA125 (p<0.05). In the detection of patients with advanced EOC, the PPV of CA125 detection was obviously lower than that of multiplex nested methylated specific PCR (p>0.05), but there was no significant difference in sensitivity (p>0.05). Serum free DNA methylation can be used as a biological marker for EOC and multiplex nested methylated specific PCR should be considered for early diagnosis since it can accurately determine tumor methylation conditions.

Hepatitis E in blood donors: investigation of the natural course of asymptomatic infection, Germany, 2011.

PubMed

Vollmer, Tanja; Diekmann, Juergen; Eberhardt, Matthias; Knabbe, Cornelius; Dreier, Jens

2016-09-01

Asymptomatic hepatitis E virus (HEV) infections have been found in blood donors from various European countries, but the natural course is rarely specified. Here, we compared the progression of HEV viraemia, serostatus and liver-specific enzymes in 10 blood donors with clinically asymptomatic genotype 3 HEV infection, measuring HEV RNA concentrations, plasma concentrations of alanine/aspartate aminotransferase, glutamate dehydrogenase and bilirubin and anti-HEV IgA, IgM and IgG antibodies. RNA concentrations ranged from 77.2 to 2.19×10(5) IU/mL, with viraemia lasting from less than 10 to 52 days. Donors showed a typical progression of a recent HEV infection but differed in the first detection of anti-HEV IgA, IgM and IgG and seropositivity of the antibody classes. The diagnostic window between HEV RNA detection and first occurrence of anti-HEV antibodies ranged from eight to 48 days, depending on the serological assay used. The progression of laboratory parameters of asymptomatic HEV infection was largely comparable to the progression of symptomatic HEV infection, but only four of 10 donors showed elevated liver-specific parameters. Our results help elucidate the risk of transfusion-associated HEV infection and provide a basis for development of screening strategies. The diagnostic window illustrates that infectious blood donors can be efficiently identified only by RNA screening. This article is copyright of The Authors, 2016.

Baseline and On-Treatment Characteristics of Serum Tumor Markers in Stage IV Oncogene-Addicted Adenocarcinoma of the Lung.

PubMed

Noonan, Sinead A; Patil, Tejas; Gao, Dexiang; King, Gentry G; Thibault, Jessica R; Lu, Xian; Bunn, Paul A; Doebele, Robert C; Purcell, W Thomas; Barón, Anna E; Camidge, D Ross

2018-01-01

The role of serum tumor markers in the modern management of advanced NSCLC remains poorly described. A single-center retrospective analysis of available carcinoembryonic antigen, CA125, CA19.9, and CA27.29 levels at baseline and during treatment of stage IV lung adenocarcinoma by oncogenic driver was conducted. A total of 142 patients were analyzed (60 with anaplastic lymphoma kinase gene [ALK] rearrangement, 50 with EGFR mutation, four with ROS1 rearrangement, and 29 with KRAS mutation). Of these, 82% had at least one marker (95% if all four markers were measured), with CA27.29 being the most commonly increased and CA19.9 the rarest. Only CA27.29 differed significantly by oncogene (it was less common in KRAS) (p = 0.016). The median times to nadir during tyrosine kinase inhibitor (TKI) therapy in EGFR and ALK cases were 16.4 and 20 weeks, respectively. Of the 41 patients with EGFR mutation or ALK or ROS1 rearrangement, 24 (59%) demonstrated an initial increase within the first 4 weeks of TKI therapy, 58% of whom then had their levels fall below baseline. An increase in marker level of 10% or more from nadir occurred in 53% of systemic and 22% of central nervous system-only progression. Serum tumor markers are frequently increased in lung adenocarcinoma regardless of driver oncogene. Changes within the first 4 weeks of therapy may be misleading. Progression is associated with marker increases, especially in sites other than the central nervous system. Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Enhancement of force generated by individual myosin heads in skinned rabbit psoas muscle fibers at low ionic strength.

PubMed

Sugi, Haruo; Abe, Takahiro; Kobayashi, Takakazu; Chaen, Shigeru; Ohnuki, Yoshiki; Saeki, Yasutake; Sugiura, Seiryo

2013-01-01

Although evidence has been presented that, at low ionic strength, myosin heads in relaxed skeletal muscle fibers form linkages with actin filaments, the effect of low ionic strength on contraction characteristics of Ca(2+)-activated muscle fibers has not yet been studied in detail. To give information about the mechanism of muscle contraction, we have examined the effect of low ionic strength on the mechanical properties and the contraction characteristics of skinned rabbit psoas muscle fibers in both relaxed and maximally Ca(2+)-activated states. By progressively decreasing KCl concentration from 125 mM to 0 mM (corresponding to a decrease in ionic strength μ from 170 mM to 50 mM), relaxed fibers showed changes in mechanical response to sinusoidal length changes and ramp stretches, which are consistent with the idea of actin-myosin linkage formation at low ionic strength. In maximally Ca(2+)-activated fibers, on the other hand, the maximum isometric force increased about twofold by reducing KCl concentration from 125 to 0 mM. Unexpectedly, determination of the force-velocity curves indicated that, the maximum unloaded shortening velocity Vmax, remained unchanged at low ionic strength. This finding indicates that the actin-myosin linkages, which has been detected in relaxed fibers at low ionic strength, are broken quickly on Ca(2+) activation, so that the linkages in relaxed fibers no longer provide any internal resistance against fiber shortening. The force-velocity curves, obtained at various levels of steady Ca(2+)-activated isometric force, were found to be identical if they are normalized with respect to the maximum isometric force. The MgATPase activity of muscle fibers during isometric force generation was found not to change appreciably at low ionic strength despite the two-fold increase in Ca(2+)-activated isometric force. These results can be explained in terms of enhancement of force generated by individual myosin heads, but not by any changes in kinetic properties of cyclic actin-myosin interaction.

Selenium-Binding Protein 1 (SBP1) autoantibodies in ovarian disorders and ovarian cancer.

PubMed

Yu-Rice, Yi; Edassery, Seby L; Urban, Nicole; Hellstrom, Ingegerd; Hellstrom, Karl Erik; Deng, Youping; Li, Yan; Luborsky, Judith L

2017-03-01

Infertility is a risk factor for ovarian cancer (OvCa). The goal was to determine if antibodies to selenium-binding protein 1 (SBP1), an autoantibody we identified in patients with premature ovarian failure (POF), occurs in both infertility and OvCa patients, and thus could be associated with preneoplasia. Anti-SBP1 was measured by immunoassay against recombinant SBP1, in sera from OvCa (n = 41), infertility (n = 92) and control (n = 87) patients. Infertility causes were POF, unexplained, irregular ovulation or endometriosis. The percent of anti-SBP1-positive sera was higher in POF (P = 0.02), irregular ovulation (P = 0.001), unexplained causes (P = 0.02), late (III-IV)-stage OvCa (P = 0.02) but was not significant in endometriosis, benign ovarian tumors/cysts, early stage (I-II) OvCa or uterine cancer compared to healthy controls. Anti-SBP1 was significantly higher in women with serous (P = 0.04) but not non-serous (P = 0.33) OvCa compared to controls. Also, we determined if anti-SBP1 was associated with CA125 or anti-TP53, markers often studied in OvCa. Anti-TP53 and CA125 were measured by established immunoassays. The ability of anti-SBP1 alone to discriminate infertility or OvCa from controls or when combined with anti-TP53 and CA125, to identify OvCa was evaluated by comparing the area under the curve (AUC) in ROC analysis. Anti-SBP1 alone discriminated infertility (AUC = 0.7; P = 0.001) or OvCa (AUC = 0.67; P = 0.03) from controls. The sensitivity and specificity of OvCa identification was increased by combining CA125, anti-TP53 and anti-SBP1 (AUC = 0.96). Therefore, anti-SBP1 occurs in infertile women with POF, ovulatory disturbances or unexplained infertility and in serous OvCa. This suggests an autoimmune process is associated with the development of serous OvCa. © 2017 Society for Reproduction and Fertility.

Are Breast Masses in Teenagers Always Benign? Undifferentiated Mesenchymal Sarcoma in a 14-Year-Old Girl

PubMed Central

Tekbas, Guven; Ince, Tülay; Kapan, Murat; Ekici, Faysal; Önder, Akin; Kucukonen, Mehmet; Bilici, Aslan; Gumus, Hatice

2012-01-01

Background This article is concerned with the evaluation of an adolescent breast mass using imaging methods. Case Report A 14-year-old girl presented with progressive asymmetric enlargement of the left breast. She had felt a breast lump about 4 months earlier, and over the last 2 months it had been growing progressively. Tumor markers, including AFP, CEA, CA15-3, and CA125, were all normal. Ultrasonography showed a hypoechoichyperechoic, solid mass. Magnetic resonance imaging of the breast revealed a well marginated mass with hypointensity on T1-weighted images and mild hyperintensity on T2-weighted images, which showed mild contrast uptake. Biopsy revealed an undifferentiated malignant mesenchymal sarcoma. The patient underwent mastectomy with axillary lymph node sampling. After the operation, she received 3 cycles of chemotherapy and radiotherapy. Conclusion Due to the rarity of breast sarcoma and inadequate imaging methods to establish an exact diagnosis, radiologists and clinicians may misdiagnose and merely follow these tumors. As in our case, the histology of the patient may be the leading factor in the management of these tumors. Even in very young patients, progressively growing breast masses should alert the clinician to check for malignancy verified by biopsy. PMID:22740802

Inflammatory profile in X-linked adrenoleukodystrophy patients: Understanding disease progression.

PubMed

Marchetti, Desirèe Padilha; Donida, Bruna; Jacques, Carlos Eduardo; Deon, Marion; Hauschild, Tatiane Cristina; Koehler-Santos, Patricia; de Moura Coelho, Daniella; Coitinho, Adriana Simon; Jardim, Laura Bannach; Vargas, Carmen Regla

2018-01-01

X-linked adrenoleukodystrophy (X-ALD) is an inherited disease characterized by progressive inflammatory demyelization in the brain, adrenal insufficiency, and an abnormal accumulation of very long chain fatty acids (VLCFA) in tissue and body fluids. Considering that inflammation might be involved in pathophysiology of X-ALD, we aimed to investigate pro- and anti-inflammatory cytokines in plasma from three different male phenotypes (CCER, AMN, and asymptomatic individuals). Our results showed that asymptomatic patients presented increased levels of pro-inflammatory cytokines IL-1β, IL-2, IL-8, and TNF-α and the last one was also higher in AMN phenotype. Besides, asymptomatic patients presented higher levels of anti-inflammatory cytokines IL-4 and IL-10. AMN patients presented higher levels of IL-2, IL-5, and IL-4. We might hypothesize that inflammation in X-ALD is related to plasmatic VLCFA concentration, since there were positive correlations between C26:0 plasmatic levels and pro-inflammatory cytokines in asymptomatic and AMN patients and negative correlation between anti-inflammatory cytokine and C24:0/C22:0 ratio in AMN patients. The present work yields experimental evidence that there is an inflammatory imbalance associated Th1, (IL-2, IL-6, and IFN-γ), Th2 (IL-4 and IL-10), and macrophages response (TNF-α and IL-1β) in the periphery of asymptomatic and AMN patients, and there is correlation between VLCFA plasmatic levels and inflammatory mediators in X-ALD. Furthermore, we might also speculate that the increase of plasmatic cytokines in asymptomatic patients could be considered an early biomarker of brain damage and maybe also a predictor of disease progression. © 2017 Wiley Periodicals, Inc.

Asymptomatic Wolff-Parkinson-White Pattern ECG in USAF Aviators.

PubMed

Davenport, Eddie D; Rupp, Karen A N; Palileo, Edwin; Haynes, Jared

2017-01-01

Wolff-Parkinson-White (WPW) pattern is occasionally found in asymptomatic aviators during routine ECGs. Aeromedical concerns regarding WPW pattern include risk of dysrhythmia or sudden cardiac death (SCD), thus affecting the safety of flight. The purpose of this study was to determine the prevalence and outcomes of aviators with asymptomatic WPW pattern and assess for risk factors that contribute to progression to dysrhythmia or symptoms. The U.S. Air Force (USAF) ECG library database containing over 1.2 million ECGs collected over the past 68 yr was used to identify 638 individual aviators with WPW pattern. Demographic, medical history, and outcome data were obtained by medical record review. Aviators who developed high risk features defined as symptoms, arrhythmia, or ablation of a high risk pathway, were compared to those who remained asymptomatic. Prevalence of WPW pattern was 0.30% among all USAF aviators. Of the 638 individuals, 64 (10%) progressed to the combined endpoint of SCD, arrhythmia, and/or ablation of a high risk pathway over 6868 patient years, with average follow-up of 10.5 yr. There were two sudden cardiac deaths (0.3%). Annual risk of possible sudden incapacitation was 0.95% and of SCD 0.03%. Those that progressed to high risk were significantly younger, had lower diastolic blood pressure, lower total cholesterol, and better physical fitness testing scores. WPW pattern on ECG found in asymptomatic aviators confers < 1% annual risk of arrhythmia or incapacitating events with the highest risk in the younger, healthier, and most fit populations.Davenport ED, Rupp KAN, Palileo E, Haynes J. Asymptomatic Wolff-Parkinson-White pattern ECG in USAF aviators. Aerosp Med Hum Perform. 2017; 88(1):56-60.

[Clinical significance and distribution of BRCA genes mutation in sporadic high grade serous ovarian cancer].

PubMed

Liu, W L; Wang, Z Z; Zhao, J Z; Hou, Y Y; Wu, X X; Li, W; Dong, B; Tong, T T; Guo, Y J

2017-01-25

Objective: To investigate the mutations of BRCA genes in sporadic high grade serous ovarian cancer (HGSOC) and study its clinical significance. Methods: Sixty-eight patients between January 2015 and January 2016 from the Affiliated Cancer Hospital of Zhengzhou University were collected who were based on pathological diagnosis of ovarian cancer and had no reported family history, and all patients firstly hospitalized were untreated in other hospitals before. (1) The BRCA genes were detected by next-generation sequencing (NGS) method. (2) The serum tumor markers included carcinoembryonic antigen (CEA), CA(125), CA(199), and human epididymis protein 4 (HE4) were detected by the chemiluminescence methods, and their correlation was analyzed by Pearson linear correlation. Descriptive statistics and comparisons were performed using two-tailed t -tests, Pearson's chi square test, Fisher's exact tests or logistic regression analysis as appropriate to research the clinicopathologic features associated with BRCA mutations, including age, International Federation of Gynecology and Obstetrics (FIGO) stage, platinum-based chemotherapy sensitivity, distant metastases, serum tumor markers (STM) . Results: (1) Fifteen cases (22%, 15/68) BRCA mutations were identified (BRCA1: 11 cases; BRCA2: 4 cases), and four novel mutations were observed. (2) The levels of CEA, CA(199), and HE4 were lower in BRCA mutations compared to that in control group, while no significant differences were found ( P >0.05), but the level of CA(125) was much higher in BRCA mutation group than that in controls ( t =-3.536, P =0.003). Further linear regression analysis found that there was a significant linear correlation between CA(125) and HE4 group ( r =0.494, P <0.01), and the same correlation as CEA and CA(199) group ( r =0.897, P <0.01). (3) Single factor analysis showed that no significant differences were observed in onset age, FIGO stage, distant metastasis, and STM between BRCA(+) and BRCA(-) group ( P >0.05), while significant differences were found in CA(125) and sensitivity to platinum-based chemotherapy between the patients with BRCA mutation and wild type ( P <0.05). The multiple factors analysis showed that the high level of CA(125) was a independent risk factor of BRCA mutations in sporadic HGSOC ( P =0.007). Conclusion: The combination of CA(125) with BRCA have great clinical significance, the mutation of BRCA gene could guild the clinical chemotherapy regiments.

125. JOB NO. LINE 5044, INTERNATIONAL RECTIFIER CORP., RACHELLE LABORATORIES, ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

125. JOB NO. LINE 5044, INTERNATIONAL RECTIFIER CORP., RACHELLE LABORATORIES, INC., LONG BEACH, CA, BY J.C. FULTON, SEPTEMBER 1982, LINE 5044, CLIFTON AND CO., ON FILE ENGINEERS DEPARTMENT, PORT OF LONG BEACH - Ford Motor Company Long Beach Assembly Plant, Assembly Building, 700 Henry Ford Avenue, Long Beach, Los Angeles County, CA

Comparison of a Novel Multiple Marker Assay Versus the Risk of Malignancy Index for the Prediction of Epithelial Ovarian Cancer in Patients with a Pelvic Mass

PubMed Central

MOORE, Richard G.; JABRE-RAUGHLEY, Moune; BROWN, Amy K.; ROBISON, Katina M.; MILLER, M. Craig; ALLARD, W. Jeffery; KURMAN, Robert J.; BAST, Robert C.; SKATES, Steven J.

2012-01-01

Objectives To compare the Risk of Malignancy Index (RMI) to the Risk of Ovarian Malignancy Algorithm (ROMA) to predict EOC in women with a pelvic mass. Study Design 457 women with imaging results from ultrasound, CT and MRI, and serum HE4 and CA 125 determined prior to surgery for pelvic mass were evaluable. RMI values were determined using CA 125, imaging score and menopausal status. ROMA values were determined using HE4, CA 125, and menopausal status. Results At a set specificity of 75%, ROMA had a sensitivity of 94.3% and RMI had a sensitivity of 84.6% for distinguishing benign from EOC (p=0.0029). In patients with stage I and II disease, ROMA achieved a sensitivity of 85.3% compared with 64.7% for RMI (p<0.0001). Conclusions The dual marker algorithm utilizing HE4 and CA125 to calculate a ROMA value achieves a significantly higher sensitivity for identifying women with EOC than does RMI. PMID:20471625

Interaction effects among IFN-γ+874, IL-2-330, IL-10-1082, IL-10-592 and IL-4-589 polymorphisms on the clinical progression of subjects infected with hepatitis B virus and/or hepatitis C virus: a retrospective nested case–control study

PubMed Central

Gao, Qiu-Ju; Xie, Jia-Xin; Wang, Li-Min; Zhou, Qiang; Zhang, Shi-Yong

2017-01-01

Background The natural outcomes of hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infections vary considerably among individuals The infection may heal naturally, or patients may succumb to chronic liver diseases, including chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. The mechanism is not fully understood. Objectives To evaluate the interaction among four single nucleotide polymorphisms (SNPs) and their influence on different clinical outcomes. Methods 277 individuals infected with HBV and/or HCV, including 81 patients with chronic hepatitis B and C, 122 asymptomatic HBV and/or HCV carriers and 74 controls who cleared HBV and HCV spontaneously, were involved in this study. The SNPs of four genes (rs2069762/−330 G/T of IL-2, rs2430561/+874A>T of IFN-γ, rs1800896/−1082G>A and rs1800872/−592C>A of IL-10 and rs2243250/−589C>T of IL-4) were analysed using restriction fragment length polymorphism-polymerase chain reaction or sequence-specific primer PCR. The gene–gene interactions were assessed using the multifactor-dimensionality reduction method. Results Interleukin (IL)-10-592 AC and IL-4-589 CC/CT showed a synergistic effect on liver inflammatory injury (p<0.01), whereas interferon (IFN)-γ+874  AA and IL-2-330 TT had a synergistic impact (p<0.05). IFN-γ+874  AA and IL-10-1082 AA had an antagonistic effect (p<0.01) on the clinical progression, including asymptomatic HBV and HCV carriers and chronic hepatitis. IL-2-330 TT and IL-10-1082 AA synergistically influenced the clinical outcome (p<0.05). IFN-γ+874 AA, IL-2-330 TT and IL-10-1082 AA interactively affected the clinical outcome including asymptomatic HBV and HCV carriers and chronic hepatitis (p<0.05). Conclusions Interactions among polymorphisms of IFN-γ+874 AA, IL-2-330 TT, IL-10-1082 AA, IL10-−592 AC and IL-4-589 CC/CT significantly influenced the clinical progression of the subjects with HBV and/or HCV infection. PMID:28838891

Interaction effects among IFN-γ+874, IL-2-330, IL-10-1082, IL-10-592 and IL-4-589 polymorphisms on the clinical progression of subjects infected with hepatitis B virus and/or hepatitis C virus: a retrospective nested case-control study.

PubMed

Gao, Qiu-Ju; Xie, Jia-Xin; Wang, Li-Min; Zhou, Qiang; Zhang, Shi-Yong

2017-08-23

The natural outcomes of hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infections vary considerably among individuals The infection may heal naturally, or patients may succumb to chronic liver diseases, including chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. The mechanism is not fully understood. To evaluate the interaction among four single nucleotide polymorphisms (SNPs) and their influence on different clinical outcomes. 277 individuals infected with HBV and/or HCV, including 81 patients with chronic hepatitis B and C, 122 asymptomatic HBV and/or HCV carriers and 74 controls who cleared HBV and HCV spontaneously, were involved in this study. The SNPs of four genes ( rs2069762/-330 G/T of IL-2 , rs2430561/+874A>T of IFN-γ, rs1800896/-1082G>A  and rs1800872/-592C>A of IL-10 and rs2243250/ -589 C>T of IL-4 ) were analysed using restriction fragment length polymorphism-polymerase chain reaction or sequence-specific primer PCR. The gene-gene interactions were assessed using the multifactor-dimensionality reduction method. Interleukin (IL)-10-592 AC and IL-4-589 CC/CT showed a synergistic effect on liver inflammatory injury (p<0.01), whereas interferon (IFN)-γ+874  AA and IL-2-330 TT had a synergistic impact (p<0.05). IFN-γ+874  AA and IL-10-1082 AA had an antagonistic effect (p<0.01) on the clinical progression, including asymptomatic HBV and HCV carriers and chronic hepatitis. IL-2-330 TT and IL-10-1082 AA synergistically influenced the clinical outcome (p<0.05). IFN-γ+874 AA, IL-2-330 TT and IL-10-1082 AA interactively affected the clinical outcome including asymptomatic HBV and HCV carriers and chronic hepatitis (p<0.05). Interactions among polymorphisms of IFN-γ+874 AA, IL-2-330 TT, IL-10-1082 AA, IL10--592 AC and IL-4-589 CC/CT significantly influenced the clinical progression of the subjects with HBV and/or HCV infection. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Effect of dietary citric acid on the performance and mineral metabolism of broiler.

PubMed

Islam, K M S; Schaeublin, H; Wenk, C; Wanner, M; Liesegang, A

2012-10-01

The objective of this study was to investigate the effect of dietary citric acid (CA) on the performance and mineral metabolism of broiler chicks. A total of 1720 Ross PM3 broiler chicks (days old) were randomly assigned to four groups (430 in each) and reared for a period of 35 days. The diets of groups 1, 2, 3 and 4 were supplemented with 0%, 0.25%, 0.75% or 1.25% CA by weight respectively. Feed and faeces samples were collected weekly and analysed for acid insoluble ash, calcium (Ca), phosphorus (P) and magnesium (Mg). The pH was measured in feed and faeces. At the age of 28 days, 10 birds from each group were slaughtered; tibiae were collected from each bird for the determination of bone mineral density, total ash, Ca, P, Mg and bone-breaking strength, and blood was collected for the measurement of osteocalcin, serum CrossLaps(®), Ca, P, Mg and 1,25(OH)(2)Vit-D in serum. After finishing the trial on day 37, all chicks were slaughtered by using the approved procedure. Birds that were fed CA diets were heavier (average body weights of 2030, 2079 and 2086 g in the 0.25%, 0.75% and 1.25% CA groups, respectively, relative to the control birds (1986 g). Feed conversion efficiency (weight gain in g per kg of feed intake) was also higher in birds of the CA-fed groups (582, 595 and 587 g/kg feed intake for 0.25%, 0.75% and 1.25% CA respectively), relative to the control birds (565 g/kg feed intake). The digestibility of Ca, P and Mg increased in the CA-fed groups, especially for the diets supplemented with 0.25% and 0.75% CA. Support for finding was also indicated in the results of the analysis of the tibia. At slaughter, the birds had higher carcass weights and higher graded carcasses in the groups that were fed the CA diets. The estimated profit margin was highest for birds fed the diet containing 0.25% CA. Birds of the 0.75% CA group were found to have the second highest estimated profit margin. Addition of CA up to a level of 1.25% of the diet increased performance, feed conversion efficiency, carcass weight and carcass quality, but only in numerical terms. The addition of CA up to 0.75% significantly increased the digestibility of macro minerals, bone ash content, bone mineral density and bone strength of the broiler chicks. It may, therefore, be concluded that the addition of 0.75% CA in a standard diet is suitable for growth, carcass traits, macromineral digestibility and bone mineral density of broiler chicks. © 2011 Blackwell Verlag GmbH.

Continuous Low-dose-rate Irradiation of Iodine-125 Seeds Inhibiting Perineural Invasion in Pancreatic Cancer.

PubMed

Lu, Zheng; Dong, Teng-Hui; Si, Pei-Ren; Shen, Wei; Bi, Yi-Liang; Min, Min; Chen, Xin; Liu, Yan

2016-10-20

Perineural invasion (PNI) is a histopathological characteristic of pancreatic cancer (PanCa). The aim of this study was to observe the treatment effect of continuous low-dose-rate (CLDR) irradiation to PNI and assess the PNI-related pain relief caused by iodine-125 ( 125 I) seed implantation. The in vitro PNI model established by co-culture with dorsal root ganglion (DRG) and cancer cells was interfered under 2 and 4 Gy of 125 I seeds CLDR irradiation. The orthotopic models of PNI were established, and 125 I seeds were implanted in tumor. The PNI-related molecules were analyzed. In 30 patients with panCa, the pain relief was assessed using a visual analog scale (VAS). Pain intensity was measured before and 1 week, 2 weeks, and 1, 3, and 6 months after 125 I seed implantation. The co-culture of DRG and PanCa cells could promote the growth of PanCa cells and DRG neurites. In co-culture groups, the increased number of DRG neurites and pancreatic cells in radiation group was significantly less. In orthotopic models, the PNI-positive rate in radiation and control group was 3/11 and 7/11; meanwhile, the degrees of PNI between radiation and control groups was significant difference (P < 0.05). At week 2, the mean VAS pain score in patients decreased by 50% and significantly improved than the score at baseline (P < 0.05). The pain scores were lower in all patients, and the pain-relieving effect was retained about 3 months. The CLDR irradiation could inhibit PNI of PanCa with the value of further study. The CLDR irradiation could do great favor in preventing local recurrence and alleviating pain.

Transcriptional effects of 1,25 dihydroxyvitamin D(3) physiological and supra-physiological concentrations in breast cancer organotypic culture.

PubMed

Milani, Cintia; Katayama, Maria Lucia Hirata; de Lyra, Eduardo Carneiro; Welsh, JoEllen; Campos, Laura Tojeiro; Brentani, M Mitzi; Maciel, Maria do Socorro; Roela, Rosimeire Aparecida; del Valle, Paulo Roberto; Góes, João Carlos Guedes Sampaio; Nonogaki, Suely; Tamura, Rodrigo Esaki; Folgueira, Maria Aparecida Azevedo Koike

2013-03-15

Vitamin D transcriptional effects were linked to tumor growth control, however, the hormone targets were determined in cell cultures exposed to supra physiological concentrations of 1,25(OH)(2)D(3) (50-100nM). Our aim was to evaluate the transcriptional effects of 1,25(OH)(2)D(3) in a more physiological model of breast cancer, consisting of fresh tumor slices exposed to 1,25(OH)(2)D(3) at concentrations that can be attained in vivo. Tumor samples from post-menopausal breast cancer patients were sliced and cultured for 24 hours with or without 1,25(OH)(2)D(3) 0.5nM or 100nM. Gene expression was analyzed by microarray (SAM paired analysis, FDR≤0.1) or RT-qPCR (p≤0.05, Friedman/Wilcoxon test). Expression of candidate genes was then evaluated in mammary epithelial/breast cancer lineages and cancer associated fibroblasts (CAFs), exposed or not to 1,25(OH)(2)D(3) 0.5nM, using RT-qPCR, western blot or immunocytochemistry. 1,25(OH)(2)D(3) 0.5nM or 100nM effects were evaluated in five tumor samples by microarray and seven and 136 genes, respectively, were up-regulated. There was an enrichment of genes containing transcription factor binding sites for the vitamin D receptor (VDR) in samples exposed to 1,25(OH)(2)D(3) near physiological concentration. Genes up-modulated by both 1,25(OH)(2)D(3) concentrations were CYP24A1, DPP4, CA2, EFTUD1, TKTL1, KCNK3. Expression of candidate genes was subsequently evaluated in another 16 samples by RT-qPCR and up-regulation of CYP24A1, DPP4 and CA2 by 1,25(OH)(2)D(3) was confirmed. To evaluate whether the transcripitonal targets of 1,25(OH)(2)D(3) 0.5nM were restricted to the epithelial or stromal compartments, gene expression was examined in HB4A, C5.4, SKBR3, MDA-MB231, MCF-7 lineages and CAFs, using RT-qPCR. In epithelial cells, there was a clear induction of CYP24A1, CA2, CD14 and IL1RL1. In fibroblasts, in addition to CYP24A1 induction, there was a trend towards up-regulation of CA2, IL1RL1, and DPP4. A higher protein expression of CD14 in epithelial cells and CA2 and DPP4 in CAFs exposed to 1,25(OH)(2)D(3) 0.5nM was detected. In breast cancer specimens a short period of 1,25(OH)(2)D(3) exposure at near physiological concentration modestly activates the hormone transcriptional pathway. Induction of CYP24A1, CA2, DPP4, IL1RL1 expression appears to reflect 1,25(OH)(2)D(3) effects in epithelial as well as stromal cells, however, induction of CD14 expression is likely restricted to the epithelial compartment.

Transcriptional effects of 1,25 dihydroxyvitamin D3 physiological and supra-physiological concentrations in breast cancer organotypic culture

PubMed Central

2013-01-01

Background Vitamin D transcriptional effects were linked to tumor growth control, however, the hormone targets were determined in cell cultures exposed to supra physiological concentrations of 1,25(OH)2D3 (50-100nM). Our aim was to evaluate the transcriptional effects of 1,25(OH)2D3 in a more physiological model of breast cancer, consisting of fresh tumor slices exposed to 1,25(OH)2D3 at concentrations that can be attained in vivo. Methods Tumor samples from post-menopausal breast cancer patients were sliced and cultured for 24 hours with or without 1,25(OH)2D3 0.5nM or 100nM. Gene expression was analyzed by microarray (SAM paired analysis, FDR≤0.1) or RT-qPCR (p≤0.05, Friedman/Wilcoxon test). Expression of candidate genes was then evaluated in mammary epithelial/breast cancer lineages and cancer associated fibroblasts (CAFs), exposed or not to 1,25(OH)2D3 0.5nM, using RT-qPCR, western blot or immunocytochemistry. Results 1,25(OH)2D3 0.5nM or 100nM effects were evaluated in five tumor samples by microarray and seven and 136 genes, respectively, were up-regulated. There was an enrichment of genes containing transcription factor binding sites for the vitamin D receptor (VDR) in samples exposed to 1,25(OH)2D3 near physiological concentration. Genes up-modulated by both 1,25(OH)2D3 concentrations were CYP24A1, DPP4, CA2, EFTUD1, TKTL1, KCNK3. Expression of candidate genes was subsequently evaluated in another 16 samples by RT-qPCR and up-regulation of CYP24A1, DPP4 and CA2 by 1,25(OH)2D3 was confirmed. To evaluate whether the transcripitonal targets of 1,25(OH)2D3 0.5nM were restricted to the epithelial or stromal compartments, gene expression was examined in HB4A, C5.4, SKBR3, MDA-MB231, MCF-7 lineages and CAFs, using RT-qPCR. In epithelial cells, there was a clear induction of CYP24A1, CA2, CD14 and IL1RL1. In fibroblasts, in addition to CYP24A1 induction, there was a trend towards up-regulation of CA2, IL1RL1, and DPP4. A higher protein expression of CD14 in epithelial cells and CA2 and DPP4 in CAFs exposed to 1,25(OH)2D3 0.5nM was detected. Conclusions In breast cancer specimens a short period of 1,25(OH)2D3 exposure at near physiological concentration modestly activates the hormone transcriptional pathway. Induction of CYP24A1, CA2, DPP4, IL1RL1 expression appears to reflect 1,25(OH)2D3 effects in epithelial as well as stromal cells, however, induction of CD14 expression is likely restricted to the epithelial compartment. PMID:23497279

Dynamic Cerebral Autoregulation in Asymptomatic Patients With Unilateral Middle Cerebral Artery Stenosis

PubMed Central

Wang, Shuang; Guo, Zhen-Ni; Xing, Yingqi; Ma, Hongyin; Jin, Hang; Liu, Jia; Yang, Yi

2015-01-01

Abstract The aim of the study was to assess the capacity of dynamic cerebral autoregulation (dCA) in asymptomatic patients with unilateral middle cerebral artery (MCA) stenosis. Fifty-seven patients with asymptomatic mild, moderate, and severe unilateral MCA stenosis and 8 patients with symptomatic severe unilateral MCA stenosis diagnosed by transcranial Doppler were enrolled. Twenty-four healthy volunteers served as controls. The noninvasive continuous cerebral blood flow velocity and arterial blood pressure were recorded simultaneously from each subject in the supine position. Transfer function analysis was applied to determine the autoregulatory parameters (phase difference [PD] and gain). The PD values in the severe stenosis groups were significantly lower than those of the control group (60.71 ± 18.63°), the asymptomatic severe stenosis group was impaired ipsilaterally (28.94 ± 27.43°, P < 0.001), and the symptomatic severe stenosis group was impaired bilaterally (13.74 ± 19.21°, P < 0.001; 19.68 ± 14.50°, P = 0.006, respectively). The PD values in the mild and moderate stenosis groups were not significantly different than the controls (44.49 ± 27.93°; 48.65 ± 25.49°, respectively). The gain values in the mild and moderate groups were higher than in the controls (1.00 ± 0.58 cm/s/mm Hg vs 0.86 ± 0.34 cm/s/mm Hg, and 1.20 ± 0.59 cm/s/mm Hg vs 0.86 ± 0.34 cm/s/mm Hg, respectively). The gain values in the severe stenosis groups were significantly lower than that in the control group: the asymptomatic severe stenosis group was lower bilaterally (0.56 ± 0.32 cm/s/mm Hg, P = 0.003; 0.60 ± 0.32 cm/s/mm Hg, P < 0.05, respectively), whereas the symptomatic severe group was lower unilaterally (on the contralateral side) (0.53 ± 0.43 cm/s/mm Hg, P < 0.05). In asymptomatic patients with unilateral MCA stenosis, only the dCA of the severe stenosis was ipsilaterally impaired. Acute stroke may aggravate the impaired dCA and even spread contralaterally. PMID:26717363

Research progress of asymptomatic bacteriuria before arthroplasty: A systematic review.

PubMed

Zhang, Qingyu; Liu, Lihua; Sun, Wei; Gao, Fuqiang; Cheng, Liming; Li, Zirong

2018-02-01

A high prevalence of asymptomatic bacteriuria exists in patients prior to arthroplasty, and urinary tract infection is considered to be a source of postoperative superficial wound and prosthetic joint infections. There is no consensus whether to screen for and treat asymptomatic bacteriuria before arthroplasty. To summarize the association between asymptomatic bacteriuria and complications after arthroplasty and to evaluate the clinical benefits of treating asymptomatic bacteriuria prior to arthroplasty. We systematically searched PubMed, Embase, and the Cochrane Library to retrieve potentially eligible articles. By screening the titles and abstracts of retrieved records and then reading the full texts of the remaining papers, we finally included 8 English-language articles in this systematic review. Asymptomatic bacteriuria prior to arthroplasty is significantly associated with an increased occurrence of postoperative prosthetic joint and superficial wound infections. However, there is little evidence for direct or hematogenous seeding of urinary infections, and treating asymptomatic bacteriuria before arthroplasty did not decrease the incidence of postoperative infectious complications. Asymptomatic bacteriuria is not a contraindication for arthroplasty, and the practice of routine preoperative screening for and treatment of asymptomatic bacteriuria should not be continued.

Tjalma syndrome (pseudo-pseudo Meigs') as initial manifestation of juvenile-onset systemic lupus erythematosus.

PubMed

Torres Jiménez, Alfonso Ragnar; Solís-Vallejo, Eunice; Céspedes-Cruz, Adriana Ivonne; Zeferino Cruz, Maritza; Rojas-Curiel, Edna Zoraida; Sánchez-Jara, Berenice

2017-05-15

Tjalma syndrome or pseudo-pseudo Meigs' syndrome is a clinical condition characterized by pleural effusion, ascites and elevated CA-125 with no associated benign or malignant ovarian tumor in a patient with systemic lupus erythematosus (SLE). Tjalma described the first case of a patient with SLE, pleural effusion, ascites and elevated CA-125. We report the first case in a 14-year old patient who presented with ascites and pleural effusion refractory to treatment and elevated CA-125, in the absence of an ovarian tumor, that warranted aggressive management. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Integrated Microfluidic Lectin Barcode Platform for High-Performance Focused Glycomic Profiling

NASA Astrophysics Data System (ADS)

Shang, Yuqin; Zeng, Yun; Zeng, Yong

2016-02-01

Protein glycosylation is one of the key processes that play essential roles in biological functions and dysfunctions. However, progress in glycomics has considerably lagged behind genomics and proteomics, due in part to the enormous challenges in analysis of glycans. Here we present a new integrated and automated microfluidic lectin barcode platform to substantially improve the performance of lectin array for focused glycomic profiling. The chip design and flow control were optimized to promote the lectin-glycan binding kinetics and speed of lectin microarray. Moreover, we established an on-chip lectin assay which employs a very simple blocking method to effectively suppress the undesired background due to lectin binding of antibodies. Using this technology, we demonstrated focused differential profiling of tissue-specific glycosylation changes of a biomarker, CA125 protein purified from ovarian cancer cell line and different tissues from ovarian cancer patients in a fast, reproducible, and high-throughput fashion. Highly sensitive CA125 detection was also demonstrated with a detection limit much lower than the clinical cutoff value for cancer diagnosis. This microfluidic platform holds the potential to integrate with sample preparation functions to construct a fully integrated “sample-to-answer” microsystem for focused differential glycomic analysis. Thus, our technology should present a powerful tool in support of rapid advance in glycobiology and glyco-biomarker development.

Integrated Microfluidic Lectin Barcode Platform for High-Performance Focused Glycomic Profiling

PubMed Central

Shang, Yuqin; Zeng, Yun; Zeng, Yong

2016-01-01

Protein glycosylation is one of the key processes that play essential roles in biological functions and dysfunctions. However, progress in glycomics has considerably lagged behind genomics and proteomics, due in part to the enormous challenges in analysis of glycans. Here we present a new integrated and automated microfluidic lectin barcode platform to substantially improve the performance of lectin array for focused glycomic profiling. The chip design and flow control were optimized to promote the lectin-glycan binding kinetics and speed of lectin microarray. Moreover, we established an on-chip lectin assay which employs a very simple blocking method to effectively suppress the undesired background due to lectin binding of antibodies. Using this technology, we demonstrated focused differential profiling of tissue-specific glycosylation changes of a biomarker, CA125 protein purified from ovarian cancer cell line and different tissues from ovarian cancer patients in a fast, reproducible, and high-throughput fashion. Highly sensitive CA125 detection was also demonstrated with a detection limit much lower than the clinical cutoff value for cancer diagnosis. This microfluidic platform holds the potential to integrate with sample preparation functions to construct a fully integrated “sample-to-answer” microsystem for focused differential glycomic analysis. Thus, our technology should present a powerful tool in support of rapid advance in glycobiology and glyco-biomarker development. PMID:26831207

Calcium and the heat-shock response in the human monocytic line U-937.

PubMed

Kantengwa, S; Capponi, A M; Bonventre, J V; Polla, B S

1990-07-01

In the human monocytic line U-937, 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] increases cytosolic free calcium concentration ([Ca2+]i). 1,25-(OH)2D3 also enhances the synthesis of heat-shock proteins (HSPs) when U-937 cells are exposed to elevated temperatures. To establish whether these two effects of 1,25-(OH)2D3 are related, we examined the effects of calcium on the heat-shock (HS) response, as well as the influence of 1,25-(OH)2D3 on this system. The equilibrium dissociation constant (Kd) of the fluorescent probe used to measure [Ca2+]i, fura-2, at 37 and 45 degrees C was found to be 191 and 234 nM, respectively. Exposure of U-937 cells to 45 degrees C did not increase [Ca2+]i under conditions in which active efflux of the dye was prevented by the organic anion transport inhibitor probenecid (1 mM). In cells preincubated in calcium-free medium, with subsequent addition of 4 mM EGTA before HS, or exposed to the calmodulin antagonist N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide (W-7), the increase in HSPs synthesis was not affected. Cell viability, assessed by [3H]thymidine uptake, was not different between cells exposed to HS in calcium-containing or calcium-free media. Moreover, the effects of 1,25-(OH)2D3 on the HS response were also observed in a calcium-depleted medium, indicating that the effects of 1,25-(OH)2D3 on HSP synthesis were not mediated by [Ca2+]i.

Ovarian Cyst Enlargement in a 14 Year Old Female with Persistent Ascities, Severe Hypothyroidism and Elevated Serum CA-125 Level.

PubMed

Motamed, F; Eftekhari, K; Kiani, M A; Rabbani, A

2012-06-01

A 14 year old female complained of abdominal pain and distention with vomiting. The physical exam showed thyroid enlargement and ascites. The imaging evaluation demonstrated a large ovarian cyst. Laboratory tests depicted hypothyroidism and marked elevation of Carbohydrate antigen 125 (CA-125) levels. As the bone age was 10 years, more retarded than the chronological age, Van Wyk and Grumbach syndrome was suspected. Treatment with thyroid hormone was initiated and the condition improved dramatically with disappearance of symptoms and signs 5 weeks later.

Asymptomatic petechial eruption on the lower legs.

PubMed

Mendese, Gary; Grande, Donald

2013-09-01

The authors report an unusual case of Rocky Mountain spotted fever that presented as an asymptomatic petechial eruption on the lower legs. Rocky Mountain spotted fever is rare in New England and, as such, is typically not on the differential diagnosis when presented with such patients. What began as an asymptomatic eruption progressed to more classic signs of the disease, including a positive Rocky Mountain spotted fever titer. The patient was successfully treated with doxycydine and within a short period of time, was completely back at baseline.

Prognostic Relevance of the Expression of CA IX, GLUT-1, and VEGF in Ovarian Epithelial Cancers

PubMed Central

Kim, Kyungbin; Park, Won Young; Kim, Jee Yeon; Sol, Mee Young; Shin, Dong Hun; Park, Do Youn; Lee, Chang Hun; Lee, Jeong Hee

2012-01-01

Background Tumor hypoxia is associated with malignant progression and treatment resistance. Hypoxia-related factors, such as carbonic anhydrase IX (CA IX), glucose transporter-1 (GLUT-1), and vascular endothelial growth factor (VEGF) permit tumor cell adaptation to hypoxia. We attempted to elucidate the correlation of these markers with variable clinicopathological factors and overall prognosis. Methods Immunohistochemistry for CA IX, GLUT-1, and VEGF was performed on formalin-fixed, paraffin-embedded tissues from 125 cases of ovarian epithelial cancer (OEC). Results CA IX expression was significantly associated with an endometrioid and mucinous histology, nuclear grade, tumor necrosis, and mitosis. GLUT-1 expression was associated with tumor necrosis and mitosis. VEGF expression was correlated only with disease recurrence. Expression of each marker was not significant in terms of overall survival in OECs; however, there was a significant correlation between poor overall survival rate and high coexpression of these markers. Conclusions The present study suggests that it is questionable whether CA IX, GLUT-1, or VEGF can be used alone as independent prognostic factors in OECs. Using at least two markers helps to predict patient outcomes in total OECs. Moreover, the inhibition of two target gene combinations might prove to be a novel anticancer therapy. PMID:23323103

Indicators of inappropriate tumour marker use through the mining of electronic health records.

PubMed

Gion, Massimo; Cardinali, Giulia; Trevisiol, Chiara; Zappa, Marco; Rainato, Giulia; Fabricio, Aline S C

2017-08-01

Although the issue of monitoring appropriateness of tumour markers (TMs) request in outpatients remains crucial, proper indicators are still demanding. The present study developed and explored indicators of inappropriate TM ordering in outpatients through the data mining of electronic health records (EHRs). Carcinoembryonic antigen (CEA), alfa-fetoprotein (AFP), carbohydrate antigen (CA)125, CA15.3, CA19.9, and prostate-specific antigen (PSA) ordered in outpatients during a year were examined by mining EHRs of a Local Health Authority in Italy. Evidence-based criteria were used to develop performance indicators. Demographic and clinical information associated with TM orders were examined. A total of 80 813 TMs were ordered in 52 536 outpatients (1.54 markers/patient). Indicators related to disease codes, gender, age, and TM repetitions were developed, and their application showed that (1) CA15.3 and CEA are prevalently requested in patients with cancer (79.2% and 65.6%) whereas the other TMs are largely requested also in patients without cancer; (2) requests of PSA in women and of CA125 or CA15.3 in men are negligible; (3) although requests in people older than 80 years are relevant (16.4% of total), the highest rate of request of all markers occurs in patients aged 40 to 79 years; (4) CA15.3 and CEA are mainly requested in cancer cases between 50 and 79 years and AFP, CA19.9, and CA125 in those between 60 and 69 years; (5) <50% of PSA orders are associated with cancer code for all age intervals; and (6) multiple repetitions of AFP, CA125, CA15.3, CA19.9, and CEA are prevalent in cancer patients or benign diseases to which TMs are appropriate, whereas PSA repetitions occur mainly in patients without cancer. The developed indicators resulted suitable to monitor TM overordering in outpatients through the mining of EHRs. The present study is a first approach towards the use of big-data mining for TM appropriateness evaluation purposes. © 2017 John Wiley & Sons, Ltd.

Development and Validation of a Protein Based Signature for the Detection of Ovarian Cancer

PubMed Central

Kim, Kyongjin; Visintin, Irene; Alvero, Ayesha B.; Mor, Gil

2009-01-01

In order to overcome the significant mortality associated with ovarian cancer, a highly sensitive and specific screening test is urgently needed. CA125 is used to monitor response to chemotherapy, detect recurrence and detect late stage ovarian cancer. However, CA-125 alone or in combination with ultrasonography has not been adequate for early detection of ovarian cancer. Here we discuss our recent report of a novel multiplex assay that uses a panel of six serum biomarkers:Leptin, Prolactin, Osteopontin, Insulin-Like Growth Factor II, Macrophage Inhibitory Factor and CA-125. The combination of these six proteins yielded 95.3 % sensitivity and 99.4% specificity. The application of this test in the clinical context and the most appropriate population which could benefit of the test is discussed. PMID:19389550

Transient Asymptomatic Pulmonary Opacities Occurring during Osimertinib Treatment.

PubMed

Noonan, Sinead A; Sachs, Peter B; Camidge, D Ross

2016-12-01

Osimertinib is an EGFR inhibitor licensed for the treatment of EGFR-mutant, T790M-positive NSCLC. Previously unreported, frequent transient asymptomatic pulmonary opacities were noted in patients during osimertinib therapy at the University of Colorado. Computed tomography imaging and clinical notes on patients with NSCLC who had been treated with osimertinib at the University of Colorado were retrospectively reviewed. Transient asymptomatic pulmonary opacities developed in seven of 20 patients (35%) while they were receiving osimertinib. The radiological patterns seen included ground-glass opacities with or without nodular consolidation. The median time to development of the first lesion was 8.7 weeks (range 1.6-43 weeks), the median time to resolution during continued osimertinib was 6 weeks (range 1-11 weeks). Transient asymptomatic pulmonary opacities may be a previously unrecognized, benign feature associated with osimertinib therapy that may be mistaken for isolated pulmonary progression or the beginning of more severe pneumonitis. If new-onset pulmonary lesions, especially those associated with ground-glass appearances, are asymptomatic and localized and there is no evidence of disease progression elsewhere, it may be reasonable to continue treatment with osimertinib and monitor the lesions for resolution. Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Divergent cellular responses during asymptomatic subclinical and clinical states of disease in cows naturally infected with Mycobacterium avium subsp. paratuberculosis

USDA-ARS?s Scientific Manuscript database

Infection of the host with Mycobacterium avium subsp. paratuberculosis (MAP) results in a chronic and progressive enteritis that traverses both subclinical and clinical stages. The mechanism(s) for the shift from asymptomatic subclinical disease state to advanced clinical disease are not fully under...

Recovery of antigen-specific T cell responses from dogs infected with Leishmania (L.) infantum by use of vaccine associated TLR-agonist adjuvant.

PubMed

Schaut, Robert G; Grinnage-Pulley, Tara L; Esch, Kevin J; Toepp, Angela J; Duthie, Malcolm S; Howard, Randall F; Reed, Steven G; Petersen, Christine A

2016-10-17

Visceral leishmaniasis (VL), caused by infection with the obligate intracellular protozoan parasite Leishmania infantum, is a fatal disease of dogs and humans. Protection against VL requires a T helper 1 (Th1) skewed CD4 + T response, but despite this knowledge, there are currently no approved-to-market vaccines for humans and only three veterinary-use vaccines globally. As VL progresses from asymptomatic to symptomatic, L. infantum-specific interferon gamma (IFNγ) driven-Th1 responses become dampened and a state of immune exhaustion established. T cell exhaustion and other immunoregulatory processes, starting during asymptomatic disease, are likely to hinder vaccine-induced responses if vaccine is administered to infected, but asymptomatic and seronegative, individuals. In this study we evaluated how immune exhaustion, shown previously by our group to worsen in concert with VL progression, effected the capacity of vaccine candidate antigen/toll-like receptor (TLR) agonist combinations to promote protective CD4 + T cell responses during progressive VL. In conjunction with Th1 responses, we also evaluated concomitant stimulation of immune-balanced IL-10 regulatory cytokine production by these vaccine products in progressive VL canine T cells. Vaccine antigen L111f in combination with TLR agonists significantly recovered CD4 + T cell IFNγ intracellular production in T cells from asymptomatic VL dogs. Vaccine antigen NS with TLR agonists significantly recovered CD4 + T cell production in both endemic control and VL dogs. Combinations of TLR agonists and vaccine antigens overcame L. infantum induced cellular exhaustion, allowing robust Th1 CD4 + T cell responses from symptomatic dogs that previously had dampened responses to antigen alone. Antigen-agonist adjuvants can be utilized to promote more robust vaccine responses from infected hosts in endemic areas where vaccination of asymptomatic, L. infantum-infected animals is likely. Copyright © 2016. Published by Elsevier Ltd.

Research progress of asymptomatic bacteriuria before arthroplasty

PubMed Central

Zhang, Qingyu; Liu, Lihua; Sun, Wei; Gao, Fuqiang; Cheng, Liming; Li, Zirong

2018-01-01

Abstract Background: A high prevalence of asymptomatic bacteriuria exists in patients prior to arthroplasty, and urinary tract infection is considered to be a source of postoperative superficial wound and prosthetic joint infections. There is no consensus whether to screen for and treat asymptomatic bacteriuria before arthroplasty. Objective: To summarize the association between asymptomatic bacteriuria and complications after arthroplasty and to evaluate the clinical benefits of treating asymptomatic bacteriuria prior to arthroplasty. Method: We systematically searched PubMed, Embase, and the Cochrane Library to retrieve potentially eligible articles. By screening the titles and abstracts of retrieved records and then reading the full texts of the remaining papers, we finally included 8 English-language articles in this systematic review. Results: Asymptomatic bacteriuria prior to arthroplasty is significantly associated with an increased occurrence of postoperative prosthetic joint and superficial wound infections. However, there is little evidence for direct or hematogenous seeding of urinary infections, and treating asymptomatic bacteriuria before arthroplasty did not decrease the incidence of postoperative infectious complications. Conclusion: Asymptomatic bacteriuria is not a contraindication for arthroplasty, and the practice of routine preoperative screening for and treatment of asymptomatic bacteriuria should not be continued. PMID:29443741

Synaptosomal binding of 125I-labelled daboiatoxin, a new PLA2 neurotoxin from the venom of Daboia russelli siamensis.

PubMed

Maung-Maung-Thwin; Gopalakrishnakone, P; Yuen, R; Tan, C H

1996-02-01

Daboiatoxin (DbTx), the PLA2 neurotoxin from Daboia russelli siamensis venom, was shown to bind specifically and saturably to rat cerebrocortical synaptosomes and synaptic membrane fragments. Two families of binding sites were detected by equilibrium binding analysis in the presence and absence of Ca2+. Scatchard analysis of biphasic plateaus revealed Kdl 5 nM and Bmax1, 6 pmoles/mg protein, and Kd2 80 nM and Bmax2 20 pmoles/mg protein, respectively, for the high- and low-affinity binding sites. The binding of 125I-DbTx to synaptosomes did not show marked dependence on Ca2+, Mg2+, Co2+ and Sr2+. Native DbTx was the only strong competitor to 125I-DbTx synaptosomal binding (IC50 12.5 nM, KI 5.5 nM). Two other crotalid PLA2 neurotoxins, crotoxin CB and mojave toxin basic subunit, and nontoxic C. Atrox PLA2 enzyme, were relatively weaker inhibitors, while two viperid PLA2 neurotoxins, ammodytoxin A and VRV PL V, were very weak inhibitors. Crotoxin CA was a poor inhibitor even at microM concentrations, whereas no inhibitory effect at all was observed with crotoxin CACB, ammodytoxin C, VRV PL VIIIa, taipoxin, beta-bungarotoxin, or with PLA2 enzymes from N. naja venom, E. schistosa venom, bee venom and porcine pancreas. All other pharmacologically active ligands examined (epinephrine, norepinephrine, histamine, choline, dopamine, serotonin, GABA, naloxone, WB-4101, atropine, hexamethonium and alpha-bun-garotoxin) also failed to interfere with 125I-DbTx binding. As those competitors that showed partial inhibition were effective only at microM concentration range compared to the Kd (5 nM) of 125I-DbTx synaptosomal binding, DbTx could well recognize a different neuronal binding site. Rabbit anti-DbTx polyclonal antisera completely blocked the specific binding. When a range of Ca2+ and K+ channels modulators were examined, Ca2+ channel blockers (omega-conotoxins GVIA and MVIIC, taicatoxin, calciseptine and nitrendiprene) did not affect the binding even at high concentrations, while charybdotoxin was the only K+ channel effector that could partially displace 125I-DbTx synaptosomal binding amongst the K+ channel blockers tested (apamin, dendrotoxin-I, iberiotoxin, MCD-peptide, 4-aminopyridine and tetraethylammonium), suggesting that neither K+ nor Ca2+ channels are associated with DbTx binding sites.

Early Detection of Ovarian Cancer using the Risk of Ovarian Cancer Algorithm with Frequent CA125 Testing in Women at Increased Familial Risk - Combined Results from Two Screening Trials.

PubMed

Skates, Steven J; Greene, Mark H; Buys, Saundra S; Mai, Phuong L; Brown, Powel; Piedmonte, Marion; Rodriguez, Gustavo; Schorge, John O; Sherman, Mark; Daly, Mary B; Rutherford, Thomas; Brewster, Wendy R; O'Malley, David M; Partridge, Edward; Boggess, John; Drescher, Charles W; Isaacs, Claudine; Berchuck, Andrew; Domchek, Susan; Davidson, Susan A; Edwards, Robert; Elg, Steven A; Wakeley, Katie; Phillips, Kelly-Anne; Armstrong, Deborah; Horowitz, Ira; Fabian, Carol J; Walker, Joan; Sluss, Patrick M; Welch, William; Minasian, Lori; Horick, Nora K; Kasten, Carol H; Nayfield, Susan; Alberts, David; Finkelstein, Dianne M; Lu, Karen H

2017-07-15

Purpose: Women at familial/genetic ovarian cancer risk often undergo screening despite unproven efficacy. Research suggests each woman has her own CA125 baseline; significant increases above this level may identify cancers earlier than standard 6- to 12-monthly CA125 > 35 U/mL. Experimental Design: Data from prospective Cancer Genetics Network and Gynecologic Oncology Group trials, which screened 3,692 women (13,080 woman-screening years) with a strong breast/ovarian cancer family history or BRCA1/2 mutations, were combined to assess a novel screening strategy. Specifically, serum CA125 q3 months, evaluated using a risk of ovarian cancer algorithm (ROCA), detected significant increases above each subject's baseline, which triggered transvaginal ultrasound. Specificity and positive predictive value (PPV) were compared with levels derived from general population screening (specificity 90%, PPV 10%), and stage-at-detection was compared with historical high-risk controls. Results: Specificity for ultrasound referral was 92% versus 90% ( P = 0.0001), and PPV was 4.6% versus 10% ( P > 0.10). Eighteen of 19 malignant ovarian neoplasms [prevalent = 4, incident = 6, risk-reducing salpingo-oophorectomy (RRSO) = 9] were detected via screening or RRSO. Among incident cases (which best reflect long-term screening performance), three of six invasive cancers were early-stage (I/II; 50% vs. 10% historical BRCA1 controls; P = 0.016). Six of nine RRSO-related cases were stage I. ROCA flagged three of six (50%) incident cases before CA125 exceeded 35 U/mL. Eight of nine patients with stages 0/I/II ovarian cancer were alive at last follow-up (median 6 years). Conclusions: For screened women at familial/genetic ovarian cancer risk, ROCA q3 months had better early-stage sensitivity at high specificity, and low yet possibly acceptable PPV compared with CA125 > 35 U/mL q6/q12 months, warranting further larger cohort evaluation. Clin Cancer Res; 23(14); 3628-37. ©2017 AACR . ©2017 American Association for Cancer Research.

Role of 18F-FDG PET/CT in diagnosing peritoneal carcinomatosis in the restaging of patient with ovarian cancer as compared to contrast enhanced CT and tumor marker Ca-125.

PubMed

Rubini, G; Altini, C; Notaristefano, A; Merenda, N; Rubini, D; Ianora, A A Stabile; Asabella, A Niccoli

2014-01-01

To investigate the role of whole-body fluorine-18-2-deoxy-2-fluoro-d-glucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) in the identification of peritoneal carcinomatosis in patients with ovarian cancer (OC). Seventy-nine patients with histologically proven stages III-IV OC who underwent (18)F-FDG PET/CT were studied retrospectively. We considered group A as 51 patients who also underwent computed-tomography with contrast-enhancement (CECT), and group B as 35 patients who had also been tested for biomarker Ca-125. Sensitivity, specificity, accuracy, positive predictive values (PPV) and negative predictive values (NPV) of (18)F-FDG PET/CT as compared to CECT and to Ca-125 were evaluated. (18)F-FDG PET/CT' sensitivity, specificity, accuracy, PPV and NPV for all 79 patients were: 85%, 92.31%, 88.61%, 91.89% and 85.71%, respectively. (18)F-FDG PET/CT sensitivity in group A was 78.6%, while it was 53.6% for CECT. (18)F-FDG PET/CT specificity, calculated in the same group, was 91.3%, while that of CECT was 60.9% (statistically significant difference, McNemar 4, P=0.039). Accuracy was 84.3% and 56.9%, respectively. (18)F-FDG PET/CT' sensitivity in group B was 86.4%, while that of Ca-125 was 81.8% (no statistical difference, McNemar 0, P=1). (18)F-FDG PET/CT specificity in group B was 84.6% while that of Ca-125 was 38.5% (clear but not statistically significant difference, McNemar 3.12, P=0.070). Accuracy calculated in the same group was 85.7% for (18)F-FDG PET/CT and 65.7% for Ca-125. (18)F-FDG PET/CT is a useful diagnostic tool when peritoneal biopsy cannot be performed and it can better select those who are candidates for adjuvant chemotherapy. Copyright © 2013 Elsevier España, S.L. and SEMNIM. All rights reserved.

Urinary Tract Infections and Asymptomatic Bacteriuria in Renal Transplant Recipients

PubMed Central

Yacoub, Rabi; Akl, Nader Kassis

2011-01-01

Asymptomatic bacteriuria and urinary tract infection are common complications after kidney transplantation. In this population, if urinary tract infection occurred in the first six months post procedure, it carries a grave impact on both graft and patient survival. Renal transplant recipients with urinary tract infection are often clinically asymptomatic as a consequence of immunosuppression. Urinary tract infection, however, may progress to acute pyelonephritis, bacteremia and the full blown picture of urosepsis. PubMed and Cochrane databases were searched. The purpose of this review is to discuss the screening and treatment of urinary tract infection and asymptomatic bacteriuria in renal transplant recipients and to evaluate the guidelines on the basis of a review of published evidence. PMID:22224004

Proteomic biomarkers apolipoprotein A1, truncated transthyretin and connective tissue activating protein III enhance the sensitivity of CA125 for detecting early stage epithelial ovarian cancer.

PubMed

Clarke, Charlotte H; Yip, Christine; Badgwell, Donna; Fung, Eric T; Coombes, Kevin R; Zhang, Zhen; Lu, Karen H; Bast, Robert C

2011-09-01

The low prevalence of ovarian cancer demands both high sensitivity (>75%) and specificity (99.6%) to achieve a positive predictive value of 10% for successful early detection. Utilizing a two stage strategy where serum marker(s) prompt the performance of transvaginal sonography (TVS) in a limited number (2%) of women could reduce the requisite specificity for serum markers to 98%. We have attempted to improve sensitivity by combining CA125 with proteomic markers. Sera from 41 patients with early stage (I/II) and 51 with late stage (III/IV) epithelial ovarian cancer, 40 with benign disease and 99 healthy individuals, were analyzed to measure 7 proteins [Apolipoprotein A1 (Apo-A1), truncated transthyretin (TT), transferrin, hepcidin, ß-2-microglobulin (ß2M), Connective Tissue Activating Protein III (CTAPIII), and Inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4)]. Statistical models were fit by logistic regression, followed by optimization of factors retained in the models determined by optimizing the Akaike Information Criterion. A validation set included 136 stage I ovarian cancers, 140 benign pelvic masses and 174 healthy controls. In a training set analysis, the 3 most effective biomarkers (Apo-A1, TT and CTAPIII) exhibited 54% sensitivity at 98% specificity, CA125 alone produced 68% sensitivity and the combination increased sensitivity to 88%. In a validation set, the marker panel plus CA125 produced a sensitivity of 84% at 98% specificity (P=0.015, McNemar's test). Combining a panel of proteomic markers with CA125 could provide a first step in a sequential two-stage strategy with TVS for early detection of ovarian cancer. Copyright © 2011. Published by Elsevier Inc.

Proteomic Biomarkers Apolipoprotein A1, Truncated Transthyretin and Connective Tissue Activating Protein III Enhance the Sensitivity of CA125 for Detecting Early Stage Epithelial Ovarian Cancer

PubMed Central

Clarke, Charlotte H.; Yip, Christine; Badgwell, Donna; Fung, Eric T.; Coombes, Kevin R.; Zhang, Zhen; Lu, Karen H.; Bast, Robert C.

2011-01-01

Objective The low prevalence of ovarian cancer demands both high sensitivity (>75%) and specificity (99.6%) to achieve a positive predictive value of 10% for successful early detection. Utilizing a two stage strategy where serum marker(s) prompt the performance of transvaginal sonography (TVS) in a limited number (2%) of women could reduce the requisite specificity for serum markers to 98%. We have attempted to improve sensitivity by combining CA125 with proteomic markers. Methods Sera from 41 patients with early stage (I/II) and 51 with late stage (III/IV) epithelial ovarian cancer, 40 with benign disease and 99 healthy individuals, were analyzed to measure 7 proteins [Apolipoprotein A1 (Apo-A1), truncated transthyretin (TT), transferrin, hepcidin, ß-2-microglobulin (ß2M), Connective Tissue Activating Protein III (CTAPIII), and Inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4)]. Statistical models were fit by logistic regression, followed by optimization of factors retained in the models determined by optimizing the Akaike Information Criterion. A validation set included 136 stage I ovarian cancers, 140 benign pelvic masses and 174 healthy controls. Results In a training set analysis, the 3 most effective biomarkers (Apo-A1, TT and CTAPIII) exhibited 54% sensitivity at 98% specificity, CA125 alone produced 68% sensitivity and the combination increased sensitivity to 88%. In a validation set, the marker panel plus CA125 produced a sensitivity of 84% at 98% specificity (P= 0.015, McNemar's test). Conclusion Combining a panel of proteomic markers with CA125 could provide a first step in a sequential two-stage strategy with TVS for early detection of ovarian cancer. PMID:21708402

Costs, effectiveness, and workload impact of management strategies for women with an adnexal mass.

PubMed

Havrilesky, Laura J; Dinan, Michaela; Sfakianos, Gregory P; Curtis, Lesley H; Barnett, Jason C; Van Gorp, Toon; Myers, Evan R

2015-01-01

We compared the estimated clinical outcomes, costs, and physician workload resulting from available strategies for deciding which women with an adnexal mass should be referred to a gynecologic oncologist. We used a microsimulation model to compare five referral strategies: 1) American Congress of Obstetricians and Gynecologists (ACOG) guidelines, 2) Multivariate Index Assay (MIA) algorithm, 3) Risk of Malignancy Algorithm (ROMA), 4) CA125 alone with lowered cutoff values to prioritize test sensitivity over specificity, 5) referral of all women (Refer All). Test characteristics and relative survival were obtained from the literature and data from a biomarker validation study. Medical costs were estimated using Medicare reimbursements. Travel costs were estimated using discharge data from Surveillance, Epidemiology and End Results-Medicare and State Inpatient Databases. Analyses were performed separately for pre- and postmenopausal women (60 000 "subjects" in each), repeated 10 000 times. Refer All was cost-effective compared with less expensive strategies in both postmenopausal (incremental cost-effectiveness ratio [ICER] $9423/year of life saved (LYS) compared with CA125) and premenopausal women (ICER $10 644/YLS compared with CA125), but would result in an additional 73 cases/year/subspecialist. MIA was more expensive and less effective than Refer All in pre- and postmenopausal women. If Refer All is not a viable option, CA125 is an optimal strategy in postmenopausal women. Referral of all women to a subspecialist is an efficient strategy for managing women with adnexal masses requiring surgery, assuming sufficient capacity for additional surgical volume. If a test-based triage strategy is needed, CA125 with lowered cutoff values is a cost-effective strategy. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Enhancement of Force Generated by Individual Myosin Heads in Skinned Rabbit Psoas Muscle Fibers at Low Ionic Strength

PubMed Central

Sugi, Haruo; Abe, Takahiro; Kobayashi, Takakazu; Chaen, Shigeru; Ohnuki, Yoshiki; Saeki, Yasutake; Sugiura, Seiryo

2013-01-01

Although evidence has been presented that, at low ionic strength, myosin heads in relaxed skeletal muscle fibers form linkages with actin filaments, the effect of low ionic strength on contraction characteristics of Ca2+-activated muscle fibers has not yet been studied in detail. To give information about the mechanism of muscle contraction, we have examined the effect of low ionic strength on the mechanical properties and the contraction characteristics of skinned rabbit psoas muscle fibers in both relaxed and maximally Ca2+-activated states. By progressively decreasing KCl concentration from 125 mM to 0 mM (corresponding to a decrease in ionic strength μ from 170 mM to 50 mM), relaxed fibers showed changes in mechanical response to sinusoidal length changes and ramp stretches, which are consistent with the idea of actin-myosin linkage formation at low ionic strength. In maximally Ca2+-activated fibers, on the other hand, the maximum isometric force increased about twofold by reducing KCl concentration from 125 to 0 mM. Unexpectedly, determination of the force-velocity curves indicated that, the maximum unloaded shortening velocity Vmax, remained unchanged at low ionic strength. This finding indicates that the actin-myosin linkages, which has been detected in relaxed fibers at low ionic strength, are broken quickly on Ca2+ activation, so that the linkages in relaxed fibers no longer provide any internal resistance against fiber shortening. The force-velocity curves, obtained at various levels of steady Ca2+-activated isometric force, were found to be identical if they are normalized with respect to the maximum isometric force. The MgATPase activity of muscle fibers during isometric force generation was found not to change appreciably at low ionic strength despite the two-fold increase in Ca2+-activated isometric force. These results can be explained in terms of enhancement of force generated by individual myosin heads, but not by any changes in kinetic properties of cyclic actin-myosin interaction. PMID:23691080

Diagnostic Accuracy of Combinations of Tumor Markers for Malignant Pleural Effusion: An Updated Meta-Analysis.

PubMed

Yang, Yuan; Liu, Ya-Lan; Shi, Huan-Zhong

2017-01-01

The role of combinations of tumor markers such as carcinoembryonic antigen (CEA), carbohydrate antigens (CA) 125, 15-3, and 19-9, and CYFRA 21-1 (a fragment of cytokeratin 19) in diagnosing malignant pleural effusion (MPE) has not been clearly established. This meta-analysis was performed to establish the overall diagnostic accuracies of combinations of these pleural fluid tumor markers for MPE. The PubMed, Ovid, Embase, Web of Science, and Cochrane bibliographic databases were searched. Sensitivity, specificity, and other measures of the accuracy of combinations of pleural CEA, CA 125, CA 15-3, CA 19-9, and CYFRA 21-1 in the diagnosis of MPE were pooled after a systematic review of English-language studies. Twenty studies met the inclusion criteria. For pleural fluid tumor marker combinations including more than 3 studies, the summary estimates of the sensitivity/specificity for diagnosing MPE were as follows: CEA + CA 125, 0.65/0.98; CEA + CA 15-3, 0.64/0.98; CEA + CA 19-9, 0.58/0.98; CEA + CYFRA 21-1, 0.82/0.92; and CA 15-3 + CYFRA 21-1, 0.88/0.94. In patients with undiagnosed pleural effusion, the combinations of positive pleural CEA + CA 15-3 and CEA + CA 19-9 are highly suspicious for pleural malignancy, but the sensitivity of these tests is poor. Therefore, their routine role in the diagnostic algorithm of these patients is questionable, and management decisions should depend on positive cytological or biopsy results from the pleura. © 2017 S. Karger AG, Basel.

Carotid artery disease progression and related neurologic events after carotid endarterectomy.

PubMed

Avgerinos, Efthymios D; Go, Catherine; Ling, Jennifer; Naddaf, Abdallah; Steinmetz, Amy; Abou Ali, Adham N; Makaroun, Michel S; Chaer, Rabih A

2016-08-01

During the last decade, there has been a dramatic improvement in best medical treatment for patients with vascular disease. Yet, there is a paucity of contemporary long-term data for restenosis and contralateral internal carotid artery (ICA) progression. This study assessed ipsilateral and contralateral disease progression and cerebrovascular events after carotid endarterectomy (CEA). A consecutive cohort of CEAs between January 1, 2000, and December 31, 2010, was retrospectively analyzed. End points were restenosis ≥50% and ≥70%, contralateral carotid disease progression (50%-69%, 70%-99%, or occlusion) and stroke. Survival analysis and Cox regression models were used to assess the effect of baseline predictors. During the 11-year study period, 1639 patients underwent 1782 CEAs (50.0% patch closure, 23.9% primary closure, 26.1% eversion, and 2.5% combined with coronary artery bypass grafting). The combined stroke/death rate was 2.6% overall and 1.8% in the asymptomatic cohort. The rate of restenosis ≥50% at 2, 5, and 10 years was 8.5%, 15.6%, 27.2%, and the rate for restenosis ≥70% was 3.4%, 6.5%, 10.2%, respectively. Restenosis ≥50% was predicted by hypertension (hazard ratio [HR], 2.09; P = .027), female gender (HR, 1.43; P = .042), and younger age (≤65 years; HR, 1.56; P = .016), but not by statins, surgical technique, symptoms, or other baseline risk factors. Restenoses remained asymptomatic in 125 of 148 (84.5%). Progression of contralateral ICA disease at 2, 5, and 10 years was estimated at 5.4%, 15.5%, and 46.8%, respectively. Contralateral progression was only predicted by smoking (HR, 1.74; P = .008). The stroke rate in patients with disease progression of the contralateral ICA was not different compared with those without progression (7.0% vs 3.3%; P = .063). Any-stroke rates at 2, 5, and 10 years were 4.6%, 7.3%, and 15.7%, respectively. Predictors were symptomatic lesion (HR, 1.48; P = .039), renal insufficiency, defined as a glomerular filtration rate (GFR) of 30 to 59 vs <30 mL/min/1.73 m 2 (HR, 0.34; P = .009) or GFR ≥60 vs GFR <30 mL/min/1.73 m 2 (HR, 0.55; P = .109), and statin use (HR, 0.59; P = .006). Restenosis or contralateral disease progression after CEA, to a level that might warrant consideration for treatment, is very low. The potentially associated stroke rates are also very low and not clearly related to disease progression. With the exception of the postoperative duplex, surveillance within short intervals of <1 or 2 years cannot be justified. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Effects of 1,25-dihydroxycholecalciferol on recovery and resolution of late transient neonatal hypocalcemia

USDA-ARS?s Scientific Manuscript database

Late transient neonatal hypocalcemia with hyperphosphatemia is potentially life-threatening. The use of 1.25 dihydroxycholecalciferol in the management of neonatal hypocalcemia is unexplored. We hypothesized adding 1.25 dihydroxycholecalciferol to intravenous continuous calcium infusion (CaI) will a...

Asymptomatic Petechial Eruption on the Lower Legs

PubMed Central

Grande, Donald

2013-01-01

The authors report an unusual case of Rocky Mountain spotted fever that presented as an asymptomatic petechial eruption on the lower legs. Rocky Mountain spotted fever is rare in New England and, as such, is typically not on the differential diagnosis when presented with such patients. What began as an asymptomatic eruption progressed to more classic signs of the disease, including a positive Rocky Mountain spotted fever titer. The patient was successfully treated with doxycydine and within a short period of time, was completely back at baseline. PMID:24062875

Long term follow up of kidney donors with asymptomatic renal stones.

PubMed

Serur, David; Charlton, Marian; Juluru, Krishna; Salama, Gayle; Locastro, Eve; Bretzlaff, Gretchen; Hartono, Choli

2017-08-01

Patients with asymptomatic kidney stones have a high rate of progression to becoming symptomatic kidney stones when followed for several years. Small kidney stones are often found incidentally on imaging when evaluating patients for kidney donation, and there is a concern that after nephrectomy, the donor may become symptomatic and incur damage to the remaining kidney. We reviewed kidney donors at our institution with asymptomatic stones and surveyed them several years after donation to see if the stones became clinically active. © 2017 Asian Pacific Society of Nephrology.

Isolation and characterization of ovarian cancer antigen CA 125 using a new monoclonal antibody (VK-8): identification as a mucin-type molecule.

PubMed

Lloyd, K O; Yin, B W; Kudryashov, V

1997-05-29

A new murine monoclonal antibody (MAb VK-8), detecting the CA 125 ovarian cancer antigen, was used to purify this antigen from OVCAR-3 ovarian cancer cells by affinity chromatography. The biochemical properties of the purified antigen are characteristic of a mucin-type glycoprotein: (1) the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3(GlcNAcbeta1 --> 6)GalNAc] structures predominating and (5) these chains carry fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures. The antigen exhibited a very high m.w. (> 10(3) kDa) in aqueous buffer as well as in urea, but was degraded by proteolytic enzymes to smaller fragments that no longer reacted with the antibody. Although this result, and other immunochemical data, indicate that OC125, the original MAb to CA125, and VK-8 antibodies detect epitopes on the protein portion of the molecule, the involvement of carbohydrate cannot be ruled out. Further insight into the structure and function of the CA125 antigen will come from cloning the gene coding for the peptide backbone, and from more detailed carbohydrate structural analysis.

Transmissibility and Pathogenicity of Ebola Virus: A Systematic Review and Meta-analysis of Household Secondary Attack Rate and Asymptomatic Infection

PubMed Central

Dean, Natalie E.; Halloran, M. Elizabeth; Yang, Yang; Longini, Ira M.

2016-01-01

Factors affecting our ability to control an Ebola outbreak include transmissibility of the virus and the proportion of transmissions occurring asymptomatically. We performed a meta-analysis of Ebola household secondary attack rate (SAR), disaggregating by type of exposure (direct contact, no direct contact, nursing care, direct contact but no nursing care). The estimated overall household SAR is 12.5% (95% confidence interval [CI], 8.6%–16.3%). Transmission was driven by direct contact, with little transmission occurring in its absence (SAR, 0.8% [95% CI, 0%–2.3%]). The greatest risk factor was the provision of nursing care (SAR, 47.9% [95% CI, 23.3%–72.6%]). There was evidence of a decline in household SAR for direct contact between 1976 and 2014 (P = .018). We estimate that 27.1% (95% CI, 14.5%–39.6%) of Ebola infections are asymptomatic. Our findings suggest that surveillance and containment measures should be effective for controlling Ebola. PMID:26932131

[Intestinal absorption of Ca47 in chronic renal insufficiency before and after treatment with 1,25 dihydroxycholecalciferol].

PubMed

Vattimo, A

1979-12-01

The effects of vitamin D3 follow its metabolisation in the liver and then in the kidney. Its most active metabolite is 1,25 (OH)2D3, produced by the liver precursor 25(OH)D3. In chronic renal insufficiency, demineralising osteopathy can be corrected by administering 1,25 (OH)2D3 to make up for its under-production by the kidneys. An assessment if is made of 47Ca intestinal transport in patients with chronic renal insufficiency before and after such treatment. It was found that the effects of the metabolite on calcium transport were dose-dependent.

Natural history and clinical manifestations of hyponatremia and hyperchlorhidrosis due to carbonic anhydrase XII deficiency.

PubMed

Feinstein, Yael; Yerushalmi, Baruch; Loewenthal, Neta; Alkrinawi, Soliman; Birk, Ohad S; Parvari, Ruti; Hershkovitz, Eli

2014-01-01

We identified patients of Bedouin origin with a mutation in carbonic anhydrase XII (CA XII) leading to hyponatremia due to excessive salt loss via sweat. The medical records of patients were reviewed for clinical and laboratory data. A total of 11 subjects were identified; 7 symptomatic patients presented with hyponatremic dehydration in infancy. Screening of the entire kindred identified 4 asymptomatic individuals with elevated sweat chloride. All symptomatic patients had failure to thrive and moderate-severe hyponatremia (106-124 mmol·l(-1)); 6 had hypochloremia (79-94 mmol·l(-1)). All asymptomatic subjects had normal or near-normal serum sodium and chloride concentrations. Both symptomatic and asymptomatic subjects had normal renal functions and normal cortisol response on low-dose ACTH test. All symptomatic patients were treated by dietary salt, which prevents episodes of hyponatremic dehydration and promotes growth. At follow-up, the chief complaints remained heat intolerance, accumulation of salt precipitates on the face and hyperhidrosis. No evidence for chronic renal, respiratory, gastrointestinal or fertility abnormalities was found. Recognizing this newly described entity and differentiating it from cystic fibrosis and pseudohypoaldosteronism are important. Patients with CA XII mutations should be followed even after early childhood, especially in hot temperatures and intense physical activity. © 2014 S. Karger AG, Basel.

Neurocognitive function in HIV-infected persons with asymptomatic cryptococcal antigenemia: a comparison of three prospective cohorts.

PubMed

Montgomery, Martha P; Nakasujja, Noeline; Morawski, Bozena M; Rajasingham, Radha; Rhein, Joshua; Nalintya, Elizabeth; Williams, Darlisha A; Huppler Hullsiek, Kathy; Kiragga, Agnes; Rolfes, Melissa A; Donahue Carlson, Renee; Bahr, Nathan C; Birkenkamp, Kate E; Manabe, Yukari C; Bohjanen, Paul R; Kaplan, Jonathan E; Kambugu, Andrew; Meya, David B; Boulware, David R

2017-06-12

HIV-infected persons with detectable cryptococcal antigen (CrAg) in blood have increased morbidity and mortality compared with HIV-infected persons who are CrAg-negative. This study examined neurocognitive function among persons with asymptomatic cryptococcal antigenemia. Participants from three prospective HIV cohorts underwent neurocognitive testing at the time of antiretroviral therapy (ART) initiation. Cohorts included persons with cryptococcal meningitis (N = 90), asymptomatic CrAg + (N = 87), and HIV-infected persons without central nervous system infection (N = 125). Z-scores for each neurocognitive test were calculated relative to an HIV-negative Ugandan population with a composite quantitative neurocognitive performance Z-score (QNPZ-8) created from eight tested domains. Neurocognitive function was measured pre-ART for all three cohorts and additionally after 4 weeks of ART (and 6 weeks of pre-emptive fluconazole) treatment among asymptomatic CrAg + participants. Cryptococcal meningitis and asymptomatic CrAg + participants had lower median CD4 counts (17 and 26 cells/μL, respectively) than the HIV-infected control cohort (233 cells/μL) as well as lower Karnofsky performance status (60 and 70 vs. 90, respectively). The composite QNPZ-8 for asymptomatic CrAg + (-1.80 Z-score) fell between the cryptococcal meningitis cohort (-2.22 Z-score, P = 0.02) and HIV-infected controls (-1.36, P = 0.003). After four weeks of ART and six weeks of fluconazole, the asymptomatic CrAg + cohort neurocognitive performance improved (-1.0 Z-score, P < 0.001). Significant deficits in neurocognitive function were identified in asymptomatic CrAg + persons with advanced HIV/AIDS even without signs or sequelae of meningitis. Neurocognitive function in this group improves over time after initiation of pre-emptive fluconazole treatment and ART, but short term adherence support may be necessary.

[Sinusal penetration of amoxicillin-clavulanic acid. Formulation 1 g./125 mg., twice daily versus formulation 500 mg./125 mg., three times daily].

PubMed

Jehl, F; Klossek, J M; Peynegre, R; Serrano, E; Castillo, L; Bobin, S; Desprez, D; Renault, C; Neel, V; Rouffiac, E; Borie, C

2002-10-19

In order to meet the evolution of pneumococcus resistance to beta-lactam antibiotics, a new formulation of amoxicillin (AMX) and clavulanic acid (CA), with twice as much AMX (1 g/125 mg vs. 500 mg/125 mg) was developed for the treatment of acute pneumonia in patients at risk. This formulation can also be used in the treatment of acute maxillary sinusitis using a 1 g/125 mg regimen twice-daily. Compare the sinusal penetration of AMX and CA (1 g/125 mg twice-daily vs. 500 mg/125 mg three times a day) when administered at both regimens to demonstrate equivalent pharmacokinetic and pharmacodynamic behaviour of the former when compared to the latter. Concentrations of AMX and CA were measured in the anterior ethmoid, maxillary, posterior ethmoid sinus and in the middle nasa concha in 62 patients undergoing surgery for nasosinusal polyps. Patients randomised in two groups corresponding to 2 oral regimens, received either 1 g/125 mg twice a day or 500 mg/125 mg three times a day for 4 days. The last dose in both groups was administered 1 h 30, 3, 5 or 8 hrs prior to surgery. Serum samples were taken simultaneously to tissue samples. AMX and CA were measured by high performance liquid chromatography. Exogenous and above all endogenous blood contamination were taken into account with the hematocrit as well as blood and tissue haemoglobin concentrations. Comparisons of tissue concentrations were made for each sampling time, according to values obtained for a specific tissue with both doses on one hand, and on the other to values obtained with a specific dose in different tissues. The calculated pharmacodynamic parameters, which are considered to be predictive for bacteriological and clinical efficacy, result directly from tissue concentrations of AMX. tissue inhibitory quotients (IQtissue = Tissue concentration/MIC). time above MICs for serum and tissue concentrations (T > MIC). As regards AMX, whatever the dose, at 1 h 30 and at 3 hrs, tissue concentrations did not differ significantly whatever the tissue studied (from 1.1 to 2.5 micrograms/g). Conversely, at 5 and 8 hrs, they were greater than after the 1 g/125 mg regimen given twice-daily (0.06-0.7 vs. 0.7-1.8 micrograms/g). If we consider a given dose, the comparison between the various tissues showed identical concentrations in the four tissues studied at each sampling time, except in two cases with the dose of 500 mg/125 mg 3 times a day. T > MIC for serum and tissue showed higher values than those required for AMX/pneumococcus association (40-50%) with, nevertheless, greater tissue values for the 1 g/125 mg dose given twice-daily when MIC was of 1 microgram/ml (40-52% vs. 50-66%). The maximum tissue inhibitory quotients were also greater with the twice-daily 1 g/125 mg dose, when calculated with MIC 50 or 90 of S. Pneumoniae, H. influenzae, M. catarrhalis or S. pyogenes. As for CA, concentrations were equivalent for both doses at each sampling time and greater than those required in vitro during respectively 4 and 5 hours for beta-lactamases H. influenzae and M. catarrhalis. A least an equivalence between both dose regimens was observed, with occasionally a superiority of the twice-daily 1 g/125 mg dose, in terms of pharmacokinetics, tissue penetration and pharmacodynamics for both AMX and CA. This new regimen therefore appears more appropriate for the treatment of acute maxillary sinusitis in adults.

Calcium-dependent transferrin receptor recycling in bovine chromaffin cells.

PubMed

Knight, Derek E

2002-04-01

The release of regulated secretory granules is known to be calcium dependent. To examine the Ca2+-dependence of other exocytic fusion events, transferrin recycling in bovine chromaffin cells was examined. Internalised 125I-transferrin was released constitutively from cells with a half-time of about 7 min. Secretagogues that triggered catecholamine secretion doubled the rate of 125I-transferrin release, the time courses of the two triggered secretory responses being similar. The triggered 125I-transferrin release came from recycling endosomes rather than from sorting endosomes or a triggered secretory vesicle pool. Triggered 125I-transferrin release, like catecholamine secretion from the same cells, was calcium dependent but the affinities for calcium were very different. The extracellular calcium concentrations that gave rise to half-maximal evoked secretion were 0.1 mm for 125I-transferrin and 1.0 mm for catecholamine, and the intracellular concentrations were 0.1 microm and 1 microm, respectively. There was significant 125I-transferrin recycling in the virtual absence of intracellular Ca2+, but the rate increased when Ca2+ was raised above 1 nm, and peaked at 1 microm when the rate had doubled. Botulinum toxin type D blocked both transferrin recycling and catecholamine secretion. These results indicate that a major component of the vesicular transport required for the constitutive recycling of transferrin in quiescent cells is calcium dependent and thus under physiological control, and also that some of the molecular machinery involved in transferrin recycling/fusion processes is shared with that for triggered neurosecretion.

The number of cycles of neoadjuvant chemotherapy is associated with prognosis of stage IIIc-IV high-grade serous ovarian cancer.

PubMed

Xu, Xia; Deng, Fei; Lv, Mengmeng; Chen, Xiaoxiang

2017-02-01

No consensus exists on the number of chemotherapy cycles to be administered before and after interval debulking surgery (IDS) in patients with advanced stage epithelial ovarian cancer. The present study aims to explore the optimal number of cycles of neoadjuvant chemotherapy (NAC) and post-operation chemotherapy to treat the International Federation of Gynecology and Obstetrics stage IIIc-IV high-grade serous ovarian cancer (HG-SOC). A total of 129 IIIc-IV stage HG-SOC cases were retrospectively analyzed. Cases were comprised of patients who underwent NAC followed by IDS and who achieved clinical complete response (CCR) at the end of primary therapy. Patients were recruited from the Jiangsu Institute of Cancer Research between 1993 and 2013. Optimal IDS-associated factors were explored with logistic regression. The association between progression-free survival (PFS), overall survival (OS) duration, and covariates was assessed by Cox proportional hazards model and log-rank test. The median number of NAC cycle was 3 (range 1-8). CA-125 decreasing kinetics (p = 0.01) was independently associated with optimal IDS. CA-125 decreasing kinetics, optimal IDS, and NAC cycles was independently associated with OS (p < 0.01, p < 0.01, p = 0.03, respectively) and PFS (p < 0.01, p < 0.01, p = 0.04, respectively). The PFS of patients who underwent ≥5 NAC cycles was shorter than those of patients who underwent <5 NAC cycles (12.3 versus 17.2 months). The PFS and OS of patients who underwent <5 cycles of adjuvant chemotherapy post-IDS were shorter than those of patients who underwent ≥5 cycles (14.2 and 20.3 versus 21.2 and 28.8 months). NAC cycles, CA-125 decreasing kinetics, and optimal debulking are independently associated with the prognosis of patients with advanced stage HG-SOC who underwent NAC/IDS and achieved CCR. The number of administered NAC cycles should not exceed 4.

Clinical implications of asymptomatic Plasmodium falciparum infections in Malawi.

PubMed

Buchwald, Andrea G; Sixpence, Alick; Chimenya, Mabvuto; Damson, Milius; Sorkin, John D; Wilson, Mark L; Seydel, Karl; Hochman, Sarah; Mathanga, Don P; Taylor, Terrie E; Laufer, Miriam K

2018-05-16

Asymptomatic Plasmodium falciparum infections are common in Malawi, however, the implications of these infections for the burden of malaria illness are unknown. Whether asymptomatic infections eventually progress to malaria illness, persist without causing symptoms, or clear spontaneously remains undetermined. We identified asymptomatic infections and evaluated the associations between persistent asymptomatic infections and malaria illness. Children and adults (N = 120) who presented at a health facility with uncomplicated malaria were followed monthly for two years. During follow-up visits, participants with malaria symptoms were tested and treated if positive. Samples from all visits were tested for parasites using both microscopy and PCR, and all malaria infections underwent genotyping. Cox frailty models were used to estimate the temporal association between asymptomatic infections and malaria illness episodes. Mixed models were used to estimate the odds of clinical symptoms associated with new versus persistent infections. Participants had a median follow-up time of 720 days. Asymptomatic infections were detected during 23% of visits. Persistent asymptomatic infections were associated with decreased risk of malaria illness in all ages (HR 0.50, p < 0.001). When asymptomatic infections preceded malaria illness, newly acquired infections were detected at 92% of subsequent clinical episodes, independent of presence of persistent infections. Malaria illness among children was more likely due to newly acquired infections (OR 1.4, 95%CI 1.3-1.5) than to persistent infections. Asymptomatic P. falciparum infections are associated with decreased incidence of malaria illness but do not protect against disease when new infection occurs.

125. TRANSFORMER SUBSTATIONS ON NORTH SIDE OF TRANSFORMER ROOM (112), ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

125. TRANSFORMER SUBSTATIONS ON NORTH SIDE OF TRANSFORMER ROOM (112), FACING SOUTH - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 West, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

[Application of (125)I seeds combined with biliary stent implantation in the treatment of malignant obstructive jaundice].

PubMed

Wang, T; Liu, S; Zheng, Y B; Song, X P; Jiang, W J; Sun, B L; Wang, L G

2016-03-23

To study the feasibility and therapeutic effect of the application of (125)I seeds combined with biliary stent implantation on the treatment of malignant obstructive jaundice. Fifty patients with malignant obstructive jaundice treated from September 2010 to February 2013 in Yantai Yuhuangding Hospital were included in this study. Among them, 24 patients received biliary stent implantation combined with (125)I seeds intraluminal brachytherapy as experimental group, and 26 were treated by biliary stent implantation as control group.The total bilirubin, direct bilirubin and tumor markers (CA-199, CA-242, CEA) before and after surgery, the biliary stent patency status was assessed, and the survival time was evaluated. The 24 patients in experimental group were implanted with 30 (125)I seeds successfully in a total of 450 seeds. Jaundice was improved greatly in both groups. The CA-199 and CA-242 after treatment in the experimental group were significantly decreased than that before treatment (P=0.003 and P=0.004). CEA was also decreased, but showed no statistical significance (P>0.05). There were no significant improvement comparing the CA-199, CA-242 and CEA before and 2 months after surgery in the control group (P>0.05). The rate of biliary stent patency was 83.3% (20/24) in the experimental group and 57.7% (15/26) in the control group (P=0.048). The mean biliary stent patency time in the experimental group was 9.84 months (range 1-15.5 months). The mean biliary stent patency time in the control group was 5.57 months (range 0.8-9 months). There was a significant difference between the two groups (P=0.018). The median survival time was 10.2 months in the experimental group and 5.4 months in the control group (P<0.05). (125)I seeds combined with biliary stent implantation can inhibit the proliferation of vascular endothelial cells and the growth of tumor effectively, and can prolong the biliary stent patency time and the survival time obviously for patients with malignant obstructive jaundice, therefore, is a safe and effective treatment in this malignancy.

Sleep Problems are Associated with Development and Progression of Lower Urinary Tract Symptoms: Results from REDUCE.

PubMed

Branche, Brandee L; Howard, Lauren E; Moreira, Daniel M; Roehrborn, Claus; Castro-Santamaria, Ramiro; Andriole, Gerald L; Hopp, Martin L; Freedland, Stephen J

2018-02-01

Although lower urinary tract symptoms and sleep problems often develop together, to our knowledge it is unknown whether sleep disturbances are linked to lower urinary tract symptoms development and progression. As measured by the 6-item MOS-Sleep (Medical Outcomes Study Sleep Scale) survey we examined the relationship between sleep problems, and the development and progression of lower urinary tract symptoms in the REDUCE (Reduction by Dutasteride of Prostate Cancer Events) study. REDUCE was a randomized trial testing prostate cancer chemoprevention with dutasteride in men with prostate specific antigen 2.5 to 10 ng/ml and a negative biopsy. At baseline men completed MOS-Sleep and a scaled average was used to calculate the sleep score. Men were followed for 4 years and I-PSS (International Prostate Symptom Score) was completed at baseline and every 6 months. Asymptomatic men had I-PSS less than 8 while symptomatic men had I-PSS 8 or greater. In the placebo arm of 2,588 men not receiving α-blockers or 5α-reductase inhibitors at baseline we tested the association between sleep problems and lower urinary tract symptom development and progression using Cox models. During followup lower urinary tract symptoms developed in 209 of 1,452 asymptomatic men (14%) and 580 of 1,136 (51%) with lower urinary tract symptoms demonstrated progression. On multivariable analysis higher sleep scores were suggestively associated with increased lower urinary tract symptoms in asymptomatic men (quartile 4 vs 1 HR 1.41, 95% CI 0.92-2.17, p = 0.12) and with lower urinary tract symptom progression in symptomatic men (per 10 points of sleep score HR 1.06, 95% CI 1.01-1.12, p = 0.029). Among men with lower urinary tract symptoms worse sleep scores were associated with the progression of lower urinary tract symptoms and among asymptomatic men worse sleep scores were suggestively associated with the development of lower urinary tract symptoms. If confirmed, these data suggest that sleep problems may precede such symptoms. Whether treating sleep problems would improve lower urinary tract symptoms requires further testing. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Nutritional quality assessment of tomato fruits after exposure to uncoated and citric acid coated cerium oxide nanoparticles, bulk cerium oxide, cerium acetate and citric acid.

PubMed

Barrios, Ana Cecilia; Medina-Velo, Illya A; Zuverza-Mena, Nubia; Dominguez, Osvaldo E; Peralta-Videa, Jose R; Gardea-Torresdey, Jorge L

2017-01-01

Little is known about the effects of surface modification on the interaction of nanoparticles (NPs) with plants. Tomato (Solanum lycopersicum L.) plants were cultivated in potting soil amended with bare and citric acid coated nanoceria (nCeO 2, nCeO 2 +CA), cerium acetate (CeAc), bulk cerium oxide (bCeO 2 ) and citric acid (CA) at 0-500 mg kg -1 . Fruits were collected year-round until the harvesting time (210 days). Results showed that nCeO 2 +CA at 62.5, 250 and 500 mg kg -1 reduced dry weight by 54, 57, and 64% and total sugar by 84, 78, and 81%. At 62.5, 125, and 500 mg kg -1 nCeO 2 +CA decreased reducing sugar by 63, 75, and 52%, respectively and at 125 mg kg -1 reduced starch by 78%, compared to control. The bCeO 2 at 250 and 500 mg kg -1 , increased reducing sugar by 67 and 58%. In addition, when compared to controls, nCeO 2 at 500 mg kg -1 reduced B (28%), Fe (78%), Mn (33%), and Ca (59%). At 125 mg kg -1 decreased Al by 24%; while nCeO 2 +CA at 125 and 500 mg kg -1 increased B by 33%. On the other hand, bCeO 2 at 62.5 mg kg -1 increased Ca (267%), but at 250 mg kg -1 reduced Cu (52%), Mn (33%), and Mg (58%). Fruit macromolecules were mainly affected by nCeO 2 +CA, while nutritional elements by nCeO 2 ; however, all Ce treatments altered, in some way, the nutritional quality of tomato fruit. To our knowledge, this is the first study comparing effects of uncoated and coated nanoceria on tomato fruit quality. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

1α,25-Dihydroxyvitamin D Inhibits the Metastatic Capability of MCF10CA1a and MDA-MB-231 Cells in an In Vitro Model of Breast to Bone Metastasis.

PubMed

Wilmanski, Tomasz; Barnard, Alle; Parikh, Mukti R; Kirshner, Julia; Buhman, Kimberly; Burgess, John; Teegarden, Dorothy

2016-10-01

Breast cancer metastasis to the bone continues to be a major health problem, with approximately 80% of advanced breast cancer patients expected to develop bone metastasis. Although the problem of bone metastasis persists, current treatment options for metastatic cancer patients are limited. In this study, we investigated the preventive role of the active vitamin D metabolite, 1α,25-dihydroxyvitamin D (1,25(OH)2D), against the metastatic potential of breast cancer cells using a novel three-dimensional model (rMET) recapitulating multiple steps of the bone metastatic process. Treatment of MCF10CA1a and MDA-MB-231 cells inhibited metastasis in the rMET model by 70% (±5.7%) and 21% (±6%), respectively. In addition, 1,25(OH)2D treatment decreased invasiveness (20 ± 11% of vehicle) and decreased the capability of MCF10CA1a cells to survive in the reconstructed bone environment after successful invasion through the basement membrane (69 ± 5% of vehicle). An essential step in metastasis is epithelial-mesenchymal transition (EMT). Treatment of MCF10CA1a cells with 1,25(OH)2D increased gene (2.04 ± 0.28-fold increase) and protein (1.87 ± 0.20-fold increase) expression of E-cadherin. Additionally, 1,25(OH)2D treatment decreased N-cadherin gene expression (42 ± 8% decrease), a marker for EMT. Collectively, the present study suggests that 1,25(OH)2D inhibits breast cancer cell metastatic capability as well as inhibits EMT, an essential step in the metastatic process.

Natural History of Rotator Cuff Disease and Implications on Management

PubMed Central

Hsu, Jason

2015-01-01

Degenerative rotator cuff disease is commonly associated with ageing and is often asymptomatic. The factors related to tear progression and pain development are just now being defined through longitudinal natural history studies. The majority of studies that follow conservatively treated painful cuff tears or asymptomatic tears that are monitored at regular intervals show slow progression of tear enlargement and muscle degeneration over time. These studies have highlighted greater risks for disease progression for certain variables, such as the presence of a full-thickness tear and involvement of the anterior aspect supraspinatus tendon. Coupling the knowledge of the natural history of degenerative cuff tear progression with variables associated with greater likelihood of successful tendon healing following surgery will allow better refinement of surgical indications for rotator cuff disease. In addition, natural history studies may better define the risks of nonoperative treatment over time. This article will review pertinent literature regarding degenerative rotator cuff disease with emphasis on variables important to defining appropriate initial treatments and refining surgical indications. PMID:26726288

Prion diseases: A little prevention can prevent a catastrophe

USDA-ARS?s Scientific Manuscript database

Chronic wasting disease and bovine spongiform encephalopathy (BSE) are two of the best known examples of transmissible spongiform encephalopathies (TSEs). These diseases are characterized by a very long asymptomatic incubation period followed by a short disease course that ends in death. TSEs are ca...

Comparison of Clostridium difficile Ribotypes Circulating in Australian Hospitals and Communities.

PubMed

Furuya-Kanamori, Luis; Riley, Thomas V; Paterson, David L; Foster, Niki F; Huber, Charlotte A; Hong, Stacey; Harris-Brown, Tiffany; Robson, Jenny; Clements, Archie C A

2017-01-01

Clostridium difficile infection (CDI) is becoming less exclusively a health care-associated CDI (HA-CDI). The incidence of community-associated CDI (CA-CDI) has increased over the past few decades. It has been postulated that asymptomatic toxigenic C. difficile (TCD)-colonized patients may play a role in the transfer of C. difficile between the hospital setting and the community. Thus, to investigate the relatedness of C. difficile across the hospital and community settings, we compared the characteristics of symptomatic and asymptomatic host patients and the pathogens from these patients in these two settings over a 3-year period. Two studies were simultaneously conducted; the first study enrolled symptomatic CDI patients from two tertiary care hospitals and the community in two Australian states, while the second study enrolled asymptomatic TCD-colonized patients from the same tertiary care hospitals. A total of 324 patients (96 with HA-CDI, 152 with CA-CDI, and 76 colonized with TCD) were enrolled. The predominant C. difficile ribotypes isolated in the hospital setting corresponded with those isolated in the community, as it was found that for 79% of the C. difficile isolates from hospitals, an isolate with a matching ribotype was isolated in the community, suggesting that transmission between these two settings is occurring. The toxigenic C. difficile strains causing symptomatic infection were similar to those causing asymptomatic infection, and patients exposed to antimicrobials prior to admission were more likely to develop a symptomatic infection (odds ratio, 2.94; 95% confidence interval, 1.20 to 7.14). Our findings suggest that the development of CDI symptoms in a setting without establishment of hospital epidemics with binary toxin-producing C. difficile strains may be driven mainly by host susceptibility and exposure to antimicrobials, rather than by C. difficile strain characteristics. Copyright © 2016 American Society for Microbiology.

Enhanced expression of extracellular calcium sensing receptor in monocyte-differentiated versus undifferentiated HL-60 cells: potential role in regulation of a nonselective cation channel

NASA Technical Reports Server (NTRS)

Yamaguchi, T.; Ye, C.; Chattopadhyay, N.; Sanders, J. L.; Vassilev, P. M.; Brown, E. M.; O'Malley, B. W. (Principal Investigator)

2000-01-01

Human promyelocytic leukemia cells (HL-60) have been used widely as a model for studying the differentiation of hematopoietic progenitor cells in vitro. After treatment with phorbol-12-myristate-13-acetate (PMA) or 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)], HL-60 cells differentiate into cells with the phenotype of monocytes/macrophages. We previously showed that peripheral blood monocytes and the murine J774 monocytic cell line express the CaR, and myeloid progenitors in the bone marrow and myeloid cells in peripheral blood other than monocytes express lower levels of the CaR. Therefore, we investigated whether undifferentiated HL-60 cells express a functional G protein-coupled, extracellular calcium (Ca(2+)(o))-sensing receptor (CaR) and if the expression of the CaR increases as these cells differentiate along the monocytic lineage. The use of reverse transcription-polymerase chain reaction (RT-PCR) with CaR-specific primers, followed by sequencing of the amplified products, identified an authentic CaR transcript in undifferentiated HL-60 cells. Both immunocytochemistry and Western blot analysis using a CaR-specific antiserum detected low levels of CaR protein expression in undifferentiated HL-60 cells. The levels of CaR protein increased considerably following treatment of the cells with PMA (50 nM) or 1,25(OH)(2)D(3) (100 nM) for 5 days. Northern analysis using a CaR-specific riboprobe identified CaR transcripts in undifferentiated HL-60 cells, but CaR mRNA levels did not change appreciably after treatment with either agent, suggesting that upregulation of CaR protein occurs at a translational level. PMA-treated HL-60 cells expressed a nonselective cation channel (NCC), and the calcimimetic CaR activator, NPS R-467, but not its less active stereoisomer, NPS S-467, as well as the polycationic CaR agonist, neomycin, activated this NCC, demonstrating that the CaR expressed in these cells is functionally active. Therefore, HL-60 cells exhibit an increase in CaR protein expression, occurring at a translational level during their differentiation into cells with a monocyte/macrophage phenotype in response to treatment with PMA or 1, 25(OH)(2)D(3), which is functionally linked to activation of a nonselective cation channel.

FROM LEFT TO RIGHT, 115, 117, 119, 121, 123, 125, ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

FROM LEFT TO RIGHT, 115, 117, 119, 121, 123, 125, 127, 129 COLLINS STREET. ATCHISON VILLAGE HOUSED WORKERS DURING WORLD WAR II - Rosie the Riveter National Historical Park, Atchison Village, Collins Street, Richmond, Contra Costa County, CA

Factors influencing pre-operative urinary calcium excretion in primary hyperparathyroidism.

PubMed

Kaderli, Reto M; Riss, Philipp; Geroldinger, Angelika; Selberherr, Andreas; Scheuba, Christian; Niederle, Bruno

2017-07-01

Normal or elevated 24-hour urinary calcium (Ca) excretion is a diagnostic marker in primary hyperparathyroidism (PHPT). It is used to distinguish familial hypocalciuric hypercalcaemia (FHH) from PHPT by calculating the Ca/creatinine clearance ratio (CCCR). The variance of CCCR in patients with PHPT is considerable. The aim of this study was to analyse the parameters affecting CCCR in patients with PHPT. The data were collected prospectively. Patients with sporadic PHPT undergoing successful surgery were included in a retrospective analysis. The analysis covered 381 patients with pre-operative workup 2 days before removal of a solitary parathyroid adenoma. The impact of serum Ca and 25-hydroxyvitamin D3 (25-OH D3) on CCCR. The coefficient of determination (R 2 ) in the multivariable model for CCCR consisting of age, Ca, 25-OH D3, 1,25-dihydroxyvitamin D3 (1,25-(OH)2 D3), testosterone (separately for males and females), intact parathyroid hormone (iPTH) and osteocalcin was 25.8%. The only significant parameters in the multivariable analysis were 1,25-(OH)2 D3 and osteocalcin with a drop in R 2 of 15.4% (P<.001) and 2.4% (P=.006), respectively. Bone mineral densities at the lumbar spine, distal radius and left femoral neck were not associated with CCCR (r=-.08, r=-.10 and r=-0.09). In multivariable analysis, 1,25-(OH)2 D3 and osteocalcin were the only factors correlating with CCCR. Vitamin D3 replacement may therefore impair the diagnostic value of CCCR and increase the importance of close monitoring of urinary Ca excretion during treatment. © 2017 John Wiley & Sons Ltd.

miR-125/Pokemon auto-circuit contributes to the progression of hepatocellular carcinoma.

PubMed

Kong, Jing; Liu, Xiaoping; Li, Xiangqian; Wu, Jinsheng; Wu, Ning; Chen, Jun; Fang, Fang

2016-01-01

Hepatocellular carcinoma (HCC) is a type of human malignant tumor occurring in hepatic tissues with high mortality. Patients benefit little from current therapeutic modalities, at least partially due to the lack of complete elucidation of molecular network regulating HCC. miR-125 and Pokemon are well-recognized tumor suppressor and oncogenes for HCC, respectively. However, the underlying mechanism by which the two genes exert their functions and the relationship between miR-125 and Pokemon is still unexplored yet. In this study, we found that there is an inverse association between miR-125 and Pokemon expression levels in HCC specimen and cell lines. Online database mining indicated that there are three putative mRNA recognition elements (MREs) of miR-125 within 3' untranslated region (3'UTR) of Pokemon. MREs of miR-125 confer the expression of luciferase with a miR-125-dependent fashion. The alteration in miR-125 abundance regulates the expression of Pokemon at both protein and mRNA levels. Overexpression of Pokemon is able to abrogate the inhibitory effect of miR-125 on HCC progression. Further study showed that Pokemon inhibits the expression of miR-125 by binding of recognition sites within its promoter. In conclusion, we found that there is an auto-regulatory circuit consisting of miR-125 and Pokemon, which promotes the progression of HCC and may be a promising therapeutic target in clinical HCC treatment.

Clinical characteristics of genital chlamydia infection in pelvic inflammatory disease.

PubMed

Park, Sung Taek; Lee, Suk Woo; Kim, Min Jeong; Kang, Young Mo; Moon, Hye Min; Rhim, Chae Chun

2017-01-13

Chlamydia infection in acute pelvic inflammatory disease (PID) is associated with serious complications including ectopic pregnancy, tubal infertility, Fitz-Hugh-Curtis syndrome and tubo-ovarian abscess (TOA). This study compared clinical and laboratory data between PID with and without chlamydia infection. The medical records of 497 women who were admitted with PID between 2002 and 2011 were reviewed. The patients were divided into two groups (PID with and without chlamydia infection), which were compared in terms of the patients' characteristics, clinical presentation, and laboratory findings, including inflammatory markers. The chlamydia and non-chlamydia groups comprised 175 and 322 women, respectively. The patients in the chlamydia group were younger and had a higher rate of TOA, a longer mean hospital stay, and had undergone more surgeries than the patients in the non- chlamydia group. The erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and CA-125 level were higher in the chlamydia group than in the non-chlamydia group, but there was no significant difference in the white blood cell count between the two groups. The CA-125 level was the strongest predictor of chlamydia infection, followed by the ESR and CRP level. The area under the receiving operating curve for CA-125, ESR, and CRP was 0.804, 0.755, and 0.663, respectively. Chlamydia infection in acute PID is associated with increased level of inflammatory markers, such as CA-125, ESR and CRP, incidence of TOA, operation risk, and longer hospitalization.

A new score for screening of malnutrition in patients with inoperable gastric adenocarcinoma.

PubMed

Esfahani, Ali; Somi, Mohammad Hossein; Asghari Jafarabadi, Mohammad; Ostadrahimi, Alireza; Ghayour Nahand, Mousa; Fathifar, Zahra; Doostzadeh, Akram; Ghoreishi, Zohreh

2017-06-01

Malnutrition is common in patients with gastric cancer. Early identification of malnourished patients results in improving quality of life. We aimed to assess the nutritional status of patients with inoperable gastric adenocarcinoma (IGA) and finding a precise malnutrition screening score for these patients before the onset of chemotherapy. Nutritional status was assessed using patient generated subjective global assessment (PG-SGA), visceral proteins, and high-sensitivity C reactive protein. Tumor markers of carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA-125) and CA 19-9 and their association with nutritional status were assessed. Then a new score for malnutrition screening was defined. Seventy-one patients with IGA completed the study. Malnourished and well-nourished patients (based on PG-SGA) were statistically different regarding albumin, prealbumin and CA-125. The best cut-off value for prealbumin for prediction of malnutrition was determined at 0.20 mg/dl and using known cut-off values for albumin (3.5 g/dl) and CA-125 (35 U/ml), a new score was defined for malnutrition screening named MS-score. According to MS-score, 92% of the patients had malnutrition and it could predict malnutrition with 96.8% sensitivity, 50% specificity and accuracy of 91.4%. MS-score has been suggested as an available and easy-to-use tool for malnutrition screening in patients with IGA. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The National Institute for Health and Clinical Excellence (NICE) guidelines for early detection of ovarian cancer: the pivotal role of the clinical laboratory.

PubMed

Sturgeon, Catharine M; Duffy, Michael J; Walker, Graeme

2011-07-01

The National Institute for Health and Clinical Excellence (NICE) has recently reviewed optimal means of early recognition and initial management of ovarian cancer, the leading cause of gynaecological death in the UK. The NICE guidelines state that general practitioners should measure serum CA125 in women presenting with persistent and continuous symptoms suggestive of ovarian cancer (e.g. abdominal distension, early satiety and loss of appetite or pelvic pain). If CA125 is ≥35 kU/L, the general practitioner should arrange an ultrasound scan of the abdomen and pelvis to enable calculation of the risk of malignancy score (RMI). Women with an RMI score of ≥250 should then be referred to a specialist multidisciplinary team. Successful implementation of these guidelines requires close liaison between primary care and laboratory medicine to ensure that CA125 is requested as a diagnostic aid only for women meeting the criteria stated in the guidelines. Preanalytical criteria must also be met and it is essential that both requestors and patients be aware of other possible causes of increases in CA125, as well as the fact that it is not raised in all patients with ovarian cancer. Guidance is being prepared to enable appropriate interpretation and implementation of the NICE guidelines. Continuous audit of the outcomes will also be essential to determine the effectiveness of this approach to early detection of ovarian cancer.

A preoperative serum signature of CEA+/CA125+/CA19-9 ≥ 1000 U/mL indicates poor outcome to pancreatectomy for pancreatic cancer.

PubMed

Liu, Liang; Xu, Huaxiang; Wang, Wenquan; Wu, Chuntao; Chen, Yong; Yang, Jingxuan; Cen, Putao; Xu, Jin; Liu, Chen; Long, Jiang; Guha, Sushovan; Fu, Deliang; Ni, Quanxing; Jatoi, Aminah; Chari, Suresh; McCleary-Wheeler, Angela L; Fernandez-Zapico, Martin E; Li, Min; Yu, Xianjun

2015-05-01

Pancreatectomy is associated with significant morbidity and unpredictable outcome, with few diagnostic tools to determine, which patients gain the most benefit from this treatment, especially before the operation. This study aimed to define a preoperative signature panel of serum markers to indicate response to pancreatectomy for pancreatic cancer. Over 1000 patients with pancreatic cancer treated at two independent high-volume institutions were included in this study and were divided into three groups, including resected, locally advanced and metastatic. Eight serum tumor markers most commonly used in gastrointestinal cancers were analyzed for patient outcome. Preoperative CA19-9 independently indicated surgical response in pancreatic cancer. Patients with CA19-9 ≥1000 U/mL generally had a poor surgical benefit. However, a subset of these patients still achieved a survival advantage when CA19-9 levels decreased postoperatively. CEA and CA125 in the presence of CA19-9 ≥1000 U/mL could independently predict the non-decrease of CA19-9 postoperatively. The combination of the three markers was useful for predicting a worse surgical outcome with a median survival of 5.1 months vs. 23.0 months (p < 0.001) for the training cohort and 7.0 months vs. 18.2 months (p < 0.001) for the validation cohort and also suggested a higher prevalence of early distant metastasis after surgery. Resected patients with this proposed signature showed no survival advantage over patients in the locally advanced group who did not receive pancreatectomy. Therefore, a preoperative serum signature of CEA(+)/CA125(+)/CA19-9 ≥1000 U/mL is associated with poor surgical outcome and can be used to select appropriate patients with pancreatic cancer for pancreatectomy. © 2014 UICC.

Alterations of carotid arterial mechanics preceding the wall thickening in patients with hypertension.

PubMed

Kim, Sung-Ai; Park, Sun-Hee; Jo, Sang-Ho; Park, Kyoung-Ha; Kim, Hyun-Sook; Han, Sang-Jin; Park, Woo-Jung; Ha, Jong-Won

2016-05-01

Carotid intima-media thickness (cIMT) is an established surrogate marker of atherosclerosis. However, cIMT may not reflect the whole arterial changes occurring in various pathologic conditions, such as hypertension. The aim of this study was to evaluate whether vascular properties of carotid artery (CA) in patients with hypertension differ from those of patients with diabetes and controls before the progression of cIMT. Vascular properties of CA were assessed in 402 consecutive asymptomatic subjects who have normal cIMT (131 with hypertension, 151 with diabetes mellitus, and 120 controls). Conventional carotid stiffness indices calculated from vessel diameter and blood pressure, and parameters from velocity-vector imaging (VVI), including vessel area, fractional area change (FAC), radial velocity, circumferential strain, and strain rate were measured to assess the differences between the groups. In univariate analysis, both patients with hypertension and diabetes showed higher elastic modulus, lower distensibility coefficients and FAC of VVI than those of controls. However, when adjusting for baseline covariates, only FAC (odds ratio [OR] = 0.82, 95% confidence interval [CI] = 0.70-0.97, p = 0.025) and vessel area (OR = 2.84, 95% CI = 1.64-4.91, p < 0.001) discriminated CA of patients with hypertension from those of controls. Also, patients with hypertension showed larger vessel area than diabetes (OR = 2.58, 95% CI = 1.75-3.80, p < 0.001) independent of baseline covariates. No significant vascular parameter was found to discriminate patients with diabetes from controls after adjustments. Despite normal cIMT, the CA of hypertensive patients was stiffer than those of controls and positive remodeling preceded the wall thickening independent of baseline covariates. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Ca2+ influx in the endothelial cells is required for the bradykinin-induced endothelium-dependent contraction in the porcine interlobar renal artery

PubMed Central

Ihara, Eikichi; Derkach, Dmitry N; Hirano, Katsuya; Nishimura, Junji; Nawata, Hajime; Kanaide, Hideo

2001-01-01

To determine the mechanism of bradykinin-induced production of endothelium-derived contracting factors, we monitored the changes in cytosolic Ca2+ concentration ([Ca2+]i) in in situ endothelial cells in porcine aortic valvular strips and the changes in [Ca2+]i of smooth muscle cells and force in porcine interlobar renal arterial strips using front-surface fluorometry of fura-2. In the presence of Nω-nitro-l-arginine methyl ester, bradykinin caused an endothelium-dependent transient elevation of [Ca2+]i and contraction in smooth muscle in the interlobar renal artery. This contraction was completely inhibited by a prostaglandin H2/thromboxane A2 receptor antagonist. In the absence of extracellular Ca2+, bradykinin failed to induce contraction. However, replenishing extracellular Ca2+ to 0.75 mm and higher induced an instantaneous contraction. However, replenishing Ca2+per se did not induce any contraction in the absence of bradykinin. Pretreatment with either 10−5m 1-(β-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenethyl)-1H-imidazole hydrochloride (SKF96365) or 0.2 mm Ni2+ abolished the contraction induced by bradykinin in the presence of extracellular Ca2+. Treatment with 10−5m indomethacin completely inhibited the contractile response induced by Ca2+ replenishment, regardless of the timing of its application, before or after the application of bradykinin. In endothelial cells in the valvular strips, bradykinin caused a transient [Ca2+]i elevation in the presence of 1.25 mm extracellular Ca2+, but [Ca2+]i returned to the resting level within 10 min. Neither 10−5m SKF96365 nor 0.2 mm Ni2+ had any effect on the peak [Ca2+]i elevation, but decreased [Ca2+]i in the declining phase. In the absence of extracellular Ca2+, bradykinin induced a transient [Ca2+]i elevation to a level similar to that seen in the presence of 1.25 mm extracellular Ca2+. However, [Ca2+]i then rapidly returned to the prestimulation level within 5 min. Subsequent Ca2+ replenishment to 0.75 mm and higher in the presence of bradykinin elevated [Ca2+]i to significantly higher levels than the resting level seen in the media containing 1.25 mm Ca2+. In conclusion, Ca2+ influx in the endothelial cells is essential for bradykinin to induce endothelium-dependent contraction in the porcine interlobar renal artery. PMID:11483701

Urinary Concentrating Ability in Women with Asymptomatic Bacteriuria in Pregnancy

PubMed Central

Williams, G. L.; Campbell, H.; Davies, K. J.

1969-01-01

The incidence of impaired renal concentrating ability in pregnant women with asymptomatic significant bacteriuria is significantly less than previously reported when osmolality readings are performed on every urine specimen obtained during the 24 hours' deprivation of fluids. The concentrating defect is more considerable as pregnancy progresses. The lower the maximum urinary osmolality the more difficult is the treatment of the patient, and the higher the incidence of acute pyelonephritis. PMID:5792611

Particle size of calcium carbonate does not affect apparent and standardized total tract digestibility of calcium, retention of calcium, or growth performance of growing pigs.

PubMed

Merriman, L A; Stein, H H

2016-09-01

Two experiments were conducted to evaluate particle size of calcium carbonate used in diets fed to growing pigs. Experiment 1 was conducted to determine apparent total tract digestibility (ATTD), standardized total tract digestibility (STTD), and retention of Ca among diets containing calcium carbonate produced to different particle sizes, and Exp. 2 was conducted to determine if growth performance of weanling pigs is affected by particle size of calcium carbonate. In Exp. 1, 4 diets based on corn and potato protein isolate were formulated to contain 0.70% Ca and 0.33% standardized total tract digestible P, but the calcium carbonate used in the diets was ground to 4 different particle sizes (200, 500, 700, or 1,125 μm). A Ca-free diet was formulated to determine basal endogenous losses of Ca. In Exp. 2, 4 diets were based on corn and soybean meal and the only difference among diets was that each diet contained calcium carbonate ground to the 4 particle sizes used in Exp. 1. In Exp. 1, 40 barrows (15.42 ± 0.70 kg initial BW) were allotted to the 5 diets with 8 replicate pigs per diet using a randomized complete block design, and in Exp. 2, 128 pigs with an initial BW of 9.61 ± 0.09 kg were randomly allotted to 4 experimental diets. Results of Exp. 1 indicated that basal endogenous losses of Ca were 0.329 g/kg DMI. The ATTD of Ca was 70.0 ± 3.2, 74.3 ± 2.7, 70.0 ± 2.9, and 72.1 ± 2.7 and the STTD of Ca was 74.2 ± 3.2, 78.5 ± 2.7, 74.1 ± 2.9, and 76.2 ± 2.7 for calcium carbonate ground to 200, 500, 700, or 1,125 μm, respectively. Retention of Ca was 67.4 ± 3.1, 70.4 ± 2.6, 63.9 ± 2.8, and 67.2 ± 2.2 for diets containing calcium carbonate ground to 200, 500, 700, or 1,125 μm, respectively. There were no differences among diets for ATTD of Ca, STTD of Ca, or retention of Ca. The ATTD of P was 64.5 ± 1.7, 66.8 ± 2.6, 64.2 ± 3.0, and 63.2 ± 1.7% and retention of P was 61.4 ± 1.4, 63.8 ± 2.8, 61.9 ± 2.8, and 60.9 ± 1.5 for diets containing calcium carbonate ground to 200, 500, 700, or 1,125 μm, respectively. Neither ATTD of P nor retention of P was influenced by the particle size of calcium carbonate. Results of Exp. 2 indicated that ADG, ADFI, and G:F were not impacted by the particle size of calcium carbonate. In conclusion, particle size of calcium carbonate did not affect ATTD of Ca, STTD of Ca, or retention of Ca; ATTD of P or retention of P; or growth performance of pigs. Any particle size of calcium carbonate in the range from 200 to 1,125 μm can therefore be used in diets fed to pigs.

DISTURBANCES IN CALCIUM METABOLISM AND CARDIOMYOCYTE NECROSIS: THE ROLE OF CALCITROPIC HORMONES

PubMed Central

Yusuf, Jawwad; Khan, M. Usman; Cheema, Yaser; Bhattacharya, Syamal K.; Weber, Karl T.

2012-01-01

Summary A synchronized dyshomeostasis of extra- and intracellular Ca2+, expressed as plasma ionized hypocalcemia and excessive intracellular Ca2+ accumulation, respectively, represents a common pathophysiologic scenario that accompanies a number of diverse disorders. These include low-renin and salt-sensitive hypertension, primary aldosteronism and hyperparathyroidism, congestive heart failure, acute and chronic hyperadrenergic stressor states, high dietary Na+, and low dietary Ca2+ with hypovitaminosis D. Homeostatic responses are invoked to restore normal extracellular [Ca2+]o, including increased plasma levels of parathyroid hormone and 1,25(OH)2D3. However, in cardiomyocytes, these calcitropic hormones concurrently promote cytosolic free [Ca2+]i and mitochondrial [Ca2+]m overloading. The latter sets into motion organellar-based oxidative stress, in which the rate of reactive oxygen species generation overwhelms their detoxification by endogenous antioxidant defenses, including those related to intrinsically coupled increments in intracellular Zn2+. In turn, the opening potential of the mitochondrial permeability transition pore increases allowing for osmotic swelling and ensuing organellar degeneration. Collectively, these pathophysiologic events represent the major components to a mitochondriocentric signal-transducer-effector pathway to cardiomyocyte necrosis. From necrotic cells there follows a spillage of intracellular contents, including troponins, and a subsequent wound healing response with reparative fibrosis, or scarring. Taken together the loss of terminally differentiated cardiomyocytes from this postmitotic organ and the ensuing replacement fibrosis each contribute to the adverse structural remodeling of myocardium and progressive nature of heart failure. In conclusion, hormone-induced ionized hypocalcemia and intracellular Ca2+ overloading comprise a pathophysiologic cascade common to diverse disorders and which initiates a mitochondriocentric pathway to nonischemic cardiomyocyte necrosis. PMID:22824113

Interactions between calcium and phosphorus in the regulation of the production of fibroblast growth factor 23 in vivo

PubMed Central

Quinn, Stephen J.; Thomsen, Alex R. B.; Pang, Jian L.; Kantham, Lakshmi; Bräuner-Osborne, Hans; Pollak, Martin; Goltzman, David

2013-01-01

Calcium and phosphorus homeostasis are highly interrelated and share common regulatory hormones, including FGF23. However, little is known about calcium's role in the regulation of FGF23. We sought to investigate the regulatory roles of calcium and phosphorus in FGF23 production using genetic mouse models with targeted inactivation of PTH (PTH KO) or both PTH and the calcium-sensing receptor (CaSR; PTH-CaSR DKO). In wild-type, PTH KO, and PTH-CaSR DKO mice, elevation of either serum calcium or phosphorus by intraperitoneal injection increased serum FGF23 levels. In PTH KO and PTH-CaSR DKO mice, however, increases in serum phosphorus by dietary manipulation were accompanied by severe hypocalcemia, which appeared to blunt stimulation of FGF23 release. Increases in dietary phosphorus in PTH-CaSR DKO mice markedly decreased serum 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] despite no change in FGF23, suggesting direct regulation of 1,25(OH)2D3 synthesis by serum phosphorus. Calcium-mediated increases in serum FGF23 required a threshold level of serum phosphorus of about 5 mg/dl. Analogously, phosphorus-elicited increases in FGF23 were markedly blunted if serum calcium was less than 8 mg/dl. The best correlation between calcium and phosphorus and serum FGF23 was found between FGF23 and the calcium × phosphorus product. Since calcium stimulated FGF23 production in the PTH-CaSR DKO mice, this effect cannot be mediated by the full-length CaSR. Thus the regulation of FGF23 by both calcium and phosphorus appears to be fundamentally important in coordinating the serum levels of both mineral ions and ensuring that the calcium × phosphorus product remains within a physiological range. PMID:23233539

A prospective evaluation of early detection biomarkers for ovarian cancer in the European EPIC cohort

PubMed Central

Terry, Kathryn L.; Schock, Helena; Fortner, Renée T.; Hüsing, Anika; Fichorova, Raina N.; Yamamoto, Hidemi S.; Vitonis, Allison F.; Johnson, Theron; Overvad, Kim; Tjønneland, Anne; Boutron-Ruault, Marie-Christine; Mesrine, Sylvie; Severi, Gianluca; Dossus, Laure; Rinaldi, Sabina; Boeing, Heiner; Benetou, Vassiliki; Lagiou, Pagona; Trichopoulou, Antonia; Krogh, Vittorio; Kuhn, Elisabetta; Panico, Salvatore; Bueno-de-Mesquita, H. Bas; Onland-Moret, N. Charlotte; Peeters, Petra H.; Gram, Inger Torhild; Weiderpass, Elisabete; Duell, Eric J.; Sanchez, Maria-Jose; Ardanaz, Eva; Etxezarreta, Nerea; Navarro, Carmen; Idahl, Annika; Lundin, Eva; Jirström, Karin; Manjer, Jonas; Wareham, Nicholas J.; Khaw, Kay-Tee; Byrne, Karl Smith; Travis, Ruth C.; Gunter, Marc J.; Merritt, Melissa A.; Riboli, Elio; Cramer, Daniel W.; Kaaks, Rudolf

2016-01-01

Purpose About 60% of ovarian cancers are diagnosed at late stage, when 5-year survival is less than 30% in contrast to 90% for local disease. This has prompted search for early detection biomarkers. For initial testing, specimens taken months or years before ovarian cancer diagnosis are the best source of information to evaluate early detection biomarkers. Here we evaluate the most promising ovarian cancer screening biomarkers in prospectively collected samples from the European Prospective Investigation into Cancer and Nutrition study. Experimental Design We measured CA125, HE4, CA72.4 and CA15.3 in 810 invasive epithelial ovarian cancer cases and 1,939 controls. We calculated the sensitivity at 95% and 98% specificity as well as Area under the Receiver Operator Curve (C-statistic) for each marker individually and in combination. Additionally, we evaluated marker performance by stage at diagnosis and time between blood draw and diagnosis. Results We observed the best discrimination between cases and controls within six months of diagnosis for CA125 (C-statistic=0.92), then HE4 (0.84), CA72.4 (0.77), and CA15.3 (0.73). Marker performance declined with longer time between blood draw and diagnosis and for earlier staged disease. However, assessment of discriminatory ability at early stage was limited by small numbers. Combinations of markers performed modestly, but significantly better than any single marker. Conclusions CA125 remains the single best marker for the early detection of invasive epithelial ovarian cancer, but can be slightly improved by combining with other markers. Identifying novel markers for ovarian cancer will require studies including larger numbers of early stage cases. PMID:27060155

A Prospective Evaluation of Early Detection Biomarkers for Ovarian Cancer in the European EPIC Cohort.

PubMed

Terry, Kathryn L; Schock, Helena; Fortner, Renée T; Hüsing, Anika; Fichorova, Raina N; Yamamoto, Hidemi S; Vitonis, Allison F; Johnson, Theron; Overvad, Kim; Tjønneland, Anne; Boutron-Ruault, Marie-Christine; Mesrine, Sylvie; Severi, Gianluca; Dossus, Laure; Rinaldi, Sabina; Boeing, Heiner; Benetou, Vassiliki; Lagiou, Pagona; Trichopoulou, Antonia; Krogh, Vittorio; Kuhn, Elisabetta; Panico, Salvatore; Bueno-de-Mesquita, H Bas; Onland-Moret, N Charlotte; Peeters, Petra H; Gram, Inger Torhild; Weiderpass, Elisabete; Duell, Eric J; Sanchez, Maria-Jose; Ardanaz, Eva; Etxezarreta, Nerea; Navarro, Carmen; Idahl, Annika; Lundin, Eva; Jirström, Karin; Manjer, Jonas; Wareham, Nicholas J; Khaw, Kay-Tee; Byrne, Karl Smith; Travis, Ruth C; Gunter, Marc J; Merritt, Melissa A; Riboli, Elio; Cramer, Daniel W; Kaaks, Rudolf

2016-09-15

About 60% of ovarian cancers are diagnosed at late stage, when 5-year survival is less than 30% in contrast to 90% for local disease. This has prompted search for early detection biomarkers. For initial testing, specimens taken months or years before ovarian cancer diagnosis are the best source of information to evaluate early detection biomarkers. Here we evaluate the most promising ovarian cancer screening biomarkers in prospectively collected samples from the European Prospective Investigation into Cancer and Nutrition study. We measured CA125, HE4, CA72.4, and CA15.3 in 810 invasive epithelial ovarian cancer cases and 1,939 controls. We calculated the sensitivity at 95% and 98% specificity as well as area under the receiver operator curve (C-statistic) for each marker individually and in combination. In addition, we evaluated marker performance by stage at diagnosis and time between blood draw and diagnosis. We observed the best discrimination between cases and controls within 6 months of diagnosis for CA125 (C-statistic = 0.92), then HE4 (0.84), CA72.4 (0.77), and CA15.3 (0.73). Marker performance declined with longer time between blood draw and diagnosis and for earlier staged disease. However, assessment of discriminatory ability at early stage was limited by small numbers. Combinations of markers performed modestly, but significantly better than any single marker. CA125 remains the single best marker for the early detection of invasive epithelial ovarian cancer, but can be slightly improved by combining with other markers. Identifying novel markers for ovarian cancer will require studies including larger numbers of early-stage cases. Clin Cancer Res; 22(18); 4664-75. ©2016 AACRSee related commentary by Skates, p. 4542. ©2016 American Association for Cancer Research.

Transient asymptomatic pulmonary opacities occurring during osimertinib treatment

PubMed Central

Noonan, Sinead A.; Sachs, Peter B.; Camidge, D. Ross

2017-01-01

Introduction Osimertinib is an Epidermal Growth Factor Receptor (EGFR) Inhibitor licensed for the treatment of EGFR mutant, T790M positive, non-small cell lung cancer (NSCLC). Previously unreported, common, transient asymptomatic pulmonary opacities (TAPOs) were noted at the University of Colorado in patients during osimertinib therapy. Methods CT imaging and clinical notes of NSCLC patients treated at the University of Colorado with osimertinib were retrospectively reviewed. Results Seven of twenty patients (35%), developed TAPOs while on osimertinib. The radiological patterns seen included ground-glass opacities with/without nodular consolidation. The median time to first lesion development was 8.7 weeks (range: 1.6 – 43 weeks) and 6 weeks (range: 1 – 11 weeks) to resolution during continued osimertinib. Conclusions TAPOs may be a previously unrecognized, benign feature associated with osimertinib therapy, which may be mistaken for isolated pulmonary progression or the beginning of more severe pneumonitis. If new onset pulmonary lesions, especially those associated with ground-glass appearances, are asymptomatic, localized and there is no evidence of disease progression elsewhere it may be reasonable to continue treatment with osimertinib and monitor these lesions for resolution. PMID:27618759

The importance of vitamin C for hydroxylation of vitamin D3 to 1,25(OH)2D3 in man.

PubMed

Cantatore, F P; Loperfido, M C; Magli, D M; Mancini, L; Carrozzo, M

1991-06-01

The effects of vitamin C on 1,25(OH)2D3 synthesis in humans were evaluated; the study included 20 females. They were divided into 2 groups. The first of the 10 subjects (age range 55-71) received ascorbic acid at a dose of 150 mg/die i.v. for 10 days; the second 10 subjects (age range 55-69) received a placebo i.v. for 10 days. In a later study (after a 30-day washout) the same two groups were tested for the second time with ascorbic acid at a dose of 1,000 mg/die i.v. for 10 days and placebo i.v. for 10 days. Serum calcium and phosphorus, serum Ca++, serum proteins, blood and urinary pH, serum 25(OH)D3 and 1,25(OH)2D3, serum PTH, urinary hydroxyprolin were tested before and after the treatments. In the first study a significant increase in serum 1,25(OH)2D3 was observed after ascorbic acid while no significant variation was observed for the other parameters. In the second study, a significant increase in serum Ca++ and a significant decrease in serum 1,25(OH)2D3 were observed after ascorbic acid while no significant variation was observed for the other parameters. The authors conclude that ascorbic acid promotes 1,25(OH)2D3 synthesis at a paraphysiologic dose (150 mg/die) in humans but this synthesis is inhibited at higher doses (1,000 mg/die). The latter effect by Ca++ or by an effect of ascorbate on 1 alpha-hydroxylase enzyme could be mediated.

Field-effect amperometric immuno-detection of protein biomarker.

PubMed

Wang, Jiapeng; Yau, Siu-Tung

2011-11-15

The field-effect enzymatic detection technique has been applied to the amperometric immunoassay of the cancer biomarker, carcinoma antigen 125 (CA 125). The detection adopted a reagentless approach, in which the analyte, CA 125, was immobilized on the detecting electrode, which was modified using carbon nanotubes, and the detection signal was obtained by measuring the reduction peak current of the enzyme that was used to label the antibody. A gating voltage was applied to the detecting electrode, inducing increase in the signal current and therefore providing amplification of the detection signal. The voltage-controlled signal amplification of the detection system has increased the sensitivity and lowered the detection limit of the system. A detection limit of 0.9U/ml was obtained in the work. Copyright © 2011 Elsevier B.V. All rights reserved.

A Phase 2 Trial of Flavopiridol (Alvocidib) and Cisplatin in Platin-Resistant Ovarian and Primary Peritoneal Carcinoma: MC0261

PubMed Central

Bible, Keith C.; Peethambaram, Prema P.; Oberg, Ann L.; Maples, William; Groteluschen, David L.; Boente, Matthew; Burton, Jill K.; Gomez Dahl, Leigh C.; Tibodeau, Jennifer D.; Isham, Crescent R.; Maguire, Jacie L.; Shridhar, Viji; Kukla, Andrea K.; Voll, Kalli J.; Mauer, Mathew J.; Colevas, Alexander D.; Wright, John; Doyle, L. Austin; Erlichman, Charles

2014-01-01

Purpose Based upon promising preclinical and phase 1 trial results, combined flavopiridol and cisplatin therapy was evaluated in patients with ovarian and primary peritoneal cancers. Methods A two cohort phase 2 trial of cisplatin (60 mg/m2 IV) immediately followed by flavopiridol (100 mg/m2 IV, 24 h infusion; 21 day cycles) was undertaken in patients with recurrent platin-sensitive or platin-resistant disease (progression > vs. ≤6 months following prior platin-based therapy). Measurable disease (RECIST) - or evaluable disease plus CA125 >2× post-treatment nadir - and ECOG performance ≤2 were required. Results Forty-five patients were enrolled between December 23, 2004 and February 25, 2010: 40 platin-resistant (Group 1), and 5 platin-sensitive (Group 2). In Group 1, the median number of treatment cycles was 3 (range 2–12). Only 10% of patients incurred grade 4 toxicities, but grade 3 toxicities were common (65%): neutropenia (17.5%); nausea (12.5%); vomiting, fatigue, thrombosis, anemia (10% each). Seven patients (17.5%) achieved a confirmed response (1 CR, 6 PR; median duration 118 days); ten additional patients (25%) attained maintained stable disease. Median time to progression was 4.3 months; overall survival was 16.1 months. Pilot translational studies assessed ascites flavopiridol level; surrogate marker studies were uninformative. In Group 2, although 4 of 5 patients responded (2 confirmed PRs with median time to progression, 10.8 months and median overall survival 20.6 months) the cohort was closed due to poor accrual. Conclusions The assessed flavopiridol and cisplatin regimen displayed clinical activity in platin resistant and sensitive ovarian/primary peritoneal cancers, meriting further study. PMID:22664059

125. HYDRAULIC CONTROLS FOR MAST TRENCH DOORS ON LEFT SIDE ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

125. HYDRAULIC CONTROLS FOR MAST TRENCH DOORS ON LEFT SIDE OF HYDRAULIC CONTROL PANEL IN UMBILICAL MAST PUMP ROOM (209), LSB (BLDG. 751) - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 East, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

Single point biochemical measurement algorithm for early diagnosis of ectopic pregnancy.

PubMed

Butler, Stephen A; Abban, Thomas K A; Borrelli, Paola T A; Luttoo, Jameel M; Kemp, Bryn; Iles, Ray K

2013-09-01

Tubal rupture as a result of an ectopic pregnancy is the leading cause of first trimester maternal mortality. Currently, the diagnosis of ectopic pregnancy depends on transvaginal ultrasound and serial serum measurements of human chorionic gonadotrophin (hCG), which requires follow up. The objective of this study was to examine whether single point measurements at presentation could distinguish between women with ectopic pregnancy, viable pregnancy, and spontaneous miscarriage. Serum total hCG (hCGt), hyperglycosylated hCG (hCGh), free beta subunit of hCG (hCGβ), progesterone (P), and CA-125 were measured by chemiluminescence immunoassay over a 3 month period in 441 women presenting at the emergency room with abdominal pain and a positive pregnancy test. Patient outcomes were followed and confirmed by histology. 65 samples were excluded due to poor sample storage, or lost to follow up. The pregnancy outcomes were 175 viable pregnancies, 175 spontaneous miscarriages, and 26 ectopic pregnancies. A serum hCGt <3736 mIU/mL cut off was 100% sensitive, with 76% specificity, for distinguishing ectopic pregnancy from viable pregnancy; but did not differentiate spontaneous miscarriage. Serum CA125 <41.98 U/mL produced 100% sensitivity and 43% specificity in distinguishing ectopic pregnancy from spontaneous miscarriage. Sequential application of hCGt and CA-125 cut off followed by ultrasound could detect 100% of ectopic pregnancies with 87% specificity for all intrauterine pregnancies. The combination of serum hCGt <3736 mIU/mL, followed by CA125 <41.98 U/mL is a promising algorithm for detecting all ectopic pregnancy at initial presentation. © 2013.

Screening of the residual normal ovarian tissue adjacent to orthotopic epithelial ovarian carcinomas in nude mice.

PubMed

Zhu, G H; Wang, S T; Yao, M Z; Cai, J H; Chen, C Y; Yang, Z X; Hong, L; Yang, S Y

2014-04-16

The objective of this study was to explore the feasibility and methods of screening the residual normal ovarian tissue adjacent to orthotopic ovarian carcinomas in nude mice. Human epithelial ovarian cancer cells (OVCAR3) were subcutaneously implanted for a tumor source and ovarian orthotopic transplantation. The cancer tissue, proximal paraneoplastic tissue, middle paraneoplastic tissue, remote paraneoplastic tissue, and normal ovarian tissue were removed. CK-7, CA125, p53, survivin, MMP-2, and TIMP-2 expression was detected by reverse transcription polymerase chain reaction. We obtained 35 paraneoplastic residual ovarian tissues with normal biopsies from 40 cases of an orthotopic epithelial ovarian carcinoma model (87.5%). CK-7, CA125, p53, survivin, MMP-2, and TIMP-2 expression was lower in proximal paraneoplastic tissue than in cancer tissue (P < 0.05) and higher than in middle and remote paraneoplastic tissue (P < 0.01). There was no statistically significant difference between the expression of these genes in middle and proximal paraneoplastic tissue as well as among residual normal ovarian tissues with different severity (P > 0.05). In ovarian tissues of 20 normal nude mice, the expression of CK- 7, CA125, p53, survivin, MMP-2, and TIMP-2 was negative. Overall, the expression levels of CK-7, CA125, p53, survivin, MMP-2, TIMP-2, and other molecular markers showed a decreasing trend in the non-cancer tissue direction. The expression levels can be used as standards to screen residual normal ovarian tissue. We can obtain relatively safe normal ovarian tissues adjacent to epithelial ovarian cancer.

Clostridium difficile rates in asymptomatic and symptomatic hospitalized patients using nucleic acid testing.

PubMed

Truong, Cynthia; Schroeder, Lee F; Gaur, Rajiv; Anikst, Victoria Emma; Komo, Ikuko; Watters, Colleen; McCalley, Erin; Kulik, Carole; Pickham, David; Lee, Nancy J; Banaei, Niaz

2017-04-01

The Clostridium difficile rate in symptomatic patients represents both those with C. difficile infection (CDI) and those with colonization. To predict the extent of CDI overdiagnosis, we compared the asymptomatic colonization rate to the symptomatic positivity rate in hospitalized patients using nucleic acid testing. Between July 2014 and April 2015, formed stool samples were collected from asymptomatic patients after admission to 3 hospital wards at the Stanford Hospital. Stool samples from symptomatic patients with suspected CDI in the same wards were collected for testing per provider order. The GeneXpert C. difficile tcdB polymerase chain reaction (PCR) assay (Cepheid, Sunnyvale, CA, USA) was performed on all stool samples and PCR cycle threshold was used as a measure of genomic equivalents. Chart review was performed to obtain clinical history and medication exposure. We found an asymptomatic C. difficile carriage rate of 11.8% (43/365) (95% confidence interval [CI], 8.5-15.1%) and a positivity rate in symptomatic patients of 15.4% (54/351) (95% CI, 11.6-19.2%; P=0.19). The median PCR cycle thresholds was not significantly different between asymptomatic carriers and symptomatic positives (29.5 versus 27.3; P=0.07). Among asymptomatic patients, 11.6% (5/43) of carriers and 8.4% (27/322; P=0.56) of noncarriers subsequently became symptomatic CDI suspects within the same hospitalization. Single and multivariate analysis did not identify any demographic or clinical factors as being significantly associated with C. difficile carriage. Asymptomatic C. difficile carriage rate was similar to symptomatic positivity rate. This suggests the majority of PCR-positive results in symptomatic patients are likely due to C. difficile colonization. Disease-specific biomarkers are needed to accurately diagnose patients with C. difficile disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Transitions in Illicit Drug Use Status over 3 Years: A Prospective Analysis of a General Population Sample

PubMed Central

Compton, Wilson M.; Dawson, Deborah A.; Conway, Kevin P.; Brodsky, Marc; Grant, Bridget F.

2015-01-01

Objective To examine 3-year transitions among nonuse, asymptomatic use and problem use of illicit drugs for US adults in the general household population. Method Data from the nationally representative NESARC study of 34,653 adults interviewed twice, 3 years apart. Three mutually exclusive categories of baseline drug status comprised past year non-users (n=32,675), past-year asymptomatic drug users (n=861), and past-year symptomatic drug users (n=1,117). Symptomatic drug use was defined as presence of one or more symptoms that operationalize DSM-IV drug abuse and dependence criteria. Variables tested for association with 3-year transitions to different status categories included sociodemographic, health, substance use and psychiatric covariates. Results Among baseline nonusers, 95.4% continued to be nonusers at follow-up, 2.1% became asymptomatic users, and 2.5% developed drug problems. Among baseline asymptomatic users, 66.6% had stopped using drugs at follow-up, 14.3% continued to be asymptomatic users and 19.1% had developed drug problems. Nearly half (49.0%) of those with drug problems at baseline had stopped using drugs at follow-up, 10.9% had transitioned to asymptomatic use and 40.1% continued to have drug problems. Younger age, male gender, white race, and not being married were associated with progression from non-use to use or problematic use, as were alcohol and tobacco categories, major depression and schizotypal, borderline and narcissistic personality disorders. Panic disorder and avoidant personality disorder were associated with less progression. Conclusions Transitions in drug use status are common. The finding that alcohol and tobacco-related variables and co-occurring psychopathology are important correlates of transitions suggests the value of addressing all co-occurring disorders and substance use in patient assessments and treatment planning, both for preventing adverse transitions and promoting positive transitions. PMID:23511653

Transitions in illicit drug use status over 3 years: a prospective analysis of a general population sample.

PubMed

Compton, Wilson M; Dawson, Deborah A; Conway, Kevin P; Brodsky, Marc; Grant, Bridget F

2013-06-01

The authors examined 3-year transitions among nonuse, asymptomatic use, and problem use of illicit drugs for U.S. adults in the general household population. Data were from the nationally representative National Epidemiologic Survey on Alcohol and Related Conditions, a study of 34,653 adults interviewed twice, 3 years apart. Respondents were categorized on three mutually exclusive categories of baseline drug status: past-year nonusers (N=32,675), past-year asymptomatic drug users (N=861), and past-year symptomatic drug users (N=1,117). Symptomatic drug use, or problem use, was defined as presence of one or more symptoms that operationalize DSM-IV drug abuse and dependence criteria. The authors assessed sociodemographic, health, substance use, and psychiatric covariates for association with 3-year transitions to different status categories. Among baseline nonusers, 95.4% continued to be nonusers at follow-up, 2.1% became asymptomatic users, and 2.5% developed problem use. Among baseline asymptomatic users, 66.6% had stopped using drugs at follow-up, 14.3% continued to be asymptomatic users, and 19.1% had developed problem use. Nearly half (49.0%) of those with problem use at baseline had stopped using drugs at follow-up, 10.9% had transitioned to asymptomatic use, and 40.1% continued to have problem use. Younger age, male sex, white race, and not being married were associated with progression from nonuse to use or problem use, as were alcohol and tobacco use and disorders, major depression, and schizotypal, borderline, and narcissistic personality disorders. Panic disorder and avoidant personality disorder were associated with less progression. Transitions in drug use status are common. The finding that alcohol and tobacco variables and co-occurring psychopathology are important correlates of transitions suggests the value of addressing all co-occurring disorders and substance use in patient assessments and treatment planning, both to prevent adverse transitions and to promote positive transitions.

Secretome Identifies Tenascin-X as a Potent Marker of Ovarian Cancer

PubMed Central

Kramer, Marianne; Pierredon, Sandra; Ribaux, Pascale; Tille, Jean-Christophe; Cohen, Marie

2015-01-01

CA-125 has been a valuable marker for the follow-up of ovarian cancer patients but it is not sensitive enough to be used as diagnostic marker. We had already used secretomic methods to identify proteins differentially secreted by serous ovarian cancer cells compared to healthy ovarian cells. Here, we evaluated the secretion of these proteins by ovarian cancer cells during the follow-up of one patient. Proteins that correlated with CA-125 levels were screened using serum samples from ovarian cancer patients as well as benign and healthy controls. Tenascin-X secretion was shown to correlate with CA-125 value in the initial case study. The immunohistochemical detection of increased amount of tenascin-X in ovarian cancer tissues compared to healthy tissues confirms the potent interest in tenascin-X as marker. We then quantified the tenascin-X level in serum of patients and identified tenascin-X as potent marker for ovarian cancer, showing that secretomic analysis is suitable for the identification of protein biomarkers when combined with protein immunoassay. Using this method, we determined tenascin-X as a new potent marker for serous ovarian cancer. PMID:26090390

Human T-cell leukemia virus type I (HTLV-1) proviral load and disease progression in asymptomatic HTLV-1 carriers: a nationwide prospective study in Japan.

PubMed

Iwanaga, Masako; Watanabe, Toshiki; Utsunomiya, Atae; Okayama, Akihiko; Uchimaru, Kaoru; Koh, Ki-Ryang; Ogata, Masao; Kikuchi, Hiroshi; Sagara, Yasuko; Uozumi, Kimiharu; Mochizuki, Manabu; Tsukasaki, Kunihiro; Saburi, Yoshio; Yamamura, Masaomi; Tanaka, Junji; Moriuchi, Yukiyoshi; Hino, Shigeo; Kamihira, Shimeru; Yamaguchi, Kazunari

2010-08-26

Definitive risk factors for the development of adult T-cell leukemia (ATL) among asymptomatic human T-cell leukemia virus type I (HTLV-1) carriers remain unclear. Recently, HTLV-1 proviral loads have been evaluated as important predictors of ATL, but a few small prospective studies have been conducted. We prospectively evaluated 1218 asymptomatic HTLV-1 carriers (426 males and 792 females) who were enrolled during 2002 to 2008. The proviral load at enrollment was significantly higher in males than females (median, 2.10 vs 1.39 copies/100 peripheral blood mononuclear cells [PBMCs]; P < .001), in those 40 to 49 and 50 to 59 years of age than that of those 40 years of age and younger (P = .02 and .007, respectively), and in those with a family history of ATL than those without the history (median, 2.32 vs 1.33 copies/100 PBMCs; P = .005). During follow-up, 14 participants progressed to overt ATL. Their baseline proviral load was high (range, 4.17-28.58 copies/100 PBMCs). None developed ATL among those with a baseline proviral load lower than approximately 4 copies. Multivariate Cox analyses indicated that not only a higher proviral load, advanced age, family history of ATL, and first opportunity for HTLV-1 testing during treatment for other diseases were independent risk factors for progression of ATL.

Timing of surgery in valvular heart disease: prophylactic surgery vs watchful waiting in the asymptomatic patient.

PubMed

Gillam, Linda D; Marcoff, Leo; Shames, Sofia

2014-09-01

In the absence of randomized controlled trial data, the management of patients with severe valvular heart disease without symptoms, ventricular dysfunction, or other identified triggers for surgery is controversial. In this review, we frame the debate between prophylactic surgery vs close follow-up until triggers occur (watchful waiting) for severe aortic stenosis and degenerative mitral regurgitation (MR), the 2 conditions for which the pros and cons of these approaches are best articulated. Classic high-gradient severe aortic stenosis is generally accurately diagnosed. In asymptomatic patients, stress testing can be used to confirm asymptomatic status and identify high-risk features including reduced exercise tolerance, exercise-induced symptoms, and absolute or relative hypotension. Resting echocardiographic predictors of disease progression and/or adverse events include very high gradients, rapid progression, and extensive calcification. Surgical risk calculators can help estimate perioperative morbidity/mortality with the ultimate choice of a medical vs a prophylactic surgical approach to be made after discussion with the patient. With degenerative MR, severity can be inaccurately estimated. Stress testing might clarify whether the patient is truly asymptomatic and identify features associated with worse prognosis and symptom onset. Selecting patients with high probability of repair can be challenging. Perioperative risk and postoperative risks including those of unanticipated valve replacement and recurrent MR after repair are also considerations. In aggregate, management of patients with valvular disease who are asymptomatic and who have no clear trigger for surgery is complex, requires individualization, and should be carried out by or in collaboration with a heart valve centre of excellence. Copyright © 2014 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

The population-based Barcelona-Asymptomatic Intracranial Atherosclerosis Study (ASIA): rationale and design.

PubMed

López-Cancio, Elena; Dorado, Laura; Millán, Mónica; Reverté, Silvia; Suñol, Anna; Massuet, Anna; Mataró, María; Galán, Amparo; Alzamora, Maite; Pera, Guillem; Torán, Pere; Dávalos, Antoni; Arenillas, Juan F

2011-02-17

Large-artery intracranial atherosclerosis may be the most frequent cause of ischemic stroke worldwide. Traditional approaches have attempted to target the disease when it is already symptomatic. However, early detection of intracranial atherosclerosis may allow therapeutic intervention while the disease is still asymptomatic. The prevalence and natural history of asymptomatic intracranial atherosclerosis in Caucasians remain unclear. The aims of the Barcelona-ASymptomatic Intracranial Atherosclerosis (ASIA) study are (1) to determine the prevalence of ASIA in a moderate-high vascular risk population, (2) to study its prognostic impact on the risk of suffering future major ischemic events, and (3) to identify predictors of the development, progression and clinical expression of this condition. Cross-over and cohort, population-based study. A randomly selected representative sample of 1,503 subjects with a mild-moderate-high vascular risk (as defined by a REGICOR score ≥ 5%) and with neither a history of cerebrovascular nor ischemic heart disease will be studied. At baseline, all individuals will undergo extracranial and transcranial Color-Coded Duplex (TCCD) ultrasound examinations to detect presence and severity of extra and intracranial atherosclerosis. Intracranial stenoses will be assessed by magnetic resonance angiography (MRA). Clinical and demographic variables will be recorded and blood samples will be drawn to investigate clinical, biological and genetic factors associated with the presence of ASIA. A long-term clinical and sonographic follow-up will be conducted thereafter to identify predictors of disease progression and of incident vascular events. The Barcelona-ASIA is a population-based study aiming to evaluate the prevalence and clinical importance of asymptomatic intracranial large-artery atherosclerosis in Caucasians. The ASIA project may provide a unique scientific resource to better understand the dynamics of intracranial atherosclerosis from its early stages and to identify new potential therapeutic targets for this condition.

Genomic tests for ovarian cancer detection and management.

PubMed

Myers, Evan R; Havrilesky, Laura J; Kulasingam, Shalini L; Sanders, Gillian D; Cline, Kathryn E; Gray, Rebecca N; Berchuck, Andrew; McCrory, Douglas C

2006-10-01

To assess the evidence that the use of genomic tests for ovarian cancer screening, diagnosis, and treatment leads to improved outcomes. PubMed and reference lists of recent reviews. We evaluated tests for: (a) single gene products; (b) genetic variations affecting risk of ovarian cancer; (c) gene expression; and (d) proteomics. For tests covered in recent evidence reports (cancer antigen 125 [CA-125] and breast cancer genes 1 and 2 [BRCA1/2]), we added studies published subsequent to the reports. We sought evidence on: (a) the analytic performance of tests in clinical laboratories; (b) the sensitivity and specificity of tests in different patient populations; (c) the clinical impact of testing in asymptomatic women, women with suspected ovarian cancer, and women with diagnosed ovarian cancer; (d) the harms of genomic testing; and (e) the impact of direct-to-consumer and direct-to-physician advertising on appropriate use of tests. We also constructed a computer simulation model to test the impact of different assumptions about ovarian cancer natural history on the relative effectiveness of different strategies. There are reasonable data on the clinical laboratory performance of most radioimmunoassays, but the majority of the data on other genomic tests comes from research laboratories. Genomic test sensitivity/specificity estimates are limited by small sample sizes, spectrum bias, and unrealistically large prevalences of ovarian cancer; in particular, estimates of positive predictive values derived from most of the studies are substantially higher than would be expected in most screening or diagnostic settings. We found no evidence relevant to the question of the impact of genomic tests on health outcomes in asymptomatic women. Although there is a relatively large literature on the association of test results and various clinical outcomes, the clinical utility of changing management based on these results has not been evaluated. We found no evidence that genomic tests for ovarian cancer have unique harms beyond those common to other tests for genetic susceptibility or other tests used in screening, diagnosis, and management of ovarian cancer. Studies of a direct-to-consumer campaign for BRCA1/2 testing suggest increased utilization, but the effect on "appropriateness" was unclear. Model simulations suggest that annual screening, even with a highly sensitive test, will not reduce ovarian cancer mortality by more than 50 percent; frequent screening has a very low positive predictive value, even with a highly specific test. Although research remains promising, adaptation of genomic tests into clinical practice must await appropriately designed and powered studies in relevant clinical settings.

Calcium and strontium isotope fractionation in aqueous solutions as a function of temperature and reaction rate; I. Calcite

NASA Astrophysics Data System (ADS)

AlKhatib, Mahmoud; Eisenhauer, Anton

2017-07-01

In order to study Strontium (Sr) partitioning and isotope fractionation of Sr and Calcium (Ca) in calcite we performed precipitation (T) experiments decoupling temperature and precipitation rate (R∗). Calcite was precipitated at 12.5, 25.0 and 37.5 °C by diffusing NH3 and CO2 gases into aqueous solutions closely following the experimental setup of Lemarchand et al. (2004). The precipitation rate (R∗) for every sample was determined applying the initial rate method and from the specific surface area of almost all samples for each reaction. The order of reaction with respect to Ca2+ ions was determined to be one and independent of T. However, the order of reaction with respect to HCO3- changed from three to one as temperature increases from 12.5, 25 °C and 37.5 °C. Strontium incorporated into calcite (expressed as DSr = [Sr/Ca]calcite/[Sr/Ca]solution) was found to be R∗ and T dependent. As a function of increasing R∗ the Δ88/86Sr-values become more negative and as temperature increases the Δ88/86Sr values also increase at constant R∗. The DSr and Δ88/86Sr-values are correlated to a high degree and depend only on R∗ being independent of temperature, complexation and varying initial ratios. Latter observation may have important implications for the study of diagenesis, the paleo-sciences and the reconstruction of past environmental conditions. Calcium isotope fractionation (Δ44/40Ca) was also found to be R∗ and T dependent. For 12.5 and 25.0 °C we observe a general increase of the Δ44/40Ca values as a function of R∗ (Lemarchand et al. type behavior, Lemarchand et al. (2004)). Whereas at 37.5 °C a significant decreasing Δ44/40Ca is observed relative to increasing R∗ (Tang et al. type behavior, Tang et al. (2008)). In order to reconcile the discrepant observations we suggest that the temperature triggered change from a Ca2+-NH3-aquacomplex covalent controlled bonding to a Ca2+-H2O-aquacomplex van-der-Waals controlled bonding caused the change in sign of the R∗ - Δ44/40Ca slope due to the switch of an equilibrium type of isotope fractionation related to the covalent bonding during lower temperatures to a kinetic type of isotope fractionation at higher temperatures. This is supported by the observation that the Δ44/40Ca ratios tend to depend on the [Ca]:[DIC] ratio at 12.5 and 25 °C but is highly independent at 37.5 °C. Our observations imply the chemical fluid composition and temperature dependent complexation controls the amount and direction of Ca isotope fractionation in contrast to the Sr isotopes which do not show any change of its fractionation behavior as a function of complexation in the liquid phase.

EGFR-mutant Non-small Cell Lung Cancer Accompanied by Transient Asymptomatic Pulmonary Opacities Successfully Treated with "Stop-And-Go" Osimertinib.

PubMed

Kobayashi, Keigo; Naoki, Katsuhiko; Kuroda, Aoi; Yasuda, Hiroyuki; Kawada, Ichiro; Soejima, Kenzo; Betsuyaku, Tomoko

2018-04-01

A 69-year-old man with post-operative recurrence of lung adenocarcinoma was treated with multiple chemotherapies, including epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors. A second biopsy revealed an EGFR T790M mutation. As 10th-line chemotherapy, osimertinib was initiated. After 24 weeks, chest computed tomography (CT) revealed asymptomatic ground-glass opacities in both lobes. After four weeks of osimertinib discontinuation, imaging revealed rapid lung cancer progression. Osimertinib was resumed. After 11 weeks, CT revealed decreased lung nodules with no exacerbation of interstitial lung disease. We describe a patient who experienced transient asymptomatic pulmonary opacities during treatment with osimertinib, which was successfully managed by a "stop-and-go" approach.

Circulating MicroRNAs as Novel Biomarkers of Stenosis Progression in Asymptomatic Carotid Stenosis.

PubMed

Dolz, Sandra; Górriz, David; Tembl, José Ignacio; Sánchez, Dolors; Fortea, Gerardo; Parkhutik, Vera; Lago, Aida

2017-01-01

Progression of asymptomatic carotid artery stenosis (ACAS) in patients with >50% luminal narrowing is considered a potential risk factor for ischemic stroke; however, subclinical molecular biomarkers of ACAS progression are lacking. Recent studies suggest a regulatory function for several microRNAs (miRNAs) on the evolution of carotid plaque, but its role in ACAS progression is mostly unknown. The aim of our study was to investigate a wide miRNA panel in peripheral blood exosomes from patients with ACAS to associate circulating miRNA expression profiles with stenosis progression. The study included 60 patients with ACAS carrying >50% luminal narrowing. First, miRNA expression profiles of circulating exosomes were determined by Affymetrix microarrays from plasma samples of 16 patients from the cohort. Second, those miRNAs among the most differentially expressed in patients with ACAS progression were quantified by real-time polymerase chain reaction in a separate replication cohort of 39 subjects within the patient sample. Our results showed that ACAS progression was associated with development of stroke. MiR-199b-3p, miR-27b-3p, miR-130a-3p, miR-221-3p, and miR-24-3p presented significant higher expression in those patients with ACAS progression. In conclusion, our study supports that specific circulating miRNA expression profiles could provide a new tool that complements the monitoring of ACAS progression, improving therapeutic approaches to prevent ischemic stroke. © 2016 American Heart Association, Inc.

125. Pre1911. Crew on main deck, starboard side at main ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

125. Pre-1911. Crew on main deck, starboard side at main hatch, looking aft. Note dark object in center of photo that may be original main deck capstan. Fred Heick collection. (K9.9571) - Ship BALCLUTHA, 2905 Hyde Street Pier, San Francisco, San Francisco County, CA

[Esophageal motor disorders in asymptomatic subjects with Trypanosoma cruzi infection].

PubMed

Torres-Aguilera, M; Remes-Troche, J M; Roesch-Dietlen, F; Vázquez-Jiménez, J G; De la Cruz-Patiño, E; Grube-Pagola, P; Ruiz-Juárez, I

2011-01-01

The indeterminate chronic or "asymptomatic" phase of Trypanosoma cruzi (Chagas' disease) infection is characterized by the absence of gastrointestinal symptoms, and has an estimated duration of 20 to 30 years. However, the intramural denervation that induces dysfunction of the gastrointestinal tract is progressive. Recently, epidemiological studies have shown that the seroprevalence for this infection in our area ranges between 2% and 3% of the population. To detect the presence of esophageal motor disorders in asymptomatic individuals chronically infected with Trypanosoma cruzi using standard esophageal manometry. A cross sectional study in 28 asymptomatic subjects (27 men, age 40.39 ± 10.79) with serological evidence of infection with Trypanosoma cruzi was performed. In all cases demographic characteristics, gastrointestinal symptoms and esophageal motility disorders using conventional manometry were analyzed. In this study 54% (n = 15) of asymptomatic subjects had an esophageal motor disorder: 5 (18%) had nutcracker esophagus, 5 (18%) nonspecific esophageal motor disorders, 3 (11%) hypertensive lower esophageal sphincter (LES), 1 (4%) an incomplete relaxation of the LES and 1 (4%) had chagasic achalasia. More than half of patients that course with Chagas' disease in the indeterminate phase and that are apparently asymptomatic have impaired esophageal motility. Presence of hypertensive LES raises the possibility that this alteration represents an early stage in the development of chagasic achalasia.

The case for and against initiating either hydroxyurea therapy, blood transfusion therapy or hematopoietic stem cell transplant in asymptomatic children with sickle cell disease.

PubMed

Kassim, Adetola A; DeBaun, Michael R

2014-02-01

The perception of an asymptomatic sickle cell disease (SCD) state is a misnomer. Children without overt symptoms, likely have subclinical disease beginning in infancy with progression into adulthood. Predictive models of SCD severity are unable to predict a subgroup of asymptomatic children likely to develop severe SCD. The introduction of penicillin prophylaxis, conjugated pneumococcal and Haemophilus influenzae type B vaccines have dramatically decreased the rate of life-threatening infections, while use of hydroxyurea in children has decreased pain and acute chest syndrome events. Use of transcranial Doppler coupled with regular blood transfusion therapy has decreased the rate of overt strokes and premature death associated with strokes. Currently, therapy for asymptomatic children includes hydroxyurea, regular blood transfusion or allogeneic hematopoietic stem cell transplant (allo-HSCT). The pros and cons of initiating hydroxyurea, regular blood transfusion or allo-HSCT in asymptomatic children with SCD. Emerging evidence from observational studies indicates that hydroxyurea prolongs survival in children and adults with sickle cell anemia. Regular blood transfusions reduce incidence of strokes, acute chest and pain episodes, but is associated with the burden of monthly visits and excessive iron stores. Although curative, the perceived risk:benefit ratio associated with allo-HSCT limits its use in asymptomatic children.

Temporal Dynamics of Host Molecular Responses Differentiate Symptomatic and Asymptomatic Influenza A Infection

PubMed Central

Huang, Yongsheng; Zaas, Aimee K.; Rao, Arvind; Dobigeon, Nicolas; Woolf, Peter J.; Veldman, Timothy; Øien, N. Christine; McClain, Micah T.; Varkey, Jay B.; Nicholson, Bradley; Carin, Lawrence; Kingsmore, Stephen; Woods, Christopher W.; Ginsburg, Geoffrey S.; Hero, Alfred O.

2011-01-01

Exposure to influenza viruses is necessary, but not sufficient, for healthy human hosts to develop symptomatic illness. The host response is an important determinant of disease progression. In order to delineate host molecular responses that differentiate symptomatic and asymptomatic Influenza A infection, we inoculated 17 healthy adults with live influenza (H3N2/Wisconsin) and examined changes in host peripheral blood gene expression at 16 timepoints over 132 hours. Here we present distinct transcriptional dynamics of host responses unique to asymptomatic and symptomatic infections. We show that symptomatic hosts invoke, simultaneously, multiple pattern recognition receptors-mediated antiviral and inflammatory responses that may relate to virus-induced oxidative stress. In contrast, asymptomatic subjects tightly regulate these responses and exhibit elevated expression of genes that function in antioxidant responses and cell-mediated responses. We reveal an ab initio molecular signature that strongly correlates to symptomatic clinical disease and biomarkers whose expression patterns best discriminate early from late phases of infection. Our results establish a temporal pattern of host molecular responses that differentiates symptomatic from asymptomatic infections and reveals an asymptomatic host-unique non-passive response signature, suggesting novel putative molecular targets for both prognostic assessment and ameliorative therapeutic intervention in seasonal and pandemic influenza. PMID:21901105

Preoperative CA125 and fibrinogen in patients with endometrial cancer: a risk model for predicting lymphovascular space invasion

PubMed Central

2017-01-01

Objective The aim of this study was to build a model to predict the risk of lymphovascular space invasion (LVSI) in women with endometrial cancer (EC). Methods From December 2010 to June 2013, 211 patients with EC undergoing surgery at Shanghai First Maternity and Infant Hospital were enrolled in this retrospective study. Those patients were divided into a positive LVSI group and a negative LVSI group. The clinical and pathological characteristics were compared between the two groups; logistic regression was used to explore risk factors associated with LVSI occurrence. The threshold values of significant factors were calculated to build a risk model and predict LVSI. Results There were 190 patients who were negative for LVSI and 21 patients were positive for LVSI out of 211 patients with EC. It was found that tumor grade, depth of myometrial invasion, number of pelvic lymph nodes, and International Federation of Gynecology and Obstetrics (FIGO) stage (p<0.05) were associated with LVSI occurrence. However, cervical involvement and age (p>0.05) were not associated with LVSI. Receiver operating characteristic (ROC) curves revealed that the threshold values of the following factors were correlated with positive LVSI: 28.1 U/mL of CA19-9, 21.2 U/mL of CA125, 2.58 mg/dL of fibrinogen (Fn), 1.84 U/mL of carcinoembryonic antigen (CEA) and (6.35×109)/L of white blood cell (WBC). Logistic regression analysis indicated that CA125 ≥21.2 (p=0.032) and Fn ≥2.58 mg/dL (p=0.014) were significantly associated with LVSI. Conclusion Positive LVSI could be predicted by CA125 ≥21.2 U/mL and Fn ≥2.58 mg/dL in women with EC. It could help gynecologists better adapt surgical staging and adjuvant therapies. PMID:27894164

Distribution of 'Candidatus Liberibacter asiaticus' Above and Below Ground in Texas Citrus.

PubMed

Louzada, Eliezer S; Vazquez, Omar Ed; Braswell, W Evan; Yanev, George; Devanaboina, Madhavi; Kunta, Madhurababu

2016-07-01

Detection of 'Candidatus Liberibacter asiaticus' represents one of the most difficult, yet critical, steps of controlling Huanglongbing disease. Efficient detection relies on understanding the underlying distribution of bacteria within trees. To that end, we studied the distribution of 'Ca. L. asiaticus' in leaves of 'Rio Red' grapefruit trees and in roots of 'Valencia' sweet orange trees grafted onto sour orange rootstock. We performed two sets of leaf collection on grapefruit trees; the first a selective sampling targeting symptomatic leaves and their neighbors and the second a systematic collection disregarding symptomology. From uprooted orange trees, we exhaustively sampled fibrous roots. In this study, the presence of 'Ca. L. asiaticus' was detected in leaves using real-time polymerase chain reaction (PCR) targeting the 16S ribosomal gene and in roots using the rpIJ/rpIL ribosomal protein genes and was confirmed with conventional PCR and sequencing of the rpIJ/rpIL gene in both tissues. Among randomly collected leaves, 'Ca. L. asiaticus' was distributed in a patchy fashion. Detection of 'Ca. L. asiaticus' varied with leaf symptomology with symptomatic leaves showing the highest frequency (74%) followed by their neighboring asymptomatic leaves (30%), while randomly distributed asymptomatic leaves had the lowest frequency (20%). Among symptomatic leaves, we found statistically significant differences in mean number of bacterial cells with respect to both increasing distance of the leaf from the trunk and cardinal direction. The titer of 'Ca. L. asiaticus' cells was significantly greater on the north side of trees than on the south and west sides. Moreover, these directions showed different spatial distributions of 'Ca. L. asiaticus' with higher titers near the trunk on the south and west sides as opposed to further from the trunk on the north side. Similarly, we found spatial variation in 'Ca. L. asiaticus' distribution among root samples. 'Ca. L. asiaticus' was detected more frequently and bacterial abundances were higher among horizontally growing roots just under the soil surface (96%) than among deeper vertically growing roots (78%). Bacterial abundance declined slightly with distance from the trunk. These results point to paths of research that will likely prove useful to combating this devastating disease.

Effects of 1,25-dihydroxyvitamin D3 on calcium and phosphorus homeostasis in sheep fed diets either adequate or restricted in calcium content.

PubMed

Wilkens, M R; Mrochen, N; Breves, G; Schröder, B

2010-04-01

It was the aim of the present study to collect basic data on calcium (Ca) and phosphorus (P) homoeostasis in sheep. Two series of experiments were carried out to investigate the effects of 1,25-dihydroxyvitammin D(3) (calcitriol) in supraphysiological dosage in combination with varying alimentary Ca supply. In the first series, blood samples were collected over 72 h to determine the concentrations of total Ca (Ca), ionized Ca (Ca(2+)), inorganic phosphate (P(i)), and the bone resorption marker CrossLaps (CL). In the second series, measurements were carried out over 12h. In addition, urine samples were collected to calculate the fractional excretions (FE) of Ca and P(i). Changes in plasma macromineral concentrations (P<0.01) as well as in CL (P<0.001) and endogenous calcitriol (P<0.05) were observed in the alimentary Ca-restricted animals, indicating that the reduction of daily Ca intake challenged the animals' macromineral homeostatic mechanisms. However, the Ca-restricted diet had an effect on neither FE of Ca nor on FE of P(i). The treatment resulted in peak serum calcitriol concentrations between 1,900 and 2,500 pg/mL, and supraphysiological concentrations were maintained for the next 48 h. Irrespective of dietary Ca, calcitriol had hypercalcemic and hyperphosphatemic effects. An increase in CL was revealed only in the Ca-restricted, calcitriol-treated sheep (P<0.01), reflecting a remarkable enhancement of Ca mobilization from the bone by calcitriol exclusively in this group. From these data, it can be concluded that the sheep can be a suitable animal model for studying catabolic effects of Ca deficiency and calcitriol on bone metabolism. Copyright 2009 Elsevier Inc. All rights reserved.

Impact of an Antimicrobial Stewardship Care Bundle to Improve the Management of Patients with Suspected or Confirmed Urinary Tract Infection.

PubMed

Collins, Curtis D; Kabara, Jared J; Michienzi, Sarah M; Malani, Anurag N

2016-12-01

Implementation of an antimicrobial stewardship program bundle for urinary tract infections among 92 patients led to a higher rate of discontinuation of therapy for asymptomatic bacteriuria (52.4% vs 12.5%; P =.004), more appropriate durations of therapy (88.7% vs 63.6%; P =.001), and significantly higher overall bundle compliance (75% vs 38.2%; P < .001). Infect Control Hosp Epidemiol 2016;1499-1501.

Evaluation of a CLEIA automated assay system for the detection of a panel of tumor markers.

PubMed

Falzarano, Renato; Viggiani, Valentina; Michienzi, Simona; Longo, Flavia; Tudini, Silvestra; Frati, Luigi; Anastasi, Emanuela

2013-10-01

Tumor markers are commonly used to detect a relapse of disease in oncologic patients during follow-up. It is important to evaluate new assay systems for a better and more precise assessment, as a standardized method is currently lacking. The aim of this study was to assess the concordance between an automated chemiluminescent enzyme immunoassay system (LUMIPULSE® G1200) and our reference methods using seven tumor markers. Serum samples from 787 subjects representing a variety of diagnoses, including oncologic, were analyzed using LUMIPULSE® G1200 and our reference methods. Serum values were measured for the following analytes: prostate-specific antigen (PSA), alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), carbohydrate antigen 15-3 (CA15-3), carbohydrate antigen 19-9 (CA19-9), and cytokeratin 19 fragment (CYFRA 21-1). For the determination of CEA, AFP, and PSA, an automatic analyzer based on chemiluminescence was applied as reference method. To assess CYFRA 21-1, CA125, CA19-9, and CA15-3, an immunoradiometric manual system was employed. Method comparison by Passing-Bablok analysis resulted in slopes ranging from 0.9728 to 1.9089 and correlation coefficients from 0.9977 to 0.9335. The precision of each assay was assessed by testing six serum samples. Each sample was analyzed for all tumor biomarkers in duplicate and in three different runs. The coefficients of variation were less than 6.3 and 6.2 % for within-run and between-run variation, respectively. Our data suggest an overall good interassay agreement for all markers. The comparison with our reference methods showed good precision and reliability, highlighting its usefulness in clinical laboratory's routine.

Serum ionized calcium, intact PTH and novel markers of bone turnover in bedridden elderly patients.

PubMed

Sorva, A; Välimäki, M; Risteli, J; Risteli, L; Elfving, S; Takkunen, H; Tilvis, R

1994-12-01

Chronic immobilization could markedly affect calcium and bone metabolism in elderly people. To investigate this, and to test the theory of 'type II' osteoporosis in bedridden elderly patients with low vitamin D status, 55 such subjects were examined. Serum concentrations of ionized calcium (Ca++), intact parathyrin (PTH) and two novel markers of bone collagen formation (carboxyterminal propeptide of type I procollagen; PICP) and resorption (carboxyterminal crosslinked telopeptide of type I collagen; ICTP) were measured. The effects on these parameters after 40 weeks of supplementation with vitamin D (1000 IU d-1) and/or calcium (1 g d-1) were subsequently prospectively evaluated. Despite low (mean 11.6 nmoll-1) serum 25-hydroxyvitamin D levels (25-OHD), those of 1,25-dihydroxy-vitamin D (1,25-(OH)2D) were mostly normal. Neither correlated with Ca++ or PTH. PTH correlated negatively not only with Ca++ (r = -0.328, P < 0.05) but also with ICTP (r = -0.306, P < 0.05). Mean PICP was normal but ICTP was elevated and tended to correlate positively with Ca++ (r = 0.268, P = 0.06). Vitamin D supplementation did not change PICP or ICTP considerably, despite slightly increased 1,25-(OH)2D and slightly decreased PTH. Ca++ values were normal and remained stable. In conclusion, Ca++ and PTH are poor indicators of vitamin D status in chronically immobilized elderly subjects. Furthermore, the results suggest that the increased bone resorption is not due to 'type II' secondary hyperparathyroidism; rather the resorption is primarily increased. Correction of vitamin D deficiency does not seem to benefit ageing bones unless adequate mechanical loading is provided.

Calcium balance in pediatric online hemodiafiltration: Beware of sodium and bicarbonate in the dialysate.

PubMed

Bacchetta, Justine; Sellier-Leclerc, Anne-Laure; Bertholet-Thomas, Aurélia; Carlier, Marie-Christine; Cartier, Régine; Cochat, Pierre; Ranchin, Bruno

2015-11-01

Online hemodiafiltration (oHDF) is increasingly used in children; we treated 28 children since 2009, adapting this technique to pediatric patients. In this service evaluation audit, we assessed plasma electrolytes to evaluate the evolution of total (tCa) and ionized (iCa) during a session, as well as dialysate calcium (dCa) concentrations. Using a 1.25 mmol Ca/L-dialysate, both tCa and iCa decreased during the session, with iCa falling below 1.1 mmol/L in 4/5 patients. In contrast, using a 1.5 mmol Ca/L-dialysate, iCa remained normal in all patients. Major discrepancies were observed between the expected and the measured dCa: 1.25 vs. 1.01 (0.83-1.04), and 1.5 vs. 1.47 (0.85-1.75) mmol/L, respectively (results presented as median [range]). These differences were explained by the modality of reconstituting dialysate: increasing bicarbonates and/or decreasing sodium requested in the dialysate decreases calcium extraction from the acid preparation. Proof of concept was given when requesting in an "ex-vivo" setting modifications in the requested sodium and bicarbonate in dialysate directly on the Fresenius machine. Nephrologists should be aware that "high bicarbonate and/or low sodium" requirements in oHDF decrease calcium in the dialysate. Copyright © 2015 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

A note on the chemistry of seawater in the range 350°-500°C

USGS Publications Warehouse

Bischoff, James L.; Rosenbauer, Robert J.

1983-01-01

The chemistry of seawater at conditions of 350° to 500°C, 220 to 1000 bars (22 to 100 MPa) is controlled by reactions involving magnesium hydroxide sulfate (MHSH) and anhydrite. During progressive heating from 350° to 500°C at 1000 bars (100 MPa), MHSH with a  ratio of 1.25 is formed via precipitation from solution and via reaction of solution with pre-existing anhydrite. During adiabatic expansion the MHSH extracts additional SO4 from seawater and converts to a stoichiometry in which . These reactions control and greatly change the concentrations of Ca, Mg, SO4 in solution and produce significant ionizable hydrogen, attaining 11.7 mmoles kg−1 at maximum conditions.

Clinical Study on Using 125I Seeds Articles Combined with Biliary Stent Implantation in the Treatment of Malignant Obstructive Jaundice.

PubMed

Wang, Tao; Liu, Sheng; Zheng, Yan-Bo; Song, Xue-Peng; Sun, Bo-Lin; Jiang, Wen-Jin; Wang, Li-Gang

2017-08-01

Aim: To study the feasibility and curative effect of 125 I seeds articles combined with biliary stent implantation in the treatment of malignant obstructive jaundice. Patients and Methods: Fifty patients with malignant obstructive jaundice were included. Twenty-four were treated by biliary stent implantation combined with intraluminal brachytherapy by 125 I seeds articles as the experimental group, while the remaining 26 were treated by biliary stent implantation only as the control group. The goal of this study was to evaluate total bilirubin, direct bilirubin and tumor markers (cancer antigen (CA)-199, CA-242 and carcinoembryonic antigen (CEA)), as well as biliary stent patency status and survival time before and after surgery. Results: Jaundice improved greatly in both groups. The decreases of CA-199 and CA-242 had statistical significance (p=0.003 and p=0.004) in the experimental group. The ratio of biliary stent patency was 83.3% (20/24) in the experimental group and 57.7% (15/26) in the control group (p=0.048). The biliary stent patency time in the experimental group was 1~15.5 (mean=9.84) months. The biliary stent patency time in the control group was 0.8~9 (mean=5.57) months, which was statistically significant (p=0.018). The median survival time was 10.2 months in the experimental group, while 5.4 months in control group (p<0.05). Conclusion: 125 I seeds articles combined with biliary stent implantation significantly prolongs biliary stent patency time and survival time for patients with malignant obstructive jaundice possibly by inhibiting the proliferation of vascular endothelial cells and the growth of tumor. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Endometrial cancer surveillance adherence reduces utilization and subsequent costs.

PubMed

Schwartz, Zachary P; Frey, Melissa K; Philips, Sarah; Curtin, John P

2017-09-01

In June 2011, the SGO recommended that physical exam and symptoms be the primary surveillance methods in patients with endometrial cancer. We sought to evaluate adherence to these guidelines by comparing the use of CT scans, paps and serum CA125 ordered for endometrial cancer surveillance before and after publication of these guidelines. A retrospective review was performed for all patients undergoing surveillance for endometrial cancer at a single institution between June 2009 and June 2013. We assessed the number of patients without symptoms or abnormal physical exam findings who underwent surveillance CT scans, paps and/or CA125 during the 2years pre- and 2years post-SGO guidelines. 92 patients (n=48 pre-6/2011, n=44 post-6/2011) were identified. Mean patient age was 58years. No significant difference in age, ethnicity, body mass index, or disease grade or stage was noted. There was a significant decline in surveillance CT scans (n=13, 27% vs. n=4, 9%, p=0.03), CA125 (n=14, 29% vs. 5, 11%, p=0.035) and paps (n=34, 71% vs. n=8 vs. 18%, p<0.001). There was no significant difference in disease status at the last follow-up. Institutional cost of surveillance also declined ($14,102.46 2years pre-guidelines, $3,054.99 2years post-guidelines). In a single urban academic public hospital, after only 2years, clinical adherence to the 2011 SGO endometrial cancer surveillance guidelines resulted in a significant decline in the use of CT scans, CA125 and paps. This reduction does not appear to affect patient outcomes and led to an appreciable decrease in surveillance costs. Copyright © 2017 Elsevier Inc. All rights reserved.

Programmable Bio-Nano-Chip Systems for Serum CA125 Quantification: Towards Ovarian Cancer Diagnostics at the Point-of-Care

PubMed Central

Raamanathan, Archana; Simmons, Glennon W.; Christodoulides, Nicolaos; Floriano, Pierre N.; Furmaga, Wieslaw B.; Redding, Spencer W.; Lu, Karen H.; Bast, Robert C.; McDevitt, John T.

2013-01-01

Point-of-care (POC) implementation of early detection and screening methodologies for ovarian cancer may enable improved survival rates through early intervention. Current laboratory-confined immunoanalyzers have long turnaround times and are often incompatible with multiplexing and POC implementation. Rapid, sensitive and multiplexable POC diagnostic platforms compatible with promising early detection approaches for ovarian cancer are needed. To this end, we report the adaptation of the programmable bio-nano-chip (p-BNC), an integrated, microfluidic, modular (Programmable) platform for CA125 serum quantitation, a biomarker prominently implicated in multi-modal and multi-marker screening approaches. In the p-BNC, CA125 from diseased sera (Bio) is sequestered and assessed with a fluorescence-based sandwich immunoassay, completed in the nano-nets (Nano) of sensitized agarose microbeads localized in individually addressable wells (Chip), housed in a microfluidic module, capable of integrating multiple sample, reagent and biowaste processing and handling steps. Antibody pairs that bind to distinct epitopes on CA125 were screened. To permit efficient biomarker sequestration in a 3-D microfluidic environment, the p-BNC operating variables (incubation times, flow rates and reagent concentrations) were tuned to deliver optimal analytical performance under 45 minutes. With short analysis times, competitive analytical performance (Inter- and intra-assay precision of 1.2% and 1.9% and LODs of 1.0 U/mL) was achieved on this mini-sensor ensemble. Further validation with sera of ovarian cancer patients (n=20) demonstrated excellent correlation (R2 = 0.97) with gold-standard ELISA. Building on the integration capabilities of novel microfluidic systems programmed for ovarian cancer, the rapid, precise and sensitive miniaturized p-BNC system shows strong promise for ovarian cancer diagnostics. PMID:22490510

Programmable bio-nano-chip systems for serum CA125 quantification: toward ovarian cancer diagnostics at the point-of-care.

PubMed

Raamanathan, Archana; Simmons, Glennon W; Christodoulides, Nicolaos; Floriano, Pierre N; Furmaga, Wieslaw B; Redding, Spencer W; Lu, Karen H; Bast, Robert C; McDevitt, John T

2012-05-01

Point-of-care (POC) implementation of early detection and screening methodologies for ovarian cancer may enable improved survival rates through early intervention. Current laboratory-confined immunoanalyzers have long turnaround times and are often incompatible with multiplexing and POC implementation. Rapid, sensitive, and multiplexable POC diagnostic platforms compatible with promising early detection approaches for ovarian cancer are needed. To this end, we report the adaptation of the programmable bio-nano-chip (p-BNC), an integrated, microfluidic, and modular (programmable) platform for CA125 serum quantitation, a biomarker prominently implicated in multimodal and multimarker screening approaches. In the p-BNCs, CA125 from diseased sera (Bio) is sequestered and assessed with a fluorescence-based sandwich immunoassay, completed in the nano-nets (Nano) of sensitized agarose microbeads localized in individually addressable wells (Chip), housed in a microfluidic module, capable of integrating multiple sample, reagent and biowaste processing, and handling steps. Antibody pairs that bind to distinct epitopes on CA125 were screened. To permit efficient biomarker sequestration in a three-dimensional microfluidic environment, the p-BNC operating variables (incubation times, flow rates, and reagent concentrations) were tuned to deliver optimal analytical performance under 45 minutes. With short analysis times, competitive analytical performance (inter- and intra-assay precision of 1.2% and 1.9% and limit of detection of 1.0 U/mL) was achieved on this minisensor ensemble. Furthermore, validation with sera of patients with ovarian cancer (n = 20) showed excellent correlation (R(2) = 0.97) with gold-standard ELISA. Building on the integration capabilities of novel microfluidic systems programmed for ovarian cancer, the rapid, precise, and sensitive miniaturized p-BNC system shows strong promise for ovarian cancer diagnostics.

Comparison of risk of malignancy indices; RMI 1-4 in borderline ovarian tumor.

PubMed

Yenen, M C; Alanbay, I; Aktürk, E; Ercan, C M; Coksuer, H; Karaşahin, E; Ozan, H; Dede, M

2012-01-01

The aim of this study was to evaluate prognostic values of the risk of malignancy index (RMI)/1-4 in patients with borderline ovarian tumors (BOTs). The study consisted of 50 patients with BOT diagnosed and treated between 2005-2010 and 50 patients with benign adnexal massses between 2009-2010 as a control comparison group in the retropsective study. Preoperative serum CA125, U score, tumor size (S), and menopausal status were recorded. The RMI 1-3 was calculated according to the formula; UxMxCA125 and RMI4 formulation was; UxMxCA125xS. S equaled 1 for tumor size <7 cm and was 2 when size a 7 cm. The RMI 1-4 indices were calculated for all patients together with the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy (DA). The performances of RMI indices were evaluated by McNemar's test and determined the best score cutoff value by the receiver operating characteristic (ROC) curve. The mean age, median value of CA125, ultrasound score, menopausal status, median values of RMI 1-4 of BOTs were statistically higher than benign adnexal masses. The sensitivity of RMI 1-4 was 26, 36, 62, and 60% at cutoff 200 level, respectively. The areas under curve of RMI 1-4 were found to be 0.676, 0.665, 0.668 and 0.734, respectively. DA of RMI 1-4 was found to be 56, 59, 50, and 71, respectively. When RMI 1-4 indices were compared with each other RMI 4 was the best RMI for BOTs. RMI 4 was the best predictive RMI for preoperative discrimination of BOT at a cutoff level of 200.

Expression levels of the innate response gene RIG-I and its regulators RNF125 and TRIM25 in HIV-1-infected adult and pediatric individuals.

PubMed

Britto, Alan M A; Amoedo, Nívea D; Pezzuto, Paula; Afonso, Adriana O; Martínez, Ana M B; Silveira, Jussara; Sion, Fernando S; Machado, Elizabeth S; Soares, Marcelo A; Giannini, Ana L M

2013-07-31

TLRs (Toll-like receptors) and RLRs (RIG-I-like receptors) mediate innate immune responses by detecting microorganism invasion. RIG-I activation results in the production of interferon (IFN) type 1 and IFN responsive genes (ISGs). As the ubiquitin ligases RNF125 and TRIM25 are involved in regulating RIG-I function, our aim was to assess whether the levels of these three genes vary between healthy and HIV-infected individuals and whether these levels are related to disease progression. Gene expression analyses for RIG-I, RNF125, and TRIM25 were performed for HIV-infected adults and the children's peripheral blood mononuclear cells (PBMCs). Reverse transcription-quantitative PCRs (RT-qPCRs) were performed in order to quantify the expression levels of RIG-I, RNF125 and TRIM25 from PBMCs purified from control or HIV-infected individuals. Controls express higher levels of the three genes when compared to HIV-infected patients. These expressions are clearly distinct between healthy and progressors, and are reproduced in adults and children. In controls, RNF125 is the highest expressed gene, whereas in progressors, RIG-I is either the highest expressed gene or is expressed similarly to RNF125 and TRIM25. A pattern of expression of RIG-I, RNF125, and TRIM25 genes in HIV patients is evident. The high expression of RNF125 in healthy individuals reflects the importance of keeping RIG-I function off, inhibiting unnecessary IFN production. Consistent with this assumption, RNF125 levels are lower in HIV patients and importantly, the RNF125/RIG-I ratio is lower in patients who progress to AIDS. Our results might help to predict disease progression and unveil the role of poorly characterized host genes during HIV infection.

Relationship between exercise pressure gradient and haemodynamic progression of aortic stenosis.

PubMed

Ringle, Anne; Levy, Franck; Ennezat, Pierre-Vladimir; Le Goffic, Caroline; Castel, Anne-Laure; Delelis, François; Menet, Aymeric; Malaquin, Dorothée; Graux, Pierre; Vincentelli, André; Tribouilloy, Christophe; Maréchaux, Sylvestre

We hypothesized that large exercise-induced increases in aortic mean pressure gradient can predict haemodynamic progression during follow-up in asymptomatic patients with aortic stenosis. We retrospectively identified patients with asymptomatic moderate or severe aortic stenosis (aortic valve area<1.5cm 2 or<1cm 2 ) and normal ejection fraction, who underwent an exercise stress echocardiography at baseline with a normal exercise test and a resting echocardiography during follow-up. The relationship between exercise-induced increase in aortic mean pressure gradient and annualised changes in resting mean pressure gradient during follow-up was investigated. Fifty-five patients (mean age 66±15 years; 45% severe aortic stenosis) were included. Aortic mean pressure gradient significantly increased from rest to peak exercise (P<0.001). During a median follow-up of 1.6 [1.1-3.2] years, resting mean pressure gradient increased from 35±13mmHg to 48±16mmHg, P<0.0001. Median annualised change in resting mean pressure gradient during follow-up was 5 [2-11] mmHg. Exercise-induced increase in aortic mean pressure gradient did correlate with annualised changes in mean pressure gradient during follow-up (r=0.35, P=0.01). Hemodynamic progression of aortic stenosis was faster in patients with large exercise-induced increase in aortic mean pressure gradient (≥20mmHg) as compared to those with exercise-induced increase in aortic mean pressure gradient<20mmHg (median annualised increase in mean pressure gradient 19 [6-28] vs. 4 [2-10] mmHg/y respectively, P=0.002). Similar results were found in the subgroup of 30 patients with moderate aortic stenosis. Large exercise-induced increases in aortic mean pressure gradient correlate with haemodynamic progression of stenosis during follow-up in patients with asymptomatic aortic stenosis. Further studies are needed to fully establish the role of ESE in the decision-making process in comparison to other prognostic markers in asymptomatic patients with aortic stenosis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Regulation of mouse lung development by the extracellular calcium-sensing receptor, CaR

PubMed Central

Finney, Brenda A; del Moral, Pierre M; Wilkinson, William J; Cayzac, Sebastien; Cole, Martin; Warburton, David; Kemp, Paul J; Riccardi, Daniela

2008-01-01

Postnatal lung function is critically dependent upon optimal embryonic lung development. As the free ionized plasma calcium concentration ([Ca2+]o) of the fetus is higher than that of the adult, the process of lung development occurs in a hypercalcaemic environment. In the adult, [Ca2+]o is monitored by the G-protein coupled, extracellular calcium-sensing receptor (CaR), but neither its ontogeny nor its potential role in lung development are known. Here, we demonstrate that CaR is expressed in the mouse lung epithelium, and that its expression is developmentally regulated, with a peak of expression at embryonic day 12.5 (E12.5) and a subsequent decrease by E18, after which the receptor is absent. Experiments carried out using the lung explant culture model in vitro show that lung branching morphogenesis is sensitive to [Ca2+]o, being maximal at physiological adult [Ca2+]o (i.e. 1.0–1.3 mm) and lowest at the higher, fetal (i.e. 1.7 mm) [Ca2+]o. Administration of the specific CaR positive allosteric modulator, the calcimimetic R-568, mimics the suppressive effects of high [Ca2+]o on branching morphogenesis while both phospholipase C and PI3 kinase inhibition reverse these effects. CaR activation suppresses cell proliferation while it enhances intracellular calcium signalling, lung distension and fluid secretion. Conditions which are restrictive either to branching or to secretion can be rescued by manipulating [Ca2+]o in the culture medium. In conclusion, fetal Cao2+, acting through a developmentally regulated CaR, is an important extrinsic factor that modulates the intrinsic lung developmental programme. Our observations support a novel role for the CaR in preventing hyperplastic lung disease in utero. PMID:18955379

Bone resorptive activity in symptomatic and asymptomatic apical lesions of endodontic origin.

PubMed

Salinas-Muñoz, M; Garrido-Flores, M; Baeza, M; Huamán-Chipana, P; García-Sesnich, J; Bologna, R; Vernal, R; Hernández, M

2017-11-01

The aim of this study is to assess the levels and diagnostic accuracy of a set of bone resorption biomarkers, including TRAP-5, RANKL, and OPG in symptomatic and asymptomatic apical lesions and controls. Apical tissues from symptomatic and asymptomatic apical periodontitis patients and periodontal ligaments from healthy teeth extracted for orthodontic reasons were processed for tissue homogenization and the levels of TRAP-5, RANKL, and OPG were determined by multiplex assay. Marker levels were analyzed by Kruskal Wallis test, and diagnostic accuracy was analyzed with ROC curves. Higher levels of RANKL, OPG, and RANKL/OPG ratio were determined in both types of apical lesions compared to healthy periodontal ligament, whereas higher TRAP-5 levels were found only in symptomatic apical lesions (p < 0.05). OPG, RANKL, and RANKL/OPG ratio showed diagnostic potential to identify apical lesions versus healthy controls (AUC = 0.69, p < 0.05); while TRAP-5 showed a potential to discriminate symptomatic versus asymptomatic apical periodontitis (AUC = 0.71, p < 0.05) and healthy controls (AUC = 0.83, p < 0.05). Apical lesions showed higher RANKL and OPG levels than healthy tissues. TRAP-5 levels were the highest in symptomatic apical lesions, suggesting that these represent a progressive state, and showed diagnostic potential. Clinically symptomatic apical periodontitis might represent biologically progressive apical lesions based on TRAP5 levels. TRAP5 has diagnostic potential to identify these lesions, representing a candidate prognostic biomarker.

Monoclonal antibody DS6 detects a tumor-associated sialoglycotope expressed on human serous ovarian carcinomas.

PubMed

Kearse, K P; Smith, N L; Semer, D A; Eagles, L; Finley, J L; Kazmierczak, S; Kovacs, C J; Rodriguez, A A; Kellogg-Wennerberg, A E

2000-12-15

A newly developed murine monoclonal antibody, DS6, immunohistochemically reacts with an antigen, CA6, that is expressed by human serous ovarian carcinomas but not by normal ovarian surface epithelium or mesothelium. CA6 has a limited distribution in normal adult tissues and is most characteristically detected in fallopian tube epithelium, inner urothelium and type 2 pneumocytes. Pre-treatment of tissue sections with either periodic acid or neuraminidase from Vibrio cholerae abolishes immunoreactivity with DS6, indicating that CA6 is a neuraminidase-sensitive and periodic acid-sensitive sialic acid glycoconjugate ("sialoglycotope"). SDS-PAGE of OVCAR5 cell lysates has revealed that the CA6 epitope is expressed on an 80 kDa non-disulfide-linked glycoprotein containing N-linked oligosaccharides. Two-dimensional non-equilibrium pH gradient gel electrophoresis indicates an isoelectric point of approximately 6.2 to 6.5. Comparison of the immunohistochemical distribution of CA6 in human serous ovarian adenocarcinomas has revealed similarities to that of CA125; however, distinct differences and some complementarity of antigen expression were revealed by double-label, 2-color immunohistochemical studies. The DS6-detected CA6 antigen appears to be distinct from other well-characterized tumor-associated antigens, including MUC1, CA125 and the histo-blood group-related antigens sLea, sLex and sTn. Copyright 2000 Wiley-Liss, Inc.

Mild cognitive impairment and asymptomatic Alzheimer disease subjects: equivalent β-amyloid and tau loads with divergent cognitive outcomes.

PubMed

Iacono, Diego; Resnick, Susan M; O'Brien, Richard; Zonderman, Alan B; An, Yang; Pletnikova, Olga; Rudow, Gay; Crain, Barbara; Troncoso, Juan C

2014-04-01

Older adults with intact cognition before death and substantial Alzheimer disease (AD) lesions at autopsy have been termed "asymptomatic AD subjects" (ASYMAD). We previously reported hypertrophy of neuronal cell bodies, nuclei, and nucleoli in the CA1 of the hippocampus (CA1), anterior cingulate gyrus, posterior cingulate gyrus, and primary visual cortex of ASYMAD versus age-matched Control and mild cognitive impairment (MCI) subjects. However, it was unclear whether the neuronal hypertrophy could be attributed to differences in the severity of AD pathology. Here, we performed quantitative analyses of the severity of β-amyloid (Aβ) and phosphorylated tau (tau) loads in the brains of ASYMAD, Control, MCI, and AD subjects (n = 15 per group) from the Baltimore Longitudinal Study of Aging. Tissue sections from CA1, anterior cingulate gyrus, posterior cingulate gyrus, and primary visual cortex were immunostained for Aβ and tau; the respective loads were assessed using unbiased stereology by measuring the fractional areas of immunoreactivity for each protein in each region. The ASYMAD and MCI groups did not differ in Aβ and tau loads. These data confirm that ASYMAD and MCI subjects have comparable loads of insoluble Aβ and tau in regions vulnerable to AD pathology despite divergent cognitive outcomes. These findings imply that cognitive impairment in AD may be caused or modulated by factors other than insoluble forms of Aβ and tau.

Prognostic Significance of Carbohydrate Antigen 19-9 in Unresectable Locally Advanced Pancreatic Cancer Treated With Dose-Escalated Intensity Modulated Radiation Therapy and Concurrent Full-Dose Gemcitabine: Analysis of a Prospective Phase 1/2 Dose Escalation Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vainshtein, Jeffrey M., E-mail: jvainsh@med.umich.edu; Schipper, Matthew; Zalupski, Mark M.

2013-05-01

Purpose: Although established in the postresection setting, the prognostic value of carbohydrate antigen 19-9 (CA19-9) in unresectable locally advanced pancreatic cancer (LAPC) is less clear. We examined the prognostic utility of CA19-9 in patients with unresectable LAPC treated on a prospective trial of intensity modulated radiation therapy (IMRT) dose escalation with concurrent gemcitabine. Methods and Materials: Forty-six patients with unresectable LAPC were treated at the University of Michigan on a phase 1/2 trial of IMRT dose escalation with concurrent gemcitabine. CA19-9 was obtained at baseline and during routine follow-up. Cox models were used to assess the effect of baseline factorsmore » on freedom from local progression (FFLP), distant progression (FFDP), progression-free survival (PFS), and overall survival (OS). Stepwise forward regression was used to build multivariate predictive models for each endpoint. Results: Thirty-eight patients were eligible for the present analysis. On univariate analysis, baseline CA19-9 and age predicted OS, CA19-9 at baseline and 3 months predicted PFS, gross tumor volume (GTV) and black race predicted FFLP, and CA19-9 at 3 months predicted FFDP. On stepwise multivariate regression modeling, baseline CA19-9, age, and female sex predicted OS; baseline CA19-9 and female sex predicted both PFS and FFDP; and GTV predicted FFLP. Patients with baseline CA19-9 ≤90 U/mL had improved OS (median 23.0 vs 11.1 months, HR 2.88, P<.01) and PFS (14.4 vs 7.0 months, HR 3.61, P=.001). CA19-9 progression over 90 U/mL was prognostic for both OS (HR 3.65, P=.001) and PFS (HR 3.04, P=.001), and it was a stronger predictor of death than either local progression (HR 1.46, P=.42) or distant progression (HR 3.31, P=.004). Conclusions: In patients with unresectable LAPC undergoing definitive chemoradiation therapy, baseline CA19-9 was independently prognostic even after established prognostic factors were controlled for, whereas CA19-9 progression strongly predicted disease progression and death. Future trials should stratify by baseline CA19-9 and incorporate CA19-9 progression as a criterion for progressive disease.« less

Comparison of non-schistosomal rectosigmoid cancer and schistosomal rectosigmoid cancer.

PubMed

Feng, Hao; Lu, Ai-Guo; Zhao, Xue-Wei; Han, Ding-Pei; Zhao, Jing-Kun; Shi, Lei; Schiergens, Tobias S; Lee, Serene M L; Zhang, Wen-Peng; Thasler, Wolfgang E

2015-06-21

To compare the clinicopathological features of patients with non-schistosomal rectosigmoid cancer and schistosomal rectosigmoid cancer. All the patients with rectosigmoid carcinoma who underwent laparoscopic radical surgical resection in the Shanghai Minimally Invasive Surgical Center at Ruijin Hospital affiliated to Shanghai Jiao-Tong University between October 2009 and October 2013 were included in this study. Twenty-six cases of colonic schistosomiasis diagnosed through colonoscopy and pathological examinations were collected. Symptoms, endoscopic findings and clinicopathological characteristics were evaluated retrospectively. There were no significant differences between patients with and without schistosomiasis in gender, age, CEA, CA19-9, preoperative biopsy findings or postoperative pathology. Patients with rectosigmoid schistosomiasis had a significantly higher CA-125 level and a larger proportion of these patients were at an early tumor stage (P = 0.003). Various morphological characteristics of schistosomiasis combined with rectosigmoid cancer could be found by colonoscopic examination: 46% were fungating mass polyps, 23% were congestive and ulcerative polyps, 23% were cauliflower-like masses, 8% were annular masses. Only 27% of the patients were diagnosed with rectal carcinoma preoperatively after the biopsy. Computed tomography (CT) scans showed thickened intestinal walls combined with linear and tram-track calcifications in 26 patients. Rectosigmoid carcinoma combined with schistosomiasis is associated with higher CA-125 values and early tumor stages. CA-125 and CT scans have a reasonable sensitivity for the accurate diagnosis.

Gonadotrophin-releasing hormone agonist combined with high-intensity focused ultrasound ablation for adenomyosis: a clinical study.

PubMed

Guo, Y; Duan, H; Cheng, J; Zhang, Y

2017-08-01

This study was to investigate the clinical efficacy of a gonadotrophin-releasing hormone agonist (GnRH-a) combined with high-intensity focused ultrasound (HIFU) ablation treatment for adenomyosis. A non-randomized prospective study. Gynaecological Minimally Invasive Centre in a single hospital. Patients with adenomyosis. Seventy-nine patients with adenomyosis were enrolled, including 55 patients in the control group treated with only HIFU and 24 patients in the study group treated with GnRH-a combined with HIFU. All the patients follow up 6 months after the HIFU procedure. The related parameters in the two groups were assessed before and 3 months as well as 6 months after treatment including serum levels of tumor marker and cytokine, volumes of uterine, adenomyotic lesion, and menstrual blood, as well as dysmenorrheal scores. Differences between the group treated with HIFU alone and the group treated with GnRH-a combined with HIFU. Before HIFU treatment, no significant difference was observed in serum levels of CA125, CA19-9, and interleukin-6 (IL-6), the volumes of uterine, adenomyotic lesion, and menstrual blood, as well as dysmenorrhea scores between the two groups. (P > 0.05). The serum CA125 levels significantly decreased in both groups after HIFU, but the serum CA125 levels in the study group were still significantly lower than those in the control group (P < 0.05). The volume of uterine and adenomyotic lesion significantly decreased in both groups after HIFU procedure, and decreased even more in the study group 3 and 6 months after treatment (P < 0.05). Dysmenorrhea scores and menstruation volumes significantly decreased in both groups after HIFU treatment. Moreover in the study group were significantly lower than those in the control group after 3 and 6 months (P < 0.05). No significant difference was observed in the rate of adverse effects between the two groups. The short-term follow-up results indicate that the combination of GnRH-a and HIFU treatment significantly decreased serum CA125 levels, volumes of uterine, adenomyotic lesion and menstrual blood, as well as dysmenorrhea scores, and improved the clinical outcomes compared with the HIFU ablation alone in patients with adenomyosis. However, the further follow-up is needed to explore the long-term effects. A combination of GnRH-a with HIFU in the treatment of adenomyosis significantly decreased serum CA125 levels, uterine and adenomyotic lesion volumes, dysmenorrhea scores, and menstrual blood volumes. © 2017 Royal College of Obstetricians and Gynaecologists.

Electronic structure and vacancy formation in La(1 - x) B(x) CoO3 (B=Mg,Ca,Ba and x=0.125)

NASA Astrophysics Data System (ADS)

Salawu, Omotayo; Gan, Liyong; Schwingenschlogl, Udo

2015-03-01

The LaCoO3 class of materials is of interest for cathodes of solid oxide fuel cells. Spin-polarized density functional theory is applied to cubic La0.75(Mg/Ca/Ba)0.125CoO3. The effect of this cation doping on the electronic and magnetic properties as well as oxygen vacancy formation energy is studied. Oxygen vacancies with proximity to the dopant are energetically favourable in most cases. We discuss the effect of distortions of the CoO6 octahedron on the electronic structure and the formation energy of oxygen vacancies. The order of formation oxygen is found to be Mg > Ca > Ba. Cation doping incorporates holes to the Co-O network which enhances the oxygen vacancy formation.

Transcriptional regulation differs in affected facioscapulohumeral muscular dystrophy patients compared to asymptomatic related carriers

PubMed Central

Arashiro, Patricia; Eisenberg, Iris; Kho, Alvin T.; Cerqueira, Antonia M. P.; Canovas, Marta; Silva, Helga C. A.; Pavanello, Rita C. M.; Verjovski-Almeida, Sergio; Kunkel, Louis M.; Zatz, Mayana

2009-01-01

Facioscapulohumeral muscular dystrophy (FSHD) is a progressive muscle disorder that has been associated with a contraction of 3.3-kb repeats on chromosome 4q35. FSHD is characterized by a wide clinical inter- and intrafamilial variability, ranging from wheelchair-bound patients to asymptomatic carriers. Our study is unique in comparing the gene expression profiles from related affected, asymptomatic carrier, and control individuals. Our results suggest that the expression of genes on chromosome 4q is altered in affected and asymptomatic individuals. Remarkably, the changes seen in asymptomatic samples are largely in products of genes encoding several chemokines, whereas the changes seen in affected samples are largely in genes governing the synthesis of GPI-linked proteins and histone acetylation. Besides this, the affected patient and related asymptomatic carrier share the 4qA161 haplotype. Thus, these polymorphisms by themselves do not explain the pathogenicity of the contracted allele. Interestingly, our results also suggest that the miRNAs might mediate the regulatory network in FSHD. Together, our results support the previous evidence that FSHD may be caused by transcriptional dysregulation of multiple genes, in cis and in trans, and suggest some factors potentially important for FSHD pathogenesis. The study of the gene expression profiles from asymptomatic carriers and related affected patients is a unique approach to try to enhance our understanding of the missing link between the contraction in D4Z4 repeats and muscle disease, while minimizing the effects of differences resulting from genetic background. PMID:19339494

Potential use of caprylic acid in broiler chickens: effect on Salmonella enteritidis.

PubMed

Skřivanová, Eva; Hovorková, Petra; Čermák, Ladislav; Marounek, Milan

2015-01-01

The effect of dietary caprylic acid (CA) on Salmonella Enteritidis, as well as the surface treatment of chicken skin contaminated with Salmonella Enteritidis was evaluated. To evaluate the dietary effect of CA on Salmonella Enteritidis, the individually housed broiler chickens (n=48) were divided into 4 groups (positive control, negative control, 2.5 g/kg of CA in the feed, and 5 g/kg of CA in the feed). The feed of all groups, except the negative control, was artificially contaminated with Salmonella Enteritidis ATCC 13076 (10(7) colony-forming units/100 g of feed). Both concentrations of dietary CA significantly decreased counts of Salmonella Enteritidis in the crop and cecum of experimental chickens (p<0.05). The effect of CA in the crop contents was more pronounced than in the cecum. Surface treatment of chilled chicken halves with CA at 1.25 and 2.5 mg/mL significantly decreased Salmonella Enteritidis contamination of chicken skin (p<0.05). The sensory evaluation of the skin and meat showed that treatment of the skin with 1.25 mg/mL of CA worsened odor and appearance of the chicken skin, while sensory traits of chicken meat were not significantly affected. Taste and overall acceptability was not influenced by CA in both meat and skin. Treatment of the skin with 2.5 mg/mL of CA resulted in more pronounced changes of the skin odor and appearance. In conclusion, dietary CA reduced carriage of Salmonella Enteritidis in chickens, whereas surface-treatment reduced or eliminated Salmonella Enteritidis contamination in the processed bird.

Vitamin D delays breast cancer progression in the PyVMT transgenic mouse model: local conversion of the precursor 25(OH)D3 into 1,25(OH)2D3 is safer and more effective than systemic administration of 1,25(OH)2D3

USDA-ARS?s Scientific Manuscript database

Metabolic activation of 1,25(OH)2D3 occurs at extra renal sites in several organs, including the breast. The purpose of this study was to determine if this local tumoral 25OHD3-1alphahydroxylase expression modulates any or all of the stages of breast tumor progression. For this purpose we used the...

Nitric oxide in the dorsal hippocampal area is involved on muscimol state-dependent memory in the step-down passive avoidance test.

PubMed

Jafari-Sabet, Majid; Khodadadnejad, Mohammad-Amin; Ghoraba, Saeed; Ataee, Ramin

2014-02-01

In the present study, the effects of intra-dorsal hippocampal (intra-CA1) injections of nitric oxide (NO) agents on muscimol state-dependent memory were examined in mice. A single-trial step-down passive avoidance task was used for the assessment of memory retrieval in adult male NMRI mice. Post-training intra-CA1 administration of a GABAA receptor agonist, muscimol (0.05 and 0.1 μg/mouse) dose dependently induced impairment of memory retention. Pre-test injection of muscimol (0.05 and 0.1 μg/mouse) induced state-dependent retrieval of the memory acquired under post-training muscimol (0.1 μg/mouse, intra-CA1) influence. Pre-test injection of a NO precursor, L-arginine (1 and 2 μg/mouse, intra-CA1) improved memory retention, although the low dose of the drug (0.5 μg/mouse) did not affect memory retention. Pre-test injection of an inhibitor of NO-synthase, L-NAME (0.5 and 1 μg/mouse, intra-CA1) impaired memory retention, although the low dose of the drug (0.25 μg/mouse) did not affect memory retention. In other series of experiments, pre-test intra-CA1 injection of L-arginine (0.25 and 0.5 μg/mouse) 5 min before the administration of muscimol (0.1 μg/mouse, intra-CA1) dose dependently inhibited muscimol state-dependent memory. Pre-test intra-CA1 administration of L-arginine (0.125, 0.25 and 0.5 μg/mouse) by itself cannot affect memory retention. Pre-test intra-CA1 injection of L-NAME (0.25 μg/mouse, intra-CA1) reversed the memory impairment induced by post-training administration of muscimol (0.1 μg/mouse, intra-CA1). Moreover, pre-test administration of L-NAME (0.125 and 0.25 μg/mouse, intra-CA1) with an ineffective dose of muscimol (0.025 μg/mouse, intra-CA1) significantly restored the retrieval and induced muscimol state-dependent memory. Pre-test intra-CA1 administration of L-NAME (0.0625, 0.125 and 0.25 μg/mouse) by itself cannot affect memory retention. It may be suggested that the nitric oxide in the dorsal hippocampal area play an important role in muscimol state-dependent memory. Copyright © 2013 Elsevier Inc. All rights reserved.

23. DETAIL VIEW OF COLUMN #072, SHOWING TOP LEANING TO ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

23. DETAIL VIEW OF COLUMN #072, SHOWING TOP LEANING TO SOUTHEAST (LEFT IN PHOTOGRAPH) WITH STEEL PIPE AS TEMPORARY SUPPORT (SEE PHOTOGRAPH NO. CA-125-A-24 BELOW) - Oakland Army Base, Transit Shed, East of Dunkirk Street & South of Burma Road, Oakland, Alameda County, CA

EGFR-mutant Non-small Cell Lung Cancer Accompanied by Transient Asymptomatic Pulmonary Opacities Successfully Treated with “Stop-And-Go” Osimertinib

PubMed Central

Kobayashi, Keigo; Naoki, Katsuhiko; Kuroda, Aoi; Yasuda, Hiroyuki; Kawada, Ichiro; Soejima, Kenzo; Betsuyaku, Tomoko

2017-01-01

A 69-year-old man with post-operative recurrence of lung adenocarcinoma was treated with multiple chemotherapies, including epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors. A second biopsy revealed an EGFR T790M mutation. As 10th-line chemotherapy, osimertinib was initiated. After 24 weeks, chest computed tomography (CT) revealed asymptomatic ground-glass opacities in both lobes. After four weeks of osimertinib discontinuation, imaging revealed rapid lung cancer progression. Osimertinib was resumed. After 11 weeks, CT revealed decreased lung nodules with no exacerbation of interstitial lung disease. We describe a patient who experienced transient asymptomatic pulmonary opacities during treatment with osimertinib, which was successfully managed by a “stop-and-go” approach. PMID:29269665

Does IGF-1 play a role in the biology of ovarian cancer?

PubMed

Majchrzak-Baczmańska, Dominika; Malinowski, Andrzej; Głowacka, Ewa; Wilczyński, Miłosz

2018-01-01

The aim of the study was to investigate serum concentrations of the insulin-like growth factor-1 in women with ovarian cancer and healthy controls, and to compare free IGF-1 levels with selected clinical and pathological param-eters. Correlation analysis was used to measure the following: IGF-1 concentration and Ca125; IGF-1 level and the height of the OC patients. The study included 70 patients with OC and 50 healthy controls. Serum concentrations of free IGF-1 were measured in all subjects. Routine diagnostic tests (CBC and USG and Ca125) were performed. Significantly higher serum concentrations of free IGF-1 were found in the study group as compared to controls. No statistically significant relationships between IGF-1 serum concentrations and tumor differentiation, histological type, and disease stage were detected. No statistically significant correlations between IGF-1 and Ca125 level or between IGF-1 and growth of OC patients were found. Serum IGF-1 participates in the etiopathogenesis of ovarian cancer in menstruating women, while local synthesis of this factor and other components of the autocrine loop of the IGF-1 system play a greater role in their post-menopausal peers.

Endometrial protein PP14 and CA-125 in recurrent miscarriage patients; correlation with pregnancy outcome.

PubMed

Dalton, C F; Laird, S M; Estdale, S E; Saravelos, H G; Li, T C

1998-11-01

The concentrations of endometrial proteins PP14 and CA-125 were measured in uterine flushings taken on days LH+10 and LH+12 (10 and 12 days after luteinizing hormone surge) of the menstrual cycle from 15 normal, fertile women and 49 women who suffered recurrent miscarriage. The concentration of PP14 was significantly lower in the flushings from the recurrent miscarriage patients than in those from fertile controls on both day LH+10 (median: 1300, range: 3-10 300 ng/ml versus median: 13 933, range: 2174-40 404 ng/ml; P < 0.01) and LH+12 (median: 1560, range: 820-12 100 ng/ml versus median: 14 047, range 1402-62 108 ng/ml; P < 0.05). Similarly concentrations of CA-125 were significantly lower in flushings from recurrent miscarriage women compared to controls on both day LH + 10 (median: 1555, range: 47-6710 U/ml versus median: 6385.5, range 2884-27 731 U/ml, P < 0.01) and LH+12 (median: 2892, range: 956-9974 U/ml versus median: 7127.5, range: 1591-21 343 U/ml; P < 0.05). In contrast there was no significant difference in the concentration of PP14 in plasma samples taken on the same days as the flushings from recurrent miscarriage patients and fertile controls. The concentrations of PP14 in uterine flushings obtained on day LH + 10 or LH + 12 from recurrent miscarriage women during a pre-pregnancy investigative cycle were significantly lower (P < 0.05) in patients who went on to miscarry (median: 1000, range: 9-2900 ng/ml) than those who went on to have a live birth (median: 1440, range: 4-12 100 ng/ml) during a subsequent pregnancy. In contrast there was no significant difference in uterine CA-125 or plasma PP14 concentrations between these two groups of recurrent miscarriage patients. The results suggest that measurements of uterine PP14 and CA-125 may be useful in the assessment of endometrial development in recurrent miscarriage patients and suggest the importance of PP14 in preparing the endometrium for embryo implantation. In addition pre-pregnancy uterine PP14 measurements may be useful in predicting subsequent pregnancy outcome.

Female sexual and pelvic floor muscles dysfunctions in familial amyloidotic polyneuropathy (FAP-Portuguese type).

PubMed

Gomes, Mario João; Martins da Silva, Antonio; Salinas, Jesus; Silva, Maria Carolina; Figueiredo, Arnaldo; Cavadas, Vitor; Coelho, Teresa

2012-05-01

The aim of this study was to investigate the prevalence of Sexual and Pelvic Floor Dysfunctions associated with familial type 1 Portuguese amyloid polyneuropathy (FAP). We studied women with FAP in three stages of the disease: asymptomatic women (n=12), women in the early stage of the disease (n=8) and 3 women in the most progressive stage of the disease. We hypothesize that women with FAP suffer from pelvic floor hypotonicity, which may hinder orgasmic function and as such, lead to deteriorated sexual function. Twenty-three women with FAP were studied. Clinical examinations were performed using the following scales: Clinical Evaluation Scale (CES), Visual Analog Scale of Quality of Life (VAS), Female Sexual Function Index (FSFI) and Pelvic Floor Manometry (PFM). Of the women, 5 (21.7%) had a score of < 26 on the FSFI, suggesting sexual dysfunction, 3 of which had FAP at the most progressive stage. None of the asymptomatic women had low FSFI scores. The manometrical rates (PFM) of tonus and strength of the pelvic floor showed significant differences between groups. Female sexual dysfunction (FSD) may occur in the initial stages of the disease but is more prevalent in women in the advanced stages of the disease. There is an increasing incidence of FSD as FAP disease progresses, namely in terms of HSDD and orgasmic sensation. In the asymptomatic group, the females revealed PFM alterations without stress urinary incontinence, which is regarded to be a discrete deterioration of pelvic floor muscle function.

The β subunit of the high-conductance calcium-activated potassium channel contributes to the high-affinity receptor for charybdotoxin

PubMed Central

Hanner, Markus; Schmalhofer, William A.; Munujos, Petraki; Knaus, Hans-Günther; Kaczorowski, Gregory J.; Garcia, Maria L.

1997-01-01

Transient expression of either α or α+β subunits of the high-conductance Ca2+-activated K+ (maxi-K) channel has been achieved in COS-1 cells. Expression has been studied using charybdotoxin (ChTX), a peptidyl inhibitor that binds in the pore on the α subunit. Although some properties of monoiodotyrosine-ChTX (125I-ChTX) binding to membranes derived from each type of transfected cells appear to be identical, other parameters of the binding reaction are markedly different. Under low ionic strength conditions, the affinity constant for 125I-ChTX measured under equilibrium binding conditions is increased ca. 50-fold in the presence of the β subunit. The rate constant for 125I-ChTX association is enhanced ca. 5-fold, whereas the dissociation rate constant is decreased more than 7-fold when the β subunit is present. These data indicate that functional coassembly of maxi-K channel subunits can be obtained in a transient expression system, and that the β subunit has profound effects on 125I-ChTX binding. We postulate that certain negatively charged residues in the large extracellular loop of β attract the positively charged 125I-ChTX to its binding site on α through electrostatic interactions, and account for effects observed on ligand association kinetics. Moreover, another residue(s) in the loop of β must contribute to stabilization of the toxin-bound state, either by a direct interaction with toxin, or through an allosteric effect on the α subunit. Certain regions in the extracellular loop of the β subunit may be in close proximity to the pore of the channel, and could play an important role in maxi-K channel function. PMID:9096310

Effects of endotoxemia on systemic plasma loss and hematocrit in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

van Lambalgen, A.A.; Rasker, M.T.; van den Bos, G.C.

1988-11-01

Endotoxemia in rats increases plasma extravasation but does not result in continuously rising hematocrit. These contradictory observations led us to design a study in anesthetized rats (C, control rats, n = 10; E, endotoxin rats, n = 10) in which we continuously measured in blood hematocrit (conductivity cell) and changes in concentration of 125I-HSA (human serum albumin) and 51Cr-labeled red cell (51Cr-RBC; multichannel analyzer) in an extracorporeal circuit. In two additional series of experiments we measured in blood samples changes in protein concentration (series II, C: n = 7, E: n = 7) and uptake of intraperitoneally injected 125I-HSA andmore » 51Cr-RBC (reflecting lymph flow rate; series III, C: n = 6, E: n = 7). Endotoxemia was induced by infusion (iv, 0.2 ml/100 g.hr) of Escherichia coli endotoxin (20 mg/kg) from t = 0 to t = 60 min; controls received saline. Experiments ended at t = 120 (series I and II) or 150 min (series III). The endotoxemia resulted in a marked rise of serum lactate (by ca 500% at t = 120); heart rate increased and central venous pressure decreased (by ca 20 and -95% at t = 120, respectively). All rats showed characteristic changes in hematocrit during endotoxemia: an increase from t = 20 to t = 45 (by ca 9%) followed by a decrease to preshock values or less at t = 120. The 51Cr activity per microliter blood cells did not change, indicating that there was no red cell mobilization. Protein concentration and 125I-HSA activity also showed a temporary increase during endotoxemia, but 125I-HSA activity per gram protein was decreased. Peritoneal uptake of 125I-HSA and 51Cr-RBC was significantly increased during endotoxemia (by 200%).« less

Diagnostic accuracy and cost-effectiveness of different strategies to triage women with adnexal masses: a prospective study.

PubMed

Piovano, E; Cavallero, C; Fuso, L; Viora, E; Ferrero, A; Gregori, G; Grillo, C; Macchi, C; Mengozzi, G; Mitidieri, M; Pagano, E; Zola, P

2017-09-01

Transvaginal sonography (TVS) and serum biomarkers are used widely in clinical practice to triage women with adnexal masses, but the effectiveness of current biomarkers is weak. The aim of this study was to determine the best method of diagnosing patients with adnexal masses, in terms of diagnostic accuracy and economic costs, among four triage strategies: (1) the International Ovarian Tumor Analysis group's simple rules (SR) for interpretation of TVS with subjective assessment (SA) by an experienced ultrasound operator when TVS results are inconclusive (referred to hereafter as SR ± SA), (2) SR ± SA and cancer antigen 125 (CA 125), (3) SR ± SA and human epididymis protein 4 (HE4) and (4) SR ± SA and the risk of malignancy algorithm (ROMA). Our main hypothesis was that the addition of the biomarkers to SR ± SA could improve triaging of these patients in terms of diagnostic accuracy (i.e. malignant vs benign). As secondary analyses, we estimated the cost effectiveness of the four strategies and the diagnostic accuracy of SR ± SA at the study hospitals. Between February 2013 and January 2015, 447 consecutive patients who were scheduled for surgery for an adnexal mass at the S. Anna and Mauriziano Hospitals in Turin were enrolled in this multicenter prospective cohort study. Preoperative TVS was performed and preoperative CA 125 and HE4 levels were measured. Pathology reports were used to assess the diagnostic accuracy of the four triage strategies and the cost of each strategy was calculated. A total of 391 patients were included in the analysis: 57% (n = 221) were premenopausal and 43% (n = 170) were postmenopausal. The overall prevalence of malignancy was 21%. SR were conclusive in 89% of patients and thus did not require SA; the overall performance of SR ± SA showed a sensitivity of 82%, specificity of 92% and positive and negative predictive values and positive and negative likelihood ratios of 74%, 95%, 10.5 and 0.19, respectively. In premenopausal women, mean cost among the four triage strategies varied from €36.41 for SR ± SA to €70.12 for SR ± SA + ROMA. The addition of biomarkers to SR ± SA showed no diagnostic advantage compared with SR ± SA alone and was more costly. Among postmenopausal women, mean cost among the four triage strategies varied from €39.52 for SR ± SA to €73.23 for SR ± SA + ROMA. Among these women, SR ± SA + CA 125 and SR ± SA + ROMA had a higher sensitivity (both 92% (95% CI, 85-99%)) than SR ± SA (81% (95% CI, 71-91%)), but SR ± SA had a higher specificity (84% (95% CI, 77-91%)). SR ± SA + CA 125 and SR ± SA + ROMA improved diagnostic accuracy, each diagnosing a third more malignant adnexal masses. In postmenopausal women, compared with SR ± SA alone, SR ± SA + CA 125 showed a net reclassification improvement (NRI) of 28.8% at an extra cost of €13.00, while the extra cost for SR ± SA + ROMA was €33.71, with a comparable gain, in terms of NRI, as that of SR ± SA + CA 125. In our study sample, SR ± SA seems to be the best strategy to triage women with adnexal masses for surgical management. Among postmenopausal women, SR ± SA + CA 125 increased the NRI at a reasonable extra cost. Our data do not justify the use of HE4 and ROMA in the initial triage of women with adnexal masses. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Klotho Prevents Renal Calcium Loss

PubMed Central

Alexander, R. Todd; Woudenberg-Vrenken, Titia E.; Buurman, Jan; Dijkman, Henry; van der Eerden, Bram C. J.; van Leeuwen, Johannes P.T.M.; Bindels, René J.

2009-01-01

Disturbed calcium (Ca2+) homeostasis, which is implicit to the aging phenotype of klotho-deficient mice, has been attributed to altered vitamin D metabolism, but alternative possibilities exist. We hypothesized that failed tubular Ca2+ absorption is primary, which causes increased urinary Ca2+ excretion, leading to elevated 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and its sequelae. Here, we assessed intestinal Ca2+ absorption, bone densitometry, renal Ca2+ excretion, and renal morphology via energy-dispersive x-ray microanalysis in wild-type and klotho−/− mice. We observed elevated serum Ca2+ and fractional excretion of Ca2+ (FECa) in klotho−/− mice. Klotho−/− mice also showed intestinal Ca2+ hyperabsorption, osteopenia, and renal precipitation of calcium-phosphate. Duodenal mRNA levels of transient receptor potential vanilloid 6 (TRPV6) and calbindin-D9K increased. In the kidney, klotho−/− mice exhibited increased expression of TRPV5 and decreased expression of the sodium/calcium exchanger (NCX1) and calbindin-D28K, implying a failure to absorb Ca2+ through the distal convoluted tubule/connecting tubule (DCT/CNT) via TRPV5. Gene and protein expression of the vitamin D receptor (VDR), 25-hydroxyvitamin D-1-α-hydroxylase (1αOHase), and calbindin-D9K excluded renal vitamin D resistance. By modulating the diet, we showed that the renal Ca2+ wasting was not secondary to hypercalcemia and/or hypervitaminosis D. In summary, these findings illustrate a primary defect in tubular Ca2+ handling that contributes to the precipitation of calcium-phosphate in DCT/CNT. This highlights the importance of klotho to the prevention of renal Ca2+ loss, secondary hypervitaminosis D, osteopenia, and nephrocalcinosis. PMID:19713312

Pituitary and Peripheral Hormone Responses to T3 Administration During Antarctic Residence

DTIC Science & Technology

1988-06-01

CA, and McMurdo, Antarctica. The basal diet consisted of 2,000-2,500 kcalories (kcal), with -40% as carbohydrate, 35% as protein, and 12.5, 12.5, 12.5...and Diet ranges may have precluded us from detecting basal non- Even though the amount of consumed calories in- stimulated differences. Others have... hypocaloric feed- exposure. MOG, microgram. * P < 0.05 compared with warm control ing cannot account for our findings because serum T 3 in climate values

Morin-like spin canting in the magnetic CaFe{sub 5}O{sub 7} ferrite: A combined neutron and Mössbauer study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Delacotte, C.; Bréard, Y.; Caignaert, V.

2017-03-15

Magnetic structure of CaFe{sub 5}O{sub 7} ferrite has been studied jointly from neutron powder diffraction data and spectroscopic Mössbauer measurements in the thermal range from 5 to 500 K. This coupled work highlights three distinct magnetic domains around two specific temperatures: T{sub M}=125 K and T{sub N}=360 K. The latter corroborates the structural monoclinic-orthorhombic transition previously reported by transmission electron microscopy techniques and X-ray thermodiffractometry. Complementary heat capacity measurements have confirmed this first order transition with a sharp peak at 360 K. Interestingly, this large study has revealed a second magnetic transition associated to a spin rotation at 125 Kmore » similar to this one reported by Morin in α-Fe{sub 2}O{sub 3} hematite at T{sub M}=260 K. - Graphical abstract: Magnetic structure of CaFe{sub 5}O{sub 7} ferrite has been studied jointly from neutron powder diffraction data and spectroscopic Mössbauer measurements in the thermal range from 5 to 500 K. This coupled work highlights three distinct magnetic domains around two specific temperatures: T{sub M}=125 K and T{sub N}=360 K. Interestingly, this large study has revealed a magnetic transition associated to a spin rotation at 125 K similar to this one reported by Morin in α-Fe{sub 2}O{sub 3} hematite at T{sub M}=260 K.« less

[Effects of Total Alkaloids of Harmaline on Learning and Memory in Vascular Dementia Rats].

PubMed

Zhang, Xiao-shuang; Sun, Jian-ning; Yu, Hui-ling

2015-11-01

To investigate the effects of total alkaloids of harmaline on learning and memory in vascular dementia rats, and its mechanism. The model rats of vascular dementia were established with bilateral carotid artery ligation. After 30 days, the model rats were randomly divided into six groups: sham group, model group, nicergoline tablets 7 mg/kg group, and 25, 12.5 and 6.25 mg/kg dose groups of total alkaloids of harmaline, the rats were given medicine for 30 days. Learning and memory abilities were tested by Morris water maze, histomorphology in hippocampal CA1 area were observed by HE staining, BAX and BCL-2 protein expression in hippocampal CA1 area were detected by immunohistochemistry. Compared with model group, 25 mg/kg group of total alkaloids of harmaline shortened the incubation period in the third and fourth day significantly, 12.5 mg/kg group of total alkaloids of harmaline shortened the incubation period in the fourth day. 25 and 12.5 mg/kg groups of total alkaloids of harmaline significantly increased the times crossing the target. Total alkaloids of harmaline improved the neurons pathological changes of rat in the hippocampus CA1 area, 25 and 12.5 mg/kg of total alkaloids of harmaline downregulated the expression of apoptosis proteins BAX, upregulated the protein expression of BCL-2. Total alkaloids of harmaline can improve the learning and memory abilities in vascular dementia rats, which probably is related to inhibiting apoptosis of hippocampus cell.

CdZnTeS quantum dots based electrochemiluminescent image immunoanalysis.

PubMed

Liang, Xiu-Li; Bao, Ning; Luo, Xiliang; Ding, Shou-Nian

2018-06-05

In this work, quaternary CdZnTeS quantum dots (QDs) with a particularly strong electrochemiluminescence (ECL) were synthesized as ECL signal labels. The strong ECL signals can be obtained at both cathode and anode with the ECL efficiencies of 19.78% and 1.62%, respectively. The sandwich-structured ECL immunosensors for the detection of alpha-fetoprotein (AFP) and cancer antigen 125 (CA125) were accomplished with direct ECL image analysis. Under optimal conditions, the QDs-based ECL image immunoanalysis possessed good linearity from 0.5 ng/mL to 20 ng/mL for AFP and from 20 U/mL to 500 U/mL for CA125 with the detection limit of 0.1 ng/mL and 6 U/mL, respectively (S/N = 3), and the lower detection limit obtained by photomultiplier tube were 0.1 fg/mL for AFP and 0.03 mU/mL for CA125 with the wide dynamic range from 0.5 fg/mL to 20 ng/mL and from 0.1 mU/mL to 500 U/mL, respectively (S/N = 3). Furthermore, the ECL immunoanalysis was evaluated with commercial enzyme-linked immunosorbent assay in human serum samples. The good results indicated that CdZnTeS QDs-based ECL biosensor has great potential for fast biomedical screening and multi-assays in clinical diagnosis. Copyright © 2018 Elsevier B.V. All rights reserved.

Prolonged exposure to 1,25(OH)2D3 and high ionized calcium induces FGF-23 production in intestinal epithelium-like Caco-2 monolayer: A local negative feedback for preventing excessive calcium transport.

PubMed

Rodrat, Mayuree; Wongdee, Kannikar; Panupinthu, Nattapon; Thongbunchoo, Jirawan; Teerapornpuntakit, Jarinthorn; Krishnamra, Nateetip; Charoenphandhu, Narattaphol

2018-02-15

Overdose of oral calcium supplement and excessive intestinal calcium absorption can contribute pathophysiological conditions, e.g., nephrolithiasis, vascular calcification, dementia, and cardiovascular accident. Since our previous investigation has indicated that fibroblast growth factor (FGF)-23 could abolish the 1,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ]-enhanced calcium absorption, we further hypothesized that FGF-23 produced locally in the enterocytes might be part of a local negative feedback loop to regulate calcium absorption. Herein, 1,25(OH) 2 D 3 was found to enhance the transcellular calcium transport across the epithelium-like Caco-2 monolayer, and this stimulatory effect was diminished by preceding prolonged exposure to high-dose 1,25(OH) 2 D 3 or high concentration of apical ionized calcium. Pretreatment with a neutralizing antibody for FGF-23 prevented this negative feedback regulation of calcium hyperabsorption induced by 1,25(OH) 2 D 3 . FGF-23 exposure completely abolished the 1,25(OH) 2 D 3 -enhanced calcium transport. Western blot analysis revealed that FGF-23 expression was upregulated in a dose-dependent manner by 1,25(OH) 2 D 3 or apical calcium exposure. Finally, calcium-sensing receptor (CaSR) inhibitors were found to prevent the apical calcium-induced suppression of calcium transport. In conclusion, prolonged exposure to high apical calcium and calcium hyperabsorption were sensed by CaSR, which, in turn, increased FGF-23 expression to suppress calcium transport. This local negative feedback loop can help prevent unnecessary calcium uptake and its detrimental consequences. Copyright © 2018 Elsevier Inc. All rights reserved.

Molecular Mechanisms for Regulation of Intestinal Calcium Absorption by Vitamin D and Other Factors

PubMed Central

Fleet, James C.; Schoch, Ryan D.

2011-01-01

Optimal intestinal calcium (Ca) absorption is necessary for the protection of bone and the prevention of osteoporosis. Ca absorption can be represented as the sum of a saturable pathway and a non-saturable pathway that is primarily dependent upon luminal Ca concentration. While models have been proposed to describe these transport components, significant gaps still exist in our understanding of these processes. Habitual low intake of Ca up-regulates the saturable transport pathway, a process mediated by increased renal production of 1,25 dihydroxyvitamin D (1,25(OH)2 D). Consistent with this, low vitamin D status as well as deletion/mutation of the vitamin D receptor (VDR) or 25 hydroxyvitamin D-1α hydroxylase (CYP27B1) genes limit Ca absorption by reducing the saturable pathway. There is some evidence that non-saturable Ca absorption in the ileum is also regulated by vitamin D status, but the mechanism is unclear. Treatment with a number of hormones can regulate Ca absorption in vivo [e.g. parathyroid hormone (PTH), thyroid hormone, growth hormone (GH)/insulin-like growth factor I (IGF-1), estrogen, testosterone]. However, some of these actions are indirect (i.e. mediated through the regulation of vitamin D metabolism or signaling), whereas only a few (e.g. estrogen, IGF-1) have been shown to persist in the absence of vitamin D signaling. PMID:21182397

1. EXTERIOR OF BUILDING 125 FROM MAIN PLANT 4 RESIDENTIAL ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

1. EXTERIOR OF BUILDING 125 FROM MAIN PLANT 4 RESIDENTIAL STREET SHOWING BUILDING AT PHOTO RIGHT CENTER (WITH WHITE JEEP PARKED IN FRONT) BETWEEN WORKER COTTAGE (BUILDING 115) AT PHOTO LEFT AND RECREATION HALL (BUILDING 109) AT PHOTO RIGHT. VIEW TO SOUTH. - Bishop Creek Hydroelectric System, Plant 4, Lightning Arrestor Vault, Bishop Creek, Bishop, Inyo County, CA

75 FR 58466 - Environmental Impact Statement: Los Angeles and San Bernardino Counties, CA; Notice of Intent

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-24

..., passenger auto and transit travel, and reducing the environmental impacts of transportation for cities and...)--Freeway/Toll Way. This would consist of engineering geometrics similar to Alternative 3 with alterations... engineering geometrics similar to Alternative 3 between SR-14 and approximately 125th St. East. From 125th St...

The Role of Vitamin D in the Bone Changes Associated with Simulated Weightlessness

NASA Technical Reports Server (NTRS)

Halloran, B. P.; Bikle, D. D.; Holton, E.; Levens, M. J.; Globus, R.

1985-01-01

The role of vitamin D in the change in bone metabolism was examined. The serum concentrations in rats sacrificed after 2, 5, 7, 10, 12 and 15 days of suspension was measured. Between days 1 and 5 of suspension and then gradually decreased towards normal between days 5 and 15. The time course of the changes in the circulating concentrations of 1,25(OH)2D and 24,25(OH)2D mirror almost precisely the changes in bone metabolism. The relationship between the changes in vitamin D metabolism and bone metabolism is investigated. Whether the bone changes are due to the change in serum concentration of 1,25(OH)2D or the changes in bone formation causing a reduction in Ca flux out of the serum pool and thereby suppressing 1,25(OH)2D production is examined. It is found that suspension had no effect on hormone concentration in the 1,25(OH)2D infused animals. Nevertheless, both vehicle and 1,25(OH)2D infused suspended rats exhibited the same reduction in bone mineral, and uptake of (45)Ca. It is suggested that the transitory reduction in circulating 1,25(OH)2D during suspension is not likely to cause the abnormalities in bone metabolism but rather that the changes in bone metabolism are primary and cause the fall in serum 1,25(OH)2D concentration. This supports the hypothesis that the metabolic abnormalities in bone associated with simulated weightlessness are due to the direct effect of unweighting on the bone.

Hypervitaminosis D mediates compensatory Ca2+ hyperabsorption in TRPV5 knockout mice.

PubMed

Renkema, Kirsten Y; Nijenhuis, Tom; van der Eerden, Bram C J; van der Kemp, Annemiete W C M; Weinans, Harrie; van Leeuwen, Johannes P T M; Bindels, René J M; Hoenderop, Joost G J

2005-11-01

Vitamin D plays an important role in Ca(2+) homeostasis by controlling Ca(2+) (re)absorption in intestine, kidney, and bone. The epithelial Ca(2+) channel TRPV5 mediates the Ca(2+) entry step in active Ca(2+) reabsorption. TRPV5 knockout (TRPV5(-/-)) mice show impaired Ca(2+) reabsorption, hypercalciuria, hypervitaminosis D, and intestinal hyperabsorption of Ca(2+). Moreover, these mice demonstrate upregulation of intestinal TRPV6 and calbindin-D(9K) expression compared with wild-type mice. For addressing the role of the observed hypervitaminosis D in the maintenance of Ca(2+) homeostasis and the regulation of expression levels of the Ca(2+) transport proteins in kidney and intestine, TRPV5/25-hydroxyvitamin-D(3)-1alpha-hydroxylase double knockout (TRPV5(-/-)/1alpha-OHase(-/-)) mice, which show undetectable serum 1,25(OH)(2)D(3) levels, were generated. TRPV5(-/-)/1alpha-OHase(-/-) mice displayed a significant hypocalcemia compared with wild-type mice (1.10 +/- 0.02 and 2.54 +/- 0.01 mM, respectively; P < 0.05). mRNA levels of renal calbindin-D(28K) (7 +/- 2%), calbindin-D(9K) (32 +/- 4%), Na(+)/Ca(2+) exchanger (12 +/- 2%), and intestinal TRPV6 (40 +/- 8%) and calbindin-D(9K) (26 +/- 4%) expression levels were decreased compared with wild-type mice. Hyperparathyroidism and rickets were present in TRPV5(-/-)/1alpha-OHase(-/-) mice, more pronounced than observed in single TRPV5 or 1alpha-OHase knockout mice. It is interesting that a renal Ca(2+) leak, as demonstrated in TRPV5(-/-) mice, persisted in TRPV5(-/-)/1alpha-OHase(-/-) mice, but a compensatory upregulation of intestinal Ca(2+) transporters was abolished. In conclusion, the elevation of serum 1,25(OH)(2)D(3) levels in TRPV5(-/-) mice is responsible for the upregulation of intestinal Ca(2+) transporters and Ca(2+) hyperabsorption. Hypervitaminosis D, therefore, is of crucial importance to maintain normocalcemia in impaired Ca(2+) reabsorption in TRPV5(-/-) mice.

Blood vitamin D(3) metabolite concentrations of adult female bearded dragons (Pogona vitticeps) remain stable after ceasing UVb exposure.

PubMed

Oonincx, D G A B; van de Wal, M D; Bosch, G; Stumpel, J B G; Heijboer, A C; van Leeuwen, J P T M; Hendriks, W H; Kik, M

2013-07-01

Vitamin D deficiency can lead to several health problems collectively called metabolic bone disease (MBD). One commonly kept reptile species prone to develop MBD if managed incorrectly is the bearded dragon (Pogona vitticeps). This study aimed to determine the extent to which adult female bearded dragons fed a diet low in vitamin D can use stored vitamin D and its metabolites to maintain plasma 25(OH)D(3) and 1,25(OH)(2)D(3) concentrations after discontinuing UVb exposure. Blood samples of healthy adult female bearded dragons, exposed to UVb radiation for over 6 months were collected (day 0) after which UVb exposure was discontinued for 83 days and blood was collected. Blood plasma was analysed for concentrations of total Ca, total P, ionized Ca, uric acid, 25(OH)D(3) and 1,25(OH)(2)D(3). There was no significant change in plasma 25(OH)D(3) and 1,25(OH)(2)D(3) concentrations during the study. While total Ca and P in whole blood was found to significantly decrease over time (P < 0.0088 and 0.0016, respectively), values were within the reference range. Plasma ionized Ca tended (P = 0.0525) to decrease during the study. Adult female bearded dragons, previously exposed to UVb, are able to maintain blood vitamin D metabolite concentrations when UVb exposure is discontinued for a period of up to 83 days. Copyright © 2013 Elsevier Inc. All rights reserved.

Clinical analysis of primary primitive neuroectodermal tumors in the female genital tract.

PubMed

Xiao, Changji; Zhao, Jing; Guo, Peng; Wang, Dan; Zhao, Dachun; Ren, Tong; Yang, Jiaxin; Shen, Keng; Lang, Jinghe; Xiang, Yang; Cui, Quancai

2014-03-01

The aim of the study was to investigate the clinical manifestations, diagnosis, treatment, and prognosis of primitive neuroectodermal tumors (PNETs) in the female genital tract. From April 2001 to May 2013, the clinicopathologic characteristics, treatments, outcomes, and prognosis of 11 patients with PNET in the female genital tract were analyzed retrospectively at our hospital. The location of PNET in the 11 patients presented here included vulva (2 patients), cervix (2 patients), uterus and its ligament (5 patients), and the ovaries (2 patients). Ages ranged from 18 to 59 years (median, 31 years).The main clinical manifestations of PNET in the female genital tract are irregular vaginal bleeding (6 patients), pelvic mass, uterine enlargement, and rapidly increasing vulvar mass (8 patients), and vulvar pain and lower abdominal pain (5 patients). The CA125 levels of 8 patients were elevated before the operations and reduced to normal when the diseases were controlled, while the levels increased as the tumor was progressive. Results for the most commonly used immunohistochemistry studies revealed CD99 in 11 of the 11 tumors, synaptophysin in 6 of the 7 positive tumors, and neuron-specific enolase in 6 of the 6 tumors. Ten patients underwent surgical resection. Nine of them underwent preoperative or/and postoperative combination chemotherapy. The follow-up of 10 patients were available and ranged from 1 to 145 months (median, 30.5 months), 3 of whom experiencing recurrence. Primitive neuroectodermal tumor is very rare and can originate from any part of the female genital tract. The tumors had different manifestations but the same pathologic features. CA125 may be an important marker for prognosis and follow-up of PNET of the female internal genital tract.

Clinical outcomes of patients with clear cell and endometrioid ovarian cancer arising from endometriosis.

PubMed

Paik, E Sun; Kim, Tae Joong; Choi, Chel Hun; Kim, Byoung Gie; Bae, Duk Soo; Lee, Jeong Won

2018-03-01

The aim of this investigation is to compare outcomes of patients according to the presence of cancer arising from endometriosis in ovarian clear cell carcinoma (CCC) and endometrioid carcinoma (EC). This study retrospectively investigated 224 CCC and EC patients treated in Samsung Medical Center from 2001 to 2015 to identify cancer arising from endometriosis according to Sampson and Scott criteria. Propensity score matching was performed to compare patients arising from endometriosis to patients without endometriosis (ratio 1:1) according to stage, age, lymph node metastasis (LNM), cancer antigen (CA)-125 level, and residual status after debulking surgery. Forty-five cases arising from endometriosis were compared with 179 cases without endometriosis. CCC and EC arising from endometriosis tended to present with early age (mean, 45.2 vs. 49.2 years; p=0.003), early-stage (stages I and II, 92.7% vs. 62.3%; p<0.001), lower CA-125 level (mean, 307.1 vs. 556.7; p=0.041), higher percentages of no gross residual disease after surgery (87.8% vs.56.8%; p=0.001), and higher percentages of negative LNM (82.9% vs. 59.0%; p=0.008) compared to cases without endometriosis. Kaplan-Meier curves for progression-free survival (PFS) and overall survival (OS) showed better outcomes for groups with cancer arising from endometriosis (p=0.014 for PFS; and p=0.010 for OS). However, the association with endometriosis was not significant in multivariate analysis. Also, after propensity score matching, survival differences between the 2 groups were not significant. CCC and EC arising from endometriosis are diagnosed at an earlier age and stage. However, cancer arising from endometriosis was not a significant prognostic factor. Copyright © 2018. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology

High-risk carotid plaque: lessons learned from histopathology.

PubMed

Kolodgie, Frank D; Yahagi, Kazuyuki; Mori, Hiroyoshi; Romero, Maria E; Trout, Hugh H; Finn, Aloke V; Virmani, Renu

2017-03-01

The pathophysiology and natural history of atherosclerotic carotid disease is predicated on a more extensive knowledge of lesion progression gained in the studies conducted in the coronary arteries, and these will be reviewed. While the precise sequence of lesion progression leading to carotid plaque vulnerability and cerebrovascular events remain less well understood, specific early and more advanced progressive lesion morphologies associated with stroke risk have been characterized. Of late, there has been a conscious effort for stroke prevention in symptomatic and asymptomatic patients to move beyond luminal stenosis as the only guidance to predict future cerebrovascular events. Driving this strategy are recent advances in medical imaging modalities to assess carotid atherosclerosis vulnerability particularly involving molecular imaging, which is now positioned at the forefront to provide a more detailed and mechanistic assessment of stroke risk. As such, we will spotlight the pathology of high-risk carotid plaques in patients with symptomatic and asymptomatic carotid disease with further reference into more recent mechanistic insights involving a recognized macrophage-mediated inflammatory change, intraplaque neoangiogenesis/hemorrhage, hypoxia, and microcalcification, as potential morphologic indicators of stroke risk. Copyright © 2017 Elsevier Inc. All rights reserved.

Analysis of the discriminative methods for diagnosis of benign and malignant solitary pulmonary nodules based on serum markers.

PubMed

Wang, Wanping; Liu, Mingyue; Wang, Jing; Tian, Rui; Dong, Junqiang; Liu, Qi; Zhao, Xianping; Wang, Yuanfang

2014-01-01

Screening indexes of tumor serum markers for benign and malignant solitary pulmonary nodules (SPNs) were analyzed to find the optimum method for diagnosis. Enzyme-linked immunosorbent assays, an automatic immune analyzer and radioimmunoassay methods were used to examine the levels of 8 serum markers in 164 SPN patients, and the sensitivity for differential diagnosis of malignant or benign SPN was compared for detection using a single plasma marker or a combination of markers. The results for serological indicators that closely relate to benign and malignant SPNs were screened using the Fisher discriminant analysis and a non-conditional logistic regression analysis method, respectively. The results were then verified by the k-means clustering analysis method. The sensitivity when using a combination of serum markers to detect SPN was higher than that using a single marker. By Fisher discriminant analysis, cytokeratin 19 fragments (CYFRA21-1), carbohydrate antigen 125 (CA125), squamous cell carcinoma antigen (SCC) and breast cancer antigen (CA153), which relate to the benign and malignant SPNs, were screened. Through non-conditional logistic regression analysis, CYFRA21-1, SCC and CA153 were obtained. Using the k-means clustering analysis, the cophenetic correlation coefficient (0.940) obtained by the Fisher discriminant analysis was higher than that obtained with logistic regression analysis (0.875). This study indicated that the Fisher discriminant analysis functioned better in screening out serum markers to recognize the benign and malignant SPN. The combined detection of CYFRA21-1, CA125, SCC and CA153 is an effective way to distinguish benign and malignant SPN, and will find an important clinical application in the early diagnosis of SPN. © 2014 S. Karger GmbH, Freiburg.

78 FR 66948 - Request for Information on the Office of Disease Prevention Draft Strategic Plan for Fiscal Years...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-07

... progression of asymptomatic disease. Prevention research targets biology, individual behavior, factors in the social and physical environments, and health services and informs and evaluates health-related policies...

Has the time to come leave the “watch-and-wait” strategy in newly diagnosed asymptomatic follicular lymphoma patients?

PubMed Central

2012-01-01

Background Historically, the median overall survival for follicular lymphoma (FL) has been considered to be 9-10 years, and no treatment had ever prolonged this time period. Studies conducted more than 20 years ago demonstrated that treating patients with asymptomatic FL at the onset of the disease did not increase their survival, and that almost 20% of these patients did not need any treatment in the first 10 years of follow-up. Based on these facts, most clinical practice guidelines recommend active surveillance policies for patients with asymptomatic FL. Discussion The introduction of antiCD-20 monoclonal antibodies, over the last 15 years, has significantly increased the median survival rate to above 14 years. This improvement was achieved before the combination of rituximab and chemotherapy regimens became extensively used in patients with symptomatic disease. Therefore, this increase in survival may currently be more significant. At present, several clinical trials have evaluated low-toxicity therapies that prolong progression-free periods, among which rituximab monotherapy, radioimmunotherapy or the combination of rituximab with bendamustine are the most relevant. Unfortunately, these clinical trials have included only patients with symptomatic FL. The results of a recently reported clinical trial show that treatment with single-agent rituximab prolongs progression-free survival rates, time to new treatment and the quality of life of asymptomatic patients, as compared with the active surveillance strategy. Longer follow-up of these results and data regarding overall survival are awaited before this treatment can be recommended as the standard initial therapy. Summary There are different therapeutic possibilities for asymptomatic FL patients, but no data are currently available to indicate which option is the best. Patients need to understand the risks and benefits of observation versus treatment before a final decision can be made. For patients who want active treatment the administration of four weekly rituximab doses should be considered. PMID:22650448

The population-based Barcelona-Asymptomatic Intracranial Atherosclerosis Study (ASIA): rationale and design

PubMed Central

2011-01-01

Background Large-artery intracranial atherosclerosis may be the most frequent cause of ischemic stroke worldwide. Traditional approaches have attempted to target the disease when it is already symptomatic. However, early detection of intracranial atherosclerosis may allow therapeutic intervention while the disease is still asymptomatic. The prevalence and natural history of asymptomatic intracranial atherosclerosis in Caucasians remain unclear. The aims of the Barcelona-ASymptomatic Intracranial Atherosclerosis (ASIA) study are (1) to determine the prevalence of ASIA in a moderate-high vascular risk population, (2) to study its prognostic impact on the risk of suffering future major ischemic events, and (3) to identify predictors of the development, progression and clinical expression of this condition. Methods/Design Cross-over and cohort, population-based study. A randomly selected representative sample of 1,503 subjects with a mild-moderate-high vascular risk (as defined by a REGICOR score ≥ 5%) and with neither a history of cerebrovascular nor ischemic heart disease will be studied. At baseline, all individuals will undergo extracranial and transcranial Color-Coded Duplex (TCCD) ultrasound examinations to detect presence and severity of extra and intracranial atherosclerosis. Intracranial stenoses will be assessed by magnetic resonance angiography (MRA). Clinical and demographic variables will be recorded and blood samples will be drawn to investigate clinical, biological and genetic factors associated with the presence of ASIA. A long-term clinical and sonographic follow-up will be conducted thereafter to identify predictors of disease progression and of incident vascular events. Discussion The Barcelona-ASIA is a population-based study aiming to evaluate the prevalence and clinical importance of asymptomatic intracranial large-artery atherosclerosis in Caucasians. The ASIA project may provide a unique scientific resource to better understand the dynamics of intracranial atherosclerosis from its early stages and to identify new potential therapeutic targets for this condition. PMID:21329527

[Demons-Meigs syndrome: information on a new case and review of the literature].

PubMed

Boufettal, H; Zaghba, N; Morad, S; Bakhatar, A; Yassine, N; Bahlaoui, A; Noun, M; Hermas, S; Samouh, N

2011-04-01

Demons-Meigs syndrome is a benign tumor of the ovary. It is very rare and its physiopathology remains obscure. We report a case of Demons-Meigs syndrome in a woman aged 51 years. It was discovered following a right pleural effusion syndrome with ascites and an abdominopelvic mass. Rate of serum CA 125 was 412IU/mL. Surgical exploration revealed ascites of one litre with no suspicious peritoneal lesion and an ovarian fibrothecoma of 70 mm. There were no post-operative complications and three months later, the level of CA 125 was negative with a total drainage of effusions. Copyright © 2011. Published by Elsevier Masson SAS.

Near Source Contributions to Teleseismic P Wave Coda and Regional Phases

DTIC Science & Technology

1991-04-27

Pasadena, CA 91-125 Mr. William J. Best Prof. F. A. Dahlen 907 Westwood Drive Geological and Geophysical Sciences Vienna, VA 22180 Princeton...Station S-CUBED University of California A Division of Maxwell Laboratory Berkeley, CA 94720 P.O.Box 1620 La Jolla, CA 92038-1620 2 Prof. William ...Geosciences- Building #77 University of Arizona Tucson, AZ 85721 Dr. William Wortman Mission Research Corporation 8560 Cinderbed Rd. Suite # 700 Newington

Manufacturing Methods and Techniques for Miniature High Voltage Hybrid Multiplier Modules

DTIC Science & Technology

1977-05-06

technologies and materials,, and to demonstrate the production line capability to fabricate at the rate of 125 acceptable units per 40 hour week. - iv...Miraloma Avenue Anaheim, CA 92803 Dr. Andrew Tlcki1 Nitron Cornoratlon 10420 Bubb Road Cunertino, CA 95014 S I Commander RAt)C * ATTN: RBRII/Mr. J. Brauer

Ultrasensitive electrochemical immunosensors for multiplexed determination using mesoporous platinum nanoparticles as nonenzymatic labels.

PubMed

Cui, Zhentao; Wu, Dan; Zhang, Yong; Ma, Hongmin; Li, He; Du, Bin; Wei, Qin; Ju, Huangxian

2014-01-07

An ultrasensitive multiplexed immunoassay method was developed at a disposable immunosensor array using mesoporous platinum nanoparticles (M-Pt NPs) as nonenzymatic labels. M-Pt NPs were prepared by ultrasonic method and employed to label the secondary antibody (Ab2) for signal amplification. The immunosensor array was constructed by covalently immobilizing capture antibody (Ab1) on graphene modified screen printed carbon electrodes (SPECs). After the sandwich-type immunoreactions, the M-Pt-Ab2 was bound to immunosensor surface to catalyze the electro-reduction of H2O2 reaction, which produced detectable signals for readout of analytes. Using breast cancer related panel of tumor markers (CA125, CA153 and CEA) as model analytes, this method showed wide linear ranges of over 4 orders of magnitude with the detection limits of 0.002 U mL(-1), 0.001 U mL(-1) and 7.0 pg mL(-1) for CA125, CA153 and CEA, respectively. The disposable immunosensor array possessed excellent clinical value in cancer screening as well as convenient point of care diagnostics. Copyright © 2013 Elsevier B.V. All rights reserved.

Regulation of gene expression by dietary Ca2+ in kidneys of 25-hydroxyvitamin D3-1 alpha-hydroxylase knockout mice.

PubMed

Hoenderop, Joost G J; Chon, Helena; Gkika, Dimitra; Bluyssen, Hans A R; Holstege, Frank C P; St-Arnaud, Rene; Braam, Branko; Bindels, Rene J M

2004-02-01

Pseudovitamin D deficiency rickets (PDDR) is an autosomal disease, characterized by undetectable levels of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), rickets and secondary hyperparathyroidism. Mice in which the 25-hydroxyvitamin D3-1 alpha-hydroxylase (1 alpha-OHase) gene was inactivated, presented the same clinical phenotype as patients with PDDR. cDNA Microarray technology was used on kidneys of 1 alpha-OHase knockout mice to study the expression profile of renal genes in this Ca2+-related disorder. Genome wide molecular events that occur during the rescue of these mice by high dietary Ca2+ intake were studied by the use of 15K cDNA microarray chips. 1 alpha-OHase knockout mice fed a normal Ca2+ diet developed severe hypocalcemia, rickets and died with an average life span of 12 +/- 2 weeks. Intriguingly, 1 alpha-OHase-/- mice supplemented with an enriched Ca2+ diet were normocalcemic and not significantly different from wild-type mice. Inactivation of the 1 alpha-OHase gene resulted in a significant regulation of +/- 1000 genes, whereas dietary Ca2+ supplementation of the 1 alpha-OHase-/- mice revealed +/- 2000 controlled genes. Interestingly, 557 transcripts were regulated in both situations implicating the involvement in the dietary Ca2+-mediated rescue mechanism of the 1 alpha-OHase-/- mice. Conspicuous regulated genes encoded for signaling molecules like the PDZ-domain containing protein channel interacting protein, FK binding protein type 4, kinases, and importantly Ca2+ transporting proteins including the Na+-Ca2+ exchanger, calbindin-D28K and the Ca2+ sensor calmodulin. Dietary Ca2+ intake normalized disturbances in the Ca2+ homeostasis due to vitamin D deficiency that were accompanied by the regulation of a subset of renal genes, including well-known renal Ca2+ transport protein genes, but also genes not previously identified as playing a role in renal Ca2+ handling.

Cytomegalovirus urinary excretion and long term outcome in children with congenital cytomegalovirus infection. Congenital CMV Longitudinal Study Group.

PubMed

Noyola, D E; Demmler, G J; Williamson, W D; Griesser, C; Sellers, S; Llorente, A; Littman, T; Williams, S; Jarrett, L; Yow, M D

2000-06-01

Cytomegalovirus (CMV) is the most frequent cause of congenital infection, and both symptomatic and asymptomatic infants may have long term sequelae. Children with congenital CMV infection are chronically infected and excrete CMV in the urine for prolonged periods. However, the effect of prolonged viral replication on the long term outcome of these children is unknown. To determine whether duration of CMV excretion is associated with outcome at 6 years of life in symptomatic and asymptomatic congenitally infected children. Longitudinal cohort study. Children congenitally infected with CMV were identified at birth and followed prospectively in a study of long term effects of congenital CMV infection. The relationship between duration of CMV urinary excretion and growth, neurodevelopment and presence and progression of sensorineural hearing loss (SNHL) at 6 years of age was determined. There was no significant difference in the duration of viral urinary excretion between children born with asymptomatic (median, 4.55 years) and symptomatic (median, 2.97 years) congenital CMV infection (P = 0.11). Furthermore there was no association between long term growth or cognitive outcome and duration of viral excretion. However, a significantly greater proportion of children who excreted CMV for <4 years had SNHL and progressive SNHL compared with children with CMV excretion >4 years (P = 0.019, P = 0.009, respectively). Children congenitally infected with CMV are chronically infected for years, but the duration of CMV urinary excretion is not associated with abnormalities of growth, or neurodevelopmental deficits. However, SNHL and progressive SNHL were associated with a shorter duration of CMV excretion.

Selected Adnexal Cystic Masses in Postmenopausal Women Can be Safely Managed by Laparoscopy

PubMed Central

Lee, Jeong-Won; Kim, Chul Jung; Lee, Ji Eun; Lee, Sun-Joo; Kim, Byoung-Gie; Lee, Je-Ho; Bae, Duk-Soo

2005-01-01

The aim of this study was to assess the efficacy and safety of laparoscopic treatment for adnexal cystic masses that were predicted to be benign in postmenopausal women. Postmenopausal women found to have an adnexal cystic mass were retrospectively evaluated with transvaginal ultrasonography, and serum CA-125 levels. The selection criteria were adnexal cystic masses greater than 3 cm but less than 10 cm, the masses were in the benign range (4-8) of Sassone's scoring system for transvaginal ultrasonography, and the patients had serum CA-125 levels less than 65 IU/mL. Two hundred nineteen women fulfilled the criteria and underwent operative laparoscopy. Almost all the masses (99.5%) were accurately predicted to be benign except for one borderline ovarian tumor. Two hundreds thirteen (97.3%) women were successfully managed by operative laparoscopy and six (2.7%) required laparotomy. For the patients managed by laparoscopy, the mean operative time was 51.3 min; the mean hospital stay was 2.5 days. There was no significant morbidity and surgery-related mortality. The combination of the Sassone's scoring system for transvaginal ultrasonography and serum CA-125 level can accurately predict benign cystic masses, and operative laparoscopy is technically feasible and safe for the management of adnexal mass in postmenopausal women. PMID:15953871

Radiographic progression of arthritic changes in shoulders with degenerative rotator cuff tears.

PubMed

Chalmers, Peter N; Salazar, Dane H; Steger-May, Karen; Chamberlain, Aaron M; Stobbs-Cucchi, Georgia; Yamaguchi, Ken; Keener, Jay D

2016-11-01

Very little longitudinal information has been available regarding the relationship of cuff tears and arthritis. The purpose of this study was to determine the midterm risk of and risk factors for rotator cuff tear arthropathy progression in a cohort of subjects with an asymptomatic rotator cuff tear. Baseline (visit 1), 5-year (visit 2), and most recent follow-up (visit 3) radiographs were reviewed in a cohort of 105 subjects enrolled for longitudinal surveillance of asymptomatic degenerative rotator cuff tears and 33 controls. The radiographs were assessed in a blinded, randomized fashion by 3 observers who graded glenohumeral arthritic changes using the Hamada scores, Samilson-Prieto (SPO) scores, and acromiohumeral interval (AHI). Osteoarthritis (SPO classification), cuff tear arthropathy (Hamada classification), and AHI progressed between visits 1 and 3 (median, 8 years; P < .001 in all cases). SPO progression was not significantly different for partial- vs. full-thickness vs. control baseline tear types (P = .19). Both full-thickness and partial-thickness tears had greater progression in Hamada scores than controls did in the first 5 years of follow-up (P = .02 and P = .03, respectively), but scores did not differ between partial- and full-thickness tears. Tears with and without enlargement did not differ in progression in SPO grade, Hamada grade, or AHI. Glenohumeral arthritic changes progress significantly but remain minimal within an 8-year period in early to moderate degenerative cuff disease. Whereas the presence of a rotator cuff tear influences progression in Hamada grade, the magnitude of radiographic progression is not influenced by tear severity or enlargement at midterm time points. Copyright © 2016 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Asymptomatic Cardiac Toxicity in Long-Term Cancer Survivors: Defining the Population and Recommendations for Surveillance

PubMed Central

Carver, Joseph R.; Szalda, Dava; Ky, Bonnie

2013-01-01

Advances in the treatment of pediatric and adult cancer have reduced the mortality rates from these disorders and have led to an ever-increasing population of long-term survivors. Chemotherapy and radiotherapy may cause premature cardiac disease that may be asymptomatic or symptomatic. All patients exposed to chemotherapy with cardiotoxic potential or chest radiotherapy have stage A heart failure and the goal of surveillance and treatment is to prevent progression to stages B-D. Screening strategies, including the use of biomarkers, echocardiography, and expert opinion surveillance and treatment recommendations, are presented. PMID:23540748

Calcium and strontium isotope fractionation during precipitation from aqueous solutions as a function of temperature and reaction rate; II. Aragonite

NASA Astrophysics Data System (ADS)

AlKhatib, Mahmoud; Eisenhauer, Anton

2017-07-01

In order to study Strontium (Sr) partitioning and isotope fractionation of Sr and Calcium (Ca) in aragonite we performed precipitation experiments decoupling temperature and precipitation rates (R∗, μmol/m2 h) in the interval of about 2.3-4.5 μmol/m2 h. Aragonite is the only pure solid phase precipitated from a stirred solutions exposed to an atmosphere of NH3 and CO2 gases throughout the spontaneous decomposition of (NH4)2CO3. The order of reaction with respect to Ca ions is one and independent of temperature. However, the order of reaction with respect to the dissolved inorganic carbon (DIC) is temperature dependent and decreases from three via two to one as temperature increases from 12.5 and 25.0 to 37.5 °C, respectively. Strontium distribution coefficient (DSr) increases with decreasing temperature. However, R∗ responds differently depending on the initial Sr/Ca concentration and temperature: at 37.5 °C DSr increase as a function of increasing R∗ but decrease for 12.5 and 25 °C. Not seen at 12.5 and 37.5 °C but at 25 °C the DSr-R∗ gradient is also changing sign depending on the initial Sr/Ca ratio. Magnesium (Mg) adsorption coefficient between aragonite and aqueous solution (DMg) decreases with temperature but increases with R∗ in the range of 2.4-3.8 μmol/m2 h. Strontium isotope fractionation (Δ88/86Sraragonite-aq) follows the kinetic type of fractionation and become increasingly negative as a function of R∗ for all temperatures. In contrast Ca isotope fractionation (Δ44/40Caaragonite-aq) shows a different behavior than the Sr isotopes. At low temperatures (12.5 and 25 °C) Ca isotope fractionation (Δ44/40Caaragonite-aq) becomes positive as a function of R∗. In contrast, at 37.5 °C and as a function of increasing R∗ the Δ44/40Caaragonite-aq show a Sr type like behavior and becomes increasingly negative. Concerning both the discrepant behavior of DSr as a function of temperature as well as for the Ca isotope fractionation as a function of temperature we infer that the switch of sign in the trace element partitioning as well as in the direction of the Ca isotope fractionation is probably due to the switch of complexation from a Ca2+-NH3 complexation at and below 25 °C to an Ca2+-H2O aquacomplex at 37.5 °C. The DSr-Δ88/86Srcalcite-aq correlation for calcite is independent of temperature in contrast to aragonite. We interpreted the strong DSr-temperature dependency of aragonite, the smaller range of Sr isotope fractionation as well as the shallower Δ88/86Srcalcite-aq-R∗ gradients to be a consequence of the increased aragonite solubility and the "Mg blocking effect". In contrast to Sr the Ca isotope fractionation values in calcite and aragonite depend both on the complexation in solution and independent on polymorphism.

Changes in bone structure and metabolism during simulated weightlessness: Endocrine and dietary factors

NASA Technical Reports Server (NTRS)

Halloran, B. P.; Wronski, T. J.

1985-01-01

The role of vitamin D, PTH and corticosterone in the skeletal alterations induced by simulated weightlessness was examined. The first objective was to determine if changes in the serum concentrations of Ca, P sub i, osteocalcin, 25-OH-D, 24,25(OH)2D or 1,25(OH)2D also occur following acute skeletal unloading. Animals were either suspended or pair fed for 2, 5, 7, 10, 12 and 15 days and the serum concentrations of Ca, P sub i, osteocalcin and the vitamin D metabolites measured. Bone histology was examined at day 5 after suspension. Acute skeletal unloading produced a transient hypercalcemia, a significant fall in serum osteocalcin and serum 1,25(OH)2D, a slight rise in serum 24,25(OH)2D, but did not affect the serum concentrations of P sub i or 25-OH-D. At the nadir in serum 1,25(OH)2D serum osteocalcin was reduced by 22%, osteoblast surface by 32% and longitudinal bone growth by 21%.

Effect of metal ions on the enzymatic hydrolysis of hemp seed oil by lipase Candida sp. 99-125.

PubMed

Lu, Jike; Wang, Pei; Ke, Zhaodi; Liu, Xin; Kang, Qiaozhen; Hao, Limin

2018-07-15

In order to study the effect of metal ions on the enzymatic hydrolysis of hemp seed oil by Candida sp. 99-125, the spectroscopy, stability and hydrolytic activity of the biocatalyst were investigated in presence of Ca 2+ , Mg 2+ , Fe 2+ , Fe 3+ , Cu 2+ , Sn 2+ , Pb 2+ , Zn 2+ and Ba 2+ metal ions, respectively. The UV spectroscopy showed that all the metal ions enhanced the absorbance but the decrease of fluorescence intensity was observed. All the metal ions could improve the lipase thermal stability except Cu 2+ and Ba 2+ . Hydrolysis of hemp seed oil proved that Ca 2+ , Fe 3+ , Pb 2+ and Ba 2+ could significantly improve the hydrolytic rate, and metal ions could influence lipase selectivity. The study revealed that metal ions could improve lipase stability, hydrolysis activity in the hydrolytic process of hemp seed oil by Candida sp. 99-125. Copyright © 2018 Elsevier B.V. All rights reserved.

Effects of aging and dietary antler supplementation on the calcium-regulating hormones and bone status in ovariectomized SAMP8 mice.

PubMed

Chen, Chun-Chi; Liu, Mei-Hui; Wang, Ming-Fu; Chen, Cheng-Chin

2007-12-31

This study was conducted to investigate the effects of aging and long-term dietary antler supplementation on the calcium-regulating hormones and bone status in ovariectomized (Ovx) SAMP8 mice. The female SAMP8 mice were divided into four groups (in each group n = 6), Ovx or sham operated at the age of 2 months, and fed with 0.2% antler containing diet or control diet from the age of 2.5 months. The samples were collected at the age of 3, 6, 9, 12, and 15 months, respectively, for physicochemical analyses, biochemical analyses, and the determination of hormones by radioimmunoassay. The results showed that plasma calcium (Ca) concentrations were maintained in a narrow range in all groups throughout the whole experimental period. With aging and/or ovariectomy, plasma parathyroid hormone (PTH) and 1,25-dihydroxycholecalciferol (1,25-(OH)2-D3) levels increased, and plasma phosphorus (P) and calcitonin (CT) levels decreased, and the femoral bone densities and Ca contents increased during the earlier stage, and then decreased gradually in all groups. Plasma PTH and 1,25-(OH)2-D3 levels in the Ovx mice were significantly higher than those in the intact mice, and plasma P concentrations, plasma CT levels, femoral bone densities, and femoral Ca contents in the Ovx mice were significantly lower than those in the intact mice. In addition, the decreases of plasma P levels, plasma CT levels, femoral bone densities, and femoral Ca contents, and the increases of plasma PTH levels were moderated by antler administration in both Ovx and intact mice. However, there was no effect of the dietary antler supplementation on the plasma 1,25-(OH)2-D3 levels in the female mice. It is concluded that prolonged dietary antler supplementation has important positive effects on bone loss with age and/ or ovarian function deficiency.

[Effects of Gushen Antai pills combined with progestin on serum β-HCG, P, E2 and CA125 in patients with threatened abortion].

PubMed

Tian, Chun-Man; Chen, Bo

2016-01-01

To investigate the clinical effect of Gushen Antai pills and progesterone in the treatment of threatened abortion, in order to provide references for early clinical intervention with threatened abortion. The 112 cases of patients with threatened abortion were randomly divided into the control group and the observation group. 56 cases in each group. Patients in the control group was injected with progesterone, the observation group was treated with Gushen Antai pills in addition to the therapy of the control group. Both groups were treated by drugs for two weeks. Their venous bloods (5 mL) were collected before treatment and in 1, 2 weeks after treatment to determine serum levels of β-HCG, P, E2 and CA125. The differences between the two groups after treatment were compared. The total effective rate of the control group and the observation group were 79% and 91.9% respectively, with a statistically significant difference between the two groups (P＜0.05). Two weeks after the treatment, the serum levels of P and E2 in the observation group were significantly higher than before treatment, but the serum CA125 levels decreased significantly after treatment (P<0.05). These indicators showed statistically significant difference compared with that of the control group (P<0.05). After treatment, the serum β-HCG levels of the two groups were significantly higher than before treatment (P<0.05), but there was no statistically significant difference between the two groups. Gushen Antai pills and progesterone had a better clinical curative effect in treatment threatened abortion, which could significantly raise serum β-HCG, P and E2, reduce serum CA125 and increase the tocolysis efficiency, and so it was worth promoted in clinic. Copyright© by the Chinese Pharmaceutical Association.

Macrootlocus, a CAD Design Tool for Feedback Control Systems

DTIC Science & Technology

1989-12-01

var Form :DecForm; Str :DecStr; begin 125 Form.Style, :. FixedDecimal; Forrr.Digits :. 0; Num2Str(Form, 1, Str ); lntToStr :. Str ; end; { lntToStr...School Monterey, CA 93943 15. Hong-on Kim SMC2665 Naval Postgraduate School Monterey, CA 93943 16. Kang, Mung Hung SMC1375 Naval Postgraduate School

[Establishment of risk evaluation model of peritoneal metastasis in gastric cancer and its predictive value].

PubMed

Zhao, Junjie; Zhou, Rongjian; Zhang, Qi; Shu, Ping; Li, Haojie; Wang, Xuefei; Shen, Zhenbin; Liu, Fenglin; Chen, Weidong; Qin, Jing; Sun, Yihong

2017-01-25

To establish an evaluation model of peritoneal metastasis in gastric cancer, and to assess its clinical significance. Clinical and pathologic data of the consecutive cases of gastric cancer admitted between April 2015 and December 2015 in Department of General Surgery, Zhongshan Hospital of Fudan University were analyzed retrospectively. A total of 710 patients were enrolled in the study after 18 patients with other distant metastasis were excluded. The correlations between peritoneal metastasis and different factors were studied through univariate (Pearson's test or Fisher's exact test) and multivariate analyses (Binary Logistic regression). Independent predictable factors for peritoneal metastasis were combined to establish a risk evaluation model (nomogram). The nomogram was created with R software using the 'rms' package. In the nomogram, each factor had different scores, and every patient could have a total score by adding all the scores of each factor. A higher total score represented higher risk of peritoneal metastasis. Receiver operating characteristic (ROC) curve analysis was used to compare the sensitivity and specificity of the established nomogram. Delong. Delong. Clarke-Pearson test was used to compare the difference of the area under the curve (AUC). The cut-off value was determined by the AUC, when the ROC curve had the biggest AUC, the model had the best sensitivity and specificity. Among 710 patients, 47 patients had peritoneal metastasis (6.6%), including 30 male (30/506, 5.9%) and 17 female (17/204, 8.3%); 31 were ≥ 60 years old (31/429, 7.2%); 38 had tumor ≥ 3 cm(38/461, 8.2%). Lauren classification indicated that 2 patients were intestinal type(2/245, 0.8%), 8 patients were mixed type(8/208, 3.8%), 11 patients were diffuse type(11/142, 7.7%), and others had no associated data. CA19-9 of 13 patients was ≥ 37 kU/L(13/61, 21.3%); CA125 of 11 patients was ≥ 35 kU/L(11/36, 30.6%); CA72-4 of 11 patients was ≥ 10 kU/L(11/39, 28.2%). Neutrophil/lymphocyte ratio (NLR) of 26 patients was ≥ 2.37(26/231, 11.3%). Multivariate analysis showed that Lauren classification (HR=8.95, 95%CI:1.32-60.59, P=0.025), CA125(HR=17.45, 95%CI:5.54-54.89, P=0.001), CA72-4(HR=20.06, 95%CI:5.05-79.68, P=0.001), and NLR (HR=4.16, 95%CI:1.17-14.75, P=0.032) were independent risk factors of peritoneal metastasis in gastric cancer. In the nomogram, the highest score was 241, including diffuse or mixed Lauren classification (54 score), CA125 ≥ 35 kU/L (66 score), CA72-4 ≥ 10 kU/L (100 score), and NLR ≥ 2.37 (21 score), which represented a highest risk of peritoneal metastasis (more than 90%). The AUC of nomogram was 0.912, which was superior than any single variable (AUC of Lauren classification: 0.678; AUC of CA125: 0.720; AUC of CA72-4: 0.792; AUC of NLR: 0.613, all P=0.000). The total score of nomogram increased according to the TNM stage, and was highest in the peritoneal metastasis group (F=49.1, P=0.000). When the cut-off value calculated by ROC analysis was set at 140, the model could best balanced the sensitivity (0.79) and the specificity (0.87). Only 5% of patients had peritoneal metastasis when their nomogram scores were lower than 140, while 58% of patients had peritoneal metastasis when their scores were ≥ 140(χ 2 =69.1, P=0.000). The risk evaluation model established with Lauren classification, CA125, CA72-4 and NLR can effectively predict the risk of peritoneal metastasis in gastric cancer, and provide the reference to preoperative staging and choice of therapeutic strategy.

The nature of iron deposits differs between symptomatic and asymptomatic carotid atherosclerotic plaques

DOE PAGES

Kopriva, David; Kisheev, Anastasye; Meena, Deiter; ...

2015-11-25

Iron within atherosclerotic plaque has been implicated as a catalyst of oxidative stress that causes progression of plaque, and plaque rupture. Iron is believed to accumulate within plaque by incorporation of erythrocytes following plaque rupture and hemorrhage. There is only indirect evidence to support this hypothesis. Plaque specimens were obtained from ten symptomatic and fifteen asymptomatic patients undergoing carotid endarterectomy at a single institution. Plaques were sectioned for study using synchrotron radiation induced X-ray fluorescence the study the distribution of zinc, calcium and iron. Histologic staining was carried out with Prussian Blue, and immunohistochemical staining was done to localize macrophagesmore » with CD68. Data were compared against patient clinical variables. Ten symptomatic (15 ± 10 days between index symptoms and surgery) and fifteen asymptomatic carotid plaques were studied. Zinc and calcium co-localized in mineralized areas of symptomatic and asymptomatic plaque. Iron was identified away from zinc and calcium in both symptomatic and asymptomatic plaques. Within the symptomatic plaques, iron was found within the thrombus associated with plaque rupture and hemorrhage. It did not stain with Prussian Blue, but was found in association with CD68 positive macrophages. In symptomatic plaques, the abundance of iron showed an association with the source patient’s LDL cholesterol (R 2 = 0.39, Significance F = 0.05). Iron in asymptomatic plaque was present as hemosiderin/ferritin that stained positive with Prussian Blue, and was observed in association with CD68 positive macrophages. Iron in acutely symptomatic plaques is found within thrombus, in the presence of macrophages. Moreover, the abundance of iron in symptomatic plaques is associated with the source patient’s LDL cholesterol. Within asymptomatic plaques, iron is found in association with macrophages, as hemosiderin/ferritin.« less

The Nature of Iron Deposits Differs between Symptomatic and Asymptomatic Carotid Atherosclerotic Plaques

PubMed Central

Kopriva, David; Kisheev, Anastasye; Meena, Deiter; Pelle, Shaneen; Karnitsky, Max; Lavoie, Andrea; Buttigieg, Josef

2015-01-01

Iron within atherosclerotic plaque has been implicated as a catalyst of oxidative stress that causes progression of plaque, and plaque rupture. Iron is believed to accumulate within plaque by incorporation of erythrocytes following plaque rupture and hemorrhage. There is only indirect evidence to support this hypothesis. Plaque specimens were obtained from ten symptomatic and fifteen asymptomatic patients undergoing carotid endarterectomy at a single institution. Plaques were sectioned for study using synchrotron radiation induced X-ray fluorescence the study the distribution of zinc, calcium and iron. Histologic staining was carried out with Prussian Blue, and immunohistochemical staining was done to localize macrophages with CD68. Data were compared against patient clinical variables. Ten symptomatic (15 ± 10 days between index symptoms and surgery) and fifteen asymptomatic carotid plaques were studied. Zinc and calcium co-localized in mineralized areas of symptomatic and asymptomatic plaque. Iron was identified away from zinc and calcium in both symptomatic and asymptomatic plaques. Within the symptomatic plaques, iron was found within the thrombus associated with plaque rupture and hemorrhage. It did not stain with Prussian Blue, but was found in association with CD68 positive macrophages. In symptomatic plaques, the abundance of iron showed an association with the source patient’s LDL cholesterol (R2 = 0.39, Significance F = 0.05). Iron in asymptomatic plaque was present as hemosiderin/ferritin that stained positive with Prussian Blue, and was observed in association with CD68 positive macrophages. Iron in acutely symptomatic plaques is found within thrombus, in the presence of macrophages. The abundance of iron in symptomatic plaques is associated with the source patient’s LDL cholesterol. Within asymptomatic plaques, iron is found in association with macrophages, as hemosiderin/ferritin. PMID:26606178

The nature of iron deposits differs between symptomatic and asymptomatic carotid atherosclerotic plaques

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kopriva, David; Kisheev, Anastasye; Meena, Deiter

Iron within atherosclerotic plaque has been implicated as a catalyst of oxidative stress that causes progression of plaque, and plaque rupture. Iron is believed to accumulate within plaque by incorporation of erythrocytes following plaque rupture and hemorrhage. There is only indirect evidence to support this hypothesis. Plaque specimens were obtained from ten symptomatic and fifteen asymptomatic patients undergoing carotid endarterectomy at a single institution. Plaques were sectioned for study using synchrotron radiation induced X-ray fluorescence the study the distribution of zinc, calcium and iron. Histologic staining was carried out with Prussian Blue, and immunohistochemical staining was done to localize macrophagesmore » with CD68. Data were compared against patient clinical variables. Ten symptomatic (15 ± 10 days between index symptoms and surgery) and fifteen asymptomatic carotid plaques were studied. Zinc and calcium co-localized in mineralized areas of symptomatic and asymptomatic plaque. Iron was identified away from zinc and calcium in both symptomatic and asymptomatic plaques. Within the symptomatic plaques, iron was found within the thrombus associated with plaque rupture and hemorrhage. It did not stain with Prussian Blue, but was found in association with CD68 positive macrophages. In symptomatic plaques, the abundance of iron showed an association with the source patient’s LDL cholesterol (R 2 = 0.39, Significance F = 0.05). Iron in asymptomatic plaque was present as hemosiderin/ferritin that stained positive with Prussian Blue, and was observed in association with CD68 positive macrophages. Iron in acutely symptomatic plaques is found within thrombus, in the presence of macrophages. Moreover, the abundance of iron in symptomatic plaques is associated with the source patient’s LDL cholesterol. Within asymptomatic plaques, iron is found in association with macrophages, as hemosiderin/ferritin.« less

The prevalence of Campylobacter pylori gastritis among asymptomatic adults.

PubMed Central

Gregson, D B; Low, D E; Cohen, M M; Cooter, N B; Connon, J J; Wolman, S L; Simor, A E

1989-01-01

To determine the prevalence of Campylobacter pylori colonization in the healthy population we studied 54 asymptomatic volunteers and 65 patients referred because of gastrointestinal symptoms. All subjects underwent gastroscopy and gastric biopsy. C. pylori was isolated from 6 volunteers (11%) and 36 patients (55%). Histologic evidence of inflammation was present in 98% of the culture-positive subjects. Linear regression analysis revealed that the prevalence of C. pylori colonization increased with age. There was no difference in the isolation rate between the two groups when adjusted for age. Four of the six culture-positive volunteers underwent repeat endoscopy and gastric biopsy 1 year later; despite remaining asymptomatic, all still had positive culture results and histologic evidence of gastritis. We conclude that the prevalence of C. pylori-associated gastritis among symptomatic patients increases with age and that the organism may be present in the gastrointestinal tract for prolonged periods without symptoms or evidence of disease progression. PMID:2785841

Influence of Asymptomatic Pneumonia on the Response to Hemorrhage and Resuscitation in Swine

DTIC Science & Technology

2010-01-01

and complete blood count (Pentra-120 Hemato- logy Analyzer, ABX Diagnostics, Irvine, CA); 3) total plasma protein, glucose, creatinine , lactate...dehydrogenase (LDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatine kinase (CK), amylase and lactate (Vitros Chemistry System...CK. Creatinine increased at 15 min in both groups and remained elevated throughout the study. Mean total protein, amylase and ALT decreased similarly

miR-125b suppresses the proliferation and migration of osteosarcoma cells through down-regulation of STAT3

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Li-hong; Li, Hui; Li, Jin-ping

2011-12-09

Highlights: Black-Right-Pointing-Pointer miR-125b is frequently down-regulated in osteosarcoma samples and human osteosarcoma cell lines. Black-Right-Pointing-Pointer Ectopic restoration of miR-125b suppresses cell proliferation and migration in vitro. Black-Right-Pointing-Pointer STAT3 is the direct and functional downstream target of miR-125b. Black-Right-Pointing-Pointer STAT3 can bind to the promoter region of miR-125b and serves as a transactivator. -- Abstract: There is accumulating evidence that microRNAs are involved in multiple processes in development and tumor progression. Abnormally expressed miR-125b was found to play a fundamental role in several types of cancer; however, whether miR-125b participates in regulating the initiation and progress of osteosarcoma still remains unclear.more » Here we demonstrate that miR-125b is frequently down-regulated in osteosarcoma samples and human osteosarcoma cell lines. The ectopic restoration of miR-125b expression in human osteosarcoma cells suppresses proliferation and migration in vitro and inhibits tumor formation in vivo. We further identified signal transducer and activator of transcription 3 (STAT3) as the direct and functional downstream target of miR-125b. Interestingly, we discovered that the expression of miR-125b is regulated by STAT3 at the level of transcription. STAT3 binds to the promoter region of miR-125b in vitro and serves as a transactivator. Taken together, our findings point to an important role in the molecular etiology of osteosarcoma and suggest that miR-125b is a potential target in the treatment of osteosarcoma.« less

Gallstones in children with sickle cell disease followed up at a Brazilian hematology center.

PubMed

Gumiero, Ana Paula dos Santos; Bellomo-Brandão, Maria Angela; Costa-Pinto, Elizete Aparecida Lomazi da

2008-01-01

Sickle cell disease causes chronic and recurrent hemolysis which is a recognized risk factor for cholelithiasis. This complication occurs in 50% of adults with sickle cell disease. Surgery is the consensual therapy for symptomatic patients, but the surgical approach is still controversial in asymptomatic individuals. To determine the frequency and to describe and discuss the outcome of children with sickle cell disease complicated with gallstones followed up at a tertiary pediatric hematology center. In a retrospective and descriptive study, 225 charts were reviewed and data regarding patient outcome were recorded. The prevalence of cholelithiasis was 45% and half the patients were asymptomatic. The mean age at the time of diagnosis of cholelithiasis and surgical treatment was 12.5 years (standard deviation = 5) and 14 years (standard deviation = 5.4), respectively. The prevalence of cholelithiasis was higher in patients with SS homozygous and Sb heterozygous thalassemia when compared to patients with sickle cell disease. In 50% of symptomatic patients, recurrent abdominal pain was the single or predominant symptom. Thirty-nine of 44 patients submitted to surgery reported symptom relief after the surgical procedure. Asymptomatic individuals who did not undergo surgical treatment were followed up for 7 years (standard deviation = 4.8), and none of them presented complications related to cholelithiasis during this period. The frequency of cholelithiasis in the study population was 45%. One-third of the patients were diagnosed before 10 years of age. Patients with the SS homozygous or Sb heterozygous phenotype were at a higher risk for the development of cholelithiasis than patients with sickle cell disease. About 50% of patients with gallstones were asymptomatic, the most of them did not undergo surgery and did not present complications during a 7-year follow-up period. Cholecystectomy must be considered in symptomatic patients. In asymptomatic patients, conservative management seems to be the better choice.

Prevalence of corneal astigmatism before cataract surgery in Western Indian Population.

PubMed

Moulick, P S; Kalra, Deepak; Sati, Alok; Gupta, Sandeep; Khan, M A; Singh, Archana

2018-01-01

The prevalence and nature of corneal astigmatism among cataract surgery candidates has not been well-documented in Indian population. The purpose of the study is to analyse prevalence and presentation patterns of corneal astigmatism (CA) in cataract surgery candidates. Keratometric values were measured in patients before cataract extraction. Descriptive statistics of CA were analysed including the assessment with age ranges. Mean CA of 223 eyes of 223 patients [mean age 61 ± 10 years (range, 29-90 years)] was 0.88 ± 0.61 (95% CI, 0.80-0.96) with 27.8%, 51.1% and 21.1% having with the rule (WTR), against the rule (ATR) and oblique astigmatism (OBL) respectively. Between 40 and 50 years, ATR exceeds WTR and reaches 100% by 80 years. A trend of less negative CA was seen up to 60 years and then increases up to 90 years. CA was below 0.25 dioptre (D) in 17.5% of eyes, between 0.25 and 1.25 D in 63.7% and ≥1.50 D in 18.8% of eyes. Considering CA < 1.25 D in majority of cataract surgery candidates, it is preferable to perform inexpensive keratorefractive procedures rather expensive toric IOLs, especially in developing world.

78 FR 15960 - Request for Information on the FY 2013-2018 Strategic Plan for the Office of Disease Prevention

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-13

... injuries and the progression of asymptomatic disease. Prevention research targets biology and genetics, individual behavior, factors in the social and physical environments, and health services; and it informs and...

The transcriptomic response of mixed neuron-glial cell cultures to 1,25-dihydroxyvitamin d3 includes genes limiting the progression of neurodegenerative diseases.

PubMed

Nissou, Marie-France; Brocard, Jacques; El Atifi, Michèle; Guttin, Audrey; Andrieux, Annie; Berger, François; Issartel, Jean-Paul; Wion, Didier

2013-01-01

Seasonal or chronic vitamin D deficiency and/or insufficiency is highly prevalent in the human population. Receptors for 1,25-dihydroxyvitamin D3, the hormonal metabolite of vitamin D, are found throughout the brain. To provide further information on the role of this hormone on brain function, we analyzed the transcriptomic profiles of mixed neuron-glial cell cultures in response to 1,25-dihydroxyvitamin D3. 1,25-dihydroxyvitamin D3 treatment increases the mRNA levels of 27 genes by at least 1.9 fold. Among them, 17 genes were related to neurodegenerative and psychiatric diseases, or brain morphogenesis. Notably, 10 of these genes encode proteins potentially limiting the progression of Alzheimer's disease. These data provide support for a role of 1,25-dihydroxyvitamin D3 in brain disease prevention. The possible consequences of circannual or chronic vitamin D insufficiencies on a tissue with a low regenerative potential such as the brain should be considered.

ERG oncoprotein expression in prostate carcinoma patients of different ethnicities.

PubMed

Kelly, Gregory M; Kong, Yink Heay; Dobi, Albert; Srivastava, Shiv; Sesterhenn, Isabell A; Pathmanathan, Rajadurai; Tan, Hui Meng; Tan, Shyh-Han; Cheong, Sok Ching

2015-01-01

Overexpression of the erythroblast transformation-specific-related gene (ERG) oncoprotein due to transmembrane protease, serine 2 ( TMPRSS2 ) -ERG fusion, the most prevalent genomic alteration in prostate cancer (CaP), is more frequently observed among Caucasian patients compared to patients of African or Asian descent. To the best of our knowledge, this is the first study to investigate the prevalence of ERG alterations in a multiethnic cohort of CaP patients. A total of 191 formalin-fixed paraffin-embedded sections of transrectal ultrasound-guided prostate biopsy specimens, collected from 120 patients treated at the Sime Darby Medical Centre, Subang Jaya, Malaysia, were analyzed for ERG protein expression by immunohistochemistry using the anti-ERG monoclonal antibody 9FY as a surrogate for the detection of ERG fusion events. The overall frequency of ERG protein expression in the population evaluated in this study was 39.2%. Although seemingly similar to rates reported in other Asian communities, the expression of ERG was distinct amongst different ethnic groups (P=0.004). Malaysian Indian (MI) patients exhibited exceedingly high expression of ERG in their tumors, almost doubling that of Malaysian Chinese (MC) patients, whereas ERG expression was very low amongst Malay patients (12.5%). When collectively analyzing data, we observed a significant correlation between younger patients and higher ERG expression (P=0.04). The prevalence of ERG expression was significantly different amongst CaP patients of different ethnicities. The higher number of ERG-expressing tumors among MI patients suggested that the TMPRSS2-ERG fusion may be particularly important in the pathogenesis of CaP amongst this group of patients. Furthermore, the more frequent expression of ERG among the younger patients analyzed suggested an involvement of ERG in the early onset of CaP. The results of this study underline the value of using ERG status to better understand the differences in the etiology of CaP initiation and progression between ethnic groups.

ERG oncoprotein expression in prostate carcinoma patients of different ethnicities

PubMed Central

KELLY, GREGORY M.; KONG, YINK HEAY; DOBI, ALBERT; SRIVASTAVA, SHIV; SESTERHENN, ISABELL A.; PATHMANATHAN, RAJADURAI; TAN, HUI MENG; TAN, SHYH-HAN; CHEONG, SOK CHING

2015-01-01

Overexpression of the erythroblast transformation-specific-related gene (ERG) oncoprotein due to transmembrane protease, serine 2 (TMPRSS2)-ERG fusion, the most prevalent genomic alteration in prostate cancer (CaP), is more frequently observed among Caucasian patients compared to patients of African or Asian descent. To the best of our knowledge, this is the first study to investigate the prevalence of ERG alterations in a multiethnic cohort of CaP patients. A total of 191 formalin-fixed paraffin-embedded sections of transrectal ultrasound-guided prostate biopsy specimens, collected from 120 patients treated at the Sime Darby Medical Centre, Subang Jaya, Malaysia, were analyzed for ERG protein expression by immunohistochemistry using the anti-ERG monoclonal antibody 9FY as a surrogate for the detection of ERG fusion events. The overall frequency of ERG protein expression in the population evaluated in this study was 39.2%. Although seemingly similar to rates reported in other Asian communities, the expression of ERG was distinct amongst different ethnic groups (P=0.004). Malaysian Indian (MI) patients exhibited exceedingly high expression of ERG in their tumors, almost doubling that of Malaysian Chinese (MC) patients, whereas ERG expression was very low amongst Malay patients (12.5%). When collectively analyzing data, we observed a significant correlation between younger patients and higher ERG expression (P=0.04). The prevalence of ERG expression was significantly different amongst CaP patients of different ethnicities. The higher number of ERG-expressing tumors among MI patients suggested that the TMPRSS2-ERG fusion may be particularly important in the pathogenesis of CaP amongst this group of patients. Furthermore, the more frequent expression of ERG among the younger patients analyzed suggested an involvement of ERG in the early onset of CaP. The results of this study underline the value of using ERG status to better understand the differences in the etiology of CaP initiation and progression between ethnic groups. PMID:25469265

Evaluation of Lumipulse® G1200 for the measurement of six tumor markers: Comparison with AIA® 2000.

PubMed

de Rancher, Marie-Aude Robert; Oudart, Jean-Baptiste; Maquart, François-Xavier; Monboisse, Jean Claude; Ramont, Laurent

2016-11-01

Tumor marker assays are daily practiced, for screening and follow up of cancers. Interassay precision is an important parameter for the interpretation of the kinetics of the markers, in order to conclude to the efficiency or failure of treatment. The aim of this study was to compare two automated Immunoassay analyzers, Lumipulse® G1200 and AIA® 2000. Both analyzers used an immunoassay system but with different antibodies. Six tumor markers commonly used were studied: AFP, PSA, CA 19-9, CA 15-3, CA 125 and CEA. 253 samples have been collected over a period of one month and analyzed by both analyzers. Regression of Passing-Badblock and Bland-Altman diagram were used to analyze the results for AFP (n=36), PSA (n=39), CA-125 (n=40), CA 15-3 (n=40), CA 19-9 (n=46) and CEA (n=52) were performed. Analytical performances of Lumipulse® G1200 highlighted the good inter-run and intra-run precision of the analyzer. We obtained a good correlation coefficient between Lumipulse G1200® and AIA 2000®, >0.96 for most markers except CA 19-9 which provided a correlation coefficient significantly lower than that obtained with other markers. The concordance for all markers was >94% except for CA 19-9 (83.7%). This study showed a good correlation between the two analyzers and, therefore, a transfer from one analyzer to the other is possible for the different markers studied. However, we found here the classical difficulty to transfer this type of analysis, due to the absence of method standardization. This difficulty was particularly illustrated by CA19-9. Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Selection of High-Quality Spermatozoa May Be Promoted by Activated Vitamin D in the Woman.

PubMed

Bøllehuus Hansen, Lasse; Rehfeld, Anders; de Neergaard, Rosanna; Nielsen, John Erik; Iversen, Lea Hedegaard; Boisen, Ida Marie; Mortensen, Li Juel; Lanske, Beate; Almstrup, Kristian; Carlsen, Elisabeth; Berg, Anders Hayden; Jørgensen, Niels; Andersen, Anders Nyboe; Juul, Anders; Blomberg Jensen, Martin

2017-03-01

The vitamin D receptor (VDR) and enzymes involved in activation (CYP2R1, CYP27B1) and inactivation (CYP24A1) of vitamin D are expressed in ovary, testes, and spermatozoa. Determine responsiveness to 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] in spermatozoa from normal and infertile men, and identify the site of exposure and how 1,25(OH)2D3 influences sperm function. Spermatozoa expressing VDR, CYP2R1, CYP27B1, and CYP24A1 were analyzed in normal and infertile men. 25-Hydroxyvitamin D (25-OHD), 24,25-dihydroxyvitamin D [24,25(OH)2D3], and 1,25(OH)2D3 were measured in serum, seminal fluid, cervical secretions, and ovarian follicular fluid. 1,25(OH)2D3 was tested on human spermatozoa. Tertiary center for fertility. Protein expression in spermatozoa and semen quality were assessed in 230 infertile and 114 healthy men. Vitamin D metabolites were measured in fluids from 245 men and 13 women, while 74 oocytes and 17 semen donors were used for sperm-function tests. VDR and CYP24A1 expressions in spermatozoa, fluid concentrations of 25-OHD, 24,25(OH)2D3, and 1,25(OH)2D3, and 1,25(OH)2D3-induced effects on intracellular calcium concentration ([Ca2+]i) and sperm-oocyte binding in vitro. VDR and CYP24A1 were expressed in a >2-fold higher fraction of spermatozoa from normal than infertile men (P < 0.01). Concentrations of 25-OHD, 24,25(OH)2D, and 1,25(OH)2D3 were undetectable in seminal fluid but high in ovarian follicular fluid. Follicular concentrations of 1,25(OH)2D3 induced a modest increase in [Ca2+]i and sperm-oocyte binding in vitro (P < 0.05). Presence of VDR and CYP24A1 mainly in spermatozoa of higher quality supports that 1,25(OH)2D3 available in the female reproductive tract may promote selection of the best gametes for fertilization. Copyright © 2017 by the Endocrine Society

Progression of Hypertrophy and Myocardial Fibrosis in Aortic Stenosis: A Multicenter Cardiac Magnetic Resonance Study.

PubMed

Everett, Russell J; Tastet, Lionel; Clavel, Marie-Annick; Chin, Calvin W L; Capoulade, Romain; Vassiliou, Vassilios S; Kwiecinski, Jacek; Gomez, Miquel; van Beek, Edwin J R; White, Audrey C; Prasad, Sanjay K; Larose, Eric; Tuck, Christopher; Semple, Scott; Newby, David E; Pibarot, Philippe; Dweck, Marc R

2018-06-01

Aortic stenosis is accompanied by progressive left ventricular hypertrophy and fibrosis. We investigated the natural history of these processes in asymptomatic patients and their potential reversal post-aortic valve replacement (AVR). Asymptomatic and symptomatic patients with aortic stenosis underwent repeat echocardiography and magnetic resonance imaging. Changes in peak aortic-jet velocity, left ventricular mass index, diffuse fibrosis (indexed extracellular volume), and replacement fibrosis (late gadolinium enhancement [LGE]) were quantified. In 61 asymptomatic patients (43% mild, 34% moderate, and 23% severe aortic stenosis), significant increases in peak aortic-jet velocity, left ventricular mass index, indexed extracellular volume, and LGE mass were observed after 2.1±0.7 years, with the most rapid progression observed in patients with most severe stenosis. Patients with baseline midwall LGE (n=16 [26%]; LGE mass, 2.5 g [0.8-4.8 g]) demonstrated particularly rapid increases in scar burden (78% [50%-158%] increase in LGE mass per year). In 38 symptomatic patients (age, 66±8 years; 76% men) who underwent AVR, there was a 19% (11%-25%) reduction in left ventricular mass index ( P <0.0001) and an 11% (4%-16%) reduction in indexed extracellular volume ( P =0.003) 0.9±0.3 years after surgery. By contrast midwall LGE (n=10 [26%]; mass, 3.3 g [2.6-8.0 g]) did not change post-AVR (n=10; 3.5 g [2.1-8.0 g]; P =0.23), with no evidence of regression even out to 2 years. In patients with aortic stenosis, cellular hypertrophy and diffuse fibrosis progress in a rapid and balanced manner but are reversible after AVR. Once established, midwall LGE also accumulates rapidly but is irreversible post valve replacement. Given its adverse long-term prognosis, prompt AVR when midwall LGE is first identified may improve clinical outcomes. URL: https://www.clinicaltrials.gov. Unique identifiers: NCT01755936 and NCT01679431. © 2018 The Authors.

A multidisciplinary approach to an unusual cause of hyperamylasaemia

PubMed Central

Logie, James John; Cox, Mary; Sharkey, Joanne; Williams, Alistair

2015-01-01

Clinical features together with elevation of pancreatic enzymes are the key diagnostic indicators of acute pancreatitis. We report a case of a woman in her 50s who presented with abdominal distension and serum amylase raised to more than 30 times the upper limit of normal. She was initially treated for acute pancreatitis, however, she was not symptomatic of this and the pancreas appeared to be normal on CT scan. Further investigations revealed the patient had a high-grade serous ovarian carcinoma with nodal metastatic spread. An amylase-secreting ovarian tumour was suspected, which was supported by elevated salivary-amylase isoenzymes, consistent with previous reports in the literature. The patient was treated with chemotherapy and surgery, during which her serum amylase and CA-125 initially fell significantly, but eventually both increased, reflecting disease progression. This case serves as an important reminder to consider non-pancreatic causes of raised serum amylase, to avoid misdiagnosis. PMID:26150631

[Association of lipid metabolism disorder with peritoneum transport ability and mortality in peritoneal dialysis patients].

PubMed

Fang, Yan-hui; Jiang, Lan-ping; Zhou, Zi-juan; Wang, Hai-yun; Xu, Hong; Li, Xue-mei; Chen, Li-meng; Li, Xue-wang

2013-06-01

To observe the features of lipid metabolism disorders of peritoneal dialysis(PD)patients and hemodialysis(HD)patients and explore the association of lipid metabolism disorder with peritoneum transport ability and mortality. The clinical data of 127 PD patients and 95 HD patients who had received regular dialysis for more than 3 months in Peking Union Medical College Hospital since March 2009 were retrospectively analyzed.Serum lipid profiles were tested.Serum hypersensitive C reactive protein(hsCRP)was examined by immune turbidimetric method.Serum carbohydrate antigen 125(CA125)and iPTH were detected by electrochemical luminescence method.Peritoneum transport ability was evaluated through peritoneal equilibration test(PET).After a 2-year follow-up,the levels of CA125 and the peritoneum transport abilities were compared between the baseline data and the end point,and the relationship between lipid disorder and the mortality was analyzed. After the 2-year follow-up,25(19.7%)PD patients died.The leading cause of death was congestive heart failure(56.0%),followed by myocardial infarction(12.0%),septic shock(12.0%),respiratory failure(8.0%),asphyxiation(8.0%),and gastrointestinal bleeding(4.0%).Compared with the survivors,the death patients were older(P=0.005),with significant lower albumin level(P=0.000)and pre-albumin level(P=0.001).However,there was no significant difference in other clinical features including body mass index(BMI),blood pressure,dialysis time,nPCR,iPTH,hemoglobin,hsCRP,and serum lipid level(all P>0.05).COX regression analysis showed that diabetes mellitus(P=0.030)and mean SBP(P=0.048)were significantly associated with the mortality of PD patients.At the baseline,the CA125 level in patients with high,high average,and low average transport status of peritoneum was(38.02±64.37),(21.21±19.41),and(17.55±23.2)U/ml,respectively(P=0.09).There was no association between the transport status and lipid(TC,TG and LDL). Congestive heart failure is the leading cause of death among PD patients.Diabetes and blood pressure are the dependent risk factors of mortality.Lipid disorder is associated with CA125,while its association with peritoneum transport ability or mortality was not found.

Enhanced biomethane potential from wheat straw by low temperature alkaline calcium hydroxide pre-treatment.

PubMed

Reilly, Matthew; Dinsdale, Richard; Guwy, Alan

2015-08-01

A factorially designed experiment to examine the effectiveness of Ca(OH)2 pre-treatment, enzyme addition and particle size, on the mesophilic (35 °C) anaerobic digestion of wheat straw was conducted. Experiments used a 48 h pre-treatment with Ca(OH)2 7.4% (w/w), addition of Accellerase®-1500, with four particle sizes of wheat straw (1.25, 2, 3 and 10mm) and three digestion time periods (5, 15 and 30 days). By combining particle size reduction and Ca(OH)2 pre-treatment, the average methane potential was increased by 315% (from 48 NmL-CH4 g-VS(-1) to 202 NmL-CH4 g-VS(-1)) after 5 days of anaerobic digestion compared to the control. Enzyme addition or Ca(OH)2 pre-treatment with 3, 2 and 1.25 mm particle sizes had 30-day batch yields of between 301 and 335 NmL-CH4 g-VS(-1). Alkali pre-treatment of 3mm straw was shown to have the most potential as a cost effective pre-treatment and achieved 290 NmL-CH4 g-VS(-1), after only 15 days of digestion. Copyright © 2015 Elsevier Ltd. All rights reserved.

Towards a Rational Design of an Asymptomatic Clinical Herpes Vaccine: The Old, the New, and the Unknown

PubMed Central

Alami Chentoufi, Aziz; Kritzer, Elizabeth; Yu, David M.; Nesburn, Anthony B.; BenMohamed, Lbachir

2012-01-01

The best hope of controlling the herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2) pandemic is the development of an effective vaccine. However, in spite of several clinical trials, starting as early as 1920s, no vaccine has been proven sufficiently safe and efficient to warrant commercial development. In recent years, great strides in cellular and molecular immunology have stimulated creative efforts in controlling herpes infection and disease. However, before moving towards new vaccine strategy, it is necessary to answer two fundamental questions: (i) why past herpes vaccines have failed? (ii) Why the majority of HSV seropositive individuals (i.e., asymptomatic individuals) are naturally “protected” exhibiting few or no recurrent clinical disease, while other HSV seropositive individuals (i.e., symptomatic individuals) have frequent ocular, orofacial, and/or genital herpes clinical episodes? We recently discovered several discrete sets of HSV-1 symptomatic and asymptomatic epitopes recognized by CD4+ and CD8+ T cells from seropositive symptomatic versus asymptomatic individuals. These asymptomatic epitopes will provide a solid foundation for the development of novel herpes epitope-based vaccine strategy. Here we provide a brief overview of past clinical vaccine trials, outline current progress towards developing a new generation “asymptomatic” clinical herpes vaccines, and discuss future mucosal “asymptomatic” prime-boost vaccines that could optimize local protective immunity. PMID:22548113

Effects of Asymptomatic Rotator Cuff Pathology On In-Vivo Shoulder Motion and Clinical Outcomes

PubMed Central

Baumer, Timothy G.; Dischler, Jack; Mende, Veronica; Zauel, Roger; van Holsbeeck, Marnix; Siegal, Daniel S.; Divine, George; Moutzouros, Vasilios; Bey, Michael J.

2017-01-01

Background The incidence of asymptomatic rotator cuff tears has been reported to range from 15–39%, but the influence of asymptomatic rotator cuff pathology on shoulder function is not well understood. The objective of this study was to assess the effects of asymptomatic rotator cuff pathology on shoulder kinematics, strength, and patient-reported outcomes. Methods 46 asymptomatic volunteers (age: 60.3±7.5) with normal shoulder function underwent a clinical ultrasound exam to document the condition of their rotator cuff. The ultrasound imaging identified subjects as healthy (n=14) or pathologic (n=32). Shoulder motion was measured with a biplane x-ray imaging system, strength was assessed with a Biodex, and patient-reported outcomes were assessed using the Western Ontario Rotator Cuff Index and VAS pain scores. Results Compared to healthy subjects, the subjects with rotator cuff pathology had significantly less abduction (p=0.050) and elevation (p=0.041) strength, their humerus was positioned more inferiorly on the glenoid (p=0.018), and the glenohumeral contact path length was longer (p=0.007). No significant differences were detected in terms of WORC, VAS, ROM, or acromiohumeral distance. Discussion The differences observed between the healthy subjects and subjects with asymptomatic rotator cuff pathology lend insight into the changes in joint mechanics, shoulder strength, and conventional clinical outcomes associated with the early stages of rotator cuff pathology. Furthermore, these findings suggest a plausible mechanical progression of kinematic and strength changes associated with the development of rotator cuff pathology. Level of evidence Basic Science Study, Kinesiology PMID:28131679

29 CFR 782.2 - Requirements for exemption in general.

Code of Federal Regulations, 2014 CFR

2014-07-01

....C.A. 2); Hansen v. Salinas Valley Ice Co. (Cal. App.) 144 P. (2d) 896; Reynolds v. Rogers Cartage Co... Service of Motor Carrier Employees, 28 M.C.C. 125, 132), and (2) engage in activities of a character....S. 649; Ex parte No. MC-28, 13 M.C.C. 481; Ex parte Nos. MC-2 and MC-3, 28 M.C.C. 125; Walling v...

29 CFR 782.2 - Requirements for exemption in general.

Code of Federal Regulations, 2013 CFR

2013-07-01

....C.A. 2); Hansen v. Salinas Valley Ice Co. (Cal. App.) 144 P. (2d) 896; Reynolds v. Rogers Cartage Co... Service of Motor Carrier Employees, 28 M.C.C. 125, 132), and (2) engage in activities of a character....S. 649; Ex parte No. MC-28, 13 M.C.C. 481; Ex parte Nos. MC-2 and MC-3, 28 M.C.C. 125; Walling v...

29 CFR 782.2 - Requirements for exemption in general.

Code of Federal Regulations, 2012 CFR

2012-07-01

....C.A. 2); Hansen v. Salinas Valley Ice Co. (Cal. App.) 144 P. (2d) 896; Reynolds v. Rogers Cartage Co... Service of Motor Carrier Employees, 28 M.C.C. 125, 132), and (2) engage in activities of a character....S. 649; Ex parte No. MC-28, 13 M.C.C. 481; Ex parte Nos. MC-2 and MC-3, 28 M.C.C. 125; Walling v...

Potentially hazardous Streptococcus suis strains latent in asymptomatic pigs in a major swine production area of Thailand.

PubMed

Meekhanon, Nattakan; Kaewmongkol, Sarawan; Phimpraphai, Waraphon; Okura, Masatoshi; Osaki, Makoto; Sekizaki, Tsutomu; Takamatsu, Daisuke

2017-05-01

Carrier pigs have been considered as the major reservoir of Streptococcus suis and couldbe a significant source of human infection. Therefore, we investigated the prevalence and characteristics of latent S. suis in asymptomatic pigs in the pig-farming area of central Thailand, and compared the data to those previously reported in other regions. We collected samples from 340 asymptomatic pigs. S. suis isolates from the samples were confirmed by species-specific PCR (recN PCR). The capsular polysaccharide synthesis gene (cps) types, virulence-associated gene profiles and sequence types (STs) of the isolates were investigated.Results/Key findings. The prevalence of S. suis found in this study was 37 % (125/340 pigs). The most prevalent genotype was mrp-/epf-/sly-. Among the 16 cps-types identified in 135 isolates, cps-type 16 was the most frequent (11 %), whereas 44 % of the isolates were non-typable. In common with the strains causing human sepsis in Thailand, two cps-type 9 isolates and a cps-type 24 isolate from slaughtered pigs belonged to ST16 and ST221, respectively. All the isolated cps-type 2 strains were confirmed as serotype 2 by co-agglutination tests, and these belonged to ST104, the unique ST commonly found in Thai patients; however, in contrast to the endemic areas, the prevalence of serotype 2 strains was relatively low (2 %) and no ST1 isolate was found. Our results showed the population structure differences between S. suis in central Thailand and other regions; however, zoonotic S. suis is certainly latent in asymptomatic pigs in this intensive swine production area.

Diagnostic significance of three-dimensional echocardiography in asymptomatic unicuspid aortic valve.

PubMed

Mladenovic, Zorica; Vranes, Danijela; Obradovic, Slobodan; Dzudovic, Boris; Angelkov Ristic, Andjelka; Ratkovic, Nenad; Jovic, Zoran; Spasic, Marijan; Maric Kocijancic, Jelena; Djruic, Predrag

2018-06-04

Unicuspid aortic valve (UAV) is a rare congenital anomaly of aorta associated with a faster progress of valvular dysfunction, aortic dilatation and with necessity for more frequent controls and precise evaluation Asymptomatic 35 year old man had abnormal systolic diastolic murmur on aortic valve during routine examination. Initial diagnostic with transthoracic echocardiography (TTE) supposed bicuspid aortic valve, while three-dimensional transesophageal echocardiography (3D TEE) and multidetector computed tomography defined unicuspid, unicomissural aortic valve with moderate aortic stenosis and regurgitation. This case report confirmed that 3D TEE gives us opportunity for early, improved and precise diagnosis of UAV. © 2018 Wiley Periodicals, Inc.

Successful treatment of ovarian cancer with apatinib combined with chemotherapy: A case report.

PubMed

Zhang, Mingzi; Tian, Zhongkai; Sun, Yehong

2017-11-01

The standard treatment for ovarian cancer is chemotherapy with 2 drugs (taxanes and platinum drugs). However, the traditional combination of the 2 drugs has many adverse effects (AEs) and the cancer cells will quickly become resistant to the drugs. Apatinib is a small-molecule antiangiogenic agent which has shown promising therapeutic effects against diverse tumor types, but it still remains unknown whether apatinib has an antitumor effect in patients with ovarian cancer. Herein, we present a successfully treated case of ovarian cancer using chemotherapy and apatinib, in order to demonstrate the effectiveness of this new combined regimen in ovarian cancer. A 51-year-old Chinese woman presented with ovarian cancer >4.5 years. The disease and the cancer antigen 125 (CA-125) had been controlled well by surgical treatment and following chemotherapy. However, the drugs could not control the disease anymore as the CA-125 level was significantly increasing. Ovarian cancer. The patient was treated with apatinib combined with epirubicin. Apatinib was administered orally, at an initial daily dose of 500 mg, and was then reduced to 250 mg qd after the appearance of intolerable hand-foot syndrome (HFS) and oral ulcer. Then, the oral ulcer disappeared and the HFS was controlled by dose adjustment, oral vitamin B6, and hand cream application. The CA-125 reverted to the normal value after treatment with the new regimen. Magnetic resonance imaging showed that the original tumor lesions had disappeared. Apatinib monotherapy as maintenance therapy was then used to successfully control the cancer with a complete response. Our study is the first, to our knowledge, to report the therapeutic effects of apatinib and epirubicin on ovarian cancer. Apatinib combined with chemotherapy and apatinib monotherapy as maintenance therapy could be a new therapeutic strategy for ovarian cancer, especially adenocarcinomas.

A Diet, Physical Activity, and Meditation Intervention in Men With Rising Prostate-Specific Antigen (PSA)

DTIC Science & Technology

2007-05-01

AD_________________ Award Number: DAMD17-03-1-0139 TITLE: A Diet , Physical Activity, and...To) 1 May 2003 – 30 Apr 2007 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER A Diet , Physical Activity, and Meditation Intervention in Men with...asymptomatic men with biochemically recurrent PrCA, as reflected by the PSA rise, is favorably affected by an intensive, vegetable-based diet , plus

Study of plasma-derived miRNAs mimic differences in Huntington's disease brain.

PubMed

Hoss, Andrew G; Lagomarsino, Valentina N; Frank, Samuel; Hadzi, Tiffany C; Myers, Richard H; Latourelle, Jeanne C

2015-12-01

Biomarkers for Huntington's disease progression could accelerate therapeutic developments and improve patient care. Brain microRNAs relating to clinical features of Huntington's disease may represent a potential Huntington's disease biomarker in blood. This study was undertaken to examine candidate microRNAs in plasma to determine whether changes observed in HD brains are detectable in peripheral samples. Four microRNAs from 26 manifest Huntington's disease, four asymptomatic Huntington's disease gene carriers, and eight controls were quantified in plasma using reverse transcription quantitative polymerase chain reaction. Linear regression was used to assess microRNA levels across control, asymptomatic gene carriers, and manifest patients. miR-10b-5p (P = 0.0068) and miR-486-5p (P = 0.044) were elevated in Huntington's disease plasma. miR-10b-5p was decreased in asymptomatic gene carriers as compared with patients with Huntington's disease (P = 0.049), but no difference between asymptomatic gene carriers and healthy controls was observed (P = 0.24). These findings suggest that microRNA changes observed in Huntington's disease brain may be detectable in plasma and have potential clinical utility. © 2015 International Parkinson and Movement Disorder Society.

Inflammatory and neurodegeneration markers during asymptomatic HSV-1 reactivation.

PubMed

Martin, Carolina; Aguila, Blanca; Araya, Paulina; Vio, Karin; Valdivia, Sharin; Zambrano, Angara; Concha, Margarita I; Otth, Carola

2014-01-01

Currently, it is unclear whether asymptomatic recurrent reactivations of herpes simplex virus type 1 (HSV-1) occur in the central nervous systems of infected people, and if these events could lead to a progressive deterioration of neuronal function. In this context, HSV-1 constitutes an important candidate to be included among the risk factors for the development of neuropathies associated with chronic neuroinflammation. The aim of this study was to assess in vivo inflammatory and neurodegenerative markers in the brain during productive and latent HSV-1 infection using a mouse model of herpes simplex encephalitis. Neuroinflammation and neurodegeneration markers were evaluated in mice trigeminal ganglia and cerebral cortex during HSV-1 infection, by immunohistochemistry, western blot, and RT-PCR. Neuronal ICP4 viral antigen expression indicative of a reactivation episode during asymptomatic latency of HSV-1 infection in mice was accompanied by upregulation of neuroinflammatory (toll-like receptor-4, interferon α/β, and p-IRF3) and early neurodegenerative markers (phospho-tau and TauC3). HSV-1 reactivation from latency induced neuroinflammatory and neurodegenerative markers in the brain of asymptomatic mice suggesting that recurrent reactivations could be associated with cumulative neuronal dysfunctions.

Infant botulism: clinical spectrum and epidemiology.

PubMed

Thompson, J A; Glasgow, L A; Warpinski, J R; Olson, C

1980-12-01

Between 1977 and 1979, 12 cases of infant botulism were diagnosed in Utah, and 87 control patients (normal, nonbotulism neurologic disease, and nonbotulism systemic disease) were evaluated. Observations from these patients suggest an expanded clinical spectrum of infant botulism including asymptomatic carriers of organism; mild hypotonia and failure to thrive; typical cases with constipation, bulbar weakness, and hypotonia; and children with a picture compatible with sudden infant death syndrome. Clostridium botulinum was isolated from the stools of three normal control infants and nine control infants who had neurologic diseases that were clearly not infant botulism. These infants were termed "asymptomatic carriers" of the organism. The occurrence of the asymptomatic carrier state suggests that a diagnosis of infant botulism cannot be made on a basis of culture results alone, but must rest in historical documentation and physical confirmation of progressive bulbar and extremity weakness with ultimate complete resolution of symptoms and findings over a period of several months. A common set of environmental features characterizes the home environment of children with infant botulism and "asymptomatic carriers" and includes: nearby constructional or agricultural soil disruption, dusty and windy conditions, a high water table, and alkaline soil conditions.

Assessment of average of normals (AON) procedure for outlier-free datasets including qualitative values below limit of detection (LoD): an application within tumor markers such as CA 15-3, CA 125, and CA 19-9.

PubMed

Usta, Murat; Aral, Hale; Mete Çilingirtürk, Ahmet; Kural, Alev; Topaç, Ibrahim; Semerci, Tuna; Hicri Köseoğlu, Mehmet

2016-11-01

Average of normals (AON) is a quality control procedure that is sensitive only to systematic errors that can occur in an analytical process in which patient test results are used. The aim of this study was to develop an alternative model in order to apply the AON quality control procedure to datasets that include qualitative values below limit of detection (LoD). The reported patient test results for tumor markers, such as CA 15-3, CA 125, and CA 19-9, analyzed by two instruments, were retrieved from the information system over a period of 5 months, using the calibrator and control materials with the same lot numbers. The median as a measure of central tendency and the median absolute deviation (MAD) as a measure of dispersion were used for the complementary model of AON quality control procedure. The u bias values, which were determined for the bias component of the measurement uncertainty, were partially linked to the percentages of the daily median values of the test results that fall within the control limits. The results for these tumor markers, in which lower limits of reference intervals are not medically important for clinical diagnosis and management, showed that the AON quality control procedure, using the MAD around the median, can be applied for datasets including qualitative values below LoD.

Cerebrospinal Fluid HIV Escape from Antiretroviral Therapy.

PubMed

Ferretti, Francesca; Gisslen, Magnus; Cinque, Paola; Price, Richard W

2015-06-01

CNS infection is a nearly constant facet of systemic CNS infection and is generally well controlled by suppressive systemic antiretroviral therapy (ART). However, there are instances when HIV can be detected in the cerebrospinal fluid (CSF) despite suppression of plasma viruses below the clinical limits of measurement. We review three types of CSF viral escape: asymptomatic, neuro-symptomatic, and secondary. The first, asymptomatic CSF escape, is seemingly benign and characterized by lack of discernable neurological deterioration or subsequent CNS disease progression. Neuro-symptomatic CSF escape is an uncommon, but important, entity characterized by new or progressive CNS disease that is critical to recognize clinically because of its management implications. Finally, secondary CSF escape, which may be even more uncommon, is defined by an increase of CSF HIV replication in association with a concomitant non-HIV infection, as a consequence of the local inflammatory response. Understanding these CSF escape settings not only is important for clinical diagnosis and management but also may provide insight into the CNS HIV reservoir.

Morin-like spin canting in the magnetic CaFe5O7 ferrite: A combined neutron and Mössbauer study

NASA Astrophysics Data System (ADS)

Delacotte, C.; Bréard, Y.; Caignaert, V.; Hardy, V.; Greneche, J. M.; Hébert, S.; Suard, E.; Pelloquin, D.

2017-03-01

Magnetic structure of CaFe5O7 ferrite has been studied jointly from neutron powder diffraction data and spectroscopic Mössbauer measurements in the thermal range from 5 to 500 K. This coupled work highlights three distinct magnetic domains around two specific temperatures: TM=125 K and TN=360 K. The latter corroborates the structural monoclinic-orthorhombic transition previously reported by transmission electron microscopy techniques and X-ray thermodiffractometry. Complementary heat capacity measurements have confirmed this first order transition with a sharp peak at 360 K. Interestingly, this large study has revealed a second magnetic transition associated to a spin rotation at 125 K similar to this one reported by Morin in α-Fe2O3 hematite at TM=260 K.

Multi-scale AM-FM motion analysis of ultrasound videos of carotid artery plaques

NASA Astrophysics Data System (ADS)

Murillo, Sergio; Murray, Victor; Loizou, C. P.; Pattichis, C. S.; Pattichis, Marios; Barriga, E. Simon

2012-03-01

An estimated 82 million American adults have one or more type of cardiovascular diseases (CVD). CVD is the leading cause of death (1 of every 3 deaths) in the United States. When considered separately from other CVDs, stroke ranks third among all causes of death behind diseases of the heart and cancer. Stroke accounts for 1 out of every 18 deaths and is the leading cause of serious long-term disability in the United States. Motion estimation of ultrasound videos (US) of carotid artery (CA) plaques provides important information regarding plaque deformation that should be considered for distinguishing between symptomatic and asymptomatic plaques. In this paper, we present the development of verifiable methods for the estimation of plaque motion. Our methodology is tested on a set of 34 (5 symptomatic and 29 asymptomatic) ultrasound videos of carotid artery plaques. Plaque and wall motion analysis provides information about plaque instability and is used in an attempt to differentiate between symptomatic and asymptomatic cases. The final goal for motion estimation and analysis is to identify pathological conditions that can be detected from motion changes due to changes in tissue stiffness.

Platelet to lymphocyte ratio as a novel prognostic tool for gallbladder carcinoma

PubMed Central

Pang, Qing; Zhang, Ling-Qiang; Wang, Rui-Tao; Bi, Jian-Bin; Zhang, Jing-Yao; Qu, Kai; Liu, Su-Shun; Song, Si-Dong; Xu, Xin-Sen; Wang, Zhi-Xin; Liu, Chang

2015-01-01

AIM: To preliminarily investigate the prognostic significance of the platelet to lymphocyte ratio (PLR) in patients with gallbladder carcinoma (GBC). METHODS: Clinical data of 316 surgical GBC patients were analyzed retrospectively, and preoperative serum platelet and lymphocyte counts were used to calculate the PLR. The optimal cut-off value of the PLR for detecting death was determined by the receiver operating characteristic (ROC) curve. The primary outcome was overall survival, which was estimated by the Kaplan-Meier method. The log-rank test was used to compare the differences in survival. Then, we conducted multivariate Cox analysis to assess the independent effect of the PLR on the survival of GBC patients. RESULTS: For the PLR, the area under the ROC curve was 0.620 (95%CI: 0.542-0.698, P = 0.040) in detecting death. The cut-off value for the PLR was determined to be 117.7, with 73.6% sensitivity and 53.2% specificity. The PLR was found to be significantly positively correlated with CA125 serum level, tumor-node-metastasis (TNM) stage, and tumor differentiation. Univariate analysis identified carcinoembryonic antigen (CEA), CA125 and CA199 levels, PLR, TNM stage, and the degree of differentiation as significant prognostic factors for GBC when they were expressed as binary data. Multivariate analysis showed that CA125 > 35 U/mL, CA199 > 39 U/mL, PLR ≥ 117.7, and TNM stage IV were independently associated with poor survival in GBC. When expressed as a continuous variable, the PLR was still an independent predictor for survival, with a hazard ratio of 1.018 (95%CI: 1.001-1.037 per 10-unit increase, P = 0.043). CONCLUSION: The PLR could be used as a simple, inexpensive, and valuable tool for predicting the prognosis of GBC patients. PMID:26074706

Specific markers, micro-environmental anomalies and tropism: opportunities for gold nanorods targeting of tumors in laser-induced hyperthermia

NASA Astrophysics Data System (ADS)

Tatini, Francesca; Ratto, Fulvio; Centi, Sonia; Landini, Ida; Nobili, Stefania; Witort, Ewa; Fusi, Franco; Capaccioli, Sergio; Mini, Enrico; Pini, Roberto

2014-03-01

Gold nanorods (GNRs) are optimal contrast agents for near-infrared (NIR) laser-induced photothermal ablation of cancer. Selective targeting of cancer cells can be pursued by attaching specific molecules on the particles surface or by the use of cellular vectors loaded with GNRs. We performed and tested various targeting approaches by means of GNRs functionalization with (i) antibodies against Cancer-Antigen-125 (CA-125), (ii) inhibitors of the carbonic anhydrase 9 (CA9) and (iii) by the use of macrophages as cellular vectors. GNRs with a NIR absorption band at 810 nm were synthesized and PEGylated. For GNRs functionalization the targets of choice were CA-125, the most widely used biomarker for ovarian cancer, and CA9, overexpressed by hypoxic cells which are often located within the tumor mass. In the case of cellular vectors, to be used as Trojan horses naturally able to reach tumor areas, the surface of PEG-GNRs was modified to achieve unspecific interactions with macrophage membranes. In all cases the cellular uptake was evaluated by silver staining and cell viability was assessed by MTT test. Then tests of laser-induced GNRs-mediated hyperthermia were performed in various cell cultures illuminating with an 810 nm diode laser (CW, 0,5-4 W/cm2 power density, 1-10 min exposure time) and cell death was evaluated. Each targeting strategy we tested may be used alone or in combination, to maximize the tumor loading and therefore the efficiency of the laser treatment. Moreover, a multiple approach could help when the tumor variability interferes with the targeting directed to a single marker.

Elevated Vitamin D Receptor Levels in Genetic Hypercalciuric Stone-Forming Rats Are Associated With Downregulation of Snail

PubMed Central

Bai, Shaochun; Wang, Hongwei; Shen, Jikun; Zhou, Randal; Bushinsky, David A; Favus, Murray J

2010-01-01

Patients with idiopathic hypercalciuria (IH) and genetic hypercalciuric stone-forming (GHS) rats, an animal model of IH, are both characterized by normal serum Ca, hypercalciuria, Ca nephrolithiasis, reduced renal Ca reabsorption, and increased bone resorption. Serum 1,25-dihydroxyvitamin D [1,25(OH)2D] levels are elevated or normal in IH and are normal in GHS rats. In GHS rats, vitamin D receptor (VDR) protein levels are elevated in intestinal, kidney, and bone cells, and in IH, peripheral blood monocyte VDR levels are high. The high VDR is thought to amplify the target-tissue actions of normal circulating 1,25(OH)2D levels to increase Ca transport. The aim of this study was to elucidate the molecular mechanisms whereby Snail may contribute to the high VDR levels in GHS rats. In the study, Snail gene expression and protein levels were lower in GHS rat tissues and inversely correlated with VDR gene expression and protein levels in intestine and kidney cells. In human kidney and colon cell lines, ChIP assays revealed endogenous Snail binding close to specific E-box sequences within the human VDR promoter region, whereas only one E-box specifically bound Snail in the rat promoter. Snail binding to rat VDR promoter E-box regions was reduced in GHS compared with normal control intestine and was accompanied by hyperacetylation of histone H3. These results provide evidence that elevated VDR in GHS rats likely occurs because of derepression resulting from reduced Snail binding to the VDR promoter and hyperacetylation of histone H3. © 2010 American Society for Bone and Mineral Research. PMID:19929616

Higher risk of progressing breast cancer in Kurdish population associated to CDH1 -160 C/A polymorphism

PubMed Central

Zarei, Farzaneh; Menbari, Mohammad Nazir; Ghaderi, Bayazid; Abdi, Mohammad; Vahabzadeh, Zakaria

2017-01-01

There is an increasing interest about studying possible effects of genetic polymorphisms and risk of cancer progression. E-cadherin (CDH1) involves in many important cellular processes including cell-cell interactions, cell development and genetic changes of this molecule has been associated with greater tumor metastasis. The present study was aimed to evaluate the possible role of CDH1 -160 C/A polymorphism as a potential risk factor for breast cancer in Kurdish population. This case-control study consisted of 100 breast cancer patients and 200 healthy controls. Clinicopathological findings of all individuals were reported and immunohistochemistry staining was carried out on tissue samples. The CDH1 -160 C/A genotype was determined by polymerase chain reaction- restriction fragment length polymorphism method (PCR-RFLP). CDH1 -160 C/A polymorphism was differently distributed between patient and control groups. The A allele of CDH1 -160 C/A polymorphism significantly increased in patients compared to controls. In addition we found that the A allele of this polymorphism might be a potential risk factor for progression of breast cancer in our studied population. Patients with A allele of CDH1 -160 C/A was in higher risk to progress invasive ductal carcinoma. The A allele was also correlated with high grade and stage IV and also with metastatic tumors in studied subjects. The CDH1 -160 C/A polymorphism is correlated with clinicopathologial findings of breast cancer patients. The A allele of CDH1 -160 C/A may be a risk factor for progression of breast cancer in Kurdish patients. PMID:29285016

Higher risk of progressing breast cancer in Kurdish population associated to CDH1 -160 C/A polymorphism.

PubMed

Zarei, Farzaneh; Menbari, Mohammad Nazir; Ghaderi, Bayazid; Abdi, Mohammad; Vahabzadeh, Zakaria

2017-01-01

There is an increasing interest about studying possible effects of genetic polymorphisms and risk of cancer progression. E-cadherin (CDH1) involves in many important cellular processes including cell-cell interactions, cell development and genetic changes of this molecule has been associated with greater tumor metastasis. The present study was aimed to evaluate the possible role of CDH1 -160 C/A polymorphism as a potential risk factor for breast cancer in Kurdish population. This case-control study consisted of 100 breast cancer patients and 200 healthy controls. Clinicopathological findings of all individuals were reported and immunohistochemistry staining was carried out on tissue samples. The CDH1 -160 C/A genotype was determined by polymerase chain reaction- restriction fragment length polymorphism method (PCR-RFLP). CDH1 -160 C/A polymorphism was differently distributed between patient and control groups. The A allele of CDH1 -160 C/A polymorphism significantly increased in patients compared to controls. In addition we found that the A allele of this polymorphism might be a potential risk factor for progression of breast cancer in our studied population. Patients with A allele of CDH1 -160 C/A was in higher risk to progress invasive ductal carcinoma. The A allele was also correlated with high grade and stage IV and also with metastatic tumors in studied subjects. The CDH1 -160 C/A polymorphism is correlated with clinicopathologial findings of breast cancer patients. The A allele of CDH1 -160 C/A may be a risk factor for progression of breast cancer in Kurdish patients.

Cognitive performance on the mini-mental state examination and the montreal cognitive assessment across the healthy adult lifespan.

PubMed

Gluhm, Shea; Goldstein, Jody; Loc, Kiet; Colt, Alexandra; Liew, Charles Van; Corey-Bloom, Jody

2013-03-01

We sought to compare age-related performance on the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) across the adult lifespan in an asymptomatic, presumably normal, sample. The MMSE is the most commonly used brief cognitive screening test; however, the MoCA may be better at detecting early cognitive dysfunction. We gave the MMSE and MoCA to 254 community-dwelling participants ranging in age from 20 to 89, stratified by decade, and we compared their scores using the Wilcoxon signed rank test. For the total sample, the MMSE and MoCA differed significantly in total scores as well as in visuospatial, language, and memory domains (for all of these scores, P<0.001). Mean MMSE scores declined only modestly across the decades; mean MoCA scores declined more dramatically. There were no consistent domain differences between the MMSE and MoCA during the third and fourth decades; however, significant differences in memory (P<0.05) and language (P<0.001) emerged in the fifth through ninth decades. We conclude that the MoCA may be a better detector of age-related decrements in cognitive performance than the MMSE, as shown in this community-dwelling adult population.

The bimanual ovarian palpation examination in the Prostate, Lung, Colorectal and Ovarian cancer screening trial: Performance and complications.

PubMed

Doroudi, Maryam; Kramer, Barnett S; Pinsky, Paul F

2017-12-01

Objective To provide evidence about the performance characteristics and consequences of bimanual ovarian palpation. Setting and methods The Prostate, Lung, Colorectal and Ovarian cancer screening trial randomized 154,900 individuals to either an intervention or control arm. Enrolled eligible participants were aged 55-74, had no history of trial cancers, and no current treatment for cancer. Intervention arm women received CA-125 tests and transvaginal ultrasound. Bimanual ovarian palpation was offered annually during the first four years of the trial. Bimanual ovarian palpation-specific sensitivity and specificity were calculated, as were rates of diagnostic procedures and resulting complications following positive bimanual ovarian palpation screens. Results A total of 20,872 women received at least one bimanual ovarian palpation, with 50,498 total bimanual ovarian palpation examinations performed. The sensitivity and specificity of bimanual ovarian palpation were 5.1% (2/39) and 99.0% (49,957/50,459), respectively; no cases were detected by bimanual ovarian palpation alone. Rates for most follow-up procedures for abnormal results in women without ovarian cancer were higher among the group with another screening test positive, except for pelvic exam, where rates were similar. No complications were reported in the bimanual ovarian palpation-only positive group. Conclusion Low sensitivity of bimanual ovarian palpation alone and in combination with other tests argue against using bimanual ovarian palpation as a screening test for ovarian cancer in asymptomatic women.

CO2 laser irradiation enhances CaF2 formation and inhibits lesion progression on demineralized dental enamel-in vitro study.

PubMed

Zancopé, Bruna R; Rodrigues, Lívia P; Parisotto, Thais M; Steiner-Oliveira, Carolina; Rodrigues, Lidiany K A; Nobre-dos-Santos, Marinês

2016-04-01

This study evaluated if Carbon dioxide (CO2) (λ 10.6 μm) laser irradiation combined with acidulated phosphate fluoride gel application (APF gel) enhances "CaF2" uptake by demineralized enamel specimens (DES) and inhibits enamel lesion progression. Thus, two studies were conducted and DES were subjected to APF gel combined or not with CO2 laser irradiation (11.3 or 20.0 J/cm(2), 0.4 or 0.7 W) performed before, during, or after APF gel application. In study 1, 165 DES were allocated to 11 groups. Fluoride as "CaF2 like material" formed on enamel was determined in 100 DES (n = 10/group), and the surface morphologies of 50 specimens were evaluated by scanning electron microscopy (SEM) before and after "CaF2" extraction. In study 2, 165 DES (11 groups, n = 15), subjected to the same treatments as in study 1, were further subjected to a pH-cycling model to simulate a high cariogenic challenge. The progression of demineralization in DES was evaluated by cross-sectional microhardness and polarized light microscopy analyses. Laser at 11.3 J/cm(2) applied during APF gel application increased "CaF2" uptake on enamel surface. Laser irradiation and APF gel alone arrested the lesion progression compared with the control (p < 0.05). Areas of melting, fusion, and cracks were observed. CO2 laser irradiation, combined with a single APF application enhanced "CaF2" uptake on enamel surface and a synergistic effect was found. However, regarding the inhibition of caries lesion progression, no synergistic effect could be demonstrated. In conclusion, the results have shown that irradiation with specific laser parameters significantly enhanced CaF2 uptake by demineralized enamel and inhibited lesion progression.

Hierarchical accumulation of RyR post-translational modifications drives disease progression in dystrophic cardiomyopathy.

PubMed

Kyrychenko, Sergii; Poláková, Eva; Kang, Chifei; Pocsai, Krisztina; Ullrich, Nina D; Niggli, Ernst; Shirokova, Natalia

2013-03-15

Duchenne muscular dystrophy (DMD) is a muscle disease with serious cardiac complications. Changes in Ca(2+) homeostasis and oxidative stress were recently associated with cardiac deterioration, but the cellular pathophysiological mechanisms remain elusive. We investigated whether the activity of ryanodine receptor (RyR) Ca(2+) release channels is affected, whether changes in function are cause or consequence and which post-translational modifications drive disease progression. Electrophysiological, imaging, and biochemical techniques were used to study RyRs in cardiomyocytes from mdx mice, an animal model of DMD. Young mdx mice show no changes in cardiac performance, but do so after ∼8 months. Nevertheless, myocytes from mdx pups exhibited exaggerated Ca(2+) responses to mechanical stress and 'hypersensitive' excitation-contraction coupling, hallmarks of increased RyR Ca(2+) sensitivity. Both were normalized by antioxidants, inhibitors of NAD(P)H oxidase and CaMKII, but not by NO synthases and PKA antagonists. Sarcoplasmic reticulum Ca(2+) load and leak were unchanged in young mdx mice. However, by the age of 4-5 months and in senescence, leak was increased and load was reduced, indicating disease progression. By this age, all pharmacological interventions listed above normalized Ca(2+) signals and corrected changes in ECC, Ca(2+) load, and leak. Our findings suggest that increased RyR Ca(2+) sensitivity precedes and presumably drives the progression of dystrophic cardiomyopathy, with oxidative stress initiating its development. RyR oxidation followed by phosphorylation, first by CaMKII and later by PKA, synergistically contributes to cardiac deterioration.

EPI-SPIRE: A Bio-Surveillance Prototype

DTIC Science & Technology

2005-05-01

application to Lyme disease vectors. Intl J GIS 16:151-166. Glass, GE, TL Yates, JB Fine, TM Shields, JB Kendall, AG Hope, CA Parmenter CJ Peters, TG...EB Hayes & BS Schwartz. 2003. Longitudinal evaluation of an educational intervention to prevent tick bites in an area of endemic Lyme disease in...34. Fine, JB, JL Robertson, GE Glass. 2004. Borrelia burgdorferi exposure in asymptomatic populations of horses in Maryland and Virginia. Am J Vet

Effects of negative pressures on epithelial tight junctions and migration in wound healing.

PubMed

Hsu, Chih-Chin; Tsai, Wen-Chung; Chen, Carl Pai-Chu; Lu, Yun-Mei; Wang, Jong-Shyan

2010-08-01

Negative-pressure wound therapy has recently gained popularity in chronic wound care. This study attempted to explore effects of different negative pressures on epithelial migration in the wound-healing process. The electric cell-substrate impedance sensing (ECIS) technique was used to create a 5 x 10(-4) cm(2) wound in the Madin-Darby canine kidney (MDCK) and human keratinocyte (HaCaT) cells. The wounded cells were cultured in a negative pressure incubator at ambient pressure (AP) and negative pressures of 75 mmHg (NP(75)), 125 mmHg (NP(125)), and 175 mmHg (NP(175)). The effective time (ET), complete wound healing time (T(max)), healing rate (R(heal)), cell diameter, and wound area over time at different pressures were evaluated. Traditional wound-healing assays were prepared for fluorescent staining of cells viability, cell junction proteins, including ZO-1 and E-cadherin, and actins. Amount of cell junction proteins at AP and NP(125) was also quantified. In MDCK cells, the ET (1.25 +/- 0.27 h), T(max) (1.76 +/- 0.32 h), and R(heal) (2.94 +/- 0.62 x 10(-4) cm(2)/h) at NP(125) were significantly (P < 0.01) different from those at three other pressure conditions. In HaCaT cells, the T(max) (7.34 +/- 0.29 h) and R(heal) (6.82 +/- 0.26 x 10(-5) cm(2)/h) at NP(125) were significantly (P < 0.01) different from those at NP(75). Prominent cell migration features were identified in cells at the specific negative pressure. Cell migration activities at different pressures can be documented with the real-time wound-healing measurement system. Negative pressure of 125 mmHg can help disassemble the cell junction to enhance epithelial migration and subsequently result in quick wound closure.

Effects of asymptomatic rotator cuff pathology on in vivo shoulder motion and clinical outcomes.

PubMed

Baumer, Timothy G; Dischler, Jack; Mende, Veronica; Zauel, Roger; van Holsbeeck, Marnix; Siegal, Daniel S; Divine, George; Moutzouros, Vasilios; Bey, Michael J

2017-06-01

The incidence of asymptomatic rotator cuff tears has been reported to range from 15% to 39%, but the influence of asymptomatic rotator cuff pathology on shoulder function is not well understood. This study assessed the effects of asymptomatic rotator cuff pathology on shoulder kinematics, strength, and patient-reported outcomes. A clinical ultrasound examination was performed in 46 asymptomatic volunteers (age: 60.3 ± 7.5 years) with normal shoulder function to document the condition of their rotator cuff. The ultrasound imaging identified the participants as healthy (n = 14) or pathologic (n = 32). Shoulder motion was measured with a biplane x-ray imaging system, strength was assessed with a Biodex (Biodex Medical Systems, Inc., Shirley, NY, USA), and patient-reported outcomes were assessed using the Western Ontario Rotator Cuff Index and visual analog scale pain scores. Compared with healthy volunteers, those with rotator cuff pathology had significantly less abduction (P = .050) and elevation (P = .041) strength, their humerus was positioned more inferiorly on the glenoid (P = .018), and the glenohumeral contact path length was longer (P = .007). No significant differences were detected in the Western Ontario Rotator Cuff Index, visual analog scale, range of motion, or acromiohumeral distance. The differences observed between the healthy volunteers and those with asymptomatic rotator cuff pathology lend insight into the changes in joint mechanics, shoulder strength, and conventional clinical outcomes associated with the early stages of rotator cuff pathology. Furthermore, these findings suggest a plausible mechanical progression of kinematic and strength changes associated with the development of rotator cuff pathology. Copyright © 2016 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Epidemiology of disappearing Plasmodium vivax malaria: a case study in rural Amazonia.

PubMed

Barbosa, Susana; Gozze, Amanda B; Lima, Nathália F; Batista, Camilla L; Bastos, Melissa da Silva; Nicolete, Vanessa C; Fontoura, Pablo S; Gonçalves, Raquel M; Viana, Susana Ariane S; Menezes, Maria José; Scopel, Kézia Katiani G; Cavasini, Carlos E; Malafronte, Rosely dos Santos; da Silva-Nunes, Mônica; Vinetz, Joseph M; Castro, Márcia C; Ferreira, Marcelo U

2014-08-01

New frontier settlements across the Amazon Basin pose a major challenge for malaria elimination in Brazil. Here we describe the epidemiology of malaria during the early phases of occupation of farming settlements in Remansinho area, Brazilian Amazonia. We examine the relative contribution of low-density and asymptomatic parasitemias to the overall Plasmodium vivax burden over a period of declining transmission and discuss potential hurdles for malaria elimination in Remansinho and similar settings. Eight community-wide cross-sectional surveys, involving 584 subjects, were carried out in Remansinho over 3 years and complemented by active and passive surveillance of febrile illnesses between the surveys. We used quantitative PCR to detect low-density asexual parasitemias and gametocytemias missed by conventional microscopy. Mixed-effects multiple logistic regression models were used to characterize independent risk factors for P. vivax infection and disease. P. vivax prevalence decreased from 23.8% (March-April 2010) to 3.0% (April-May 2013), with no P. falciparum infections diagnosed after March-April 2011. Although migrants from malaria-free areas were at increased risk of malaria, their odds of having P. vivax infection and disease decreased by 2-3% with each year of residence in Amazonia. Several findings indicate that low-density and asymptomatic P. vivax parasitemias may complicate residual malaria elimination in Remansinho: (a) the proportion of subpatent infections (i.e. missed by microscopy) increased from 43.8% to 73.1% as P. vivax transmission declined; (b) most (56.6%) P. vivax infections were asymptomatic and 32.8% of them were both subpatent and asymptomatic; (c) asymptomatic parasite carriers accounted for 54.4% of the total P. vivax biomass in the host population; (d) over 90% subpatent and asymptomatic P. vivax had PCR-detectable gametocytemias; and (e) few (17.0%) asymptomatic and subpatent P. vivax infections that were left untreated progressed to clinical disease over 6 weeks of follow-up and became detectable by routine malaria surveillance.

Epidemiology of Disappearing Plasmodium vivax Malaria: A Case Study in Rural Amazonia

PubMed Central

Lima, Nathália F.; Batista, Camilla L.; Bastos, Melissa da Silva; Nicolete, Vanessa C.; Fontoura, Pablo S.; Gonçalves, Raquel M.; Viana, Susana Ariane S.; Menezes, Maria José; Scopel, Kézia Katiani G.; Cavasini, Carlos E.; Malafronte, Rosely dos Santos; da Silva-Nunes, Mônica; Vinetz, Joseph M.; Castro, Márcia C.; Ferreira, Marcelo U.

2014-01-01

Background New frontier settlements across the Amazon Basin pose a major challenge for malaria elimination in Brazil. Here we describe the epidemiology of malaria during the early phases of occupation of farming settlements in Remansinho area, Brazilian Amazonia. We examine the relative contribution of low-density and asymptomatic parasitemias to the overall Plasmodium vivax burden over a period of declining transmission and discuss potential hurdles for malaria elimination in Remansinho and similar settings. Methods Eight community-wide cross-sectional surveys, involving 584 subjects, were carried out in Remansinho over 3 years and complemented by active and passive surveillance of febrile illnesses between the surveys. We used quantitative PCR to detect low-density asexual parasitemias and gametocytemias missed by conventional microscopy. Mixed-effects multiple logistic regression models were used to characterize independent risk factors for P. vivax infection and disease. Principal Findings/Conclusions P. vivax prevalence decreased from 23.8% (March–April 2010) to 3.0% (April–May 2013), with no P. falciparum infections diagnosed after March–April 2011. Although migrants from malaria-free areas were at increased risk of malaria, their odds of having P. vivax infection and disease decreased by 2–3% with each year of residence in Amazonia. Several findings indicate that low-density and asymptomatic P. vivax parasitemias may complicate residual malaria elimination in Remansinho: (a) the proportion of subpatent infections (i.e. missed by microscopy) increased from 43.8% to 73.1% as P. vivax transmission declined; (b) most (56.6%) P. vivax infections were asymptomatic and 32.8% of them were both subpatent and asymptomatic; (c) asymptomatic parasite carriers accounted for 54.4% of the total P. vivax biomass in the host population; (d) over 90% subpatent and asymptomatic P. vivax had PCR-detectable gametocytemias; and (e) few (17.0%) asymptomatic and subpatent P. vivax infections that were left untreated progressed to clinical disease over 6 weeks of follow-up and became detectable by routine malaria surveillance. PMID:25166263

Transcriptional profiling of ileocecal valve of Holstein dairy cows infected with mycobacterium avium subsp. paratuberculosis

USDA-ARS?s Scientific Manuscript database

Johne’s disease is a chronic infection of the small intestine caused by Mycobacterium avium subspecies paratuberculosis (MAP), an intracellular bacterium. The events of pathogen survival within the host cell(s), chronic inflammation and the progression from asymptomatic subclinical stage to an advan...

FMRI of visual working memory in high school football players.

PubMed

Shenk, Trey E; Robinson, Meghan E; Svaldi, Diana O; Abbas, Kausar; Breedlove, Katherine M; Leverenz, Larry J; Nauman, Eric A; Talavage, Thomas M

2015-01-01

Visual working memory deficits have been observed in at-risk athletes. This study uses a visual N-back working memory functional magnetic resonance imaging task to longitudinally assess asymptomatic football athletes for abnormal activity. Athletes were increasingly "flagged" as the season progressed. Flagging may provide early detection of injury.

Man Versus Machine Part 2: Comparison of Radiologists' Interpretations and NeuroQuant Measures of Brain Asymmetry and Progressive Atrophy in Patients With Traumatic Brain Injury.

PubMed

Ross, David E; Ochs, Alfred L; DeSmit, Megan E; Seabaugh, Jan M; Havranek, Michael D

2015-01-01

This study is an expanded version of an earlier study, which compared NeuroQuant measures of MRI brain volume with the radiologist's traditional approach in outpatients with mild or moderate traumatic brain injury. NeuroQuant volumetric analyses were compared with the radiologists' interpretations. NeuroQuant found significantly higher rates of atrophy (50.0%), abnormal asymmetry (83.3%), and progressive atrophy (70.0%) than the radiologists (12.5%, 0% and 0%, respectively). Overall, NeuroQuant was more sensitive for detecting at least one sign of atrophy, abnormal asymmetry, or progressive atrophy (95.8%) than the traditional radiologist's approach (12.5%).

Vitamin D Status in Monkey Candidates for Space Flight

NASA Technical Reports Server (NTRS)

Arnaud, S. B.; Wronski, T. J.; Koslovskeya, I.; Dotsenko, R.; Navidi, M.; Wade, Charles E. (Technical Monitor)

1994-01-01

In preparation for the Cosmos 2229 Biosatellite space flight experiments in Rhesus monkeys, we evaluated the status of vitamin D in animals of different origins: candidates for space flight raised in Moscow (IMBP) and animals housed at Ames Research Ctr. (ARC) for pilot studies. Diets at IMBP were natural foods found by analysis to contain 1.4% Ca, 2.8% P and<240 IU D3/kg and at ARC standard monkey chow with 0.9% Ca, 0.5% P and 6600 IU D3/kg. We measured body weights (BW), serum calcium (TCa), total protein (TP), phosphorus (Pi), alkaline phosphatase (AP), 25-hydroxyvitamin D (25D) and 1,25-dihydroxyvitamin D (1,25D) in 16 IMBP and 15 ARC male animals and indices of bone formation in cancellous bone obtained from iliac crest biopsy of 6 IMBP and 13 ARC animals. BW were the same in juveniles at IMBP as ARC although ARC monkeys were born a year later. Mean(1SD) TCa and TP were higher and 25D lower (1819 vs. 93+18 ng/ml,p<.001) in IMBP than ARC animals. 1,25D (174156 vs. 212+77 pg/ml), Pi and AP were similar. In bone, osteoid and osteoblast surfaces averaged 38114% and 33+15% in all, with %vol. of osteoid higher in IMBP than ARC monkeys of the same BW (p<.05) Indices of bone formation were inversely related to 25D, not 1,25D. Of interest are similar 1,25D levels associated with a wide range of substrate and extensive osteoid in bone of D replete animals.

The potential predictive value of circulating immune cell ratio and tumor marker in atezolizumab treated advanced non-small cell lung cancer patients.

PubMed

Zhuo, Minglei; Chen, Hanxiao; Zhang, Tianzhuo; Yang, Xue; Zhong, Jia; Wang, Yuyan; An, Tongtong; Wu, Meina; Wang, Ziping; Huang, Jing; Zhao, Jun

2018-05-04

The PD-L1 antibody atezolizumab has shown promising efficacy in patients with advanced non-small cell lung cancer. But the predictive marker of clinical benefit has not been identified. This study aimed to search for potential predictive factors in circulating blood of patients receiving atezolizumab. Ten patients diagnosed with advanced non-small cell lung cancer were enrolled in this open-label observing study. Circulating immune cells and plasma tumor markers were examined in peripheral blood from these patients before and after atezolizumab treatment respectively. Relation between changes in circulating factors and anti-tumor efficacy were analyzed. Blood routine test showed that atezolizumab therapy induced slightly elevation of white blood cells count generally. The lymphocyte ratio was increased slightly in disease controlled patients but decreased prominently in disease progressed patients in response to atezolizumab therapy. Flow cytometric analysis revealed changes in percentage of various immune cell types, including CD4+ T cell, CD8+ T cell, myeloid-derived suppressor cell, regulatory T cell and PD-1 expressing T cell after atezolizumab. Levels of plasma tumor marker CEA, CA125 and CA199 were also altered after anti-PD-L1 therapy. In comparison with baseline, the disease progressed patients showed sharp increase in tumor marker levels, while those disease controlled patients were seen with decreased regulatory T cell and myeloid-derived suppressor cell ratios. The circulating immune cell ratios and plasma tumor marker levels were related with clinical efficacy of atezolizumab therapy. These factors could be potential predictive marker for anti-PD-L1 therapy in advanced non-small cell lung cancer.

Leiurotoxin I (scyllatoxin), a peptide ligand for Ca2(+)-activated K+ channels. Chemical synthesis, radiolabeling, and receptor characterization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Auguste, P.; Hugues, M.; Grave, B.

1990-03-15

Leiurotoxin I (scyllatoxin) is a 31-amino acid polypeptide from the venom of the scorpion Leiurus quinquestriatus hebraeus which has been previously isolated and sequenced by others. This paper reports (i) the total synthesis of this scorpion neurotoxin as well as some aspects of its structure-function relationships; (ii) the synthesis of the analog (Tyr2)leiurotoxin I (scyllatoxin) that has been monoiodinated at high specific radioactivity (2000 Ci/mmol) and has served for the characterization of the properties of {sup 125}I-(Tyr2)leiurotoxin I binding sites (Kd = 80 pM, molecular mass of 27 and 57 kDa for two polypeptides in the leiurotoxin I binding protein);more » (iii) the similarity of physiological actions between leiurotoxin I and apamin. Both toxins contract Taenia coli previously relaxed with epinephrine, both toxins block the after-hyperpolarization due to Ca2(+)-activated K+ channel activity in muscle cells in culture; (iv) the probable identity of binding sites for apamin and leiurotoxin I. In spite of a different chemical structure apamin competitively inhibits {sup 125}I-(Tyr2) leiurotoxin I binding and vice versa. Moreover, the peculiar effects of K+ on {sup 125}I-(Tyr2)leiurotoxin I binding are identical to those previously observed for {sup 125}I-apamin binding.« less

Superconductivity in (Cu 0.5Tl 0.25Li 0.25)Ba 2Ca 2Cu 3- ySi yO 10- δ samples

NASA Astrophysics Data System (ADS)

Khan, Nawazish A.; Qasim, Irfan; Khurram, A. A.

2010-07-01

The (Cu 0.5Tl 0.25Li 0.25)Ba 2Ca 2Cu 3- ySi yO 10- δ ( y = 0, 0.25 0.5, 0.75, 1.0, 1.25) superconductor samples have been prepared by solid-state reaction method. The critical temperature and as well as the magnitude of diamagnetism is increased up to Si concentration y = 1.0, however, from the doping level y = 1.25 a decrease in the critical temperature along with the vanishing of the diamagnetism was observed. The carrier's in the conducting CuO 2/SiO 2 planes were optimized by carrying out post-annealing in oxygen and an increase in the critical temperature was observed in all Si doped samples. The doping efficiency of Cu 0.5Tl 0.5Ba 2O 4- δ charge reservoir layer in (Cu 0.5Tl 0.25Li 0.25)Ba 2Ca 2Cu 3- ySi yO 10- δ ( y = 0, 0.25 0.5, 0.75, 1.0, 1.25) samples is enhanced by doping Li +1 ion; as alkali metals are known to easily loose their outer most electron which could be supplied to CuO 2/SiO 2 conducting planes and would suppress the anti-ferromagnetism in the inner conducting planes. The FTIR absorption measurements have provided an indirect evidence of Si substitution at in CuO 2 planes.

[Isolated splenic metastases from cervical cancer: a rare entity].

PubMed

Villalón-López, José Sebastián; Souto-del Bosque, Rosalía; Montañez-Lugo, Juan Ignacio; Chávez-González, Bruno

2014-01-01

Splenic metastases from solid tumors are a rare event with an incidence of only 2.9% to 9%. Splenic metastases from cervical cancer are a rare entity. Only a few cases have been reported of isolated spleen metastases from cervical cancer. We present the case of a 76-year-old woman with moderately differentiated endocervical adenocarcinoma stromal and endocervical invasion. Clinical stage was Ib1 and Ca-125 values of 150 U. She was managed with hysterectomy and pelvic lymphadenectomy. She received pelvic radiotherapy (45 Gy) followed 24 Gy of brachytherapy. Two years later she presented with abdominal pain. Abdominal computed tomography showed two splenic parenchymal lesions without disease in the remainder of the abdominal cavity and chest with a Ca-125 of 2,733 U. The patient is submitted to splenectomy. Histopathology demonstrates splenic metastases of well-differentiated adenocarcinoma from the endocervix. Immunohistochemical stain showed positivity from carcinoembryonic antigen; estrogen and progesterone receptors are negative. Ca-125 level 8 weeks after surgery was 16 U/ml. The patient received six cycles of adjuvant chemotherapy with paclitaxel and cisplatin. At 12 months follow-up the patient is alive and without evidence of tumor activity. The spleen is an uncommon site of metastasis. Splenectomy is considered the appropriate treatment in order to avoid complications such as splenic rupture and splenic vein thrombosis as well as to improve pain control from splenomegaly. Twelve months after surgery our patient is alive and without evidence of tumor activity.

Effect of screening on ovarian cancer mortality: the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Randomized Controlled Trial.

PubMed

Buys, Saundra S; Partridge, Edward; Black, Amanda; Johnson, Christine C; Lamerato, Lois; Isaacs, Claudine; Reding, Douglas J; Greenlee, Robert T; Yokochi, Lance A; Kessel, Bruce; Crawford, E David; Church, Timothy R; Andriole, Gerald L; Weissfeld, Joel L; Fouad, Mona N; Chia, David; O'Brien, Barbara; Ragard, Lawrence R; Clapp, Jonathan D; Rathmell, Joshua M; Riley, Thomas L; Hartge, Patricia; Pinsky, Paul F; Zhu, Claire S; Izmirlian, Grant; Kramer, Barnett S; Miller, Anthony B; Xu, Jian-Lun; Prorok, Philip C; Gohagan, John K; Berg, Christine D

2011-06-08

Screening for ovarian cancer with cancer antigen 125 (CA-125) and transvaginal ultrasound has an unknown effect on mortality. To evaluate the effect of screening for ovarian cancer on mortality in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Randomized controlled trial of 78,216 women aged 55 to 74 years assigned to undergo either annual screening (n = 39,105) or usual care (n = 39,111) at 10 screening centers across the United States between November 1993 and July 2001. Intervention The intervention group was offered annual screening with CA-125 for 6 years and transvaginal ultrasound for 4 years. Participants and their health care practitioners received the screening test results and managed evaluation of abnormal results. The usual care group was not offered annual screening with CA-125 for 6 years or transvaginal ultrasound but received their usual medical care. Participants were followed up for a maximum of 13 years (median [range], 12.4 years [10.9-13.0 years]) for cancer diagnoses and death until February 28, 2010. Mortality from ovarian cancer, including primary peritoneal and fallopian tube cancers. Secondary outcomes included ovarian cancer incidence and complications associated with screening examinations and diagnostic procedures. Ovarian cancer was diagnosed in 212 women (5.7 per 10,000 person-years) in the intervention group and 176 (4.7 per 10,000 person-years) in the usual care group (rate ratio [RR], 1.21; 95% confidence interval [CI], 0.99-1.48). There were 118 deaths caused by ovarian cancer (3.1 per 10,000 person-years) in the intervention group and 100 deaths (2.6 per 10,000 person-years) in the usual care group (mortality RR, 1.18; 95% CI, 0.82-1.71). Of 3285 women with false-positive results, 1080 underwent surgical follow-up; of whom, 163 women experienced at least 1 serious complication (15%). There were 2924 deaths due to other causes (excluding ovarian, colorectal, and lung cancer) (76.6 per 10,000 person-years) in the intervention group and 2914 deaths (76.2 per 10,000 person-years) in the usual care group (RR, 1.01; 95% CI, 0.96-1.06). Among women in the general US population, simultaneous screening with CA-125 and transvaginal ultrasound compared with usual care did not reduce ovarian cancer mortality. Diagnostic evaluation following a false-positive screening test result was associated with complications. Trial Registration clinicaltrials.gov Identifier: NCT00002540.

Cellular distribution of calmodulin and calmodulin-binding proteins in Vicia faba L

NASA Technical Reports Server (NTRS)

Ling, V.; Assmann, S. M.

1992-01-01

The distribution of calmodulin (CaM) and CaM-binding proteins within Vicia faba was investigated. Both CaM and CaM-binding proteins were found to be differentially distributed among organs, tissues, and protoplast types. CaM levels, on a per protein basis, were found to be the highest in leaf epidermis, containing 3-fold higher levels of CaM than in total leaf. Similarly, guard cell and epidermal cell protoplasts were also found to have higher levels of CaM than mesophyll cell protoplasts. 125I-CaM blot overlay assays were performed to qualitatively examine CaM-binding proteins in these protoplast types as well as in whole tissues and organs. CaM-binding proteins with Mr 52,000, 78,000, and 115,000 were common in all metabolically active plant parts. Unique CaM-binding protein bands were detected in guard cell protoplasts (Mr 39,000, 88,000), stems (Mr 45,000, 60,000, 64,000), and roots (Mr 62,000), suggesting the presence of specialized CaM-dependent processes in these cells and organs.

Cediranib, an Oral Inhibitor of Vascular Endothelial Growth Factor Receptor Kinases, Is an Active Drug in Recurrent Epithelial Ovarian, Fallopian Tube, and Peritoneal Cancer

PubMed Central

Matulonis, Ursula A.; Berlin, Suzanne; Ivy, Percy; Tyburski, Karin; Krasner, Carolyn; Zarwan, Corrine; Berkenblit, Anna; Campos, Susana; Horowitz, Neil; Cannistra, Stephen A.; Lee, Hang; Lee, Julie; Roche, Maria; Hill, Margaret; Whalen, Christin; Sullivan, Laura; Tran, Chau; Humphreys, Benjamin D.; Penson, Richard T.

2009-01-01

Purpose Angiogenesis is important for epithelial ovarian cancer (EOC) growth, and blocking angiogenesis can lead to EOC regression. Cediranib is an oral tyrosine kinase inhibitor (TKI) of vascular endothelial growth factor receptor (VEGFR) -1, VEGFR-2, VEGFR-3, and c-kit. Patients and Methods We conducted a phase II study of cediranib for recurrent EOC or peritoneal or fallopian tube cancer; cediranib was administered as a daily oral dose, and the original dose was 45 mg daily. Because of toxicities observed in the first 11 patients, the dose was lowered to 30 mg. Eligibility included ≤ two lines of chemotherapy for recurrence. End points included response rate (via Response Evaluation Criteria in Solid Tumors [RECIST] or modified Gynecological Cancer Intergroup CA-125), toxicity, progression-free survival (PFS), and overall survival (OS). Results Forty-seven patients were enrolled; 46 were treated. Clinical benefit rate (defined as complete response [CR] or partial response [PR], stable disease [SD] > 16 weeks, or CA-125 nonprogression > 16 weeks), which was the primary end point, was 30%; eight patients (17%; 95% CI, 7.6% to 30.8%) had a PR, six patients (13%; 95% CI, 4.8% to 25.7%) had SD, and there were no CRs. Eleven patients (23%) were removed from study because of toxicities before two cycles. Grade 3 toxicities (> 20% of patients) included hypertension (46%), fatigue (24%), and diarrhea (13%). Grade 2 hypothyroidism occurred in 43% of patients. Grade 4 toxicities included CNS hemorrhage (n = 1), hypertriglyceridemia/hypercholesterolemia/elevated lipase (n = 1), and dehydration/elevated creatinine (n = 1). No bowel perforations or fistulas occurred. Median PFS was 5.2 months, and median OS has not been reached; median follow-up time is 10.7 months. Conclusion Cediranib has activity in recurrent EOC, tubal cancer, and peritoneal cancer with predictable toxicities observed with other TKIs. PMID:19826113

Cediranib, an oral inhibitor of vascular endothelial growth factor receptor kinases, is an active drug in recurrent epithelial ovarian, fallopian tube, and peritoneal cancer.

PubMed

Matulonis, Ursula A; Berlin, Suzanne; Ivy, Percy; Tyburski, Karin; Krasner, Carolyn; Zarwan, Corrine; Berkenblit, Anna; Campos, Susana; Horowitz, Neil; Cannistra, Stephen A; Lee, Hang; Lee, Julie; Roche, Maria; Hill, Margaret; Whalen, Christin; Sullivan, Laura; Tran, Chau; Humphreys, Benjamin D; Penson, Richard T

2009-11-20

Angiogenesis is important for epithelial ovarian cancer (EOC) growth, and blocking angiogenesis can lead to EOC regression. Cediranib is an oral tyrosine kinase inhibitor (TKI) of vascular endothelial growth factor receptor (VEGFR) -1, VEGFR-2, VEGFR-3, and c-kit. We conducted a phase II study of cediranib for recurrent EOC or peritoneal or fallopian tube cancer; cediranib was administered as a daily oral dose, and the original dose was 45 mg daily. Because of toxicities observed in the first 11 patients, the dose was lowered to 30 mg. Eligibility included 16 weeks, or CA-125 nonprogression > 16 weeks), which was the primary end point, was 30%; eight patients (17%; 95% CI, 7.6% to 30.8%) had a PR, six patients (13%; 95% CI, 4.8% to 25.7%) had SD, and there were no CRs. Eleven patients (23%) were removed from study because of toxicities before two cycles. Grade 3 toxicities (> 20% of patients) included hypertension (46%), fatigue (24%), and diarrhea (13%). Grade 2 hypothyroidism occurred in 43% of patients. Grade 4 toxicities included CNS hemorrhage (n = 1), hypertriglyceridemia/hypercholesterolemia/elevated lipase (n = 1), and dehydration/elevated creatinine (n = 1). No bowel perforations or fistulas occurred. Median PFS was 5.2 months, and median OS has not been reached; median follow-up time is 10.7 months. Cediranib has activity in recurrent EOC, tubal cancer, and peritoneal cancer with predictable toxicities observed with other TKIs.

Novel activating mutation of human calcium-sensing receptor in a family with autosomal dominant hypocalcaemia.

PubMed

Baran, Natalia; ter Braak, Michael; Saffrich, Rainer; Woelfle, Joachim; Schmitz, Udo

2015-05-15

Autosomal dominant hypocalcaemia (ADH) is caused by activating mutations in the calcium sensing receptor gene (CaR) and characterised by mostly asymptomatic mild to moderate hypocalcaemia with low, inappropriately serum concentration of PTH. The purpose of the present study was to biochemically and functionally characterise a novel mutation of CaR. A female proband presenting with hypocalcaemia was diagnosed to have "idiopathic hypoparathyroidism" at the age of 10 with a history of muscle pain and cramps. Further examinations demonstrated hypocalcaemia in nine additional family members, affecting three generations. P136L CaR mutation was predicted to cause gain of function of CaR. Affected family members showed relevant hypocalcaemia (mean ± SD; 1.9 ± 0.1 mmol/l). Patient history included mild seizures and recurrent nephrolithiasis. Genetic analysis confirmed that hypocalcaemia cosegregated with a heterozygous mutation at codon 136 (CCC → CTC/Pro → Leu) in exon 3 of CaR confirming the diagnosis of ADH. For in vitro studies P136L mutant CaR was generated by site-directed mutagenesis and examined in transiently transfected HEK293 cells. Extracellular calcium stimulation of transiently transfected HEK293 cells showed significantly increased intracellular Ca(2+) mobilisation and MAPK activity for mutant P136L CaR compared to wild type CaR. The present study gives insight about a novel activating mutation of CaR and confirms that the novel P136L-CaR mutation is responsible for ADH in this family. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

First molecular identification of kobuviruses in wolves (Canis lupus) in Italy.

PubMed

Melegari, Irene; Sarchese, Vittorio; Di Profio, Federica; Robetto, Serena; Carella, Emanuele; Bermudez Sanchez, Sandra; Orusa, Riccardo; Martella, Vito; Marsilio, Fulvio; Di Martino, Barbara

2018-02-01

Canine kobuviruses (CaKoVs) were first identified in diarrhoeic and asymptomatic dogs in 2011 in the USA. Subsequent studies have demonstrated a worldwide distribution of these viruses, but it is not clear if CaKoVs play a role as enteric pathogens of dogs. More recently, CaKoV RNA has been detected in wild carnivores, including red fox, golden jackal, side-striped jackal and spotted hyena. In this study, we addressed the hypothesis that wolves are susceptible to CaKoV infections. A total of 185 wolf stool samples were collected from necropsied animals and from transects in the Liguria, Piemonte and Valle D'Aosta regions of Italy, and CaKoV RNA was identified in two of these specimens. Both samples were obtained from necropsied wolves, with a prevalence rate of 4.9% (2/41). Sequence analysis of the full-length VP1 region showed that these strains displayed the highest nucleotide (nt) sequence identity (86.3-98.5%) to canine strains identified in the UK and Africa, and to kobuviruses that were previously detected in other African wild carnivores. This suggests that genetically related CaKoV strains circulate in domestic and wild carnivores, with interspecies transmission being not uncommon among carnivores of different ecosystems.

Some Common Abbreviations

MedlinePlus

... blood test for CA-125 A to measure cancer activity. CABG Coronary artery bypass graft A type of ... NKDA No known drug allergies NSAID Non-steroidal anti-inflammatory ... detect cervical cancer. PAT Paroxysmal atrial tachycardia A disturbance of the ...

Measurements of Cell Physiology: Ionized Calcium, pH and Glutathione

DTIC Science & Technology

1993-01-01

above before incubation, with traacetic acid )) (Fig. 31.1), has spectral properties that make subsequent incubation at 30’C (11, 12). An additional option... acid ) to the cell suspension simulta suh use othoseu or cwill reduce Ca:* to -20 rnM, thus abolishing the usual cross- cytometry, such as those used...31.8. PBL from asymptomatic HIV-inlected patienis or an Cl- exchange. Acid extrusion is primarily accomplished by uninfected control donor were

Prediction of Indications for Valve Replacement Among Asymptomatic or Minimally Symptomatic Patients With Chronic Aortic Regurgitation and Normal Left Ventricular Performance

PubMed Central

Borer, Jeffrey S.; Hochreiter, Clare; Herrold, Edmond McM; Supino, Phyllis; Aschermann, Michael; Wencker, Detlef; Devereux, Richard B.; Roman, Mary J.; Szulc, Massimiliano; Kligfield, Paul; Isom, O. Wayne

2013-01-01

Background Optimal criteria for valve replacement are unclear in asymptomatic/minimally symptomatic patients with aortic regurgitation (AR) and normal left ventricular (LV) performance at rest. Moreover, previous studies have not assessed the prognostic capacity of load-adjusted LV performance (“contractility”) variables, which may be fundamentally related to clinical state. Therefore, 18 years ago, we set out to test prospectively the hypothesis that objective noninvasive measures of LV size and performance and, specifically, of load-adjusted variables, assessed at rest and during exercise (ex), could predict the development of currently accepted indications for operation for AR. Methods and Results Clinical variables and measures of LV size, performance, and end-systolic wall stress (ESS) were assessed annually in 104 patients by radionuclide cineangiography at rest and maximal ex and by echocardiography at rest; ESS was derived during ex. During an average 7.3-year follow-up among patients who had not been operated on, 39 of 104 patients either died suddenly (n = 4) or developed operable symptoms only (n = 22) or subnormal LV performance with or without symptoms (n= 13) (progression rate = 6.2%/y). By multivariate Cox model analysis, change (Δ) in LV ejection fraction (EF) from rest to ex, normalized for ΔESS from rest to ex (ΔLVEF-ΔESS index), was the strongest predictor of progression to any end point or to sudden cardiac death alone. Unadjusted ΔLVEF was almost as efficient. Symptom status modified prediction on the basis of the ΔLVEF-ΔESS index. The population tercile at highest risk by ΔLVEF-ΔESS progressed to end points at a rate of 13.3%/y, and the lowest-risk tercile progressed at 1.8%/y. Conclusions Currently accepted symptom and LV performance indications for valve replacement, as well as sudden cardiac death, can be predicted in asymptomatic/minimally symptomatic patients with AR by load-adjusted ΔLVEF-ΔESS index, which includes data obtained during exercise. PMID:9494022

Modelling the Course of an HIV Infection: Insights from Ecology and Evolution

PubMed Central

Alizon, Samuel; Magnus, Carsten

2012-01-01

The Human Immunodeficiency Virus (HIV) is one of the most threatening viral agents. This virus infects approximately 33 million people, many of whom are unaware of their status because, except for flu-like symptoms right at the beginning of the infection during the acute phase, the disease progresses more or less symptom-free for 5 to 10 years. During this asymptomatic phase, the virus slowly destroys the immune system until the onset of AIDS when opportunistic infections like pneumonia or Kaposi’s sarcoma can overcome immune defenses. Mathematical models have played a decisive role in estimating important parameters (e.g., virion clearance rate or life-span of infected cells). However, most models only account for the acute and asymptomatic latency phase and cannot explain the progression to AIDS. Models that account for the whole course of the infection rely on different hypotheses to explain the progression to AIDS. The aim of this study is to review these models, present their technical approaches and discuss the robustness of their biological hypotheses. Among the few models capturing all three phases of an HIV infection, we can distinguish between those that mainly rely on population dynamics and those that involve virus evolution. Overall, the modeling quest to capture the dynamics of an HIV infection has improved our understanding of the progression to AIDS but, more generally, it has also led to the insight that population dynamics and evolutionary processes can be necessary to explain the course of an infection. PMID:23202449

Immunologic mapping of glycomes: implications for cancer diagnosis and therapy.

PubMed

Zhou, Dapeng; Levery, Steven B; Hsu, Fong-Fu; Wang, Peng G; Teneberg, Susann; Almeida, Igor C; Li, Yunsen; Xu, Huaxi; Wang, Lai-Xi; Xia, Chengfeng; Ibrahim, Nuhad K; Michael, Katja

2011-06-01

Cancer associated glycoconjugates are important biomarkers, as exemplified by globo-H, CA125, CA15.3 and CA27.29. However, the exact chemical structures of many such biomarkers remain unknown because of technological limitations. In this article, we propose the "immunologic mapping" of cancer glycomes based on specific immune recognition of glycan structures, which can be hypothesized theoretically, produced chemically, and examined biologically by immuno-assays. Immunologic mapping of glycans not only provides a unique perspective on cancer glycomes, but also may lead to the invention of powerful reagents for diagnosis and therapy.

Immunologic mapping of glycomes: implications for cancer diagnosis and therapy

PubMed Central

Zhou, Dapeng; Levery, Steven B.; Hsu, Fong-Fu; Wang, Peng G.; Teneberg, Susann; Almeida, Igor C.; Li, Yunsen; Xu, Huaxi; Wang, Lai-Xi; Xia, Chengfeng; Ibrahim, Nuhad K; Michael, Katja

2013-01-01

Cancer associated glycoconjugates are important biomarkers, as exemplified by globo-H, CA125, CA15.3 and CA27.29. However, the exact chemical structures of many such biomarkers remain unknown because of technological limitations. In this article, we propose the “immunologic mapping” of cancer glycomes based on specific immune recognition of glycan structures, which can be hypothesized theoretically, produced chemically, and examined biologically by immuno-assays. Immunologic mapping of glycans not only provides a unique perspective on cancer glycomes, but also may lead to the invention of powerful reagents for diagnosis and therapy. PMID:21622287

Endemic chronic kidney disease of unknown etiology in Sri Lanka: Correlation of pathology with clinical stages.

PubMed

Wijetunge, S; Ratnatunga, N V I; Abeysekera, T D J; Wazil, A W M; Selvarajah, M

2015-01-01

Chronic kidney disease of unknown etiology (CKDU) is endemic among the rural farming communities in several localities in and around the North Central region of Sri Lanka. This is an interstitial type renal disease and typically has an insidious onset and slow progression. This study was conducted to identify the pathological features in the different clinical stages of CKDU. This is a retrospective study of 251 renal biopsies identified to have a primary interstitial disease from regions endemic for CKDU. Pathological features were assessed and graded in relation to the clinical stage. The mean age of those affected by endemic CKDU was 37.3 ± 12.5 years and the male to female ratio was 3.3:1. The predominant feature of stage I disease was mild and moderate interstitial fibrosis; most did not have interstitial inflammation. The typical stage II disease had moderate interstitial fibrosis with or without mild interstitial inflammation. Stage III disease had moderate and severe interstitial fibrosis, moderate interstitial inflammation, tubular atrophy and some glomerulosclerosis. Stage IV disease typically had severe interstitial fibrosis and inflammation, tubular atrophy and glomerulosclerosis. The mean age of patients with stage I disease (27 ± 10.8 years) was significantly lower than those of the other stages. About 79.2%, 55%, 49.1% and 50% in stage I, II, III and IV disease respectively were asymptomatic at the time of biopsy.

Phanerozoic continental growth and gold metallogeny of Asia

USGS Publications Warehouse

Goldfarb, Richard J.; Taylor, Ryan D.; Collins, Gregory S.; Goryachev, Nicolay A.; Orlandini, Omero Felipe

2014-01-01

The Asian continent formed during the past 800 m.y. during late Neoproterozoic through Jurassic closure of the Tethyan ocean basins, followed by late Mesozoic circum-Pacific and Cenozoic Himalayan orogenies. The oldest gold deposits in Asia reflect accretionary events along the margins of the Siberia, Kazakhstan, North China, Tarim–Karakum, South China, and Indochina Precambrian blocks while they were isolated within the Paleotethys and surrounding Panthalassa Oceans. Orogenic gold deposits are associated with large-scale, terrane-bounding fault systems and broad areas of deformation that existed along many of the active margins of the Precambrian blocks. Deposits typically formed during regional transpressional to transtensional events immediately after to as much as 100 m.y. subsequent to the onset of accretion or collision. Major orogenic gold provinces associated with this growth of the Asian continental mass include: (1) the ca. 750 Ma Yenisei Ridge, ca. 500 Ma East Sayan, and ca. 450–350 Ma Patom provinces along the southern margins of the Siberia craton; (2) the 450 Ma Charsk belt of north-central Kazakhstan; (3) the 310–280 Ma Kalba belt of NE Kazakhstan, extending into adjacent NW Xinjiang, along the Siberia–Kazakhstan suture; (4) the ca. 300–280 Ma deposits within the Central Asian southern and middle Tien Shan (e.g., Kumtor, Zarmitan, Muruntau), marking the closure of the Turkestan Ocean between Kazakhstan and the Tarim–Karakum block; (5) the ca. 190–125 Ma Transbaikal deposits along the site of Permian to Late Jurassic diachronous closure of the Mongol–Okhotsk Ocean between Siberia and Mongolia/North China; (6) the probable Late Silurian–Early Devonian Jiagnan belt formed along the margin of Gondwana at the site of collision between the Yangtze and Cathaysia blocks; (7) Triassic deposits of the Paleozoic Qilian Shan and West Qinling orogens along the SW margin of the North China block developed during collision of South China; and (8) Jurassic(?) ores on the margins of the Subumusu block in Myanmar and Malaysia. Circum-Pacific tectonism led to major orogenic gold province formation along the length of the eastern side of Asia between ca. 135 and 120 Ma, although such deposits are slightly older in South Korea and slightly younger in the Amur region of the Russian Southeast. Deformation related to collision of the Kolyma–Omolon microcontinent with the Pacific margin of the Siberia craton led to formation of 136–125 Ma ores of the Yana–Kolyma belt (Natalka, Sarylakh) and 125–119 Ma ores of the South Verkhoyansk synclinorium (Nezhdaninskoe). Giant ca. 125 Ma gold provinces developed in the Late Archean uplifted basement of the decratonized North China block, within its NE edge and into adjacent North Korea, in the Jiaodong Peninsula, and in the Qinling Mountains. The oldest gold-bearing magmatic–hydrothermal deposits of Asia include the ca. 485 Ma Duobaoshan porphyry within a part of the Tuva–Mongol arc, ca. 355 Ma low-sulfidation epithermal deposits (Kubaka) of the Omolon terrane accreted to eastern Russia, and porphyries (Bozshakol, Taldy Bulak) within Ordovican to Early Devonian oceanic arcs formed off the Kazakhstan microcontinent. The Late Devonian to Carboniferous was marked by widespread gold-rich porphyry development along the margins of the closing Ob–Zaisan, Junggar–Balkhash, and Turkestan basins (Amalyk, Oyu Tolgoi); most were formed in continental arcs, although the giant Oyu Tolgoi porphyry was part of a near-shore oceanic arc. Permian subduction-related deformation along the east side of the Indochina block led to ca. 300 Ma gold-bearing skarn and disseminated gold ore formation in the Truong Son fold belt of Laos, and along the west side to ca. 250 Ma gold-bearing skarns and epithermal deposits in the Loei fold belt of Laos and Thailand. In the Mesozoic Transbaikal region, extension along the basin margins subsequent to Mongol–Okhotsk closure was associated with ca. 150–125 Ma formation of important auriferous epithermal (Balei), skarn (Bystray), and porphyry (Kultuminskoe) deposits. In northeastern Russia, Early Cretaceous Pacific margin subduction and Late Cretaceous extension were associated with epithermal gold-deposit formation in the Uda–Murgal (Julietta) and Okhotsk–Chukotka (Dukat, Kupol) volcanic belts, respectively. In southeastern Russia, latest Cretaceous to Oligocene extension correlates with other low-sulfidation epithermal ores that formed in the East Sikhote–Alin volcanic belt. Other extensional events, likely related to changing plate dynamics along the Pacific margin of Asia, relate to epithermal–skarn–porphyry districts that formed at ca. 125–85 Ma in northeastmost China and ca. 105–90 Ma in the Coast Volcanic belt of SE China. The onset of strike slip along a part of the southeastern Pacific margin appears to correlate with the giant 148–135 Ma gold-rich porphyry–skarn province of the lower and middle Yangtze River. It is still controversial as to whether true Carlin-like gold deposits exist in Asia. Those deposits that most closely resemble the Nevada (USA) ores are those in the Permo-Triassic Youjiang basin of SW China and NE Vietnam, and are probably Late Triassic in age, although this is not certain. Other Carlin-like deposits have been suggested to exist in the Sepon basin of Laos and in the Mongol–Okhotsk region (Kuranakh) of Transbaikal.

Asymptomatic dystrophinopathy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Morrone, A.; Hoffman, E.P.; Hoop, R.C.

1997-03-31

A 4-year-old girl was referred for evaluation for a mild but persistent serum aspartate aminotransferase (AST) elevation detected incidentally during routine blood screening for a skin infection. Serum creatine kinase activity was found to be increased. Immuno-histochemical study for dystrophin in her muscle biopsy showed results consistent with a carrier state for muscular dystrophy. Molecular work-up showed the proposita to be a carrier of a deletion mutation of exon 48 of the dystrophin gene. Four male relatives also had the deletion mutation, yet showed no clinical symptoms of muscular dystrophy (age range 8-58 yrs). Linkage analysis of the dystrophin genemore » in the family showed a spontaneous change of an STR45 allele, which could be due to either an intragenic double recombination event, or CA repeat length mutation leading to identical size alleles. To our knowledge, this is the first documentation of an asymptomatic dystrophinopathy in multiple males of advanced age. Based on molecular findings, this family would be given a diagnosis of Becker muscular dystrophy. This diagnosis implies the development of clinical symptoms, even though this family is clearly asymptomatic. This report underscores the caution which must be exercised when giving presymptomatic diagnoses based on molecular studies. 28 refs., 4 figs., 1 tab.« less

The Uptake of Secondary Prevention by Adults with Intellectual and Developmental Disabilities

ERIC Educational Resources Information Center

Ouellette-Kuntz, H.; Cobigo, V.; Balogh, R.; Wilton, A.; Lunsky, Y.

2015-01-01

Background: Secondary prevention involves the early detection of disease while it is asymptomatic to prevent its progression. For adults with intellectual and developmental disabilities, secondary prevention is critical as they may not have the ability to recognize the early signs and symptoms of disease or lack accessible information about these.…

Smoldering Multiple Myeloma

PubMed Central

Gao, Minjie; Yang, Guang; Kong, Yuanyuan; Wu, Xiaosong; Shi, Jumei

2015-01-01

Smoldering multiple myeloma (SMM) is an asymptomatic precursor stage of multiple myeloma (MM) characterized by clonal bone marrow plasma cells (BMPC) ≥ 10% and/or M protein level ≥ 30 g/L in the absence of end organ damage. It represents an intermediate stage between monoclonal gammopathy of undetermined significance (MGUS) and symptomatic MM. The risk of progression to symptomatic MM is not uniform, and several parameters have been reported to predict the risk of progression. These include the level of M protein and the percentage of BMPC, the proportion of immunophenotypically aberrant plasma cells, and the presence of immunoparesis, free light-chain (FLC) ratio, peripheral blood plasma cells (PBPC), pattern of serum M protein evolution, abnormal magnetic resonance imaging (MRI), cytogenetic abnormalities, IgA isotype, and Bence Jones proteinuria. So far treatment is still not recommended for SMM, because several trials suggested that patients with SMM do not benefit from early treatment. However, the Mateos et al. trial showed a survival benefit after early treatment with lenalidomide plus dexamethasone in patients with high-risk SMM. This trial has prompted a reevaluation of early treatment in an asymptomatic patient population. PMID:26000300

Disruption of the Gardos channel (KCa3.1) in mice causes subtle erythrocyte macrocytosis and progressive splenomegaly.

PubMed

Grgic, Ivica; Kaistha, Brajesh P; Paschen, Steffen; Kaistha, Anuradha; Busch, Christoph; Si, Han; Köhler, Kernt; Elsässer, Hans-Peter; Hoyer, Joachim; Köhler, Ralf

2009-06-01

Gardos channel, the erythrocyte Ca(2+)-activated K(+) channel (K(Ca)3.1), is considered a major regulator of red blood cell (RBC) volume by mediating efflux of potassium and thus cell dehydration and shrinkage. However, the functional importance of K(Ca)3.1 in RBC in vivo is incompletely understood. Here, we used K(Ca)3.1(-/-)-mice to investigate the consequences of K(Ca)3.1 deficiency for RBC indices, functions, and sequestration. RBCs of K(Ca)3.1(-/-)-mice of all ages were mildly macrocytic but their biconcave appearance being preserved. RBC number, total hemoglobin, and hematocrit were unchanged in the adult K(Ca)3.1(-/-)-mice and increased in the premature K(Ca)3.1(-/-)-mice. Filterability, Ca(2+)-dependent volume decrease and osmotic tolerance of RBCs lacking K(Ca)3.1 were noticeably reduced when compared to RBC of wild-type littermates. Deformability to increasing shear stress was unchanged. Strikingly, K(Ca)3.1(-/-)-mice developed progressive splenomegaly which was considerable ( approximately 200% of controls) in the >6-month-old mice and was paralleled by increased iron deposition in the aged mice presumably as a consequence of enhanced RBC sequestration. Daily injections of the K(Ca)3.1-blocker TRAM-34 (120 mg/kg) also produced mild splenomegaly in wild-type mice. We conclude that genetic deficit of erythroid K(Ca)3.1 causes mild RBC macrocytosis, presumably leading to reduced filterability, and impairs volume regulation. These RBC defects result in mild but progressive splenomegaly.

Clinical Sequelae of Thrombus in an Inferior Vena Cava Filter

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ahmad, Iftikhar; Yeddula, Kalpana; Wicky, Stephan

The purpose of this study was to assess the long-term clinical sequelae of inferior vena cava (IVC) filter thrombus and the effect of anticoagulation on filter thrombus. Of 1,718 patients who had IVC filters placed during 2001-2008, 598 (34.8%) had follow-up abdominal CT. Filter thrombus was seen in 111 of the 598 (18.6%). There were 44 men (39.6%). The mean age at filter placement was 64 years. The medical diseases included cancer in 64, trauma in 15, stroke in 12, and others in 20. The frequency of filter thrombus on CT and asymptomatic filter thrombus on CT was calculated. Themore » frequency of pulmonary embolism (PE) in patients with filter thrombus was calculated. The frequency of thrombus progression or regression (on CT, available in 56) was calculated. The effect of anticoagulation on filter thrombus regression/progression was evaluated using the Fisher exact test by comparing the group of patients who received anticoagulants versus those who did not. A P-value of <0.05 was considered significant. The overall frequency of filter thrombus was 18.6%. Total occlusion of the IVC filter was seen in 12 of 598 (2%). The filter thrombus was asymptomatic in 110 (18.3%). Filter thrombus was detected after a median of 35 days (range, 0-2082) following filter placement. Thrombus extended above the filter in 4 (3.6%); IVC thrombus below the filter was seen in 35(31.5%). Thrombus in the filter occluded <25% of the filter volume in 58 (52.3%), 25-50% in 21 (18.9%), and 50-75% in 20 (18%). Total IVC occlusion was seen in 12 (10.8%). Eighty-three patients received anticoagulation. Sixteen patients developed symptoms of PE. PE was confirmed on CT in 3 of 15 (2.7%). On follow-up, filter thrombus regressed completely in 19 (33.9%) after a median of 6 months. Filter thrombus decreased in size in 13 (23.2%) and it progressed without IVC occlusion in 7 (12.6%). In one (1.7%), filter thrombus progressed to IVC occlusion. Filter thrombus remained stable in 16 (28.6%). There was no significant difference in thrombus regression or progression rates whether or not the patients received anticoagulation for filter thrombus. In conclusion, asymptomatic thrombus in the filter is common and it rarely progresses to complete caval occlusion. Anticoagulation has little effect on the resolution of filter thrombosis and future occurrence of PE.« less

The value of DCE-MRI in assessing histopathological and molecular biological features in induced rat epithelial ovarian carcinomas.

PubMed

Yuan, Su Juan; Qiao, Tian Kui; Qiang, Jin Wei; Cai, Song Qi; Li, Ruo Kun

2017-09-26

To investigate dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) for assessing histopathological and molecular biological features in induced rat epithelial ovarian carcinomas (EOCs). 7,12-dimethylbenz[A]anthracene (DMBA) was applied to induce EOCs in situ in 46 SD rats. Conventional MRI and DCE-MRI were performed to evaluate the morphology and perfusion features of the tumors, including the time-signal intensity curve (TIC), volume transfer constant (K trans ), rate constant (K ep ), extravascular extracellular space volume ratio (V e ) and initial area under the curve (IAUC). DCE-MRI parameters were correlated with histological grade, microvascular density (MVD), vascular endothelial growth factor (VEGF) and fraction of Ki67-positive cells and the serum level of cancer antigen 125 (CA125). Thirty-five of the 46 rats developed EOCs. DCE-MRI showed type III TIC more frequently than type II (29/35 vs. 6/35, p < 0.001) in EOCs. The two types of TIC of tumors had significant differences in the histological grade, MVD, expression of VEGF and Ki67, and the serum level of CA125 (all p < 0.01). K trans , K ep and IAUC values showed significant differences in different histological grades in overall and pairwise comparisons except for IAUC in grade 2 vs. grade 3 (all p < 0.01). There was no significant difference in V e values among the three grade groups (p > 0.05). K trans , K ep and IAUC values were positively correlated with MVD, VEGF and Ki67 expression (all p < 0.01). V e was not significantly correlated with MVD, VEGF expression, Ki67 expression and the CA125 level (all p > 0.05). TIC types and perfusion parameters of DCE-MRI can reflect tumor grade, angiogenesis and cell proliferation to some extent, thereby helping treatment planning and predicting prognosis.

Value of 18F-FDG PET/CT Combined With Tumor Markers in the Evaluation of Ascites.

PubMed

Han, Na; Sun, Xun; Qin, Chunxia; Hassan Bakari, Khamis; Wu, Zhijian; Zhang, Yongxue; Lan, Xiaoli

2018-05-01

The purpose of this study is to investigate the value of 18 F-FDG PET/CT combined with assessment of tumor markers in serum or ascites for the diagnosing and determining the prognosis of benign and malignant ascites. Patients with ascites of unknown cause who underwent evaluation with FDG PET/CT were included in this retrospective study. The maximum standardized uptake value (SUV max ) and levels of the tumor markers carbohydrate antigen-125 (CA-125) and carcinoembryonic antigen (CEA) in serum and ascites were recorded. The diagnostic values of FDG PET/CT, CEA and CA-125 levels in serum or ascites, and the combination of imaging plus tumor marker assessment were evaluated. Factors that were predictive of survival were also analyzed. A total of 177 patients were included. Malignant ascites was eventually diagnosed in 104 patients, and benign ascites was diagnosed in the remaining 73 patients. With the use of FDG PET/CT, 44 patients (42.3%) were found to have primary tumors. The sensitivity, specificity, and accuracy of FDG PET/CT were 92.3%, 83.6%, and 88.7%, respectively. CA-125 levels in serum and ascites showed much better sensitivity than did CEA levels, but they showed significantly lower specificity. If the combination of tumor markers and FDG PET/CT was analyzed, the sensitivity, specificity, and accuracy of tumor markers in serum were 96.6%, 78.1%, and 88.7%, and those of tumor markers in ascites were 97.7%, 80.0%, and 90.4%, respectively. Sex may be an important factor affecting survival time (hazard ratio, 0.471; p = 0.004), but age, CEA level, and FDG PET/CT findings could not predict survival. FDG PET/CT combined with assessment of tumor markers, especially CEA, increased the efficacy of diagnosis of ascites of unknown causes. Male sex conferred a poorer prognosis, whereas age, CEA level, and FDG uptake had no predictive significance in patients with malignant ascites.

Successful treatment of ovarian cancer with apatinib combined with chemotherapy

PubMed Central

Zhang, Mingzi; Tian, Zhongkai; Sun, Yehong

2017-01-01

Abstract Rationale: The standard treatment for ovarian cancer is chemotherapy with 2 drugs (taxanes and platinum drugs). However, the traditional combination of the 2 drugs has many adverse effects (AEs) and the cancer cells will quickly become resistant to the drugs. Apatinib is a small-molecule antiangiogenic agent which has shown promising therapeutic effects against diverse tumor types, but it still remains unknown whether apatinib has an antitumor effect in patients with ovarian cancer. Herein, we present a successfully treated case of ovarian cancer using chemotherapy and apatinib, in order to demonstrate the effectiveness of this new combined regimen in ovarian cancer. Patients concerns: A 51-year-old Chinese woman presented with ovarian cancer >4.5 years. The disease and the cancer antigen 125 (CA-125) had been controlled well by surgical treatment and following chemotherapy. However, the drugs could not control the disease anymore as the CA-125 level was significantly increasing. Diagnosis: Ovarian cancer. Interventions: The patient was treated with apatinib combined with epirubicin. Apatinib was administered orally, at an initial daily dose of 500 mg, and was then reduced to 250 mg qd after the appearance of intolerable hand–foot syndrome (HFS) and oral ulcer. Then, the oral ulcer disappeared and the HFS was controlled by dose adjustment, oral vitamin B6, and hand cream application. Outcomes: The CA-125 reverted to the normal value after treatment with the new regimen. Magnetic resonance imaging showed that the original tumor lesions had disappeared. Apatinib monotherapy as maintenance therapy was then used to successfully control the cancer with a complete response. Our study is the first, to our knowledge, to report the therapeutic effects of apatinib and epirubicin on ovarian cancer. Lessons: Apatinib combined with chemotherapy and apatinib monotherapy as maintenance therapy could be a new therapeutic strategy for ovarian cancer, especially adenocarcinomas. PMID:29137078

Endometrial metastasis of colorectal cancer with coincident endometrial adenocarcinoma.

PubMed

Colling, Richard; Lopes, Tito; Das, Nagiindra; Mathew, Joe

2010-11-05

Metastasis to the uterine corpus is uncommon and secondary colorectal tumours of the endometrium are rare. We describe a uterine tumour with components of both primary endometrial and metastatic colorectal carcinomata. In this case, a 72-year-old obese woman presented with a 2-week history of postmenopausal bleeding per vaginum and weight loss. She had an abdominoperineal resection 3 years previously for a Dukes stage B rectal carcinoma. A transvaginal ultrasonography showed a thickened endometrium. Histology immunophenotyping showed a CK7+, CK20+, CA125- and CEA+ colorectal metastasis (a profile consistent with her previous cancer) associated with a primary CK7+, CK20-, CA125+ and CEA- endometroid endometrial adenocarcinoma. We conclude this represents endometrial metastasis of colorectal carcinoma with coincident primary endometrial adenocarcinoma. We speculate as to whether the endometrial carcinoma arose de novo or was induced by the colorectal metastasis, or whether the primary endometrial tumour provided a fertile site for the colorectal metastasis.

Study of Aided Diagnosis of Hepatic Carcinoma Based on Artificial Neural Network Combined with Tumor Marker Group

NASA Astrophysics Data System (ADS)

Tan, Shanjuan; Feng, Feifei; Wu, Yongjun; Wu, Yiming

To develop a computer-aided diagnostic scheme by using an artificial neural network (ANN) combined with tumor markers for diagnosis of hepatic carcinoma (HCC) as a clinical assistant method. 140 serum samples (50 malignant, 40 benign and 50 normal) were analyzed for α-fetoprotein (AFP), carbohydrate antigen 125 (CA125), carcinoembryonic antigen (CEA), sialic acid (SA) and calcium (Ca). The five tumor marker values were then used as ANN inputs data. The result of ANN was compared with that of discriminant analysis by receiver operating characteristic (ROC) curve (AUC) analysis. The diagnostic accuracy of ANN and discriminant analysis among all samples of the test group was 95.5% and 79.3%, respectively. Analysis of multiple tumor markers based on ANN may be a better choice than the traditional statistical methods for differentiating HCC from benign or normal.

Silencing of CD40 in vivo reduces progression of experimental atherogenesis through an NF-κB/miR-125b axis and reveals new potential mediators in the pathogenesis of atherosclerosis.

PubMed

Hueso, Miguel; De Ramon, Laura; Navarro, Estanislao; Ripoll, Elia; Cruzado, Josep M; Grinyo, Josep M; Torras, Joan

2016-12-01

CD40/CD40L signaling exerts a critical role in the development of atherosclerosis, and microRNAs (miRNAs) are key regulators in vascular inflammation and plaque formation. In this work, we investigated mRNA/miRNA expression during progression of atherosclerotic lesions through CD40 silencing. We silenced CD40 with a specific siRNA in ApoE -/- mice and compared expression of mRNA/miRNA in ascending aorta with scrambled treated mice. siRNA-CD40 treated mice significantly reduced the extension and severity of atherosclerotic lesions, as well as the number of F4/80 + , galectin-3 + macrophages and NF-κB + cells in the intima. Genome-wide mRNA/miRNA profiling allowed the identification of transcripts, which were significantly upregulated during atherosclerosis; among them, miR-125b and miR-30a, Xpr1, a regulator of macrophage differentiation, Taf3, a core transcription factor and the NF-κB activator Ikkβ, whereas, the NF-κB inhibitor Ikbα was downregulated during disease progression. All those changes were reversed upon CD40 silencing. Interestingly, TAF3, XPR1 and miR-125b were also overexpressed in human atherosclerotic plaques. Murine Taf3 and Xpr1 were detected in the perivascular adipose tissue (PVAT), and Taf3 also in intimal foam cells. Finally, expression of miR-125b was regulated by the CD40-NF-κB signaling axis in RAW264.7 macrophages. CD40 silencing with a specific siRNA ameliorates progression of experimental atherosclerosis in ApoE -/- mice, and evidences a role for NF-κB, Taf3, Xpr1, and miR-125b in the pathogenesis of atherosclerosis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Morning Glory Syndrome with Carotid and Middle Cerebral Artery Vasculopathy.

PubMed

Nezzar, Hachemi; Mbekeani, Joyce N; Dalens, Helen

2015-12-01

To report a case of incidental asymptomatic atypical morning glory syndrome (MGS) with concomitant ipsilateral carotid and middle cerebral dysgenesis. A 6-year-old child was discovered to have incidental findings of MGS, with atypia. All visual functions were normal including vision and stereopsis. Neuroimaging revealed ipsilateral carotid and middle cerebral vascular narrowing without associated collateral vessels or cerebral ischemia commonly seen in Moyamoya disease. Subsequent annual examinations have been stable, without signs of progression. This case demonstrates disparity between structural aberrations and final visual and neurological function and reinforces the association between MGS and intracranial vascular disruption. Full ancillary ophthalmic and neuroimaging studies should be performed in all patients with MGS with interval reassessments, even when the patient is asymptomatic and functionally intact.

Localization and Distribution of 'Candidatus Liberibacter asiaticus' in Citrus and Periwinkle by Direct Tissue Blot Immuno Assay with an Anti-OmpA Polyclonal Antibody.

PubMed

Ding, Fang; Duan, Yongping; Paul, Cristina; Brlansky, Ronald H; Hartung, John S

2015-01-01

'Candidatus Liberibacter asiaticus' (CaLas), a non-cultured member of the α-proteobacteria, is the causal agent of citrus Huanglongbing (HLB). Due to the difficulties of in vitro culture, antibodies against CaLas have not been widely used in studies of this pathogen. We have used an anti-OmpA polyclonal antibody based direct tissue blot immunoassay to localize CaLas in different citrus tissues and in periwinkle leaves. In citrus petioles, CaLas was unevenly distributed in the phloem sieve tubes, and tended to colonize in phloem sieve tubes on the underside of petioles in preference to the upper side of petioles. Both the leaf abscission zone and the junction of the petiole and leaf midrib had fewer CaLas bacteria compared to the main portions of the petiole and the midribs. Colonies of CaLas in phloem sieve tubes were more frequently found in stems with symptomatic leaves than in stems with asymptomatic leaves with an uneven distribution pattern. In serial sections taken from the receptacle to the peduncle, more CaLas were observed in the peduncle sections adjacent to the stem. In seed, CaLas was located in the seed coat. Many fewer CaLas were found in the roots, as compared to the seeds and petioles when samples were collected from trees with obvious foliar symptoms. The direct tissue blot immuno assay was adapted to whole periwinkle leaves infected by CaLas. The pathogen was distributed throughout the lateral veins and the results were correlated with results of qPCR. Our data provide direct spatial and anatomical information for CaLas in planta. This simple and scalable method may facilitate the future research on the interaction of CaLas and host plant.

Up-regulation of angiotensin II receptors by in vitro differentiation of murine N1E-115 neuroblastoma cells.

PubMed

Reagan, L P; Ye, X H; Mir, R; DePalo, L R; Fluharty, S J

1990-12-01

In vitro differentiation of murine neuroblastoma N1E-115 cells induced by low serum (0.5%) and dimethyl sulfoxide (1.5%) increased the uptake of 45Ca2+ as well as basal and forskolin-stimulated adenylate cyclase activity. Associated with these biochemical indices of differentiation was an increase in the density of binding sites for the angiotensin II (Ang II) receptor agonist 125I-[Sar1]-Ang II and the antagonist 125I-[Sar1,Ile8]-Ang II (125I-SARILE). This up-regulation was apparent within 24 hr and was maximal at 72 hr. Other manipulations that independently increased intracellular cAMP or Ca2+ levels produced a qualitatively similar up-regulation of Ang II receptors. In vitro differentiation did not diminish the specificity of these receptors for Ang-II related peptides. Sarcosine-substituted Ang II receptor antagonists such as [Sar1,Gly8]-Ang II, [Sar1,Thr8]-Ang II, or SARILE itself competed for 125I-SARILE in a monophasic fashion, whereas the competition displayed by the agonists Ang II, angiotensin III, and Crinia-Ang II for 125I-SARILE-labeled sites was biphasic, consisting of distinct high and low affinity components. Moreover, in vitro differentiation predominantly increased the density of high affinity sites for angiotensin III and Crinia-Ang II, but the lower affinity site for Ang II, and in all three cases the majority of this increased binding was insensitive to guanine nucleotides. Collectively, these results demonstrate that the expression of Ang II receptors on neuron-like cells is regulated by the biochemical events accompanying differentiation and suggest that the biphasic nature of the binding of some angiotensin agonists may be indicative of multiple receptor subtypes.

Myxedema coma and cardiac ischemia in relation to thyroid hormone replacement therapy in a 38-year-old Japanese woman.

PubMed

Taguchi, Takafumi; Iwasaki, Yasumasa; Asaba, Koichi; Takao, Toshihiro; Hashimoto, Kozo

2007-12-01

Although thyroid hormone deficiency, either clinical or subclinical, is an established risk factor for cardiovascular disease, coronary ischemia in a premenopausal woman in her 30s is relatively rare. A 38-year-old woman was referred to our hospital with severe breathlessness and depressed consciousness. Physical examination found facial, abdominal, and pretibial edema; coarse hair, hoarse voice, and dry skin; engorged jugular veins; a distant heart sound; and reduced bilateral entry of air into the chest. Laboratory examinations revealed severe hypothyroidism, hyperlipidemia, and elevated serum levels of carcinoembryonic antigen (CEA) and carbohydrate antigen 125 (CA125). A computed tomography scan showed massive pleural and pericardial effusions. After 3 months of levothyroxine replacement therapy (initial dose: 12.5 microg/d; maintenance dose: 125 microg/d), all abnormal laboratory values associated with hypothyroidism returned to within normal ranges, with the exception of a transient and paradoxical rise in serum thyroid-stimulating hormone levels. However, 3 weeks after the initiation of therapy, the patient reported intermittent chest pains during the course of therapy, and a coronary artery angiogram revealed diffuse stenosis of all 3 branches. The patient underwent coronary artery bypass grafting, with subsequent improvement in coronary perfusion. Careful cardiovascular evaluation is recommended before the start of thyroid hormone replacement therapy. In addition, care should be taken in the interpretation of serum biomarkers of malignancy (eg, CEA, CA125) in patients with myxedema, as values may be elevated in a hypothyroid state. Long-standing hypothyroidism may be associated with severe coronary atherosclerosis, even in a relatively young, premenopausal woman. The potential adverse cardiovascular effects of thyroid hormone must be considered during replacement therapy, even in relatively young patients.

1,25-dihydroxyvitamin D3 receptor is upregulated in aortic smooth muscle cells during hypervitaminosis D.

PubMed

Rajasree, S; Umashankar, P R; Lal, A V; Sarma, P Sankara; Kartha, C C

2002-03-01

Several studies have demonstrated that excess of vitamin D3 is toxic particularly to vascular tissues. A notable pathological feature is arterial calcification. The nature of the toxic metabolite in hypervitaminosis D and the pathogenesis of arterial calcification are not clearly understood. The present study was undertaken to explore whether arterial calcification is a sequel of increased calcium uptake by arterial smooth muscle mediated by up regulation of vitamin D receptor in the cells in response to elevated circulating levels of vitamin D3 in serum. The experimental study was performed in 20 New Zealand white female rabbits aged 6 months. Animals in the test group were injected 10,000 IU of cholecalciferol intramuscularly twice a week for one month. Six control animals were given intra-muscular injections of plain cottonseed oil. Animals were sacrificed and aortas were examined for pathological lesions, 1,25-dihyroxyvitamin D3 (1,25(OH)2 D3) receptor levels and 45Ca uptake in smooth muscle cells. Serum samples collected at intervals were assayed for levels of 25-OH-D3 and calcium. The results showed that in animals given injections of cholecalciferol, serum levels of 25-OH-D3 were elevated. In four of these animals calcification and aneurysmal changes were seen in the aorta. Histological lesions comprised of fragmentation of elastic fibers as well as extensive loss of elastic layers. 1,25(OH)2 D3 receptor levels were up regulated and 45Ca uptake enhanced in aortas of animals which were given excessive vitamin D3. The evidences gathered suggest that excess vitamin D is arteriotoxic and that the vitamin induces arterial calcification through up regulation of 1,25(OH)2D3 receptor and increased calcium uptake in smooth muscle cells of the arteries.

Quantitative autoradiography of the binding sites for ( sup 125 I) iodoglyburide, a novel high-affinity ligand for ATP-sensitive potassium channels in rat brain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gehlert, D.R.; Gackenheimer, S.L.; Mais, D.E.

1991-05-01

We have developed a high specific activity ligand for localization of ATP-sensitive potassium channels in the brain. When brain sections were incubated with ({sup 125}I)iodoglyburide (N-(2-((((cyclohexylamino)carbonyl)amino)sulfonyl)ethyl)-5-{sup 125}I-2- methoxybenzamide), the ligand bound to a single site with a KD of 495 pM and a maximum binding site density of 176 fmol/mg of tissue. Glyburide was the most potent inhibitor of specific ({sup 125}I)iodoglyburide binding to rat forebrain sections whereas iodoglyburide and glipizide were slightly less potent. The binding was also sensitive to ATP which completely inhibited binding at concentrations of 10 mM. Autoradiographic localization of ({sup 125}I)iodoglyburide binding indicated a broadmore » distribution of the ATP-sensitive potassium channel in the brain. The highest levels of binding were seen in the globus pallidus and ventral pallidum followed by the septohippocampal nucleus, anterior pituitary, the CA2 and CA3 region of the hippocampus, ventral pallidum, the molecular layer of the cerebellum and substantia nigra zona reticulata. The hilus and dorsal subiculum of the hippocampus, molecular layer of the dentate gyrus, cerebral cortex, lateral olfactory tract nucleus, olfactory tubercle and the zona incerta contained relatively high levels of binding. A lower level of binding (approximately 3- to 4-fold) was found throughout the remainder of the brain. These results indicate that the ATP-sensitive potassium channel has a broad presence in the rat brain and that a few select brain regions are enriched in this subtype of neuronal potassium channels.« less

[A clinical study on the pathogenesis of lung cancer-related cerebral infarction].

PubMed

Xie, X R; Qin, C; Chen, L; Cheng, D B; Huang, J Y; Wei, X X; Yu, L X; Liang, Z J

2017-02-01

Objective: To explore the risk factors for lung cancer-related cerebral infarction. Methods: The hospitalized active lung cancer patients on anti-cancer therapy with no traditional stroke risk factors, who experienced an acute cerebral infarct in the First Affiliated Hospital of Guangxi Medical University from January 2005 to December 2015, were consecutively collected as the LCRS (lung cancer-related stroke) group. The active lung cancer patients without cerebral infarction hospitalized at the same peroid matched with the LCRS group for age and gender were collected as the LC (lung cancer) group. Clinical data from the two groups were analyzed. Results: A total of 139 LCRS patients and 139 LC patients were enrolled in the study, with 110 male and 29 female in each group, and there were no significant difference for the mean age between the LCRS group (52.1±10.4 years old ) and the LC group (52.1±10.1 years old). Two or more acute ischemic lesions of the brain were showed by MRI in most patients in the LCRS group (117 cases, 84.2%). Compared with the LC group, more patients in the LCRS group were found with adenocarcinoma, metastasis, elevated plasma D-dimer, CA125 and CA199 levels [88 cases (63.3%) vs 47 cases (33.8%); 98 cases (70.5%) vs 56 cases (40.3%); (468.38±291.37) μg/L vs (277.59±191.22) μg/L; (221.42±146.34) U/ml vs (106.84±69.97) U/ml; (254.68±185.84) U/ml vs (97.15±63.64) U/ml; with all P <0.001]. By logistic regression analysis of multiple factors, the elevated plasma D-dimer, CA125 and CA199 levels were showed to be independent risk factors for the cerebral infarction ( OR =1.003, 95% CI 1.001-1.004; OR =1.006, 95% CI 1.003-1.010; OR =1.011, 95% CI 1.007-1.015). Conclusions: The elevated plasma D-dimer, CA125 and CA199 levels are the risk factors for the lung cancer related cerebral infarction, which may lead to hypercoagulation and induce cerebral infarction eventually.

Comparison of LUMIPULSE(®) G1200 With Kryptor and Modular E170 for the Measurement of Seven Tumor Markers.

PubMed

Marlet, Julien; Bernard, Maguy

2016-01-01

Tumor marker measurements are becoming essential for prognosis and follow-up of patients in oncology. In this context, we aimed to compare a new analyzer, Lumipulse(®) G1200 (Fujirebio group, distributed in Europe by the Innogenetics group) with Kryptor(®) (Thermo Fisher Scientific B.R.A.H.M.S, Asnières, France) and Modular(®) Elecsys E170 (Roche Diagnostics, Meylan, France) for the measurement of seven tumor markers: PSA, AFP, CEA, CA 15-3, CA 125, CA 19-9, and Cyfra 21-1. A total of 471 serum samples from patients with elevated tumor markers and 100 serum from healthy patients were analyzed with Lumipulse(®) G1200 and either Kryptor(®) (for AFP) or Modular(®) (for the six other markers). The good precision of Lumipulse(®) G1200 assays was confirmed with CVs < 2.5% and < 5.0%, obtained, respectively, for within-run imprecision and intermediate imprecision (except for Cyfra 21-1: CV < 13%). For all markers, Lumipulse results were well correlated with Modular or Kryptor results (r ≥ 0.94). Concordance of results interpretation was > 95% and tumor marker kinetics were all similar. We confirmed the analytical performances of Lumipulse(®) tumor marker assays except for the CYFRA 21-1 assay for which performances were poor in this study. We noticed a few discrepancies for the CEA assay. Besides, values obtained for CA 19-9 were higher with Lumipulse leading to a bias (slope = 1.5). But for the four other tumor markers assays (PSA, AFP, CA 125, CA 15-3), the results were directly transferable between Lumipulse and Kryptor or Modular, thus facilitating an eventual substitution of one system by another. © 2014 Wiley Periodicals, Inc.

Temporal progression of 'Candidatus Liberibacter asiaticus' infection in citrus and acquisition efficiency by Diaphorina citri.

PubMed

Coletta-Filho, Helvecio D; Daugherty, Matthew P; Ferreira, Cléderson; Lopes, João R S

2014-04-01

Over the last decade, the plant disease huanglongbing (HLB) has emerged as a primary threat to citrus production worldwide. HLB is associated with infection by phloem-limited bacteria ('Candidatus Liberibacter' spp.) that are transmitted by the Asian citrus psyllid, Diaphorina citri. Transmission efficiency varies with vector-related aspects (e.g., developmental stage and feeding periods) but there is no information on the effects of host-pathogen interactions. Here, acquisition efficiency of 'Candidatus Liberibacter asiaticus' by D. citri was evaluated in relation to temporal progression of infection and pathogen titer in citrus. We graft inoculated sweet orange trees with 'Ca. L. asiaticus'; then, at different times after inoculation, we inspected plants for HLB symptoms, measured bacterial infection levels (i.e., titer or concentration) in plants, and measured acquisition by psyllid adults that were confined on the trees. Plant infection levels increased rapidly over time, saturating at uniformly high levels (≈10(8) copy number of 16S ribosomal DNA/g of plant tissue) near 200 days after inoculation-the same time at which all infected trees first showed disease symptoms. Pathogen acquisition by vectors was positively associated with plant infection level and time since inoculation, with acquisition occurring as early as the first measurement, at 60 days after inoculation. These results suggest that there is ample potential for psyllids to acquire the pathogen from trees during the asymptomatic phase of infection. If so, this could limit the effectiveness of tree rouging as a disease management tool and would likely explain the rapid spread observed for this disease in the field.

A small molecule polyamine oxidase inhibitor blocks androgen-induced oxidative stress and delays prostate cancer progression in the transgenic adenocarcinoma of the mouse prostate model.

PubMed

Basu, Hirak S; Thompson, Todd A; Church, Dawn R; Clower, Cynthia C; Mehraein-Ghomi, Farideh; Amlong, Corey A; Martin, Christopher T; Woster, Patrick M; Lindstrom, Mary J; Wilding, George

2009-10-01

High levels of reactive oxygen species (ROS) present in human prostate epithelia are an important etiologic factor in prostate cancer (CaP) occurrence, recurrence, and progression. Androgen induces ROS production in the prostate by a yet unknown mechanism. Here, to the best of our knowledge, we report for the first time that androgen induces an overexpression of spermidine/spermine N1-acetyltransferase, the rate-limiting enzyme in the polyamine oxidation pathway. As prostatic epithelia produce a large excess of polyamines, the androgen-induced polyamine oxidation that produces H2O2 could be a major reason for the high ROS levels in the prostate epithelia. A small molecule polyamine oxidase inhibitor N,N'-butanedienyl butanediamine (MDL 72,527 or CPC-200) effectively blocks androgen-induced ROS production in human CaP cells, as well as significantly delays CaP progression and death in animals developing spontaneous CaP. These data show that polyamine oxidation is not only a major pathway for ROS production in prostate, but inhibiting this pathway also successfully delays CaP progression.

Neuromedin B receptor activation causes tyrosine phosphorylation of p125FAK by a phospholipase C independent mechanism which requires p21rho and integrity of the actin cytoskeleton.

PubMed

Tsuda, T; Kusui, T; Jensen, R T

1997-12-23

Recent studies show that tyrosine phosphorylation by a number of neuropeptides may be an important intracellular pathway in mediating changes in cell function, particularly related to growth. Neuromedin B (NMB), a mammalian bombesin related peptide, functions through a distinct receptor, the neuromedin B receptor (NMB-R), of which little is known about its cellular basis of action. In the present study we explored the ability of NMB-R activation to cause tyrosine phosphorylation of focal adhesion kinase (p125(FAK)), an important substrate for tyrosine phosphorylation by other neuropeptides. NMB caused rapid increases in p125(FAK) phosphorylation which reached maximum at 2 min in both rat C6 glioblastoma cells which possess native NMB-Rs and rat neuromedin B receptor (rNMR-R) transfected BALB 3T3 cells. NMB had a half-maximal effect was at 0.4 nM and was 30-fold more potent than gastrin-releasing peptide (GRP). The stoichiometric relationships between increased p125(FAK) tyrosine phosphorylation and other cellular processes was similar in both C6 cells and rNMB-R transfected cells. TPA (1 microM) caused 45% and the calcium ionophore, A23187, 11% of maximal tyrosine phosphorylation of p125(FAK) seen with NMB. A23187 potentiated the effect of TPA. Pretreatment with the selective PKC inhibitor, GF109203X, inhibited TPA-induced p125(FAK) tyrosine phosphorylation, but it had no effect on the NMB stimulation. Pretreatment with thapsigargin completely inhibited NMB-stimulated increases in [Ca2+]i, but had no effect on NMB-stimulation of p125(FAK) phosphorylation either alone or with GF109203X. The tyrosine kinase inhibitor, tyrphostin A25, inhibited NMB-induced phosphorylation of p125(FAK) by 52%. However, tyrphostin A25 did not inhibit NMB-stimulated increases in [3H]inositol phosphates. Cytochalasin D, an agent which disrupts actin microfilaments, inhibited BN- and TPA-induced tyrosine phosphorylation of p125(FAK) completely. In contrast, colchicine, an agent which disrupts microtubules, had no effect. Pretreatment with Clostridium botulinum C3 exoenzyme which inactivates the small GTP-binding protein rho p21, also inhibited tyrosine phosphorylation of p125(FAK) by 55%. These results demonstrate that activation of NMB-R can cause rapid tyrosine phosphorylation of p125(FAK). NMB-induced tyrosine phosphorylation of p125(FAK) is independent of NMB-induced changes in [Ca2+]i or PKC. The integrity of the actin cytoskeleton but not of microtubules is necessary for NMB-stimulated phosphorylation of p125(FAK). The ras-related small GTP-binding protein rho p21 is at least partially involved in mediating NMB-induced tyrosine phosphorylation of p125(FAK). These results suggest that similar to some other neuropeptides, activation of this pathway may be an important mechanism in mediating cellular changes by this receptor such as growth.

Correlation of 125I-LSD autoradiographic labeling with serotonin voltage clamp responses in Aplysia neurons

DOE Office of Scientific and Technical Information (OSTI.GOV)

Evans, M.L.; Kadan, M.J.; Hartig, P.R.

Autoradiographic receptor binding studies using 125I-LSD (2-(125I)lysergic acid diethyamide) revealed intense labelling on the soma of a symmetrically located pair of cells in the abdominal ganglion of Aplysia californica. This binding was blocked by micromolar concentrations of serotonin and lower concentrations of the serotonergic antagonists, cyproheptadine and mianserin. Electrophysiological investigation of responses to serotonin of neurons in the left upper quadrant, where one of the labeled neurons is located, revealed a range of serotonin responses. Cells L3 and L6 have a K+ conductance increase in response to serotonin that is not blocked by cyproheptadine or mianserin. Cells L2 and L4more » have a biphasic response to serotonin: a Na+ conductance increase, which can be blocked by cyproheptadine and mianserin, followed by a voltage dependent Ca2+ conductance which is blocked by Co2+ but not the serotonergic antagonists. Cell L1, and its symmetrical pair, R1, have in addition to the Na+ and Ca2+ responses observed in L2 and L4, a Cl- conductance increase blocked by LSD, cyproheptadine and mianserin. LSD had little effect on the other responses. The authors conclude that the symmetrically located cells L1 and R1 have a Cl- channel linked to a cyproheptadine- and mianserin-sensitive serotonin receptor that is selectively labelled by 125I-LSD. This receptor has many properties in common with the mammalian serotonin 1C receptor.« less

Synthesis of calbindin-D28K during mineralization in human bone marrow stromal cells.

PubMed Central

Faucheux, C; Bareille, R; Amedee, J

1998-01-01

1alpha,25-Dihydroxyvitamin D3 [1,25(OH)2D3] is known to modulate Ca2+ metabolism in several cell types. Vitamin-D-dependent calcium binding proteins such as calbindin-D28K (28 kDa calcium binding proteins) have been shown to be regulated by 1,25(OH)2D3 but the mechanisms controlling calbindin synthesis are still poorly understood in human osteoblast cell culture models. The human bone marrow stromal cells (HBMSC) described in this paper developed a calcified matrix, expressed osteocalcin (OC), osteopontin (OP) and responded to 1,25(OH)2D3. The expression of vitamin D receptor mRNA was demonstrated by reverse transcription-PCR. Calbindin-D28K protein was identified only in cells arising from the sixth subculture, which exhibited a calcified matrix and all of the osteoblastic markers, e.g. OC and OP. It was demonstrated by dot-immunodetection using immunological probes, and by in situ hybridization using labelled cDNA probes. Moreover, vitamin D3 enhanced calbindin-D28K synthesis as well as OC synthesis and alkaline phosphatase activity. Uptake of 45Ca induced into the matrix by 1,25(OH)2D3 supports the hypothesis that the calcium-enriched matrix could trap calbindin-D proteins. In conclusion, the studies in vitro described in the present paper indicate, for the first time, a possible role of calbindin-D28K in mineralized matrix formation in HBMSC. PMID:9677345

Hypercalcemia in dogs with adenocarcinoma derived from apocrine glands of the anal sac. Biochemical and histomorphometric investigations.

PubMed

Meuten, D J; Segre, G V; Capen, C C; Kociba, G J; Voelkel, E F; Levine, L; Tashjian, A H; Chew, D J; Nagode, L A

1983-04-01

Hypercalcemia, hypercalciuria, and hyperphosphaturia were present in female dogs with adenocarcinomas derived from apocrine glands of the anal sac (CA). Remission of hypercalcemia accompanied tumor excision in all six dogs undergoing surgery, whereas tumor recurrence or growth of metastases was associated with a return of hypercalcemia. Preoperatively, the plasma concentrations of immunoreactive parathyroid hormone in all dogs were undetectable or in the low normal range. Plasma concentrations of 13,14-dihydro-15-keto-prostaglandin E2 (PGE2M) and serum 1,25-dihydroxyvitamin D were not significantly different from control dogs. Urinary cyclic AMP and hydroxyproline were increased in dogs with CA. No immunoreactive parathyroid hormone was detected in extracts from tumor tissue, and parathyroid glands from dogs with CA had ultrastructural characteristics of secretory inactivity. Lumbar vertebrae from hypercalcemic dogs had decreased trabecular bone volume and increased osteoclastic bone resorption compared with age-matched control dogs. After tumor excision, serum total calcium returned to the normal range, whereas immunoreactive parathyroid hormone increased 2- to 20-fold and 1,25-dihydroxyvitamin D decreased 2- to 8-fold. Postoperative hypocalcemia was not observed. These results indicate that CA produces a hypercalcemic factor other than immunoreactive parathyroid hormone or prostaglandin E2 that increases osteoclastic osteolysis distant from the tumor and results in hypercalcemia, hypercalciuria, and hyperphosphaturia.

Progression of external and internal carotid artery stenosis is associated with a higher risk of ischemic neurologic events in patients with asymptomatic carotid artery stenosis.

PubMed

Masoomi, Reza; Shah, Zubair; Dawn, Buddhadeb; Vamanan, Karthik; Nanjundappa, Aravinda; Gupta, Kamal

2017-10-01

A small percentage of patients with asymptomatic carotid artery stenosis (ACAS) who are on optimal medical management do go on to develop ischemic stroke or transient ischemic attacks (IS/TIA). Several diagnostic tools have been studied to identify those patients who are at increased risk. However, most of these diagnostic tools are not available for routine clinical use or are resource intensive. We performed a retrospective study to assess the incremental value of external carotid artery stenosis progression (ECASP) along with internal carotid artery stenosis progression (ICASP) in predicting risk of ipsilateral IS/TIA in a cohort of patients with ACAS. We conducted a retrospective analysis of patients with ACAS who had at least two serial duplex ultrasounds (DUS) at our center. A total of 356 patients (712 carotid arteries) were included in the study (mean age 74.7±9 years, 49.2% male) with a mean follow-up of 60.7±32.7 months. In univariate analysis, concurrent progression of ICA and ECA stenosis on the same side arteries was associated with a very significant increased risk of ipsilateral IS/TIA (14.7% vs 4.6%, p<0.001). Also, multivariable regression analysis showed that concurrent ECA/ICA progression was an independent predictor of IS/TIA (OR=3.6, 95% CI 1.64-7.8; p=0.001). ECASP along with ICASP is significantly associated with increased risk of ipsilateral IS/TIA and provides incremental risk stratification over that provided by ICASP alone. The ECA is routinely evaluated in clinical practice, and it could serve as an additional marker for identifying higher risk patients with ACAS.

[Severe asymptomatic carotid stenosis: a neurological perspective].

PubMed

de la Cruz-Cosme, Carlos; Segura, Tomás

2012-09-01

Asymptomatic carotid stenosis is a relatively frequent pathology, although when considering the possibility of managing it surgically, there is still an important amount of disagreement concerning the criteria to be taken into account. This study conducts a broad examination of the condition, from its concept and epidemiology to the studies that triggered the boom in its surgical treatment during the nineties. The research also reviews the tools available for a better selection of cases that could potentially benefit most from surgery, the presence of silent brain lesions, the severity of the stenosis, its progression, the characteristics of the plaque, colaterality and vasoreactivity studies, the detection of micro-emboli, the presence of risk factors independently associated to the symptomatic conversion of the stenosis, and other elements that have recently been reported either clinically or experimentally. Finally, the article outlines the current state of the surgical technique and the advances being made in its pharmacological treatment. This review is not intended to be a set of clinical practice guidelines, but to offer a global integrating overview of the management of high-grade asymptomatic carotid stenosis.

Muir-Torre Syndrome

MedlinePlus

... inner lining of the uterus CA-125 blood test to look for a protein found to be elevated in the blood of some women with ovarian cancer Screening options may change over time as new technologies are developed and more is learned about Muir- ...

Peripheral and central immune cell reservoirs in tissues from asymptomatic cats chronically infected with feline immunodeficiency virus.

PubMed

Eckstrand, C D; Sparger, E E; Pitt, K A; Murphy, B G

2017-01-01

Feline immunodeficiency virus (FIV) infection in cats results in life-long viral persistence and progressive immunopathology. We have previously described a cohort of experimentally infected cats demonstrating a progressive decline of peripheral blood CD4+ T-cell over six years in the face of apparent peripheral viral latency. More recently we reported findings from this same cohort that revealed popliteal lymph node tissue as sites for ongoing viral replication suggesting that tissue reservoirs are important in FIV immunopathogenesis during the late asymptomatic phase of infection. Results reported herein characterize important tissue reservoirs of active viral replication during the late asymptomatic phase by examining biopsied specimens of spleen, mesenteric lymph node (MLN), and intestine from FIV-infected and uninfected control cats. Peripheral blood collected coincident with harvest of tissues demonstrated severe CD4+ T-cell depletion, undetectable plasma viral gag RNA and rarely detectable peripheral blood mononuclear cell (PBMC)-associated viral RNA (vRNA) by real-time PCR. However, vRNA was detectable in all three tissue sites from three of four FIV-infected cats despite the absence of detectable vRNA in plasma. A novel in situ hybridization assay identified B cell lymphoid follicular domains as microanatomical foci of ongoing FIV replication. Additionally, we demonstrated that CD4+ leukocyte depletion in tissues, and CD4+ and CD21+ leukocytes as important cellular reservoirs of ongoing replication. These findings revealed that tissue reservoirs support foci of ongoing viral replication, in spite of highly restricted viral replication in blood. Lentiviral eradication strategies will need address tissue viral reservoirs.

Peripheral and central immune cell reservoirs in tissues from asymptomatic cats chronically infected with feline immunodeficiency virus

PubMed Central

Sparger, E. E.; Pitt, K. A.

2017-01-01

Feline immunodeficiency virus (FIV) infection in cats results in life-long viral persistence and progressive immunopathology. We have previously described a cohort of experimentally infected cats demonstrating a progressive decline of peripheral blood CD4+ T-cell over six years in the face of apparent peripheral viral latency. More recently we reported findings from this same cohort that revealed popliteal lymph node tissue as sites for ongoing viral replication suggesting that tissue reservoirs are important in FIV immunopathogenesis during the late asymptomatic phase of infection. Results reported herein characterize important tissue reservoirs of active viral replication during the late asymptomatic phase by examining biopsied specimens of spleen, mesenteric lymph node (MLN), and intestine from FIV-infected and uninfected control cats. Peripheral blood collected coincident with harvest of tissues demonstrated severe CD4+ T-cell depletion, undetectable plasma viral gag RNA and rarely detectable peripheral blood mononuclear cell (PBMC)-associated viral RNA (vRNA) by real-time PCR. However, vRNA was detectable in all three tissue sites from three of four FIV-infected cats despite the absence of detectable vRNA in plasma. A novel in situ hybridization assay identified B cell lymphoid follicular domains as microanatomical foci of ongoing FIV replication. Additionally, we demonstrated that CD4+ leukocyte depletion in tissues, and CD4+ and CD21+ leukocytes as important cellular reservoirs of ongoing replication. These findings revealed that tissue reservoirs support foci of ongoing viral replication, in spite of highly restricted viral replication in blood. Lentiviral eradication strategies will need address tissue viral reservoirs. PMID:28384338

326 Lung Age/Chronological Age Index as Indicator of Clinical Improvement or Severity in Asthma Patients

PubMed Central

Castrejon-Vázquez, Isabel; Vargas, Maria Eugenia; Sabido, Raúl Cicero; Tapía, Jorge Galicia

2012-01-01

Background Spirometry is a very useful clinical test to evaluate pulmonary function in asthma. However pulmonary function could be affected by the sex, time of clinical evolution, lung age (LA) and chronological age (CA). The aim of this study was to evaluate LA/CA as index of clinical improvement or severity in asthma patients. Methods The tenets of the Declaration of Helsinki were followed, and all patients gave their informed consent to participate in this study. Asthma severity was evaluated according with GINA classification. Spirometry was performed at the beginning of this study, at 46 days, 96 days, 192 days and after 8 months. Statistical analysis was performed using t test, 2-way ANOVA test, correlation and multiple regression models as well as ROC curves were also performed, a P < 0.05 was considered as significant. Results 70 asthma patients were included (22 male and 48 female), mean CA was 35-years old; mean LA was 48-years with a LA/CA index = 1.4, time of clinical evolution was 13 years. A LA/CA index = 1 (range 0.5 to 0.9) was observed in asymptomatic patients. LA/CA index over 1 were related with airway inflammation, and a LA/CA index more than 2 correlated with GINA step 3. Interestingly when we analyzed CA and LA, we observed that in female group more than 10 years of difference between CA and LA, (GINA Step2 and 3); while in male we observed (GINA Step1, Step2 and Step3). LA/CA index ≤ 1 was considered as normal. Conclusions LA/CA index is a good as clinical indicator of clinical improvement or severity in asthma patients in with excellent correlation of pulmonary function and age.

Growth and maturity status of elite British junior tennis players.

PubMed

Myburgh, Gillian K; Cumming, Sean P; Coelho E Silva, Manuel; Cooke, Karl; Malina, Robert M

2016-10-01

Growth and maturation impact the selection, development and progression of youth athletes. Individual differences in the growth and maturity may afford a performance advantage, clouding coaches and practitioners' perceptions regarding current ability and future potential. This may result in the exclusion of talented, yet less physically gifted athletes. Participants were 91 male (n = 47) and female (n = 44) elite British Junior tennis players, 8-17 years of age (12.5 ± 1.9 years). Height and body mass were measured and compared to growth charts; hand-wrist radiographs were taken. Skeletal age (SA) was estimated with the Fels method and contrasted to chronological age (CA). Mean height and body mass of individual players ranged between the 50th and 90th centiles for age and sex. Females were advanced in SA relative to CA (0.3-0.89 years.) from 8 years. Males were average to delayed in maturation from 8 to 12 years, but advanced in SA from 14 to 16 years (0.75-1.23 years). Individual differences in growth and maturation appear to contribute towards the selection of elite junior tennis players, with a bias towards males and females who are advanced in maturation and comparatively tall and heavy for their age. This has important implications for talent identification and development.

Natural antibody response to Plasmodium falciparum merozoite antigens MSP5, MSP9 and EBA175 is associated to clinical protection in the Brazilian Amazon

PubMed Central

2013-01-01

Background Antibodies have an essential role in the acquired immune response against blood stage P. falciparum infection. Although several antigens have been identified as important antibody targets, it is still elusive which antigens have to be recognized for clinical protection. Herein, we analyzed antibodies from plasmas from symptomatic or asymptomatic individuals living in the same geographic area in the Western Amazon, measuring their recognition of multiple merozoite antigens. Methods Specific fragments of genes encoding merozoite proteins AMA1 and members of MSP and EBL families from circulating P. falciparum field isolates present in asymptomatic and symptomatic patients were amplified by PCR. After cloning and expression of different versions of the antigens as recombinant GST-fusion peptides, we tested the reactivity of patients’ plasmas by ELISA and the presence of IgG subclasses in the most reactive plasmas. Results 11 out of 24 recombinant antigens were recognized by plasmas from either symptomatic or asymptomatic infections. Antibodies to MSP9 (X2DF=1 = 9.26/p = 0.0047) and MSP5 (X2DF=1 = 8.29/p = 0.0069) were more prevalent in asymptomatic individuals whereas the opposite was observed for MSP1 block 2-MAD20 (X2DF=1 = 6.41/p = 0.0206, Fisher’s exact test). Plasmas from asymptomatic individuals reacted more intensely against MSP4 (U = 210.5, p < 0.03), MSP5 (U = 212, p < 0.004), MSP9 (U = 189.5, p < 0.002) and EBA175 (U = 197, p < 0.014, Mann-Whitney’s U test). IgG1 and IgG3 were predominant for all antigens, but some patients also presented with IgG2 and IgG4. The recognition of MSP5 (OR = 0.112, IC95% = 0.021-0.585) and MSP9 (OR = 0.125, IC95% = 0.030-0.529, cross tab analysis) predicted 8.9 and 8 times less chances, respectively, to present symptoms. Higher antibody levels against MSP5 and EBA175 were associated by odds ratios of 9.4 (IC95% = 1.29-69.25) and 5.7 (IC95% = 1.12-29.62, logistic regression), respectively, with an asymptomatic status. Conclusions Merozoite antigens were targets of cytophilic antibodies and antibodies against MSP5, MSP9 and EBA175 were independently associated with decreased symptoms. PMID:24373342

Medical therapy and intervention do not improve uncomplicated isolated mesenteric artery dissection outcomes over observation alone.

PubMed

Loeffler, Jacob W; Obara, Hideaki; Fujimura, Naoki; Bove, Paul; Newton, Daniel H; Zettervall, Sara L; van Petersen, Andre S; Geelkerken, Robert H; Charlton-Ouw, Kristofer M; Shalhub, Sherene; Singh, Niten; Roussel, Arnaud; Glebova, Natalia O; Harlander-Locke, Michael P; Gasper, Warren J; Humphries, Misty D; Lawrence, Peter F

2017-07-01

Isolated dissection of the mesenteric vessels is rare but increasingly recognized. This study aimed to evaluate patient characteristics, primary treatment, and subsequent outcomes of mesenteric dissection using multi-institutional data. All patients at participant hospitals between January 2003 and December 2015 with dissection of the celiac artery (or its branches) or dissection of the superior mesenteric artery (SMA) were included. Patients with an aortic dissection were excluded. Demographic, treatment, and follow-up data were collected. The primary outcomes included late vessel thrombosis (LVT) and aneurysmal degeneration (AD). Twelve institutions identified 227 patients (220 with complete treatment records) with a mean age of 55 ± 12.5 years. Median time to last follow up was 15 months (interquartile range, 3.8-32). Most patients were men (82% vs 18% women) and symptomatic at presentation (162 vs 65 asymptomatic). Isolated SMA dissection was more common than celiac artery dissection (n = 158 and 81, respectively). Concomitant dissection of both arteries was rare (n = 12). The mean dissection length was significantly longer in symptomatic patients than in asymptomatic patients in both the celiac artery (27 vs 18 mm; P = .01) and the SMA (64 vs 40 mm; P < .001). Primary treatment was medical in 146 patients with oral anticoagulation or antiplatelet therapy (n = 76 and 70, respectively), whereas 56 patients were observed. LVT occurred in six patients, and 16 patients developed AD (3% and 8%, respectively). For symptomatic patients without evidence of ischemia (n = 134), there was no difference in occurrence of LVT with medical therapy compared with observation alone (9% vs 0%; P = .35). No asymptomatic patient (n = 64) had an episode of LVT at 5 years. AD rates did not differ among symptomatic patients without ischemia treated with medical therapy or observed (9% vs 5%; P = .95). Surgical or endovascular intervention was performed in 18 patients (3 ischemia, 13 pain, 1 AD, 1 asymptomatic). Excluding the patients treated for ischemia, there was no difference in LVT with surgical intervention vs medical management (one vs five; P = .57). Asymptomatic patients with isolated mesenteric artery dissection may be observed and followed up with intermittent imaging. Symptomatic patients tend to have longer dissections than asymptomatic patients. Symptomatic isolated mesenteric artery dissection without evidence of ischemia does not require anticoagulation and may be treated with antiplatelet therapy or observation alone. Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Exercise testing in asymptomatic severe aortic stenosis.

PubMed

Magne, Julien; Lancellotti, Patrizio; Piérard, Luc A

2014-02-01

The management and the clinical decision making in asymptomatic patients with aortic stenosis are challenging. An "aggressive" management, including early aortic valve replacement, is debated in these patients. However, the optimal timing for surgery remains controversial due to the lack of prospective data on the determinants of aortic stenosis progression, multicenter studies on risk stratification, and randomized studies on patient management. Exercise stress testing with or without imaging is strictly contraindicated in symptomatic patients with severe aortic stenosis. Exercise stress test is now recommended by current guidelines in asymptomatic patients and may provide incremental prognostic value. Indeed, the development of symptoms during exercise or an abnormal blood pressure response are associated with poor outcome and should be considered as an indication for surgery, as suggested by the most recently updated European Society of Cardiology 2012 guidelines. Exercise stress echocardiography may also improve the risk stratification and identify asymptomatic patients at higher risk of a cardiac event. When the test is combined with imaging, echocardiography during exercise should be recommended rather than post-exercise echocardiography. During exercise, an increase >18 to 20 mm Hg in mean pressure gradient, absence of improvement in left ventricular ejection fraction (i.e., absence of contractile reserve), and/or a systolic pulmonary arterial pressure >60 mm Hg (i.e., exercise pulmonary hypertension) are suggestive signs of advanced stages of the disease and impaired prognosis. Hence, exercise stress test may identify resting asymptomatic patients who develop exercise abnormalities and in whom surgery is recommended according to current guidelines. Exercise stress echocardiography may further unmask a subset of asymptomatic patients (i.e., without exercise stress test abnormalities) who are at high risk of reduced cardiac event free survival. In these patients, early surgery could be beneficial, whereas regular follow-up seems more appropriate in patients without echocardiographic abnormalities during exercise. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

23. POWER ROOM INTERIOR, DETAIL OF FAIRBANKSMORSE DIESEL ENGINE, DIRECTLY ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

23. POWER ROOM INTERIOR, DETAIL OF FAIRBANKS-MORSE DIESEL ENGINE, DIRECTLY CONNECTED TO FAIRBANKS-MORSE 30 KW DC GENERATOR, 125 VOLTS, 240 AMPS, 800 RPM. INSTALLED 1930. - Death Valley Ranch, Power House, Death Valley Junction, Inyo County, CA

Asymptomatic cardiopulmonary changes caused by adenoid hypertrophy.

PubMed

Abdel-Aziz, Mosaad

2011-07-01

Adenoid hypertrophy is the most common cause of pediatric upper airway obstruction, and it can lead to cardiopulmonary complications such as pulmonary hypertension, cor pulmonale, and even heart failure. The aim of this study was to detect the asymptomatic cardiopulmonary changes that could happen in children with adenoid hypertrophy.Eighty children with adenoid hypertrophy were included in this study. Chest x-ray was used to assess the cardiothoracic ratio, whereas echocardiography was used for measuring the pulmonary arterial pressures, right ventricular diastolic filling parameters, and right ventricular end-diastolic diameters. All patients underwent adenoidectomy with or without tonsillectomy, and they were subjected again to echocardiographic assessment 6 months after the operation. No patient showed an increase in the cardiothoracic ratio on x-ray. Preoperative echocardiography showed an increase in pulmonary artery pressure (22.7 [SD, 3.8] mm Hg), a decrease in right ventricular diastolic filling parameters (E/A = 1.03 [SD, 0.17]), and an increase in right ventricular end-diastolic diameters (1.89 [SD, 0.19] cm). Postoperatively, pulmonary artery pressure decreased to 17.2 [SD, 2.1] mm Hg, right ventricular diastolic filling (E/A) increased to 1.25 [SD, 0.11], and right ventricular end-diastolic diameters decreased to 1.68 [SD, 0.12] cm. The comparison between preoperative and postoperative results for each individual parameter was statistically significant. Clinically asymptomatic cardiopulmonary changes due to adenoid hypertrophy are not rare. Early diagnosis and treatment of upper airway obstruction can prevent these serious complications. Echocardiographic examination should be recommended for these patients as a part of preoperative preparation to avoid anesthetic complications.

Evidence for Extending the Duration of Chemoprophylaxis following Free Flap Harvest from the Lower Extremity: Prospective Screening for Deep Venous Thrombosis.

PubMed

Rau, Aline S; Harry, Brian L; Leem, Ted H; Song, John I; Deleyiannis, Frederic W-B

2016-08-01

The purpose of this study was to investigate the incidence of symptomatic and asymptomatic deep venous thrombosis in patients undergoing harvest of a free flap from the lower extremity who were receiving standard chemoprophylaxis while hospitalized. A retrospective review of 65 consecutive patients undergoing surgery between 2011 and 2013 was performed to determine the incidence of symptomatic deep venous thrombosis. These patients were screened for deep venous thrombosis based on development of symptoms. Prospective evaluation of a similar consecutive population of 37 patients between 2014 and 2015 was then performed to determine the incidence of asymptomatic deep venous thrombosis. These patients underwent routine duplex ultrasonography of both legs at postoperative weeks 1 and 4. Symptomatic deep venous thrombosis occurred in 2.9 percent of all patients. In the prospective cohort, 8.1 percent of the patients were found to have an acute deep venous thrombosis by postoperative week 1. At postoperative week 4, 16.7 percent of the patients developed a new, acute deep venous thrombosis. The estimated costs of screening and treating deep venous thrombosis in the retrospective group and the prospective group were $222 and $2259, respectively. The cost of routine chemoprophylaxis without duplex screening for an additional 14 days after discharge was $125 per patient. The rate of asymptomatic deep venous thrombosis may be much higher than previously appreciated in this population of very high-risk patients, especially during the 2 weeks after discharge. Extending the duration of chemoprophylaxis to 4 weeks after surgery may be warranted. Therapeutic, IV.

Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phase 3 randomised controlled trial.

PubMed

Cristofanilli, Massimo; Turner, Nicholas C; Bondarenko, Igor; Ro, Jungsil; Im, Seock-Ah; Masuda, Norikazu; Colleoni, Marco; DeMichele, Angela; Loi, Sherene; Verma, Sunil; Iwata, Hiroji; Harbeck, Nadia; Zhang, Ke; Theall, Kathy Puyana; Jiang, Yuqiu; Bartlett, Cynthia Huang; Koehler, Maria; Slamon, Dennis

2016-04-01

In the PALOMA-3 study, the combination of the CDK4 and CDK6 inhibitor palbociclib and fulvestrant was associated with significant improvements in progression-free survival compared with fulvestrant plus placebo in patients with metastatic breast cancer. Identification of patients most suitable for the addition of palbociclib to endocrine therapy after tumour recurrence is crucial for treatment optimisation in metastatic breast cancer. We aimed to confirm our earlier findings with this extended follow-up and show our results for subgroup and biomarker analyses. In this multicentre, double-blind, randomised phase 3 study, women aged 18 years or older with hormone-receptor-positive, HER2-negative metastatic breast cancer that had progressed on previous endocrine therapy were stratified by sensitivity to previous hormonal therapy, menopausal status, and presence of visceral metastasis at 144 centres in 17 countries. Eligible patients-ie, any menopausal status, Eastern Cooperative Oncology Group performance status 0-1, measurable disease or bone disease only, and disease relapse or progression after previous endocrine therapy for advanced disease during treatment or within 12 months of completion of adjuvant therapy-were randomly assigned (2:1) via a centralised interactive web-based and voice-based randomisation system to receive oral palbociclib (125 mg daily for 3 weeks followed by a week off over 28-day cycles) plus 500 mg fulvestrant (intramuscular injection on days 1 and 15 of cycle 1; then on day 1 of subsequent 28-day cycles) or placebo plus fulvestrant. The primary endpoint was investigator-assessed progression-free survival. Analysis was by intention to treat. We also assessed endocrine therapy resistance by clinical parameters, quantitative hormone-receptor expression, and tumour PIK3CA mutational status in circulating DNA at baseline. This study is registered with ClinicalTrials.gov, NCT01942135. Between Oct 7, 2013, and Aug 26, 2014, 521 patients were randomly assigned, 347 to fulvestrant plus palbociclib and 174 to fulvestrant plus placebo. Study enrolment is closed and overall survival follow-up is in progress. By March 16, 2015, 259 progression-free-survival events had occurred (145 in the fulvestrant plus palbociclib group and 114 in the fulvestrant plus placebo group); median follow-up was 8·9 months (IQR 8·7-9·2). Median progression-free survival was 9·5 months (95% CI 9·2-11·0) in the fulvestrant plus palbociclib group and 4·6 months (3·5-5·6) in the fulvestrant plus placebo group (hazard ratio 0·46, 95% CI 0·36-0·59, p<0·0001). Grade 3 or 4 adverse events occurred in 251 (73%) of 345 patients in the fulvestrant plus palbociclib group and 38 (22%) of 172 patients in the fulvestrant plus placebo group. The most common grade 3 or 4 adverse events were neutropenia (223 [65%] in the fulvestrant plus palbociclib group and one [1%] in the fulvestrant plus placebo group), anaemia (ten [3%] and three [2%]), and leucopenia (95 [28%] and two [1%]). Serious adverse events (all causalities) occurred in 44 patients (13%) of 345 in the fulvestrant plus palbociclib group and 30 (17%) of 172 patients in the fulvestrant plus placebo group. PIK3CA mutation was detected in the plasma DNA of 129 (33%) of 395 patients for whom these data were available. Neither PIK3CA status nor hormone-receptor expression level significantly affected treatment response. Fulvestrant plus palbociclib was associated with significant and consistent improvement in progression-free survival compared with fulvestrant plus placebo, irrespective of the degree of endocrine resistance, hormone-receptor expression level, and PIK3CA mutational status. The combination could be considered as a therapeutic option for patients with recurrent hormone-receptor-positive, HER2-negative metastatic breast cancer that has progressed on previous endocrine therapy. Pfizer. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Frequency of diabetes mellitus and hyperglycemia in chagasic and non-chagasic women].

PubMed

dos Santos, V M; da Cunha, S F; Teixeira, V de P; Monteiro, J P; dos Santos, J A; dos Santos, T A; dos Santos, L A; da Cunha, D F

1999-01-01

Medical records of > or = 40 years old female seen at University Hospital from June/93 to July/95 were submitted to a cross-sectional study. According to Chagas' disease tests, patients were divided into chagasic (n = 362) and controls (n = 285). Diabetes mellitus was defined on the basis of two fasting blood glucose levels > or = 140 mg/dl and hyperglycemia as fasting blood glucose > 110 mg/dl. Chagasic patients were divided into groups with the cardiac form of the disease (n = 179), with megas (n = 58), and asymptomatic (n = 125). Groups were compared by the chi 2 test, analysis of variance, Student's "t" test, and Kruskal-Wallis and Mann-Whitney tests. A significant difference was assumed when p < 0.05. Chagasic and control groups were matched for age, white color and body mass index. Diabetes mellitus was more prevalent in patients with the cardiac form of Chagas' disease than in controls, or patients with the megas or the asymptomatic form (15.1%, 7.4%, 7.4%, and 5.6%, respectively); the same was observed for hyperglycemia (37.4%, 26.7%, 25.9%, 27.2%), in agreement with the hypothesis that the reduced parasympathetic activity caused by Trypanosoma cruzi leads to relative sympathetic hyperactivity.

[Comparative study of diagnostic methods for visceral leishmaniasis in dogs from Ilha Solteira, SP].

PubMed

de Assis, Juliana; de Queiroz, Nina Marí Gual Pimenta; da Silveira, Rita de Cássia Vieira; Nunes, Cáris Maroni; Oliveira, Trícia Maria Ferreira de Sousa; Junior, Antonio Carlos Faconti de Noronha; Neves, Maria Francisca; Machado, Rosangela Zacarias; Buzetti, Wilma Aparecida Starke

2010-01-01

The purpose of the present work was a comparative study of diagnostic methods for Canine Visceral Leishmaniasis (CVL) using serological methods, enzyme-linked immunosorbent assay (ELISA) and indirect fluorescent antibody test (IFAT), histochemical (HE) and immunohistochemical (IMHC) tests using spleen, lymph node and liver canine tissues. In addition, Polymerase Chain Reaction (PCR) was done in blood and in tissues in order to compare and confirm no conclusive and negative diagnosis by the methods above. For this study, 34 dogs were divided according to clinical signs in asymptomatic, oligosymptomatic and polisymptomatic Leishmania-infected dogs euthanized by Zoonotic Disease Control Center (CCZ) from Ilha Solteira, SP, Brazil. The positivism indexes of ELISA, IMHC, IFAT and HE were 65.0, 62.0, 56.0 and 56.0%, respectively with the highest numbers of positive dogs in polisymptomatic (92.0%) followed by oligosymptomatic (57.0%) and asymptomatic dogs (12.5%). Furthermore, PCR confirmed the positive results and detected DNA in tissues from 100% of negative dogs and 89.0% suspects raising the animal positivism index up to 97.0%. In conclusion, PCR was the most sensitive and a valuable method for a definitive CVL diagnosis.

Crystal structures of Boro-AFm and sBoro-AFt phases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Champenois, Jean-Baptiste; Mesbah, Adel; Clermont Universite, ENSCCF, Institut de Chimie de Clermont-Ferrand, BP 10448, F-63000 Clermont-Ferrand

2012-10-15

Crystal structures of boron-containing AFm (B-AFm) and AFt (B-AFt) phases have been solved ab-initio and refined from X-ray powder diffraction. {sup 11}B NMR and Raman spectroscopies confirm the boron local environment in both compounds: three-fold coordinated in B-AFm corresponding to HBO{sub 3}{sup 2-} species, and four-fold coordinated in B-AFt corresponding to B (OH){sub 4}{sup -} species. B-AFm crystallizes in the rhombohedral R3{sup Macron }c space group and has the 3CaO{center_dot}Al{sub 2}O{sub 3}{center_dot}CaHBO{sub 3}{center_dot}12H{sub 2}O (4CaO{center_dot}Al{sub 2}O{sub 3}{center_dot}1/2B{sub 2}O{sub 3}{center_dot}12.5H{sub 2}O, C{sub 4}AB{sub 1/2}H{sub 12.5}) general formulae with planar trigonal HBO{sub 3}{sup 2-} anions weakly bonded at the centre of themore » interlayer region. One HBO{sub 3}{sup 2-} anion is statistically distributed with two weakly bonded water molecules on the same crystallographic site. B-AFt crystallizes in the trigonal P3cl space group and has the 3CaO{center_dot}Al{sub 2}O{sub 3}{center_dot}Ca(OH){sub 2}{center_dot}2Ca(B (OH){sub 4}){sub 2}{center_dot}24H{sub 2}O (6CaO{center_dot}Al{sub 2}O{sub 3}{center_dot}2B{sub 2}O{sub 3}{center_dot}33H{sub 2}O, C{sub 6}AB{sub 2}H{sub 33}) general formulae with tetrahedral B (OH){sub 4}{sup -} anions located in the channel region of the structure. All tetrahedral anions are oriented in a unique direction, leading to a hexagonal c lattice parameter about half that of ettringite.« less

A Thapsigargin-Resistant Intracellular Calcium Sequestering Compartment in Rat Brain

DTIC Science & Technology

2000-03-31

touted as inhibitors of the PMCAs, but their effects have yet to be thoroughly examined on all P-type ATPases [23, 125]. SERCAs: a family ofP·type ATPases... effective in reducing the sensitivity to TG by 1aOO-fold [151]. The potent, seledive blockade of Ca2+ accumulation in the ER by TG has made it possible...accumulation while the calcium ionophore A23187 is 100%) effective [140]. Thus, 10-150/0 of net Ca2+ uptake into brain microsomal compartments is

Internal Administrative Control: Its Applicability to the Marine Corps.

DTIC Science & Technology

1984-06-01

activities and units, or ly regulatory and sulervisozy agencies. Ziautz contends that "internal auditing is a very effective source oil mcnitcring in many...to ccapare the perfcrmance cf a functional area with the standards set forth in the SOE, it should be determined if the SCP is 100 currezt and complies...SC 2990’ COMCABWEST El Toro CA 92709 CG Fourth MAW New Orleans LA 70146 CG MCB Camp Lejeune NC 28542 CG MCAGCC Twentynine Palms CA 92278 125

Calcium Signals: The Lead Currency of Plant Information Processing

PubMed Central

Kudla, Jörg; Batistič, Oliver; Hashimoto, Kenji

2010-01-01

Ca2+ signals are core transducers and regulators in many adaptation and developmental processes of plants. Ca2+ signals are represented by stimulus-specific signatures that result from the concerted action of channels, pumps, and carriers that shape temporally and spatially defined Ca2+ elevations. Cellular Ca2+ signals are decoded and transmitted by a toolkit of Ca2+ binding proteins that relay this information into downstream responses. Major transduction routes of Ca2+ signaling involve Ca2+-regulated kinases mediating phosphorylation events that orchestrate downstream responses or comprise regulation of gene expression via Ca2+-regulated transcription factors and Ca2+-responsive promoter elements. Here, we review some of the remarkable progress that has been made in recent years, especially in identifying critical components functioning in Ca2+ signal transduction, both at the single-cell and multicellular level. Despite impressive progress in our understanding of the processing of Ca2+ signals during the past years, the elucidation of the exact mechanistic principles that underlie the specific recognition and conversion of the cellular Ca2+ currency into defined changes in protein–protein interaction, protein phosphorylation, and gene expression and thereby establish the specificity in stimulus response coupling remain to be explored. PMID:20354197

Red nodule on the face with “spontaneous” regression*

PubMed Central

Sanchis-Sánchez, Celia; Santos-Alarcón, Sergio; Benavente-Villegas, Felipe César; Mateu-Puchades, Almudena; Soriano-Sarrió, María Pilar

2017-01-01

Pseudolymphomatous folliculitis is a rare entity included among the cutaneous pseudolymphomas. A 32-year-old man, with an unremarkable medical history, presented with a two-month history of an asymptomatic solitary nodule on his left cheek. Histopathological examination demonstrated a dense nodular and diffuse dermal lymphocytic infiltrate with numerous histiocytes and dendritic cells that surrounded hypertrophic hair follicles. Pseudolymphomatous folliculitis commonly presents in the fourth decade of life, with no sex predominance, as an asymptomatic, rapidly growing and solitary red dome-shaped nodule on the face. It has a benign clinical course as the lesions usually resolve with surgical excision or regress spontaneously after incisional biopsy. Although there is no report of pseudolymphomatous folliculitis progressing into lymphoma in the literature, follow-up of these patients is recommended. PMID:29267472

A Small Molecule Polyamine Oxidase Inhibitor Blocks Androgen-Induced Oxidative Stress and Delays Prostate Cancer Progression in the TRAMP Mouse Model

PubMed Central

Basu, Hirak S.; Thompson, Todd A.; Church, Dawn R.; Clower, Cynthia C.; Mehraein-Ghomi, Farideh; Amlong, Corey A.; Martin, Christopher T.; Woster, Patrick M.; Lindstrom, Mary J.; Wilding, George

2009-01-01

High levels of reactive oxygen species (ROS) present in human prostate epithelia are an important etiological factor in prostate cancer (CaP) occurrence, recurrence and progression. Androgen induces ROS production in the prostate by a yet unknown mechanism. Here, to the best of our knowledge, we report for the first time that androgen induces an overexpression of spermidine/spermine N1-acetyltransferase (SSAT), the rate-limiting enzyme in the polyamine oxidation pathway. As prostatic epithelia produce a large excess of polyamines, the androgen-induced polyamine oxidation that produces H2O2 could be a major reason for the high ROS levels in the prostate epithelia. A small molecule polyamine oxidase inhibitor N,N'-butanedienyl butanediamine (MDL 72,527 or CPC-200) effectively blocks androgen-induced ROS production in human CaP cells as well as significantly delays CaP progression and death in animals developing spontaneous CaP. These data demonstrate that polyamine oxidation is not only a major pathway for ROS production in prostate, but inhibiting this pathway also successfully delays prostate cancer progression. PMID:19773450

Hydrogen peroxide inhibits iodide influx and enhances iodide efflux in cultured FRTL-5 rat thyroid cells.

PubMed

Sugawara, M; Yamaguchi, D T; Lee, H Y; Yanagisawa, K; Murakami, S; Summer, C N; Johnson, D G; Levin, S R

1990-05-01

This study describes the effects of hydrogen peroxide on the two iodide transport systems, I influx and I efflux, in the cultured FRTL-5 rat thyroid cells. I influx was measured by the amount of I taken up by the cells during incubation with Na125I and NaI for 7 min, and I efflux was measured by calculating the rate of 125I release from the 125I-loaded cells in the presence and absence of 5 mmol/l H2O2. Exposure to greater than 100 mumol/l H2O2 for 40 min caused a significant inhibition of I influx; the inhibition was reversible and non-competitive with iodide. Thyroid Na+K+ ATPase activity, a major mechanism to drive I influx, decreased by 40% after the cells were exposed to 5 mmol/l H2O2 for 10 min. H2O2 enhanced I efflux only when Ca2+ was present in the medium. The mechanism of an enhanced I efflux by H2O2 appears to be mediated through the elevation of free cytosolic Ca2+ concentration. Our data indicate that H2O2 can affect I transport by inhibiting I influx and enhancing I efflux.

Battling Malaria in Rural Zambia with Modern Technology: A Qualitative Study on the Value of Cell Phones, Geographical Information Systems, Asymptomatic Carriers and Rapid Diagnostic Tests to Identify, Treat and Control Malaria.

PubMed

Nygren, David; Isaksson, Arvid Lissel

2014-02-04

During the last decade much progress has been made in reducing malaria transmission in Macha, Southern Province, Zambia. Introduction of artemisinin combination therapies as well as mass screenings of asymptomatic carriers is believed to have contributed the most. When an endemic malaria situation is moving towards a non-endemic situation the resident population loses acquired immunity and therefore active case detection and efficient surveillance is crucial to prevent epidemic outbreaks. Our purpose was to evaluate the impact of cell phone surveillance and geographical information systems on malaria control in Macha. Furthermore, it evaluates what screening and treatment of asymptomatic carriers and implementation of rapid diagnostic tests in rural health care has led to. Ten in-depth semi-structured interviews, field observations and data collection were performed at the Macha Research Trust and at surrounding rural health centers. This qualitative method was inspired by rapid assessment procedure. The cell phone surveillance has been easily integrated in health care, and its integration with Geographical Information Systems has provided the ability to follow malaria transmission on a weekly basis. In addition, active case detection of asymptomatic carriers has been fruitful, which is reflected in it soon being applied nationwide. Furthermore, rapid diagnostic tests have provided rural health centers with reliable malaria diagnostics, thereby decreasing excessive malaria treatments and selection for drug resistance. This report reflects the importance of asymptomatic carriers in targeting malaria elimination, as well as development of effective surveillance systems when transmission decreases. Such an approach would be cost-efficient in the long run through positive effects in reduced child mortality and relief in health care.

[Minimal and mild endometriosis: Impact of the laparoscopic surgery on pelvic pain and fertility. CNGOF-HAS Endometriosis Guidelines].

PubMed

Ploteau, S; Merlot, B; Roman, H; Canis, M; Collinet, P; Fritel, X

2018-03-01

Minimal and mild endometriosis (stage 1 and 2 AFSR) can lead to chronic pelvic pain and infertility but can also exist in asymptomatic patients. The prevalence of asymptomatic patients with minimal and mild endometriosis is not clear but typical endometriosis lesions are found in about 5 to 10% of asymptomatic women and more than 50% of painful and/or infertile women. Laparoscopic treatment of minimal and mild endometriotic lesions is justified in case of pelvic pain because their destruction decrease significatively the pain compared with diagnostic laparoscopy alone. In this context, ablation and excision give identical results in terms of pain reduction. Moreover, literature shows no interest in uterine nerve ablation in case of dysmenorrhea due to minimal and mild endometriosis. Then, it is recommended to treat these lesions during a laparoscopy realised as part of pelvic pain. On the other hand, it is not recommended to treat asymptomatic patients. With regard to treatment of minimal and mild endometriosis in infertile patients, only two studies can be selected and both show that laparoscopy with excision or ablation and ablation of adhesions is superior to diagnostic laparoscopy alone in terms of pregnancy rate. However, it is not recommended to treat these lesions when they are asymptomatic because there is no evidence that they can progress with symptomatic disease. There is no study assessing the interest to treat these lesions when they are found fortuitously. Adhesion barrier utilisation permits to reduce post-operative adhesions, however literature failed to demonstrate the clinical profit in terms of reduction of the risk of pain or infertility. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Low Temperature Reaction Experiments Between Basalt, Seawater and CO2, and Implications for Carbon Dioxide Sequestration in Deep-Sea Basalts

NASA Astrophysics Data System (ADS)

Marieni, C.; Teagle, D. A. H.; Matter, J. M.

2015-12-01

Reactions between divalent cation-rich silicate minerals and CO2-bearing fluids to form (Ca, Mg, Fe) carbonate minerals could facilitate the safe and permanent storage of anthropogenic carbon dioxide. Deep-sea basalt formations provide large storage reservoir capacities and huge potential sources of Ca2+, Mg2+ and Fe2+. However, better knowledge of silicate mineral reaction rates with carbonate-bearing fluids is required to understand the overall carbon storage potential of these reservoirs. This study investigates key reactions associated with progressive seawater-rock interaction using far-from equilibrium dissolution experiments. The experiments were carried out at 40 ˚C and at constant CO2 partial pressure of 1 atm. Mid-ocean ridge basalts from the Juan de Fuca and Mid-Atlantic Ridges and a gabbro from the Troodos ophiolite were reacted with 500 mL of CO2-charged seawater using thick-walled fluorinated polypropylene bottles combined with rubber stoppers. The starting material was crushed, sieved and thoroughly cleaned to remove fine particles (< 63 μm) to ensure a particle grain size between 63 and 125 μm for all the samples. The seawater chemistry and the pH were monitored throughout the experiments by daily analysis of 1 mL of fluid. The pH increased rapidly from 4.8 to 5.0 before stabilizing at 5.1 after 10 days of reaction time. The analysis of anions (S, Cl) highlighted a substantial evaporation (up to 15 %) during the experiments, requiring a correction factor for the measured dissolved ion concentrations. Evaporation corrected silicon (Si) and calcium (Ca) concentrations in the seawater increased by 5900 % and 14 %, resulting in total dissolved Si and Ca from basalt of 0.3 % and 2.4 %, respectively. The results are comparable with literature data for fresh water experiments conducted on basaltic glass at higher temperature or pressure, illustrating the considerable potential of the mineral sequestration of CO2 in submarine basalts.

The vitamin D system is deregulated in pancreatic diseases

PubMed Central

Hummel, Doris; Aggarwal, Abhishek; Borka, Katalin; Bajna, Erika; Kállay, Enikö; Horváth, Henrik Csaba

2014-01-01

The vitamin D system is deregulated during development and progression of several cancer types. Data on the expression of the vitamin D system in the diseased pancreas are missing. The aim of this study was to investigate the expression of the vitamin D receptor (VDR), 1,25-dihydroxyvitamin D3 24-hydroxylase (CYP24A1), and the calcium-sensing receptor (CaSR), a vitamin D target gene, in the different regions of the pancreas in patients with chronic pancreatitis (n = 6) and pancreatic ductal adenocarcinomas (PDAC) (n = 17). We analyzed the expression of these genes at mRNA and protein level with quantitative real-time RT-PCR and immunostaining. mRNA expression of CYP24A1 and VDR was significantly increased in tumors compared with the adjacent non-tumorous tissue (p < 0.01), while CaSR mRNA expression decreased. Both the VDR and the CaSR protein were highly expressed in the endocrine compared with the exocrine pancreas. In CP the CYP24A1 expression was highest in the endocrine pancreas, while in PDACs in the transformed ducts. In the PDAC patients CYP24A1 expression in the islets was significantly lower than in CP patients. Our data suggest that during ductal adenocarcinoma development the vitamin D system in the pancreas becomes deregulated on two levels: in the islets CYP24A1 expression decreases weakening the negative feedback regulation of the vitamin D-dependent insulin synthesis/secretion. In the transformed ducts CYP24A1 expression increases, impairing the antiproliferative effect of vitamin D in these cells. PMID:25090635

Speleothems in a wave-cut notch, Cayman Brac, British West Indies: The integrated product of subaerial precipitation, dissolution, and microbes

NASA Astrophysics Data System (ADS)

Jones, Brian

2010-12-01

A wave-cut notch that is deeply incised into the vertical cliff faces of Cayman Brac is adorned with stalactites, stalagmites, and columns. The prefix "notch" is applied to each type of speleothem in order to distinguish them from cave speleothems. These speleothemic deposits must have formed since the highstand, ~ 125,000 years ago, which was responsible for the development of the notch. The laminated notch speleothems are formed largely of aragonite (small and large crystals) and calcite (columnar, fiber, and grain-coating mats) along with minor amounts of dolomite, a Mg-Si precipitate (kerolite?), gypsum, and halite. Laminae, typically < 2 mm thick, are commonly bounded by dissolution discontinuities that truncate the older laminae and their formative aragonite and calcite crystals. The patchy tan, grey, to green surface coloration of the notch speleothems reflects the random distribution of the subaerial biofilms, which are formed of a diverse array of filamentous and non-filamentous microbes. The notch speleothems are the integrated product of precipitation and dissolution that was, in some places, microbially mediated. Interpretations based on their mineralogy and internal structures indicate that the composition of the formative waters must have temporally fluctuated with periods of precipitation being interrupted by periods of dissolution. The microbes that formed the subaerial biofilms may have influenced some of these processes. The aragonite, calcite, and kerolite (?) probably formed as evaporation and loss of Ca through precipitation progressively increased the Mg:Ca and the Si/(Ca + Mg) ratios. The dolomite, gypsum, and halite probably formed during early diagenesis during the evaporation of seawater that percolated into the interiors of the notch speleothems.

Characterization of Bacillus subtilis YfkE (ChaA): a calcium-specific Ca2+/H+ antiporter of the CaCA family.

PubMed

Fujisawa, Makoto; Wada, Yuko; Tsuchiya, Takahiro; Ito, Masahiro

2009-08-01

YfkE, a protein from Bacillus subtilis, exhibits homology to the Ca(2+):Cation Antiporter (CaCA) Family. In a fluorescence-based assay of everted membrane vesicles prepared from Na(+)(Ca(2+))/H(+) antiporter-defective mutant Escherichia coli KNabc, YfkE exhibited robust Ca(2+)/H(+) antiport activity, with a K (m) for Ca(2+) estimated at 12.5 muM at pH 8.5 and 113 muM at pH 7.5. Neither Na(+) nor K(+) served as a substrate. Mg(2+) also did not serve as a substrate, but inhibited the Ca(2+)/H(+) antiporter activity. The Ca(2+) transport capability of YfkE was also observed directly by transport assays in everted membrane vesicles using radiolabeled (45)Ca(2+). Transcriptional analysis from the putative yfkED operon using beta-garactosidase activity as a reporter revealed that both of the yfkE and yfkD genes are regulated by forespore-specific sigma factor, SigG, and the general stress response regulator, SigB. These results suggest that YfkE may be needed for Ca(2+) signaling in the sporulation or germination process in B. subtilis. ChaA is proposed as the designation for YfkE of B. subtilis.

Cross state-dependency of learning between tramadol and MK-801 in the mouse dorsal hippocampus: involvement of nitric oxide (NO) signaling pathway.

PubMed

Jafari-Sabet, Majid; Amiri, Shiva; Ataee, Ramin

2018-04-21

Tramadol, an atypical μ-opioid receptor agonist, as a psychoactive drug, is frequently abused by human beings. Understanding the neurobiological mechanisms of drug-associated learning and memory formation may help prevent drug addiction and relapse. Previous study revealed that dorsal hippocampus (CA1) plays a crucial role in the retrieval of tramadol-associated memory and that its role depends on the expression of CA1 N-methyl-D-aspartate (NMDA) receptors (Jafari-Sabet et al. Can J Physiol Pharmacol 96:45-50, 2018). To clarify the exact mechanisms involved, the activation of CA1 nitric oxide (NO) signaling pathway by L-arginine (a nitric oxide precursor) on the interaction between tramadol and MK-801 in memory retrieval was examined. The dorsal hippocampal CA1 regions of adult male NMRI mice were bilaterally cannulated and a single-trial step-down inhibitory avoidance apparatus was used for the assessment of memory retrieval. Post-training and/or pre-test microinjection of tramadol (0.5 and 1 μg/mouse) and/or a non-competitive NMDA receptor antagonist, MK-801 (0.25 and 0.5 μg/mouse), induced amnesia which were reversed when the same doses of the drugs were administered 24 h later in a pre-test session, suggesting tramadol state-dependent learning (SDL) and MK-801 SDL. The amnesia induced by post-training microinjection of tramadol (1 μg/mouse) was reversed by pre-test microinjection of MK-801 (0.25 and 0.5 μg/mouse). Pre-test microinjection of MK-801 (0.125 and 0.25 μg/mouse) with an ineffective dose of tramadol (0.25 μg/mouse) potentiated tramadol SDL. The amnesia induced by post-training microinjection of MK-801 (0.5 μg/mouse) was reversed by pre-test microinjection of tramadol (0.5 and 1 μg/mouse). Pre-test microinjection of tramadol (0.25 and 0.5 μg/mouse) with an ineffective dose of MK-801 (0.125 μg/mouse) potentiated MK-801 SDL. Pre-test microinjection of ineffective doses of L-arginine (0.125, 025, and 0.5 μg/mouse) improved amnesia induced by the co-administration of tramadol and MK-801. Pre-test microinjection of L-arginine (0.125, 025, and 0.5 μg/mouse) could not reverse amnesia induced by post-training microinjection of tramadol while same doses of L-arginine improved MK-801 response on tramadol SDL. The results strongly propose that activation of CA1 NO signaling pathway has a pivotal role in cross SDL among tramadol and MK-801.

Geochemistry of highly basic calcium hydroxide groundwater in Jordan

USGS Publications Warehouse

Barnes, I.; Presser, T.S.; Saines, M.; Dickson, P.; Van Groos, A. F. K.

1982-01-01

Highly-alkaline (pH > 12.5) meteoric waters of a Ca2+OH--type issue from naturally calcined bituminous marl. The cold (16.5 ??? T(??C) ??? 19.1) waters are super-saturated with minerals thought to be of high-temperature origin. ?? 1982.

Effects of oral calcium supplementation on mineral and acid-base status, energy metabolites, and health of postpartum dairy cows.

PubMed

Martinez, N; Sinedino, L D P; Bisinotto, R S; Daetz, R; Lopera, C; Risco, C A; Galvão, K N; Thatcher, W W; Santos, J E P

2016-10-01

Two experiments were conducted to characterize blood concentrations of minerals and acid-base status after oral dosing of Ca salts and to determine the effects of oral Ca on mineral and metabolic status and incidence diseases. The hypotheses were that administration of oral Ca as CaCl2 and CaSO4 maintains blood total Ca (tCa) concentrations ≥2.125 mM and reduces the incidence of diseases in early lactation. In experiment 1, 18 Holstein cows on the day of calving were assigned to receive a single dose of 0, 43, or 86g of Ca as an oral bolus. Blood was sampled before and after treatments to characterize acid-base status and concentrations of minerals. In experiment 2, 450 Holstein cows considered of low (LRM; normal calving) or high risk (HRM; dystocia, twins, stillbirth, retained placenta, vulvo-vaginal laceration, or a combination of these) of metritis (primiparous-LRM=84; primiparous-HRM=84; multiparous-LRM=138; multiparous-HRM=138) on the day of calving were blocked by parity and then randomly assigned to control, no Ca supplementation; 86g of Ca on d 0 and 1 postpartum (CaS1); or 86g of Ca on d 0 and 1 postpartum followed by 43g/d on d 2 to 4 postpartum (CaS4). Blood was sampled before and 30 min after treatment on d 0, and 30 min after treatments on d 1 to 4, and d 7 and 10 for determination of concentrations of minerals and metabolites and blood acid-base responses. Disease incidence was evaluated for the first 30 DIM. Concentrations of ionized Ca (iCa) increased for 2h in cows supplemented with 43g of Ca and fewer than 8h in cows supplemented with 86g of Ca. The changes in iCa concentrations from pretreatment to 30 min after 86g of Ca supplemented on d 0 were 0.11±0.03 mM in multiparous cows and 0.25±0.03 mM in primiparous cows. Oral Ca reduced the incidence of subclinical hypocalcemia (SCH; tCa <2.125mM) in the first 4 d in the experiment (control=69.3%; CaS1=57.5%; CaS4=34.2%). Calcium supplementation decreased the prevalence of SCH on d 0 and 1 postpartum in all cows. Stopping oral Ca in CaS1 on d 1 postpartum, however, caused a rebound in SCH on d 2 to 4 postpartum in primiparous cows. Oral Ca increased the incidence of metritis (control=22.7%; CaS1=34.8%; CaS4=32.8%), primarily because of an increase in LRM primiparous cows (control=17.9%; CaS1=35.7%; CaS4=42.9%). Oral Ca increased morbidity in primiparous cows (control=38.1%; CaS1=61.8%; CaS4=60.3%) but had no effect on multiparous cows (control=38.2%; CaS1=35.1%; CaS4=30.1%). Large doses of oral Ca as salts of chloride and sulfate in the first days postpartum should be avoided in primiparous cows and used only in cows at risk of clinical hypocalcemia. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Serum thyrotrophin at baseline predicts the natural course of subclinical hyperthyroidism.

PubMed

Das, G; Ojewuyi, T A; Baglioni, P; Geen, J; Premawardhana, L D; Okosieme, O E

2012-07-01

Optimal therapeutic strategies for subclinical hyperthyroidism are undecided. Overt disease develops in a minority of cases, but the risk factors for progression remain unclear. We examined whether a baseline thyrotrophin (TSH) predicted progression to overt hyperthyroidism in asymptomatic individuals with subclinical hyperthyroidism. This was a retrospective study of 323 patients with subclinical hyperthyroidism seen in our institution from 2003 to 2010 (mean age 71 years, males 26·9%, females 73·1%, mean follow-up duration 32 months, range 6-93 months). Serum TSH and free thyroxine (FT4) were documented at baseline and during follow-up. After excluding individuals with nonthyroid causes of low TSH, patients were grouped according to initial TSH as: TSH 0·10-0·39 mU/l (grade I) and TSH < 0·10 mU/l (grade II). Only 38 patients (11·8%) developed overt hyperthyroidism with annual progression rates of 0·6-3·7%. Most patients reverted to normal thyroid status (31·6%) or remained subclinically hyperthyroid (56·7%). Progression to frank hyperthyroidism was higher in grade II than in grade I patients (20·3% vs 6·8%, P < 0·001, Chi square test). Kaplan-Meier curves showed faster progression rates in grade II than grade I (P < 0·001, log rank test). In stepwise multivariate Cox regression analysis, TSH < 0·1 mU/l was associated with overt hyperthyroidism (hazard ratio 3·4, confidence interval 1·6-7·0), whereas age, gender, FT4 and aetiological diagnosis were not associated with hyperthyroidism. Thyrotrophin predicts overt hyperthyroidism in asymptomatic individuals with subclinical hyperthyroidism. Patients with TSH < 0·10 mU/l have a higher risk of progressing to hyperthyroidism than those with TSH 0·10-0·39 mU/l. © 2012 Blackwell Publishing Ltd.

Large magnetoresistance in antiferromagnetic CaMnO3-δ

NASA Astrophysics Data System (ADS)

Zeng, Z.; Greenblatt, M.; Croft, M.

1999-04-01

CaMnO3-δ with δ=0, 0.06, and 0.11 was prepared by the Pechini citrate gel process at 1100 °C. Oxygen defects were created by quenching the sample from high temperature. Chemical analysis and x-ray absorption show that the formal valence of Mn in CaMnO3 is close to 4+, and that Mn(III) is created in the quenched samples. Moreover the x-ray absorption near-edge spectra results support the creation of two Mn(III) five coordinate sites for each O vacancy. CaMnO3-δ (δ=0-0.11) are n-type semiconductors and order antiferromagnatically with Néel temperatures close to 125 K. The activation energy decreases with increasing δ. A relatively large (~40%) negative magnetoresistance (MR) is observed for CaMnO2.89. This result shows that a substantial MR can occur in these G-type antiferromagnetic materials.

Quantitative analysis and predictors of embolic filter debris load during carotid artery stenting in asymptomatic patients.

PubMed

Piazza, Michele; Squizzato, Francesco; Chincarini, Chiara; Fedrigo, Marny; Castellani, Chiara; Angelini, Annalisa; Grego, Franco; Antonello, Michele

2018-03-01

The objective of this study was to perform a quantitative analysis and to identify predictors of embolic filter debris (EFD) load during carotid artery stenting (CAS) in asymptomatic patients. All patients with asymptomatic carotid stenosis >70% undergoing CAS between 2008 and 2016 were included in a prospective database. A distal filter protection device was used in all patients. At the end of the procedure, the filter was fixed in formalin and then analyzed with a stereomicroscope. Morphometric analysis was performed with Image-Pro Plus software (Media Cybernetics, Rockville, Md). The total area of the filter membrane and the area covered by particulate material were quantified. The quantity of membrane occupied by debris was expressed as percentage of covered surface area. Anatomic and clinical variables were evaluated for their association with EFD load using multiple logistic regression. Among the 278 patients undergoing CAS, an open-cell stent was implanted in 211 patients (76%); 67 patients (24%) received a closed-cell stent. Overall technical success and clinical success were both 99%; no perioperative death was reported. Stroke rate was 1.8% (major, n = 1 [0.4%]; minor, n = 4 [1.4%]); transient ischemic attacks occurred in 5% of cases (n = 14). The quantitative analysis of the filter revealed that EFD was present in 74% of cases (n = 207). The mean EFD load was 10% of the filter surface (median, 1; range, 0-80); it was <10% in 203 patients (73%), between 11% and 20% in 39 patients (14%), between 21% and 30% in 14 patients (5%), and >31% in 22 (8%). Patients with any type of ischemic neurologic event after CAS (stroke and transient ischemic attack) had a significantly higher mean EFD load compared with uneventful cases (26.7% ± 19.0% vs 8.5% ± 13.5%; P < .001). The observational frequency distribution analysis identified the presence of >12.5% EFD load as the optimal cutoff for the association with clinically relevant perioperative ischemic events (sensitivity, 78%; specificity, 77%; area under the curve, 0.81). The multivariate analysis demonstrated that age >75 years (odds ratio [OR], 2.56; P = .003), pre-existing ipsilateral ischemic cerebral lesions (OR, 2.09; P = .047), hypoechogenic plaque on the preoperative duplex ultrasound examination (OR, 6.05; P < .001), and plaque length >15 mm (OR, 1.79; P = .049) were independent predictors of EFD load >12.5%. The majority of asymptomatic carotid stenoses treated with CAS have detectable embolic debris in the protecting filter. Age >75 years, pre-existing ipsilateral cerebral ischemic lesions, hypoechogenic plaque, and plaque length >15 mm should be taken into consideration as independent predictors of clinically relevant embolic debris during the procedure. Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Comparisons of the survival time of patients with ovarian cancer adopting post-operative chemotherapy by use of paclitaxel combined with carboplatin or nedaplatin.

PubMed

Gao, Hongfei; Yuan, Lijun; Han, Yimin

2016-06-24

The current study aims to evaluate and compare the efficacy of post-operative chemotherapy using paclitaxel plus carboplatin or nedaplatin in patients with ovarian cancer, as well as the effects of different combinational therapies on the survival times of patients. Ninety-four patients were recruited for the study. These ovarian cancer patients were admitted into the Cancer Hospital Affiliated with Harbin Medical University for surgery from January 2008 to October 2009. They were divided into different groups according to their post-operative chemotherapy schemes: paclitaxel plus carboplatin (CBP group, n = 48) and paclitaxel plus nedaplatin (NDP group, n = 46). Variance analysis was used to compare the effects of different chemotherapy schemes and pathological types of ovarian cancer on the level of CA125 in serum at different treatment time points. Univariate and multivariate analyses were employed to evaluate the survival times of patients in different groups and pathological types and ages. No significant differences were observed regarding the effects of various chemotherapy schemes (P = 0.561) and pathological types (P = 0.903) on the level of CA125 in serum of patients with ovarian cancer. However, the duration of chemotherapy had a profound impact on the level of CA125 in serum (P < 0.001). The survival times of patients was not affected by age (P = 0.101) and pathological type of ovarian cancer (P = 0.94) significantly. However, it was significantly affected by the chemotherapy scheme. Combined chemotherapy using carboplatin plus paclitaxel should be considered as the preferred treatment scheme for the initial treatment of ovarian cancer.

Radioimmunoassay of tumor markers in serum of patients with renal carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cordoni-Voutsas, M.; Glaubitt, D.; Wagner, W.

1984-01-01

Having noted an increased serum level of TPA and CEA in patients with renal carcinoma the authors extended these studies by using a larger number of tumor markers. In 15 patients (11 men and 4 women after menopause) aged 33 to 74 years who had renal carcinoma, among them 3 with tumor metastases, the serum concentration of TPA, CA 12-5, CEA, AFP, ferritin, prolactin, ..beta..-HCG, and ..beta../sub 2/-microglobulin was measured by radioimmunoassay. Monoclonal antibodies were used in the determination of serum CA 12-5 and CEA. In all patients surgical treatment, irradiation, or cytostatic therapy had not been performed. In serummore » the normal range was exceeded by TPA in 7 patients, CA 12-5 in 3, CEA and AFP in one each, ferritin in 12, prolactin in 2, and ..beta../sub 2/-microglobulin in 10 patients. In one man serum prolactin was reduced. Serum ..beta..-HCG was normal in all patients. According to these results serum ferritin, TPA, and ..beta../sub 2/-microglobulin are of great value as tumor markers in patients with renal carcinoma. In several patients the increase of serum ..beta../sub 2/-microglobulin may be ascribed partly to deterioration of renal function. As no consistent patterns of tumor markers in serum were observed it is recommended to determine several tumor markers and not only one of them during the follow-up of patients. Radioimmunoassays for measuring the serum level of tumor markers, especially ferritin, TPA, and ..beta../sub 2/-microglobulin, may considerably assist in the management of patients with renal carcinoma by providing early information about tumor recurrence or metastases.« less

A novel multiple marker bioassay utilizing HE4 and CA125 for the prediction of ovarian cancer in patients with a pelvic mass

PubMed Central

Moore, Richard G.; McMeekin, D. Scott; Brown, Amy K.; DiSilvestro, Paul; Miller, M. Craig; Allard, W. Jeffrey; Gajewski, Walter; Kurman, Robert; Bast, Robert C.; Skates, Steven J.

2012-01-01

Introduction Patients diagnosed with epithelial ovarian cancer (EOC) have improved outcomes when cared for at centers experienced in the management of EOC. The objective of this trial was to validate a predictive model to assess the risk for EOC in women with a pelvic mass. Methods Women diagnosed with a pelvic mass and scheduled to have surgery were enrolled on a multicenter prospective study. Preoperative serum levels of HE4 and CA125 were measured. Separate logistic regression algorithms for premenopausal and postmenopausal women were utilized to categorize patients into low and high risk groups for EOC. Results Twelve sites enrolled 531 evaluable patients with 352 benign tumors, 129 EOC, 22 LMP tumors, 6 non EOC and 22 non ovarian cancers. The postmenopausal group contained 150 benign cases of which 112 were classified as low risk giving a specificity of 75.0% (95% CI 66.9-81.4), and 111 EOC and 6 LMP tumors of which 108 were classified as high risk giving a sensitivity of 92.3% (95% CI=85.9-96.4). The premenopausal group had 202 benign cases of which 151 were classified as low risk providing a specificity of 74.8% (95% CI=68.2--80.6), and 18 EOC and 16 LMP tumors of which 26 were classified as high risk, providing a sensitivity of 76.5% (95% CI=58.8--89.3). Conclusion An algorithm utilizing HE4 and CA125 successfully classified patients into high and low risk groups with 93.8% of EOC correctly classified as high risk. This model can be used to effectively triage patients to centers of excellence. PMID:18851871

Three new potential ovarian cancer biomarkers detected in human urine with equalizer bead technology.

PubMed

Petri, Anette Lykke; Simonsen, Anja Hviid; Yip, Tai-Tung; Hogdall, Estrid; Fung, Eric T; Lundvall, Lene; Hogdall, Claus

2009-01-01

To examine whether urine can be used to measure specific ovarian cancer proteomic profiles and whether one peak alone or in combination with other peaks or CA125 has the sensitivity and specificity to discriminate between ovarian cancer pelvic mass and benign pelvic mass. A total of 209 women were admitted for surgery for pelvic mass at the Gynaecological Department at Rigshospitalet, Copenhagen. Of the women, 156 had benign gynaecological tumors, 13 had borderline tumors and 40 had malignant epithelial ovarian cancer. The prospectively and preoperatively collected urine samples were aliquotted and frozen at -80 degrees until the time of analysis. The urine was fractionated using equalizer bead technology and then analyzed with surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. Biomarkers were purified and identified using combinations of chromatographic techniques and tandem mass spectrometry. Benign and malignant ovarian cancer cases were compared; 21 significantly different peaks (p<0.001) were visualized using Mann-Whitney analysis, ranging in m/z values from 1,500 to 185,000. The three most significant peaks were purified and identified as fibrinogen alpha fragment (m/z=2570.21), collagen alpha 1 (III) fragment (m/z=2707.32) and fibrinogen beta NT fragment (m/z=4425.09). The area under the receiver operator characteristic curve (ROC AUC) value for these three peaks in combination was 0.88, and their ROC AUC value in combination with CA125 was 0.96. This result supports the feasibility of using urine as a clinical diagnostic medium, and the ROC AUC value for the three most significant peaks in combination with or without CA125 demonstrates the enhanced prediction performance of combined marker analysis.

Clinical Significance of Tissue Factor Pathway Inhibitor 2, a Serum Biomarker Candidate for Ovarian Clear Cell Carcinoma

PubMed Central

Arakawa, Noriaki; Kobayashi, Hiroshi; Yonemoto, Naohiro; Masuishi, Yusuke; Ino, Yoko; Shigetomi, Hiroshi; Furukawa, Naoto; Ohtake, Norihisa; Miyagi, Yohei; Hirahara, Fumiki; Hirano, Hisashi; Miyagi, Etsuko

2016-01-01

Background There is currently no reliable serum biomarker for ovarian clear cell carcinoma (CCC), a highly lethal histological subtype of epithelial ovarian cancer (EOC). Previously, using a proteome-based approach, we identified tissue factor pathway inhibitor 2 (TFPI2) as a candidate serum biomarker for CCC. In this study, we sought to evaluate the clinical diagnostic performance of TFPI2 in preoperative prediction of CCC. Methods Serum TFPI2 levels were measured in serum samples from a retrospective training set consisting of patients with benign and borderline ovarian tumors, EOC subtypes, and uterine diseases. Via receiver operating characteristic (ROC) analyses, we compared the diagnostic performance of TFPI2 with that of CA125 in discrimination of patients with ovarian CCC from other patient groups. The observed diagnostic performances were examined in a prospective validation set. Results The 268-patient training set included 29 patients with ovarian CCC. Unlike CA125, which was also elevated in patients with endometriosis and several EOC subtypes, serum TFPI2 levels were specifically elevated only in ovarian CCC patients, consistent with the mRNA expression pattern in tumor tissues. The area under the ROC curve (AUC) of serum TFPI2 was obviously higher than that of CA125 for discrimination of CCC from other ovarian diseases (AUC = 0.891 versus 0.595). Applying a cut-off value of 280 pg/mL, TFPI2 could distinguish early-stage (FIGO I and II) CCC from endometriosis with 72.2% sensitivity, 93.3% specificity, and 88.8% accuracy. Similar results were confirmed in an independent 156-patient prospective validation set. Conclusions TFPI2 is a useful serum biomarker for preoperative clinical diagnosis of CCC. PMID:27798689

Clinical Significance of Tissue Factor Pathway Inhibitor 2, a Serum Biomarker Candidate for Ovarian Clear Cell Carcinoma.

PubMed

Arakawa, Noriaki; Kobayashi, Hiroshi; Yonemoto, Naohiro; Masuishi, Yusuke; Ino, Yoko; Shigetomi, Hiroshi; Furukawa, Naoto; Ohtake, Norihisa; Miyagi, Yohei; Hirahara, Fumiki; Hirano, Hisashi; Miyagi, Etsuko

2016-01-01

There is currently no reliable serum biomarker for ovarian clear cell carcinoma (CCC), a highly lethal histological subtype of epithelial ovarian cancer (EOC). Previously, using a proteome-based approach, we identified tissue factor pathway inhibitor 2 (TFPI2) as a candidate serum biomarker for CCC. In this study, we sought to evaluate the clinical diagnostic performance of TFPI2 in preoperative prediction of CCC. Serum TFPI2 levels were measured in serum samples from a retrospective training set consisting of patients with benign and borderline ovarian tumors, EOC subtypes, and uterine diseases. Via receiver operating characteristic (ROC) analyses, we compared the diagnostic performance of TFPI2 with that of CA125 in discrimination of patients with ovarian CCC from other patient groups. The observed diagnostic performances were examined in a prospective validation set. The 268-patient training set included 29 patients with ovarian CCC. Unlike CA125, which was also elevated in patients with endometriosis and several EOC subtypes, serum TFPI2 levels were specifically elevated only in ovarian CCC patients, consistent with the mRNA expression pattern in tumor tissues. The area under the ROC curve (AUC) of serum TFPI2 was obviously higher than that of CA125 for discrimination of CCC from other ovarian diseases (AUC = 0.891 versus 0.595). Applying a cut-off value of 280 pg/mL, TFPI2 could distinguish early-stage (FIGO I and II) CCC from endometriosis with 72.2% sensitivity, 93.3% specificity, and 88.8% accuracy. Similar results were confirmed in an independent 156-patient prospective validation set. TFPI2 is a useful serum biomarker for preoperative clinical diagnosis of CCC.

Regenerative treatment of an immature, traumatized tooth with apical periodontitis: report of a case.

PubMed

Cotti, Elisabetta; Mereu, Manuela; Lusso, Daniela

2008-05-01

This case report describes the treatment of a necrotic immature permanent central incisor with complete crown fracture, suspected root fracture, and sinus tract, which was not treated with conventional apexification techniques. Instead, a regenerative approach based on the trauma literature's methods for revascularization was provided. The root canal was gently debrided of necrotic tissue with a sharp spoon excavator and irrigated for only one third of its length with NaOCl and then medicated with calcium hydroxide. After 15 days the sinus tract had healed, and the tooth was asymptomatic. The tooth was accessed, calcium hydroxide was removed, bleeding was stimulated to form an intracanal blood clot, and mineral trioxide aggregate was placed coronally to the blood clot. After 8 months, a coronal calcified barrier was radiographically evident and accompanied with progressive thickening of the root wall and apical closure. Two and a half years after treatment was initiated, the tooth remained asymptomatic, and the sinus tract had not reappeared. The progressive increase in the thickness of the dentinal walls and subsequent apical development suggest that appropriate biologic responses can occur with this type of treatment of the necrotic immature permanent tooth with sinus tract.

Syphilis. A tale of twisted treponemes.

PubMed Central

Flores, J L

1995-01-01

Despite the widespread availability of effective treatment, the incidence of primary and secondary syphilis in the United States is on the rise. In addition, syphilis is occurring in a substantial number of patients infected with the human immunodeficiency virus (HIV), thus adding to the complexities of diagnosis and treatment. Primary syphilis represents a disseminated infection, often accompanied by abnormalities of the cerebrospinal fluid, that may pass unrecognized and progress to the myriad manifestations of secondary syphilis. The diagnosis of syphilis in patients with mucosal or skin lesions may be made by darkfield examination; once lesions have resolved, serologic tests are required. Patients with latent syphilis may have asymptomatic neurosyphilis and risk progression to tertiary disease. The diagnosis of asymptomatic neurosyphilis is necessary to determine the optimal treatment of patients with latent disease. The diagnosis of active neurosyphilis generally requires an inflammatory cerebrospinal fluid profile and a reactive cerebrospinal fluid VDRL test. Syphilis is common in HIV-infected patients, who may have an altered antibody response to infection and an apparent increased incidence of neurologic complications. The preferred treatment at all stages is penicillin, which is also the only recommended therapy for neurosyphilis. The optimal treatment of syphilis in HIV-infected patients is unknown. Images Figure 1. PMID:8553639

DOE Office of Scientific and Technical Information (OSTI.GOV)

Steiner, B.; Cousot, D.; Trzeciak, A.

The platelet glycoprotein IIb-IIIa complex (GP IIb-IIIa) is a member of the integrin receptor family that recognizes adhesive proteins containing the Arg-Gly-Asp (RGD) sequence. In the present study the binding characteristics of the synthetic hexapeptide Tyr-Asn-Arg-Gly-Asp-Ser (YNRGDS, a sequence present in the fibrinogen alpha-chain at position 570-575) to purified GP IIb-IIIa were determined by equilibrium dialysis. The binding of 125I-YNRGDS to GP IIb-IIIa was specific, saturable, and reversible. The apparent dissociation constant was 1.0 +/- 0.2 microM, and the maximal binding capacity was 0.92 +/- 0.02 mol of 125I-YNRGDS/mol of GP IIb-IIIa, indicating that GP IIb-IIIa contains a single bindingmore » site for RGD peptides. The binding of 125I-YNRGDS to purified GP IIb-IIIa showed many of the characteristics of fibrinogen binding to activated platelets: the binding was inhibited by fibrinogen, by the monoclonal antibody A2A9, and by the dodecapeptide from the C terminus of the fibrinogen gamma-chain. In addition, the binding of 125I-YNRGDS to GP IIb-IIIa was divalent cation-dependent. Our data suggest that two divalent cation binding sites must be occupied for YNRGDS to bind: one site is specific for calcium and is saturated at 1 microM free Ca2+, whereas the other site is less specific and reaches saturation at millimolar concentrations of either Ca2+ or Mg2+. The results of the present study support the hypothesis that the RGD domains within the adhesive proteins are responsible for their binding to GP IIb-IIIa.« less

A Pilot Study of Circulating MicroRNA-125b as a Diagnostic and Prognostic Biomarker for Epithelial Ovarian Cancer.

PubMed

Zhu, Tao; Gao, Wen; Chen, Xi; Zhang, Ying; Wu, Meijuan; Zhang, Ping; Wang, Shihua

2017-01-01

Early diagnosis of epithelial ovarian cancer is critical for patient survival. The objective of this pilot study is to identify a circulating micro (mi)RNA as a potential biomarker for epithelial ovarian cancer. A total of 135 epithelial ovarian cancer patients and 54 benign ovarian tumor patients were recruited for this study. Using customized TaqMan low density miRNA arrays, we first screened expression levels of 48 miRNAs in sera from 18 epithelial ovarian cancer patients and 16 benign ovarian tumor patients. The most significantly and differentially expressed miRNA was then further examined in all serum samples using real-time polymerase chain reaction. Its expression was further analyzed in relationship with clinicopathological factors and patient survival. Array screening data showed that expression levels of serum miRNA-20a, miRNA-125b, miRNA-126, miRNA-355, and let-7c were significantly different between malignant and benign ovarian tumor patients. Subsequent real-time polymerase chain reaction results showed that serum miRNA-125b levels were significantly higher in epithelial ovarian cancer patients compared to benign controls. Moreover, serum miRNA-125b levels were significantly higher in ovarian cancer patients in early stages I and II, and in patients having no residual tumor following surgery, but were not associated with differentiation and histological types of ovarian cancer. Notably, the higher level of miR-125b was significantly positively correlated with progression-free survival (P = 0.035) and marginally, with overall survival (P = 0.069). miRNA-125b plays an important role in the pathogenesis and progression of epithelial ovarian cancer. Circulating miRNA-125b has the potential to become a novel biomarker for early diagnosis and prognosis prediction of epithelial ovarian cancer.

MicroRNA miR-125b induces senescence in human melanoma cells.

PubMed

Glud, Martin; Manfé, Valentina; Biskup, Edyta; Holst, Line; Dirksen, Anne Marie Ahlburg; Hastrup, Nina; Nielsen, Finn C; Drzewiecki, Krzysztof T; Gniadecki, Robert

2011-06-01

MicroRNAs (miRNAs) are small noncoding RNA molecules involved in gene regulation. Aberrant expression of miRNA has been associated with the development or progression of several diseases, including cancer. In a previous study, we found that the expression of miRNA-125b (miR-125b) was two-fold lower in malignant melanoma producing lymph node micrometastases than in nonmetastasizing tumors. To get further insight into the functional role of miR-125b, we assessed whether its overexpression or silencing affects apoptosis, proliferation, or senescence in melanoma cell lines. We showed that overexpression of miR-125b induced typical senescent cell morphology, including increased cytoplasmatic/nucleus ratio and intensive cytoplasmatic β-galactosidase expression. In contrast, inhibition of miR-125b resulted in 30-35% decreased levels of spontaneous apoptosis. We propose that downregulation of miR-125b in an early cutaneous malignant melanoma can contribute to the increased metastatic capability of this tumor.

A comprehensive analysis of coregulator recruitment, androgen receptor function and gene expression in prostate cancer

PubMed Central

Hu, Qiang; Senapati, Dhirodatta; Venkadakrishnan, Varadha Balaji; Wang, Dan; DePriest, Adam D; Schlanger, Simon E; Ben-Salem, Salma; Valenzuela, Malyn May; Willard, Belinda; Mudambi, Shaila; Swetzig, Wendy M; Das, Gokul M; Shourideh, Mojgan; Koochekpour, Shahriah; Falzarano, Sara Moscovita; Magi-Galluzzi, Cristina; Yadav, Neelu; Chen, Xiwei; Lao, Changshi; Wang, Jianmin; Billaud, Jean-Noel

2017-01-01

Standard treatment for metastatic prostate cancer (CaP) prevents ligand-activation of androgen receptor (AR). Despite initial remission, CaP progresses while relying on AR. AR transcriptional output controls CaP behavior and is an alternative therapeutic target, but its molecular regulation is poorly understood. Here, we show that action of activated AR partitions into fractions that are controlled preferentially by different coregulators. In a 452-AR-target gene panel, each of 18 clinically relevant coregulators mediates androgen-responsiveness of 0–57% genes and acts as a coactivator or corepressor in a gene-specific manner. Selectivity in coregulator-dependent AR action is reflected in differential AR binding site composition and involvement with CaP biology and progression. Isolation of a novel transcriptional mechanism in which WDR77 unites the actions of AR and p53, the major genomic drivers of lethal CaP, to control cell cycle progression provides proof-of-principle for treatment via selective interference with AR action by exploiting AR dependence on coregulators. PMID:28826481

Body mass index and extent of MRI-detected inflammation: opposite effects in rheumatoid arthritis versus other arthritides and asymptomatic persons.

PubMed

Mangnus, Lukas; Nieuwenhuis, Wouter P; van Steenbergen, Hanna W; Huizinga, Tom W J; Reijnierse, Monique; van der Helm-van Mil, Annette H M

2016-10-22

In the population a high body mass index (BMI) has been associated with slightly increased inflammatory markers. Within rheumatoid arthritis (RA), however, a high BMI has been associated with less radiographic progression; this phenomenon is unexplained. We hypothesized that the phenomenon is caused by an inverse relationship between BMI and inflammation in hand and foot joints with RA. To explore this hypothesis, local inflammation was measured using magnetic resonance imaging (MRI) in early arthritis patients presenting with RA or other arthritides and in asymptomatic volunteers. A total of 195 RA patients, 159 patients with other inflammatory arthritides included in the Leiden Early Arthritis Clinic, and 193 asymptomatic volunteers underwent a unilateral contrast-enhanced 1.5 T MRI scan of metacarpophalangeal, wrist, and metatarsophalangeal joints. Each MRI scan was scored by two readers on synovitis, bone marrow edema (BME), and tenosynovitis; the sum yielded the total MRI inflammation score. Linear regression on log-transformed MRI data was used. A higher BMI was associated with higher MRI inflammation scores in arthritides other than RA (β = 1.082, p < 0.001) and in asymptomatic volunteers (β = 1.029, p = 0.040), whereas it was associated with lower MRI inflammation scores in RA (β = 0.97, p = 0.005). Evaluating the different types of inflammation, a higher BMI was associated with higher synovitis, BME, and tenosynovitis scores in arthritides other than RA (respectively β = 1.084, p < 0.001, β = 1.021, p = 0.24, and β = 1.054, p = 0.003), but with lower synovitis and BME scores in RA (respectively β = 0.98, p = 0.047 and β = 0.95, p = 0.002). Increased BMI is correlated with less severe MRI-detected synovitis and BME in RA. This might explain the paradox in RA where obesity correlates with less severe radiographic progression.

[Interaction of human factor X with thromboplastin].

PubMed

Kiselev, S V; Zubairov, D M; Timarbaev, V N

2003-01-01

The binding of 125I-labeled human factor X to native and papaine-treated tissue tromboplastin in the presence of CaCl2 or EDTA was studied. The Scatchard analysis suggests the existence of high (Kd=l,8 x10(-9) M) and low affinity binding sites on the thromboplastin surface. The removal of Ca2+ reduced affinity of factor X to the high affinity sites. This was accompanied by some increase of their number. Proteolysis by papaine decreased affinity of high affinity sites and caused the increase of their number in the presence of Ca2+. In the absence of Ca2+ the affinity remained unchanged, but the number of sites decreased. At low concentrations of factor X positive cooperativity for high affinity binding sites was observed. It did not depend on the presence of Ca2+. The results indirectly confirm the role of hydrophobic interactons in Ca2+ dependent binding of factor X to thromboplastin and the fact that heterogeneity of this binding is determined by mesophase structure of the thromboplastin phospholipids.

3. BUILDING 8814, WEST SIDE AND SOUTH REAR, SHOWING BLAST ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

3. BUILDING 8814, WEST SIDE AND SOUTH REAR, SHOWING BLAST DOOR. BUILDING 8826 IS IN BACKGROUND. - Edwards Air Force Base, Air Force Rocket Propulsion Laboratory, Observation Bunker 1-D-3, Test Area 1-125, northwest end of Altair Boulevard, Boron, Kern County, CA

2. BUILDING 8814, NORTH FRONT AND EAST SIDE. Looking south ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

2. BUILDING 8814, NORTH FRONT AND EAST SIDE. Looking south southwest toward water tank complex. - Edwards Air Force Base, Air Force Rocket Propulsion Laboratory, Observation Bunker 1-D-3, Test Area 1-125, northwest end of Altair Boulevard, Boron, Kern County, CA

19. POWER ROOM INTERIOR, PELTON WATER TURBINE AND FLYBALL GOVERNOR ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

19. POWER ROOM INTERIOR, PELTON WATER TURBINE AND FLYBALL GOVERNOR DIRECTLY CONNECTED TO 7 KW AC GENERATOR (ON RIGHT), 125 VOLTS, 56 AMPS. INSTALLED IN 1926, STILL IN USE FOR OUTSIDE LIGHTING. - Death Valley Ranch, Power House, Death Valley Junction, Inyo County, CA

The evaluation of the genotoxicity of two food preservatives: sodium benzoate and potassium benzoate.

PubMed

Zengin, N; Yüzbaşıoğlu, D; Unal, F; Yılmaz, S; Aksoy, H

2011-04-01

In this study, the genotoxic effects of sodium benzoate (SB) and potassium benzoate (PB) were investigated in cultured human peripheral lymphocytes using chromosomal aberrations (CA), sister chromatid exchange (SCE), and micronuclei (MN). The level of nuclear DNA damage of SB and PB were also evaluated using the comet assay. The lymphocytes were incubated with different concentrations of SB (6.25, 12.5, 25, 50, and 100 μg/ml) and PB (62.5, 125, 250, 500, and 1000 μg/ml). A significant increase was observed in CA, SCE, and MN, in almost all treatments compared to negative controls. SB and PB significantly decreased the mitotic index (MI) in all the treatments, compared to the negative controls. However, neither of the additives affected the replication index (RI). Although SB significantly increased DNA damage, PB did not cause a significant increase in DNA damage. The present results indicate that SB and PB are clastogenic, mutagenic and cytotoxic to human lymphocytes in vitro. Copyright © 2010 Elsevier Ltd. All rights reserved.

A New Strategy to Synthesize Anisotropic SmCo 5 Nanomagnets

DOE PAGES

Shen, Bo; Yu, Chao; Su, Dong; ...

2018-04-06

We report a simple strategy to synthesize anisotropic SmCo 5 nanoplates. The strategy involves the pre-synthesis of 125 x 12 nm Sm(OH) 3 nanorods and 10 nm Co nanoparticles followed by self-assembly of these nanorods and nanoparticles into Sm(OH) 3-Co nanocomposites. Once embedded in CaO matrix, the nanocomposite is subject to high temperature (850 °C) annealing in the presence of Ca, leading to the formation of 125 x 10 nm SmCo 5 nanoplates, which are dispersible in ethanol, allowing the alignment in epoxy resin under a 20 kOe magnetic field. The aligned SmCo 5 nanoplates show a square hysteresis behaviormore » with room temperature coercivity reaching 30.1 kOe, which is among the highest values ever reported for SmCo 5 made from chemical methods. The work provides a new approach to high-performance anisotropic SmCo 5 for permanent magnet applications.« less

A New Strategy to Synthesize Anisotropic SmCo 5 Nanomagnets

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shen, Bo; Yu, Chao; Su, Dong

We report a simple strategy to synthesize anisotropic SmCo 5 nanoplates. The strategy involves the pre-synthesis of 125 x 12 nm Sm(OH) 3 nanorods and 10 nm Co nanoparticles followed by self-assembly of these nanorods and nanoparticles into Sm(OH) 3-Co nanocomposites. Once embedded in CaO matrix, the nanocomposite is subject to high temperature (850 °C) annealing in the presence of Ca, leading to the formation of 125 x 10 nm SmCo 5 nanoplates, which are dispersible in ethanol, allowing the alignment in epoxy resin under a 20 kOe magnetic field. The aligned SmCo 5 nanoplates show a square hysteresis behaviormore » with room temperature coercivity reaching 30.1 kOe, which is among the highest values ever reported for SmCo 5 made from chemical methods. The work provides a new approach to high-performance anisotropic SmCo 5 for permanent magnet applications.« less

CD147 reinforces [Ca2+]i oscillations and promotes oncogenic progression in hepatocellular carcinoma.

PubMed

Tang, Juan; Guo, Yun-Shan; Yu, Xiao-Ling; Huang, Wan; Zheng, Ming; Zhou, Ying-Hui; Nan, Gang; Wang, Jian-Chao; Yang, Hai-Jiao; Yu, Jing-Min; Jiang, Jian-Li; Chen, Zhi-Nan

2015-10-27

Oscillations in intracellular Ca2+ concentrations ([Ca2+]i) mediate various cellular function. Although it is known that [Ca2+]i oscillations are susceptible to dysregulation in tumors, the tumor-specific regulators of [Ca2+]i oscillations are poorly characterized. We discovered that CD147 promotes hepatocellular carcinoma (HCC) metastasis and proliferation by enhancing the amplitude and frequency of [Ca2+]i oscillations in HCC cells. CD147 activates two distinct signaling pathways to regulate [Ca2+]i oscillations. By activating FAK-Src-IP3R1 signaling pathway, CD147 promotes Ca2+ release from endoplasmic reticulum (ER) and enhances the amplitude of [Ca2+]i oscillations. Furthermore, CD147 accelerates ER Ca2+refilling and enhances the frequency of [Ca2+]i oscillations through activating CaMKP-PAK1-PP2A-PLB-SERCA signaling pathway. Besides, CD147-promoted ER Ca2+ release and refilling are tightly regulated by changing [Ca2+]i. CD147 may activate IP3R1 channel under low [Ca2+]i conditions and CD147 may activate SERCA pump under high [Ca2+]i conditions. CD147 deletion suppresses HCC tumorigenesis and increases the survival rate of liver-specific CD147 knockout mice by regulating [Ca2+]i oscillations in vivo. Together, these results reveal that CD147 functions as a critical regulator of ER-dependent [Ca2+]i oscillations to promote oncogenic progression in HCC.

CD147 reinforces [Ca2+]i oscillations and promotes oncogenic progression in hepatocellular carcinoma

PubMed Central

Zheng, Ming; Zhou, Ying-Hui; Nan, Gang; Wang, Jian-Chao; Yang, Hai-Jiao; Yu, Jing-Min; Jiang, Jian-Li; Chen, Zhi-Nan

2015-01-01

Oscillations in intracellular Ca2+ concentrations ([Ca2+]i) mediate various cellular function. Although it is known that [Ca2+]i oscillations are susceptible to dysregulation in tumors, the tumor-specific regulators of [Ca2+]i oscillations are poorly characterized. We discovered that CD147 promotes hepatocellular carcinoma (HCC) metastasis and proliferation by enhancing the amplitude and frequency of [Ca2+]i oscillations in HCC cells. CD147 activates two distinct signaling pathways to regulate [Ca2+]i oscillations. By activating FAK-Src-IP3R1 signaling pathway, CD147 promotes Ca2+ release from endoplasmic reticulum (ER) and enhances the amplitude of [Ca2+]i oscillations. Furthermore, CD147 accelerates ER Ca2+ refilling and enhances the frequency of [Ca2+]i oscillations through activating CaMKP-PAK1-PP2A-PLB-SERCA signaling pathway. Besides, CD147-promoted ER Ca2+ release and refilling are tightly regulated by changing [Ca2+]i. CD147 may activate IP3R1 channel under low [Ca2+]i conditions and CD147 may activate SERCA pump under high [Ca2+]i conditions. CD147 deletion suppresses HCC tumorigenesis and increases the survival rate of liver-specific CD147 knockout mice by regulating [Ca2+]i oscillations in vivo. Together, these results reveal that CD147 functions as a critical regulator of ER-dependent [Ca2+]i oscillations to promote oncogenic progression in HCC. PMID:26498680

Surgical Treatment of Metastatic Ovarian Tumors From Extragenital Primary Sites.

PubMed

Sal, Veysel; Demirkiran, Fuat; Topuz, Samet; Kahramanoglu, Ilker; Yalcin, Ibrahim; Bese, Tugan; Sozen, Hamdullah; Tokgozoglu, Nedim; Salihoglu, Yavuz; Turan, Hasan; Iyibozkurt, Cem; Kolomuc, Tugba; Sofiyeva, Nigar; Berkman, Sinan; Arvas, Macit

2016-05-01

The purpose of this study was to investigate the outcomes and prognostic factors of metastasectomy in patients with metastatic ovarian tumors from extragenital primary sites. All patients with pathologically confirmed metastatic ovarian tumors between January 1997 and June 2015 were included in this study. A total of 131 patients were identified. The data were obtained from the patients' medical records. Clinicopathological features were evaluated by both univariate and multivariate analyses. The primary sites were colorectal region (53.4%), stomach (26%), and breast (13%). Preoperative serum CA 125 and CA 19-9 levels were elevated in 29.4% and 39.8% of the patients, respectively. Cytoreductive surgery was performed in 41.2% of the patients. Seventy-three (55.7%) patients had no residual disease after surgery. Sixty-six (49.6%) patients had combined metastases at the time of the surgery to sites including the liver, pancreas, lung, bone, lymph nodes, bladder, or the intestine. With a median follow-up of 33 months, the median survival time was 22 months. The estimated 5-year survival probability is 0.26. On univariate analysis, primary cancer site, combined metastasis outside the ovaries, residual disease, preoperative serum CA 125 and CA 19-9 levels, and histologic type were significant parameters for overall survival. Furthermore, residual disease, preoperative serum CA 19-9 level, and primary cancer site were found to be independent prognostic factors on multivariate analysis. The most common primary sites for ovarian metastasis are gastrointestinal tract. Metastasectomy may have beneficial effects on survival, especially if the residual disease is less than 5 mm. Prospective studies warranted to evaluate the value of metastasectomy in patients with ovarian metastasis.

Cervical Disc Deformation During Flexion–Extension in Asymptomatic Controls and Single-Level Arthrodesis Patients

PubMed Central

Anderst, William; Donaldson, William; Lee, Joon; Kang, James

2016-01-01

The aim of this study was to characterize cervical disc deformation in asymptomatic subjects and single-level arthrodesis patients during in vivo functional motion. A validated model-based tracking technique determined vertebral motion from biplane radiographs collected during dynamic flexion–extension. Level-dependent differences in disc compression–distraction and shear deformation were identified within the anterior and posterior annulus (PA) and the nucleus of 20 asymptomatic subjects and 15 arthrodesis patients using a mixed-model statistical analysis. In asymptomatic subjects, disc compression and shear deformation per degree of flexion–extension progressively decreased from C23 to C67. The anterior and PA experienced compression–distraction deformation of up to 20%, while the nucleus region was compressed between 0% (C67) and 12% (C23). Peak shear deformation ranged from 16% (at C67) to 33% (at C45). In the C5–C6 arthrodesis group, C45 discs were significantly less compressed than in the control group in all disc regions (all p ≤ 0.026). In the C6–C7 arthrodesis group, C56 discs were significantly less compressed than the control group in the nucleus (p = 0.023) and PA (p = 0.014), but not the anterior annulus (AA; p = 0.137). These results indicate in vivo disc deformation is level-dependent, and single-level anterior arthrodesis alters the compression–distraction deformation in the disc immediately superior to the arthrodesis. PMID:23861160

MECHANISMS IN ENDOCRINOLOGY: Kidney involvement in patients with primary hyperparathyroidism: an update on clinical and molecular aspects.

PubMed

Verdelli, C; Corbetta, S

2017-01-01

Primary hyperparathyroidism (PHPT) is the third most common endocrine disease. Kidney is a target of both chronic elevated PTH and calcium in PHPT. The classic PHPT complications of symptomatic kidney stones and nephrocalcinosis have become rare and the PHPT current presentation is asymptomatic with uncertain and long-lasting progression. Nonetheless, the routine use of imaging and of biochemical determinations have revealed the frequent occurrence of asymptomatic kidney stones, hypercalciuria and reduced kidney function in asymptomatic PHPT patients. Though the pathogenesis is far from being elucidated, PHPT is associated with reduced renal function, in terms of estimated glomerular filtration rate, and related increased morbidity and mortality. In the last decade, the effort of the Kidney Disease: Improving Global Outcomes (KDIGO) panel of experts highlighted that even mild reduction of kidney function is associated with increased risk of cardiovascular disease. These considerations provided the basis for the Fourth Workshop recommendations of a more extensive diagnostic workout about kidney features and of wider criteria for parathyroid surgery including asymptomatic kidney disease. Moreover, kidney involvement in PHPT is likely to be affected by variants of genes coding the key molecules regulating the calcium and ions renal handling; these features might have clinical relevance and should be considered both during diagnostic workout and follow-up. Finally, the effects of parathyroid surgery and of medical treatment on kidney involvement of PHPT are reviewed. © 2017 European Society of Endocrinology.

[Urinary tract infections in pregnancy: when to treat, how to treat, and what to treat with].

PubMed

Kladenský, J

2012-04-01

Urinary tract infections (UTI) in pregnant women are a relatively frequent occurrence and the spectrum of these infections ranges from lower urinary tract disease (asymptomatic bacteriuria, acute cystitis) to upper urinary tract disease (acute pyelonephritis). Anatomical and functional changes in the urinary tract in pregnancy result in significantly higher susceptibility to progression of the infection from asymptomatic bacteriuria to the stage of acute pyelonephritis. Untreated asymptomatic bacteriuria in pregnancy leads, in as much as 40%, to the development of acute pyelonephritis with all the subsequent negative effects not only for the woman herself, but particularly for the fetus. Bacteriuria in pregnancy accounts for a significantly higher number of newborns with a low birth weight, low gestational age and higher neonatal mortality rate. Therefore, it is necessary to perform screening for bacteriuria in pregnant women and, when the finding is positive, to treat this bacteriuria. The selection of an appropriate antimicrobial agent to treat urinary tract infection in pregnancy is limited by the safety of a given drug not only for the woman, but particularly for the fetus. The article provides an overview of medications that can be safely used throughout the pregnancy or only in certain stages of pregnancy. The selection of an appropriate antibiotic should always be preceded by the result of urine culture. The article presents the principles and rules for treating asymptomatic bacteriuria, acute cystitis and acute pyelonephritis in pregnant women.

Endemic chronic kidney disease of unknown etiology in Sri Lanka: Correlation of pathology with clinical stages

PubMed Central

Wijetunge, S.; Ratnatunga, N. V. I.; Abeysekera, T. D. J.; Wazil, A. W. M.; Selvarajah, M.

2015-01-01

Chronic kidney disease of unknown etiology (CKDU) is endemic among the rural farming communities in several localities in and around the North Central region of Sri Lanka. This is an interstitial type renal disease and typically has an insidious onset and slow progression. This study was conducted to identify the pathological features in the different clinical stages of CKDU. This is a retrospective study of 251 renal biopsies identified to have a primary interstitial disease from regions endemic for CKDU. Pathological features were assessed and graded in relation to the clinical stage. The mean age of those affected by endemic CKDU was 37.3 ± 12.5 years and the male to female ratio was 3.3:1. The predominant feature of stage I disease was mild and moderate interstitial fibrosis; most did not have interstitial inflammation. The typical stage II disease had moderate interstitial fibrosis with or without mild interstitial inflammation. Stage III disease had moderate and severe interstitial fibrosis, moderate interstitial inflammation, tubular atrophy and some glomerulosclerosis. Stage IV disease typically had severe interstitial fibrosis and inflammation, tubular atrophy and glomerulosclerosis. The mean age of patients with stage I disease (27 ± 10.8 years) was significantly lower than those of the other stages. About 79.2%, 55%, 49.1% and 50% in stage I, II, III and IV disease respectively were asymptomatic at the time of biopsy. PMID:26628792

Intergenerational responses of wheat (Triticum aestivum L.) to ...

EPA Pesticide Factsheets

The intergenerational impact of engineered nanomaterials in plants is a key knowledge gap in the literature. A soil microcosm study was performed to assess the effects of multi-generational exposure of wheat (Triticum aestivum L.) to cerium oxide nanoparticles (CeO2-NPs). Seeds from plants that were exposed to 0, 125, and 500 mg CeO2-NPs/kg soil (Ce-0, Ce-125 or Ce-500, respectively) in first generation (S1) were cultivated in factorial combinations of Ce-0, Ce-125 or Ce-500 to produce second generation (S2) plants. The factorial combinations for first/second generation treatments in Ce-125 were S1-Ce-0/S2-Ce-0, S1-Ce-0/S2-Ce-125, S1-Ce-125/S2-Ce-0 and S1-Ce-125/S2-Ce-125, and in Ce-500 were S1-Ce-0/S2-Ce-0, S1-Ce-0/S2-Ce-500, S1-Ce-500/S2-Ce-0 and S1-Ce-500/S2-Ce-500. Agronomic, elemental, and isotopic data were collected in second generation plants. Results showed that plants treated during the first generation only with either Ce-125 or Ce-500 (e.g. S1-Ce-125/S2-Ce-0 or S1-Ce-500/S2-Ce-0) had reduced accumulation of Ce (61 or 50%), Fe (49 or 58%) and Mn (34 or 41%) in roots, and δ15N (11 or 8%) in grains compared to the plants not treated in both generations (i.e. S1-Ce-0/S2-Ce-0). In addition, plants treated in both generations with Ce-125 (i.e. S1-Ce-125/S2-Ce-125) produced grains that had lower Mn, Ca, K, Mg and P relative to plants treated in the second generation only (i.e. S1-Ce-0/S2-Ce-125). The findings demonstrated that first generation exposure of

MUC1, MUC2, MUC4, MUC5AC and MUC6 expression in the progression of prostate cancer.

PubMed

Cozzi, Paul J; Wang, Jian; Delprado, Warick; Perkins, Alan C; Allen, Barry J; Russell, Pamela J; Li, Yong

2005-01-01

Molecular changes are vital for the development of prognostic markers and therapeutic modalities of prostate cancer (CaP). There is growing interest in mucins as treatment targets in human malignancies, including CaP. The role of their expression in the progression of CaP is however unclear. We examined the expressions MUC1, MUC2, MUC4, MUC5AC and MUC6 in CaP tissues using tissue microarrays (TMAs) to look for tumor-associated antigens (TAAs) for targeted therapy. In this study, 120 paraffin-embedded specimens were selected from patients who underwent radical retro-pubic prostatectomy (RRP) or trans-urethral-resection of the prostate (TURP) for primary, untreated CaP and 10 matched lymph node metastases. A series of MUC monoclonal antibodies (mAbs) was used on TMAs by standard immunohistochemistry. Our results indicate that the over-expression of MUC1 was detected in 58% of primary CaP tissues and 90% of lymph node metastases but not in normal prostate or benign tissues, while the expression of MUC2, MUC4, MUC5AC and MUC6 was found to be negative in both normal and cancer tissues. Of the MUC1 positive tumors 86% were Gleason grade 7 or higher. Over-expression of MUC1 was found in late stage CaP while MUC2, 4, 5AC and 6 were negative in CaP. MUC1 is a TAA that is highly related to tumor progression in CaP patients. This antigen is ideal for targeted therapy to control micrometastases and hormone refractory disease but additional studies are necessary to assess its usefulness in patient biopsies and CaP bone metastases before clinical trial.

Correlations between gene expression highlight a different activation of ACE/TLR4/PTGS2 signaling in symptomatic and asymptomatic plaques in atherosclerotic patients.

PubMed

Ferronato, Silvia; Scuro, Alberto; Gomez-Lira, Macarena; Mazzucco, Sara; Olivato, Silvia; Turco, Alberto; Elisa, Orlandi; Malerba, Giovanni; Romanelli, Maria Grazia

2018-06-19

Inflammation has a key role and translates the effects of many known risk factors for the disease in atherosclerotic vulnerable plaques. Aiming to look into the elements that induce the development of either a vulnerable or stable atherosclerotic plaque, and considering that inflammation has a central role in the progression of lesions, we analyzed the expression of genes involved in the ACE/TLR4/PTGS2 signaling in carotid plaques of symptomatic and asymptomatic patients. Patients with internal carotid artery stenosis undergoing carotid endarterectomy at Verona University Hospital were included in this study. A total of 71 patients was considered for gene expression analysis (29 atherothrombotic stroke patients and 42 asymptomatic patients). Total RNA was extracted from the excised plaques and expression of PTGS2, ACE, TLR4, PTGER4, PTGER3, EPRAP and ACSL4 genes was analyzed by real-time PCR. The correlation between the pair of genes was studied by Spearman coefficient. From the analyzed genes, we did not observe any individual difference in gene expression but the network of co-expressed genes suggests a different activation of pathways in the two groups of plaques.

Strained enabled Ferroelectricity in CaTiO3 Thin Films Probed by Nonlinear Optics and Scanning Probe Microscopy

NASA Astrophysics Data System (ADS)

Vlahos, Eftihia; Kumar, Amit; Denev, Sava; Brooks, Charles; Schlom, Darrell; Eklund, Carl-Johan; Rabe, Karin M.; Fennie, Craig J.; Gopalan, Venkatraman

2009-03-01

Calcium titanate, CaTiO3 is not a ferroelectric in its bulk form. However, first principles calculations predict that biaxially tensile strained CaTiO3 thin films should become ferroelectric. Here, we indeed confirm that strained CaTiO3 films become ferroelectric with a Curie temperature of ˜125K. Optical second harmonic generation (SHG) measurements, polarization studies, and in-situ electric-field measurements for a number of films with different strain values will be presented: CaTiO3/DyScO3(110), CaTiO3/SrTiO3 (100),CaTiO3/GdScO3/NdGaO3(110), CaTiO3/LaSrAlO3(001) as well as for a single crystal CaTiO3. From these studies, we conclude that strained CaTiO3 films are ferroelectric with a point group symmetry of mm2, and show reversible domain switching characteristics under an electric field. We also present results of variable temperature piezoelectric force microscopy for imaging the polar domains in the ferroelectric phase. These results suggest that strain is a valuable tool for inducing polar, long range ferroelectric order in even non-polar ceramic materials such as CaTiO3.

Localization and Distribution of 'Candidatus Liberibacter asiaticus’ in Citrus and Periwinkle by Direct Tissue Blot Immuno Assay with an Anti-OmpA Polyclonal Antibody

PubMed Central

Ding, Fang; Duan, Yongping; Paul, Cristina; Brlansky, Ronald H.; Hartung, John S.

2015-01-01

‘Candidatus Liberibacter asiaticus’ (CaLas), a non-cultured member of the α-proteobacteria, is the causal agent of citrus Huanglongbing (HLB). Due to the difficulties of in vitro culture, antibodies against CaLas have not been widely used in studies of this pathogen. We have used an anti-OmpA polyclonal antibody based direct tissue blot immunoassay to localize CaLas in different citrus tissues and in periwinkle leaves. In citrus petioles, CaLas was unevenly distributed in the phloem sieve tubes, and tended to colonize in phloem sieve tubes on the underside of petioles in preference to the upper side of petioles. Both the leaf abscission zone and the junction of the petiole and leaf midrib had fewer CaLas bacteria compared to the main portions of the petiole and the midribs. Colonies of CaLas in phloem sieve tubes were more frequently found in stems with symptomatic leaves than in stems with asymptomatic leaves with an uneven distribution pattern. In serial sections taken from the receptacle to the peduncle, more CaLas were observed in the peduncle sections adjacent to the stem. In seed, CaLas was located in the seed coat. Many fewer CaLas were found in the roots, as compared to the seeds and petioles when samples were collected from trees with obvious foliar symptoms. The direct tissue blot immuno assay was adapted to whole periwinkle leaves infected by CaLas. The pathogen was distributed throughout the lateral veins and the results were correlated with results of qPCR. Our data provide direct spatial and anatomical information for CaLas in planta. This simple and scalable method may facilitate the future research on the interaction of CaLas and host plant. PMID:25946013

Distribution of Plasmodium spp. infection in asymptomatic carriers in perennial and low seasonal malaria transmission settings in West Africa.

PubMed

Gbalégba, Constant G N; Ba, Hampâté; Silué, Kigbafori D; Ba, Ousmane; Tia, Emmanuel; Chouaibou, Mouhamadou; Tian-Bi, Nathan T Y; Yapi, Grégoire Y; Koné, Brama; Utzinger, Jürg; Koudou, Benjamin G

2018-04-25

Since 2000, substantial progress has been made in reducing malaria worldwide. However, some countries in West Africa remain a hotspot for malaria with all age groups at risk. Asymptomatic carriers of Plasmodium spp. are important sources of infections for malaria vectors and thus contribute to the anchoring of the disease in favourable eco-epidemiological settings. The objective of this study was to assess the asymptomatic malaria case rates in Korhogo and Kaedi, two urban areas in northern Côte d'Ivoire and southern Mauritania, respectively. Cross-sectional surveys were carried out during the rainy season in 2014 and the dry season in 2015 in both settings. During each season, 728 households were randomly selected and a household-based questionnaire was implemented to collect demographic and epidemiological data, including of malaria preventive methods used in communities. Finger-prick blood samples were obtained for biological examination using microscopy and rapid diagnostic tests (RDTs). Overall, 2672 households and 15 858 consenting participants were surveyed. Plasmodium spp. infection was confirmed in 12.4% (n = 832) and 0.3% (n = 22) of the assessed individuals in Korhogo and Kaedi, respectively. In Korhogo, the prevalence of asymptomatic malaria was 10.5% (95% CI: 9.7-11.2) as determined by microscopy and 9.3% (95% CI: 8.6-10.0%) when assessed by RDT. In Kaedi, asymptomatic malaria prevalence was 0.2% (95% CI: 0.1-0.4%) according to microscopy, while all RDTs performed were negative (n = 8372). In Korhogo, asymptomatic malaria infection was significantly associated with age and season, with higher risk within the 5-14 years-old, and during the rainy season. In Kaedi, the risk of asymptomatic malaria infection was associated with season only (higher during the dry season; crude OR (cOR): 6.37, 95% CI: 1.87-21.63). P. falciparum was the predominant species identified in both study sites representing 99.2% (n = 825) in Korhogo and 59.1% (n = 13) in Kaedi. Gametocytes were observed only in Korhogo and only during the rainy season at 1.3% (95% CI: 0.7-2.4%). Our findings show a low prevalence of clinical malaria episodes with a significant proportion of asymptomatic carriers in both urban areas. National policies for malaria infections are focused on treatment of symptomatic cases. Malaria control strategies should be designed for monitoring and managing malaria infections in asymptomatic carriers. Additional measures, including indoor residual spraying, effective use of long-lasting insecticidal nets is strongly needed to reduce the number of Plasmodium spp. infections in Korhogo and Kaedi.

The hydrophilic domain of phospholamban inhibits the Ca2+ transport step of the Ca(2+)-ATPase.

PubMed Central

Hughes, G; East, J M; Lee, A G

1994-01-01

The peptide MEKVQYLTRSAIRRASTIEMPQQAR-Cys corresponding to residues 1-25 of phospholamban was found to inhibit the ATPase activity of skeletal muscle Ca(2+)-ATPase, but to have no effect on the Ca(2+)-dependence of its activity. The peptide was found to decrease the rate of the Ca2+ transport step (E1PCa2-->E2P) by a factor of 2.4. The rate of this same step was decreased by poly(L-Arg) by a factor of 2.2. The peptide shifted the E2-E1 equilibrium of the ATPase towards E1 by a factor of 4 due to stronger binding to the E1 than to the E2 conformation of the ATPase; dissociation constants for binding to E1 and E2 were estimated as 3 and 10 microM respectively. The peptide had no effect on the level of phosphorylation by Pi in the absence of Ca2+ or on the rate of phosphorylation by ATP in the presence of Ca2+. PMID:7980411

Aragonite pteropod flux to the Somali Basin, NW Arabian Sea

NASA Astrophysics Data System (ADS)

Singh, A. D.; Conan, S. M.-H.

2008-05-01

Aragonite export fluxes of pteropods (>250, 150-250 and 125-150 μm) in the Somali Basin were estimated using a 9-month time-series sediment trap (MST9-E) from June 1992 to February 1993. The trap with 23 time-series sediment collectors placed at 1032 m water depth collected settling particles over a total of 249 days. Pteropods showed large seasonal variations in both the numerical and mass fluxes (>125 μm) with their maxima at the end of the SW Monsoon during September and early October. It was also observed that records of pteropod fluxes varied in different size fractions. The average numerical flux and mass flux of pteropods (>125 μm) from the 9-month record of the sediment trap was estimated to be about 1830 shells m -2 d -1 and 18 mg m -2 d -1, respectively. We estimate that about 22.5% of the total CaCO 3 in the Somali Basin was contributed by aragonitic pteropods (>125 μm).

Effect of Age, Estrogen Status, and Late-Life GPER Activation on Cardiac Structure and Function in the Fischer344×Brown Norway Female Rat.

PubMed

Alencar, Allan K; da Silva, Jaqueline S; Lin, Marina; Silva, Ananssa M; Sun, Xuming; Ferrario, Carlos M; Cheng, Cheping; Sudo, Roberto T; Zapata-Sudo, Gisele; Wang, Hao; Groban, Leanne

2017-02-01

Age-associated changes in cardiac structure and function, together with estrogen loss, contribute to the progression of heart failure with preserved ejection fraction in older women. To investigate the effects of aging and estrogen loss on the development of its precursor, asymptomatic left ventricular diastolic dysfunction, echocardiograms were performed in 10 middle-aged (20 months) and 30 old-aged (30 months) female Fischer344×Brown-Norway rats, 4 and 8 weeks after ovariectomy (OVX) and sham procedures (gonads left intact). The cardioprotective potential of administering chronic G1, the selective agonist to the new G-protein-coupled estrogen receptor (GPER), was further evaluated in old rats (Old-OVX+G1) versus age-matched, vehicle-treated OVX and gonadal intact rats. Advanced age and estrogen loss led to decreases in myocardial relaxation and elevations in filling pressure, in part, due to reductions in phosphorylated phospholamban and increases in cardiac collagen deposition. Eight weeks of G-protein-coupled estrogen receptor activation in Old-OVX+G1 rats reversed the adverse effects of age and estrogen loss on myocardial relaxation through increases in sarcoplasmic reticulum Ca 2+ ATPase expression and reductions in interstitial fibrosis. These findings may explain the preponderance of heart failure with preserved ejection fraction in older postmenopausal women and provide a promising, late-life therapeutic target to reverse or halt the progression of left ventricular diastolic dysfunction. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

TRIBUTYLTIN INCREASES CYTOSOLIC FREE CA++ CONCENTRATION IN THYMOCYTES BY MOBILIZING INTRACELLULAR CA++, ACTIVATING A CA++ ENTRY PATHWAY, AND INHIBITING CA++ EFFLUX. (R823881)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

[Many faces of sarcoidosis].

PubMed

Prosch, H; Vonbank, K; Loewe, C; Beitzke, D

2016-01-01

Sarcoidosis is a systemic, inflammatory, granulomatous disease of unknown origin that can involve any organ. More than 90% of patients have thoracic sarcoidosis, which most frequently presents with bilateral hilar lymphadenopathy. In approximately 20% of patients with thoracic sarcoidosis there is involvement of the lung parenchyma as well as mostly asymptomatic cardiac sarcoidosis in up to 55% of patients. Most patients are asymptomatic and the diagnosis is an incidental finding on chest X-ray or during clarification of unspecific symptoms, such as fatigue or cough. In approximately two thirds of patients the disease undergoes spontaneous remission and in one third the disease follows a chronic or even progressive course. Furthermore, sarcoidosis can also be manifested in the abdominal organs, the central nervous system (CNS) and the musculoskeletal system. These manifestations are frequently subclinical and require targeted diagnostics when sarcoidosis is clinically suspected.

Treatment of Carotid Artery Disease: Endarterectomy or Angioplasty?

PubMed Central

Marchidann, Adrian; Marshall, Randolph S.

2011-01-01

The management of carotid stenosis has enjoyed renewed interest in the neurological community in recent years due to the advent of endovascular approaches. In concert, progress in medical treatment of these patients has rekindled the debate regarding the best management of carotid stenosis overall, both for symptomatic and asymptomatic disease. For symptomatic carotid stenosis, the major decision required is choosing the type of intervention best suited for individual patients — carotid endarterectomy (CEA) versus carotid artery stenting (CAS). For patients with asymptomatic carotid stenosis, intensive medical management has evolved significantly over the past decade to decrease the risk of ischemic stroke to match surgical intervention under most circumstances. This review will examine the supporting evidence for each intervention, and discuss the recent advances in medical and endovascular therapy that provide the data for a new era in clinical decision making. PMID:20960240

Phase II of oral gimatecan in patients with recurrent epithelial ovarian, fallopian tube or peritoneal cancer, previously treated with platinum and taxanes

PubMed Central

Pecorelli, S.; Ray-Coquard, I.; Tredan, O.; Colombo, N.; Parma, G.; Tisi, G.; Katsaròs, D.; Lhommé, C.; Lissoni, A. A.; Vermorken, J. B.; du Bois, A.; Poveda, A.; Frigerio, L.; Barbieri, P.; Carminati, P.; Brienza, S.; Guastalla, J. P.

2010-01-01

Background: A prospective phase II study was conducted to evaluate the efficacy and toxicity of oral gimatecan in patients with recurrent epithelial ovarian, fallopian tube or peritoneal cancer. Patients and methods: Patients had a maximum of three prior chemotherapy lines with no more than two prior platinum-containing regimens and a progression-free interval after the last dose of platinum <12 months. A total dose of 4 mg/m2/cycle (0.8 mg/m2/day from day 1 to day 5) was administered, repeated every 28 days. Results: From June 2005 to December 2005, 69 assessable patients were enrolled. The best overall response to study treatment by combined CA-125 and RECIST criteria was partial response in 17 patients (24.6%) and disease stabilization in 22 patients (31.9%). The median time to progression and overall survival were 3.8 and 16.2 months, respectively. A total of 312 cycles were administered. Neutropenia grade 4 and thrombocytopenia grade 4 occurred in 17.4% and 7.2% of patients, respectively. Diarrhea grade 4 was never observed. Asthenia and fatigue were reported by 36.2% and 18.8% of patients, but were all grade 2 or less. Conclusion: Gimatecan is a new active agent in previously treated ovarian cancer with myelosuppression as main toxicity. PMID:19906760

[Acetabular Osteolysis in Total Hip Replacement - When to Retain the Cup?].

PubMed

Lutz, B; Faschingbauer, M; Bieger, R; Reichel, H; Kappe, T

2016-08-01

Periacetabular osteolysis is a frequent long-term complication of cementless total hip arthroplasty. The decision whether to retain or to revise a cup in the presence of osteolysis remains a challenge. The options are regular clinical and radiological check-ups, isolated liner exchange with and without bone grafting, and complete cup revision. Thorough preoperative diagnostics, including a medical history, examination and imaging, are mandatory for correct decision making. In most patients, computed tomography is useful to assess periacetabular osteolysis. If the cup is well-fixed and positioned in an asymptomatic patient without progressive osteolysis and no implant defect or higher grade polyethylene wear and no signs of infection, continuous clinical and radiological monitoring is preferred. If imaging reveals cup loosening, malposition, osteolysis localised in a weight-bearing area, imminent or present periprosthetic fractures, rapid progressive osteolysis, implant defects or massive inlay wear, surgical treatment may be preferred. Cup revision is usually performed in such patients. If the cup is well-positioned and well-fixed in the X-ray, the procedure has to be discussed with the patient individually. Apart from patient-specific risk factors, the risk of further progression has to be assessed. Isolated liner exchange can be performed if the patient is asymptomatic and the cup proves to be stable intraoperatively. It is still unclear whether filling osteolyses through screw holes or osseous windows is of long-term benefit. Georg Thieme Verlag KG Stuttgart · New York.

41. Photocopy of progress photograph ca. 1974, photographer unknown. Original ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

41. Photocopy of progress photograph ca. 1974, photographer unknown. Original photograph Property of United States Air Force, 21" Space Command. This is the source for views 41 to 47. CAPE COD AIR STATION PAVE PAWS FACILITY - SHOWING BUILDING "RED IRON" STEEL STRUCTURE NEARING COMPLETION. - Cape Cod Air Station, Technical Facility-Scanner Building & Power Plant, Massachusetts Military Reservation, Sandwich, Barnstable County, MA

Evaluation of lead and essential elements in whole blood during pregnancy: a cross-sectional study.

PubMed

Liu, K; Mao, X; Shi, J; Lu, Y; Liu, C

2016-08-01

Physiological concentrations of some elements fluctuate during pregnancy due to the increased requirements of growing fetus and changes in the maternal physiology. The aim of the study is to evaluate the distribution at different stages of pregnancy in healthy Chinese women and to show the association between trace elements and gestational age-specific reference intervals. A cross-sectional study was performed in 1089 pregnant women and 677 nonpregnant control women. Five element concentrations, including Cu, Zn, Ca, Mg, Pb in the blood were determined by atomic absorption spectrometry. Spearman's rank correlation test was used to assess the relationship between weeks of gestation and blood element concentrations. The mean levels of Cu and Mg were 23.64 ± 4.69 μmol/L and 1.36 ± 0.12 mmol/L, respectively, in the control women. While 0.68 % of all pregnant women showed Cu levels below the normal ranges, the levels of Mg were comparable in different groups. Though the overall mean blood zinc and Ca concentrations (83.84 ± 17.50 μmol/L and 1.60 ± 0.15 mmol/L, respectively) increased gradually with the progress of gestation, the Zn and Ca deficiency levels (16.6 and 3.6 %, respectively) decreased with the advance of gestation. Compared with nonpregnant group, the concentrations of Cu, Zn, Ca, Mg, Pb during the different stages of pregnancy, as a whole, were significantly different. Positive correlations were observed between weeks of gestation and blood Cu, Ca, Pb concentrations (r = 0.301, 0.221, 0.223; P < 0.05). There was a negative correlation blood Mg concentrations and weeks of gestation (r = -0.321; P < 0.05). A weak positive correlation was noted between Zn concentrations and weeks of gestation (r = 0.125; P < 0.05). The importance of Cu and Mg deficiency and supplementation is well realized, but, Zn/Ca deficiency and Pb exposure is still exist; the overall deficiency of pregnant women was not so optimistic. During pregnancy, the established reference values will provide an important guidance for the reasonable supplementation of essential elements and surveillance of lead overexposure.

Activation of the Ca2+-sensing receptor increases renal claudin-14 expression and urinary Ca2+ excretion

PubMed Central

Dimke, Henrik; Desai, Prajakta; Borovac, Jelena; Lau, Alyssa; Pan, Wanling; Alexander, R. Todd

2016-01-01

Kidney stones are a prevalent clinical condition imposing a large economic burden on the health-care system. Hypercalciuria remains the major risk factor for development of a Ca2+-containing stone. The kidney’s ability to alter Ca2+ excretion in response to changes in serum Ca2+ is in part mediated by the Ca2+-sensing receptor (CaSR). Recent studies revealed renal claudin-14 (Cldn14) expression localized to the thick ascending limb (TAL) and its expression to be regulated via the CaSR. We find that Cldn14 expression is increased by high dietary Ca2+ intake and by elevated serum Ca2+ levels induced by prolonged 1,25-dihydroxyvitamin D3 administration. Consistent with this, activation of the CaSR in vivo via administration of the calcimimetic cinacalcet hydrochloride led to a 40-fold increase in Cldn14 mRNA. Moreover, overexpression of Cldn14 in two separate cell culture models decreased paracellular Ca2+ flux by preferentially decreasing cation permeability, thereby increasing transepithelial resistance. These data support the existence of a mechanism whereby activation of the CaSR in the TAL increases Cldn14 expression, which in turn blocks the paracellular reabsorption of Ca2+. This molecular mechanism likely facilitates renal Ca2+ losses in response to elevated serum Ca2+. Moreover, dys-regulation of the newly described CaSR-Cldn14 axis likely contributes to the development of hypercalciuria and kidney stones. PMID:23283989

Host virus and pneumococcus-specific immune responses in high-count monoclonal B-cell lymphocytosis and chronic lymphocytic leukemia: implications for disease progression

PubMed Central

Criado, Ignacio; Muñoz-Criado, Santiago; Rodríguez-Caballero, Arancha; Nieto, Wendy G.; Romero, Alfonso; Fernández-Navarro, Paulino; Alcoceba, Miguel; Contreras, Teresa; González, Marcos; Orfao, Alberto; Almeida, Julia

2017-01-01

Patients diagnosed with chronic lymphocytic leukemia (CLL) display a high incidence of infections due to an associated immunodeficiency that includes hypogammaglobulinemia. A higher risk of infections has also been recently reported for high-count monoclonal B-cell lymphocytosis, while no information is available in low-count monoclonal B-cell lymphocytosis. Here, we evaluated the status of the humoral immune system in patients with chronic lymphocytic leukemia (n=58), as well as in low- (n=71) and high- (n=29) count monoclonal B-cell lymphocytosis versus healthy donors (n=91). Total free plasma immunoglobulin titers and specific levels of antibodies against cytomegalovirus, Epstein-Barr virus, influenza and S.pneumoniae were measured by nephelometry and ELISA-based techniques, respectively. Overall, our results show that both CLL and high-count monoclonal B-cell lymphocytosis patients, but not low-count monoclonal B-cell lymphocytosis subjects, present with relatively high levels of antibodies specific for the latent viruses investigated, associated with progressively lower levels of S.pneumoniae-specific immunoglobulins. These findings probably reflect asymptomatic chronic reactivation of humoral immune responses against host viruses associated with expanded virus-specific antibody levels and progressively decreased protection against other micro-organisms, denoting a severe humoral immunodeficiency state not reflected by the overall plasma immunoglobulin levels. Alternatively, these results could reflect a potential role of ubiquitous viruses in the pathogenesis of the disease. Further analyses are necessary to establish the relevance of such asymptomatic humoral immune responses against host viruses in the expansion of the tumor B-cell clone and progression from monoclonal B-cell lymphocytosis to CLL. PMID:28385786

Amelioration of chronic fluoride toxicity by calcium and fluoride-free water in rats.

PubMed

Shankar, Priyanka; Ghosh, Sudip; Bhaskarachary, K; Venkaiah, K; Khandare, Arjun L

2013-07-14

The study was undertaken to explore the amelioration of chronic fluoride (F) toxicity (with low and normal Ca) in rats. The study was conducted in two phases. In phase I (6 months), seventy-six Wistar, weanling male rats were assigned to four treatment groups: normal-Ca (0·5 %) diet (NCD), Ca+F - ; low-Ca (0·25 %) diet (LCD), Ca - F - ; NCD +100 parts per million (ppm) F water, Ca+F+; LCD +100 ppm F water, Ca - F+. In phase II (reversal experiment, 3 months), LCD was replaced with the NCD. Treatment groups Ca+F+ and Ca - F+ were divided into two subgroups to compare the effect of continuation v. discontinuation along with Ca supplementation on reversal of chronic F toxicity. In phase I, significantly reduced food efficiency ratio (FER), body weight gain (BWG), faecal F excretion, serum Ca and increased bone F deposition were observed in the treatment group Ca - F+. Reduced serum 25-hydroxy-vitamin D3, increased 1,25-dihydroxy-vitamin D3 and up-regulation of Ca-sensing receptor, vitamin D receptor and S100 Ca-binding protein G (S100G) were observed in treatment groups Ca - F - and Ca - F+. In phase II (reversal phase), FER, BWG and serum Ca in treatment groups Ca - F+/Ca+F - and Ca - F+/Ca+F+ were still lower, as compared with other groups. However, other variables were comparable. Down-regulation of S100G was observed in F-fed groups (Ca+F+/Ca+F+ and Ca - F+/Ca+F+) in phase II. It is concluded that low Ca aggravates F toxicity, which can be ameliorated after providing adequate Ca and F-free water. However, chronic F toxicity can interfere with Ca absorption by down-regulating S100G expression irrespective of Ca nutrition.

Modified high-affinity binding of Ni2+, Ca2+ and Zn2+ to natural mutants of human serum albumin and proalbumin.

PubMed

Kragh-Hansen, U; Brennan, S O; Minchiotti, L; Galliano, M

1994-07-01

High-affinity binding of radioactive Ni2+, Ca2+ and Zn2+ to six genetic albumin variants and to normal albumin isolated from the same heterozygote carriers was studied by equilibrium dialysis at pH 7.4. The three cations bind differently to albumin. Ni2+ binds to a site in the N-terminal region of the protein which is partially blocked by the presence of a propeptide as in proalbumin (proAlb) Varese (Arg-2-->His), proAlb Christchurch (Arg-1-->Gln) and proAlb Blenheim (Asp1-->Val) and by the presence of only an extra Arg residue (Arg-1) as in Arg-Alb and albumin (Alb) Redhill. The association constants are decreased by more than one order of magnitude in these cases, suggesting biological consequences for the ligand. The additional structural changes in Alb Redhill have no effect on Ni2+ binding. Finally, the modification of Alb Blenheim (Asp1-->Val) reduces the binding constant to 50%. Ca2+ binding is decreased to about 60-80% by the presence of a propeptide and the mutation Asp1-->Val. Arg-1 alone does not affect binding, whereas Alb Redhill binds Ca2+ more strongly than the normal protein (125%). In contrast with binding of Ni2+ and Ca2+, albumin shows heterogeneity with regard to binding of Zn2+, i.e. the number of high-affinity sites was calculated to be, on average, 0.43. The binding constant for Zn2+ is increased to 125% in the case of proAlb Varese, decreased to 50-60% for proAlb Christchurch and Alb Redhill but is normal for proAlb Blenheim, Alb Blenheim and Arg-Alb. The effects of the mutations on binding of Ca2+ and Zn2+ indicate that primary binding, when operative, is to as yet unidentified sites in domain I of the albumin molecule.

Gene expression profiling and functional characterization of macrophages in response to circulatory microparticles produced during Trypanosoma cruzi infection and Chagas disease

PubMed Central

Chowdhury, Imran; Koo, Sue-jie; Gupta, Shivali; Liang, Lisa Yi; Bahar, Bojlul; Silla, Laura; Burgos, Julio Nuñez; Barrientos, Natalia; Zago, Maria Paola; Garg, Nisha Jain

2016-01-01

BACKGROUND Chronic inflammation and oxidative stress are hallmarks of chagasic cardiomyopathy (CCM). In this study, we determined if microparticles (MPs) generated during Trypanosoma cruzi (Tc) infection carry the host’s signature of inflammatory/oxidative state and provide information regarding the progression of clinical disease. METHDOS The MPs were harvested from supernatants of human PBMCs in vitro incubated with T. cruzi (control: LPS-treated), plasma of seropositive humans with clinically asymptomatic (CA) or symptomatic (CS) disease state (normal/healthy (NH) controls) and plasma of mice immunized with a protective vaccine before challenge infection (control: unvaccinated/infected). Macrophages (mφs) were incubated with MPs, and we probed the gene expression profile using the inflammatory signaling cascade and cytokine/chemokine arrays, phenotypic markers of macrophage activation by flow cytometry, cytokine profile by an ELISA and Bioplex assay, and oxidative/nitrosative stress and mitotoxicity by colorimetric and fluorometric assays. RESULTS Tc- and LPS-induced MPs stimulated proliferation, inflammatory gene expression profile and •NO release in human THP-1 mφs. LPS-MPs were more immunostimulatory than Tc-MPs. Endothelial cells, T lymphocytes and mφs were the major source of MPs shed in plasma of chagasic humans and experimentally infected mice. The CS-MPs and CA-MPs (vs. NH-MPs) elicited >2-fold increase in •NO and mitochondrial oxidative stress in THP-1 mφs; however, CS-MPs (vs. CA-MPs) elicited a more pronounced and disease-state-specific inflammatory gene expression profile (IKBKB, NR3C1, and TIRAP vs. CCR4, EGR2 and CCL3), cytokine release (IL2+IFNγ>GCSF), and surface markers of mφ activation (CD14 and CD16). The circulatory MPs of non-vaccinated/infected mice induced 7.5-fold and 40% increase in •NO and IFNγ production, respectively, while these responses were abolished when RAW264.7 mφs were incubated with circulatory MPs of vaccinated/infected mice. CONCLUSION Circulating MPs reflect in vivo levels of oxidative, nitrosative, and inflammatory state and have potential utility in evaluating disease severity and efficacy of vaccines and drug therapies against CCM. PMID:27902980

Group A beta-hemolytic streptococcal pharyngitis and carriage rate among Egyptian children: a case-control study.

PubMed

Abd El-Ghany, Shereen Mohamed; Abdelmaksoud, Abeer Ahmed; Saber, Sally Mohamed; Abd El Hamid, Dalia Hosni

2015-01-01

Improper prescription of antibiotics for treatment of acute pharyngitis predisposes to emergence of a carrier state and antibiotic-resistant strains of group A streptococci (GAS). We sought to identify the frequency and antimicrobial susceptibility patterns of group A streptococci among Egyptian children with acute pharyngitis compared with asymptomatic children. Case-control study conducted from September 2013 to August 2014 at a pediatric outpatient clinic in Egypt. Throat swabs were collected from children with acute pharyngitis and from asymptomatic children. We evaluated the accuracy of McIsaac scores and the rapid antigen detection test (RADT) for diagnosis of GAS pharyngitis with throat culture as a reference test. Antimicrobial susceptibility testing of GAS isolates was done by the disc diffusion method. Of 142 children with acute pharyngitis (cases) and 300 asymptomatic children (controls) (age range, 4-16 years), GAS pharyngitis was diagnosed in 60/142 children (42.2%); 48/300 (16%) were found to be carriers. All GAS isolates in the case group were sensitive to penicillin; however, an MIC90 (0.12 micro g/mL) for penicillin is high and an alarming sign. The resistance rate to macrolides was 70% with the cMLSB phenotype in 65.1%. The sensitivities and specificities were 78.3% and 73.2% for McIsaac score of >=4 and 81.1% and 93.9% for RADT, respectively. GAS isolates in the control group were 100% sensitive to penicillin, while 12.5% and 37.5% were resistant to macrolides and tetracycline, respectively. An increased MIC90 for GAS isolates to penicillin is an alarming sign. A high frequency of resistance to macrolides was also observed.

Incremental prognostic value of coronary computed tomography angiography over coronary calcium scoring for major adverse cardiac events in elderly asymptomatic individuals

PubMed Central

Han, Donghee; Hartaigh, Bríain Ó; Gransar, Heidi; Lee, Ji Hyun; Rizvi, Asim; Baskaran, Lohendran; Schulman-Marcus, Joshua; Dunning, Allison; Achenbach, Stephan; Al-Mallah, Mouaz H; Berman, Daniel S; Budoff, Matthew J; Cademartiri, Filippo; Maffei, Erica; Callister, Tracy Q; Chinnaiyan, Kavitha; Chow, Benjamin J W; DeLago, Augustin; Hadamitzky, Martin; Hausleiter, Joerg; Kaufmann, Philipp A; Raff, Gilbert; Shaw, Leslee J; Villines, Todd C; Kim, Yong-Jin; Leipsic, Jonathon; Feuchtner, Gudrun; Cury, Ricardo C; Pontone, Gianluca; Andreini, Daniele; Marques, Hugo; Rubinshtein, Ronen; Hindoyan, Niree; Jones, Erica C; Gomez, Millie; Lin, Fay Y; Chang, Hyuk-Jae; Min, James K

2018-01-01

Abstract Aims Coronary computed tomography angiography (CCTA) and coronary artery calcium score (CACS) have prognostic value for coronary artery disease (CAD) events beyond traditional risk assessment. Age is a risk factor with very high weight and little is known regarding the incremental value of CCTA over CAC for predicting cardiac events in older adults. Methods and results Of 27 125 individuals undergoing CCTA, a total of 3145 asymptomatic adults were identified. This study sample was categorized according to tertiles of age (cut-off points: 52 and 62 years). CAD severity was classified as 0, 1–49, and ≥50% maximal stenosis in CCTA, and further categorized according to number of vessels ≥50% stenosis. The Framingham 10-year risk score (FRS) and CACS were employed as major covariates. Major adverse cardiovascular events (MACE) were defined as a composite of all-cause death or non-fatal MI. During a median follow-up of 26 months (interquartile range: 18–41 months), 59 (1.9%) MACE occurred. For patients in the top age tertile, CCTA improved discrimination beyond a model included FRS and CACS (C-statistic: 0.75 vs. 0.70, P-value = 0.015). Likewise, the addition of CCTA improved category-free net reclassification (cNRI) of MACE in patients within the highest age tertile (e.g. cNRI = 0.75; proportion of events/non-events reclassified were 50 and 25%, respectively; P-value <0.05, all). CCTA displayed no incremental benefit beyond FRS and CACS for prediction of MACE in the lower age tertiles. Conclusion CCTA provides added prognostic value beyond cardiac risk factors and CACS for the prediction of MACE in asymptomatic older adults. PMID:28977374

Aberrant Splicing Promotes Proteasomal Degradation of L-type CaV1.2 Calcium Channels by Competitive Binding for CaVβ Subunits in Cardiac Hypertrophy.

PubMed

Hu, Zhenyu; Wang, Jiong-Wei; Yu, Dejie; Soon, Jia Lin; de Kleijn, Dominique P V; Foo, Roger; Liao, Ping; Colecraft, Henry M; Soong, Tuck Wah

2016-10-12

Decreased expression and activity of Ca V 1.2 calcium channels has been reported in pressure overload-induced cardiac hypertrophy and heart failure. However, the underlying mechanisms remain unknown. Here we identified in rodents a splice variant of Ca V 1.2 channel, named Ca V 1.2 e21+22 , that contained the pair of mutually exclusive exons 21 and 22. This variant was highly expressed in neonatal hearts. The abundance of this variant was gradually increased by 12.5-folds within 14 days of transverse aortic banding that induced cardiac hypertrophy in adult mouse hearts and was also elevated in left ventricles from patients with dilated cardiomyopathy. Although this variant did not conduct Ca 2+ ions, it reduced the cell-surface expression of wild-type Ca V 1.2 channels and consequently decreased the whole-cell Ca 2+ influx via the Ca V 1.2 channels. In addition, the Ca V 1.2 e21+22 variant interacted with Ca V β subunits significantly more than wild-type Ca V 1.2 channels, and competition of Ca V β subunits by Ca V 1.2 e21+22 consequently enhanced ubiquitination and subsequent proteasomal degradation of the wild-type Ca V 1.2 channels. Our findings show that the resurgence of a specific neonatal splice variant of Ca V 1.2 channels in adult heart under stress may contribute to heart failure.

Spectroscopic Confirmation of Five Galaxy Clusters at z > 1.25 in the 2500 deg^2 SPT-SZ Survey

NASA Astrophysics Data System (ADS)

Khullar, Gourav; Bleem, Lindsey; Bayliss, Matthew; Gladders, Michael; South Pole Telescope (SPT) Collaboration

2018-06-01

We present spectroscopic confirmation of 5 galaxy clusters at 1.25 < z < 1.5, discovered in the 2500 deg2 South Pole Telescope Sunyaev-Zel’dovich (SPT-SZ) survey. These clusters, taken from a nearly redshift-independent mass-limited sample of clusters, have multi-wavelength follow-up imaging data from the X-ray to the near-IR, and currently form the most homogenous massive high-redshift cluster sample in existence. We briefly describe the analysis pipeline used on the low S/N spectra of these faint galaxies, and describing the multiple techniques used to extract robust redshifts from a combination of absorption-line (Ca II H&K doublet - λλ3934,3968Å) and emission-line ([OII] λλ3727,3729Å) spectral features. We present several ensemble analyses of cluster member galaxies that demonstrate the reliability of the measured redshifts. We also identify modest [OII] emission and pronounced CN and Hδ absorption in a composite stacked spectrum of 28 low S/N passive galaxy spectra with redshifts derived primarily from Ca II H&K features. This work increases the number of spectroscopically-confirmed SPT-SZ galaxy clusters at z > 1.25 from 2 to 7, further demonstrating the efficacy of SZ selection for the highest redshift massive clusters, and enabling further detailed study of these confirmed systems.

Sarcoidosis mimicking toxoplasmosis with severe hypercalcaemia and normal 1,25-dihydroxy vitamin D.

PubMed

Levy, Y; Hayek, T; Finkelstein, R

1996-09-01

We report a case of a female patient with sarcoidosis who presented with a generalized lymphadenopathy and a strong IgG serological test of toxoplasmosis. Progressive lymphadenopathy with a rising plasma calcium (up to 15 mg dL-1) with a normal plasma 1,25-dihydroxy vitamin D concentration occurred later. Corticosteroid therapy resulted in prompt clinical and biochemical responses with normalization of plasma calcium and a significant reduction in 1,25-dihydroxy vitamin D concentration. This is an exceptional presentation of sarcoidosis with severe hypercalcaemia and normal vitamin D metabolites.

Icotinib and whole-brain radiotherapy for the treatment in patients with brain metastases from EGFR-mutant nonsmall cell lung cancer

PubMed Central

Jiang, Ai-Ying; Zhang, Jing; Luo, Hai-Long; Gao, Feng; Lv, Yu-Feng

2018-01-01

Abstract This study aimed to explore the effect and toxicity of icotinib and whole-brain radiotherapy (IWBRT) for the treatment of brain metastases from nonsmall cell lung cancer (BMNSCLC) with epidermal growth factor receptor (EGFR)-mutant among Chinese Han population. A total of 55 patients with EGFR-mutant BMNSCLC were included. They received orally icotinib (125 mg/tablet, 125 mg each time, 3 times daily) until disease progression. In addition, they also underwent whole-brain radiotherapy (3-Gy fractions once daily, 5 days weekly for a total dose of 30 Gy) in an attempt to extend their survival time. The outcomes consisted of complete response (CR), partial response (PR), stable disease (SD), progress disease (PD), overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). In addition, toxicity was also recorded in this study. The CR, PR, SD, PD, ORR, PFS, and OS were 38.2%, 52.8%, 5.4%, 3.6%, 90.1%, 12.5%, and 48.0% months, respectively. In addition, mild toxicity was observed in this study. This study demonstrated that IWBRT is efficacious with acceptable toxicity for patients with EGFR-mutant BMNSCLC among Chinese Han population. PMID:29642161

Icotinib and whole-brain radiotherapy for the treatment in patients with brain metastases from EGFR-mutant nonsmall cell lung cancer: A retrospective study.

PubMed

Jiang, Ai-Ying; Zhang, Jing; Luo, Hai-Long; Gao, Feng; Lv, Yu-Feng

2018-04-01

This study aimed to explore the effect and toxicity of icotinib and whole-brain radiotherapy (IWBRT) for the treatment of brain metastases from nonsmall cell lung cancer (BMNSCLC) with epidermal growth factor receptor (EGFR)-mutant among Chinese Han population.A total of 55 patients with EGFR-mutant BMNSCLC were included. They received orally icotinib (125 mg/tablet, 125 mg each time, 3 times daily) until disease progression. In addition, they also underwent whole-brain radiotherapy (3-Gy fractions once daily, 5 days weekly for a total dose of 30 Gy) in an attempt to extend their survival time. The outcomes consisted of complete response (CR), partial response (PR), stable disease (SD), progress disease (PD), overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). In addition, toxicity was also recorded in this study.The CR, PR, SD, PD, ORR, PFS, and OS were 38.2%, 52.8%, 5.4%, 3.6%, 90.1%, 12.5%, and 48.0% months, respectively. In addition, mild toxicity was observed in this study.This study demonstrated that IWBRT is efficacious with acceptable toxicity for patients with EGFR-mutant BMNSCLC among Chinese Han population.

1. BUILDING 8814, NORTH FRONT AND WEST SIDE. BUILDING 8832, ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

1. BUILDING 8814, NORTH FRONT AND WEST SIDE. BUILDING 8832, TEST STAND 1-E, IN LEFT DISTANCE. Looking southeast. - Edwards Air Force Base, Air Force Rocket Propulsion Laboratory, Observation Bunker 1-D-3, Test Area 1-125, northwest end of Altair Boulevard, Boron, Kern County, CA

What happens to asymptomatic lower pole kidney stones smaller than 10 mm in children during watchful waiting?

PubMed

Telli, Onur; Hamidi, Nurullah; Bagci, Uygar; Demirbas, Arif; Hascicek, Ahmet Metin; Soygur, Tarkan; Burgu, Berk

2017-05-01

The optimal management of lower pole kidney (LPK) stones in children is controversial. The aim of this study was to determine the outcomes of children with asymptomatic isolated LPK stones smaller than 10 mm during follow-up. A total of 242 patients with 284 stones presenting at our institution between June 2004 and December 2014 with an asymptomatic, single LPK stone with a diameter of <10 mm were enrolled in the study. All children were assigned to receive first-line therapy and then categorized according to the need for medical intervention. Age, gender, stone laterality, stone size and type, associated urinary tract problems, and uncontrolled metabolic status were assessed as predictive factors of medical treatment for small (<10 mm) asymptomatic LPK stones. Stone-free rates were compared between interventions. The mean age and mean stone size were 9.4 ± 1.9 years and 7.4 ± 0.6 mm at admission, respectively. Stone progression rate was 61.2%, and the mean time for intervention was 19.2 ± 4.6 months. Flexible ureterorenoscopy (n = 68) or micro-percutaneous nephrolithotomy (n = 4) were performed for 72 stones (25.4%; group 1), and extracorporeal shock wave lithotripsy was performed for 102 stones (35.9%; group 2). The stone-free rates were 81.8 and 79.3% in group 1 and 2, respectively (p > 0.05). The remaining asymptomatic stones (110, 38.8%; group 3) were managed by continued observation, and at the end of the observation time (mean 40.8 ± 20.8 months) the spontaneous passage rate was 9.1% in this group. In the multivariate analysis, stone size of >7 mm, concurrent renal anomalies, and stones composed of magnesium ammonium phosphate (struvite) and cystine were statistically significant predictors of the need for intervention. Children with stones larger than 7 mm, renal anomalies, or stones composed of metabolically active cystine or struvite are more likely to require intervention, and those with asymptomatic LPK stones smaller than 10 mm can be managed by continued observation.

Inaccuracy of Enzyme-Linked Immunosorbent Assay Using Soluble and Recombinant Antigens to Detect Asymptomatic Infection by Leishmania infantum

PubMed Central

Moreno, Elizabeth Castro; Gonçalves, Andréa Vieira; Chaves, Anderson Vieira; Melo, Maria Norma; Lambertucci, José Roberto; Andrade, Antero Silva Ribeiro; Negrão-Corrêa, Deborah; Antunes, Carlos Mauricio de Figueiredo; Carneiro, Mariângela

2009-01-01

Background One of the most important drawbacks in visceral leishmaniasis (VL) population studies is the difficulty of diagnosing asymptomatic carriers. The aim of this study, conducted in an urban area in the Southeast of Brazil, was to evaluate the performance of serology to identify asymptomatic VL infection in participants selected from a cohort with a two-year follow-up period. Methodology Blood samples were collected in 2001 from 136 cohort participants (97 positive and 39 negatives, PCR/hybridization carried out in 1999). They were clinically evaluated and none had progressed to disease from their asymptomatic state. As controls, blood samples from 22 control individuals and 8 patients with kala-azar were collected. Two molecular biology techniques (reference tests) were performed: PCR with Leishmania-generic primer followed by hybridization using L. infantum probe, and PCR with specific primer to L. donovani complex. Plasma samples were tested by ELISA using three different antigens: L. infantum and L. amazonensis crude antigens, and rK39 recombinant protein. Accuracy of the serological tests was evaluated using sensitivity, specificity, likelihood ratio and ROC curve. Findings The presence of Leishmania was confirmed, by molecular techniques, in all kala-azar patients and in 117 (86%) of the 136 cohort participants. Kala-azar patients showed high reactivity in ELISAs, whereas asymptomatic individuals presented low reactivity against the antigens tested. When compared to molecular techniques, the L. amazonensis and L. infantum antigens showed higher sensitivity (49.6% and 41.0%, respectively) than rK39 (26.5%); however, the specificity of rK39 was higher (73.7%) than L. amazonensis (52.6%) and L. infantum antigens (36.8%). Moreover, there was low agreement among the different antigens used (kappa<0.10). Conclusions Serological tests were inaccurate for diagnosing asymptomatic infections compared to molecular methods; this could lead to misclassification bias in population studies. Therefore, studies which have used serological assays to estimate prevalence, to evaluate intervention programs or to identify risk factors for Leishmania infection, may have had their results compromised. PMID:19841736

The relationship between liver stiffness measurement and outcome in patients with chronic hepatitis C and cirrhosis: a retrospective longitudinal hospital study.

PubMed

Sultanik, P; Kramer, L; Soudan, D; Bouam, S; Meritet, J-F; Vallet-Pichard, A; Fontaine, H; Bousquet, L; Boueyre, E; Corouge, M; Sogni, P; Pol, S; Mallet, V

2016-09-01

There is a relationship between liver stiffness measurement (LSM) and outcome of HCV patients. To evaluate the performance of LSM to predict outcome of HCV patients at risk of liver-related complication. We established a retrospective longitudinal cohort of 341 HCV patients with unequivocal cirrhosis. All underwent LSM and were followed from September 2006 to July 2015. Outcome measure was a composite end-point of end-stage liver disease (ESLD) and/or hepatocellular carcinoma (HCC). Cox models and areas under receiver operating characteristic (AUROC) curves were used to evaluate independent risk factors of outcome. Overall, LSM was below the 12.5 kPa threshold in 129 (37.8%) patients, including three-fourth and one-third of patients with or without a sustained virological response respectively. Liver disease progressed in 136 (39.9%) patients after a median observational period of 23.5 months. Older age, male gender, alcohol use disorders, metabolic syndrome and LSM were independent risk factors of liver disease progression. Age, alcohol use disorders and LSM were independently associated with ESLD. Age, gender and metabolic syndrome, but not LSM, were associated with HCC. The AUROC curves for disease progression, ESLD and HCC were 0.67, 0.70 and 0.58 respectively. Patients with a liver stiffness >12.5 kPa were at the highest risk of liver disease progression; below 12.5 kPa, liver stiffness was not discriminant. Liver stiffness measurement is not a surrogate of disease progression of HCV patients with cirrhosis. HCV patients with cirrhosis should undergo the recommended follow-up, regardless of liver stiffness measurement. © 2016 John Wiley & Sons Ltd.

Successful control of nosocomial transmission of the USA300 clone of community-acquired meticillin-resistant Staphylococcus aureus in a UK paediatric burns centre.

PubMed

Patel, M; Thomas, H C; Room, J; Wilson, Y; Kearns, A; Gray, J

2013-08-01

An outbreak of the PVL-positive USA300 clone of community-acquired meticillin-resistant Staphylococcus aureus (CA-MRSA) occurred in a UK paediatric burns centre from January to February 2010. Four patients, two staff members and one family member of a patient were affected. The outbreak strain had similar antibiotic susceptibilities to other MRSA seen in the hospital, and was only identified when a patient and a staff member presented simultaneously with skin infections. Infection control measures included screening and decolonization of staff and patients, environmental sampling and enhanced cleaning. Isolation of the outbreak strain from an asymptomatic staff member and the environment demonstrates the potential for CA-MRSA to survive and become endemic in UK hospitals. Copyright © 2013 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

NEW ULTRA-WIDE-FIELD ANGIOGRAPHIC GRADING SCHEME FOR RADIATION RETINOPATHY AFTER IODINE-125 BRACHYTHERAPY FOR UVEAL MELANOMA.

PubMed

McCannel, Tara A; Kim, EunAh; Kamrava, Mitchell; Lamb, James; Caprioli, Joseph; Yang, Dong; McCannel, Colin A

2017-10-06

Radiation retinopathy remains incompletely characterized and may cause severe vision loss. Ultra-wide-field fluorescein angiography provides a pan-fundus view of vascular alterations caused by radiation treatment and may predict visual and ocular outcomes. We have developed a grading scheme to describe pan-fundus severity and to predict the progression of radiation retinopathy in patients treated for uveal melanoma with iodine-125 brachytherapy. A retrospective review of patients treated with standard iodine-125 brachytherapy for uveal melanoma at the Ophthalmic Oncology Center at the University of California, Los Angeles, who had undergone both baseline and postbrachytherapy ultra-wide-field fluorescein angiography. A grading scheme was devised based on observations of vascular leakage, retinal perfusion status, and retinal proliferation. The correlation of grade severity with patient characteristics, tumor features, visual acuity, optical coherence tomography findings, and neovascular glaucoma was measured with chi-square and one-way analysis of variance analyses. Sixty-seven patients were identified for review. Consistent wide-field angiographic patterns after brachytherapy were observed and graded as follows: Grade 0: normal; Grade 1: late foveal leakage; Grade 2: late peripheral leakage; Grade 3: presence of nonperfusion; and Grade 4: retinal neovascularization. Six eyes (8.9%) were Grade 0; 16 (23.8%) were Grade 1; 25 (37.3%) were Grade 2; 16 (23.4%) were Grade 3; and 4 (6.0%) were Grade 4. Higher grade radiation severity correlated significantly with duration of follow-up (P < 0.02); younger age (P = 0.035); worse visual acuity (P = 0.001); cystoid macular edema or atrophy on optical coherence tomography (P < 0.0001); and neovascular glaucoma (P = 0.003). Wide-field fluorescein angiography revealed distinct fundus-wide patterns of vascular damage, which were progressive in nature in eyes treated with iodine-125 brachytherapy for uveal melanoma and correlated with signs of progressive vascular injury. This grading scheme may have prognostic value to predict the progression of radiation retinopathy and to prognosticate visual outcomes in patients undergoing brachytherapy.

125I Brachytherapy in Locally Advanced Nonsmall Cell Lung Cancer After Progression of Concurrent Radiochemotherapy

PubMed Central

Xiang, Zhanwang; Li, Guohong; Liu, Zhenyin; Huang, Jinhua; Zhong, Zhihui; Sun, Lin; Li, Chuanxing; Zhang, Funjun

2015-01-01

Abstract To investigate the safety and effectiveness of computed tomography (CT)-guided 125I seed implantation for locally advanced nonsmall cell lung cancer (NSCLC) after progression of concurrent radiochemotherapy (CCRT). We reviewed 78 locally advanced NSCLC patients who had each one cycle of first-line CCRT but had progressive disease identified from January 2006 to February 2015 at our institution. A total of 37 patients with 44 lesions received CT-guided percutaneous 125I seed implantation and second-line chemotherapy (group A), while 41 with 41 lesions received second-line chemotherapy (group B). Patients in group A and B received a total of 37 and 41 first cycle of CCRT treatment. The median follow-up was 19 (range 3–36) months. After the second treatment, the total response rate (RR) in tumor response accounted for 63.6% in group A, which was significantly higher than that of group B (41.5%) (P = 0.033). The median progression-free survival time (PFST) was 8.00 ± 1.09 months and 5.00 ± 0.64 months in groups A and B (P = 0.011). The 1-, 2-, and 3-year overall survival (OS) rates for group A were 56.8%, 16.2%, and 2.7%, respectively. For group B, OS rates were 36.6%, 9.8%, and 2.4%, respectively. The median OS time was 14.00 ± 1.82 months and 10.00 ± 1.37 months for groups A and B, respectively (P = 0.059). Similar toxicity reactions were found in both groups. Tumor-related clinical symptoms were significantly reduced and the patients’ quality of life was obviously improved. CT-guided 125I seed implantation proved to be potentially beneficial in treating localized advanced NSCLC; it achieved good local control rates and relieved clinical symptoms without increasing side effects. PMID:26656370

Is calcitonin an active hormone in the onset and prevention of hypocalcemia in dairy cattle?

PubMed

Rodríguez, E M; Bach, A; Devant, M; Aris, A

2016-04-01

The objective of this study was to assess the potential importance of calcitonin (CALC) in the onset of subclinical hypocalcemia (experiment 1) and in the physiological mechanisms underlying the prevention of bovine hypocalcemia under metabolic acidosis (experiments 2 and 3). In experiment 1, 15 Holstein cows naturally incurring subclinical hypocalcemia during the first 5d postpartum were classified as low subclinical hypocalcemia (LSH) when blood Ca concentrations were between 7.5 and 8.5mg/dL, or as high subclinical hypocalcemia (HSH) when blood Ca concentrations were between 6.0 and 7.6 mg/dL. Blood samples were taken daily from d -5 to 5 relative to parturition to determine concentrations of parathyroid hormone (PTH), CALC, and 1,25(OH)2D3. In experiment 2, 24 Holstein bulls (497 ± 69 kg of body weight and 342 ± 10.5d of age) were assigned to 2 treatments (metabolic acidosis or control). Metabolic acidosis was induced by an oral administration of ammonium chloride (2.5 mEq/d) during 10 d, and animals were slaughtered thereafter. Blood samples were collected before slaughter to determine CALC, PTH, 1,25(OH)2D3, and samples of urine, kidney, parathyroid, and thyroid glands were obtained immediately after slaughter to determine expression of several genes in these tissues. Last, in experiment 3, we tested the activity of CALC under metabolic acidosis in vitro using breast cancer cell (T47D) cultures. Although PTH tended to be greater in HSH than in LSH, the levels of 1,25(OH)2D3 were lower in HSH cows (experiment 1). Blood CALC concentration was not affected by the severity of subclinical hypocalcemia, but it was influenced by days from calving (experiment 1). The expression of PTH receptor (PTHR) in the kidney was increased under metabolic acidosis (experiment 2). Furthermore, the activity of CALC was impaired under acidic blood pH (experiment 3). In conclusion, the CALC rise in HSH cows after calving impaired the recovery of blood Ca concentrations because the PTHR response was not sufficient to activate 1,25(OH)2D3 and compensate for the CALC effect. Metabolic acidosis prevents hypocalcemia because the expression of PTHR is upregulated in the kidney, resulting in an increased PTH activity and a subsequent increase in 1,25(OH)2D3 serum concentrations. Moreover, an impairment of CALC activity at low pH enhances the hypercalcemic role of PTH. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Clinical characteristics of African Americans vs Caucasian Americans with multiple sclerosis.

PubMed

Cree, B A C; Khan, O; Bourdette, D; Goodin, D S; Cohen, J A; Marrie, R A; Glidden, D; Weinstock-Guttman, B; Reich, D; Patterson, N; Haines, J L; Pericak-Vance, M; DeLoa, C; Oksenberg, J R; Hauser, S L

2004-12-14

African American (AA) individuals are thought to develop multiple sclerosis (MS) less frequently than Caucasian American (CA) individuals. To compare the clinical characteristics of AA and CA patients with MS. The clinical features of MS were compared in a large retrospective cohort of AA (n = 375) and CA (n = 427) subjects. The proportion of women to men was similar in AA and CA subjects (81% [AA] vs 77% [CA]; p = 0.122). There were no differences in the proportions of subjects with relapsing-remitting, secondary progressive, primary progressive, and progressive relapsing MS. The median time to diagnosis was 1 year after symptom onset in AA subjects and 2 years after symptom onset in CA subjects (p = 0.0013). The age at onset was approximately 2.5 years later in AA than CA subjects (33.7 vs 31.1 years; p = 0.0001). AA subjects presented with multisite signs and symptoms at disease onset more often than CA subjects (p = 0.018). Clinical involvement restricted to the optic nerves and spinal cord (opticospinal MS) occurred in 16.8% of AA patients compared with 7.9% of CA patients (p < 0.001). Transverse myelitis also occurred more frequently in AA subjects (28 vs 18%; p = 0.001). Survival analysis revealed that AA subjects were at higher risk for development of ambulatory disability than CA subjects. After adjusting for baseline variations and differences in therapeutic interventions, AAs were at 1.67-fold greater risk for requiring a cane to ambulate than CA patients (p < 0.001). There was a trend suggesting that AAs were also at greater risk for development of wheelchair dependency (p = 0.099). Adjusted Cox proportional hazard models showed that this effect was in part attributable to the older age at onset in AAs (p < 0.001). Compared with multiple sclerosis (MS) in Caucasian Americans, African American patients with MS have a greater likelihood of developing opticospinal MS and transverse myelitis and have a more aggressive disease course.

Rat Sertoli cells acquire a beta-adrenergic response during primary culture.

PubMed Central

Kierszenbaum, A L; Spruill, W A; White, M G; Tres, L L; Perkins, J P

1985-01-01

Two-dimensional polyacrylamide gel electrophoresis and the radioligand (-)-[125I]iodopindolol (125I-Pin) have been used to study isoproterenol-dependent protein phosphorylation and beta-adrenergic receptor availability, respectively, in cultured Sertoli cells and freshly isolated seminiferous tubular segments of sexually immature and mature rats. Sertoli cells prepared from sexually immature rats show progressive 125I-Pin binding in primary cultures that correlates with isoproterenol-induced cell shape changes, redistribution of immunoreactive vimentin, and phosphorylation of this intermediate filament protein. The development of 125I-Pin binding to Sertoli cell lysates is blocked by cycloheximide. Seminiferous tubules do not show significant isoproterenol-dependent vimentin phosphorylation nor 125I-Pin binding. However, vimentin phosphorylation can be induced by follicle-stimulating hormone or a cyclic nucleotide analog. This study stresses the need for correlating pharmacological-induced responses observed in Sertoli cell primary cultures with those in the intact seminiferous tubule. Images PMID:2984678

Cervical Spondylotic Myelopathy: What the Neurologist Should Know

PubMed Central

de Oliveira Vilaça, Celmir; Orsini, Marco; Leite, Marco A. Araujo; de Freitas, Marcos R.G.; Davidovich, Eduardo; Fiorelli, Rossano; Fiorelli, Stenio; Fiorelli, Camila; Oliveira, Acary Bulle; Pessoa, Bruno Lima

2016-01-01

Cervical spondylotic myelopathy is a well-known cause of disability among older people. A significant amount of these patients is asymptomatic. Once the symptoms start, the worsening may follow a progressive manner. We should suspect of spondylotic myelopathy in any individual over 55 years presenting progressive changes in gait or losing fine motor control of the upper limbs. Despite its frequent prevalence, this condition is still neglected and many times confused with other supratentorial lesions regarding diagnostic. Here we address some of most important aspects of this disease, calling attention to pathophysiology, the natural history, presentation, differential diagnosis, clinical assessment, and treatment. PMID:27994827

Progress in the structural understanding of voltage-gated calcium channel (CaV) function and modulation.

PubMed

Minor, Daniel L; Findeisen, Felix

2010-01-01

Voltage-gated calcium channels (CaVs) are large, transmembrane multiprotein complexes that couple membrane depolarization to cellular calcium entry. These channels are central to cardiac action potential propagation, neurotransmitter and hormone release, muscle contraction, and calcium-dependent gene transcription. Over the past six years, the advent of high-resolution structural studies of CaV components from different isoforms and CaV modulators has begun to reveal the architecture that underlies the exceptionally rich feedback modulation that controls CaV action. These descriptions of CaV molecular anatomy have provided new, structure-based insights into the mechanisms by which particular channel elements affect voltage-dependent inactivation (VDI), calcium‑dependent inactivation (CDI), and calcium‑dependent facilitation (CDF). The initial successes have been achieved through structural studies of soluble channel domains and modulator proteins and have proven most powerful when paired with biochemical and functional studies that validate ideas inspired by the structures. Here, we review the progress in this growing area and highlight some key open challenges for future efforts.

High-risk syndrome for neuromyelitis optica: a descriptive and comparative study.

PubMed

Collongues, N; Marignier, R; Zéphir, H; Blanc, F; Vukusic, S; Outteryck, O; Fleury, M; Ruet, A; Borgel, F; Thouvenot, E; Moreau, T; Defer, G; Derache, N; Pelletier, J; Audoin, B; Debouverie, M; Labauge, P; Gout, O; Camu, W; Brassat, D; Brochet, B; Vermersch, P; Confavreux, C; de Seze, J

2011-06-01

Neuromyelitis optica (NMO) frequently begins with a monofocal episode of optic neuritis or myelitis. A concept named high-risk syndrome (HRS) for NMO has been proposed for patients with monofocal episodes and NMO-IgG antibodies. To describe HRS patients and compare them with NMO patients. We identified 30 patients with HRS: 18 with extensive myelitis (HRM) and 12 with optic neuritis (HRON), in a database pooling patients from 25 centres in France. Clinical, laboratory/magnetic resonance imaging (MRI) data and outcome were analysed and compared with a national cohort of 125 NMO patients extracted from the same database. Mean follow-up was 4.8 years. Mean age at onset was 42.8 years (range: 12.4-70) with a female:male ratio of 0.9. Asymptomatic lesions were report on visual evoked potentials in 4/8 tested HRM patients and on spinal cord MRI in 2/7 HRON patients. Three patients died, two owing to a cervical lesion. HRS and NMO patients had similar clinical/paraclinical data, except for a predominance of men in the HRS group and a later mean age at onset in the HRM subgroup. The description of HRS patients is compatible with a monofocal form of NMO. Asymptomatic lesions could be included in a new set of NMO diagnostic criteria.

Particulate air pollution induces arrhythmia via oxidative stress and calcium calmodulin kinase II activation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Jin-Bae; Kim, Changsoo; Choi, Eunmi

2012-02-15

Ambient particulate matter (PM) can increase the incidence of arrhythmia. However, the arrhythmogenic mechanism of PM is poorly understood. This study investigated the arrhythmogenic mechanism of PM. In Sprague–Dawley rats, QT interval was increased from 115.0 ± 14.0 to 142.1 ± 18.4 ms (p = 0.02) after endotracheal exposure of DEP (200 μg/ml for 30 min, n = 5). Ventricular premature contractions were more frequently observed after DEP exposure (100%) than baseline (20%, p = 0.04). These effects were prevented by pretreatment of N-acetylcysteine (NAC, 5 mmol/L, n = 3). In 12 Langendorff-perfused rat hearts, DEP infusion of 12.5 μg/mlmore » for 20 min prolonged action potential duration (APD) at only left ventricular base increasing apicobasal repolarization gradients. Spontaneous early afterdepolarization (EAD) and ventricular tachycardia (VT) were observed in 8 (67%) and 6 (50%) hearts, respectively, versus no spontaneous triggered activity or VT in any hearts before DEP infusion. DEP-induced APD prolongation, EAD and VT were successfully prevented with NAC (5 mmol/L, n = 5), nifedipine (10 μmol/L, n = 5), and active Ca{sup 2+}/calmodulin-dependent protein kinase II (CaMKII) blockade, KN 93 (1 μmol/L, n = 5), but not by thapsigargin (200 nmol/L) plus ryanodine (10 μmol/L, n = 5) and inactive CaMKII blockade, KN 92 (1 μmol/L, n = 5). In neonatal rat cardiomyocytes, DEP provoked ROS generation in dose dependant manner. DEP (12.5 μg/ml) induced apoptosis, and this effect was prevented by NAC and KN 93. Thus, this study shows that in vivo and vitro exposure of PM induced APD prolongation, EAD and ventricular arrhythmia. These effects might be caused by oxidative stress and CaMKII activation. -- Highlights: ► The ambient PM consistently prolonged repolarization. ► The ambient PM induced triggered activity and ventricular arrhythmia. ► These effects were prevented by antioxidants, I{sub CaL} blockade and CaMKII blockade. ► The ambient PM can induce arrhythmia via oxidative stress and activation of CaMKII.« less

Effects of deoxynivalenol on calcium homeostasis of concanavalin A--Stimulated splenic lymphocytes of chickens in vitro.

PubMed

Ren, Zhihua; Wang, Yachao; Deng, Huidan; Deng, Youtian; Deng, Junliang; Zuo, Zhicai; Wang, Ya; Peng, Xi; Cui, Hengmin; Shen, Liuhong; Yu, Shumin; Cao, Suizhong

2016-04-01

In this study, the in vitro effects of the treatment of concanavalin A (Con A)--stimulated splenic lymphocytes with DON were examined. Splenic lymphocytes isolated from chickens were stimulated with 12.5 μg/mL Con A and exposed to deoxynivalenol (DON) (0-50 μg/mL) for 48 h. The intracellular calcium concentration ([Ca(2+)]i), pH, calmodulin (CaM) mRNA levels, and Na(+),K(+)-ATPase and Ca(2+)-ATPase activities were detected. With the DON exposure concentrations increased, the [Ca(2+)]i and CaM mRNA levels gradually increased in a dose-dependent manner, and all the evaluated conconcentrations affected ATPase activity to the same extent. There were significant differences (P<0.05 or P<0.01) between the treatment groups and the control group. These results indicate that an imbalance in calcium homeostasis and intracellular acidification are components of DON cytotoxicity in chicken lymphocytes. Copyright © 2016 Elsevier GmbH. All rights reserved.

Dramatically enhanced non-Ohmic properties and maximum stored energy density in ceramic-metal nanocomposites: CaCu3Ti4O12/Au nanoparticles

PubMed Central

2013-01-01

Non-Ohmic and dielectric properties of a novel CaCu3Ti4O12/Au nanocomposite were investigated. Introduction of 2.5 vol.% Au nanoparticles in CaCu3Ti4O12 ceramics significantly reduced the loss tangent while its dielectric permittivity remained unchanged. The non-Ohmic properties of CaCu3Ti4O12/Au (2.5 vol.%) were dramatically improved. A nonlinear coefficient of ≈ 17.7 and breakdown electric field strength of 1.25 × 104 V/m were observed. The maximum stored energy density was found to be 25.8 kJ/m3, which is higher than that of pure CaCu3Ti4O12 by a factor of 8. Au addition at higher concentrations resulted in degradation of dielectric and non-Ohmic properties, which is described well by percolation theory. PMID:24257060

Antenatal Vitamin D Preserves Placental Vascular and Fetal Growth in Experimental Chorioamnionitis Due to Intra-amniotic Endotoxin Exposure.

PubMed

Cookson, Michael W; Ryan, Sharon L; Seedorf, Gregory J; Dodson, R Blair; Abman, Steve H; Mandell, Erica W

2018-05-01

 Chorioamnionitis (CA) is associated with a high risk for the development of bronchopulmonary dysplasia (BPD) after preterm birth, but mechanisms that increase susceptibility for BPD and strategies to prevent BPD are uncertain. As a model of CA, antenatal intra-amniotic (IA) endotoxin (ETX) exposure alters placental structure, causes fetal growth restriction, increases perinatal mortality, and causes sustained cardiorespiratory abnormalities throughout infancy. Vitamin D (Vit D) has been shown to have both anti-inflammatory and proangiogenic properties. Antenatal IA treatment with Vit D (1,25-(OH) 2 D 3 ) during IA ETX exposure improves survival and increases vascular and alveolar growth in infant rats. Whether IA ETX causes decreased placental vascular development and if the protective effects of prenatal Vit D treatment are due to direct effects on the fetus or to improved placental vascular development remain unknown.  The objective of this study was to determine if IA ETX impairs placental vascular development and Vit D metabolism, and whether 1,25-(OH) 2 D 3 treatment improves placental vascularity after IA ETX exposure during late gestation in pregnant rats.  Fetal rats were exposed to ETX (10 mg), ETX + 1,25-(OH) 2 D 3 (1 ng/mL), 1,25-(OH) 2 D 3 (1 ng/mL), or saline (control) via IA injection at E20 and delivered 2 days later. To assess placental vascular development, histologic sections from the placenta were stained for CD31 and vessel density per high power field (HPF) was determined and analyzed using Matlab software. To determine the effects of ETX on placental Vit D metabolism, Vit D receptor (VDR) and activity of the Vit D conversion enzyme, CYP27B1, were assayed from placental homogenates. Angiogenic mediators were measured by reverse transcription polymerase chain reaction by RNA extracted from placental tissue.  IA ETX reduced placenta and newborn birth weights by 22 and 20%, respectively, when compared with controls (placental weight: 0.60 vs. 0.47 g; p  < 0.0001; birth weight: 4.68 vs. 5.88 g; p  < 0.0001). IA 1,25-(OH) 2 D 3 treatment increased birth weight by 12% in ETX-exposed pups (5.25 vs. 4.68 g; p  < 0.001). IA ETX decreased placental vessel density by 24% in comparison with controls (1,114 vs. 848 vessels per HPF; p  < 0.05). Treatment with IA 1,25-(OH) 2 D 3 increased placenta vessel density twofold after ETX exposure (1,739 vs. 848); p  < 0.0001), and increased vessel density compared with saline controls by 56% (1,739 vs. 1,114; p  < 0.0001). IA ETX decreased both VDR and CYP27B1 expression by 83 and 35%, respectively ( p  < 0.01).  IA ETX decreases placental growth and vessel density and decreases placental VDR and CYP27B1 protein expression, and that antenatal 1,25-(OH) 2 D 3 restores placental weight and vessel density, as well as birth weight. We speculate that 1,25-(OH) 2 D 3 treatment preserves placental function in experimental CA and that these effects may be mediated by increased vascular growth. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Increased expression of HOXB2 and HOXB13 proteins is associated with HPV infection and cervical cancer progression.

PubMed

Gonzalez-Herrera, Al; Salgado-Bernabe, M; Velazquez-Velazquez, Ck; Salcedo-Vargas, M; Andrade-Manzano, A; Avila-Moreno, F; Pina-Sanchez, P

2015-01-01

Cervical cancer (CeCa) is the second most common cancer in women in developing countries, and human papilloma virus (HPV) is the primary etiological factor. Aberrant expression of HOX transcription factors has been observed in several types of cancer. To date, however, no reports exist on the expression of HOXB2 and HOXB13 proteins during neoplastic progression in CeCa and its correlation with HPV infection. Expression of HOXB2 and HOXB13 proteins was assessed in tissue microarrays from normal cervical epithelium, cervical intraepithelial neoplasias grade 1-3, and CeCa. HPV was detected by PCR and sequencing. Expression of HOX-positive cells was determined in each diagnostic group. Percentage of HOXB2- and HOXB13-positive cells gradually increased from means of 10.9% and 16.7%, respectively, in samples from healthy women, to 75.2% and 88.6% in those from CeCa patients. Frequency of HPV infection also increased from 13% in healthy tissue samples to 92.3% in CeCa. Both HOXB2 and HOXB13 proteins were preferentially expressed in HPV+ samples. The present study represents the first report on the expression of both HOXB2 and HOXB13 proteins through cervix tumorigenesis, providing evidence that increased expression of such proteins is a common event during progression to CeCa.

Experiment K-6-05. The maturaton of bone and dentin matrices in rats flown on Cosmos 1887

NASA Technical Reports Server (NTRS)

Simmons, D.; Grynpas, M.; Rosenberg, G.; Durnova, G.

1990-01-01

The chemistry, hydroxyapatite crystal size, and maturation of the bone and dentin is characterized in rats exposed to microgravity for 12.5d in a Soviet Biosatellite (Cosmos-1887). Calvarial and vertebral bone ash was subnormal, but contained a normal percent composition of Ca, P, and Mg. These tissues varied from the norm by having lower Ca/P and higher Ca/Mg ratios than any of their age-matched controls (Vivarium and Synchronous Groups). Gradient density analyses (calvaria) indicated a strong shift to the lower sp.gr. fractions which was commensurate with impaired rates of matrix-mineral maturation. X-ray diffraction data were confirmatory. Bone hydroxyapatite crystal growth in Flight rats was preferentially altered in a way to reduce the dimension of their C-axis. Flight rat dentin was normal with respect to age-matched control Ca, P, Mg, and Zn concentrations and their Ca/P and Ca/Mg ratios. These observations affirm the concept that microgravity adversely affects the maturation of newly formed matrix and mineral moieties in bone.

Comparison of 0.46% calcium diets with and without added anions with a 0.7% calcium anionic diet as a means to reduce periparturient hypocalcemia.

PubMed

Goff, Jesse P; Koszewski, Nicholas J

2018-06-01

Most studies demonstrating that diets with low dietary cation-anion difference (DCAD) reduce hypocalcemia in cows add enough anions to the diet to reduce urine pH below 7.0. One objective of these experiments was to determine whether there is any benefit to periparturient plasma Ca concentration if diet anion addition results in a lesser degree of acidification of the cow and urine pH does not go below 7.0. Another method for reducing hypocalcemia involves feeding a prepartal diet that is Ca deficient. This places the cow in negative Ca balance before calving, stimulating parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D secretion before calving and thus promoting Ca homeostasis at calving. As practiced in the field, low-Ca diets are often about 0.5% Ca. Our second objective was to determine whether a 0.46% Ca diet would be sufficiently low in Ca to stimulate PTH secretion before calving. A meta-analysis of the literature suggests that a 0.5% Ca, low-DCAD diet will reduce hypocalcemia better than a 0.7% Ca diet. A third objective was to compare periparturient plasma Ca in cows fed 0.46 or 0.72% Ca diets with similar DCAD. In experiment 1, anions (primarily chloride) or anions plus Ca were added to a 1.4% K basal diet to create the following diets: 0.46% Ca and +167 mEq/kg of DCAD, 0.46% Ca and -13 mEq/kg of DCAD, and 0.72% Ca and -17 mEq/kg of DCAD. In experiment 2, the same amounts of anion were added to a 2.05% K basal diet to create the following diets: 0.46% Ca and +327 mEq/kg of DCAD, 0.46% Ca and +146 mEq/kg of DCAD, and 0.72% Ca and +140 mEq/kg of DCAD. In experiment 1, cows fed the diet with 0.46% Ca and +167 mEq/kg of DCAD had significantly lower plasma Ca concentration after calving than cows fed the 0.46 or 0.72% Ca diets with anions. Periparturient plasma Ca concentrations did not differ in cows fed the low-DCAD diets with 0.46 or 0.72% Ca. Urine pH was reduced from 8.27 in the diet with 0.46% Ca and +167 mEq/kg of DCAD to 7.07 and 7.41 in the 0.46 and 0.72% Ca anion diets, respectively. Precalving plasma PTH and 1,25-dihydroxyvitamin D concentrations were similar in cows fed the 0.46% Ca diets and the 0.72% Ca diets, suggesting that the 0.46% Ca diets were not low enough in Ca to place the cow in negative Ca balance before calving. In experiment 2, adding the anion supplements to a 2.05% K diet did not reduce urine pH below 8.0. Periparturient plasma Ca concentrations did not differ in cows in any group in experiment 2. Precalving diets that are 0.46% Ca fed ad libitum are too high in Ca to stimulate Ca homeostasis before calving. Adding anions to a diet can benefit periparturient cow plasma Ca concentration, but only if it alters acid-base status enough to reduce urine pH below 7.5. The Authors. Published by FASS Inc. and Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).

Interdigital athlete's foot. The interaction of dermatophytes and resident bacteria.

PubMed

Leyden, J J; Kligman, A M

1978-10-01

Quantitative cultures in 140 cases of interdigital "athlete's foot" established the following clinical-microbiological correlations. In 39 cases of mild, scaling, relatively asymptomatic variety, fungi were recovered in 84% of cases. As the disease progressed to maceration, hyperkeratosis, and increased symptoms, recovery of fungi fell to 55% in moderately symptomatic and to 36% in severe cases. Symptomatic cases had increasing numbers of resident aerobic organisms, particularly large colony diphtheroids. Experimental manipulations of the interspace microflora in volunteers, monitored with quantitative cultures, demonstrated that symptomatic, macerated, hyperkeratotic process results from an overgrowth of resident organisms if the stratum corneum barrier is damaged by preexisting fungi, while overgrowth of the same organisms in normal, fungus-free interspaces does not produce lesions. These experiments support the conclusion that athlete's foot represents a continuum from a relatively asymptomatic, scaling eruption produced by fungi to a symptomatic, macerated, hyperkeratotic variety that is caused by an overgrowth of bacteria.

ERP-based detection of brain pathology in rat models for preclinical Alzheimer's disease

NASA Astrophysics Data System (ADS)

Nouriziabari, Seyed Berdia

Early pathological features of Alzheimer's disease (AD) include the accumulation of hyperphosphorylated tau protein (HP-tau) in the entorhinal cortex and progressive loss of basal forebrain (BF) cholinergic neurons. These pathologies are known to remain asymptomatic for many years before AD is clinically diagnosed; however, they may induce aberrant brain processing which can be captured as an abnormality in event-related potentials (ERPs). Here, we examined cortical ERPs while a differential associative learning paradigm was applied to adult male rats with entorhinal HP-tau, pharmacological blockade of muscarinic acetylcholine receptors, or both conditions. Despite no impairment in differential associative and reversal learning, each pathological feature induced distinct abnormality in cortical ERPs to an extent that was sufficient for machine classifiers to accurately detect a specific type of pathology based on these ERP features. These results highlight a potential use of ERPs during differential associative learning as a biomarker for asymptomatic AD pathology.

Management of asymptomatic gene carriers of transthyretin familial amyloid polyneuropathy

PubMed Central

Barroso, Fabio; González‐Duarte, Alejandra; Conceição, Isabel; Obici, Laura; Keohane, Denis; Amass, Leslie

2016-01-01

ABSTRACT Transthyretin familial amyloid polyneuropathy (TTR‐FAP) is a rare, severe, and irreversible, adult‐onset, hereditary disorder caused by autosomal‐dominant mutations in the TTR gene that increase the intrinsic propensity of transthyretin protein to misfold and deposit systemically as insoluble amyloid fibrils in nerve tissues, the heart, and other organs. TTR‐FAP is characterized by relentless, progressively debilitating polyneuropathy, and leads to death, on average, within 10 years of symptom onset without treatment. With increased availability of disease‐modifying treatment options for a wider spectrum of patients with TTR‐FAP, timely detection of the disease may offer substantial clinical benefits. This review discusses mutation‐specific predictive genetic testing in first‐degree relatives of index patients diagnosed with TTR‐FAP and the structured clinical follow‐up of asymptomatic gene carriers for prompt diagnosis and early therapeutic intervention before accumulation of substantial damage. Muscle Nerve 54: 353–360, 2016 PMID:27273296

Single visit nonsurgical endodontic therapy for periapical cysts: A clinical study

PubMed Central

Maity, Ipsita; Meena, N.; Kumari, R. Anitha

2014-01-01

Aims: The aim of this study was to assess the outcome of single sitting root canal treatment (RCT) of asymptomatic teeth with periapical cysts. Materials and Methods: Ten maxillary anterior teeth showing periapical lesion on the radiograph was further screened by ultrasound with color power Doppler (CPD) for confirmation of a cyst. The average dimension of the lesions ranged from 1.3 to 1.9 cm. Single sitting RCT was performed on all the selected teeth. Postoperative healing was monitored at regular interval of 3 months, 6 months, and 1 year by using subjective feedback, radiograph, and ultrasound with CPD study. Results: Eight among the ten cases showed either signs of complete healing or healing in progress by the end of 6-12 months. Conclusions: It was observed that single sitting nonsurgical endodontic management of asymptomatic teeth with periapical cyst confirmed by ultrasound was successful in selected cases. PMID:24963246

Single visit nonsurgical endodontic therapy for periapical cysts: A clinical study.

PubMed

Maity, Ipsita; Meena, N; Kumari, R Anitha

2014-04-01

The aim of this study was to assess the outcome of single sitting root canal treatment (RCT) of asymptomatic teeth with periapical cysts. Ten maxillary anterior teeth showing periapical lesion on the radiograph was further screened by ultrasound with color power Doppler (CPD) for confirmation of a cyst. The average dimension of the lesions ranged from 1.3 to 1.9 cm. Single sitting RCT was performed on all the selected teeth. Postoperative healing was monitored at regular interval of 3 months, 6 months, and 1 year by using subjective feedback, radiograph, and ultrasound with CPD study. Eight among the ten cases showed either signs of complete healing or healing in progress by the end of 6-12 months. It was observed that single sitting nonsurgical endodontic management of asymptomatic teeth with periapical cyst confirmed by ultrasound was successful in selected cases.