Sample records for elevated ca-125 level

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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 ...

  10. Serum CA125: a tumor marker for monitoring response to treatment and follow-up in patients with non-Hodgkin's lymphoma.

    PubMed

    Zidan, Jamal; Hussein, Osamah; Basher, Walid; Zohar, Shmuel

    2004-01-01

    Serum CA125 is an important prognostic factor in patients with non-Hodgkin's lymphoma (NHL). Elevation of CA125 level correlates with advanced disease, poor response to treatment, and poor survival rates. The aim of the current study is to evaluate CA125 levels in patients with NHL and to investigate the correlations between high CA125 level and other presenting features. Thirty-eight patients (14 with low-grade and 24 with aggressive histologically proven NHL) were studied prospectively. Serum CA125 assessment was done at diagnosis, during treatment, and at follow-up. The associations between CA125 levels and other presenting features were examined. CA125 levels were elevated in 43% of patients with low-grade NHL and in 46% of patients with aggressive NHL (i.e., 45% of all patients). A higher CA125 level was associated with advanced disease, bone marrow involvement, extranodal involvement, poor performance status, the presence of B symptoms, and high serum lactate dehydrogenase level. Complete responses occurred in 86% of patients with normal CA125 levels and in 59% of patients with elevated CA125 levels. In both low-grade and aggressive NHL, the estimated 5-year overall survival rate was higher in patients with normal CA125 levels than in patients with elevated CA125 levels (88% versus 50% and 70% versus 27%, respectively). High serum CA125 is an important prognostic factor in NHL and correlates with more advanced disease, low response rates, and worse survival. CA125 measurements may be used for staging, monitoring response to treatment, and follow-up of patients with NHL. Copyright AlphaMed Press

  11. Correlation of CA-125 serum level and clinico-pathological characteristic of patients with endometriosis.

    PubMed

    Karimi-Zarchi, Mojgan; Dehshiri-Zadeh, Najmeh; Sekhavat, Leili; Nosouhi, Fahime

    2016-11-01

    Cancer antigen 125 (CA-125) is a glycoprotein biomarker that is used in women with pelvic masses such as endometriosis and maybe is useful in practice of patients suspicious to endometriosis. The aim of this study was to evaluate the association between preoperative serum CA-125 levels and clinic pathological characteristic in women with endometriosis, and find out the best serum CA-125 levels cut-off in pre and post menopause women. Serum CA-125 levels in 87 women aged 21-54 years suspected to endometriosis with pelvic pain, dysmenorrhea, or dyspareunia were measured preoperatively. Also the association between clinic pathological characteristic and serum CA-125 level were analyzed. The mean age of women was 32.22±6.91. The mean serum CA-125 level was 49.93±4.30 U/mL. There was a significant correlation between the endometriosis stage, lesion size, adhesion score and preoperative CA-125 plasma concentration. However, we did not found significant differences in age, marital status, patient's complaints, and pelvic pain associated to Ca125 serum level. The suggested preoperative serum cut-off levels in premenopausal and postmenopausal patients were 37 U/ml and 35 U/ml, respectively. According to the results, preoperative serum CA-125 is an important predictor for patients with endometriosis and it should be taken into consideration when surgical management is suspected, especially if stage of disease, lesion size and adhesion score are undertaken.

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. The effect of CA125 on metastasis of ovarian cancer: old marker new function.

    PubMed

    Yuan, Qin; Song, Jiayin; Yang, Weiwei; Wang, Hongyan; Huo, Qianyu; Yang, Jie; Yu, Xiaoxu; Liu, Yunde; Xu, Chen; Bao, Huijing

    2017-07-25

    CA125 has been used extensively to screen for neoplasms, especially in ovarian cancer. The serum CA125 level can be used as a better prognosis evaluation and it may dynamic monitoring the disease progression. We explored the effect of CA125 on ovarian cancer cell migration and its underlying mechanism. Transwell assays showed that exposure to 0.2 μg/ml or 0.4 μg/ml CA125 for 48 h increased migration of A2780 and OVCAR-3 ovarian cancer cells. This effect of CA125 was blocked addition of 200 ng/ml DKK-1, a Wnt pathway inhibitor. Conversely, addition of CA125 reversed the inhibitory effect of Wnt inhibition in A2780 cells pretreated with DKK-1. Examination of CA125 levels in serum from 97 ovarian cancer patients revealed no relationship between a patient's age or CA125 level currently used clinically for ovarian cancer diagnosis and metastasis. However, using receiver operating characteristic (ROC) curves, we identified a new cut-off value for the serum CA125 concentration (82.9 U/ml) that is predictive of metastasis. The area under the curve is 0.632. This new cut-off value has the potential to serve as a clinically useful indicator of metastasis in ovarian cancer patients.

  20. The effect of CA125 on metastasis of ovarian cancer: old marker new function

    PubMed Central

    Yang, Weiwei; Wang, Hongyan; Huo, Qianyu; Yang, Jie; Yu, Xiaoxu; Liu, Yunde; Xu, Chen; Bao, Huijing

    2017-01-01

    CA125 has been used extensively to screen for neoplasms, especially in ovarian cancer. The serum CA125 level can be used as a better prognosis evaluation and it may dynamic monitoring the disease progression. We explored the effect of CA125 on ovarian cancer cell migration and its underlying mechanism. Transwell assays showed that exposure to 0.2 μg/ml or 0.4 μg/ml CA125 for 48 h increased migration of A2780 and OVCAR-3 ovarian cancer cells. This effect of CA125 was blocked addition of 200 ng/ml DKK-1, a Wnt pathway inhibitor. Conversely, addition of CA125 reversed the inhibitory effect of Wnt inhibition in A2780 cells pretreated with DKK-1. Examination of CA125 levels in serum from 97 ovarian cancer patients revealed no relationship between a patient's age or CA125 level currently used clinically for ovarian cancer diagnosis and metastasis. However, using receiver operating characteristic (ROC) curves, we identified a new cut-off value for the serum CA125 concentration (82.9 U/ml) that is predictive of metastasis. The area under the curve is 0.632. This new cut-off value has the potential to serve as a clinically useful indicator of metastasis in ovarian cancer patients. PMID:28637006

  1. [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.

  2. Usefulness of CA125 and their kinetic parameters and positron emission tomography/computed tomography (PET/CT) with fluorodeoxyglucose ([18F] FDG) in the detection of recurrent ovarian cancer levels.

    PubMed

    Palomar Muñoz, Azahara; Cordero García, José Manuel; Talavera Rubio, Prado; García Vicente, Ana M; González García, Beatriz; Bellón Guardia, María Emiliana; Soriano Castrejón, Ángel; Aranda Aguilar, Enrique

    2017-12-21

    To assess the usefulness of cancer antigen 125 (CA125) serum levels and kinetic values, velocity (CA125vel) and doubling time (CA125dt), as well as fluorodeoxyglucose ([ 18 F]FDG) positron emission tomography/computed tomography (PET/CT), in the detection of ovarian cancer recurrence. To assess the optimal cut-off for CA125, CA125vel and CA125dt to detect relapse with [ 18 F]FDG-PET/CT. A retrospective analysis was performed of 59 [ 18 F]FDG-PET/CT (48 patients) for suspected recurrence of ovarian cancer. Receiver operating characteristic (ROC) curves were plotted and area-under-the curve (AUC) statistics were computed for CA125, CA125vel and CA125dt. The results obtained in the group with normal and high (>35U/ml) CA125 levels were compared. Forty-four cases of recurrence were diagnosed (7 had CA125 ≤35U/ml), whereas 15 showed no disease. All of them were correctly catalogued by PET/CT. In ROC analysis, the discriminatory power of CA125 was relatively high (AUC 0.835) and the optimal cut-off point to reflect active disease was 23.9U/ml. The ROC analyses for the CA125vel and CA125dt showed an AUC of 0.849 and 0.728, respectively, with an optimal cut-off point of 1.96U/ml/month and 0.76 months, respectively. In patients with normal CA125 and recurrence of ovarian cancer, the CA125vel was significantly higher than in patients without recurrence (p=0.029). [ 18 F]FDG-PET/CT is more accurate than CA125 parameters in the detection of ovarian cancer recurrence. CA125 serum levels are essential; nevertheless, CA125 kinetic values must be considered to detect relapse. Particularly in patients with CA125 within normal values, in which a higher CA125vel is indicative of recurrence. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  3. 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...

  4. 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...

  5. 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...

  6. 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...

  7. 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...

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. Lowering glucose level elevates [Ca2+]i in hypothalamic arcuate nucleus NPY neurons through P/Q-type Ca2+ channel activation and GSK3β inhibition

    PubMed Central

    Chen, Yu; Zhou, Jun; Xie, Na; Huang, Chao; Zhang, Jun-qi; Hu, Zhuang-li; Ni, Lan; Jin, You; Wang, Fang; Chen, Jian-guo; Long, Li-hong

    2012-01-01

    Aim: To identify the mechanisms underlying the elevation of intracellular Ca2+ level ([Ca2+]i) induced by lowering extracellular glucose in rat hypothalamic arcuate nucleus NPY neurons. Methods: Primary cultures of hypothalamic arcuate nucleus (ARC) neurons were prepared from Sprague-Dawley rats. NPY neurons were identified with immunocytochemical method. [Ca2+]i was measured using fura-2 AM. Ca2+ current was recorded using whole-cell patch clamp recording. AMPK and GSK3β levels were measured using Western blot assay. Results: Lowering glucose level in the medium (from 10 to 1 mmol/L) induced a transient elevation of [Ca2+]i in ARC neurons, but not in hippocampal and cortical neurons. The low-glucose induced elevation of [Ca2+]i in ARC neurons depended on extracellular Ca2+, and was blocked by P/Q-type Ca2+channel blocker ω-agatoxin TK (100 nmol/L), but not by L-type Ca2+ channel blocker nifedipine (10 μmol/L) or N-type Ca2+channel blocker ω-conotoxin GVIA (300 nmol/L). Lowering glucose level increased the peak amplitude of high voltage-activated Ca2+ current in ARC neurons. The low-glucose induced elevation of [Ca2+]i in ARC neurons was blocked by the AMPK inhibitor compound C (20 μmol/L), and enhanced by the GSK3β inhibitor LiCl (10 mmol/L). Moreover, lowering glucose level induced the phosphorylation of AMPK and GSK3β, which was inhibited by compound C (20 μmol/L). Conclusion: Lowering glucose level enhances the activity of P/Q type Ca2+channels and elevates [Ca2+]i level in hypothalamic arcuate nucleus neurons via inhibition of GSK3β. PMID:22504905

  14. 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

  15. 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

  16. 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

  17. 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.

  18. Clinical Interpretation of Elevated CA 19-9 Levels in Obstructive Jaundice Following Benign and Malignant Pancreatobiliary Disease.

    PubMed

    Kim, Min Seong; Jeon, Tae Joo; Park, Ji Young; Choi, Jeongmin; Shin, Won Chang; Park, Seong Eun; Seo, Ji Young; Kim, Young Moon

    2017-08-25

    Elevated carbohydrate antigen (CA) 19-9 level may be unable to differentiate between benign and malignant pancreatobiliary disease with obstructive jaundice. The study aims to determine the clinical interpretation and the diagnostic value of CA 19-9 level in pancreatobiliary diseases with coexistent obstructive jaundice. We retrospectively reviewed the data of 981 patients who underwent biliary drainage due to obstructive jaundice following pancreatobiliary disease at Sanggye Paik Hospital for 5 years. 114 patients with serial follow-up data for CA 19-9 level were included in this study (80 patients with malignancy and 34 patients with benign diseases). We compared the levels of CA 19-9 levels and the biochemical value before and after biliary drainage. The rate of CA 19-9 elevation (>37 U/mL) was significantly different between the benign group and the malignant group (59% vs. 90%, p=0.001). Despite the decrease in serum bilirubin after biliary drainage, CA 19-9 levels remained elevated in 12% of patients in the benign group and in 63% of patients in the malignant group (p<0.001). Finally, 12% of patients in the benign group turned out to have malignant disease. A receiver operating characteristic analysis provided a cut-off value of 38 U/mL for differentiating benign disease from malignant disease after biliary drainage (area under curve, 0.787; 95% confidence interval, 0.703 to 0.871; sensitivity, 62%; specificity, 88%). This study suggested that we should consider the possibility of malignant causes if the CA 19-9 levels remain high or are more than 38 U/mL after resolution of biliary obstruction.

  19. 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

  20. CLEIA CA125 evidences: good analytical performance avoiding "Hook effect".

    PubMed

    Falzarano, R; Viggiani, V; Michienzi, S; Colaprisca, B; Longo, F; Frati, L; Anastasi, E

    2013-02-01

    Cancer antigen 125 (CA125) is a coelomic epithelium-related antigen carried by a high molecular weight glycoprotein complex. It is commonly used as a tumor marker for ovarian cancer to monitor disease progression and response to therapy and as an early detection for recurrence after treatment. The aim of this study was to test the reliability of two different assay methods, a radioimmunometric assay (RIA) and an automated chemiluminescent enzyme immunoassay (CLEIA) system, by measuring CA125 serum levels using both methods in 357 patients and comparing the results. Patients were recruited from Oncologic Unit A, Policlinico Umberto I, Roma. Eighty-six were healthy donors, while 271 were oncologic patients representing a variety of diagnoses. Within this group, 76 patients were diagnosed with an ovarian related pathology (28 cancerous and 48 benign). The evaluation of CA125 marker blood levels showed a high agreement in healthy donors group (R (2) = 0.9003). Interesting results emerged when sera collected from oncologic patients were assessed: significant differences between the two assays were found in nine samples. When assayed again with RIA after a dilution, new values agreed with undiluted CLEIA values (R (2) = 0.9847). Our data suggest an overall good comparison between the two methods. However, some artifacts were obtained with RIA and indicate an underlying presence of "hook effect". CLEIA automated assay showed a good reliability and should be preferred to one-step radioimmunoassays in order to minimize errors.

  1. Interdependence of skeletal sclerosis and elevated circulating levels of 1,25-dihydroxyvitamin D in osteopetrotic (op and tl) rats.

    PubMed

    Popoff, S N; Osier, L K; Zerwekh, J E; Marks, S C

    1994-01-01

    Osteopetrosis describes a heterogeneous group of inherited, metabolic bone disorders characterized by reduced bone resorption which coexists with elevated circulating levels of 1,25-dihydroxyvitamin D [1,25(OH)2D]. To determine whether or not skeletal sclerosis and high concentrations of 1,25(OH)2D are interdependent, this study used two distinct, nonallelic osteopetrotic mutations in the rat, osteopetrosis (op) and toothless (tl). The op rat is a mutation in which skeletal sclerosis can be cured (mutant) or induced (normal) following the transfer of normal or mutant osteoclast progenitors, respectively. Although these procedures are ineffective in rats of tl stock, infusions of pharmacological doses of macrophage colony-stimulating factor (CSF-1) can stimulate bone resorption and eliminate most of the excess skeletal matrix in tl mutants. This study examined the effects of cure/induction in neonatal mutant/normal rats of op stock and CSF-1 infusions in mutant rats of tl stock on skeletal (bone resorption) and serum [1,25(OH)2D] parameters as a function of time after treatment. Osteopetrotic mutants transplanted (cured) with normal spleen cells demonstrated cellular changes in osteoclast phenotype within 2-3 days followed by histologic and radiographic evidence for increased bone resorption that culminated in a normal appearance of the skeleton by 4 weeks. The markedly elevated serum levels of 1,25(OH)2D observed in untreated mutants fell significantly in transplanted mutants by the end of the first week and were similar to those in normal littermates at 3 and 4 weeks. Normal littermates transplanted (induced) with mutant spleen cells showed a progressive increase in skeletal sclerosis paralleled by significant increases in circulating levels of 1,25(OH)2D.(ABSTRACT TRUNCATED AT 250 WORDS)

  2. 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

  3. A Nanoparticle-Lectin Immunoassay Improves Discrimination of Serum CA125 from Malignant and Benign Sources.

    PubMed

    Gidwani, Kamlesh; Huhtinen, Kaisa; Kekki, Henna; van Vliet, Sandra; Hynninen, Johanna; Koivuviita, Niina; Perheentupa, Antti; Poutanen, Matti; Auranen, Annika; Grenman, Seija; Lamminmäki, Urpo; Carpen, Olli; van Kooyk, Yvette; Pettersson, Kim

    2016-10-01

    Measurement of serum cancer antigen 125 (CA125) is the standard approach for epithelial ovarian cancer (EOC) diagnostics and follow-up. However, the clinical specificity is not optimal because increased values are also detected in healthy controls and in benign diseases. CA125 is known to be differentially glycosylated in EOC, potentially offering a way to construct CA125 assays with improved cancer specificity. Our goal was to identify carbohydrate-reactive lectins for discriminating between CA125 originating from EOC and noncancerous sources. CA125 from the OVCAR-3 cancer cell line, placental homogenate, and ascites fluid from patients with cirrhosis were captured on anti-CA125 antibody immobilized on microtitration wells. A panel of lectins, each coated onto fluorescent europium-chelate-doped 97-nm nanoparticles (Eu(+3)-NPs), was tested for detection of the immobilized CA125. Serum samples from high-grade serous EOC or patients with endometriosis and healthy controls were analyzed. By using macrophage galactose-type lectin (MGL)-coated Eu(+3)-NPs, an analytically sensitive CA125 assay (CA125(MGL)) was achieved that specifically recognized the CA125 isoform produced by EOC, whereas the recognition of CA125 from nonmalignant conditions was reduced. Serum CA125(MGL) measurement better discriminated patients with EOC from endometriosis compared to conventional immunoassay. The discrimination was particularly improved for marginally increased CA125 values and for earlier detection of EOC progression. The new CA125(MGL) assay concept could help reduce the false-positive rates of conventional CA125 immunoassays. The improved analytical specificity of this test approach is dependent on a discriminating lectin immobilized in large numbers on Eu(+3)-NPs, providing both an avidity effect and signal amplification. © 2016 American Association for Clinical Chemistry.

  4. 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.

  5. 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

  6. CA-125 AUC as a predictor for epithelial ovarian cancer relapse.

    PubMed

    Mano, António; Falcão, Amílcar; Godinho, Isabel; Santos, Jorge; Leitão, Fátima; de Oliveira, Carlos; Caramona, Margarida

    2008-01-01

    The aim of the present work was to evaluate the usefulness of CA-125 normalized in time area under the curve (CA-125 AUC) to signalise epithelial ovarian cancer relapse. Data from a hundred and eleven patients were submitted to two different approaches based on CA-125 AUC increase values to predict patient relapse. In Criterion A total CA-125 AUC normalized in time value (AUC(i)) was compared with the immediately previous one (AUC(i-1)) using the formulae AUC(i) > or = F * AUC(i-1) (several F values were tested) to find the appropriate close related increment associated to patient relapse. In Criterion B total CA-125 AUC normalised in time was calculated and several cut-off values were correlated with patient relapse prediction capacity. In Criterion A the best accuracy was achieved with a factor (F) of 1.25 (increment of 25% from the previous status), while in Criterion B the best accuracies were achieved with cut-offs of 25, 50, 75 and 100 IU/mL. The mean lead time to relapse achieved with Criterion A was 181 days, while with Criterion B they were, respectively, 131, 111, 63 and 11 days. Based on our results we believe that conjugation and sequential application of both criteria in patient relapse detection should be highly advisable. CA-125 AUC rapid burst in asymptomatic patients should be firstly evaluated using Criterion A with a high accuracy (0.85) and with a substantial mean lead time to relapse (181 days). If a negative answer was obtained then Criterion B should performed to confirm the absence of relapse.

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. CaEDTA vs CaEDTA plus BAL to treat children with elevated blood lead levels.

    PubMed

    O'Connor, M E

    1992-07-01

    The effectiveness of CaEDTA alone vs CaEDTA plus BAL was compared retrospectively in a group of 72 children with lead levels between 2.41 mumol/L (50 micrograms/dL) and 2.90 mumol/L (60 micrograms/dL). The children who received both drugs had higher median zinc protoporphyrin (ZnP) concentrations at the initiation of therapy than children who received CaEDTA alone (160 micrograms/dL vs 96 micrograms/dL, p less than .01). There was a significantly increased incidence of vomiting and abnormal liver-function test results in the children who received both drugs. The children who received CaEDTA alone had a greater percent mean fall in lead level at one to three weeks postchelation (30.5% vs 18.1%, p less than .05). Children who received both CaEDTA and BAL had a greater percent decrease in ZnP at four to eight months postchelation, but there was no difference in percent decrease in lead levels. Children who received both drugs also had a greater number of repeat courses of chelation by six months. The addition of BAL to CaEDTA for treatment of children with lead levels of 2.41 mumol/L (50 micrograms/dL) to 2.90 mumol/L (60 micrograms/dL) produced greater toxicity and does not seem to prevent repeat chelations within six months.

  13. Elevated 1,25-dihydroxyvitamin D levels in patients with chronic obstructive pulmonary disease treated with prednisone

    NASA Technical Reports Server (NTRS)

    Bikle, D. D.; Halloran, B.; Fong, L.; Steinbach, L.; Shellito, J.

    1993-01-01

    Glucocorticoid administration is a well established cause of osteopenia. Mechanisms underlying the deleterious effect of glucocorticoids on bone may include direct inhibition of bone formation as well as indirect effects through changes in intestinal calcium absorption, renal calcium excretion, and/or levels of the calciotropic hormones. To further examine the potential role of the calciotropic hormones we measured serum levels of PTH and 1,25 dihydroxyvitamin D [1,25(OH)2D], as well as serum and urine levels of calcium and vertebral bone density in patients with chronic obstructive pulmonary disease being managed with or without prednisone. Patients treated with prednisone had lower spinal bone density (53 vs. 106 mg/cm3) and higher serum calcium (2.40 vs. 2.33 mmol/l), urine calcium (6.9 vs. 2.7 mmol/24h), and 1,25(OH)2D levels (147 vs. 95 pmol/L). Compared to the patients not treated with glucocorticoids. PTH levels also tended to be higher (33 vs. 26 microliters-eq/ml), but the difference was not significant. Serum and urine calcium levels correlated positively with 1,25(OH)2D levels, but none of these measurements correlated with PTH levels. Our results suggest that prednisone treatment alters the regulation of 1,25(OH)2D production, and this may contribute to the loss of bone mineral induced by prednisone.

  14. 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.

  15. 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

  16. 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

  17. 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

  18. A simple resonance Rayleigh scattering method for determination of trace CA125 using immuno-AuRu nanoalloy as probe via ultrasonic irradiation

    NASA Astrophysics Data System (ADS)

    Tang, Meiling; Wen, Guiqing; Luo, Yanghe; Liang, Aihui; Jiang, Zhiliang

    2015-01-01

    AuRu nanoalloy (GR) with Au/Ru molar ratio of 32/1 was prepared by the sodium borohydride reduction method. It was used to label the CA125 antibody (Ab) to obtain an immunonanoprobe (GRAb) for cancer antigen 125 (CA125). In pH 7.0 citric acid-Na2HPO4 buffer solution and irradiation of ultrasound, the probes were aggregated nonspecifically to big clusters that showed a strong resonance Rayleigh scattering (RRS) peak at 278 nm. Upon addition of CA125, GRAb reacted specifically with CA125 to form dispersive immunocomplexes of CA125-GRAb in the solution and this process enhanced by the ultrasonic cavitation effect, which led to the RRS intensity decreased greatly. The decreased RRS intensity was linear to the concentration of CA125 in the range of 1.3-80 U/mL, with a detection limit of 0.6 U/mL. The proposed method was applied to detect CA125 in real sample, with satisfactory results.

  19. 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.

  20. 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.

  1. 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

  2. Postoperative elevation of CA15-3 due to pernicious anemia in a patient without evidence of breast cancer recurrence.

    PubMed

    Adachi, Yayoi; Kikumori, Toyone; Miyajima, Noriyuki; Inaishi, Takahiro; Onishi, Eiji; Shibata, Masahiro; Nakanishi, Kenichi; Takeuchi, Dai; Hayashi, Hironori; Kodera, Yasuhiro

    2015-12-01

    Cancer antigen 15-3 (CA15-3) is considered as a marker for breast cancer recurrence. However, we encountered a case where the patient showed postoperative elevation of the CA15-3 level due to pernicious anemia without evidence of breast cancer recurrence. The patient was a 60-year-old postmenopausal woman. She had undergone partial mastectomy and sentinel lymph node biopsy (SLNB) for her T1 left breast cancer. SLNB had indicated no lymph node metastases. The tumor was positive for hormone receptors and negative for human epidermal growth factor receptor 2. Therefore, an aromatase inhibitor and external beam irradiation had been administered as adjuvant therapy. However, the CA15-3 level was found to be elevated at 6 months postoperatively. Although imaging studies did not indicate breast cancer recurrence, CA15-3 levels continued to increase. Based on the findings of blood tests and gastroendoscopy, a diagnosis of pernicious anemia due to vitamin B12 deficiency was finally confirmed at 2 years and 6 months postoperatively. The CA15-3 level returned to normal after vitamin B12 administration. The possibility of pernicious anemia should be considered in cases of postoperative elevated CA15-3 levels with no evidence of recurrence in patients with early breast cancer.

  3. Mitochondrial DNA 5178 C/A polymorphism modulates the effects of coffee consumption on elevated levels of serum liver enzymes in male Japanese health check-up examinees: an exploratory cross-sectional study.

    PubMed

    Kokaze, Akatsuki; Yoshida, Masao; Ishikawa, Mamoru; Matsunaga, Naomi; Karita, Kanae; Ochiai, Hirotaka; Shirasawa, Takako; Nanri, Hinako; Mitsui, Kiyomi; Hoshimo, Hiromi; Takashima, Yutaka

    2016-06-04

    Longevity-associated mitochondrial DNA 5178 cytosine/adenine (Mt5178 C/A) polymorphism modulates the effects of coffee consumption on the risk of hypertension, dyslipidemia, and abnormal glucose tolerance. The objective of this study was to investigate whether Mt5178 C/A polymorphism modifies the effects of coffee consumption on abnormally elevated levels of serum liver enzymes in male Japanese health check-up examinees. A total of 421 male subjects (mean age ± SD, 54.1 ± 7.7 years) were selected from among individuals visiting the hospital for regular medical check-ups. After Mt5178 C/A genotyping, a cross-sectional study assessing the joint effects of Mt5178 C/A polymorphism and coffee consumption on elevated levels of serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT), and serum gamma-glutamyl transpeptidase (GGT) was then conducted. For men with Mt5178C, after adjustment for age, body mass index, alcohol consumption, habitual smoking, green tea consumption, antihypertensive treatment, and antidiabetic treatment, elevated levels of serum AST, as defined as ≥30 U/L; those of serum ALT, as defined as ≥25 U/L; or those of serum GGT, as defined as ≥60 or >51 U/L, may depend on coffee consumption (P for trend = 0.013, P for trend <0.001, P for trend = 0.002, and P for trend <0.001, respectively). On the other hand, no significant joint effects of Mt5178A genotype and coffee consumption on elevated levels of serum liver enzymes were observed. The present results suggest that Mt5178 C/A polymorphism modifies the effects of coffee consumption on abnormally elevated levels of serum liver enzymes in male Japanese health check-up examinees.

  4. 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.

  5. Physician Knowledge and Awareness of CA-125 As a Screen for Ovarian Cancer in the Asymptomatic, Average-Risk Population

    ERIC Educational Resources Information Center

    Stewart, Sherri L.; Rim, Sun Hee; Gelb, Cynthia A.

    2012-01-01

    Effective early detection strategies for ovarian cancer do not exist. Current screening guidelines recommend against routine screening using CA-125 alone or in combination with transvaginal ultrasonography (TVS). In this study, the authors used the 2008 "DocStyles" survey to measure clinician beliefs about the effectiveness of CA-125 and…

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. Effects of deoxygenation on active and passive Ca2+ transport and on the cytoplasmic Ca2+ levels of sickle cell anemia red cells.

    PubMed

    Etzion, Z; Tiffert, T; Bookchin, R M; Lew, V L

    1993-11-01

    Elevated [Ca2+]i in deoxygenated sickle cell anemia (SS) red cells (RBCs) could trigger a major dehydration pathway via the Ca(2+)-sensitive K+ channel. But apart from an increase in calcium permeability, the effects of deoxygenation on the Ca2+ metabolism of sickle cells have not been previously documented. With the application of 45Ca(2+)-tracer flux methods and the combined use of the ionophore A23187, Co2+ ions, and intracellular incorporation of the Ca2+ chelator benz-2, in density-fractionated SS RBCs, we show here for the first time that upon deoxygenation, the mean [Ca2+]i level of SS discocytes was significantly increased, two- to threefold, from a normal range of 9.4 to 11.4 nM in the oxygenated cells, to a range of 21.8 to 31.7 nM in the deoxygenated cells, closer to K+ channel activatory levels. Unlike normal RBCs, deoxygenated SS RBCs showed a two- to fourfold increase in pump-leak Ca2+ turnover. Deoxygenation of the SS RBCs reduced their Ca2+ pump Vmax, more so in reticulocyte- and discocyte-rich than in dense cell fractions, and decreased their cytoplasmic Ca2+ buffering. Analysis of these results suggests that both increased Ca2+ influx and reduced Ca2+ pump extrusion contribute to the [Ca2+]i elevation.

  15. 9. EAST ELEVATION OF SKIDOO MILL, LOOKING WEST. THE LEVELS ...

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

    9. EAST ELEVATION OF SKIDOO MILL, LOOKING WEST. THE LEVELS OF THE MILL CAN BE CLEARLY SEEN HERE. THE UPPER MOST LEVEL CONSISTS OF A CONVEORY THAT BROUGHT ORE TO A JAW CRUSHER. THE CRUSHED ORE WAS CHANNELED DIRECTLY INTO A LARGE ORE BIN LOCATED BEHIND THE COVERED WALL (CENTER). THE NEXT LEVEL SHOWS THE BULL (DRIVE) WHEEL ON THE UPPER PART OF THE STAMP BATTERIES. THE NEXT LEVEL DOWN (STAIRS) IS THE LOWER PORTION OF THE STAMP BATTERIES WITH THE MORTAR BLOCKS AND APRONS. THE NEXT LEVEL DOWN (LOWER RIGHT) HELD CONCENTRATION (SHAKING) TABLES AND A CLASSIFIER. MOST EXTERIOR WALL COVERING, TIMBERS, AND ROOF IS MISSING FROM THE MILL. SEE CA-290-42 (CT) FOR IDENTICAL COLOR TRANSPARENCY - Skidoo Mine, Park Route 38 (Skidoo Road), Death Valley Junction, Inyo County, CA

  16. 42. EAST ELEVATION OF SKIDOO MILL, LOOKING WEST. THE LEVELS ...

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

    42. EAST ELEVATION OF SKIDOO MILL, LOOKING WEST. THE LEVELS OF THE MILL CAN BE CLEARLY SEEN HERE. THE UPPER MOST LEVEL CONSISTS OF A CONVEORY THAT BROUGHT ORE TO A JAW CRUSHER. THE CRUSHED ORE WAS CHANNELED DIRECTLY INTO A LARGE ORE BIN LOCATED BEHIND THE COVERED WALL (CENTER). THE NEXT LEVEL SHOWS THE BULL (DRIVE) WHEEL ON THE UPPER PART OF THE STAMP BATTERIES THE NEXT LEVEL DOWN (STAIRS) IS THE LOWER PORTION OF THE STAMP BATTERIES WITH MORTAR BLOCKS AND APRONS. THE NEXT LEVEL DOWN (LOWER RIGHT) HELD CONCENTRATION (SHAKING) TABLES AND A CLASSIFIER. MOST EXTERIOR WALL COVERING, TIMBERS, AND ROOF IS MISSING FROM THE MILL. SEE CA-290-9 FOR IDENTICAL B&W NEGATIVE. - Skidoo Mine, Park Route 38 (Skidoo Road), Death Valley Junction, Inyo County, CA

  17. [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.

  18. 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

  19. Transient elevation of cytoplasmic calcium ion concentration at a single cell level precedes morphological changes of epidermal keratinocytes during cornification.

    PubMed

    Murata, Teruasa; Honda, Tetsuya; Egawa, Gyohei; Yamamoto, Yasuo; Ichijo, Ryo; Toyoshima, Fumiko; Dainichi, Teruki; Kabashima, Kenji

    2018-04-26

    Epidermal keratinocytes achieve sequential differentiation from basal to granular layers, and undergo a specific programmed cell death, cornification, to form an indispensable barrier of the body. Although elevation of the cytoplasmic calcium ion concentration ([Ca 2+ ] i ) is one of the factors predicted to regulate cornification, the dynamics of [Ca 2+ ] i in epidermal keratinocytes is largely unknown. Here using intravital imaging, we captured the dynamics of [Ca 2+ ] i in mouse skin. [Ca 2+ ] i was elevated in basal cells on the second time scale in three spatiotemporally distinct patterns. The transient elevation of [Ca 2+ ] i also occurred at the most apical granular layer at a single cell level, and lasted for approximately 40 min. The transient elevation of [Ca 2+ ] i at the granular layer was followed by cornification, which was completed within 10 min. This study demonstrates the tightly regulated elevation of [Ca 2+ ] i preceding the cornification of epidermal keratinocytes, providing possible clues to the mechanisms of cornification.

  20. 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.

  1. Dopamine elevates and lowers astroglial Ca2+ through distinct pathways depending on local synaptic circuitry.

    PubMed

    Jennings, Alistair; Tyurikova, Olga; Bard, Lucie; Zheng, Kaiyu; Semyanov, Alexey; Henneberger, Christian; Rusakov, Dmitri A

    2017-03-01

    Whilst astrocytes in culture invariably respond to dopamine with cytosolic Ca 2+ rises, the dopamine sensitivity of astroglia in situ and its physiological roles remain unknown. To minimize effects of experimental manipulations on astroglial physiology, here we monitored Ca 2+ in cells connected via gap junctions to astrocytes loaded whole-cell with cytosolic indicators in area CA1 of acute hippocampal slices. Aiming at high sensitivity of [Ca 2+ ] measurements, we also employed life-time imaging of the Ca 2+ indicator Oregon Green BAPTA-1. We found that dopamine triggered a dose-dependent, bidirectional Ca 2+ response in stratum radiatum astroglia, a jagged elevation accompanied and followed by below-baseline decreases. The elevation depended on D1/D2 receptors and engaged intracellular Ca 2+ storage and removal whereas the dopamine-induced [Ca 2+ ] decrease involved D2 receptors only and was sensitive to Ca 2+ channel blockade. In contrast, the stratum lacunosum moleculare astroglia generated higher-threshold dopamine-induced Ca 2+ responses which did not depend on dopamine receptors and were uncoupled from the prominent inhibitory action of dopamine on local perforant path synapses. Our findings thus suggest that a single neurotransmitter-dopamine-could either elevate or decrease astrocyte [Ca 2+ ] depending on the receptors involved, that such actions are specific to the regional neural circuitry and that they may be causally uncoupled from dopamine actions on local synapses. The results also indicate that [Ca 2+ ] elevations commonly detected in astroglia can represent the variety of distinct mechanisms acting on the microscopic scale. GLIA 2017;65:447-459. © 2016 The Authors Glia Published by Wiley Periodicals, Inc.

  2. 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

  3. 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.

  4. Elevated CaMKIIα and hyperphosphorylation of Homer mediate circuit dysfunction in a Fragile X Syndrome mouse model

    PubMed Central

    Guo, Weirui; Ceolin, Laura; Collins, Katie; Perroy, Julie; Huber, Kimberly M.

    2015-01-01

    Summary Abnormal metabotropic glutamate receptor 5 (mGluR5) function, as a result of disrupted scaffolding with its binding partner Homer, contributes to the pathophysiology of Fragile X Syndrome, a common inherited from of intellectual disability and autism caused by mutations in Fmr1. How loss of Fmr1 disrupts mGluR5-Homer scaffolds is unknown, and little is known about the dynamic regulation of mGluR5-Homer scaffolds in wildtype neurons. Here we demonstrate that brief (minutes) elevations in neural activity cause CaMKIIα-mediated phosphorylation of long Homer proteins and dissociation from mGluR5 at synapses. In Fmr1 knockout cortex, Homers are hyperphosphorylated as a result of elevated CaMKIIα protein. Genetic or pharmacological inhibition of CaMKIIα or replacement of Homers with dephosphomimetics restores mGluR5-Homer scaffolds and multiple Fmr1 KO phenotypes, including circuit hyperexcitability and/or seizures. This work links translational control of an FMRP target mRNA, CaMKIIα, to the molecular, cellular and circuit level brain dysfunction in a complex neurodevelopmental disorder. PMID:26670047

  5. 48. MAIN WAREHOUSE THIRD LEVEL Elevator drive mechanism is ...

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

    48. MAIN WAREHOUSE - THIRD LEVEL Elevator drive mechanism is seen to the right, while drive wheels, belt wheels and chain drives are visible in the wooden wall framing. The horizontal metal conveyor (at the top of the wall Just under the inverted 'V' brace) is part of the empty can supply system connected to the external can conveyor. See Photo No. 28. - Hovden Cannery, 886 Cannery Row, Monterey, Monterey County, CA

  6. 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

  7. Elevated CaMKIIα and Hyperphosphorylation of Homer Mediate Circuit Dysfunction in a Fragile X Syndrome Mouse Model.

    PubMed

    Guo, Weirui; Ceolin, Laura; Collins, Katie A; Perroy, Julie; Huber, Kimberly M

    2015-12-15

    Abnormal metabotropic glutamate receptor 5 (mGluR5) function, as a result of disrupted scaffolding with its binding partner Homer, contributes to the pathophysiology of fragile X syndrome, a common inherited form of intellectual disability and autism caused by mutations in Fmr1. How loss of Fmr1 disrupts mGluR5-Homer scaffolds is unknown, and little is known about the dynamic regulation of mGluR5-Homer scaffolds in wild-type neurons. Here, we demonstrate that brief (minutes-long) elevations in neural activity cause CaMKIIα-mediated phosphorylation of long Homer proteins and dissociation from mGluR5 at synapses. In Fmr1 knockout (KO) cortex, Homers are hyperphosphorylated as a result of elevated CaMKIIα protein. Genetic or pharmacological inhibition of CaMKIIα or replacement of Homers with dephosphomimetics restores mGluR5-Homer scaffolds and multiple Fmr1 KO phenotypes, including circuit hyperexcitability and/or seizures. This work links translational control of an FMRP target mRNA, CaMKIIα, to the molecular-, cellular-, and circuit-level brain dysfunction in a complex neurodevelopmental disorder. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Normalization of Elevated Tumor Marker CA27-29 after Bilateral Lung Transplantation in a patient with Breast Cancer and Idiopathic Pulmonary Fibrosis.

    PubMed

    Copur, Mehmet Sitki; Wurdeman, Julie Marie; Nelson, Debra; Ramaekers, Ryan; Gauchan, Dron; Crockett, David

    2017-12-11

    Solid tumors involving glandular organs express mucin glycoprotein which is eventually shed into the circulation. As aresult these proteins can easily be measured in the serum and be used as potential tumor markers. The most commonly used tumor markers for breast cancer are CA 27-29 and CA 15-3, which both measure the glycoprotein product of the mucin-1 (MUC1) gene. CA 27-29 has been approved by the US Food and Drug Administration for monitoring disease activity in breast cancer patients. Most oncology clinical practice guidelines do not recommend the use of tumor markers for routine surveillance of early stage disease but recognize their utility in the metastatic setting. Herein, we present a patient with stage III-A breast cancer and pre-existing hypersensitivity pneumonitis who is found to have an elevated serum tumor marker CA 27-29. After successful curative intent treatment of her early stage breast cancer, she developed gradual and progressive worsening of her lung disease with eventual development of severe pulmonary fibrosis requiring bilateral lung transplantation. As part of the pre-transplant evaluation, she was found to have an elevation of serum tumor marker CA 27-29. While the diagnostic evaluation, including imaging studies was negative for the presence of recurrent disease, the serial serum tumor marker CA 27-29 levels remained persistently elevated. The decision was made for her to undergo bilateral lung transplantation. Shortly after surgery her CA27-29 tumor marker level returned to normal range, and it has continued to remain in the normal range with no evidence of breast cancer recurrence.

  9. Increase in Ca2+ current by sustained cAMP levels enhances proliferation rate in GH3 cells.

    PubMed

    Rodrigues, Andréia Laura; Brescia, Marcella; Koschinski, Andreas; Moreira, Thaís Helena; Cameron, Ryan T; Baillie, George; Beirão, Paulo S L; Zaccolo, Manuela; Cruz, Jader S

    2018-01-01

    Ca 2+ and cAMP are important intracellular modulators. In order to generate intracellular signals with various amplitudes, as well as different temporal and spatial properties, a tightly and precise control of these modulators in intracellular compartments is necessary. The aim of this study was to evaluate the effects of elevated and sustained cAMP levels on voltage-dependent Ca 2+ currents and proliferation in pituitary tumor GH3 cells. Effect of long-term exposure to forskolin and dibutyryl-cyclic AMP (dbcAMP) on Ca 2+ current density and cell proliferation rate were determined by using the whole-cell patch-clamp technique and real time cell monitoring system. The cAMP levels were assayed, after exposing transfected GH3 cells with the EPAC-1 cAMP sensor to forskolin and dbcAMP, by FRET analysis. Sustained forskolin treatment (24 and 48h) induced a significant increase in total Ca 2+ current density in GH3 cells. Accordingly, dibutyryl-cAMP incubation (dbcAMP) also elicited increase in Ca 2+ current density. However, the maximum effect of dbcAMP occurred only after 72h incubation, whereas forskolin showed maximal effect at 48h. FRET-experiments confirmed that the time-course to elevate intracellular cAMP was distinct between forskolin and dbcAMP. Mibefradil inhibited the fast inactivating current component selectively, indicating the recruitment of T-type Ca 2+ channels. A significant increase on cell proliferation rate, which could be related to the elevated and sustained intracellular levels of cAMP was observed. We conclude that maintaining high levels of intracellular cAMP will cause an increase in Ca 2+ current density and this phenomenon impacts proliferation rate in GH3 cells. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Sustained intracellular Ca2+ elevation induced by a brief BDNF application in rat visual cortex neurons.

    PubMed

    Mizoguchi, Yoshito; Nabekura, Junichi

    2003-08-06

    A 1-2 min application of brain-derived neurotrophic factor (BDNF; 20 ng/ml) induced sustained elevation of intracellular Ca2+ lasting > 90 min, using the fura-2 imaging of intracellular Ca2+ mobilization, in visual cortical pyramidal neurons isolated from rats. BDNF increased intracellular Ca2+ through the PLC-gamma phosphorylation after the TrkB receptor tyrosine kinase activation. Either K252a or U73122 suppressed intracellular Ca2+ in the absence of BDNF. We suggest that sustained activation of Trk B receptor tyrosine kinase and PLC-gamma occurs after a brief BDNF application and contributes to the short-term maintenance (< 30 min) of the sustained intracellular Ca2+ elevation.

  11. 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.

  12. Flowering responses of insect-pollinated plants to elevated CO{sub 2} levels

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

    Cushman, J.H.; Koch, G.W.; Chiariello, N.R.

    1995-06-01

    Elevated atmospheric CO{sub 2} concentrations have been predicted or shown to substantially influence plants, communities and ecosystems in a variety of ways. Here, we examined the effects of elevated CO{sub 2} levels on the timing and magnitude of flowering for two insect-pollinated annual plant species in a serpentine grassland. We focused on Lasthenia californica and Linanthus parviflorus and addressed three questions: (1) Do elevated CO{sub 2} levels influence flowering phenologies and is this species specific? (2) Do elevated CO{sub 2} levels affect flower production and is this due to altered numbers of individuals, flowers per plant, or both? and (3)more » Are effects on flowering due to elevated CO{sub 2} levels per se or changes in environmental conditions associated with methods used to manipulate CO{sub 2} levels? To address these questions, we used the ecosystem experiment at Stanford University`s Jasper Ridge Biological Preserve (San Mateo Co., CA). This system consists of 20 open-topped chambers - half receiving ambient CO{sub 2} (360 ppm) and half receiving elevated CO{sub 2} (720 ppm) - and 10 untreated plots serving as chamber controls. Results from the 1994 season demonstrated that there were species-specific responses to elevated CO{sub 2} levels and the field chambers. For Lasthenia californica, elevated CO{sub 2} per se did not affect relative abundance, inflorescence production, or phenology, but chambers did significantly increase inflorescence production and extend the duration of flowering. For Linanthus parviflorus, elevated CO{sub 2} levels significantly increased relative abundance and flower production, and extended the flowering period slightly, while the chambers significantly decreased flower production early in the season and increased it later in the season.« less

  13. 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.

  14. 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

  15. Elevated fibroblast growth factor 23 levels as a cause of early post-renal transplantation hypophosphatemia.

    PubMed

    Han, S Y; Hwang, E A; Park, S B; Kim, H C; Kim, H T

    2012-04-01

    Hypophosphatemia is a common complication after renal transplantation. Hyperparathyroidism has long been thought to be the cause, but hypophosphatemia can persist after high parathyroid hormone (PTH) levels normalize. Furthermore, calcitriol levels remain inappropriately low after transplantation, suggesting that mechanisms other than PTH contribute. Fibroblast growth factor 23 (FGF-23) induces phosphaturia, inhibits calcitriol synthesis, and accumulates in chronic kidney disease. We performed prospective study to investigate if FGF-23 early after renal transplantation contributes to hypophosphatemia. We measured FGF-23 levels before and at 1, 2, 4, and 12 weeks after transplantation in 20 renal transplant recipients. Serum creatinine, calcium (Ca), phosphate (Pi), intact PTH (PTH), and 1,25-dihydroxy vitamin D (1,25(OH)(2)VitD) were measured at the same time. FGF-23 levels decreased by 97% at 4 weeks after renal transplantation (PRT) (7,471 ± 11,746 vs 225 ± 295 pg/mL; P < .05) but were still above normal. PTH and Pi levels also decreased significantly after renal transplantation, and Ca and 1,25(OH)(2)VitD slightly increased. PRT hypophosphatemia of <2.5 mg/dL developed in 15 (75%) and 12 (60%) patients at 4 weeks and 12 weeks respectively. Compared with nonhypophosphatemic patients, the levels of FGF-23 of hypophosphatemic patients were higher (303 ± 311 vs 10 ± 6.9 pg/mL; P = .02) at 4 weeks PRT. FGF-23 levels were inversely correlated with Pi (r(2) = 0.406; P = .011); PTH was not independently associated with Pi (r(2) = 0.132; P = .151). FGF-23 levels decrease dramatically after renal transplantation. During the early PRT period, Pi rapidly decreased, suggesting that FGF-23 is cleared by the kidney, but residual FGF-23 may contribute to the PRT hypophosphatemia. FGF-23, but not PTH levels, was independently associated with PRT hypophosphatemia. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. [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.

  17. Teaching an old hormone new tricks: cytosolic Ca2+ elevation involvement in plant brassinosteroid signal transduction cascades.

    PubMed

    Zhao, Yichen; Qi, Zhi; Berkowitz, Gerald A

    2013-10-01

    Brassinosteroids (BRs) are hormones that control many aspects of plant growth and development, acting at the cell level to promote division and expansion. BR regulation of plant and plant cell function occurs through altered expression of many genes. Transcriptional reprogramming downstream from cell perception of this hormone is currently known to be mediated by a phosphorylation/dephosphorylation ("phosphorelay") cascade that alters the stability of two master transcription regulators. Here, we provide evidence that BR perception by their receptor also causes an elevation in cytosolic Ca(2+), initiating a Ca(2+) signaling cascade in Arabidopsis (Arabidopsis thaliana) cell cytosol. BR-dependent increases in the expression of some genes (INDOLE-3-ACETIC ACID-INDUCIBLE1 and PHYTOCHROME B ACTIVATION-TAGGED SUPPRESSOR1) were impaired in wild-type plants by a Ca(2+) channel blocker and also in the defense-no-death (dnd1) mutant, which lacks a functional cyclic GMP-activated cell membrane Ca(2+)-conducting channel. Alternatively, mutations that impair the BR phosphorelay cascade did not much affect the BR-dependent expression of these genes. Similar effects of the Ca(2+) channel blocker and dnd1 mutation were observed on a BR plant growth phenotype, deetiolation of the seedling hypocotyl. Further evidence presented in this report suggests that a BR-dependent elevation in cyclic GMP may be involved in the Ca(2+) signaling cascade initiated by this hormone. The work presented here leads to a new model of the molecular steps that mediate some of the cell responses to this plant hormone.

  18. 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.

  19. [Clinical and prognostic significance of preoperative serum CA153, CEA and TPS levels in patients with primary breast cancer].

    PubMed

    Chen, Yan; Zheng, Yu-hong; Lin, Ying-ying; Hu, Min-hua; Chen, Yan-song

    2011-11-01

    To investigate the clinical and prognostic values of preoperative serum CA153, CEA and TPS levels in patients with primary breast cancer. A total of 386 hospitalized patients with stage I ∼ IV breast cancer from Nov 1998 to Feb 2009 were followed up, and their clinicopathological data were analyzed retrospectively to determine the factors affecting their prognosis. First, preoperative serum CA153 expression level was significantly associated with the age of onset and tumor size (P < 0.05), the expression of serum CEA was correlated with tumor size (P < 0.05), and the expression of serum tissue polypeptide specific antigen (TPS) was correlated with tumor size and lymph node metastases (P < 0.05). Second, the overall survival was significantly shorter among patients with elevated serum CA153, CEA or TPS, respectively (P < 0.05 for overall). Finally, multivariate Cox regression analysis indicated that estrogen receptor status (ER) and elevated preoperative values of CA 153 are independent prognostic factors for overall survival (P < 0.05), and CA 153 is a risk factor but estrogen receptor status is a protective factor for overall survival. Higher preoperative expression of serum CA153, CEA or TPS is closely correlated with clinicopathological characteristics and overall survival. The prognosis is poorer in primary breast cancer patients with higher CA15-3 expression level, and pre-treatment CA153 expression level can be used as an independent prognostic parameter in patients with primarily breast cancer.

  20. 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.

  1. Increased cancer antigen 27.29 (CA27.29) level in patients with mycosis fungoides.

    PubMed

    Cen, Putao; Duvic, Madeleine; Cohen, Philip R; Kurzrock, Razelle

    2008-03-01

    Mycosis fungoides, also called cutaneous T-cell lymphoma, comprise a group of extranodal, indolent non-Hodgkin's lymphomas of T-cell origin with primary involvement of the skin. There are few data available on tumor markers in these patients. Cancer antigen 27.29 (CA27.29), which is expressed on most carcinoma cells, is a soluble form of the glycoprotein MUC1. Measuring CA27.29 has been approved by the US Food and Drug Administration for monitoring disease activity in patients with breast cancer. We sought to assess whether CA27.29 levels were increased in patients with cutaneous T-cell lymphoma and whether there was a correlation of this marker with tumor response. We evaluated the CA27.29 blood levels from 6 patients with advanced mycosis fungoides (who had no evidence of breast cancer) and reviewed their charts for information about history and physical examinations, laboratory data, pathology findings, and radiologic examinations. We demonstrated that 3 of 6 patients with advanced mycosis fungoides had markedly elevated CA27.29 blood levels. In the two patients who had serial blood levels drawn, CA27.29 increased or decreased during treatment as the disease progressed or responded, respectively. This study reflects pilot data on a limited number of patients. Our observations suggest that CA27.29 merits further investigation as a tumor marker in patients who have cutaneous T-cell lymphoma.

  2. 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

  3. Metabolomic assessment reveals an elevated level of glucosinolate content in CaCl₂ treated broccoli microgreens.

    PubMed

    Sun, Jianghao; Kou, Liping; Geng, Ping; Huang, Huilian; Yang, Tianbao; Luo, Yaguang; Chen, Pei

    2015-02-18

    Preharvest calcium application has been shown to increase broccoli microgreen yield and extend shelf life. In this study, we investigated the effect of calcium application on its metabolome using ultra-high-performance liquid chromatography with mass spectrometry. The data collected were analyzed using principal component analysis and orthogonal projection to latent structural discriminate analysis. Chemical composition comparison shows that glucosinolates, a very important group of phytochemicals, are the major compounds enhanced by preharvest treatment with 10 mM calcium chloride (CaCl2). Aliphatic glucosinolates (glucoerucin, glucoiberin, glucoiberverin, glucoraphanin, pentyl glucosinolate, and hexyl glucosinolate) and indolic glucosinolates (glucobrassicin, neoglucobrassicin, and 4-hydroxyglucobrassicin) were increased significantly in the CaCl2 treated microgreens using metabolomic approaches. Targeted glucosinolate analysis using the ISO 9167-1 method was further employed to confirm the findings. Results indicate that glucosinolates can be considered as a class of compounds that are responsible for the difference between two groups and a higher glucosinolate level was found in CaCl2 treated groups at each time point after harvest in comparison with the control group.

  4. Potentiation of inositol trisphosphate-induced Ca2+ mobilization in Xenopus oocytes by cytosolic Ca2+.

    PubMed Central

    Yao, Y; Parker, I

    1992-01-01

    1. The ability of cytosolic Ca2+ ions to modulate inositol 1,4,5-trisphosphate (Insp3)-induced Ca2+ liberation from intracellular stores was studied in Xenopus oocytes using light flash photolysis of caged InsP3. Changes in cytosolic free Ca2+ level were effected by inducing Ca2+ entry through ionophore and voltage-gated plasma membrane channels and by injection of Ca2+ through a micropipette. Their effects on Ca2+ liberation were monitored by video imaging of Fluo-3 fluorescence and by voltage clamp recording of Ca(2+)-activated membrane Cl- currents. 2. Treatment of oocytes with the Ca2+ ionophores A23187 and ionomycin caused a transient elevation of cytosolic Ca2+ level when cells were bathed in Ca(2+)-free solution, which probably arose because of release of Ca2+ from intracellular stores. 3. Membrane current and Fluo-3 Ca2+ signals evoked by photoreleased InsP3 in ionophore-treated oocytes were potentiated when the intracellular Ca2+ level was elevated by raising the Ca2+ level in the bathing solution. 4. Responses to photoreleased InsP3 were similarly potentiated following activation of Ca2+ entry through voltage-gated Ca2+ channels expressed in the plasma membrane. 5. Ca(2+)-activated membrane currents evoked by depolarization developed a delayed 'hump' component during sustained photorelease of InsP3, probably because Ca2+ ions entering through the membrane channels triggered liberation of Ca2+ from intracellular stores. 6. Ba2+ and Sr2+ ions were able to substitute for Ca2+ in potentiating InsP3-mediated Ca2+ liberation. 7. Gradual photorelease of InsP3 by weak photolysis light evoked Ca2+ liberation that began at particular foci and then propagated throughout, but not beyond that area of the oocyte exposed to the light. Local elevations of intracellular Ca2+ produced by microinjection of Ca2+ acted as new foci for the initiation of Ca2+ liberation by InsP3. 8. In resting oocytes, intracellular injections of Ca2+ resulted only in localized elevation of

  5. Cardiac hypertrophy elevates serum levels of fibroblast growth factor 23.

    PubMed

    Matsui, Isao; Oka, Tatsufumi; Kusunoki, Yasuo; Mori, Daisuke; Hashimoto, Nobuhiro; Matsumoto, Ayumi; Shimada, Karin; Yamaguchi, Satoshi; Kubota, Keiichi; Yonemoto, Sayoko; Higo, Tomoaki; Sakaguchi, Yusuke; Takabatake, Yoshitsugu; Hamano, Takayuki; Isaka, Yoshitaka

    2018-05-08

    Several experimental studies have shown that fibroblast growth factor 23 (FGF23) induces left ventricular hypertrophy (LVH). However, the opposite directional relationship, namely a potential effect of LVH on FGF23, remains uncertain. Here we evaluated the effects of LVH on FGF23 using cardiomyocyte-specific calcineurin A transgenic mice. At six weeks, these mice showed severe LVH, with elevated levels of serum intact FGF23. FGF23 levels were elevated in cardiomyocytes, but not osteocytes, of the transgenic animals. Moreover, transverse aortic constriction also upregulated myocardial FGF23 expression in wild type mice. The promoter region of the FGF23 gene contains two putative nuclear factors of activated T cells (NFAT)-binding sites, with NFAT1 activating the promoter in a proximal NFAT-binding site dependent manner. Neither serum, urinary, or fractional excretion values of calcium and phosphate nor serum levels of 1,25(OH) 2 vitamin D were different between wild type and transgenic mice. Moreover, the renal expression of FGF receptors and α-Klotho was comparable. However, plasma levels of antidiuretic hormone were significantly increased in the transgenic mice, and aquaporin-2 immunohistochemical staining was mainly positive in the apical membrane of the collecting duct, compared to a primarily cytoplasmic staining in wild type mice. Real-time PCR analyses of kidney CYP27B1 and CYP24A1 expression in wild type mice showed that exogenous antidiuretic hormone blocked FGF23's actions on these vitamin D activating or inactivating enzymes. Finally, the renal resistance of transgenic mice to FGF23 was partly overcome by tolvaptan. Thus, LVH in transgenic mice is associated with an increase in myocardial and serum intact FGF23, with the kidneys being protected against FGF23 excess by elevated antidiuretic hormone levels. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  6. 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.

  7. Association of CA 15-3 and CEA with clinicopathological parameters in patients with metastatic breast cancer.

    PubMed

    Geng, Biao; Liang, Man-Man; Ye, Xiao-Bing; Zhao, Wen-Ying

    2015-01-01

    The objective of this study was to investigate the association of serum cancer antigen 15-3 (CA 15-3) and carcinoembryonic antigen (CEA) levels with clinicopathological parameters in patients diagnosed with metastatic breast cancer (MBC). We retrospectively evaluated the medical records of 284 patients diagnosed with MBC between January, 2007 and December, 2012 who fulfilled the specified criteria and the association between the levels of the two tumor marker and clinicopathological parameters was analyzed. Of the 284 patients, elevated CA 15-3 and CEA levels at initial diagnosis of recurrence were identified in 163 (57.4%) and 97 (34.2%) patients, respectively. Elevated CA 15-3 and CEA levels were significantly associated with breast cancer molecular subtypes (P<0.001 and P=0.032, respectively). Cases with luminal subtypes exhibited a higher percentage of elevated CA 15-3 and CEA levels compared to non-luminal subtypes. Elevated CA 15-3 level was correlated with bone metastasis (P=0.017). However, elevation of CEA was observed regardless of the site of metastasis. Elevation of CA 15-3 was significantly more common in MBC with multiple metastatic sites compared to MBC with a single metastasis (P=0.001). However, the incidence of elevated CEA levels did not differ between patients with a single and those with multiple metastatic sites. In conclusion, elevated CA 15-3 and CEA levels at initial diagnosis of recurrence were found to be associated with breast cancer molecular subtypes, whereas an elevated CA 15-3 level was significantly correlated with bone metastasis and an elevated CEA level was observed regardless of metastatic site. The proportion of MBC cases with elevated CA 15-3 levels differed according to the number of metastatic sites.

  8. 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

  9. 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.

  10. 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.

  11. The role of luminal Ca2+ in the generation of Ca2+ waves in rat ventricular myocytes

    PubMed Central

    Lukyanenko, Valeriy; Subramanian, Saisunder; Györke, Inna; Wiesner, Theodore F; Györke, Sandor

    1999-01-01

    We used confocal Ca2+ imaging and fluo-3 to investigate the transition of localized Ca2+ releases induced by focal caffeine stimulation into propagating Ca2+ waves in isolated rat ventricular myocytes. Self-sustaining Ca2+ waves could be initiated when the cellular Ca2+ load was increased by elevating the extracellular [Ca2+] ([Ca2+]o) and they could also be initiated at normal Ca2+ loads when the sensitivity of the release sites to cytosolic Ca2+ was enhanced by low doses of caffeine. When we prevented the accumulation of extra Ca2+ in the luminal compartment of the sarcoplasmic reticulum (SR) with thapsigargin, focal caffeine pulses failed to trigger self-sustaining Ca2+ waves on elevation of [Ca2+]o. Inhibition of SR Ca2+ uptake by thapsigargin in cells already preloaded with Ca2+ above normal levels did not prevent local Ca2+ elevations from triggering propagating waves. Moreover, wave velocity increased by 20 %. Tetracaine (0·75 mM) caused transient complete inhibition of both local and propagating Ca2+ signals, followed by full recovery of the responses due to increased SR Ca2+ accumulation. Computer simulations using a numerical model with spatially distinct Ca2+ release sites suggested that increased amounts of releasable Ca2+ might not be sufficient to generate self-sustaining Ca2+ waves under conditions of Ca2+ overload unless the threshold of release site Ca2+ activation was set at relatively low levels (< 1·5 μM). We conclude that the potentiation of SR Ca2+ release channels by luminal Ca2+ is an important factor in Ca2+ wave generation. Wave propagation does not require the translocation of Ca2+ from the spreading wave front into the SR. Instead, it relies on luminal Ca2+ sensitizing Ca2+ release channels to cytosolic Ca2+. PMID:10373699

  12. CaSR-mediated interactions between calcium and magnesium homeostasis in mice.

    PubMed

    Quinn, Stephen J; Thomsen, Alex R B; Egbuna, Ogo; Pang, Jian; Baxi, Khanjan; Goltzman, David; Pollak, Martin; Brown, Edward M

    2013-04-01

    Calcium (Ca) and magnesium (Mg) homeostasis are interrelated and share common regulatory hormones, including parathyroid hormone (PTH) and vitamin D. However, the role of the calcium-sensing receptor (CaSR) in Mg homeostasis in vivo is not well understood. We sought to investigate the interactions between Mg and Ca homeostasis using genetic mouse models with targeted inactivation of PTH (PTH KO) or both PTH and the calcium-sensing receptor (CaSR) (double knockout, DKO). Serum Mg is lower in PTH KO and DKO mice than in WT mice on standard chow, whereas supplemental dietary Ca leads to equivalent Mg levels for all three genotypes. Mg loading increases serum Mg in all genotypes; however, the increase in serum Mg is most pronounced in the DKO mice. Serum Ca is increased with Mg loading in the PTH KO and DKO mice but not in the WT mice. Here, too, the hypercalcemia is much greater in the DKO mice. Serum and especially urinary phosphate are reduced during Mg loading, which is likely due to intestinal chelation of phosphate by Mg. Mg loading decreases serum PTH in WT mice and increases serum calcitonin in both WT and PTH KO mice but not DKO mice. Furthermore, Mg loading elevates serum 1,25-dihydroxyvitamin D in all genotypes, with greater effects in PTH KO and DKO mice, possibly due to reduced levels of serum phosphorus and FGF23. These hormonal responses to Mg loading and the CaSR's role in regulating renal function may help to explain changes in serum Mg and Ca found during Mg loading.

  13. Only extra-high dose of ketamine affects l-glutamate-induced intracellular Ca(2+) elevation and neurotoxicity.

    PubMed

    Shibuta, Satoshi; Morita, Tomotaka; Kosaka, Jun; Kamibayashi, Takahiko; Fujino, Yuji

    2015-09-01

    The neurotoxic effects of anesthetics on the developing brain are a concern. Although most of the anesthetics are GABAA agonists or NMDA antagonists, the differences in these effects on prospective glutamate-neurotoxicity in the brain is not fully understood. We examined the degree of L-glutamate-induced intracellular calcium ([Ca(2+)]i) elevation and neurotoxicity in neurons exposed to anesthetics. Primary cortical neurons from E17 rats were preincubated with 1-100 μM of ketamine or thiopental sodium (TPS) for the first 72 h of culturing. Two weeks later, the neurons were exposed to L-glutamate. The extent of glutamate toxicity was evaluated using Ca(2+)-imaging and morphological experiments. Preincubation with 100 μM ketamine but not with other concentrations of ketamine and TPS for the first 72 h in culture significantly enhanced L-glutamate-induced [Ca(2+)]i elevation 2 weeks later. Morphology experiments showed that vulnerability to L-glutamate-mediated neurotoxicity was only altered in neurons preincubated with 100 μM ketamine but not with TPS. Although preincubation with high concentration of ketamine showed enhancement of L-glutamate-induced [Ca(2+)]i elevation 2 weeks later, long-term exposure to TPS or ketamine at clinical doses during developmental periods may not result in a dose-related potentiation of exogenous glutamate-induced neurotoxicity, once the intravenous anesthetics are discontinued. Copyright © 2015 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

  14. Maternal Hypercalcemia Due to Failure of 1,25-Dihydroxyvitamin-D3 Catabolism in a Patient With CYP24A1 Mutations

    PubMed Central

    Hsiao, Edward C.; O'Donnell, Betsy; Salmeen, Kirsten; Nussbaum, Robert; Krebs, Michael; Baumgartner-Parzer, Sabina; Kaufmann, Martin; Jones, Glenville; Bikle, Daniel D.; Wang, YongMei; Mathew, Allen S.; Shoback, Dolores; Block-Kurbisch, Ingrid

    2015-01-01

    Context: Calcium metabolism changes in pregnancy and lactation to meet fetal needs, with increases in 1,25-dihydroxyvitamin D [1,25-(OH)2D] during pregnancy playing an important role. However, these changes rarely cause maternal hypercalcemia. When maternal hypercalcemia occurs, further investigation is essential, and disorders of 1,25-(OH)2D catabolism should be carefully considered in the differential diagnosis. Case: A patient with a childhood history of recurrent renal stone disease and hypercalciuria presented with recurrent hypercalcemia and elevated 1,25-(OH)2D levels during pregnancy. Laboratory tests in the fourth pregnancy showed suppressed PTH, elevated 1,25-(OH)2D, and high-normal 25-hydroxyvitamin D levels, suggesting disordered vitamin D metabolism. Analysis revealed low 24,25-dihydroxyvitamin D3 and high 25-hydroxyvitamin D3 levels, suggesting loss of function of CYP24A1 (25-hydroxyvitamin-D3-24-hydroxylase). Gene sequencing confirmed that she was a compound heterozygote with the E143del and R396W mutations in CYP24A1. Conclusions: This case broadens presentations of CYP24A1 mutations and hypercalcemia in pregnancy. Furthermore, it illustrates that patients with CYP24A1 mutations can maintain normal calcium levels during the steady state but can develop hypercalcemia when challenged, such as in pregnancy when 1,25-(OH)2D levels are physiologically elevated. PMID:26097993

  15. Transcriptional upregulation of α2δ-1 elevates arterial smooth muscle cell voltage-dependent Ca2+ channel surface expression and cerebrovascular constriction in genetic hypertension.

    PubMed

    Bannister, John P; Bulley, Simon; Narayanan, Damodaran; Thomas-Gatewood, Candice; Luzny, Patrik; Pachuau, Judith; Jaggar, Jonathan H

    2012-10-01

    A hallmark of hypertension is an increase in arterial myocyte voltage-dependent Ca2+ (CaV1.2) currents that induces pathological vasoconstriction. CaV1.2 channels are heteromeric complexes composed of a pore-forming CaV1.2α1 with auxiliary α2δ and β subunits. Molecular mechanisms that elevate CaV1.2 currents during hypertension and the potential contribution of CaV1.2 auxiliary subunits are unclear. Here, we investigated the pathological significance of α2δ subunits in vasoconstriction associated with hypertension. Age-dependent development of hypertension in spontaneously hypertensive rats was associated with an unequal elevation in α2δ-1 and CaV1.2α1 mRNA and protein in cerebral artery myocytes, with α2δ-1 increasing more than CaV1.2α1. Other α2δ isoforms did not emerge in hypertension. Myocytes and arteries of hypertensive spontaneously hypertensive rats displayed higher surface-localized α2δ-1 and CaV1.2α1 proteins, surface α2δ-1:CaV1.2α1 ratio, CaV1.2 current density and noninactivating current, and pressure- and depolarization-induced vasoconstriction than those of Wistar-Kyoto controls. Pregabalin, an α2δ-1 ligand, did not alter α2δ-1 or CaV1.2α1 total protein but normalized α2δ-1 and CaV1.2α1 surface expression, surface α2δ-1:CaV1.2α1, CaV1.2 current density and inactivation, and vasoconstriction in myocytes and arteries of hypertensive rats to control levels. Genetic hypertension is associated with an elevation in α2δ-1 expression that promotes surface trafficking of CaV1.2 channels in cerebral artery myocytes. This leads to an increase in CaV1.2 current-density and a reduction in current inactivation that induces vasoconstriction. Data also suggest that α2δ-1 targeting is a novel strategy that may be used to reverse pathological CaV1.2 channel trafficking to induce cerebrovascular dilation in hypertension.

  16. 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.

  17. 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

  18. β-Adrenergic stimulation increases the intra-sarcoplasmic reticulum Ca2+ threshold for Ca2+ wave generation

    PubMed Central

    Domeier, Timothy L; Maxwell, Joshua T; Blatter, Lothar A

    2012-01-01

    β-Adrenergic signalling induces positive inotropic effects on the heart that associate with pro-arrhythmic spontaneous Ca2+ waves. A threshold level of sarcoplasmic reticulum (SR) Ca2+ ([Ca2+]SR) is necessary to trigger Ca2+ waves, and whether the increased incidence of Ca2+ waves during β-adrenergic stimulation is due to an alteration in this threshold remains controversial. Using the low-affinity Ca2+ indicator fluo-5N entrapped within the SR of rabbit ventricular myocytes, we addressed this controversy by directly monitoring [Ca2+]SR and Ca2+ waves during β-adrenergic stimulation. Electrical pacing in elevated extracellular Ca2+ ([Ca2+]o= 7 mm) was used to increase [Ca2+]SR to the threshold where Ca2+ waves were consistently observed. The β-adrenergic agonist isoproterenol (ISO; 1 μm) increased [Ca2+]SR well above the control threshold and consistently triggered Ca2+ waves. However, when [Ca2+]SR was subsequently lowered in the presence of ISO (by lowering [Ca2+]o to 1 mm and partially inhibiting sarcoplasmic/endoplasmic reticulum calcium ATPase with cyclopiazonic acid or thapsigargin), Ca2+ waves ceased to occur at a [Ca2+]SR that was higher than the control threshold. Furthermore, for a set [Ca2+]SR level the refractoriness of wave occurrence (Ca2+ wave latency) was prolonged during β-adrenergic stimulation, and was highly dependent on the extent that [Ca]SR exceeded the wave threshold. These data show that acute β-adrenergic stimulation increases the [Ca2+]SR threshold for Ca2+ waves, and therefore the primary cause of Ca2+ waves is the robust increase in [Ca2+]SR above this higher threshold level. Elevation of the [Ca2+]SR wave threshold and prolongation of wave latency represent potentially protective mechanisms against pro-arrhythmogenic Ca2+ release during β-adrenergic stimulation. PMID:22988136

  19. Unexpected effect of dry olive leaf extract on the level of DNA damage in lymphocytes of lead intoxicated workers, before and after CaNa2EDTA chelation therapy.

    PubMed

    Čabarkapa, Andrea; Dekanski, Dragana; Živković, Lada; Milanović-Čabarkapa, Mirjana; Bajić, Vladan; Topalović, Dijana; Giampieri, Francesca; Gasparrini, Massimiliano; Battino, Maurizio; Spremo-Potparević, Biljana

    2017-08-01

    The CaNa 2 EDTA chelation therapy is often practiced with antioxidant supplementation. Dry olive leaf extract (DOLE) is natural product with antioxidant and DNA protective properties. The effects of DOLE on the levels of DNA damage were investigated ex vivo in peripheral blood lymphocytes (PBLs) of 19 workers occupationally exposed to lead (Pb), before and after CaNa 2 EDTA chelation therapy. DOLE demonstrated pronounced radical scavenging activity in concentrations ≥1 mg/mL, and showed no genotoxicity per se, in concentrations 0.125-1 mg/mL. The level of DNA damage in PBLs of workers before chelation therapy was elevated (24.21 ± 14.26) compared to controls (6.0 ± 3.37). The incubation of PBLs before chelation therapy with selected concentration of DOLE lead to a severe increase of DNA damage (64.03 ± 20.96), exhibiting prooxidant rather than antioxidant effect. After the five-day CaNa 2 EDTA chelation regimen, DNA damage in PBLs of workers decreased (8.26 ± 4.62) significantly compared to baseline. Treatment of PBLs with DOLE after chelation, again produced high level of damage (41.82 ± 23.17) and the acute prooxidant effects of DOLE remained, but, DNA damage was less severe than before chelation. The DOLE exhibits prooxidant effect in presence of Pb in lymphocytes of exposed workers, and its effect is less pronounced following the removal of Pb after standard chelation therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. The site of net absorption of Ca from the intestinal tract of growing pigs and effect of phytic acid, Ca level and Ca source on Ca digestibility.

    PubMed

    González-Vega, J Caroline; Walk, Carrie L; Liu, Yanhong; Stein, Hans H

    2014-01-01

    An experiment was conducted to test the hypothesis that the standardised digestibility of Ca in calcium carbonate and Lithothamnium calcareum Ca is not different regardless of the level of dietary Ca, and that phytic acid affects the digestibility of Ca in these two ingredients to the same degree. The objectives were to determine where in the intestinal tract Ca absorption takes place and if there are measurable quantities of basal endogenous Ca fluxes in the stomach, small intestine or large intestine. Diets contained calcium carbonate or L. calcareum Ca as the sole source of Ca, 0% or 1% phytic acid and 0.4% or 0.8% Ca. A Ca-free diet was also formulated and used to measure endogenous fluxes and losses of Ca. Nine growing pigs (initial body weight 23.8 ± 1.3 kg) were cannulated in the duodenum and in the distal ileum, and faecal, ileal and duodenal samples were collected. Duodenal endogenous fluxes of Ca were greater (p < 0.05) than ileal endogenous fluxes and total tract endogenous losses of Ca, but ileal endogenous fluxes were less (p < 0.05) than total tract endogenous losses. Standardised digestibility of Ca was not affected by the level of phytic acid, but decreased (p < 0.05) as Ca level increased in L. calcareum Ca diets, but that was not the case if calcium carbonate was the source of Ca (interaction, p < 0.05). The standardised duodenal digestibility (SDD), standardised ileal digestibility (SID) and standardised total tract digestibility (STTD) of Ca were not different if calcium carbonate was the source of dietary Ca. However, the STTD of Ca in L. calcareum Ca was greater (p < 0.05) than the SID and SDD of Ca. The SDD, SID and STTD of Ca in calcium carbonate were greater (p < 0.05) than those of L. calcareum Ca. In conclusion, under the conditions of this experiment, standardised digestibility of Ca is not affected by the level of phytic acid, but may be affected by dietary Ca level depending on the Ca source. Calcium from calcium carbonate is mostly

  1. Heterologous desensitization of both phosphoinositide and Ca2+ signaling in SH-SY5Y neuroblastoma cells: a role for intracellular Ca2+ store depletion?

    PubMed

    Willars, G B; Nahorski, S R

    1995-03-01

    Measurement of the intracellular Ca2+ concentration ([Ca2+]i) in fura-2-loaded single cells of the human neuroblastoma line SH-SY5Y indicated coexpression of muscarinic and bradykinin receptors linked to activation of phosphoinositidase C (PIC). Both agonists elevated [Ca2+]i and inositol-1,4,5-trisphosphate [Ins(1,4,5)P3] levels in populations of adherent cells, although in cells used directly upon attainment of confluence the responses to carbachol were greater than those to bradykinin and displayed additional sustained components. This model system was used to examine heterologous interactions when a second PIC-linked agonist was added 100-300 sec after but in the continued presence of the first. Maximal (1 mM) carbachol concentrations abolished the elevation of [Ca2+]i produced by bradykinin but the muscarinic antagonist atropine (10 microM) restored the response, provided that extracellular Ca2+ was present throughout the experiment or was added before bradykinin. Carbachol also abolished bradykinin-mediated Ins(1,4,5)P3 elevation. In contrast, bradykinin did not influence [Ca2+]i or Ins(1,4,5)P3 responses to carbachol in the presence of extracellular Ca2+. In cells maintained at confluence for 2 weeks, the rapid peak elevations of [Ca2+]i and Ins(1,4,5)P3 levels induced by carbachol and bradykinin were approximately equivalent in magnitude. In these cells carbachol again abolished bradykinin-mediated elevation of [Ca2+]i but only attenuated, rather than abolished, the elevation of Ins(1,4,5)P3 levels. The [Ca2+]i and Ins(1,4,5)P3 responses to bradykinin were fully restored 100 sec after atropine only in the presence of extracellular Ca2+. Thus, depletion of an intracellular Ins(1,4,5)P3-sensitive Ca2+ store may underlie the ability of carbachol to produce not only heterologous desensitization of the [Ca2+]i elevation induced by bradykinin but also that of the Ins(1,4,5)P3 response. This suggests a feed-forward activation of PIC by Ca2+ released from Ins(1

  2. Elevated Blood Lead Levels Are Associated with Reduced Risk of Malaria in Beninese Infants.

    PubMed

    Moya-Alvarez, Violeta; Mireku, Michael Osei; Ayotte, Pierre; Cot, Michel; Bodeau-Livinec, Florence

    2016-01-01

    Elevated blood lead levels (BLL) and malaria carry an important burden of disease in West Africa. Both diseases might cause anemia and they might entail long-term consequences for the development and the health status of the child. Albeit the significant impact of malaria on lead levels described in Nigeria, no evaluation of the effect of elevated BLL on malaria risk has been investigated so far. Between 2010 and 2012, blood lead levels of 203 Beninese infants from Allada, a semi-rural area 50km North from Cotonou, were assessed at 12 months of age. To assess lead levels, blood samples were analyzed by mass spectrometry. In parallel, clinical, microbiological and hematological data were collected. More precisely, hemoglobin, serum ferritin, CRP, vitamin B12, folate levels, and Plasmodium falciparum parasitemia were assessed and stool samples were also analyzed. At 12 months, the mean BLL of infants was 7.41 μg/dL (CI: 65.2; 83), and 128 infants (63%) had elevated blood lead levels, defined by the CDC as BLL>5 μg/dL. Lead poisoning, defined as BLL>10 μg/dL, was found in 39 infants (19%). Twenty-five infants (12.5%) had a positive blood smear at 12 months and 144 infants were anemic (71%, hemoglobin<110 g/L). Elevated blood lead levels were significantly associated with reduced risk of a positive blood smear (AOR = 0.38, P-value = 0.048) and P. falciparum parasite density (beta-estimate = -1.42, P-value = 0.03) in logistic and negative binomial regression multivariate models, respectively, adjusted on clinical and environmental indicators. Our study shows for the first time that BLL are negatively associated with malarial risk considering other risk factors. Malaria is one of the main causes of morbidity and mortality in infants under 5 years worldwide, and lead poisoning is the 6th most important contributor to the global burden of diseases measured in disability adjusted life years (DALYs) according to the Institute of Health Metrics. In conclusion, due to the

  3. 1,25-Dihydroxyvitamin D Levels in Pediatric Intensive Care Units: Risk Factors and Association With Clinical Course.

    PubMed

    McNally, J Dayre; Menon, Kusum; Lawson, Margaret L; Williams, Kathryn; Doherty, Dermot R

    2015-08-01

    Multiple adult and some pediatric critical care studies have suggested that poor vitamin D status is associated with illness severity and outcome. The majority have evaluated vitamin D status through serum 25-hydroxyvitamin D [25(OH)D]. Critical illness-related organ dysfunction may result in impaired conversion of 25(OH)D to the active hormone 1,25-dihydroxyvitamin D [1,25(OH)2D]. Consequently 1,25(OH)2D levels could be an independent additive prognostic marker in the intensive care unit. The distribution of 1,25(OH)2D levels, prevalence of low levels, investigation of risk factors, and tests for associations with markers of illness severity and outcome are reported. This was a secondary analysis of data and samples collected as part of a prospective cohort study in six Canadian pediatric intensive care units (PICUs). Admission blood 1,25(OH)2D concentrations were measured. The median cohort 1,25(OH)2D level was 93.3 pmol/L (interquartile range, 53.0-121.9) with 13% (95% confidence interval, 9-17) and 21% (95% confidence interval, 17-27) of patients having levels of <40 and <50 pmol/L, respectively. Low 1,25(OH)2D levels occurred more often in patients with low 25(OH)D and hepatic, renal, and parathyroid organ dysfunction. After adjustment for 25(OH)D, low 1,25(OH)2D levels were not associated with catecholamine or fluid administration, ventilation, PICU length of stay, or mortality. Critically ill children are at risk for low 1,25(OH)2D levels, particularly in the presence of established risk factors. However, the lack of association between the 1,25(OH)2D level and selected outcome measures, after controlling for 25(OH)D, does not suggest value in measuring this metabolite at the time of PICU admission.

  4. 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.

  5. 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.

  6. Elevated soluble MUC1 levels and decreased anti-MUC1 antibody levels in patients with multiple myeloma.

    PubMed

    Treon, S P; Maimonis, P; Bua, D; Young, G; Raje, N; Mollick, J; Chauhan, D; Tai, Y T; Hideshima, T; Shima, Y; Hilgers, J; von Mensdorff-Pouilly, S; Belch, A R; Pilarski, L M; Anderson, K C

    2000-11-01

    Soluble MUC1 (sMUC1) levels are elevated in many MUC1(+) cancers. We and others have shown that MUC1 is expressed on multiple myeloma (MM) plasma cells and B cells. In this study, we measured sMUC1 levels in bone marrow (BM) plasma from 71 MM patients and 21 healthy donors (HDs), and in peripheral blood (PB) plasma from 42 MM patients and 13 HDs using an immunoassay that detects the CA27.29 epitope of MUC1. sMUC1 levels were found to be significantly greater (mean 31.76 U/mL, range 5.69 to 142.48 U/mL) in MM patient BM plasma versus HD BM plasma (mean 9.68 U/mL, range 0.65 to 39.83 U/mL) (P <. 001). Importantly, BM plasma sMUC1 levels were related to tumor burden because sMUC1 levels were significantly higher for MM patients with active disease (34.62 U/mL, range 5.69 to 142.48 U/mL) versus MM patients with minimal residual disease (16.16 U/mL, range 5.7 to 56.68 U/mL) (P =.0026). sMUC1 levels were also elevated in the PB plasma of MM patients (32.79 U/mL, range 4.15 to 148.84 U/mL) versus HDs (18.47 U/mL, range 8.84 to 42.49) (P =.0052). Lastly, circulating immunglobulin M (IgM) and IgG antibodies to MUC1 were measured in 114 MM patients and 31 HDs, because natural antibodies to MUC1 have been detected in patients with other MUC1-bearing malignancies. These studies demonstrated lower levels of circulating IgM (P <.001) and IgG (P =.078) antibodies to MUC1 in MM patients compared with HDs. Our data therefore show that in MM patients, sMUC1 levels are elevated and correlate with disease burden, whereas anti-MUC1 antibody levels are decreased.

  7. Mechanical Properties and Fracture Behaviors of the As-Extruded Mg-5Al-3Ca Alloys Containing Yttrium at Elevated Temperature.

    PubMed

    Son, Hyeon-Taek; Kim, Yong-Ho; Kim, Taek-Soo; Lee, Seong-Hee

    2016-02-01

    Effects of yttrium (Y) addition on mechanical properties and fracture behaviors of the as-extruded Mg-Al-Ca based alloys at elevated temperature were investigated by a tensile test. After hot extrusion, the average grain size was refined by Y addition and eutectic phases were broken down into fine particles. Y addition to Mg-5Al-3Ca based alloy resulted in the improvement of strength and ductility at elevated temperature due to fine grain and suppression of grain growth by formation of thermally stable Al2Y intermetallic compound.

  8. 1. BUILDING 8698, TEST STAND 13, WEST ELEVATION. NOTE TUNNEL ...

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

    1. BUILDING 8698, TEST STAND 1-3, WEST ELEVATION. NOTE TUNNEL BETWEEN BLDG. 8668 AND TEST STAND 1-3. TEST AREA 1-120 IN THE MIDDLE DISTANCE, AND TEST AREA 1-125 ON THE HORIZON. Looking northeast from the roof of Building 8668, Instrumentation and Control Center. Note: Photograph CA-236-F-2 is an 8" x 10" enlargement from a 4" x 5" negative. This view is a photocopy of a recent resin coated print made from a print held at the Main Base History Office, Edwards Air Force Base, California. Photographer unknown. Date and file number unknown. - Edwards Air Force Base, Air Force Rocket Propulsion Laboratory, Test Stand 1-3, Test Area 1-115, northwest end of Saturn Boulevard, Boron, Kern County, CA

  9. Increased Calcium Levels and Prolonged Shelf Life in Tomatoes Expressing Arabidopsis H+/Ca2+ Transporters1

    PubMed Central

    Park, Sunghun; Cheng, Ning Hui; Pittman, Jon K.; Yoo, Kil Sun; Park, Jungeun; Smith, Roberta H.; Hirschi, Kendal D.

    2005-01-01

    Here we demonstrate that fruit from tomato (Lycopersicon esculentum) plants expressing Arabidopsis (Arabidopsis thaliana) H+/cation exchangers (CAX) have more calcium (Ca2+) and prolonged shelf life when compared to controls. Previously, using the prototypical CAX1, it has been demonstrated that, in yeast (Saccharomyces cerevisiae) cells, CAX transporters are activated when the N-terminal autoinhibitory region is deleted, to give an N-terminally truncated CAX (sCAX), or altered through specific manipulations. To continue to understand the diversity of CAX function, we used yeast assays to characterize the putative transport properties of CAX4 and N-terminal variants of CAX4. CAX4 variants can suppress the Ca2+ hypersensitive yeast phenotypes and also appear to be more specific Ca2+ transporters than sCAX1. We then compared the phenotypes of sCAX1- and CAX4-expressing tomato lines. The sCAX1-expressing tomato lines demonstrate increased vacuolar H+/Ca2+ transport, when measured in root tissue, elevated fruit Ca2+ level, and prolonged shelf life but have severe alterations in plant development and morphology, including increased incidence of blossom-end rot. The CAX4-expressing plants demonstrate more modest increases in Ca2+ levels and shelf life but no deleterious effects on plant growth. These findings suggest that CAX expression may fortify plants with Ca2+ and may serve as an alternative to the application of CaCl2 used to extend the shelf life of numerous agriculturally important commodities. However, judicious regulation of CAX transport is required to assure optimal plant growth. PMID:16244156

  10. 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)

  11. [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

  12. 40 CFR 93.125 - Enforceability of design concept and scope and project-level mitigation and control measures.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Transit Laws § 93.125 Enforceability of design concept and scope and project-level mitigation and control... 40 Protection of Environment 20 2014-07-01 2013-07-01 true Enforceability of design concept and scope and project-level mitigation and control measures. 93.125 Section 93.125 Protection of Environment...

  13. 40 CFR 93.125 - Enforceability of design concept and scope and project-level mitigation and control measures.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Transit Laws § 93.125 Enforceability of design concept and scope and project-level mitigation and control... 40 Protection of Environment 20 2011-07-01 2011-07-01 false Enforceability of design concept and scope and project-level mitigation and control measures. 93.125 Section 93.125 Protection of Environment...

  14. 40 CFR 93.125 - Enforceability of design concept and scope and project-level mitigation and control measures.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Transit Laws § 93.125 Enforceability of design concept and scope and project-level mitigation and control... 40 Protection of Environment 21 2013-07-01 2013-07-01 false Enforceability of design concept and scope and project-level mitigation and control measures. 93.125 Section 93.125 Protection of Environment...

  15. 40 CFR 93.125 - Enforceability of design concept and scope and project-level mitigation and control measures.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Transit Laws § 93.125 Enforceability of design concept and scope and project-level mitigation and control... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Enforceability of design concept and scope and project-level mitigation and control measures. 93.125 Section 93.125 Protection of Environment...

  16. 40 CFR 93.125 - Enforceability of design concept and scope and project-level mitigation and control measures.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Transit Laws § 93.125 Enforceability of design concept and scope and project-level mitigation and control... 40 Protection of Environment 21 2012-07-01 2012-07-01 false Enforceability of design concept and scope and project-level mitigation and control measures. 93.125 Section 93.125 Protection of Environment...

  17. Plasma Membrane Ca2+-Permeable Channels are Differentially Regulated by Ethylene and Hydrogen Peroxide to Generate Persistent Plumes of Elevated Cytosolic Ca2+ During Transfer Cell Trans-Differentiation.

    PubMed

    Zhang, Hui-ming; van Helden, Dirk F; McCurdy, David W; Offler, Christina E; Patrick, John W

    2015-09-01

    The enhanced transport capability of transfer cells (TCs) arises from their ingrowth wall architecture comprised of a uniform wall on which wall ingrowths are deposited. The wall ingrowth papillae provide scaffolds to amplify plasma membranes that are enriched in nutrient transporters. Using Vicia faba cotyledons, whose adaxial epidermal cells spontaneously and rapidly (hours) undergo a synchronous TC trans-differentiation upon transfer to culture, has led to the discovery of a cascade of inductive signals orchestrating deposition of ingrowth wall papillae. Auxin-induced ethylene biosynthesis initiates the cascade. This in turn drives a burst in extracellular H2O2 production that triggers uniform wall deposition. Thereafter, a persistent and elevated cytosolic Ca(2+) concentration, resulting from Ca(2+) influx through plasma membrane Ca(2+)-permeable channels, generates a Ca(2+) signal that directs formation of wall ingrowth papillae to specific loci. We now report how these Ca(2+)-permeable channels are regulated using the proportionate responses in cytosolic Ca(2+) concentration as a proxy measure of their transport activity. Culturing cotyledons on various combinations of pharmacological agents allowed the regulatory influence of each upstream signal on Ca(2+) channel activity to be evaluated. The findings demonstrated that Ca(2+)-permeable channel activity was insensitive to auxin, but up-regulated by ethylene through two independent routes. In one route ethylene acts directly on Ca(2+)-permeable channel activity at the transcriptional and post-translational levels, through an ethylene receptor-dependent pathway. The other route is mediated by an ethylene-induced production of extracellular H2O2 which then acts translationally and post-translationally to up-regulate Ca(2+)-permeable channel activity. A model describing the differential regulation of Ca(2+)-permeable channel activity is presented. © The Author 2015. Published by Oxford University Press on

  18. 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.

  19. NCLX Protein, but Not LETM1, Mediates Mitochondrial Ca2+ Extrusion, Thereby Limiting Ca2+-induced NAD(P)H Production and Modulating Matrix Redox State*

    PubMed Central

    De Marchi, Umberto; Santo-Domingo, Jaime; Castelbou, Cyril; Sekler, Israel; Wiederkehr, Andreas; Demaurex, Nicolas

    2014-01-01

    Mitochondria capture and subsequently release Ca2+ ions, thereby sensing and shaping cellular Ca2+ signals. The Ca2+ uniporter MCU mediates Ca2+ uptake, whereas NCLX (mitochondrial Na/Ca exchanger) and LETM1 (leucine zipper-EF-hand-containing transmembrane protein 1) were proposed to exchange Ca2+ against Na+ or H+, respectively. Here we study the role of these ion exchangers in mitochondrial Ca2+ extrusion and in Ca2+-metabolic coupling. Both NCLX and LETM1 proteins were expressed in HeLa cells mitochondria. The rate of mitochondrial Ca2+ efflux, measured with a genetically encoded indicator during agonist stimulations, increased with the amplitude of mitochondrial Ca2+ ([Ca2+]mt) elevations. NCLX overexpression enhanced the rates of Ca2+ efflux, whereas increasing LETM1 levels had no impact on Ca2+ extrusion. The fluorescence of the redox-sensitive probe roGFP increased during [Ca2+]mt elevations, indicating a net reduction of the matrix. This redox response was abolished by NCLX overexpression and restored by the Na+/Ca2+ exchanger inhibitor CGP37157. The [Ca2+]mt elevations were associated with increases in the autofluorescence of NAD(P)H, whose amplitude was strongly reduced by NCLX overexpression, an effect reverted by Na+/Ca2+ exchange inhibition. We conclude that NCLX, but not LETM1, mediates Ca2+ extrusion from mitochondria. By controlling the duration of matrix Ca2+ elevations, NCLX contributes to the regulation of NAD(P)H production and to the conversion of Ca2+ signals into redox changes. PMID:24898248

  20. 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

  1. miR-125b predicts childhood acute lymphoblastic leukaemia poor response to BFM chemotherapy treatment.

    PubMed

    Piatopoulou, Despina; Avgeris, Margaritis; Marmarinos, Antonios; Xagorari, Marieta; Baka, Margarita; Doganis, Dimitrios; Kossiva, Lydia; Scorilas, Andreas; Gourgiotis, Dimitrios

    2017-09-05

    Despite the favourable survival rates of childhood acute lymphoblastic leukaemia (ALL), a significant number of patients present resistance to antileukaemic agents and dismal prognosis. In this study, we analysed miR-125b expression in childhood ALL and evaluated its clinical utility for patients treated with Berlin-Frankfurt-Münster (BFM) protocol. The study included 272 bone marrow specimens obtained on diagnosis and on BFM day 33 from 125 patients and 64 healthy children. Following extraction, RNA was polyadenylated and reverse transcribed. miR-125b levels were quantified by quantitative PCR. Cytogenetics, immunohistotype and MRD were analysed according to international guidelines. Downregulated miR-125b levels were detected in childhood ALL patients and correlated with adverse prognosis. Following BFM induction, miR-125b levels were significantly increased, however, elevated day 33/diagnosis miR-125b ratio was associated with unfavourable disease features. Loss of miR-125b during diagnosis and higher day 33/diagnosis ratio were correlated with stronger risk for disease short-term relapse and patients' worse survival. Moreover, multivariate regression models highlighted the independent prognostic value of miR-125b for childhood ALL. Finally, the combination of miR-125b with clinically used disease markers clearly enhanced the prediction of patients' resistance to BFM chemotherapy. miR-125b significantly improves the prognosis of childhood ALL patients' outcome under BFM treatment.

  2. Elevated CO2 stimulates marsh elevation gain, counterbalancing sea-level rise

    USGS Publications Warehouse

    Langley, J.A.; McKee, K.L.; Cahoon, D.R.; Cherry, J.A.; Megonigala, J.P.

    2009-01-01

    Tidal wetlands experiencing increased rates of sea-level rise (SLR) must increase rates of soil elevation gain to avoid permanent conversion to open water. The maximal rate of SLR that these ecosystems can tolerate depends partly on mineral sediment deposition, but the accumulation of organic matter is equally important for many wetlands. Plant productivity drives organic matter dynamics and is sensitive to global change factors, such as rising atmospheric CO2 concentration. It remains unknown how global change will influence organic mechanisms that determine future tidal wetland viability. Here, we present experimental evidence that plant response to elevated atmospheric [CO2] stimulates biogenic mechanisms of elevation gain in a brackish marsh. Elevated CO2 (ambient + 340 ppm) accelerated soil elevation gain by 3.9 mm yr−1in this 2-year field study, an effect mediated by stimulation of below-ground plant productivity. Further, a companion greenhouse experiment revealed that the CO2 effect was enhanced under salinity and flooding conditions likely to accompany future SLR. Our results indicate that by stimulating biogenic contributions to marsh elevation, increases in the greenhouse gas, CO2, may paradoxically aid some coastal wetlands in counterbalancing rising seas.

  3. Elevated CO2 stimulates marsh elevation gain, counterbalancing sea-level rise.

    PubMed

    Langley, J Adam; McKee, Karen L; Cahoon, Donald R; Cherry, Julia A; Megonigal, J Patrick

    2009-04-14

    Tidal wetlands experiencing increased rates of sea-level rise (SLR) must increase rates of soil elevation gain to avoid permanent conversion to open water. The maximal rate of SLR that these ecosystems can tolerate depends partly on mineral sediment deposition, but the accumulation of organic matter is equally important for many wetlands. Plant productivity drives organic matter dynamics and is sensitive to global change factors, such as rising atmospheric CO(2) concentration. It remains unknown how global change will influence organic mechanisms that determine future tidal wetland viability. Here, we present experimental evidence that plant response to elevated atmospheric [CO(2)] stimulates biogenic mechanisms of elevation gain in a brackish marsh. Elevated CO(2) (ambient + 340 ppm) accelerated soil elevation gain by 3.9 mm yr(-1) in this 2-year field study, an effect mediated by stimulation of below-ground plant productivity. Further, a companion greenhouse experiment revealed that the CO(2) effect was enhanced under salinity and flooding conditions likely to accompany future SLR. Our results indicate that by stimulating biogenic contributions to marsh elevation, increases in the greenhouse gas, CO(2), may paradoxically aid some coastal wetlands in counterbalancing rising seas.

  4. Elevated CO2 stimulates marsh elevation gain, counterbalancing sea-level rise

    PubMed Central

    Langley, J. Adam; McKee, Karen L.; Cahoon, Donald R.; Cherry, Julia A.; Megonigal, J. Patrick

    2009-01-01

    Tidal wetlands experiencing increased rates of sea-level rise (SLR) must increase rates of soil elevation gain to avoid permanent conversion to open water. The maximal rate of SLR that these ecosystems can tolerate depends partly on mineral sediment deposition, but the accumulation of organic matter is equally important for many wetlands. Plant productivity drives organic matter dynamics and is sensitive to global change factors, such as rising atmospheric CO2 concentration. It remains unknown how global change will influence organic mechanisms that determine future tidal wetland viability. Here, we present experimental evidence that plant response to elevated atmospheric [CO2] stimulates biogenic mechanisms of elevation gain in a brackish marsh. Elevated CO2 (ambient + 340 ppm) accelerated soil elevation gain by 3.9 mm yr−1 in this 2-year field study, an effect mediated by stimulation of below-ground plant productivity. Further, a companion greenhouse experiment revealed that the CO2 effect was enhanced under salinity and flooding conditions likely to accompany future SLR. Our results indicate that by stimulating biogenic contributions to marsh elevation, increases in the greenhouse gas, CO2, may paradoxically aid some coastal wetlands in counterbalancing rising seas. PMID:19325121

  5. NCLX protein, but not LETM1, mediates mitochondrial Ca2+ extrusion, thereby limiting Ca2+-induced NAD(P)H production and modulating matrix redox state.

    PubMed

    De Marchi, Umberto; Santo-Domingo, Jaime; Castelbou, Cyril; Sekler, Israel; Wiederkehr, Andreas; Demaurex, Nicolas

    2014-07-18

    Mitochondria capture and subsequently release Ca(2+) ions, thereby sensing and shaping cellular Ca(2+) signals. The Ca(2+) uniporter MCU mediates Ca(2+) uptake, whereas NCLX (mitochondrial Na/Ca exchanger) and LETM1 (leucine zipper-EF-hand-containing transmembrane protein 1) were proposed to exchange Ca(2+) against Na(+) or H(+), respectively. Here we study the role of these ion exchangers in mitochondrial Ca(2+) extrusion and in Ca(2+)-metabolic coupling. Both NCLX and LETM1 proteins were expressed in HeLa cells mitochondria. The rate of mitochondrial Ca(2+) efflux, measured with a genetically encoded indicator during agonist stimulations, increased with the amplitude of mitochondrial Ca(2+) ([Ca(2+)]mt) elevations. NCLX overexpression enhanced the rates of Ca(2+) efflux, whereas increasing LETM1 levels had no impact on Ca(2+) extrusion. The fluorescence of the redox-sensitive probe roGFP increased during [Ca(2+)]mt elevations, indicating a net reduction of the matrix. This redox response was abolished by NCLX overexpression and restored by the Na(+)/Ca(2+) exchanger inhibitor CGP37157. The [Ca(2+)]mt elevations were associated with increases in the autofluorescence of NAD(P)H, whose amplitude was strongly reduced by NCLX overexpression, an effect reverted by Na(+)/Ca(2+) exchange inhibition. We conclude that NCLX, but not LETM1, mediates Ca(2+) extrusion from mitochondria. By controlling the duration of matrix Ca(2+) elevations, NCLX contributes to the regulation of NAD(P)H production and to the conversion of Ca(2+) signals into redox changes. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  6. Extracellular nucleotides act through P2U purinoceptors to elevate [Ca2+]i and enhance basic fibroblast growth factor-induced proliferation in sheep chondrocytes.

    PubMed

    Kaplan, A D; Kilkenny, D M; Hill, D J; Dixon, S J

    1996-11-01

    Extracellular nucleotides interact with specific cell surface receptors to mediate a variety of biological responses, including elevation of the cytosolic free Ca2+ concentration ([Ca2+]i) in a number of cell types. Although extracellular ATP has been shown to affect chondrocyte function, the underlying mechanisms are poorly understood. In the present study, we investigated whether Ca2+-mobilizing purinoceptors are present on sheep chondrocytes. Chondrocytes were isolated from the proximal tibial growth plate of day 120-130 sheep fetuses. Early passage cells were loaded with indo-1 or fluo-3, and [Ca2+]i was monitored by fluorescence spectrophotometry. ATP (0.3-100 microM) induced transient elevation of [Ca2+]i, lasting approximately 1 min. Half-maximal elevation of [Ca2+]i was observed at an ATP concentration of 5.0 +/- 0.2 microM. Responses were still observed in the absence of extracellular Ca2+, and were abolished by pretreatment with thapsigargin, consistent with the release of Ca2+ from intracellular stores. Several nucleotides were tested for their ability to elevate [Ca2+]i. In order of potency, these were UTP approximately ATP > ADP approximately 2-methylthio-ATP. No responses were elicited by benzoylbenzoic-ATP, a P2Z-selective agonist; alpha,beta-methylene-ATP, an agonist selective for certain P2X purinoceptors; AMP; adenosine; or pyrophosphate (all at 100 microM), demonstrating specificity. Taken together, these data indicate that nucleotides elevate [Ca2+]i in chondrocytes through interaction with the P2U purinoceptor subtype. Although pretreatment with pertussis toxin virtually abolished the Ca2+ response to lysophosphatidic acid, the response to UTP was relatively insensitive, suggesting that P2U purinoceptors are not linked to a pertussis toxin-sensitive G protein in chondrocytes. In contrast, the Ca2+ response to UTP was markedly inhibited by the biologically active phorbol ester 12-O-tetradecanoyl-beta-phorbol 13-acetate, but not by the inactive

  7. 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.

  8. Elevation of blood lead levels in emergency department patients with extra-articular retained missiles.

    PubMed

    Nguyen, Ann; Schaider, Jeffrey J; Manzanares, Mariah; Hanaki, Roy; Rydman, Robert J; Bokhari, Faran

    2005-02-01

    Patients who survive gunshot wounds often have retained missiles. Unlike intra-articular retained missiles, extra-articular retained missiles (EARMs) are not routinely removed. Cases of lead toxicity from EARMs have been described. This study seeks to determine whether blood lead levels are elevated in emergency department patients with EARMs compared with matched controls, whether clinical symptoms of lead toxicity are more prevalent in patients with EARMs than in controls, and whether longer missile retention times or recent hypermetabolic conditions are associated with higher blood lead levels. One hundred twenty adults with EARMs and 120 age- and gender-matched controls with no history of gunshot wound were prospectively enrolled on presentation to a large urban emergency department. Whole blood lead (WBL), zinc protoporphyrin, and hemoglobin levels were obtained. Patients completed a questionnaire regarding time since gunshot injury; symptoms of lead toxicity; and occurrence within 30 days of any surgery, alcohol abuse, illicit drug abuse, diabetic ketoacidosis, hyperthyroidism, infection, fracture, pregnancy, or lactation. Five EARM patients (4%) and no control patients (0%) had WBL greater than our threshold for medical follow-up (20 microg/dL). Mean WBL was 6.71 microg/dL (95% confidence interval [CI], 5.68-7.74 microg/dL) in EARM patients and 3.16 mug/dL (95% CI, 2.79-3.53 microg/dL) in controls. This difference was statistically significant when analyzed by matched pairs t test (p = 0.0001). There was no difference in the number of symptoms associated with lead toxicity that were noted by EARM patients versus controls (p = 0.377). Longer duration of missile retention was not associated with higher blood lead levels (r = 0.125, p = 0.172). Of the five hypermetabolic conditions analyzed, only fractures were associated with elevated blood lead levels (9.95 microg/dL [95% CI, 5.77-14.13 microg/dL] in EARM patients with fractures vs. 6.23 microg/dL [95% CI, 5

  9. Reactive oxygen species triggering systemic programmed cell death process via elevation of nuclear calcium ion level in tomatoes resisting tobacco mosaic virus.

    PubMed

    Li, Yang; Li, Qi; Hong, Qiang; Lin, Yichun; Mao, Wang; Zhou, Shumin

    2018-05-01

    Programmed cell death (PCD) plays a positive role in the systemic response of plants to pathogen resistance. It has been confirmed that local tobacco mosaic virus (TMV) infecting tomato leaves can induce systemic PCD process in root-tip tissues. But up to now the underlying physiological mechanisms are poorly understood. This study focused on the detailed investigation of the physiological responses of root-tip cells during the initiation of systemic PCD. Physiological, biochemical examination and cytological observation showed that 1 day post-inoculation (dpi) of TMV inoculation there was an increase in calcium fluorescence intensity in root tip tissue cells. Then at 2 dpi, 4 dpi, 8 dpi and 15 dpi, the fluorescence intensity of calcium ion continued to increase. However, at 5 dpi, the reactive oxygen species (ROS) began to accumulate in the root-tip cells. And finally at 20 dpi, the obvious PCD reaction was detected. In addition, the experimental results also showed that the above process involved the elevation of two types of intracellular Ca 2+ , including cytoplasmic calcium ([Ca 2+ ] cyt ) and nuclear calcium ([Ca 2+ ] nuc ). The [Ca 2+ ] cyt , as a pilot signal could lead to the subsequent elevation of intracellular ROS concentration. Then, the high levels of ROS stimulated an increase of [Ca 2+ ] nuc and eventually caused PCD reactions in the root-tip tissues. In particular, the high level of nuclear calcium is an essential mediator in systemic PCD of plants. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. Ca2+ spike initiation from sensitized inositol 1,4,5-trisphosphate-sensitive Ca2+ stores in megakaryocytes.

    PubMed

    Ikeda, M; Kurokawa, K; Maruyama, Y

    1994-06-01

    Ca(2+)-mediated Ca2+ spikes were analysed in fura-2-loaded megakaryocytes. Direct Ca2+ loading using whole-cell dialysis induced an all-or-none Ca2+ spike on top of a tonic increase in cellular Ca2+ concentration ([Ca2+]i) with a latency of 3-7 s. The latency decreased with increasingly higher concentrations of Ca2+ in the dialysing solution. Spike size and its initiation did not correlate with the tonic level of [Ca2+]i. Thapsigargin completely abolished the Ca(2+)-induced spike initiation, suggesting that Ca2+ spikes originate from thapsigargin-sensitive Ca2+ pools. An inhibitor of phosphatidylinositide-specific phospholipase C (PLC), 2-nitro-4-carboxyphenyl-N,N-diphenyl-carbamate prolonged the latency without changes of spike size in most cases (6/9 cells), but abolished the spike initiation in the other cells (3/9). The results suggest that an increase in [Ca2+]i charges up the inositol-1,4,5-trisphosphate-(InsP3)- and thapsigargin-sensitive Ca2+ pools which progressively sensitize to low or slightly elevated levels of InsP3 by the action of Ca(2+)-dependent PLC until a critical Ca2+ content is reached, and then the Ca2+ spike is triggered. Thus, the limiting step of Ca2+ spike triggering is the initial filling process and the level of InsP3 in megakaryocytes.

  11. 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.

  12. Puerperal Mastitis: a Reproductive Event of Importance Affecting Anti-Mucin Antibody Levels and Ovarian Cancer Risk

    PubMed Central

    Cramer, Daniel W.; Williams, Kristina; Vitonis, Allison F.; Yamamoto, Hidemi S.; Stuebe, Alison; Welch, William R.; Titus, Linda; Fichorova, Raina N.

    2013-01-01

    Purpose Test the hypothesis that puerperal mastitis may alter immunity related to the mucin (MUC) family of glycoproteins and lower risk for ovarian cancer. Methods In two case-control studies conducted in New England between 1998–2008, we examined the association between self-reported mastitis and ovarian cancer in 1,483 women with epithelial ovarian cancer and 1,578 controls. IgG1 antibodies against (MUC1) CA15.3 and (MUC16) CA125 were measured using electrochemiluminescence assays in a subset of controls (n=200). Preoperative CA125 was recorded in 649 cases. The association between ovarian cancer and mastitis was assessed using unconditional logistic regression to calculate adjusted odds ratios, OR, and 95% confidence intervals (CI). Associations between mastitis and anti-CA15.3 and anti-CA125 antibodies and preoperative CA125 levels were evaluated using adjusted linear regression models. Results Prior mastitis was associated with a significantly lower risk for ovarian cancer: OR (and 95% CI) of 0.67 (0.48, 0.94) adjusted for parity, breastfeeding, and other potential confounders. The association was strongest with 2 or more episodes of mastitis; and risk declined progressively with increasing number of children and episodes of mastitis. Among controls, prior mastitis was associated with significantly higher anti-CA15.3 and anti-CA125 antibody levels and, among cases, with significantly lower preoperative CA125 levels. Conclusion Puerperal that mastitis may produce long-lasting anti-mucin antibodies that may lower the risk for ovarian cancer, plausibly through enhanced immune surveillance. Studying immune reactions related to MUC1 and MUC16 in the 10–20% of breastfeeding women who develop mastitis may suggest ways to duplicate its effects through vaccines based on both antigens. PMID:23925696

  13. Drastic lake level changes of Lake Van (eastern Turkey) during the past ca. 600 ka: climatic, volcanic and tectonic control

    NASA Astrophysics Data System (ADS)

    Cukur, D.; Krastel, S.; Schmincke, H.; Sumita, M.; Tomonaga, Y.; Damci, E.

    2013-12-01

    Lake Van is the largest soda lake in the world with a present surface of 3,574 km2 and a maximum water depth of 450 m. Sedimentary deposits in the lake preserve one of the most complete record of continental climate in the Middle East since the Middle Pleistocene. We studied these deposits to characterize the evolution of the lake level and its possible relationships with changes in climate, volcanic, and regional tectonics since the formation of the lake ca. 600 ka ago. Changes in lake level were determined based on high-resolution seismic reflection profiles showing erosional surfaces, changes in stratal geometries such as downward shifts in coastal onlap, and recognition of distinctive stratigraphic features such as prograding delta clinoforms. Our results show that Lake Van has undergone drastic changes in surface elevation by as much as 600 meters over the past ca. 600 ka. Five major lowstands occurred at ca. ~600 ka, ca. 365-340 ka, ca 290-230 ka; ca. 150-130 ka; and ca. 30-14 ka. During a first period (A) (ca. 600-ca 230 ka) lake levels changed drastically by hundreds of m but at longer time intervals between low and high stands. Changes occurred more frequently but mostly by a few tens of m during the past ca. 230 ka years where we can distinguish a first period (B1) of stepwise transgressions between ca. 230 and 150 ka followed by a short regression between ca. 150 and 130 ka. Lake level rose stepwise again during period B2 lasting until ca 30 ka. During the past 30 ka a regression and a final transgression each lasted ca. 15 ka years. The major lowstand periods in Lake Van occurred during glacial periods, arguing for a climatic control of these lake-level fluctuations (i.e., significantly reduced precipitation leading to lake level low stands). Although climate forcing may have been the dominant cause for the drastic lake level changes of Lake Van, volcanic and tectonic forcing factors are also invoked. For example, the number of distinct tephra layers

  14. 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.

  15. 41 CFR 102-192.125 - What is the appropriate managerial level for an agency mail manager?

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 41 Public Contracts and Property Management 3 2014-01-01 2014-01-01 false What is the appropriate managerial level for an agency mail manager? 102-192.125 Section 102-192.125 Public Contracts and Property... level that enables him or her to speak for the agency and fulfill the requirements of Subparts B, C, D...

  16. 41 CFR 102-192.125 - What is the appropriate managerial level for an agency mail manager?

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 41 Public Contracts and Property Management 3 2012-01-01 2012-01-01 false What is the appropriate managerial level for an agency mail manager? 102-192.125 Section 102-192.125 Public Contracts and Property... level that enables him or her to speak for the agency and fulfill the requirements of Subparts B, C, D...

  17. 41 CFR 102-192.125 - What is the appropriate managerial level for an agency mail manager?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 41 Public Contracts and Property Management 3 2013-07-01 2013-07-01 false What is the appropriate managerial level for an agency mail manager? 102-192.125 Section 102-192.125 Public Contracts and Property... level that enables him or her to speak for the agency and fulfill the requirements of Subparts B, C, D...

  18. 41 CFR 102-192.125 - What is the appropriate managerial level for an agency mail manager?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false What is the appropriate managerial level for an agency mail manager? 102-192.125 Section 102-192.125 Public Contracts and Property... level that enables him or her to speak for the agency and fulfill the requirements of Subparts B, C, D...

  19. 41 CFR 102-192.125 - What is the appropriate managerial level for an agency mail manager?

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 41 Public Contracts and Property Management 3 2011-01-01 2011-01-01 false What is the appropriate managerial level for an agency mail manager? 102-192.125 Section 102-192.125 Public Contracts and Property... level that enables him or her to speak for the agency and fulfill the requirements of Subparts B, C, D...

  20. Testosterone replacement elevates the serum uric acid levels in patients with female to male gender identity disorder.

    PubMed

    Kurahashi, Hiroaki; Watanabe, Masami; Sugimoto, Morito; Ariyoshi, Yuichi; Mahmood, Sabina; Araki, Motoo; Ishii, Kazushi; Nasu, Yasutomo; Nagai, Atsushi; Kumon, Hiromi

    2013-01-01

    Gender identity disorder (GID) results from a disagreement between a person's biological sex and the gender to which he or she identifies. With respect to the treatment of female to male GID, testosterone replacement therapy (TRT) is available. The uric acid (UA) level can be influenced by testosterone; however, the early effects and dose-dependency of TRT on the serum UA concentration have not been evaluated in this population. We herein conducted a dose-response analysis of TRT in 160 patients with female to male GID. The TRT consisted of three treatment groups who received intramuscular injections of testosterone enanthate: 125 mg every two weeks, 250 mg every three weeks and 250 mg every two weeks. Consequently, serum UA elevation was observed after three months of TRT and there was a tendency toward testosterone dose-dependency. The onset of hyperuricemia was more prevalent in the group who received the higher dose. We also demonstrated a positive correlation between increased levels of serum UA and serum creatinine. Since the level of serum creatinine represents an individual's muscle volume and the muscle is a major source of purine, which induces UA upregulation, the serum UA elevation observed during TRT is at least partially attributed to an increase in muscle mass. This is the first study showing an association between serum UA elevation and a TRT-induced increase in muscle mass. The current study provides important information regarding TRT for the follow-up and management of the serum UA levels in GID patients.

  1. CA19-9 serum levels predict micrometastases in patients with gastric cancer

    PubMed Central

    Potrc, Stojan; Mis, Katarina; Plankl, Mojca; Mars, Tomaz

    2016-01-01

    Abstract Background We explored the prognostic value of the up-regulated carbohydrate antigen (CA19-9) in node-negative patients with gastric cancer as a surrogate marker for micrometastases. Patients and methods Micrometastases were determined using reverse transcription quantitative polymerase chain reaction (RT-qPCR) for a subgroup of 30 node-negative patients. This group was used to determine the cut-off for preoperative CA19-9 serum levels as a surrogate marker for micrometastases. Then 187 node-negative T1 to T4 patients were selected to validate the predictive value of this CA19-9 threshold. Results Patients with micrometastases had significantly higher preoperative CA19-9 serum levels compared to patients without micrometastases (p = 0.046). CA19-9 serum levels were significantly correlated with tumour site, tumour diameter, and perineural invasion. Although not reaching significance, subgroup analysis showed better five-year survival rates for patients with CA19-9 serum levels below the threshold, compared to patients with CA19-9 serum levels above the cut-off. The cumulative survival for T2 to T4 node-negative patients was significantly better with CA19-9 serum levels below the cut-off (p = 0.04). Conclusions Preoperative CA19-9 serum levels can be used to predict higher risk for haematogenous spread and micrometastases in node-negative patients. However, CA19-9 serum levels lack the necessary sensitivity and specificity to reliably predict micrometastases. PMID:27247553

  2. Factors Associated With Elevated Blood Lead Levels in Children.

    PubMed

    Chaudhary, Sakshi; Firdaus, Uzma; Ali, Syed Manazir; Mahdi, Abbas Ali

    2018-01-15

    To determine the prevalence and correlates of elevated blood lead level in children (6-144 months) of Aligarh. A hospital-based cross-sectional study was conducted. Venous blood was obtained for lead estimation and a structured questionnaire was filled. A total of 260 children were enrolled. The prevalence of elevated blood lead level was 44.2%, seen mostly in children below 5 years of age. Old and deteriorating wall paints at home was found to be significantly associated with elevated levels. Lead-based house paints are potential source of lead exposure. Meticulous renovation and painting of the walls with safe paints is desirable.

  3. 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

  4. MicroRNA-125b is a novel negative regulator of p53.

    PubMed

    Le, Minh T N; Teh, Cathleen; Shyh-Chang, Ng; Xie, Huangming; Zhou, Beiyan; Korzh, Vladimir; Lodish, Harvey F; Lim, Bing

    2009-04-01

    The p53 transcription factor is a key tumor suppressor and a central regulator of the stress response. To ensure a robust and precise response to cellular signals, p53 gene expression must be tightly regulated from the transcriptional to the post-translational levels. Computational predictions suggest that several microRNAs are involved in the post-transcriptional regulation of p53. Here we demonstrate that miR-125b, a brain-enriched microRNA, is a bona fide negative regulator of p53 in both zebrafish and humans. miR-125b-mediated down-regulation of p53 is strictly dependent on the binding of miR-125b to a microRNA response element in the 3' untranslated region of p53 mRNA. Overexpression of miR-125b represses the endogenous level of p53 protein and suppresses apoptosis in human neuroblastoma cells and human lung fibroblast cells. In contrast, knockdown of miR-125b elevates the level of p53 protein and induces apoptosis in human lung fibroblasts and in the zebrafish brain. This phenotype can be rescued significantly by either an ablation of endogenous p53 function or ectopic expression of miR-125b in zebrafish. Interestingly, miR-125b is down-regulated when zebrafish embryos are treated with gamma-irradiation or camptothecin, corresponding to the rapid increase in p53 protein in response to DNA damage. Ectopic expression of miR-125b suppresses the increase of p53 and stress-induced apoptosis. Together, our study demonstrates that miR-125b is an important negative regulator of p53 and p53-induced apoptosis during development and during the stress response.

  5. MicroRNA-125b is a novel negative regulator of p53

    PubMed Central

    Le, Minh T.N.; Teh, Cathleen; Shyh-Chang, Ng; Xie, Huangming; Zhou, Beiyan; Korzh, Vladimir; Lodish, Harvey F.; Lim, Bing

    2009-01-01

    The p53 transcription factor is a key tumor suppressor and a central regulator of the stress response. To ensure a robust and precise response to cellular signals, p53 gene expression must be tightly regulated from the transcriptional to the post-translational levels. Computational predictions suggest that several microRNAs are involved in the post-transcriptional regulation of p53. Here we demonstrate that miR-125b, a brain-enriched microRNA, is a bona fide negative regulator of p53 in both zebrafish and humans. miR-125b-mediated down-regulation of p53 is strictly dependent on the binding of miR-125b to a microRNA response element in the 3′ untranslated region of p53 mRNA. Overexpression of miR-125b represses the endogenous level of p53 protein and suppresses apoptosis in human neuroblastoma cells and human lung fibroblast cells. In contrast, knockdown of miR-125b elevates the level of p53 protein and induces apoptosis in human lung fibroblasts and in the zebrafish brain. This phenotype can be rescued significantly by either an ablation of endogenous p53 function or ectopic expression of miR-125b in zebrafish. Interestingly, miR-125b is down-regulated when zebrafish embryos are treated with γ-irradiation or camptothecin, corresponding to the rapid increase in p53 protein in response to DNA damage. Ectopic expression of miR-125b suppresses the increase of p53 and stress-induced apoptosis. Together, our study demonstrates that miR-125b is an important negative regulator of p53 and p53-induced apoptosis during development and during the stress response. PMID:19293287

  6. 5. Downstream elevation, view to southeast. Dark stains on side ...

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

    5. Downstream elevation, view to southeast. Dark stains on side of main girder are from deck drain scuppers, marking deck level within the girders. Compare this view and CA-126-7 to CA-126-19 for indication of severity of siltation of Salt River channel has silted. - Salt River Bridge, Spanning Salt River at Dillon Road, Ferndale, Humboldt County, CA

  7. TRPV1: Contribution to Retinal Ganglion Cell Apoptosis and Increased Intracellular Ca2+ with Exposure to Hydrostatic Pressure

    PubMed Central

    Sappington, Rebecca M.; Sidorova, Tatiana; Long, Daniel J.; Calkins, David J.

    2013-01-01

    Purpose Elevated hydrostatic pressure induces retinal ganglion cell (RGC) apoptosis in culture. The authors investigated whether the transient receptor potential vanilloid 1 (TRPV1) channel, which contributes to pressure sensing and Ca2+-dependent cell death in other systems, also contributes to pressure-induced RGC death and whether this contribution involves Ca2+. Methods trpv1 mRNA expression in RGCs was probed with the use of PCR and TRPV1 protein localization through immunocytochemistry. Subunit-specific antagonism (iodo-resiniferatoxin) and agonism (capsaicin) were used to probe how TRPV1 activation affects the survival of isolated RGCs at ambient and elevated hydrostatic pressure (+70 mm Hg). Finally, for RGCs under pressure, the authors tested whether EGTA chelation of Ca2+ improves survival and whether, with the Ca2+ dye Fluo-4 AM, TRPV1 contributes to increased intracellular Ca2+. Results RGCs express trpv1 mRNA, with robust TRPV1 protein localization to the cell body and axon. For isolated RGCs under pressure, TRPV1 antagonism increased cell density and reduced apoptosis to ambient levels (P ≤ 0.05), whereas for RGCs at ambient pressure, TRPV1 agonism reduced density and increased apoptosis to levels for elevated pressure (P ≤ 0.01). Chelation of extracellular Ca2+ reduced RGC apoptosis at elevated pressure by nearly twofold (P ≤ 0.01). Exposure to elevated hydrostatic pressure induced a fourfold increase in RGC intracellular Ca2+ that was reduced by half with TRPV1 antagonism. Finally, in the DBA/2 mouse model of glaucoma, levels of TRPV1 in RGCs increased with elevated IOP. Conclusions RGC apoptosis induced by elevated hydrostatic pressure arises substantially through TRPV1, likely through the influx of extracellular Ca2+. PMID:18952924

  8. Effect of [6]-shogaol on cytosolic Ca2+ levels and proliferation in human oral cancer cells (OC2).

    PubMed

    Chen, Chung-Yi; Yang, Yu-Han; Kuo, Soong-Yu

    2010-08-27

    The effect of [6]-shogaol (1) on cytosolic free Ca(2+) concentrations ([Ca(2+)](i)) and viability has not been explored previously in oral epithelial cells. The present study has examined whether 1 alters [Ca(2+)](i) and viability in OC2 human oral cancer cells. Compound 1 at concentrations > or = 5 microM increased [Ca(2+)](i) in a concentration-dependent manner with a 50% effective concentration (EC(50)) value of 65 microM. The Ca(2+) signal was reduced substantially by removing extracellular Ca(2+). In a Ca(2+)-free medium, the 1-induced [Ca(2+)](i) elevation was mostly attenuated by depleting stored Ca(2+) with thapsigargin (an endoplasmic reticulum Ca(2+) pump inhibitor). The [Ca(2+)](i) signal was inhibited by La(3+) but not by L-type Ca(2+) channel blockers. The elevation of [Ca(2+)](i) caused by 1 in a Ca(2+)-containing medium was not affected by modulation of protein kinase C activity, but was inhibited by 82% with the phospholipase A2 inhibitor aristolochic acid I (20 microM). U73122, a selective inhibitor of phospholipase C, abolished 1-induced [Ca(2+)](i) release. At concentrations of 5-100 microM, 1 killed cells in a concentration-dependent manner. These findings suggest that [6]-shogaol induces a significant rise in [Ca(2+)](i) in oral cancer OC2 cells by causing stored Ca(2+) release from the thapsigargin-sensitive endoplasmic reticulum pool in an inositol 1,4,5-trisphosphate-dependent manner and by inducing Ca(2+) influx via a phospholipase A2- and La(3+)-sensitive pathway.

  9. Nanosecond UV lasers stimulate transient Ca2+ elevations in human hNT astrocytes.

    PubMed

    Raos, B J; Graham, E S; Unsworth, C P

    2017-06-01

    Astrocytes respond to various stimuli resulting in intracellular Ca 2+ signals that can propagate through organized functional networks. Recent literature calls for the development of techniques that can stimulate astrocytes in a fast and highly localized manner to emulate more closely the characteristics of astrocytic Ca 2+ signals in vivo. In this article we demonstrate, for the first time, how nanosecond UV lasers are capable of reproducibly stimulating Ca 2+ transients in human hNT astrocytes. We report that laser pulses with a beam energy of 4-29 µJ generate transient increases in cytosolic Ca 2+ . These Ca 2+ transients then propagate to adjacent astrocytes as intercellular Ca 2+ waves. We propose that nanosecond laser stimulation provides a valuable tool for enabling the study of Ca 2+ dynamics in human astrocytes at both a single cell and network level. Compared to previously developed techniques nanosecond laser stimulation has the advantage of not requiring loading of photo-caged or -sensitising agents, is non-contact, enables stimulation with a high spatiotemporal resolution and is comparatively cost effective.

  10. Perturbation of myo-inositol-1,4,5-trisphosphate levels during agonist-induced Ca2+ oscillations.

    PubMed Central

    Chatton, J Y; Cao, Y; Stucki, J W

    1998-01-01

    Agonist-induced Ca2+ oscillations in rat hepatocytes involve the production of myo-inositol-1,4,5-trisphosphate (IP3), which stimulates the release of Ca2+ from intracellular stores. The oscillatory frequency is conditioned by the agonist concentration. This study investigated the role of IP3 concentration in the modulation of oscillatory frequency by using microinjected photolabile IP3 analogs. Photorelease of IP3 during hormone-induced oscillations evoked a Ca2+ spike, after which oscillations resumed with a delay corresponding to the period set by the agonists. IP3 photorelease had no influence on the frequency of oscillations. After photorelease of 1-(alpha-glycerophosphoryl)-D-myo-inositol-4,5-diphosphate (GPIP2), a slowly metabolized IP3 analog, the frequency of oscillations initially increased by 34% and declined to its original level within approximately 6 min. Both IP3 and GPIP2 effects can be explained by their rate of degradation: the half-life of IP3, which is a few seconds, can account for the lack of influence of IP3 photorelease on the frequency, whereas the slower metabolism of GPIP2 allowed a transient acceleration of the oscillations. The phase shift introduced by IP3 is likely the result of the brief elevation of Ca2+ during spiking that resets the IP3 receptor to a state of maximum inactivation. A mathematical model of Ca2+ oscillations is in satisfactory agreement with the observed results. PMID:9449352

  11. Effect of pertussis and cholera toxins administered supraspinally on CA3 hippocampal neuronal cell death and the blood glucose level induced by kainic acid in mice.

    PubMed

    Kim, Chea-Ha; Park, Soo-Hyun; Sim, Yun-Beom; Sharma, Naveen; Kim, Sung-Su; Lim, Su-Min; Jung, Jun-Sub; Suh, Hong-Won

    2014-12-01

    The effect of cholera toxin (CTX) or pertussis toxin (PTX) administered supraspinally on hippocampal neuronal cell death in CA3 region induced by kainic acid (KA) was examined in mice. After the pretreatment with either PTX or CTX intracerebroventricularly (i.c.v.), mice were administered i.c.v. with KA. The i.c.v. treatment with KA caused a neuronal cell death in CA3 region and PTX, but not CTX, attenuated the KA-induced neuronal cell death. In addition, i.c.v. treatment with KA caused an elevation of the blood glucose level. The i.c.v. PTX pretreatment alone caused a hypoglycemia and inhibited KA-induced hyperglycemic effect. However, i.c.v. pretreatment with CTX did not affect the basal blood glucose level and KA-induced hyperglycemic effect. Moreover, KA administered i.c.v. caused an elevation of corticosterone level and reduction of the blood insulin level. Whereas, i.c.v. pretreatment with PTX further enhanced KA-induced up-regulation of corticosterone level. Furthermore, i.c.v. administration of PTX alone increased the insulin level and KA-induced hypoinsulinemic effect was reversed. In addition, PTX pretreatment reduces the KA-induced seizure activity. Our results suggest that supraspinally administered PTX, exerts neuroprotective effect against KA-induced neuronal cells death in CA3 region and neuroprotective effect of PTX is mediated by the reduction of KA-induced blood glucose level. Copyright © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

  12. ELEVATED GAMMA-AMINOBUTYRIC ACID LEVELS IN CHRONIC SCHIZOPHRENIA

    PubMed Central

    Öngür, Dost; Prescot, Andrew P.; McCarthy, Julie; Cohen, Bruce M.; Renshaw, Perry F.

    2010-01-01

    Background Despite widely-replicated abnormalities of gamma-aminobutyric acid (GABA) neurons in schizophrenia postmortem, few studies have measured tissue GABA levels in vivo. We used proton magnetic resonance spectroscopy to measure tissue GABA levels in participants with schizophrenia and healthy controls in the anterior cingulate cortex (ACC) and parieto-occipital cortex (POC). Methods 21 schizophrenia participants effectively treated on a stable medication regimen (mean age 39.0, 14 male) and 19 healthy controls (mean age 36.3, 12 male) underwent a proton magnetic resonance spectroscopy scan using GABA-selective editing at 4 Tesla after providing informed consent. Data were collected from two 16.7cc voxels and analyzed using LCModel. Results We found elevations in GABA/Cr in the schizophrenia group compared with controls (F(1,65)=4.149, p=0.046) in both brain areas (15.5% elevation in ACC, 11.9% in POC). We also found a positive correlation between GABA/Cr and Glu/Cr which was not accounted for by %GM or brain region. Conclusions We found elevated GABA/Cr in participants with chronically treated schizophrenia. Postmortem studies report evidence for dysfunctional GABAergic neurotransmission in schizophrenia. Elevated GABA levels, whether primary to illness or compensatory to another process, may be associated with dysfunctional GABAergic neurotransmission in chronic schizophrenia. PMID:20598290

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. Targeted delivery of 1,25-dihydroxyvitamin D3 to colon tissue and identification of a major 1,25-dihydroxyvitamin D3 glycoside from Solanumglaucophyllum plant leaves.

    PubMed

    Zimmerman, Duane R; Koszewski, Nicholas J; Hoy, Derrel A; Goff, Jesse P; Horst, Ronald L

    2015-04-01

    Leaves of the Solanum glaucophyllum (Sg) plant, indigenous to South America, have long been known for their calcinogenic toxicity in ruminant animals. It was determined the leaves contained glycosidic derivatives of 1,25-dihydroxyvitamin D3 (1,25D3) and liberation of the free hormone by rumen bacterial populations elicited a hypercalcemic response. Our interest in the leaves is predicated on the concept that the glycoside forms of 1,25D3 would target release of the active hormone in the lower gut of non-ruminant mammals. This would provide a means of delivering 1,25D3 directly to the colon, where the hormone has been shown to have beneficial effects in models of inflammatory bowel disease (IBD) and colon cancer. We fed mice for 10 days with variable amounts of Sg leaf. Feeding 7-333μg leaf/day produced no changes in plasma Ca(2+) and 1,25D3 concentrations, and only at ≥1000μg leaf/day did these values become significantly elevated compared to controls. Gene expression studies from colon tissue indicated a linear relationship between the amount of leaf consumed and expression of the Cyp24a1 gene. In contrast, Cyp24a1 gene expression in the duodenums and ileums of these mice was unchanged compared to controls. One of the major 1,25D3-glycosides was isolated from leaves following extraction and purification by Sep-Pak cartridges and HPLC fractionation. Ultraviolet absorbance was consistent with modification of the 1-hydroxyl group, and positive ion ESI mass spectrometry indicated a diglycoside of 1,25D3. 2-Dimensional NMR analyses were carried out and established the C1 proton of the A-ring was interacting with a C1' sugar proton, while the C3 proton of the A-ring was linked with a second C1' sugar proton. The structure of the isolated compound is therefore consistent with a β-linked 1,3-diglycoside of 1,25D3. Thus, Sg leaf administered to mice at up to 333 ug/day can elicit colon-specific enhancement of Cyp24a1 gene expression without inducing hypercalcemia, and

  18. Evaluation of serum CA27.29, CA15-3 and CEA in patients with breast cancer.

    PubMed

    Hou, M F; Chen, Y L; Tseng, T F; Lin, C M; Chen, M S; Huang, C J; Huang, Y S; Hsieh, J S; Huang, T J; Jong, S B; Huang, Y F

    1999-09-01

    The Truquant BR radioimmunoassay (RIA) using monoclonal antibody BR 27.29 to recognize a peptide sequence on the MUC-1 gene product for quantification of the CA 27.29 antigen in serum was used in this report to evaluate in 145 patients with breast cancer and compared the other conventional serum markers such as CA15-3 and CEA. The upper limit of normal (25 u/ml) was determined from CA27.29 values 12.4 +/- 4.1 u/ml (mean +/- 3 S.D.) for 112 female subjects apparently free of disease. The CA15-3 levels above 25 u/ml and CEA levels above 5 ng/ml were considered positive values. Thirty-seven cases of 145 patients studied had elevated CA 27.29 levels (sensitivity: 25.5%), 35 of 145 had positive CA15-3 levels (sensitivity 24.1%) and 27 of 145 patients had positive CEA levels (sensitivity: 18.6%) (p < 0.05). One hundred and ten cases of the breast cancer patients (75.8%) did not have metastatic disease. In this group CA 27.29 sensitivity was 6.4%, while CA15-3 sensitivity was 5.5% and CEA sensitivity was 4.5% (p > 0.05). Mean values were 10.2 +/- 9.2 u/ml for CA 27.29, 14.1 +/- 5.6 u/ml for CA 15-3 and 1.7 +/- 1.5 ng/ml for CEA. Thirty-five patients (24.2%) had metastatic disease. In this group CA 27.29 sensitivity was 85.7%, CA15-3 sensitivity was 82.8% and CEA sensitivity was 62.8% (p < 0.05). Mean values for CA27.29 was 152.6 +/- 131.6 u/ml, CA15-3 was 123.1 +/- 107.6 u/ml and 21.8 +/- 36.9 ng/ml of CEA. With regard to the correlation of three tumor markers with clinical stages, patients had significantly higher levels of CA27.29 than CEA, but they were similar to CA 15-3 in metastatic breast cancer. These results suggest CA27.29 to be more sensitive and specific than CEA, but that it is similar to CA15-3 for metastatic breast cancer detection and monitoring.

  19. 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

  20. Influence of Common Bean (Phaseolus vulgaris) Grown in Elevated CO2 on Apatite Dissolution

    NASA Astrophysics Data System (ADS)

    Olsen, A. A.; Morra, B.

    2016-12-01

    We ran a series of experiments to test the hypothesis that release of plant nutrients contained in apatite will be accelerated by the growth of Langstrath Stringless green bean in the presence of atmospheric CO2 meant to simulate possible future atmospheric conditions due a higher demand of nutrients and growth rate caused by elevated CO2. We hypothesize that elevated atmospheric CO2 will lead to both increased root growth and organic acid exudation. These two traits will lead to improved acquisition of P derived from apatite. Experiments were designed to investigate the effect of these changes on soil mineral weathering using plants grown under two conditions, ambient CO2 (400ppm) and elevated CO2 (1000ppm). Plants were grown in flow-through microcosms consisting of a mixture of quartz and apatite sands. Mini-greenhouses were utilized to control CO2 levels. Plant growth was sustained by a nutrient solution lacking in Ca and P. Calcium and P content of the leachate and plant tissue served as a proxy for apatite dissolution. Plants were harvested biweekly during the eight-week experiment and analyzed for Ca and P to calculate apatite dissolution kinetics. Preliminary results suggest that approximately four times more P and Ca are present in the leachate from experiments containing plants under both ambient and elevated CO2 levels than in abiotic experiments; however, the amounts of both P and Ca released in experiments conducted under both ambient and elevated CO2 levels are similar. Additionally, the amount of P in plant tissue grown under ambient and elevated CO2 conditions is similar. Plants grown in elevated CO2 had a greater root to shoot ratio. The planted microcosms were found to have a lower pH than abiotic controls most likely due to root respiration and exudation of organic acids.

  1. Elevated gamma-aminobutyric acid levels in chronic schizophrenia.

    PubMed

    Ongür, Dost; Prescot, Andrew P; McCarthy, Julie; Cohen, Bruce M; Renshaw, Perry F

    2010-10-01

    Despite widely replicated abnormalities of gamma-aminobutyric acid (GABA) neurons in schizophrenia postmortem, few studies have measured tissue GABA levels in vivo. We used proton magnetic resonance spectroscopy to measure tissue GABA levels in participants with schizophrenia and healthy control subjects in the anterior cingulate cortex and parieto-occipital cortex. Twenty-one schizophrenia participants effectively treated on a stable medication regimen (mean age 39.0, 14 male) and 19 healthy control subjects (mean age 36.3, 12 male) underwent a proton magnetic resonance spectroscopy scan using GABA-selective editing at 4 Tesla after providing informed consent. Data were collected from two 16.7-mL voxels and analyzed using LCModel. We found elevations in GABA/creatine in the schizophrenia group compared with control subjects [F(1,65) = 4.149, p = .046] in both brain areas (15.5% elevation in anterior cingulate cortex, 11.9% in parieto-occipital cortex). We also found a positive correlation between GABA/creatine and glutamate/creatine, which was not accounted for by % GM or brain region. We found elevated GABA/creatinine in participants with chronically treated schizophrenia. Postmortem studies report evidence for dysfunctional GABAergic neurotransmission in schizophrenia. Elevated GABA levels, whether primary to illness or compensatory to another process, may be associated with dysfunctional GABAergic neurotransmission in chronic schizophrenia. Copyright © 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  2. The Role of CA19-9 in Predicting Tumour Resectability in Carcinoma Head of Pancreas

    PubMed Central

    Viswanathan, Subramanian; Antomy, Thomas Babu; Thirumuruganand, Sathyamoorthy; Kumaresan, Dhandapani Subramanian

    2016-01-01

    Introduction Carbohydrate antigen 19-9 (CA 19-9) is a tumour associated antigen. Blood levels may be elevated in benign as well as malignant conditions. Its sensitivity (70-90%) and specificity (68-91%) are inadequate for accurate diagnosis. It can be used to predict the extent of disease and outcome after resection. Aim The aim of the present study was to assess the role of CA 19-9 in predicting the resectability of the tumour in the head of pancreas. Materials and Methods This was a prospective study which included 30 patients and study period was from May 2012 to October 2014. Data collected from all patients with carcinoma of the head of pancreas on the basis of contrast enhanced computed tomography/Magnetic resonance cholangiopancreaticography. CA 19-9 levels were measured and recorded. Patients who were medically unfit for surgery or those who didn’t warrant palliative surgery were excluded from the study. During surgery the operative findings on operability were documented and tabulated against corresponding CA 19-9 levels. Results Of the 30 patients who were operated, 13(43.3%) patients had operable tumours and underwent Whipple’s procedure and 17(56.7%) underwent palliative bypass procedure. Of the 30, CA 19-9 levels were elevated in 9(30.0%) and were normal in 21(70.0%). Among 13(43.3%) who had operable tumours, CA 19-9 was elevated in 4(13.3) and was normal in 9(30.0%). Of the 17(56.7%) who had inoperable tumours CA 19-9 was elevated in 5(16.7%) and was normal in 12(40.0%). Among the 17 who had inoperable tumours, 8(47.1%) were diagnosed preoperatively and of them CA 19-9 levels were raised in 2(11.8%) and normal in 6(35.3%). In the group of 9(52.9%) who had inoperable tumours diagnosed intraoperatively, CA 19-9 was raised in 3(17.6%) of them and was normal in the remaining 6(35.3%) of them. Conclusion Based on the study findings, it can be stated that there is no significant correlation with resectability of pancreatic adenocarcinoma and CA 19-9 and

  3. The Role of CA19-9 in Predicting Tumour Resectability in Carcinoma Head of Pancreas.

    PubMed

    Pandiaraja, Jayabal; Viswanathan, Subramanian; Antomy, Thomas Babu; Thirumuruganand, Sathyamoorthy; Kumaresan, Dhandapani Subramanian

    2016-03-01

    Carbohydrate antigen 19-9 (CA 19-9) is a tumour associated antigen. Blood levels may be elevated in benign as well as malignant conditions. Its sensitivity (70-90%) and specificity (68-91%) are inadequate for accurate diagnosis. It can be used to predict the extent of disease and outcome after resection. The aim of the present study was to assess the role of CA 19-9 in predicting the resectability of the tumour in the head of pancreas. This was a prospective study which included 30 patients and study period was from May 2012 to October 2014. Data collected from all patients with carcinoma of the head of pancreas on the basis of contrast enhanced computed tomography/Magnetic resonance cholangiopancreaticography. CA 19-9 levels were measured and recorded. Patients who were medically unfit for surgery or those who didn't warrant palliative surgery were excluded from the study. During surgery the operative findings on operability were documented and tabulated against corresponding CA 19-9 levels. Of the 30 patients who were operated, 13(43.3%) patients had operable tumours and underwent Whipple's procedure and 17(56.7%) underwent palliative bypass procedure. Of the 30, CA 19-9 levels were elevated in 9(30.0%) and were normal in 21(70.0%). Among 13(43.3%) who had operable tumours, CA 19-9 was elevated in 4(13.3) and was normal in 9(30.0%). Of the 17(56.7%) who had inoperable tumours CA 19-9 was elevated in 5(16.7%) and was normal in 12(40.0%). Among the 17 who had inoperable tumours, 8(47.1%) were diagnosed preoperatively and of them CA 19-9 levels were raised in 2(11.8%) and normal in 6(35.3%). In the group of 9(52.9%) who had inoperable tumours diagnosed intraoperatively, CA 19-9 was raised in 3(17.6%) of them and was normal in the remaining 6(35.3%) of them. Based on the study findings, it can be stated that there is no significant correlation with resectability of pancreatic adenocarcinoma and CA 19-9 and it doesn't predict vascular involvement and liver metastasis.

  4. Uterine fibroids with positive 18F-FDG PET/CT image and significantly increased CA19-9: A case report.

    PubMed

    Ma, Yan; Shao, Xiaonan

    2017-12-01

    Uterine fibroids are the most common pelvic solid tumors and common to 25% of women. F-fluorodexyglucose (F-FDG) is an energy metabolism tracer. Although FDG is generally concentrated in malignant lesions with high glucose metabolism, it can also accumulate in normal tissues, benign lesions, and inflammatory sites. The exact mechanism of FDG uptake by uterine fibroids is not clear. Here, we report a case of uterine fibroids with positive F-FDG positron emission tomography/computed tomography (PET/CT) imaging and significantly increased CA19-9. The patient was a 43-year-old woman and admitted to our hospital because of "1-year-extended menstrual periods." At admission, she had normal CA125, AFP, and CEA level and CA19-9>1000.00 U/mL. Gynecological transvaginal ultrasound found enlarged uterus with an anterior hypoechoic area of 3.9 × 4.2 cm. CT and contrast-enhanced CT showed significantly enhanced mass shadow on the left anterior wall of uterus. F-FDG PET/CT showed increased FDG metabolism of tumor in the anterior wall of the uterus. Laparoscopic hysterectomy was performed. Pathological examination demonstrated subserosal leiomyoma. Her CA19-9 level dropped to 91.50 U/mL 1 day after surgery. Significantly elevated CA19-9 was positioned in the uterus by PET/CT imaging, which not only avoided unnecessary gastrointestinal endoscopy and reduced the suffering of patients, but also strengthened the operation confidence in gynecologists. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

  5. Elevated urinary level of vitamin D-binding protein as a novel biomarker for diabetic nephropathy

    PubMed Central

    TIAN, XIAO-QIN; ZHAO, LI-MIN; GE, JIA-PU; ZHANG, YAN; XU, YAN-CHENG

    2014-01-01

    Improving the early prediction and detection of diabetic nephropathy (DN) remains a great challenge in disease management. The aim of this study was to evaluate the early detection power of urinary vitamin D-binding protein (VDBP) for the diagnosis of DN. Urine samples were obtained from 45 healthy volunteers and 105 diabetic patients with normoalbuminuria (DM group), microalbuminuria (DN1 group) and macroalbuminuria (DN2 group) (n=35 per group). The VDBP expression patterns in urine from patients and controls were quantified by western blot analysis. The excretion levels of urinary VDBP were quantified with enzyme-linked immunosorbent assay. The quantification results were obtained by correcting for creatinine expression and showed that urinary VDBP levels were significantly elevated in the patients of the DN1 and DN2 groups compared with those of the DM group and normal controls (1,011.33±325.30 and 1,406.34±239.66 compared with 466.54±213.63 and 125.48±98.27 ng/mg, respectively) (P<0.001). Receiver operating characteristic analysis of urinary VDBP levels for the diagnosis of DN rendered an optimum cut-off value of 552.243 ng/mg corresponding to 92.86% sensitivity and 85.00% specificity, which also showed an area under the ROC curve of 0.966. In conclusion, the findings of the present study suggest that urinary VDBP may be a potential biomarker for the early detection and prevention of DN. Further studies are required to examine the pathogenic mechanisms of elevated VDBP levels and their role in the diagnosis of DN. PMID:24396416

  6. Relationship between serum calcium and CA 19-9 levels in colorectal cancer

    PubMed Central

    Fuszek, Peter; Lakatos, Peter; Tabak, Adam; Papp, Janos; Nagy, Zsolt; Takacs, Istvan; Horvath, Henrik Csaba; Lakatos, Peter Laszlo; Speer, Gabor

    2004-01-01

    AIM: To examine the calcium metabolism of colorectal cancer (CRC) in patients with colorectal cancer and control patients. METHODS: Seventy newly diagnosed CRC patients were included. The healthy control group was age and gender matched (n = 32). Particular attention was devoted to the relationship between serum calcium of patients, and levels of AFP, CEA, carbohydrate antigen 19-9 (CA 19-9) (that could be considered as prognostic factors). Furthermore, the Ca-sensing receptor (CaSR) gene A986S polymorphism was investigated in these patients, as well as the relationship between different CaSR genotypes and the data stated above. RESULTS: A lower level of ionized calcium (also corrected for albumin) was found in the serum of CRC patients with normal 25 (OH) vitamin D levels. The ionized calcium concentration was inversely correlated with the serum level of CA 19-9. There was no difference in the distribution of CaSR genotypes, between CRC patients and general population. The genotypes did not correlate with other data examined. CONCLUSION: Based on these results, lower levels of serum calcium might be a pathogenic and prognostic factor in colorectal cancer. PMID:15222030

  7. Efficacy of a Calcium Sucrose Phosphate Based Toothpaste in Elevating the Level of Calcium, Phosphate Ions in Saliva and Reducing Plaque: A Clinical Trial

    PubMed Central

    Menon, Leena Unnikrishnan; Varma, R. Balagopal; Kumaran, Parvathy; Xavier, Arun Mamachan; Govinda, Bhat Sangeetha; Kumar, J. Suresh

    2018-01-01

    Aim: To evaluate and compare the efficacy of “calcium sucrose phosphate” (CaSP) toothpaste (Enafix 5%) with ordinarily used calcium, phosphate-containing toothpaste in elevating the level of calcium, phosphate ions in saliva. Secondary aims were to evaluate substantivity and plaque-reducing ability of CaSP toothpaste. Materials and Methods: Thirty study participants of age group 6–13 years were divided into two groups: Group X (Control group) was made to continue brushing with their regularly used calcium, phosphate-containing toothpaste and Group Y (Test group) was allotted CaSP toothpaste. 1 ml of unstimulated saliva was periodically collected from both groups to determine any alteration in the salivary calcium, phosphate level. Parameters such as substantivity and plaque-reducing ability of CaSP toothpaste were also evaluated. Salivary mineral's intergroup comparison was evaluated by Student's t-test while its intragroup comparison along with the plaque amount variation in Group Y was evaluated by ANOVA and Tukey's post hoc test. Results: Group Y showed an increase in the salivary calcium level though not statistically significant. The increase was pronounced in samples collected on day 1. Group Y showed a consistent level of calcium, phosphate in samples collected immediately and 6 h postbrushing, indicating its substantivity. In addition, Group Y had an impact in reducing the plaque level when the 1st-month plaque score was compared with the 12th-month score. Conclusion: CaSP leads to an increase in the salivary calcium level though it was not statistically significant. Supervised brushing and dietary habits showed a positive effect on both the groups. CaSP toothpaste also showed substantivity and plaque-reducing ability.

  8. The trophoblast cell surface antigen 2 and miR-125b axis in urothelial bladder cancer

    PubMed Central

    Lazzarini, Raffaella; Gesuita, Rosaria; Guerra, Emanuela; Tossetta, Giovanni; Castellucci, Clara; Giannubilo, Stefano Raffaele; Procopio, Antonio; Alberti, Saverio; Mazzucchelli, Roberta

    2017-01-01

    Human trophoblast cell surface antigen 2 (Trop-2) is a 40-kDa transmembrane glycoprotein that was first identified as a marker of human trophoblast cells. Trop-2 acts on cell proliferation, adhesion, and migration by activating a number of intracellular signalling pathways. Elevated Trop-2 expression has been demonstrated in several types of cancer and correlated with aggressiveness and poor prognosis. Since no data are available on Trop-2 in bladder cancer (BC), the purpose of the study was to determine its levels in tissue specimens from normal individuals and patients with BC at different stages. Moreover, since according to recent evidence Trop-2 is a miR-125b target, miR-125b expression was also assessed in tissue specimens. Finally, the effect of the Trop-2/miR-125b axis on the proliferation and migration of BC cells was evaluated in vitro. The Trop-2/miR-125b axis was seen to be differentially expressed in normal urothelium, non-invasive BC and invasive BC tissue. Significant miR-125b down-regulation was associated with a significant increase in Trop-2 protein levels in BC tissue and correlated with disease severity. In vitro analysis confirmed the role of miR-125b in down-modulation of Trop-2 protein levels and showed that Trop-2/miR-125b axis affects cellular proliferation in bladder tissue. In conclusion, our findings highlight a role for the Trop-2/miR-125b axis in BC progression and suggest Trop-2 and miR-125b as diagnostic/prognostic marker candidates as well as druggable targets for innovative therapeutic approaches. PMID:28938585

  9. Mechanisms of respiration intensification of rat pancreatic acini upon carbachol-induced Ca(2+) release.

    PubMed

    Manko, B O; Manko, V V

    2013-08-01

    Acetylcholine as one of the main secretagogues modulates mitochondrial functions in acinar pancreacytes, presumably due to increase in ATP hydrolysis or Ca(2+) transport into mitochondria. The aim of this work was to investigate the mechanisms of carbachol (CCh) action on respiration and oxidative phosphorylation of isolated pancreatic acini. Respiration of intact or permeabilized rat pancreatic acini was studied at 37 °C using a Clark oxygen electrode. Respiration rate of isolated acini in rest was 0.27 ± 0.01 nmol O2 s(-1) 10(-6) cells. Addition of 10 μM CCh into respiration chamber evoked biphasic stimulation of respiration. Rapid increase of respiration by 20.1% lasted for approx. 1 min, followed by decrease to level by 11.5% higher than control. Addition of 1 μm CCh caused monophasic increase by 11.5%. Preincubation (5 min) with 1 or 10 μm CCh elevated respiration rate by 12.5 or 11.2% respectively. FCCP prevented the effect of CCh. Preincubation with 1 (but not 10) μm CCh increased FCCP-uncoupled respiration rate. Thapsigargin slightly elevated respiration, but ryanodine did not. Application of 2-aminoethoxydiphenyl borate or ruthenium red prevented the effects of CCh on respiration, while oligomycin abolished them. Preincubation with 1 μm CCh prior to cell permeabilization increased respiration rate at pyruvate+malate oxidation, but not at succinate oxidation. In contrast, preincubation with 10 μm CCh decreased pyruvate+malate oxidation. Medium CCh dose (1 μm) intensifies respiration and oxidative phosphorylation of acinar pancreacytes by feedforward mechanism via Ca(2+) transport into mitochondria and activation of Ca(2+) /ADP-sensitive mitochondrial dehydrogenases. Prolonged action of high CCh dose (10 μm) might impair mitochondrial functions. © 2013 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  10. Bumetanide hyperpolarizes Madin-Darby canine kidney cells and enhances cellular gentamicin uptake via elevating cytosolic Ca2+ thus facilitating intermediate conductance Ca2+-activated potassium channels

    PubMed Central

    Wang, Tian; Yang, Yu-qin; Karasawa, Takatoshi; Wang, Qi; Phillips, Amanda; Guan, Bing-Cai; Ma, Ke-Tao; Jiang, Meiyan; Xie, Ding-Hua; Steyger, Peter S.; Jiang, Zhi-Gen

    2012-01-01

    Loop diuretics such as bumetanide and furosemide enhance aminoglycoside ototoxicity when co-administered to patients and animal models. The underlying mechanism(s) is poorly understood. We investigated the effect of these diuretics on cellular uptake of aminoglycosides, using Texas Red-tagged gentamicin (GTTR), and intracellular/whole-cell recordings of Madin-Darby Canine kidney (MDCK) cells. We found that bumetanide and furosemide concentration-dependently enhanced cytoplasmic GTTR fluorescence by ~60%. This enhancement was suppressed by La3+, a non-selective cation channel (NSCC) blocker, and by K+ channel blockers Ba2+ and clotrimazole, but not by tetraethylammonium (TEA), 4-aminopyridine (4-AP) or glipizide, nor by Cl− channel blockers diphenylamine-2-carboxylic acid (DPC), niflumic acid (NFA), and CFTRinh-172. Bumetanide and furosemide hyperpolarized MDCK cells by ~14 mV, increased whole-cell I/V slope conductance; the bumetanide-induced net current I/V showed a reversal potential (Vr) ~−80 mV. Bumetanide-induced hyperpolarization and I/V change was suppressed by Ba2+ or clotrimazole, and absent in elevated [Ca2+]i, but not affected by apamin, 4-AP, TEA, glipizide, DPC, NFA or CFTRinh-172. Bumetanide and furosemide stimulated a surge of Fluo-4-indicated cytosolic Ca2+. Ba2+ and clotrimazole alone depolarized cells by ~18 mV and reduced I/V slope with a net current Vr near −85 mV, and reduced GTTR uptake by ~20%. La3+ alone hyperpolarized the cells by ~−14 mV, reduced the I/V slope with a net current Vr near −10 mV, and inhibited GTTR uptake by ~50%. In the presence of La3+, bumetanide caused negligible potential or I/V change. We conclude that NSCCs constitute a major cell entry pathway for cationic aminoglycosides; bumetanide enhances aminoglycoside uptake by hyperpolarizing cells that increases cation influx driving force; and bumetanide-induced hyperpolarization is caused by elevating the intracellular Ca2+ and thus a facilitation of the

  11. Bumetanide hyperpolarizes madin-darby canine kidney cells and enhances cellular gentamicin uptake by elevating cytosolic Ca(2+) thus facilitating intermediate conductance Ca(2+)--activated potassium channels.

    PubMed

    Wang, Tian; Yang, Yu-Qin; Karasawa, Takatoshi; Wang, Qi; Phillips, Amanda; Guan, Bing-Cai; Ma, Ke-Tao; Jiang, Meiyan; Xie, Ding-Hua; Steyger, Peter S; Jiang, Zhi-Gen

    2013-04-01

    Loop diuretics such as bumetanide and furosemide enhance aminoglycoside ototoxicity when co-administered to patients and animal models. The underlying mechanism(s) is poorly understood. We investigated the effect of these diuretics on cellular uptake of aminoglycosides, using Texas Red-tagged gentamicin (GTTR), and intracellular/whole-cell recordings of Madin-Darby canine kidney (MDCK) cells. We found that bumetanide and furosemide dose-dependently enhanced cytoplasmic GTTR fluorescence by ~60 %. This enhancement was suppressed by La(3+), a non-selective cation channel (NSCC) blocker, and by K(+) channel blockers Ba(2+) and clotrimazole, but not by tetraethylammonium (TEA), 4-aminopyridine (4-AP) or glipizide, nor by Cl(-) channel blockers diphenylamine-2-carboxylic acid (DPC), niflumic acid (NFA), and CFTRinh-172. Bumetanide and furosemide hyperpolarized MDCK cells by ~14 mV, increased whole-cell I/V slope conductance; the bumetanide-induced net current I/V showed a reversal potential (V r) ~-80 mV. Bumetanide-induced hyperpolarization and I/V change was suppressed by Ba(2+) or clotrimazole, and absent in elevated [Ca(2+)]i, but was not affected by apamin, 4-AP, TEA, glipizide, DPC, NFA, or CFTRinh-172. Bumetanide and furosemide stimulated a surge of Fluo-4-indicated cytosolic Ca(2+). Ba(2+) and clotrimazole alone depolarized cells by ~18 mV and reduced I/V slope with a net current V r near -85 mV, and reduced GTTR uptake by ~20 %. La(3+) alone hyperpolarized the cells by ~-14 mV, reduced the I/V slope with a net current V r near -10 mV, and inhibited GTTR uptake by ~50 %. In the presence of La(3+), bumetanide-caused negligible change in potential or I/V. We conclude that NSCCs constitute a major cell entry pathway for cationic aminoglycosides; bumetanide enhances aminoglycoside uptake by hyperpolarizing cells that increases the cation influx driving force; and bumetanide-induced hyperpolarization is caused by elevating intracellular Ca(2+) and thus facilitating

  12. Interfering Effect of Black Tea Consumption on Diagnosis of Pancreatic Cancer by CA 19-9.

    PubMed

    Al-Janabi, Ali Abdul Hussein S; Tawfeeq, Ekhlas F

    2017-06-01

    The study aims to determine the possible effects of black tea consumption on the level of CA 19-9 antigen in the human body. The level of CA 19-9 was measured in 270 healthy individuals who consumed heavy amounts of black tea. About 43.3 % of involved individuals were revealed to have elevated levels of CA 19-9. Males with high values of CA 19-9 represented the greatest number of involved individuals. The cutoff value of high levels of CA 19-9 in all individuals was ranged 69-105 U/ml. Consuming heavy amounts of black tea could be considered an important interfering factor that affects the levels of CA 19-9. The cutoff or predictive value of CA 19-9 in heavy-consuming people of black tea was determined.

  13. 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.

  14. 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...

  15. Elevated CO2 enhances biological contributions to elevation change in coastal wetlands by offsetting stressors associated with sea-level rise

    USGS Publications Warehouse

    Cherry, J.A.; McKee, K.L.; Grace, J.B.

    2009-01-01

    1. Sea-level rise, one indirect consequence of increasing atmospheric CO2, poses a major challenge to long-term stability of coastal wetlands. An important question is whether direct effects of elevated CO 2 on the capacity of marsh plants to accrete organic material and to maintain surface elevations outweigh indirect negative effects of stressors associated with sea-level rise (salinity and flooding). 2. In this study, we used a mesocosm approach to examine potential direct and indirect effects of atmospheric CO2 concentration, salinity and flooding on elevation change in a brackish marsh community dominated by a C3 species, Schoenoplectus americanus, and a C4 grass, Spartina patens. This experimental design permitted identification of mechanisms and their role in controlling elevation change, and the development of models that can be tested in the field. 3. To test hypotheses related to CO2 and sea-level rise, we used conventional anova procedures in conjunction with structural equation modelling (SEM). SEM explained 78% of the variability in elevation change and showed the direct, positive effect of S. americanus production on elevation. The SEM indicated that C3 plant response was influenced by interactive effects between CO2 and salinity on plant growth, not a direct CO2 fertilization effect. Elevated CO2 ameliorated negative effects of salinity on S. americanus and enhanced biomass contribution to elevation. 4. The positive relationship between S. americanus production and elevation change can be explained by shoot-base expansion under elevated CO 2 conditions, which led to vertical soil displacement. While the response of this species may differ under other environmental conditions, shoot-base expansion and the general contribution of C3 plant production to elevation change may be an important mechanism contributing to soil expansion and elevation gain in other coastal wetlands. 5. Synthesis. Our results revealed previously unrecognized interactions and

  16. Calreticulin expression in relation to exchangeable Ca(2+) level that changes dynamically during anthesis, progamic phase, and double fertilization in Petunia.

    PubMed

    Lenartowski, Robert; Suwińska, Anna; Lenartowska, Marta

    2015-01-01

    Calcium (Ca(2+)) plays essential roles in plant sexual reproduction, but the sites and the mechanism of Ca(2+) mobile storage during pollen-pistil interactions have not been fully defined. Because the Ca(2+)-buffering protein calreticulin (CRT) is able to bind and sequester Ca(2+), it can serve as a mobile intracellular store of easily releasable Ca(2+) and control its local concentration within the cytoplasm. Our previous studies showed an enhanced expression of Petunia hybrida CRT gene (PhCRT) during pistil transmitting tract maturation, pollen germination and tube outgrowth on the stigma, gamete fusion, and early embryogenesis. Here, we demonstrate that elevated expression of CRT results in the accumulation of this protein in response to anthesis, pollination, sperm cells deposition within the receptive synergid and fertilization, when the level of exchangeable Ca(2+) changes dynamically. CRT localizes mainly to the endoplasmic reticulum and Golgi compartments in the pistil transmitting tract cells, germinated pollen/tubes, and sporophytic/gametophytic cells of the ovule and corresponds with loosely bound Ca(2+). Additionally, the immunogold research shows, for the first time, highly selective CRT distribution in specific nuclear sub-domains. On the basis of our results, we discuss the possible functions of CRT with respect to the critical role of Ca(2+) homeostasis during key events of the multi-step process of generative reproduction in angiosperms.

  17. Sea level and turbidity controls on mangrove soil surface elevation change

    USGS Publications Warehouse

    Lovelock, Catherine E.; Fernanda Adame, Maria; Bennion, Vicki; Hayes, Matthew; Reef, Ruth; Santini, Nadia; Cahoon, Donald R.

    2015-01-01

    Increases in sea level are a threat to seaward fringing mangrove forests if levels of inundation exceed the physiological tolerance of the trees; however, tidal wetlands can keep pace with sea level rise if soil surface elevations can increase at the same pace as sea level rise. Sediment accretion on the soil surface and belowground production of roots are proposed to increase with increasing sea level, enabling intertidal habitats to maintain their position relative to mean sea level, but there are few tests of these predictions in mangrove forests. Here we used variation in sea level and the availability of sediments caused by seasonal and inter-annual variation in the intensity of La Nina-El Nino to assess the effects of increasing sea level on surface elevation gains and contributing processes (accretion on the surface, subsidence and root growth) in mangrove forests. We found that soil surface elevation increased with mean sea level (which varied over 250 mm during the study) and with turbidity at sites where fine sediment in the water column is abundant. In contrast, where sediments were sandy, rates of surface elevation gain were high, but not significantly related to variation in turbidity, and were likely to be influenced by other factors that deliver sand to the mangrove forest. Root growth was not linked to soil surface elevation gains, although it was associated with reduced shallow subsidence, and therefore may contribute to the capacity of mangroves to keep pace with sea level rise. Our results indicate both surface (sedimentation) and subsurface (root growth) processes can influence mangrove capacity to keep pace with sea level rise within the same geographic location, and that current models of tidal marsh responses to sea level rise capture the major feature of the response of mangroves where fine, but not coarse, sediments are abundant.

  18. 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.

  19. 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

  20. 7. ENTRANCE VIEW OF ELEVATOR SHAFT AT GROUND LEVEL. VIEW ...

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

    7. ENTRANCE VIEW OF ELEVATOR SHAFT AT GROUND LEVEL. VIEW SHOWS VERTICAL LADDER AND CAGE ALONG ELEVATOR SHAFT. - U.S. Naval Base, Pearl Harbor, Signal Tower, Corner of Seventh Street & Avenue D east of Drydock No. 1, Pearl City, Honolulu County, HI

  1. Mastoparan-Induced Intracellular Ca2+ Fluxes May Regulate Cell-to-Cell Communication in Plants.

    PubMed

    Tucker, E. B.; Boss, W. F.

    1996-06-01

    The relationship of Ca2+ and plasmodesmatal closure was examined in staminal hairs of Setcreasea purpurea by microinjecting cells with active mastoparan (Mas-7), inactive mastoparan (Mas-17), active inositol-1,4,5-trisphosphate (IP3), or inactive IP3. Calcium green dextran 10,000 was used to study cellular free Ca2+, and carboxyfluorescein was used to monitor plasmodesmatal closure. When Mas-7 was microinjected into the cytoplasm of cell 1 (the tip cell of a chain of cells), a rapid increase in calcium green dextran-10,000 fluorescence was observed in the cytoplasmic areas on both sides of the plasmodesmata connecting cells 1 and 2 during the same time that the diffusion of carboxyfluorescein through them was blocked. The inhibition of cell-to-cell diffusion was transient, and the closed plasmodesmata reopened within 30 s. The elevated Ca2+ level near plasmodesmata was also transient and returned to base level in about 1.5 min. The transient increase in Ca2+, once initiated in cell 1, repeated with an oscillatory period of 3 min. Elevated Ca2+ and oscillations of Ca2+ were also observed near interconnecting cell walls throughout the chain of cells, indicating that the signal had been transmitted. Previously, we reported that IP3 closed plasmodesmata; now we report that it stimulated Ca2+ and oscillations similar to Mas-7. The effect was specific for similar concentrations of Mas-7 over Mas-17 and active IP3 over inactive IP3. It is important that the Ca2+ channel blocker La3+ eliminated the responses from Mas-7 and IP3, indicating that an influx of Ca2+ was required. These results support the contention that plasmodesmata functioning is regulated via Ca2+ and that IP3 may be an intermediary between the stimulus and Ca2+ elevations.

  2. Mastoparan-Induced Intracellular Ca2+ Fluxes May Regulate Cell-to-Cell Communication in Plants.

    PubMed Central

    Tucker, E. B.; Boss, W. F.

    1996-01-01

    The relationship of Ca2+ and plasmodesmatal closure was examined in staminal hairs of Setcreasea purpurea by microinjecting cells with active mastoparan (Mas-7), inactive mastoparan (Mas-17), active inositol-1,4,5-trisphosphate (IP3), or inactive IP3. Calcium green dextran 10,000 was used to study cellular free Ca2+, and carboxyfluorescein was used to monitor plasmodesmatal closure. When Mas-7 was microinjected into the cytoplasm of cell 1 (the tip cell of a chain of cells), a rapid increase in calcium green dextran-10,000 fluorescence was observed in the cytoplasmic areas on both sides of the plasmodesmata connecting cells 1 and 2 during the same time that the diffusion of carboxyfluorescein through them was blocked. The inhibition of cell-to-cell diffusion was transient, and the closed plasmodesmata reopened within 30 s. The elevated Ca2+ level near plasmodesmata was also transient and returned to base level in about 1.5 min. The transient increase in Ca2+, once initiated in cell 1, repeated with an oscillatory period of 3 min. Elevated Ca2+ and oscillations of Ca2+ were also observed near interconnecting cell walls throughout the chain of cells, indicating that the signal had been transmitted. Previously, we reported that IP3 closed plasmodesmata; now we report that it stimulated Ca2+ and oscillations similar to Mas-7. The effect was specific for similar concentrations of Mas-7 over Mas-17 and active IP3 over inactive IP3. It is important that the Ca2+ channel blocker La3+ eliminated the responses from Mas-7 and IP3, indicating that an influx of Ca2+ was required. These results support the contention that plasmodesmata functioning is regulated via Ca2+ and that IP3 may be an intermediary between the stimulus and Ca2+ elevations. PMID:12226302

  3. Correction of the mineralization defect in hyp mice treated with protease inhibitors CA074 and pepstatin

    PubMed Central

    Rowe, Peter S.N.; Matsumoto, Naoko; Jo, Oak D.; Shih, Remi N.J.; Oconnor, Jeannine; Roudier, Martine P.; Bain, Steve; Liu, Shiguang; Harrison, Jody; Yanagawa, Norimoto

    2012-01-01

    Increased expression of several osteoblastic proteases and MEPE (a bone matrix protein) occurs in X-linked hypophosphatemic rickets (hyp). This is associated with an increased release of a protease-resistant MEPE peptide (ASARM peptide), a potent inhibitor of mineralization. Cathepsin B cleaves MEPE releasing ASARM peptide and hyp osteoblast/osteocyte cells hypersecrete cathepsin D, an activator of cathepsin B. Our aims were to determine whether cathepsin inhibitors correct the mineralization defect in vivo and whether hyp-bone ASARM peptide levels are reduced after protease treatment. Normal littermates and hyp mice (n = 6) were injected intraperitoneally once a day for 4 weeks with pepstatin, CAO74 or vehicle. Animals were then sacrificed and bones plus serum removed for comprehensive analysis. All hyp mice groups (treated and untreated) remained hypophosphatemic with serum 1,25 vitamin D3 inappropriately normal. Serum PTH was significantly elevated in all hyp mice groups relative to normal mice (P = 0.0017). Untreated hyp mice had six-fold elevated levels of serum alkaline-phosphatase and two-fold elevated levels of ASARM peptides relative to normal mice (P < 0.001). In contrast, serum alkaline phosphatase and serum ASARM peptides were significantly reduced (normalized) in hyp mice treated with CA074 or pepstatin. Serum FGF23 levels remained high in all hyp animal groups (P < 0.0001). Hyp mice treated with protease inhibitors showed dramatic reductions in unmineralized osteoid (femurs) compared to control hyp mice (Goldner staining). Also, hyp animals treated with protease inhibitors showed marked and significant improvements in growth plate width (42%), osteoid thickness (40%) and cortical area (40%) (P < 0.002). The mineralization apposition rate, bone formation rate and mineralization surface were normalized by protease-treatment. High-resolution pQCT mineral histomorphometry measurements and uCT also confirmed a marked mineralization improvement. Finally

  4. Contribution of elevated intracellular calcium to pulmonary arterial myocyte alkalinization during chronic hypoxia

    PubMed Central

    Luke, Trevor; Shimoda, Larissa A.

    2016-01-01

    Abstract In the lung, exposure to chronic hypoxia (CH) causes pulmonary hypertension, a debilitating disease. Development of this condition arises from increased muscularity and contraction of pulmonary vessels, associated with increases in pulmonary arterial smooth muscle cell (PASMC) intracellular pH (pHi) and Ca2+ concentration ([Ca2+]i). In this study, we explored the interaction between pHi and [Ca2+]i in PASMCs from rats exposed to normoxia or CH (3 weeks, 10% O2). PASMC pHi and [Ca2+]i were measured with fluorescent microscopy and the dyes BCECF and Fura-2. Both pHi and [Ca2+]i levels were elevated in PASMCs from hypoxic rats. Exposure to KCl increased [Ca2+]i and pHi to a similar extent in normoxic and hypoxic PASMCs. Conversely, removal of extracellular Ca2+ or blockade of Ca2+ entry with NiCl2 or SKF 96365 decreased [Ca2+]i and pHi only in hypoxic cells. Neither increasing pHi with NH4Cl nor decreasing pHi by removal of bicarbonate impacted PASMC [Ca2+]i. We also examined the roles of Na+/Ca2+ exchange (NCX) and Na+/H+ exchange (NHE) in mediating the elevated basal [Ca2+]i and Ca2+-dependent changes in PASMC pHi. Bepridil, dichlorobenzamil, and KB-R7943, which are NCX inhibitors, decreased resting [Ca2+]i and pHi only in hypoxic PASMCs and blocked the changes in pHi induced by altering [Ca2+]i. Exposure to ethyl isopropyl amiloride, an NHE inhibitor, decreased resting pHi and prevented changes in pHi due to changing [Ca2+]i. Our findings indicate that, during CH, the elevation in basal [Ca2+]i may contribute to the alkaline shift in pHi in PASMCs, likely via mechanisms involving reverse-mode NCX and NHE. PMID:27076907

  5. 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

  6. 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.

  7. Plants with elevated levels of glucan

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

    Pauly, Markus; Kraemer, Florian J.; Hake, Sarah

    The present disclosure relates to mutations in licheninase genes encoding polypeptides with decreased licheninase activity, which when expressed in plants results in elevated levels of glucan in the plants. In particular, the disclosure relates to licheninase nucleic acids and polypeptides related to glucan accumulation in plants, plants with reduced expression of a licheninase nucleic acid, and methods related to the generation of plants with increased glucan content in the cell walls of leaf tissue.

  8. Bax regulates neuronal Ca2+ homeostasis.

    PubMed

    D'Orsi, Beatrice; Kilbride, Seán M; Chen, Gang; Perez Alvarez, Sergio; Bonner, Helena P; Pfeiffer, Shona; Plesnila, Nikolaus; Engel, Tobias; Henshall, David C; Düssmann, Heiko; Prehn, Jochen H M

    2015-01-28

    Excessive Ca(2+) entry during glutamate receptor overactivation ("excitotoxicity") induces acute or delayed neuronal death. We report here that deficiency in bax exerted broad neuroprotection against excitotoxic injury and oxygen/glucose deprivation in mouse neocortical neuron cultures and reduced infarct size, necrotic injury, and cerebral edema formation after middle cerebral artery occlusion in mice. Neuronal Ca(2+) and mitochondrial membrane potential (Δψm) analysis during excitotoxic injury revealed that bax-deficient neurons showed significantly reduced Ca(2+) transients during the NMDA excitation period and did not exhibit the deregulation of Δψm that was observed in their wild-type (WT) counterparts. Reintroduction of bax or a bax mutant incapable of proapoptotic oligomerization equally restored neuronal Ca(2+) dynamics during NMDA excitation, suggesting that Bax controlled Ca(2+) signaling independently of its role in apoptosis execution. Quantitative confocal imaging of intracellular ATP or mitochondrial Ca(2+) levels using FRET-based sensors indicated that the effects of bax deficiency on Ca(2+) handling were not due to enhanced cellular bioenergetics or increased Ca(2+) uptake into mitochondria. We also observed that mitochondria isolated from WT or bax-deficient cells similarly underwent Ca(2+)-induced permeability transition. However, when Ca(2+) uptake into the sarco/endoplasmic reticulum was blocked with the Ca(2+)-ATPase inhibitor thapsigargin, bax-deficient neurons showed strongly elevated cytosolic Ca(2+) levels during NMDA excitation, suggesting that the ability of Bax to support dynamic ER Ca(2+) handling is critical for cell death signaling during periods of neuronal overexcitation. Copyright © 2015 the authors 0270-6474/15/351706-17$15.00/0.

  9. 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

  10. Inhibition of muscarinic-stimulated polyphosphoinositide hydrolysis and Ca2+ mobilization in cat iris sphincter smooth muscle cells by cAMP-elevating agents.

    PubMed

    Ding, K H; Husain, S; Akhtar, R A; Isales, C M; Abdel-Latif, A A

    1997-09-01

    The effects of carbachol (CCh) on inositol 1,4,5-trisphosphate (IP3) production and intracellular calcium ([Ca2+]i) mobilization, and their regulation by cAMP-elevating agents were investigated in SV-40 transformed cat iris sphincter smooth muscle (SV-CISM-2) cells. CCh produced time- and dose-dependent increases in IP3 production; the t1/2 and EC50 values were 68 s and 0.5 microM, respectively. The muscarinic agonist provoked a transient increase in [Ca2+]i which reached maximum within 77 s, and increased [Ca2+]i mobilization in a concentration-dependent manner with an EC50 of 1.4 microM. Thapsigargin, a Ca(2+)-pump inhibitor, caused a rapid rise in [Ca2+]i and subsequent addition of CCh was without effect. Both CCh-induced IP3 production and CCh-induced [Ca2+]i mobilization were more potently antagonized by 4-DAMP, an M3 muscarinic receptor antagonist, than by pirenzepine, an M1 receptor antagonist, suggesting that both responses are mediated through the M3 receptor subtype. Treatment of the cells with U73122, a phospholipase C (PLC) inhibitor, resulted in a concentration-dependent decrease in both CCh-stimulated IP3 production and [Ca2+]i mobilization. These data indicate close correlation between enhanced IP3 production and [Ca2+]i mobilization in these smooth muscle cells and suggest that the CCh-stimulated increase in [Ca2+]i could be mediated through increased IP3 production. Isoproterenol (ISO) inhibited CCh-induced IP3 production (IC50 = 80 nM) and [Ca2+]i mobilization (IC50 = 0.17 microM) in a concentration-dependent manner. Microsomal fractions isolated from SV-CISM-2 cells contained phospholipase C (PLC) which was stimulated by CCh (10 microM) and GTP gamma S (0.1 microM). Pretreatment of the cells with ISO or forskolin, 5 microM each, produced membrane fractions in which CCh-stimulated PLC activity was significantly attenuated. Furthermore, when microsomal fractions isolated from SV-CISM-2 cells were phosphorylated with Protein kinase A (PKA), the CCh

  11. Intravital Förster resonance energy transfer imaging reveals elevated [Ca2+]i and enhanced sympathetic tone in femoral arteries of angiotensin II-infused hypertensive biosensor mice

    PubMed Central

    Wang, Youhua; Chen, Ling; Wier, W Gil; Zhang, Jin

    2013-01-01

    Artery narrowing in hypertension can only result from structural remodelling of the artery, or increased smooth muscle contraction. The latter may occur with, or without, increases in [Ca2+]i. Here, we sought to measure, in living hypertensive mice, possible changes in artery dimensions and/or [Ca2+]i, and to determine some of the mechanisms involved. Ca2+/calmodulin biosensor (Förster resonance energy transfer-based) mice were made hypertensive by s.c. infusion of angiotensin II (Ang II, 400 ng kg−1 min−1, 2–3 weeks). Intravital fluorescence microscopy was used to determine [Ca2+]i and outer diameter of surgically exposed, intact femoral artery (FA) of anaesthetized mice. Active contractile FA ‘tone’ was calculated from the basal-state diameter and the passive (i.e. Ca2+-free) diameter (PD). Compared to saline control, FAs of Ang II-infused mice had (1) ∼21% higher active tone and (2) ∼78 nm higher smooth muscle [Ca2+]i, but (3) the same PDs. The local Ang II receptor (AT1R) blocker losartan had negligible effect on tone or [Ca2+]i in control FAs, but reduced the basal tone by ∼9% in Ang II FAs. Both i.v. hexamethonium and locally applied prazosin abolished the difference in FA tone and [Ca2+]i, suggesting a dominant role of sympathetic nerve activity (SNA). Changes in diameter and [Ca2+]i in response to locally applied phenylephrine, Ang II, arginine vasopressin, elevated [K+]o and acetylcholine were not altered. In summary, FAs of living Ang II hypertensive mice have higher [Ca2+]i, and are more constricted, due, primarily, to elevated SNA and some increased arterial AT1R activation. Evidence of altered artery reactivity or remodeling was not found. PMID:23981717

  12. Intravital Förster resonance energy transfer imaging reveals elevated [Ca2+]i and enhanced sympathetic tone in femoral arteries of angiotensin II-infused hypertensive biosensor mice.

    PubMed

    Wang, Youhua; Chen, Ling; Wier, W Gil; Zhang, Jin

    2013-11-01

    Artery narrowing in hypertension can only result from structural remodelling of the artery, or increased smooth muscle contraction. The latter may occur with, or without, increases in [Ca(2+)]i. Here, we sought to measure, in living hypertensive mice, possible changes in artery dimensions and/or [Ca(2+)]i, and to determine some of the mechanisms involved. Ca(2+)/calmodulin biosensor (Förster resonance energy transfer-based) mice were made hypertensive by s.c. infusion of angiotensin II (Ang II, 400 ng kg(-1) min(-1), 2-3 weeks). Intravital fluorescence microscopy was used to determine [Ca(2+)]i and outer diameter of surgically exposed, intact femoral artery (FA) of anaesthetized mice. Active contractile FA 'tone' was calculated from the basal-state diameter and the passive (i.e. Ca(2+)-free) diameter (PD). Compared to saline control, FAs of Ang II-infused mice had (1) ∼21% higher active tone and (2) ∼78 nm higher smooth muscle [Ca(2+)]i, but (3) the same PDs. The local Ang II receptor (AT1R) blocker losartan had negligible effect on tone or [Ca(2+)]i in control FAs, but reduced the basal tone by ∼9% in Ang II FAs. Both i.v. hexamethonium and locally applied prazosin abolished the difference in FA tone and [Ca(2+)]i, suggesting a dominant role of sympathetic nerve activity (SNA). Changes in diameter and [Ca(2+)]i in response to locally applied phenylephrine, Ang II, arginine vasopressin, elevated [K(+)]o and acetylcholine were not altered. In summary, FAs of living Ang II hypertensive mice have higher [Ca(2+)]i, and are more constricted, due, primarily, to elevated SNA and some increased arterial AT1R activation. Evidence of altered artery reactivity or remodeling was not found.

  13. [The effects of methionine and choline on the expression levels of CaMKII and CREB mRNA and proteins in rats exposed to lead].

    PubMed

    Feng, Chang; Fan, Guang-qin; Wu, Feng-yun; Lin, Fen; Li, Yan-shu; Chen, Ying

    2012-07-01

    To study the effects of methionine and choline on the expression levels of CaMKII and CREB mRNA and proteins in hippocampus of rats exposed to lead. Male SD rats were divided into five groups. (1) control group, (2) group exposed to lead+2 by drinking water with 0.40 g/L lead acetate, (3) group exposed to methionine and choline (1:1, 400 mg/kg), (4) group exposed to 0.40 g/L lead acetate plus methionine and choline (1:1, 100 mg/kg), (5) group exposed to 0.40 g/L lead acetate plus methionine and choline (1:1, 400 mg/kg). In 8 weeks after exposure, all rats were killed. Then CREB mRNA and CaMK II mRNA expression levels in hippocampus were detected by real-time PCR, CREB and CaMK II protein expression levels in hippocampus were measured by western blot assay. The expression levels (0.743 ± 0.185 and 0.729 ± 0.199) of CaMKII mRNA and CREB mRNA in the hippocampus of lead group were significantly lower than those (0.950 ± 0.238 and 0.901 ± 0.232) of control group (P < 0.05), also the expression levels (0.271 ± 0.045 and 0.212 ± 0.058) of CREB protein and pCREB protein in the hippocampus of lead group were significantly lower than those (0.319 ± 0.058 and 0.506 ± 0.125) of control group (P < 0.05). The expression levels (1.014 ± 0.210 and 1.126 ± 0.379) of CaMKII mRNA and the expression levels (1.029 ± 0.335 and 0.932 ± 0.251) of CREB mRNA in the hippocampus of 2 groups exposed to lead acetate plus methionine and choline were significantly higher than those of lead group (P < 0.05). The expression levels (0.407 ± 0.951 and 0.563 ± 0.178) of CREB protein and pCREB protein in the hippocampus of group exposed to lead acetate plus 400 mg/kg methionine and choline were significantly higher than those of lead group (P < 0.05). Methionine and choline could decrease the inhibition effects of lead on the expression of CaMKII and CREB mRNA or CREB and pCREB proteins in the hippocampus of rats.

  14. 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

  15. High prevalence of elevated blood lead levels in both rural and urban Iowa newborns: Spatial patterns and area-level covariates

    PubMed Central

    Zahrieh, David; Young, Sean G.; Oleson, Jacob; Ryckman, Kelli K.; Wels, Brian; Simmons, Donald L.; Saftlas, Audrey

    2017-01-01

    Lead in maternal blood can cross the placenta and result in elevated blood lead levels in newborns, potentially producing negative effects on neurocognitive function, particularly if combined with childhood lead exposure. Little research exists, however, into the burden of elevated blood lead levels in newborns, or the places and populations in which elevated lead levels are observed in newborns, particularly in rural settings. Using ~2300 dried bloods spots collected within 1–3 days of birth among Iowa newborns, linked with the area of mother’s residence at the time of birth, we examine the spatial patterns of elevated (>5 μg/dL) blood lead levels and the ecological-level predictors of elevated blood lead levels. We find that one in five newborns exceed the 5 μg/dL action level set by the US Centers for Disease Control & Prevention (CDC). Bayesian spatial zero inflated regression indicates that elevated blood lead in newborns is associated with areas of increased pre-1940s housing and childbearing-age women with low educational status in both rural and urban settings. No differences in blood lead levels or the proportion of children exceeding 5 μg/dL are observed between urban and rural maternal residence, though a spatial cluster of elevated blood lead is observed in rural counties. These characteristics can guide the recommendation for testing of infants at well-baby appointments in places where risk factors are present, potentially leading to earlier initiation of case management. The findings also suggest that rural populations are at as great of risk of elevated blood lead levels as are urban populations. Analysis of newborn dried blood spots is an important tool for lead poisoning surveillance in newborns and can direct public health efforts towards specific places and populations where lead testing and case management will have the greatest impact. PMID:28520816

  16. Systems Modeling of Ca2+ Homeostasis and Mobilization in Platelets Mediated by IP3 and Store-Operated Ca2+ Entry

    PubMed Central

    Dolan, Andrew T.; Diamond, Scott L.

    2014-01-01

    Resting platelets maintain a stable level of low cytoplasmic calcium ([Ca2+]cyt) and high dense tubular system calcium ([Ca2+]dts). During thrombosis, activators cause a transient rise in inositol trisphosphate (IP3) to trigger calcium mobilization from stores and elevation of [Ca2+]cyt. Another major source of [Ca2+]cyt elevation is store-operated calcium entry (SOCE) through plasmalemmal calcium channels that open in response to store depletion as [Ca2+]dts drops. A 34-species systems model employed kinetics describing IP3-receptor, DTS-plasmalemma puncta formation, SOCE via assembly of STIM1 and Orai1, and the plasmalemma and sarco/endoplasmic reticulum Ca2+-ATPases. Four constraints were imposed: calcium homeostasis before activation; stable in zero extracellular calcium; IP3-activatable; and functional SOCE. Using a Monte Carlo method to sample three unknown parameters and nine initial concentrations in a 12-dimensional space near measured or expected values, we found that model configurations that were responsive to stimuli and demonstrated significant SOCE required high inner membrane electric potential (>−70 mV) and low resting IP3 concentrations. The absence of puncta in resting cells was required to prevent spontaneous store depletion in calcium-free media. Ten-fold increases in IP3 caused saturated calcium mobilization. This systems model represents a critical step in being able to predict platelets’ phenotypes during hemostasis or thrombosis. PMID:24806937

  17. NO and H2O2 contribute to SO2 toxicity via Ca2+ signaling in Vicia faba guard cells.

    PubMed

    Yi, Min; Bai, Heli; Xue, Meizhao; Yi, Huilan

    2017-04-01

    NO and H 2 O 2 have been implicated as important signals in biotic and abiotic stress responses of plants to the environment. Previously, we have shown that SO 2 exposure increased the levels of NO and H 2 O 2 in plant cells. We hypothesize that, as signaling molecules, NO and H 2 O 2 mediate SO 2 -caused toxicity. In this paper, we show that SO 2 hydrates caused guard cell death in a concentration-dependent manner in the concentration range of 0.25 to 6 mmol L -1 , which was associated with elevation of intracellular NO, H 2 O 2 , and Ca 2+ levels in Vicia faba guard cells. NO donor SNP enhanced SO 2 toxicity, while NO scavenger c-PTIO and NO synthesis inhibitors L-NAME and tungstate significantly prevented SO 2 toxicity. ROS scavenger ascorbic acid (AsA) and catalase (CAT), Ca 2+ chelating agent EGTA, and Ca 2+ channel inhibitor LaCl 3 also markedly blocked SO 2 toxicity. In addition, both c-PTIO and AsA could completely block SO 2 -induced elevation of intracellular Ca 2+ level. Moreover, c-PTIO efficiently blocked SO 2 -induced H 2 O 2 elevation, and AsA significantly blocked SO 2 -induced NO elevation. These results indicate that extra NO and H 2 O 2 are produced and accumulated in SO 2 -treated guard cells, which further activate Ca 2+ signaling to mediate SO 2 toxicity. Our findings suggest that both NO and H 2 O 2 contribute to SO 2 toxicity via Ca 2+ signaling.

  18. 4th level of 1913 elevator indicating sacking scale, part of ...

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

    4th level of 1913 elevator indicating sacking scale, part of the bagging system and nate to the sewing machine. Discharge spout for the grain bin to the left - Stewart Company Grain Elevator, 16 West Carson Street, Pittsburgh, Allegheny County, PA

  19. [Usefulness of preoperative assay CEA and CA 19-9 in colorectal cancer patients].

    PubMed

    Grotowski, M; Maruszyński, M; Piechota, W

    2001-12-01

    Carcinoembryonic antigen (CEA) and carbohydrate antigen (CA19-9) are well known tumor markers expressed by colorectal cancer (CRC), particularly in advanced cases. In this study serological expression of CEA and CA19-9 concerning different clinicopathological factors and sensitivity of diagnosis of CRC by combination of both markers were evaluated. Eighty one patients with diagnosed CRC were in this study included. According to Dukes' classification there were 11 in stage A, 34 in stage B, 17 in stage C and 19 in stage D. Blood samples were collected before operation. CEA and CA19-9 were determined by MEIA (normal range 0-3 ng/ml for CEA and 0-37 U/ml for CA19-9). The statistical analysis revealed that the CEA well correlated with histological type, liver metastasis and term of symptoms. The CA19-9 well correlated with liver metastasis, peritoneal dissemination, nodal involvement and cancer localization. The levels of CEA and CA19-9 increased with stage of the tumor, but only in stage D the difference was statistically significant (for CEA p = 0.005, for CA19-9 p = 0.039). At time of diagnosis 50.6% of the patients had elevated serum levels of CEA and 29.6% of CA19-9. In combination of both antigens this elevation was in 54.3% of CRC patients. The common use of CEA and CA19-9 was more efficacious in identification of patients at high risk. The combination assay of CEA and CA19-9 did not cause a significant increase of sensitivity in diagnosis CRC.

  20. 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

  1. Decreased fractional urinary calcium excretion and serum 1,25-dihydroxyvitamin D and IGF-I levels in preeclampsia.

    PubMed

    Halhali, Ali; Díaz, Lorenza; Avila, Euclides; Ariza, Ana Carolina; Garabédian, Michèle; Larrea, Fernando

    2007-03-01

    During preeclampsia several alterations of calcium metabolism have been described, the most common of them is hypocalciuria, which pathophysiology is still unclear. In order to assess the contribution of calciotropic hormones to urinary calcium excretion, a cross-sectional study was done including 26 preeclamptic Mexican women (PE group) and 26 normotensive control pregnant women (NT group). Total and fractional urinary calcium excretion were significantly lower (P<0.0001) in the PE group than in the NT group (82+/-7 versus 171+/-7 mg/24h and 0.62+/-0.38 versus 1.38+/-0.71%, respectively), without significant differences in creatinine clearance, urinary sodium excretion and phosphate tubular reabsorption. In addition, serum 1,25-(OH)(2)D and IGF-I levels were significantly (P<0.05) lower in the PE than in NT group (43+/-9 versus 50+/-9 pg/mL and 195+/-67 versus 293+/-105 ng/mL, respectively), without significant differences in serum PTH levels. In the NT group, association analysis showed that total and fractional urinary calcium excretions positively correlated with serum levels of 1,25-(OH)(2)D (P<0.01) and IGF-I (P<0.001). In the PE group, total urinary calcium excretion positively correlated only with serum 1,25-(OH)(2)D (P<0.05). In conclusion, the results obtained in this study confirm that PE is associated with hypocalciuria and suggest that 1,25-(OH)(2)D and/or IGF-I may be involved in the regulation of urinary calcium excretion.

  2. 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.

  3. Serum levels of endothelial and neural cell adhesion molecules in prostate cancer.

    PubMed

    Lynch, D F; Hassen, W; Clements, M A; Schellhammer, P F; Wright, G L

    1997-08-01

    Tumorigenesis and progression to metastatic disease are accompanied by changes in the expression of cell adhesion molecules (CAMs). Normally expressed CAMs, such as E-cadherin, are lost, while others, i.e., ICAM-1, VCAM-1, NCAM, and E-selectin, are altered and overexpressed in progressive disease and metastases. Abnormal levels of these latter CAMs have been observed in melanoma and carcinomas of the colon and breast, and NCAM is overexpressed in small-cell lung carcinoma (SCLC). The objective of this study was to determine if serum levels of ICAM-1, VCAM-1, NCAM, and E-selectin could differentiate patients with benign prostate hypertrophy (BPH) from those with prostate carcinoma (CaP) and identify prostate cancers with high potential for progression to metastatic disease. Serum levels of these CAMs were determined by ELISA in serum from normal males and females and from patients with BPH and CaP before and after treatment. Sera from patients with breast carcinoma, colon carcinoma, melanoma, and small-cell lung carcinoma were also evaluated, as soluble CAMs have been reported to be elevated in these cancer patients. ICAM-1 levels were elevated in sera from patients with breast carcinoma (P = 0.0004) and melanoma (P = 0.0001). VCAM-1 levels were elevated in sera from patients with colon carcinoma (P = 0.0001). NCAM levels were elevated in the sera of patients with SCLC (P = 0.0001). Normal levels of ICAM-1, E-selectin, and NCAM were found in both BPH and pretreatment CaP patients. Median NCAM levels in hormone-refractive CaP patients were significantly greater than in BPH (P = 0.0005) and CaP patients with pathologically determined organ-confined (P = 0.0014) or nonorgan-confined disease (P = 0.0385). VCAM-1 levels were significantly elevated in both BPH patients (P = 0.0002) and CaP patients (P = 0.0002) when compared with levels for normal age-matched donors. None of the CAMs were found to offer an advantage over prostatic-specific antigen (PSA) for monitoring Ca

  4. 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.

  5. 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

  6. Front Elevation and Floor Plan in 1893, 1894, and 1909; ...

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

    Front Elevation and Floor Plan in 1893, 1894, and 1909; Office End Elevation, Waiting End Elevation, Section A (1894), Section B (1894), Signage (ca. 1908-1911), Map of Rail Lines & Depots on Soldiers' Home - National Home for Disabled Volunteer Soldiers, Pacific Branch, Streetcar Depot, Corner of Pershing & Dewey Avenues, Los Angeles, Los Angeles County, CA

  7. Somatostatin promotes glucose generation of Ca2+oscillations in pancreatic islets both in the absence and presence of tolbutamide.

    PubMed

    Hellman, Bo; Dansk, Heléne; Grapengiesser, Eva

    2018-06-01

    Many cellular processes, including pulsatile release of insulin, are triggered by increase of cytoplasmic Ca 2+ . This study examines how somatostatin affects glucose generation of cytoplasmic Ca 2+ oscillations in mouse islets in absence and presence of tolbutamide blockade of the K ATP channels. Ca 2+ was measured with dual wavelength microflurometry in isolated islets loaded with the indicator Fura-2. Rise of glucose from 3 to 20 mM evoked introductory lowering of Ca 2+ prolonged by activation of somatostatin receptors. During continued superfusion exposure to somatostatin triggered oscillations mediated by periodic increase from the basal level (absence of tolbutamide) or by periodic interruption of an elevated level (presence of tolbutamide). In the latter situation the oscillations were transformed into sustained elevation by activation of muscarinic receptors (acetylcholine) or increase of cyclic AMP (IBMX, 8-bromo-cyclic AMP, forskolin). The observed effect of cyclic AMP raises the question whether high proportions of the glucagon-producing α-cells promote steady-state elevation of Ca 2+ . In support for this idea somatostatin was found to trigger glucose-induced Ca 2+ oscillations essentially in small islets that contain very few α-cells. The results indicate that somatostatin promotes glucose generation of Ca 2+ oscillations with similar characteristics both in the absence and presence of functional K ATP channels. Copyright © 2018. Published by Elsevier Ltd.

  8. Uric Acid Level and Elevated Blood Pressure in U.S. Adolescents

    PubMed Central

    Loeffler, Lauren F.; Navas-Acien, Ana; Brady, Tammy M.; Miller, Edgar R.; Fadrowski, Jeffrey J.

    2012-01-01

    Uric acid is associated with cardiovascular disease (CVD) and CVD risk factors in adults, including chronic kidney disease, coronary artery disease, stroke, diabetes, preeclampsia, and hypertension. We examined the association between uric acid and elevated blood pressure in a large, nationally representative cohort of U.S. adolescents, a population with a relatively low prevalence of CVD and CVD risk factors. Among 6,036 adolescents 12-17 years of age examined in the 1999-2006 National Health and Nutrition Examination Survey (NHANES) the mean age was 14.5 years, 17% were obese (body mass index [BMI] ≥95th percentile), and 3.3% had elevated blood pressure. Mean serum uric acid level was 5.0 mg/dL and 34% had a uric acid level ≥5.5 mg/dL. In analyses adjusted for age, sex, race/ethnicity and BMI percentile, the odds ratio of elevated blood pressure, defined as a systolic or diastolic blood pressure ≥95th percentile for age, sex and height, for each 0.1 mg/dL increase in uric acid level was 1.38 (95% confidence interval [CI], 1.16 to 1.65). Compared to <5.5 mg/dL, participants with a uric acid level ≥5.5 mg/dL had a 2.03 times higher odds of having elevated blood pressure (95% CI, 1.38 to 3.00). In conclusion, increasing levels of serum uric acid are associated with elevated blood pressure in healthy U.S. adolescents. Additional prospective studies and clinical trials are needed to determine if uric acid is merely a marker in a complex metabolic pathway, or causal of hypertension and thus a potential screening and therapeutic target. PMID:22353609

  9. Treating elevated cholesterol levels: the great Satan in perspective.

    PubMed

    Gibaldi, M; Kradjan, W

    1996-03-01

    The purpose of this review is to provide perspective on the developments leading to the recognition of high cholesterol levels as a risk factor for coronary heart disease (CHD). Another objective is to consider the unfolding controversies regarding the relative value of cholesterol-lowering drug therapy in primary and secondary prevention. Should physicians use lipid-lowering drugs to treat patients with elevated cholesterol levels but no clinical evidence of coronary disease, or limit intervention to patients with a previous history of angina, coronary angioplasty, coronary artery bypass surgery, or myocardial infarction? This review finds inadequate data to support a recommendation for screening large populations for the presence of elevated cholesterol levels or for primary prevention in those known to have high cholesterol. On the other hand, there is mounting evidence to support vigorous intervention in those with known coronary disease. Further study is needed to determine whether a subset of patients with one or more well-defined risk factors would benefit from primary prevention.

  10. Brain-derived neurotrophic factor (BDNF) induces sustained intracellular Ca2+ elevation through the up-regulation of surface transient receptor potential 3 (TRPC3) channels in rodent microglia.

    PubMed

    Mizoguchi, Yoshito; Kato, Takahiro A; Seki, Yoshihiro; Ohgidani, Masahiro; Sagata, Noriaki; Horikawa, Hideki; Yamauchi, Yusuke; Sato-Kasai, Mina; Hayakawa, Kohei; Inoue, Ryuji; Kanba, Shigenobu; Monji, Akira

    2014-06-27

    Microglia are immune cells that release factors, including proinflammatory cytokines, nitric oxide (NO), and neurotrophins, following activation after disturbance in the brain. Elevation of intracellular Ca(2+) concentration ([Ca(2+)]i) is important for microglial functions such as the release of cytokines and NO from activated microglia. There is increasing evidence suggesting that pathophysiology of neuropsychiatric disorders is related to the inflammatory responses mediated by microglia. Brain-derived neurotrophic factor (BDNF) is a neurotrophin well known for its roles in the activation of microglia as well as in pathophysiology and/or treatment of neuropsychiatric disorders. In this study, we sought to examine the underlying mechanism of BDNF-induced sustained increase in [Ca(2+)]i in rodent microglial cells. We observed that canonical transient receptor potential 3 (TRPC3) channels contribute to the maintenance of BDNF-induced sustained intracellular Ca(2+) elevation. Immunocytochemical technique and flow cytometry also revealed that BDNF rapidly up-regulated the surface expression of TRPC3 channels in rodent microglial cells. In addition, pretreatment with BDNF suppressed the production of NO induced by tumor necrosis factor α (TNFα), which was prevented by co-adiministration of a selective TRPC3 inhibitor. These suggest that BDNF induces sustained intracellular Ca(2+) elevation through the up-regulation of surface TRPC3 channels and TRPC3 channels could be important for the BDNF-induced suppression of the NO production in activated microglia. We show that TRPC3 channels could also play important roles in microglial functions, which might be important for the regulation of inflammatory responses and may also be involved in the pathophysiology and/or the treatment of neuropsychiatric disorders. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  11. Adolescent female rats exhibiting activity-based anorexia express elevated levels of GABA(A) receptor α4 and δ subunits at the plasma membrane of hippocampal CA1 spines.

    PubMed

    Aoki, Chiye; Sabaliauskas, Nicole; Chowdhury, Tara; Min, Jung-Yun; Colacino, Anna Rita; Laurino, Kevin; Barbarich-Marsteller, Nicole C

    2012-05-01

    Activity-based anorexia (ABA) is an animal model for anorexia nervosa that has revealed genetic links to anxiety traits and neurochemical characteristics within the hypothalamus. However, few studies have used this animal model to investigate the biological basis for vulnerability of pubertal and adolescent females to ABA, even though the great majority of the anorexia nervosa cases are females exhibiting the first symptoms during puberty. GABAergic inhibition of the hippocampus strongly regulates anxiety as well as plasticity throughout life. We recently showed that the hippocampal CA1 of female mice undergo a dramatic change at puberty onset--from expressing virtually none of the nonsynaptic α4βδ GABA(A) receptors (GABARs) prepubertally to expressing these GABARs at ~7% of the CA1 dendritic spine membranes at puberty onset. Furthermore, we showed that this change underlies the enhanced modulation of anxiety, neuronal excitability, and NMDA receptor-dependent synaptic plasticity in the hippocampus by the stress neurosteroid, THP (3α-OH-5α[β]-pregnan-20-one or [allo]pregnanolone). Here, we used quantitative electron microscopy to determine whether ABA induction in female rats during adolescence also elevates the expression of α4 and δ subunits of α4βδ GABARs, as was observed at puberty onset for mice. Our analysis revealed that rats also exhibit a rise of α4 and δ subunits of α4βδ GABARs at puberty onset, in that these subunits are detectable at ~6% of the dendritic spine membranes of CA1 pyramidal cells at puberty onset (postnatal day 32-36; P32-36) but this drops to about 2% by P40-P44. The levels of α4 and δ subunits at the CA1 spines remained low following exposure of females to either of the two environmental factors needed to generate ABA--food restriction and access to a running wheel for 4 days--from P40 to P44. This pattern contrasted greatly from those of ABA animals, for which the two environmental factors were combined. Within the

  12. Synaptic muscarinic response types in hippocampal CA1 interneurons depend on different levels of presynaptic activity and different muscarinic receptor subtypes

    PubMed Central

    Bell, L. Andrew; Bell, Karen A.; McQuiston, A. Rory

    2013-01-01

    Depolarizing, hyperpolarizing and biphasic muscarinic responses have been described in hippocampal inhibitory interneurons, but the receptor subtypes and activity patterns required to synaptically activate muscarinic responses in interneurons have not been completely characterized. Using optogenetics combined with whole cell patch clamp recordings in acute slices, we measured muscarinic responses produced by endogenously released acetylcholine (ACh) from cholinergic medial septum/diagonal bands of Broca inputs in hippocampal CA1. We found that depolarizing responses required more cholinergic terminal stimulation than hyperpolarizing ones. Furthermore, elevating extracellular ACh with the acetylcholinesterase inhibitor physostigmine had a larger effect on depolarizing versus hyperpolarizing responses. Another subpopulation of interneurons responded biphasically, and periodic release of ACh entrained some of these interneurons to rhythmically burst. M4 receptors mediated hyperpolarizing responses by activating inwardly rectifying K+ channels, whereas the depolarizing responses were inhibited by the nonselective muscarinic antagonist atropine but were unaffected by M1, M4 or M5 receptor modulators. In addition, activation of M4 receptors significantly altered biphasic interneuron firing patterns. Anatomically, interneuron soma location appeared predictive of muscarinic response types but response types did not correlate with interneuron morphological subclasses. Together these observations suggest that the hippocampal CA1 interneuron network will be differentially affected by cholinergic input activity levels. Low levels of cholinergic activity will preferentially suppress some interneurons via hyperpolarization and increased activity will recruit other interneurons to depolarize, possibly because of elevated extracellular ACh concentrations. These data provide important information for understanding how cholinergic therapies will affect hippocampal network function

  13. Stimulation-induced Ca(2+) influx at nodes of Ranvier in mouse peripheral motor axons.

    PubMed

    Zhang, Zhongsheng; David, Gavriel

    2016-01-01

    In peripheral myelinated axons of mammalian spinal motor neurons, Ca(2+) influx was thought to occur only in pathological conditions such as ischaemia. Using Ca(2+) imaging in mouse large motor axons, we find that physiological stimulation with trains of action potentials transiently elevates axoplasmic [C(2+)] around nodes of Ranvier. These stimulation-induced [Ca(2+)] elevations require Ca(2+) influx, and are partially reduced by blocking T-type Ca(2+) channels (e.g. mibefradil) and by blocking the Na(+)/Ca(2+) exchanger (NCX), suggesting an important contribution of Ca(2+) influx via reverse-mode NCX activity. Acute disruption of paranodal myelin dramatically increases stimulation-induced [Ca(2+)] elevations around nodes by allowing activation of sub-myelin L-type (nimodipine-sensitive) Ca(2+) channels. The Ca(2+) that enters myelinated motor axons during normal activity is likely to contribute to several signalling pathways; the larger Ca(2+) influx that occurs following demyelination may contribute to the axonal degeneration that occurs in peripheral demyelinating diseases. Activity-dependent Ca(2+) signalling is well established for somata and terminals of mammalian spinal motor neurons, but not for their axons. Imaging of an intra-axonally injected fluorescent [Ca(2+)] indicator revealed that during repetitive action potential stimulation, [Ca(2+)] elevations localized to nodal regions occurred in mouse motor axons from ventral roots, phrenic nerve and intramuscular branches. These [Ca(2+)] elevations (∼ 0.1 μm with stimulation at 50 Hz, 10 s) were blocked by removal of Ca(2+) from the extracellular solution. Effects of pharmacological blockers indicated contributions from both T-type Ca(2+) channels and reverse mode Na(+)/Ca(2+) exchange (NCX). Acute disruption of paranodal myelin (by stretch or lysophosphatidylcholine) increased the stimulation-induced [Ca(2+)] elevations, which now included a prominent contribution from L-type Ca(2+) channels. These

  14. Evidence that elevated CO2 levels can indirectly increase rhizosphere denitrifier activity

    NASA Technical Reports Server (NTRS)

    Smart, D. R.; Ritchie, K.; Stark, J. M.; Bugbee, B.

    1997-01-01

    We examined the influence of elevated CO2 concentration on denitrifier enzyme activity in wheat rhizoplanes by using controlled environments and solution culture techniques. Potential denitrification activity was from 3 to 24 times higher on roots that were grown under an elevated CO2 concentration of 1,000 micromoles of CO2 mol-1 than on roots grown under ambient levels of CO2. Nitrogen loss, as determined by a nitrogen mass balance, increased with elevated CO2 levels in the shoot environment and with a high NO3- concentration in the rooting zone. These results indicated that aerial CO2 concentration can play a role in rhizosphere denitrifier activity.

  15. Pre-immunotherapy serum CA27.29 (MUC-1) mucin level and CD69+ lymphocytes correlate with effects of Theratope sialyl-Tn-KLH cancer vaccine in active specific immunotherapy.

    PubMed

    Reddish, M A; MacLean, G D; Poppema, S; Berg, A; Longenecker, B M

    1996-06-01

    Patients with metastatic breast, colorectal or ovarian cancers received active specific immunotherapy (ASI) with Theratope sialyl-Tn-KLH (keyhole limpet hemocyanin) cancer vaccine emulsified in Detox adjuvant. The median log2 anti-STn IgG titer generated by ASI, estimated by enzyme-linked immunosorbent assay with solid-phase ovine submaxillary mucin, was 5.322 (range = 0 - 9.322). Following ASI, 51 patients who generated titers higher than the median value for anti-STn+ mucin IgG survived longer than 46 patients who generated lower titers below the median. 38 of the patients were phenotyped for CD69 prior to ASI. The patients with lower numbers of CD69+ peripheral blood lymphocytes prior to immunotherapy (pre-ASI) also had low serum CA27.29 cancer antigen (MUC-1) levels, and had longer times to disease progression and improved survival following ASI. Elevated pre-ASI serum CA27.29 tumor antigen levels were associated with higher numbers of CD69+ PBL, with decreased anti-STn antibody production and decreased survival following ASI. The data are compatible with the hypothesis that elevated serum MUC-1 mucin is specifically immunosuppressive.

  16. 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.

  17. Elevated Serum Pesticide Levels and Risk for Alzheimer Disease

    PubMed Central

    Richardson, Jason R.; Roy, Ananya; Shalat, Stuart L.; von Stein, Richard T.; Hossain, Muhammad M.; Buckley, Brian; Gearing, Marla; Levey, Allan I.; German, Dwight C.

    2014-01-01

    IMPORTANCE The causes of late-onset Alzheimer disease (AD) are not yet understood but likely include a combination of genetic, environmental, and lifestyle factors. Limited epidemiological studies suggest that occupational pesticide exposures are associated with AD. Previously, we reported that serum levels of dichlorodiphenyldichloroethylene (DDE), the metabolite of the pesticide dichlorodiphenyltrichloroethane (DDT), were elevated in a small number of patients with AD (n=20). OBJECTIVE To evaluate the association between serum levels of DDE and AD and whether the apolipoprotein E (APOE) genotype modifies the association. DESIGN, SETTING, AND PARTICIPANTS A case-control study consisting of existing samples from patients with AD and control participants from the Emory University Alzheimer’s Disease Research Center and the University of Texas Southwestern Medical School’s Alzheimer’s Disease Center. Serum levels of DDE were measured in 79 control and 86 AD cases. MAIN OUTCOMES AND MEASURES Serum DDE levels, AD diagnosis, severity of AD measured by the Mini-Mental State Examination score, and interaction with APOE4 status. RESULTS Levels of DDE were 3.8-fold higher in the serum of those with AD (mean [SEM], 2.64 [0.35] ng/mg cholesterol) when compared with control participants (mean [SEM], 0.69 [0.1] ng/mg cholesterol; P < .001). The highest tertile of DDE levels was associated with an odds ratio of 4.18 for increased risk for AD (95% CI, 2.54–5.82; P < .001) and lower Mini-Mental State Examination scores (−1.605; range, −3.095 to −0.114; P < .0001). The Mini-Mental State Examination scores in the highest tertile of DDE were −1.753 points lower in the subpopulation carrying an APOE ε4 allele compared with those carrying an APOE ε3 allele (P interaction = .04). Serum levels of DDE were highly correlated with brain levels of DDE (ρ = 0.95). Exposure of human neuroblastoma cells to DDT or DDE increased levels of amyloid precursor protein. CONCLUSIONS

  18. Elevated serum pesticide levels and risk for Alzheimer disease.

    PubMed

    Richardson, Jason R; Roy, Ananya; Shalat, Stuart L; von Stein, Richard T; Hossain, Muhammad M; Buckley, Brian; Gearing, Marla; Levey, Allan I; German, Dwight C

    2014-03-01

    The causes of late-onset Alzheimer disease (AD) are not yet understood but likely include a combination of genetic, environmental, and lifestyle factors. Limited epidemiological studies suggest that occupational pesticide exposures are associated with AD. Previously, we reported that serum levels of dichlorodiphenyldichloroethylene (DDE), the metabolite of the pesticide dichlorodiphenyltrichloroethane (DDT), were elevated in a small number of patients with AD (n=20). To evaluate the association between serum levels of DDE and AD and whether the apolipoprotein E (APOE) genotype modifies the association. A case-control study consisting of existing samples from patients with AD and control participants from the Emory University Alzheimer's Disease Research Center and the University of Texas Southwestern Medical School's Alzheimer's Disease Center. Serum levels of DDE were measured in 79 control and 86 AD cases. Serum DDE levels, AD diagnosis, severity of AD measured by the Mini-Mental State Examination score, and interaction with APOE4 status. Levels of DDE were 3.8-fold higher in the serum of those with AD (mean [SEM], 2.64 [0.35] ng/mg cholesterol) when compared with control participants (mean [SEM], 0.69 [0.1] ng/mg cholesterol; P < .001). The highest tertile of DDE levels was associated with an odds ratio of 4.18 for increased risk for AD (95% CI, 2.54-5.82; P < .001) and lower Mini-Mental State Examination scores (-1.605; range, -3.095 to -0.114; P < .0001). The Mini-Mental State Examination scores in the highest tertile of DDE were -1.753 points lower in the subpopulation carrying an APOE ε4 allele compared with those carrying an APOE ε3 allele (P interaction = .04). Serum levels of DDE were highly correlated with brain levels of DDE (ρ = 0.95). Exposure of human neuroblastoma cells to DDT or DDE increased levels of amyloid precursor protein. Elevated serum DDE levels are associated with an increased risk for AD and carriers of an APOE4 ε4 allele may

  19. A community-based epidemiological study of elevated serum alanine aminotransferase levels in Kinmen, Taiwan

    PubMed Central

    Liu, Chi-Ming; Tung, Tao-Hsin; Liu, Jorn-Hon; Chen, Victor Tze-Kai; Lin, Ching-Heng; Hsu, Chung-Te; Chou, Pesus

    2005-01-01

    AIM: To explore any gender-related differences in prevalence of and condition-associated factors related to an elevated serum alanine aminotransferase (ALT) level amongst residents of Kinmen, Taiwan. METHODS: A total of 11 898 of a potential 20 112 regional residents aged 30 years or more completed a related questionnaire that was carried out by the Yang-Ming Crusade between 1991 and 1994 inclusively, with blood samples being collected by public nurses. The overall questionnaire response rate was 59.3% (52.4% for males and 66.0% for females). RESULTS: The prevalence of an elevated serum ALT level for this sub-population was found to be 7.2%, the prevalence revealing a statistically significant decrease with increasing population age (P<0.0001). Males exhibited a greater prevalence of elevated serum ALT level than did females (9.4% vs 5.3%, P<0.0001). Using multiple logistic regression analysis, in addition to male gender, a younger age, greater waist circumference, presence of type-2 diabetes and hyperuricemia were the significant factors associated with an elevated serum ALT level for both males and females. Gender-related differences as regards associated factors were also revealed. For males, obesity was significantly related to an elevated serum ALT level (OR = 1.28, 95%CI: 1.00-1.66) but this was not so for females (OR = 1.09, 95%CI: 0.84-1.42). Hypertriglyceridemia (OR = 1.80, 95%CI: 1.36-2.39) and hyperuricemia (OR = 1.61, 95%CI: 1.03-2.52) were significantly related to elevated serum ALT levels only for females. CONCLUSION: Several gender-related differences were noted pertaining to the prevalence of and relationship between obesity, hypertriglyceridemia and hyperuricemia and elevated serum ALT level in the present study. PMID:15786537

  20. Elevated blood pressure, race/ethnicity, and C-reactive protein levels in children and adolescents.

    PubMed

    Lande, Marc B; Pearson, Thomas A; Vermilion, Roger P; Auinger, Peggy; Fernandez, Isabel D

    2008-12-01

    Adult hypertension is independently associated with elevated C-reactive protein levels, after controlling for obesity and other cardiovascular risk factors. The objective of this study was to determine, with a nationally representative sample of children, whether the relationship between elevated blood pressure and C-reactive protein levels may be evident before adulthood. Cross-sectional data for children 8 to 17 years of age who participated in the National Health and Nutrition Examination Survey between 1999 and 2004 were analyzed. Bivariate analyses compared children with C-reactive protein levels of >3 mg/L versus elevated blood pressure and C-reactive protein levels. Among 6112 children, 3% had systolic blood pressure of >or=95th percentile and 1.3% had diastolic blood pressure of >or=95th percentile. Children with C-reactive protein levels of >3 mg/L had higher systolic blood pressure, compared with children with C-reactive protein levels of levels of <40 mg/dL, and Hispanic ethnicity were independent predictors of elevated C-reactive protein levels. Diastolic blood pressure did not differ between groups. Linear regression analyses showed that systolic blood pressure of >or=95th percentile was independently associated with C-reactive protein levels in boys but not girls. Subset analyses according to race/ethnicity demonstrated that the independent association of elevated systolic blood pressure with C-reactive protein levels was largely limited to black boys. These data indicate that there is interplay between race/ethnicity, elevated systolic blood pressure, obesity, and inflammation in children, a finding that has potential implications for disparities in cardiovascular disease later in life.

  1. Synergistic role of ADP and Ca2+ in diastolic myocardial stiffness

    PubMed Central

    Sequeira, Vasco; Najafi, Aref; McConnell, Mark; Fowler, Ewan D; Bollen, Ilse A E; Wüst, Rob C I; dos Remedios, Cris; Helmes, Michiel; White, Ed; Stienen, Ger J M; Tardiff, Jil; Kuster, Diederik W D; van der Velden, Jolanda

    2015-01-01

    Abstract Heart failure (HF) with diastolic dysfunction has been attributed to increased myocardial stiffness that limits proper filling of the ventricle. Altered cross-bridge interaction may significantly contribute to high diastolic stiffness, but this has not been shown thus far. Cross-bridge interactions are dependent on cytosolic [Ca2+] and the regeneration of ATP from ADP. Depletion of myocardial energy reserve is a hallmark of HF leading to ADP accumulation and disturbed Ca2+ handling. Here, we investigated if ADP elevation in concert with increased diastolic [Ca2+] promotes diastolic cross-bridge formation and force generation and thereby increases diastolic stiffness. ADP dose-dependently increased force production in the absence of Ca2+ in membrane-permeabilized cardiomyocytes from human hearts. Moreover, physiological levels of ADP increased actomyosin force generation in the presence of Ca2+ both in human and rat membrane-permeabilized cardiomyocytes. Diastolic stress measured at physiological lattice spacing and 37°C in the presence of pathological levels of ADP and diastolic [Ca2+] revealed a 76 ± 1% contribution of cross-bridge interaction to total diastolic stress in rat membrane-permeabilized cardiomyocytes. Inhibition of creatine kinase (CK), which increases cytosolic ADP, in enzyme-isolated intact rat cardiomyocytes impaired diastolic re-lengthening associated with diastolic Ca2+ overload. In isolated Langendorff-perfused rat hearts, CK inhibition increased ventricular stiffness only in the presence of diastolic [Ca2+]. We propose that elevations of intracellular ADP in specific types of cardiac disease, including those where myocardial energy reserve is limited, contribute to diastolic dysfunction by recruiting cross-bridges, even at low Ca2+, and thereby increase myocardial stiffness. Key points Diastolic dysfunction in heart failure patients is evident from stiffening of the passive properties of the ventricular wall. Increased actomyosin

  2. 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

  3. A ryanodine receptor-dependent Ca(i)(2+) asymmetry at Hensen's node mediates avian lateral identity.

    PubMed

    Garic-Stankovic, Ana; Hernandez, Marcos; Flentke, George R; Zile, Maija H; Smith, Susan M

    2008-10-01

    In mouse, the establishment of left-right (LR) asymmetry requires intracellular calcium (Ca(i)(2+)) enrichment on the left of the node. The use of Ca(i)(2+) asymmetry by other vertebrates, and its origins and relationship to other laterality effectors are largely unknown. Additionally, the architecture of Hensen's node raises doubts as to whether Ca(i)(2+) asymmetry is a broadly conserved mechanism to achieve laterality. We report here that the avian embryo uses a left-side enriched Ca(i)(2+) asymmetry across Hensen's node to govern its lateral identity. Elevated Ca(i)(2+) was first detected along the anterior node at early HH4, and its emergence and left-side enrichment by HH5 required both ryanodine receptor (RyR) activity and extracellular calcium, implicating calcium-induced calcium release (CICR) as the novel source of the Ca(i)(2+). Targeted manipulation of node Ca(i)(2+) randomized heart laterality and affected nodal expression. Bifurcation of the Ca(i)(2+) field by the emerging prechordal plate may permit the independent regulation of LR Ca(i)(2+) levels. To the left of the node, RyR/CICR and H(+)V-ATPase activity sustained elevated Ca(i)(2+). On the right, Ca(i)(2+) levels were actively repressed through the activities of H(+)K(+) ATPase and serotonin-dependent signaling, thus identifying a novel mechanism for the known effects of serotonin on laterality. Vitamin A-deficient quail have a high incidence of situs inversus hearts and had a reversed calcium asymmetry. Thus, Ca(i)(2+) asymmetry across the node represents a more broadly conserved mechanism for laterality among amniotes than had been previously believed.

  4. Cadmium is acutely toxic for murine hepatocytes: effects on intracellular free Ca(2+) homeostasis.

    PubMed

    Wang, S S; Chen, L; Xia, S K

    2007-01-01

    We studied cadmium toxicity in murine hepatocytes in vitro. Cadmium effects on intracellular free Ca(2+) concentration ([Ca(2+)](i)) were assayed, using a laser scanning confocal microscope with a fluorescent probe, Fluo-3/AM. The results showed that administration of cadmium chloride (CdCl(2), 5, 10, 25 microM) resulted in a dose-dependent decrease of hepatocyte viability and an elevated aspartate aminotransferase (AST) activity in the culture medium (p<0.05 for 25 microM CdCl(2) vs. control). Significant increases of lactate dehydrogenase (LDH) activities in 10 and 25 microM CdC1(2)-exposed groups were observed (p<0.05 and p<0.01, respectively). A greatly decreased albumin content and a more malondialdehyde (MDA) formation also occurred after CdC1(2) treatment. The Ca(2+) concentrations in the culture medium of CdCl(2)-exposed hepatocytes were significantly decreased, while [Ca(2+)](i) appeared to be significantly elevated (p<0.05 or p<0.01 vs. control). We found that in Ca(2+)-containing hydroxyethyl piperazine ethanesulfonic acid-buffered salt solution (HBSS) only, CdCl(2) elicited [Ca(2+)](i) increases, which comprised an initially slow ascent and a strong elevated phase. However, in Ca(2+)-containing HBSS with addition of 2-aminoethoxydiphenyl borane (2-APB), CdCl(2) caused a mild [Ca(2+)](i) elevation in the absence of an initial rise phase. Removal of extracellular Ca(2+) showed that CdCl(2) induced an initially slow [Ca(2+)](i) rise alone without being followed by a markedly elevated phase, but in a Ca(2+)-free HBSS with addition of 2-APB, CdCl(2) failed to elicit the [Ca(2+)](i) elevation. These results suggest that abnormal Ca(2+) homeostasis due to cadmium may be an important mechanism of the development of the toxic effect in murine hepatocytes. [Ca(2+)](i) elevation in acutely cadmium-exposed hepatocytes is closely related to the extracellular Ca(2+) entry and an excessive release of Ca(2+) from intracellular stores.

  5. Dendrochronologically dated pine stumps document phase-wise bog expansion at a northwest German site between ca. 6700 and ca. 3400 BC

    NASA Astrophysics Data System (ADS)

    Maike Achterberg, Inke Elisabeth; Eckstein, Jan; Birkholz, Bernhard; Bauerochse, Andreas; Leuschner, Hanns Hubert

    2018-01-01

    The investigated northwest German mire site at Totes Moor is densely covered with subfossil pine stumps (Pinus sylvestris L.) from the fen-bog transition. This facilitates the spatio-temporal reconstruction of mire development, which is based on 212 in situ tree stumps in the case study presented here. Six dendrochronologically dated site chronologies together cover 2345 years between 6703 and 3403 BC. The gaps in between are 6 to 550 years long. Additionally, a floating chronology of 309 years, containing 30 trees, was radiocarbon-dated to the beginning of the 7th millennium cal BC. Peat-stratigraphical survey was carried out additionally, and elevations a.s.l. were determined at several locations. Tree dying-off phases, which indicate water level rise at the site, mostly in context of the local fen-bog transition, are evident for ca. 6600-6450, ca. 6350-5750, ca. 5300-4900, ca. 4700-4550, ca. 3900-3850, ca. 3700-3600, ca. 3500-3450 and ca. 3400 BC. The spatial distribution of the dated in situ trees illustrates the phase-wise expansion of raised bog over fen peat at the site. The documented bog expansion pulses likely correspond to climatic wet sifts.

  6. TPS and CA 19-9 measurements in the follow-up of patients with pancreatic cancer and chronic pancreatitis.

    PubMed

    Slesak, B; Harlozinska-Szmyrka, A; Knast, W; Sedlaczek, P; Einarsson, R; van Dalen, A

    2004-01-01

    The aim of this study was to assess the value of TPS and CA 19-9 in a long-term follow-up analysis of 11 patients with chronic pancreatitis (CP) and 15 patients with pancreatic cancer (PC). In all monitored patients with chronic pancreatitis the initial TPS level was below 200 U/L, whereas CA 19-9 was elevated in two of them. In one patient a dramatic increase in the TPS concentration (820 U/L) was measured at the last follow-up visit (after 8.6 months), which led to the detection of PC. In all patients with PC the preoperative TPS level exceeded 200 U/L, whereas CA 19-9 was elevated in only nine patients. After the Kausch-Whipple operation 11 patients showed no evidence of disease and in eight of these patients both TPS and CA 19-9 were within the reference range; however, in three patients liver metastases were detected after 8-24 months from the last tumor marker measurement. In four of the 15 patients both markers were elevated at the end of the follow-up period and distant metastases were clinically confirmed. Our results indicate that in patients with CP and PC undergoing long-term follow-up, TPS reflects the clinical status of patients more accurately than CA 19-9.

  7. Calcification by juvenile corals under heterotrophy and elevated CO2

    NASA Astrophysics Data System (ADS)

    Drenkard, E. J.; Cohen, A. L.; McCorkle, D. C.; de Putron, S. J.; Starczak, V. R.; Zicht, A. E.

    2013-09-01

    Ocean acidification (OA) threatens the existence of coral reefs by slowing the rate of calcium carbonate (CaCO3) production of framework-building corals thus reducing the amount of CaCO3 the reef can produce to counteract natural dissolution. Some evidence exists to suggest that elevated levels of dissolved inorganic nutrients can reduce the impact of OA on coral calcification. Here, we investigated the potential for enhanced energetic status of juvenile corals, achieved via heterotrophic feeding, to modulate the negative impact of OA on calcification. Larvae of the common Atlantic golf ball coral, Favia fragum, were collected and reared for 3 weeks under ambient (421 μatm) or significantly elevated (1,311 μatm) CO2 conditions. The metamorphosed, zooxanthellate spat were either fed brine shrimp (i.e., received nutrition from photosynthesis plus heterotrophy) or not fed (i.e., primarily autotrophic). Regardless of CO2 condition, the skeletons of fed corals exhibited accelerated development of septal cycles and were larger than those of unfed corals. At each CO2 level, fed corals accreted more CaCO3 than unfed corals, and fed corals reared under 1,311 μatm CO2 accreted as much CaCO3 as unfed corals reared under ambient CO2. However, feeding did not alter the sensitivity of calcification to increased CO2; ∆ calcification/∆Ω was comparable for fed and unfed corals. Our results suggest that calcification rates of nutritionally replete juvenile corals will decline as OA intensifies over the course of this century. Critically, however, such corals could maintain higher rates of skeletal growth and CaCO3 production under OA than those in nutritionally limited environments.

  8. Elevated voltage level I.sub.DDQ failure testing of integrated circuits

    DOEpatents

    Righter, Alan W.

    1996-01-01

    Burn in testing of static CMOS IC's is eliminated by I.sub.DDQ testing at elevated voltage levels. These voltage levels are at least 25% higher than the normal operating voltage for the IC but are below voltage levels that would cause damage to the chip.

  9. 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

  10. Selenium Speciation in the Fountain Creek Watershed (Colorado, USA) Correlates with Water Hardness, Ca and Mg Levels.

    PubMed

    Carsella, James S; Sánchez-Lombardo, Irma; Bonetti, Sandra J; Crans, Debbie C

    2017-04-30

    The environmental levels of selenium (Se) are regulated and strictly enforced by the Environmental Protection Agency (EPA) because of the toxicity that Se can exert at high levels. However, speciation plays an important role in the overall toxicity of Se, and only when speciation analysis has been conducted will a detailed understanding of the system be possible. In the following, we carried out the speciation analysis of the creek waters in three of the main tributaries-Upper Fountain Creek, Monument Creek and Lower Fountain Creek-located in the Fountain Creek Watershed (Colorado, USA). There are statistically significant differences between the Se, Ca and Mg, levels in each of the tributaries and seasonal swings in Se, Ca and Mg levels have been observed. There are also statistically significant differences between the Se levels when grouped by Pierre Shale type. These factors are considered when determining the forms of Se present and analyzing their chemistry using the reported thermodynamic relationships considering Ca 2+ , Mg 2+ , SeO₄ 2- , SeO₃ 2- and carbonates. This analysis demonstrated that the correlation between Se and water hardness can be explained in terms of formation of soluble CaSeO₄. The speciation analysis demonstrated that for the Fountain Creek waters, the Ca 2+ ion may be mainly responsible for the observed correlation with the Se level. Considering that the Mg 2+ level is also correlating linearly with the Se levels it is important to recognize that without Mg 2+ the Ca 2+ would be significantly reduced. The major role of Mg 2+ is thus to raise the Ca 2+ levels despite the equilibria with carbonate and other anions that would otherwise decrease Ca 2+ levels.

  11. Outcomes and Cost Analysis of Surveillance Strategies After Initial Treatment for Women With Recurrent Ovarian Cancer.

    PubMed

    Alexander, Vinita M; Gordon, Alan N; Howard, David H; Khanna, Namita

    2017-09-01

    The aim of this study was to determine whether there is a survival or cost benefit dependent on detection strategy of recurrent ovarian cancer (ie, imaging, physical examination findings, report of symptoms, or rising cancer antigen 125 [CA-125] levels). A retrospective chart review of 112 ovarian cancer patients was conducted, and method of detection of recurrent disease was determined from medical records. The following primary outcomes were determined using Cox proportional hazards regression model: progression-free survival (PFS) after diagnosis of recurrence and time to death after diagnosis of recurrence (overall survival [OS]). Several approaches to disease surveillance were proposed, and a cost model was applied. Median time to recurrence was 13.5 months. Overall, 6.3% presented with only physical examination findings; 24.1%, with elevating CA-125 levels; 34.8%, with imaging; and 32.1%, with symptoms. Most patients presenting with recurrent disease diagnosed by rising CA-125 were white (62.9%); those with imaging and symptomatic recurrences were blacks (56.4% and 57.1%, respectively). There was a small but not statistically significant OS benefit for recurrence detected via CA-125 (P = 0.85; OS per detection method: PE, 20.7 months; CA-125, 26.8 months; imaging, 17.8 months; and symptoms, 6.6 months). We modeled costs of surveillance in our patient cohort; up to 40.8% of cases of ovarian cancer recurrences would have been missed if no imaging were obtained during surveillance. Results indicate minimal differences in PFS and statistically insignificant differences in OS, depending on detection method. Notably, black patients with Medicaid presented most often with symptomatic recurrences, which surprisingly did not affect patient OS and PFS; and interestingly, pr\\ivate or self-pay insurance was associated with decreased OS among black patients. From our cost analysis, we estimate that the most cost-effective surveillance strategy for the first year costs $9

  12. Elevated voltage level I{sub DDQ} failure testing of integrated circuits

    DOEpatents

    Righter, A.W.

    1996-05-21

    Burn in testing of static CMOS IC`s is eliminated by I{sub DDQ} testing at elevated voltage levels. These voltage levels are at least 25% higher than the normal operating voltage for the IC but are below voltage levels that would cause damage to the chip. 4 figs.

  13. 8. EAST ELEVATION OF SKIDOO MILL AND UPPER ORE BIN, ...

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

    8. EAST ELEVATION OF SKIDOO MILL AND UPPER ORE BIN, LOOKING WEST FROM ACCESS ROAD. THE ROADWAY ON THIS LEVEL (CENTER) WAS USED FOR UNLOADING ORE BROUGHT ON BURROWS INTO THE ORE BIN AT THE TOP LEVEL OF THE MILL. THE ORE BIN IN THE UPPER LEFT WAS ADDED LATER WHEN ORE WAS BROUGHT TO THE MILL BY TRUCKS. - Skidoo Mine, Park Route 38 (Skidoo Road), Death Valley Junction, Inyo County, CA

  14. CA27.29 as a tumour marker for risk evaluation and therapy monitoring in primary breast cancer patients.

    PubMed

    Rack, Brigitte; Jückstock, Julia; Trapp, Elisabeth; Weissenbacher, Tobias; Alunni-Fabbroni, Marianna; Schramm, Amelie; Widschwendter, Peter; Lato, Krisztian; Zwingers, Thomas; Lorenz, Ralf; Tesch, Hans; Schneeweiss, Andreas; Fasching, Peter; Mahner, Sven; Beckmann, Matthias W; Lichtenegger, Werner; Janni, Wolfgang

    2016-10-01

    Several trials showed that tumour markers are associated with an impaired prognosis for breast cancer. Whether earlier treatment can improve the course of the disease remains controversial. The SUCCESS Trial compares FEC (500/100/500)-docetaxel (100) vs. FEC (500/100/500)-docetaxel/gemcitabine (75/2000) as well as 2 vs. 5 years of zoledronate in high-risk primary breast cancer patients. In 2669 patients, CA27.29 was measured before and after chemotherapy with the ST AIA-PACK CA27.29 reagent for the AIA-600II automated enzyme immunoassay (Tosoh Bioscience, Belgium). Values above 31 U/ml were considered positive. Of the patients, 7.6 % (n = 202, mean 19, range 3-410) and 19.1 % (n = 511, mean 21, range 3-331) had elevated marker levels before and after chemotherapy, respectively. Of the patients, 4.9 and 78 % showed elevated and low CA27.29, respectively, at both time points. After treatment, 35 % of the pre-therapy positive patients were negative, and 15 % of the initially negative patients became positive. The correlation between both time points was significant (p < 0.0001). No correlations among nodal status, grading, hormonal status, HER2 status and CA27.29 levels were found. However, tumour size (p = 0.02), older age (p < 0.001) and post-menopausal status (p = 0.006) were significantly associated with higher CA27.29 levels. Before treatment, the prevalence of elevated CA27.29 was equally distributed between both treatment arms, whereas after chemotherapy, 13.7 % of the patients in the FEC-doc arm showed an increased level vs. 25.4 % of the patients in the FEC-doc/gemcitabine arm (p < 0.0001). However, we could not show a significant association between the G-CSF application (yes vs. no) and CA27.29 status before/after chemotherapy (p = 0.75). These results indicate a close relationship between CA27.29 levels and tumour mass. Increased values after the completion of chemotherapy might be attributed to treatment effects and should be

  15. 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

  16. Cerebrospinal fluid dehydroepiandrosterone levels are correlated with brain dehydroepiandrosterone levels, elevated in Alzheimer's disease, and related to neuropathological disease stage.

    PubMed

    Naylor, Jennifer C; Hulette, Christine M; Steffens, David C; Shampine, Lawrence J; Ervin, John F; Payne, Victoria M; Massing, Mark W; Kilts, Jason D; Strauss, Jennifer L; Calhoun, Patrick S; Calnaido, Rohana P; Blazer, Daniel G; Lieberman, Jeffrey A; Madison, Roger D; Marx, Christine E

    2008-08-01

    It is currently unknown whether cerebrospinal fluid (CSF) neurosteroid levels are related to brain neurosteroid levels in humans. CSF and brain dehydroepiandrosterone (DHEA) levels are elevated in patients with Alzheimer's disease (AD), but it is unclear whether CSF DHEA levels are correlated with brain DHEA levels within the same subject cohort. We therefore determined DHEA and pregnenolone levels in AD patients (n = 25) and cognitively intact control subjects (n = 16) in both CSF and temporal cortex. DHEA and pregnenolone levels were determined by gas chromatography/mass spectrometry preceded by HPLC. Frozen CSF and temporal cortex specimens were provided by the Alzheimer's Disease Research Center at Duke University Medical Center. Data were analyzed by Mann-Whitney U test statistic and Spearman correlational analyses. CSF DHEA levels are positively correlated with temporal cortex DHEA levels (r = 0.59, P < 0.0001) and neuropathological disease stage (Braak and Braak) (r = 0.42, P = 0.007). CSF pregnenolone levels are also positively correlated with temporal cortex pregnenolone levels (r = 0.57, P < 0.0001) and tend to be correlated with neuropathological disease stage (Braak) (r = 0.30, P = 0.06). CSF DHEA levels are elevated (P = 0.032), and pregnenolone levels tend to be elevated (P = 0.10) in patients with AD, compared with cognitively intact control subjects. These findings indicate that CSF DHEA and pregnenolone levels are correlated with temporal cortex brain levels of these neurosteroids and that CSF DHEA is elevated in AD and related to neuropathological disease stage. Neurosteroids may thus be relevant to the pathophysiology of AD.

  17. Ca2+-driven intestinal HCO(3)(-) secretion and CaCO3 precipitation in the European flounder in vivo: influences on acid-base regulation and blood gas transport.

    PubMed

    Cooper, Christopher A; Whittamore, Jonathan M; Wilson, Rod W

    2010-04-01

    Marine teleost fish continuously ingest seawater to prevent dehydration and their intestines absorb fluid by mechanisms linked to three separate driving forces: 1) cotransport of NaCl from the gut fluid; 2) bicarbonate (HCO(3)(-)) secretion and Cl(-) absorption via Cl(-)/HCO(3)(-) exchange fueled by metabolic CO(2); and 3) alkaline precipitation of Ca(2+) as insoluble CaCO(3), which aids H(2)O absorption). The latter two processes involve high rates of epithelial HCO(3)(-) secretion stimulated by intestinal Ca(2+) and can drive a major portion of water absorption. At higher salinities and ambient Ca(2+) concentrations the osmoregulatory role of intestinal HCO(3)(-) secretion is amplified, but this has repercussions for other physiological processes, in particular, respiratory gas transport (as it is fueled by metabolic CO(2)) and acid-base regulation (as intestinal cells must export H(+) into the blood to balance apical HCO(3)(-) secretion). The flounder intestine was perfused in vivo with salines containing 10, 40, or 90 mM Ca(2+). Increasing the luminal Ca(2+) concentration caused a large elevation in intestinal HCO(3)(-) production and excretion. Additionally, blood pH decreased (-0.13 pH units) and plasma partial pressure of CO(2) (Pco(2)) levels were elevated (+1.16 mmHg) at the highest Ca perfusate level after 3 days of perfusion. Increasing the perfusate [Ca(2+)] also produced proportional increases in net acid excretion via the gills. When the net intestinal flux of all ions across the intestine was calculated, there was a greater absorption of anions than cations. This missing cation flux was assumed to be protons, which vary with an almost 1:1 relationship with net acid excretion via the gill. This study illustrates the intimate link between intestinal HCO(3)(-) production and osmoregulation with acid-base balance and respiratory gas exchange and the specific controlling role of ingested Ca(2+) independent of any other ion or overall osmolality in marine

  18. Neighborhood Screening in Communities Throughout the Nation for Children with Elevated Blood Lead Levels

    PubMed Central

    Anderson, Dudley G.; Clark, John L.

    1974-01-01

    From the spring of 1971 to September 1973, neighborhood surveys were conducted in 58 communities throughout the nation to determine whether children with confirmed elevated blood lead levels could be identified. Another purpose of these screenings was to assist communities in identifying children with elevated blood lead levels and thereby demonstrate to community officials that such children do exist in communities screened. The children screened were not a random sample. In those communities where the initial elevated blood levels were confirmed all but seven had one or more children requiring followup and/or treatment. Of those children screened, black children had an elevated rate about three times as great as nonblack children. With few exceptions, the homes in the neighborhoods had at least one interior surface with sufficient quantities of lead paint to be dangerous if the paint were ingested. PMID:4831146

  19. 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

  20. Chronic Glucocorticoids Increase Hippocampal Vulnerability to Neurotoxicity under Conditions That Produce CA3 Dendritic Retraction But Fail to Impair Spatial Recognition Memory

    PubMed Central

    Conrad, Cheryl D.; McLaughlin, Katie J.; Harman, James S.; Foltz, Cainan; Wieczorek, Lindsay; Lightner, Elizabeth; Wright, Ryan L.

    2007-01-01

    We previously found that chronic stress conditions producing CA3 dendritic retraction and spatial memory deficits make the hippocampus vulnerable to the neurotoxin ibotenic acid (IBO). The purpose of this study was to determine whether exposure to chronic corticosterone (CORT) under conditions that produce CA3 dendritic retraction would enhance CA3 susceptibility to IBO. Male Sprague Dawley rats were chronically treated for 21 d with CORT in drinking water (400 μg/ml), and half were given daily injections of phenytoin (40 mg/kg), an antiepileptic drug that prevents CA3 dendritic retraction. Three days after treatments stopped, IBO was infused into the CA3 region. Conditions producing CA3 dendritic retraction (CORT and vehicle) exacerbated IBO-induced CA3 damage compared with conditions in which CA3 dendritic retraction was not observed (vehicle and vehicle, vehicle and phenytoin, CORT and phenytoin). Additionally, spatial recognition memory was assessed using the Y-maze, revealing that conditions producing CA3 dendritic retraction failed to impair spatial recognition memory. Furthermore, CORT levels in response to a potentially mild stressor (injection and Y-maze exposure) stayed at basal levels and failed to differ among key groups (vehicle and vehicle, CORT and vehicle, CORT and phenytoin), supporting the interpretations that CORT levels were unlikely to have been elevated during IBO infusion and that the neuroprotective actions of phenytoin were not through CORT alterations. These data are the first to show that conditions with prolonged glucocorticoid elevations leading to structural changes in hippocampal dendritic arbors can make the hippocampus vulnerable to neurotoxic challenges. These findings have significance for many disorders with elevated glucocorticoids that include depression, schizophrenia, Alzheimer’s disease, and Cushing’s disease. PMID:17670974

  1. [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.

  2. Hypercalcemia in hyperthyroidism: patterns of serum calcium, parathyroid hormone, and 1,25-dihydroxyvitamin D3 levels during management of thyrotoxicosis.

    PubMed

    Iqbal, Ayesha A; Burgess, Elizabeth H; Gallina, Daniel L; Nanes, Mark S; Cook, Curtiss B

    2003-01-01

    To present two cases of hypercalcemia associated with thyrotoxicosis and to describe serial biochemical findings during the course of treatment of hyperthyroidism. We report two cases, illustrate the changes in serum calcium, parathyroid hormone, and 1,25-dihydroxyvitamin D3 levels during management of thyrotoxicosis, and compare our findings with those in previous studies. Hypercalcemia attributable to thyrotoxicosis is well documented, but the mechanism for the hypercalcemia is incompletely understood. Our first patient had a complicated medical history and several potential causes of hypercalcemia, including recurrent hyperparathyroidism, metastatic breast cancer, and relapse of previously treated thyrotoxicosis. A suppressed parathyroid hormone level and negative bone and computed tomographic scans excluded the first two factors. After thyroid ablation with 131I, the serum calcium and thyroxine levels decreased, and the parathyroid hormone and 1,25-dihydroxyvitamin D3 levels normalized. Our second patient, who was referred to our institution with a preliminary diagnosis of hypercalcemia associated with malignant disease and who had no symptoms of hyperthyroidism, was found to have a high free thyroxine level, diffuse enlargement of the thyroid, and high uptake (58%) of 123I on a thyroid scan. After thyroid ablation, the serum calcium, 1,25-dihydroxyvitamin D3, and intact parathyroid hormone levels normalized, and the free thyroxine level declined. The probable pathogenesis of hypercalcemia in thyrotoxicosis is reviewed with respect to thyroid hormone and its effect on bone turnover. Physicians should consider thyrotoxicosis in the differential diagnosis of hypercalcemia.

  3. Citrus bergamia Risso Elevates Intracellular Ca2+ in Human Vascular Endothelial Cells due to Release of Ca2+ from Primary Intracellular Stores

    PubMed Central

    Kang, Purum; Han, Seung Ho; Moon, Hea Kyung; Lee, Jeong-Min; Kim, Hyo-Keun; Min, Sun Seek; Seol, Geun Hee

    2013-01-01

    The purpose of the present study is to examine the effects of essential oil of Citrus bergamia Risso (bergamot, BEO) on intracellular Ca2+ in human umbilical vein endothelial cells. Fura-2 fluorescence was used to examine changes in intracellular Ca2+ concentration [Ca2+]i . In the presence of extracellular Ca2+, BEO increased [Ca2+]i , which was partially inhibited by a nonselective Ca2+ channel blocker La3+. In Ca2+-free extracellular solutions, BEO increased [Ca2+]i in a concentration-dependent manner, suggesting that BEO mobilizes intracellular Ca2+. BEO-induced [Ca2+]i increase was partially inhibited by a Ca2+-induced Ca2+ release inhibitor dantrolene, a phospholipase C inhibitor U73122, and an inositol 1,4,5-triphosphate (IP3)-gated Ca2+ channel blocker, 2-aminoethoxydiphenyl borane (2-APB). BEO also increased [Ca2+]i in the presence of carbonyl cyanide m-chlorophenylhydrazone, an inhibitor of mitochondrial Ca2+ uptake. In addition, store-operated Ca2+ entry (SOC) was potentiated by BEO. These results suggest that BEO mobilizes Ca2+ from primary intracellular stores via Ca2+-induced and IP3-mediated Ca2+ release and affect promotion of Ca2+ influx, likely via an SOC mechanism. PMID:24348719

  4. Rapid actions of calcitriol and its side chain analogues CB1093 and GS1500 on intracellular calcium levels in skeletal muscle cells: a comparative study

    PubMed Central

    Vazquez, Guillermo; Sellés, Juana; de Boland, Ana Russo; Boland, Ricardo

    1999-01-01

    The ability of synthetic analogues of the secosteroid hormone 1α,25-dihydroxy-vitamin-D3 [calcitriol, CT; 1,25(OH)2D3] to exert non-genomic (rapid) effects on target cells has been scarcely studied. To evaluate the pharmacological potential of the CT side-chain analogues CB1093 and GS1500, we compared their fast effects on intracellular calcium concentration ([Ca2+]i) in chick skeletal muscle cells with those elicited by the natural hormone.Both analogues, similarly to CT, specifically induced rapid (30–60 s) and sustained rises in [Ca2+]i levels. CB1093 and GS1500 were more potent than the natural hormone at concentrations as low as 10−13 M (4.5 fold stimulation) and 10−12 M (2.5 fold), respectively, whereas higher concentrations (10−9–10−8 M) of CT were more effective than the analogues in elevating [Ca2+]i. Cyclic AMP was markedly increased by both analogues pointing for a role of this messenger in the fast actions of the synthetic compounds.In Ca2+ free medium CT and analogues elicited a transient elevation in [Ca2+]i. The PLC inhibitors U73122 (2 μM) and neomycin (0.5 mM), as well as depletion of intracellular stores with thapsigargin (1 μM), completely prevented CB1093/GS1500-dependent changes in [Ca2+]i suggesting that, similarly to CT, these analogues mobilized Ca2+ from an IP3/thapsigargin-sensitive store.The voltage-dependent calcium channel (VDCC) blocker nifedipine (2 μM) reduced by 50–60% the influx phase of the [Ca2+]i response to CB1093 and GS1500, indicating that VDCC contributed partially to Ca2+ entry. The Ca2+ readdition protocol suggested that analogue-dependent activation of a SOC entry pathway accounted, to the same extent as for CT, for the remaining non-VDCC mediated Ca2+ influx. PMID:10372825

  5. Mitochondrial Ca2+ homeostasis during Ca2+ influx and Ca2+ release in gastric myocytes from Bufo marinus

    PubMed Central

    Drummond, Robert M; Mix, T Christian H; Tuft, Richard A; Walsh, John V; Fay, Fredric S

    2000-01-01

    The Ca2+-sensitive fluorescent indicator rhod-2 was used to monitor mitochondrial Ca2+ concentration ([Ca2+]m) in gastric smooth muscle cells from Bufo marinus. In some studies, fura-2 was used in combination with rhod-2, allowing simultaneous measurement of cytoplasmic Ca2+ concentration ([Ca2+]i) and [Ca2+]m, respectively. During a short train of depolarizations, which causes Ca2+ influx from the extracellular medium, there was an increase in both [Ca2+]i and [Ca2+]m. The half-time (t½) to peak for the increase in [Ca2+]m was considerably longer than the t½ to peak for the increase in [Ca2+]i. [Ca2+]m remained elevated for tens of seconds after [Ca2+]i had returned to its resting value. Stimulation with caffeine, which causes release of Ca2+ from the sarcoplasmic reticulum (SR), also produced increases in both [Ca2+]i and [Ca2+]m. The values of t½ to peak for the increase in [Ca2+] in both cytoplasm and mitochondria were similar; however, [Ca2+]i returned to baseline values much faster than [Ca2+]m. Using a wide-field digital imaging microscope, changes in [Ca2+]m were monitored within individual mitochondria in situ, during stimulation of Ca2+ influx or Ca2+ release from the SR. Mitochondrial Ca2+ uptake during depolarizing stimulation caused depolarization of the mitochondrial membrane potential. The mitochondrial membrane potential recovered considerably faster than the recovery of [Ca2+]m. This study shows that Ca2+ influx from the extracellular medium and Ca2+ release from the SR are capable of increasing [Ca2+]m in smooth muscle cells. The efflux of Ca2+ from the mitochondria is a slow process and appears to be dependent upon the amount of Ca2+ in the SR. PMID:10713963

  6. Elevated serum aminotransferase levels in children at risk for obstructive sleep apnea.

    PubMed

    Kheirandish-Gozal, Leila; Sans Capdevila, Oscar; Kheirandish, Ebrahim; Gozal, David

    2008-01-01

    Fatty liver disease (FLD) is a highly prevalent condition in obese (Ob) children, who are at increased risk for obstructive sleep apnea (OSA). However, the contribution of OSA to FLD remains unknown. Prospective study. Polysomnographic evaluation and assessment of plasma levels of insulin, glucose, and lipids, and liver function tests. A total of 518 consecutive snoring children 4 to 17 years of age who were being evaluated for habitual snoring and suspected OSA. A total of 376 children had body mass index z score of < 1.20 (non-Ob children), 3 children (<1%) had elevated serum aminotransferase (LFT) levels, and 248 had OSA (65.9%). Among the 142 overweight/Ob children, 46 had elevated LFT levels (32.4%); of these children, 42 had OSA (91.3%). In contrast, OSA was present in only 71.8% of Ob children without elevated LFT level (p < 0.01). Insulin resistance and hyperlipidemia were more likely to occur in children with FLD. Furthermore, FLD was improved after treatment of OSA in 32 of 42 Ob children (p < 0.0001). Increased liver enzyme levels are frequently found in Ob snoring children, particularly among those with OSA and/or metabolic dysfunction. Effective treatment of OSA results in improved liver function test results in the vast majority of these patients.

  7. Ca2+-driven intestinal HCO3− secretion and CaCO3 precipitation in the European flounder in vivo: influences on acid-base regulation and blood gas transport

    PubMed Central

    Cooper, Christopher A.; Whittamore, Jonathan M.

    2010-01-01

    Marine teleost fish continuously ingest seawater to prevent dehydration and their intestines absorb fluid by mechanisms linked to three separate driving forces: 1) cotransport of NaCl from the gut fluid; 2) bicarbonate (HCO3−) secretion and Cl− absorption via Cl−/HCO3− exchange fueled by metabolic CO2; and 3) alkaline precipitation of Ca2+ as insoluble CaCO3, which aids H2O absorption). The latter two processes involve high rates of epithelial HCO3− secretion stimulated by intestinal Ca2+ and can drive a major portion of water absorption. At higher salinities and ambient Ca2+ concentrations the osmoregulatory role of intestinal HCO3− secretion is amplified, but this has repercussions for other physiological processes, in particular, respiratory gas transport (as it is fueled by metabolic CO2) and acid-base regulation (as intestinal cells must export H+ into the blood to balance apical HCO3− secretion). The flounder intestine was perfused in vivo with salines containing 10, 40, or 90 mM Ca2+. Increasing the luminal Ca2+ concentration caused a large elevation in intestinal HCO3− production and excretion. Additionally, blood pH decreased (−0.13 pH units) and plasma partial pressure of CO2 (Pco2) levels were elevated (+1.16 mmHg) at the highest Ca perfusate level after 3 days of perfusion. Increasing the perfusate [Ca2+] also produced proportional increases in net acid excretion via the gills. When the net intestinal flux of all ions across the intestine was calculated, there was a greater absorption of anions than cations. This missing cation flux was assumed to be protons, which vary with an almost 1:1 relationship with net acid excretion via the gill. This study illustrates the intimate link between intestinal HCO3− production and osmoregulation with acid-base balance and respiratory gas exchange and the specific controlling role of ingested Ca2+ independent of any other ion or overall osmolality in marine teleost fish. PMID:20130227

  8. DETAIL VIEW ON THE MAIN ASSEMBLY LEVEL OF ELEVATOR SHOWING ...

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

    DETAIL VIEW ON THE MAIN ASSEMBLY LEVEL OF ELEVATOR SHOWING THE DOUBLED COLUMN FOR THE BUILDING EXPANSION JOINT AT COLUMN LINE AA-18. - Offutt Air Force Base, Glenn L. Martin-Nebraska Bomber Plant, Building D, Peacekeeper Drive, Bellevue, Sarpy County, NE

  9. Plasma membrane calcium ATPases: From generic Ca(2+) sump pumps to versatile systems for fine-tuning cellular Ca(2.).

    PubMed

    Strehler, Emanuel E

    2015-04-24

    The plasma membrane calcium ATPases (PMCAs) are ATP-driven primary ion pumps found in all eukaryotic cells. They are the major high-affinity calcium extrusion system for expulsion of Ca(2+) ions from the cytosol and help restore the low resting levels of intracellular [Ca(2+)] following the temporary elevation of Ca(2+) generated during Ca(2+) signaling. Due to their essential role in the maintenance of cellular Ca(2+) homeostasis they were initially thought to be "sump pumps" for Ca(2+) removal needed by all cells to avoid eventual calcium overload. The discovery of multiple PMCA isoforms and alternatively spliced variants cast doubt on this simplistic assumption, and revealed instead that PMCAs are integral components of highly regulated multi-protein complexes fulfilling specific roles in calcium-dependent signaling originating at the plasma membrane. Biochemical, genetic, and physiological studies in gene-manipulated and mutant animals demonstrate the important role played by specific PMCAs in distinct diseases including those affecting the peripheral and central nervous system, cardiovascular disease, and osteoporosis. Human PMCA gene mutations and allelic variants associated with specific disorders continue to be discovered and underline the crucial role of different PMCAs in particular cells, tissues and organs. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Restoration of the anti-proliferative and anti-migratory effects of 1,25-dihydroxyvitamin D by silibinin in vitamin D-resistant colon cancer cells.

    PubMed

    Bhatia, Vandanajay; Falzon, Miriam

    2015-07-01

    Colorectal carcinoma (CRC) is the third most common cancer in developed countries. A large fraction of cases are linked to chronic intestinal inflammation, with concomitant increased TNF-α release and elevated Snail1/Snail2 levels. These transcription factors in turn suppress vitamin D receptor (VDR) expression, resulting in loss of responsiveness to the protective anti-proliferative and anti-migratory effects of 1,25-dihydroxyvitamin D (1,25D). Experimental and epidemiologic evidence support the use of natural products to target CRC. Here we show that the flavonolignan silibinin reverses the TNF-α-induced upregulation of Snail1 and Snail2 in the 1,25D-resistant human colon carcinoma cells HT-29. These silibinin effects are accompanied by an increase in VDR levels; Snail1 overexpression reverses these silibinin effects. Silibinin also restores promoter activity from a vitamin D-response element (VDRE) reporter construct. While 1,25D had no significant effect on HT-29 and SW480-R cell proliferation and migration, co-treatment with silibinin restored 1,25D responsiveness. In addition, co-treatment with silibinin plus 1,25D decreased proliferation and migration at doses where silibinin alone had no effect. These findings demonstrate that this combination may present a novel approach to target CRC in conditions of chronic colonic inflammation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  11. Restoration of the anti-proliferative and anti-migratory effects of 1,25-dihydroxyvitamin D by silibinin in vitamin D-resistant colon cancer cells

    PubMed Central

    Bhatia, Vandanajay; Falzon, Miriam

    2015-01-01

    Colorectal carcinoma (CRC) is the third most common cancer in developed countries. A large fraction of cases are linked to chronic intestinal inflammation, with concomitant increased TNF-α release and elevated Snail1/Snail2 levels. These transcription factors in turn suppress vitamin D receptor (VDR) expression, resulting in loss of responsiveness to the protective anti-proliferative and anti-migratory effects of 1,25-dihydroxyvitamin D (1,25D). Experimental and epidemiologic evidence support the use of natural products to target CRC. Here we show that the flavonolignan silibinin reverses the TNF-α-induced upregulation of Snail1 and Snail2 in the 1,25D-resistant human colon carcinoma cells HT-29. These silibinin effects are accompanied by an increase in VDR levels; Snail1 overexpression reverses these silibinin effects. Silibinin also restores promoter activity from a vitamin D-response element (VDRE) reporter construct. While 1,25D had no significant effect on HT-29 and SW480-R cell proliferation and migration, co-treatment with silibinin restored 1,25D responsiveness. In addition, co-treatment with silibinin plus 1,25D decreased proliferation and migration at doses where silibinin alone had no effect. These findings demonstrate that this combination may present a novel approach to target CRC in conditions of chronic colonic inflammation. PMID:25846868

  12. IGF-1 and pAKT signaling promote hippocampal CA1 neuronal survival following injury to dentate granule cells.

    PubMed

    Wine, Robert N; McPherson, Christopher A; Harry, G Jean

    2009-10-01

    Insulin-like growth factor-1 (IGF-1) protects neurons from apoptosis and in vivo offers neuroprotective support to hippocampal CA1 pyramidal neurons following ischemia or seizure. IGF-1 signals through IGF-1 receptors activating phosphytidylinositol 3-kinase (PI3K)/Akt or pMAPK pathways. IGF-1 can be induced with injury and microglia and astrocytes may serve as a source of this neurotrophic factor to promote neuronal survival. An acute systemic injection of trimethyltin (TMT; 2 mg/kg, ip) to mice induces apoptosis of dentate granule neurons within 24 h and a differential response of microglia with ramified microglia present in the CA-1 region. Using this model, we studied the role of IGF-1 in the survival of CA-1 pyramidal neurons under conditions of altered synaptic input due to changes in the dentate gyrus. Within 24 h of injection, IGF-1 mRNA levels were elevated in the hippocampus and IGF-1 protein detected in both astrocytes and microglia. IGF-1 was redistributed within the CA-1 neurons corresponding with an increase in cytoplasmic pAkt, elevated PKBalpha/Akt protein levels, and a decrease in the antagonist, Rho. pMAPK was not detected in CA-1 neurons and ERK2 showed a transient decrease followed by a significant increase, suggesting a lack of recruitment of the pMAPK signaling pathway for neuronal survival. In mice deficient for IGF-1, a similar level of apoptosis was observed in dentate granule neurons as compared to wildtype; however, TMT induced a significant level CA-1 neuronal death, further supporting a role for IGF-1 in the survival of CA-1 neurons.

  13. Elevated IL-8 levels during sickle cell crisis.

    PubMed

    Duits, A J; Schnog, J B; Lard, L R; Saleh, A W; Rojer, R A

    1998-11-01

    The vaso-occlusive process (VOC) in sickle cell disease is of a complex nature. It involves intricate interactions between sickle red blood cells, endothelium and probably also leukocytes. As these interactions are regulated by cytokines, we analyzed the role of the potent neutrophil chemokine IL-8 by measuring serum levels in sickle cell patients during sickle cell crisis. These results were compared to nonsymptomatics and healthy controls. In patients having a vaso-occlusive crisis both HbSS and HbSC patients showed significantly enhanced serum IL-8 levels compared to healthy controls. Several of these patients showed extremely elevated serum IL-8 levels which were independent of the crisis inducing factor. Furthermore, a sickle cell patient with VOC as a complication of rhGM-CSF treatment similarly showed high IL-8 serum levels at crisis onset. Nonsymptomatic sickle cell patients serum IL-8 levels were comparable to healthy controls. These results implicate a role for IL-8 at or during (the initiation of) sickle cell crisis.

  14. Amyotrophic lateral sclerosis (ALS), a novel rare cause of elevated plasma troponin T levels.

    PubMed

    Von Lueder, Thomas G; Melsom, Morten Nissen; Atar, Dan; Agewall, Stefan

    2011-01-01

    In this article, we report on a patient with chronic and modestly elevated plasma troponin T (TnT) levels and frequent hospitalizations following the first admission until his death one year later. The patient was initially admitted for dyspnea and discharged from hospital with a diagnosis of non-ST elevation acute myocardial infarction (AMI). Coronary angiography and echocardiography were normal, but the patient received the (false) diagnosis of AMI at two further admissions, based purely on elevated TnT. Shortly thereafter, severe respiratory failure with restrictive-type spirometry pattern became the predominant clinical symptom, with constantly elevated TnT levels at frequent re-admissions. Due to inconsistent follow-up by primarily junior and non-specialist staff at a number of different wards, pulmonary function tests and previous smoking history were mis-interpreted as typical of chronic obstructive pulmonary disease (COPD). The patient received standard COPD treatment without any improvement. After a year of gradually worsening respiratory failure and repeated hospitalizations, thorough assessment by a pulmonologist and neurologist established the final diagnosis of amyotrophic lateral sclerosis (ALS). The patient died shortly thereafter. While progressive respiratory failure is well-known to determine morbidity and mortality in patients with ALS, chronically elevated TnT levels in the absence of coronary artery disease have, to our best knowledge, not been described so far. We suggest that chronic myocardial hypoxia due to ALS-related hypoxic respiratory failure was the most likely underlying etiology for the elevated TnT levels seen here but other mechanism such as immune-mediated myocardial injury cannot be excluded.

  15. [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

  16. 49 CFR 571.125 - Standard No. 125; Warning devices.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 6 2010-10-01 2010-10-01 false Standard No. 125; Warning devices. 571.125 Section... Motor Vehicle Safety Standards § 571.125 Standard No. 125; Warning devices. S1. Scope. This standard... affixed to both faces of the warning device. Alternatively, a dual purpose orange fluorescent and red...

  17. 49 CFR 571.125 - Standard No. 125; Warning devices.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 6 2011-10-01 2011-10-01 false Standard No. 125; Warning devices. 571.125 Section... Motor Vehicle Safety Standards § 571.125 Standard No. 125; Warning devices. S1. Scope. This standard... affixed to both faces of the warning device. Alternatively, a dual purpose orange fluorescent and red...

  18. 49 CFR 571.125 - Standard No. 125; Warning devices.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 6 2012-10-01 2012-10-01 false Standard No. 125; Warning devices. 571.125 Section... Motor Vehicle Safety Standards § 571.125 Standard No. 125; Warning devices. S1. Scope. This standard... affixed to both faces of the warning device. Alternatively, a dual purpose orange fluorescent and red...

  19. 49 CFR 571.125 - Standard No. 125; Warning devices.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 6 2013-10-01 2013-10-01 false Standard No. 125; Warning devices. 571.125 Section... Motor Vehicle Safety Standards § 571.125 Standard No. 125; Warning devices. S1. Scope. This standard... affixed to both faces of the warning device. Alternatively, a dual purpose orange fluorescent and red...

  20. 49 CFR 571.125 - Standard No. 125; Warning devices.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 6 2014-10-01 2014-10-01 false Standard No. 125; Warning devices. 571.125 Section... Motor Vehicle Safety Standards § 571.125 Standard No. 125; Warning devices. S1. Scope. This standard... affixed to both faces of the warning device. Alternatively, a dual purpose orange fluorescent and red...

  1. Extracellular Ca2+-induced force restoration in K+-depressed skeletal muscle of the mouse involves an elevation of [K+]i: implications for fatigue

    PubMed Central

    Leader, John P.; Loiselle, Denis S.; Higgins, Amanda; Lin, Wei; Renaud, Jean-Marc

    2015-01-01

    We examined whether a Ca2+-K+ interaction was a potential mechanism operating during fatigue with repeated tetani in isolated mouse muscles. Raising the extracellular Ca2+ concentration ([Ca2+]o) from 1.3 to 10 mM in K+-depressed slow-twitch soleus and/or fast-twitch extensor digitorum longus muscles caused the following: 1) increase of intracellular K+ activity by 20–60 mM (raised intracellular K+ content, unchanged intracellular fluid volume), so that the K+-equilibrium potential increased by ∼10 mV and resting membrane potential repolarized by 5–10 mV; 2) large restoration of action potential amplitude (16–54 mV); 3) considerable recovery of excitable fibers (∼50% total); and 4) restoration of peak force with the peak tetanic force-extracellular K+ concentration ([K+]o) relationship shifting rightward toward higher [K+]o. Double-sigmoid curve-fitting to fatigue profiles (125 Hz for 500 ms, every second for 100 s) showed that prior exposure to raised [K+]o (7 mM) increased, whereas lowered [K+]o (2 mM) decreased, the rate and extent of force loss during the late phase of fatigue (second sigmoid) in soleus, hence implying a K+ dependence for late fatigue. Prior exposure to 10 mM [Ca2+]o slowed late fatigue in both muscle types, but was without effect on the extent of fatigue. These combined findings support our notion that a Ca2+-K+ interaction is plausible during severe fatigue in both muscle types. We speculate that a diminished transsarcolemmal K+ gradient and lowered [Ca2+]o contribute to late fatigue through reduced action potential amplitude and excitability. The raised [Ca2+]o-induced slowing of fatigue is likely to be mediated by a higher intracellular K+ activity, which prolongs the time before stimulation-induced K+ efflux depolarizes the sarcolemma sufficiently to interfere with action potentials. PMID:25571990

  2. Elevated Serum Pesticide Levels and Risk of Parkinson Disease

    PubMed Central

    Richardson, Jason R.; Shalat, Stuart L.; Buckley, Brian; Winnik, Bozena; O’Suilleabhain, Padraig; Diaz-Arrastia, Ramon; Reisch, Joan; German, Dwight C.

    2012-01-01

    Background Exposure to pesticides has been reported to increase the risk of Parkinson disease (PD), but identification of the specific pesticides is lacking. Three studies have found elevated levels of organochlorine pesticides in postmortem PD brains. Objective To determine whether elevated levels of organochlorine pesticides are present in the serum of patients with PD. Design Case-control study. Setting An academic medical center. Participants Fifty patients with PD, 43 controls, and 20 patients with Alzheimer disease. Main Outcome Measures Levels of 16 organochlorine pesticides in serum samples. Results β-Hexachlorocyclohexane (β-HCH) was more often detectable in patients with PD (76%) compared with controls (40%) and patients with Alzheimer disease (30%). The median level of β-HCH was higher in patients with PD compared with controls and patients with Alzheimer disease. There were no marked differences in detection between controls and patients with PD concerning any of the other 15 organochlorine pesticides. Finally, we observed a significant odds ratio for the presence of β-HCH in serum to predict a diagnosis of PD vs control (odds ratio, 4.39; 95% confidence interval, 1.67–11.6) and PD vs Alzheimer disease (odds ratio, 5.20), which provides further evidence for the apparent association between serum β-HCH and PD. Conclusions These data suggest that β-HCH is associated with a diagnosis of PD. Further research is warranted regarding the potential role of β-HCH as a etiologic agent for some cases of PD. PMID:19597089

  3. Elevated serum RANTES chemokine levels in autoimmune Addison disease.

    PubMed

    Fichna, Marta; Żurawek, Magdalena; Budny, Bartłomiej; Komarowska, Hanna; Niechciał, Elżbieta; Fichna, Piotr; Ruchała, Marek

    2018-04-30

    INTRODUCTION    Regulated on activation, normal T‑cell expressed and secreted chemokine (RANTES), the product of the CCL5 gene, is involved in trafficking immune cells into the inflammation site. It acts as coactivator of T cells and promotes polarization of the immune response towards the Th1 profile. In autoimmune Addison disease (AAD), the adrenal cortex is gradually destroyed by adrenal‑specific immune cell infiltration. RANTES might be implicated in autoimmune adrenal failure through recruitment and activation of the immune cells. Furthermore, the promoter CCL5 variant, rs2107538, seems to be associated with autoimmune endocrine conditions: diabetes and thyroid disease. OBJECTIVES    Our analysis was designed to evaluate the prevalence of rs2107538 and serum RANTES levels in AAD. PATIENTS AND METHODS    rs2107538 was genotyped using TaqMan technology in 239 individuals with AAD and 542 controls, while serum RANTES levels were evaluated by an enzyme‑linked immunosorbent assay in 114 patients with AAD and 111 healthy age- and sex‑matched individuals. RESULTS    No differences were found in rs2107538 genotype or allele frequencies between patients and controls (P = 0.53 and P = 0.39, respectively), and no association was detected with age at AAD onset (P = 0.14). Serum RANTES levels were elevated in patients with AAD compared with controls (mean [SD], 59.2 [30.3] ng/ml vs 45.5 [20.4] ng/ml, P = 0.001). Healthy carriers of various rs2107538 genotypes demonstrated differences in serum RANTES levels (P = 0.02), whereas AAD patients did not (P = 0.26). No correlation was found between circulating RANTES levels and age, AAD duration, serum autoantibodies, hydrocortisone dose, and body mass (P >0.05). CONCLUSIONS    This study demonstrates for the first time elevated serum RANTES levels in AAD and confirms that rs2107538 may affect serum chemokine levels.

  4. Serum CA 19-9 as a prognostic factor in patients with metastatic gastric cancer.

    PubMed

    Jo, Jae-Cheol; Ryu, Min-Hee; Koo, Dong-Hoe; Ryoo, Baek-Yeol; Kim, Hwa Jung; Kim, Tae Won; Choi, Kee Don; Lee, Gin Hyug; Jung, Hwoon-Yong; Yook, Jeong Hwan; Oh, Sung Tae; Kim, Byung Sik; Kim, Jin-Ho; Kang, Yoon-Koo

    2013-12-01

    To evaluate tumor markers as prognostic factors in patients with metastatic or recurrent gastric cancer receiving first-line chemotherapy. Between January 2000 and December 2008, 1178 patients with metastatic or recurrent gastric cancer were assayed for expression of three serum tumor markers, CA 19-9, CA 72-4 and carcinoembryonic antigen (CEA), prior to the initiation of first-line chemotherapy. Elevated serum concentrations of carbohydrate antigen (CA) 19-9 (>37 U/mL), CA 72-4 (>4 U/mL) and carcinoembryonic antigen (CEA) (>6 ng/mL) were observed in 38, 56 and 33% of patients, respectively. Univariate analysis showed that elevated serum concentration of each of the three markers, CA 19-9 (P = 0.001), CA 72-4 (P = 0.001) and CEA (P = 0.030), was significantly associated with poor patient prognosis. However, multivariate analysis showed that an elevated CA 19-9 concentration only was significantly associated with shorter survival (hazard ratio [HR] 1.22; 95% CI, 1.08-1.37, P = 0.002). In the good risk and moderate risk groups, previously defined by clinical factors alone, survival was significantly lower in patients with elevated CA 19-9 (P < 0.001 and P = 0.021, respectively), but this difference was not observed in the poor-risk group. Elevated serum CA 19-9 concentration in patients with metastatic or recurrent gastric cancer, especially in good or moderate risk groups, is an independent negative predictor of prognosis. © 2012 Wiley Publishing Asia Pty Ltd.

  5. Modulation of intracellular Ca(2+) via alpha(1B)-adrenoreceptor signaling molecules, G alpha(h) (transglutaminase II) and phospholipase C-delta 1.

    PubMed

    Kang, Sung Koo; Kim, Dae Kyong; Damron, Derek S; Baek, Kwang Jin; Im, Mie-Jae

    2002-04-26

    We characterized the alpha(1B)-adrenoreceptor (alpha(1B)-AR)-mediated intracellular Ca(2+) signaling involving G alpha(h) (transglutaminase II, TGII) and phospholipase C (PLC)-delta 1 using DDT1-MF2 cell. Expression of wild-type TGII and a TGII mutant lacking transglutaminase activity resulted in significant increases in a rapid peak and a sustained level of intracellular Ca(2+) concentration ([Ca(2+)](i)) in response to activation of the alpha(1B)-AR. Expression of a TGII mutant lacking the interaction with the receptor or PLC-delta 1 substantially reduced both the peak and sustained levels of [Ca(2+)](i). Expression of TGII mutants lacking the interaction with PLC-delta 1 resulted in a reduced capacitative Ca(2+) entry. Reduced expression of PLC-delta 1 displayed a transient elevation of [Ca(2+)](i) and a reduction in capacitative Ca(2+) entry. Expression of the C2-domain of PLC-delta 1, which contains the TGII interaction site, resulted in reduction of the alpha(1B)-AR-evoked peak increase in [Ca(2+)](i), while the sustained elevation in [Ca(2+)](i) and capacitative Ca(2+) entry remained unchanged. These findings demonstrate that stimulation of PLC-delta 1 via coupling of the alpha(1B)-AR with TGII evokes both Ca(2+) release and capacitative Ca(2+) entry and that capacitative Ca(2+) entry is mediated by the interaction of TGII with PLC-delta 1.

  6. [Children with hyperthyroidism due to elevated hCG levels].

    PubMed

    Jöbsis, Jasper J; van Trotsenburg, A S Paul; Merks, Johannes H M; Kamp, Gerdine A

    2014-01-01

    We describe two children with hyperthyroidism secondary to elevated hCG levels: one patient with gestational trophoblastic disease and one patient with choriocarcinoma. hCG resembles other glycoproteins that can lead to hyperthyroidism through TSH receptor activation. Also, through its LH-mimicking effect, hCG can induce high oestradiol levels, resulting in stormy pubertal development. False negative hCG tests due to the high-dose hook effect may complicate the diagnostic process. In patients with antibody-negative thyrotoxicosis, the diagnosis of hCG-induced hyperthyroidism must be considered.

  7. Elevated lipoprotein (a) levels are an independent risk factor for retinal vein occlusion.

    PubMed

    Kuhli-Hattenbach, Claudia; Miesbach, Wolfgang; Lüchtenberg, Marc; Kohnen, Thomas; Hattenbach, Lars-Olof

    2017-03-01

    To investigate the prevalence of lipoprotein (a) [Lp(a)] and other thrombophilic disorders among retinal vein occlusion (RVO) patients with regard to age and various risk factors. We retrospectively reviewed the medical records of 100 patients with central, hemicentral or branch RVO who had undergone routine thrombophilia screening. Data were compared with 100 controls. Both cohorts were divided into three subgroups (≤45 years, >45-≤60 years or >60 years), depending on the patients' age at the time of the RVO or a previous thromboembolic event. Elevated Lp(a) plasma levels were significantly more prevalent among RVO patients than among controls (p < 0.0001; OR: 4.8). Moreover, we determined age ≤60 years by the time of the first thromboembolic event as a strong predictor of elevated Lp(a) (p = 0.0002). The coincidence of elevated Lp(a) with other coagulation disorders further increased the OR for RVO to 9.3 (95% CI 2.1-41.8). Multivariate analysis revealed the presence of cardiovascular risk factors (OR: 3.1, p = 0.0004), elevated lipoprotein (a) levels (OR: 5.2, p = 0.0001) and increased factor VIII activity (OR: 5.9, p = 0.001) as independent risk factors for the development of RVO among patients. Our results indicate that elevated plasma levels of Lp(a) are associated with the development of RVO. Selective screening of young patients and subjects with a personal or family history of thromboembolism may be helpful in identifying RVO patients with elevated Lp(a). © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  8. Cobalt chloride compromises transepithelial barrier properties of CaCo-2 BBe human gastrointestinal epithelial cell layers.

    PubMed

    DiGuilio, K M; Valenzano, M C; Rybakovsky, E; Mullin, J M

    2018-01-05

    Elevation of the transcription factor HIF-1 is a prominent mediator of not only processes that accompany hypoxia, but also the tumor microenvironment and tissue regeneration. This study uses mediators of "chemical hypoxia" to ask the question whether HIF-1α elevation in a healthy epithelial cell layer leads to leakiness in its tight junctional seals. Transepithelial electrical resistance and transepithelial diffusion of 14 C-D-mannitol and other radiolabeled probes are used as indicators of transepithelial barrier function of CaCo-2 BBe human gastrointestinal epithelial cell layers cultured on permeable supports. Western immunoblot analyses of integral tight junctional proteins (occludin and claudins) are used as further indicators of barrier function change. Cobalt, an inhibitor of the prolyl hydroxylase enzymes governing HIF-1α breakdown in the cell, induces transepithelial leakiness in CaCo-2 BBe cell layers in a time and concentration-dependent manner. This increased leakiness is accompanied by significant changes in certain specific integral tight junctional (TJ) proteins such as a decreased level of occludin and increased level of claudin-5. Similar results regarding barrier function compromise also occur with other chemical inhibitors of HIF-1α breakdown, namely ciclopiroxolamine (CPX) and dimethyloxalylglycine (DMOG). The increased leak is manifested by both decreased transepithelial electrical resistance (R t ) and increased paracellular diffusion of D-mannitol (J m ). The induced transepithelial leak shows significant size selectivity, consistent with induced effects on TJ permeability. Less-differentiated cell layers were significantly more affected than well-differentiated cell layers regarding induced transepithelial leak. A genetically modified CaCo-2 variant with reduced levels of HIF-1β, showed reduced transepithelial leak in response to cobalt exposure, further indicating that elevation of HIF-1α levels induced by agents of "chemical hypoxia

  9. Tidal marsh plant responses to elevated CO2 , nitrogen fertilization, and sea level rise.

    PubMed

    Adam Langley, J; Mozdzer, Thomas J; Shepard, Katherine A; Hagerty, Shannon B; Patrick Megonigal, J

    2013-05-01

    Elevated CO2 and nitrogen (N) addition directly affect plant productivity and the mechanisms that allow tidal marshes to maintain a constant elevation relative to sea level, but it remains unknown how these global change drivers modify marsh plant response to sea level rise. Here we manipulated factorial combinations of CO2 concentration (two levels), N availability (two levels) and relative sea level (six levels) using in situ mesocosms containing a tidal marsh community composed of a sedge, Schoenoplectus americanus, and a grass, Spartina patens. Our objective is to determine, if elevated CO2 and N alter the growth and persistence of these plants in coastal ecosystems facing rising sea levels. After two growing seasons, we found that N addition enhanced plant growth particularly at sea levels where plants were most stressed by flooding (114% stimulation in the + 10 cm treatment), and N effects were generally larger in combination with elevated CO2 (288% stimulation). N fertilization shifted the optimal productivity of S. patens to a higher sea level, but did not confer S. patens an enhanced ability to tolerate sea level rise. S. americanus responded strongly to N only in the higher sea level treatments that excluded S. patens. Interestingly, addition of N, which has been suggested to accelerate marsh loss, may afford some marsh plants, such as the widespread sedge, S. americanus, the enhanced ability to tolerate inundation. However, if chronic N pollution reduces the availability of propagules of S. americanus or other flood-tolerant species on the landscape scale, this shift in species dominance could render tidal marshes more susceptible to marsh collapse. © 2013 Blackwell Publishing Ltd.

  10. Calcium-sensing receptor (CaSR): pharmacological properties and signaling pathways.

    PubMed

    Conigrave, Arthur D; Ward, Donald T

    2013-06-01

    In this article we consider the mechanisms by which the calcium-sensing receptor (CaSR) induces its cellular responses via the control (activation or inhibition) of signaling pathways. We consider key features of CaSR-mediated signaling including its control of the heterotrimeric G-proteins Gq/11, Gi/o and G12/13 and the downstream consequences recognizing that very few CaSR-mediated cell phenomena have been fully described. We also consider the manner in which the CaSR contributes to the formation of specific signaling scaffolds via peptide recognition sequences in its intracellular C-terminal along with the origins of its high level of cooperativity, particularly for Ca(2+)o, and its remarkable resistance to desensitization. We also consider the nature of the mechanisms by which the CaSR controls oscillatory and sustained Ca(2+)i mobilizing responses and inhibits or elevates cyclic adenosine monophosphate (cAMP) levels dependent on the cellular and signaling context. Finally, we consider the diversity of the receptor's ligands, ligand binding sites and broader compartment-dependent physiological roles leading to the identification of pronounced ligand-biased signaling for agonists including Sr(2+) and modulators including l-amino acids and the clinically effective calcimimetic cinacalcet. We note the implications of these findings for the development of new designer drugs that might target the CaSR in pathophysiological contexts beyond those established for the treatment of disorders of calcium metabolism. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Depolarization- and transmitter-induced changes in intracellular Ca2+ of rat cerebellar granule cells in explant cultures.

    PubMed

    Connor, J A; Tseng, H Y; Hockberger, P E

    1987-05-01

    Digital imaging of the Ca indicator fura-2 has been used to study the responses of developing granule cells in culture to depolarization and transmitter action. Unstimulated cells bathed in Krebs saline exhibited cytoplasmic Ca ion concentrations, [Ca2+], that were generally in the 30-60 nM range. Exposure of cells to high-potassium (25 mM) saline depolarized the membrane potential and produced an immediate rise in [Ca2+] that recovered within 2-3 min in normal saline. The response grew progressively larger over the first 20 d in culture. Transient increases in [Ca2+] to levels greater than 1 microM were observed after 12-14 d in vitro, at which time the cells displayed intense electrical activity when exposed to high K. At this stage, the increases were attenuated by blocking action potential activity with TTX. In TTX-treated or immature cells, in which the transient phase of the Ca change was relatively small, a second exposure to high K typically produced a much larger Ca response that the initial exposure. The duration of this facilitation of the response persisted for periods longer than 5 min. Application of the neurotransmitter GABA induced a transient increase in membrane conductance, with a reversal potential near resting potential (approx. -60 mV), and caused an intracellular Ca2+ increase that outlasted the exposure to GABA by several minutes. Glutamate, or kainate, induced an increase in membrane conductance but with a reversal potential more positive than spike threshold. These agents also elevated intracellular Ca2+, but unlike the case with GABA, this Ca response reversed rapidly upon removal of the transmitter. The facilitatory effect of repeated exposures to high-K saline, as well as the persistent Ca elevation following a brief GABA application, suggests that granule cells possess the capability of displaying activity-dependent changes in Ca levels in culture.

  12. Elevated ground-level O(3) changes the diversity of anoxygenic purple phototrophic bacteria in paddy field.

    PubMed

    Feng, Youzhi; Lin, Xiangui; Yu, Yongchang; Zhu, Jianguo

    2011-11-01

    The knowledge of the impact of elevated ground-level O(3) below ground the agro-ecosystem is limited. A field experiment in China Ozone Free-Air Concentration Enrichment (FACE-O(3)) facility on a rice-wheat rotation system was carried out to investigate responses of anoxygenic phototrophic purple bacteria (AnPPB) to elevated ground-level O(3). AnPPB community structures and sizes in paddy soil were monitored by molecular approaches including PCR-DGGE and real-time quantitative PCR based upon the pufM gene on three typical rice growth stages. Repetitive sequence-based PCR (rep-PCR) in combination with culture-reliant method was conducted to reveal changes in genotypic diversity. Elevated ground-level O(3) statistically reduce AnPPB abundance and percentage in total bacterial community in flooded rice soil via decreasing their genotypic diversity and metabolic versatility. Concomitantly, their community composition changed after rice anthesis stage under elevated ground-level O(3). Our results from AnPPB potential responses imply that continuously elevated ground-level O(3) in the future would eventually harm the health of paddy ecosystem through negative effect on soil microorganisms.

  13. Differential skeletal responses of hindlimb unloaded rats on a vitamin D-deficient diet to 1,25-dihydroxyvitamin D3 and its analog, seocalcitol (EB1089)

    NASA Technical Reports Server (NTRS)

    Narayanan, Ramesh; Allen, Matthew R.; Gaddy, Dana; Bloomfield, Susan A.; Smith, Carolyn L.; Weigel, Nancy L.

    2004-01-01

    Conditions of disuse in bed rest patients, as well as microgravity experienced by astronauts are accompanied by reduced mechanical loading, reduced calcium absorption, and lower serum levels of 1,25(OH)2D3 (1,25-D), the active metabolite of vitamin D, all contributing to bone loss. To determine whether 1,25-D or a less calcemic analog, Seocalcitol or EB1089 (1 alpha,25-dihydroxy-22,24-diene-24,26,27-trihomovitamin D3) can alleviate bone loss in a rat hindlimb unloading model of disuse osteopenia, mature male rats originally on a vitamin D replete diet containing 1.01% calcium were transferred to a vitamin D-deficient diet containing 0.48% calcium and then tail suspended and treated for 28 days with vehicle, 0.05 microg/kg 1,25-D, or 0.05 microg/kg EB1089. The vitamin D-deficient diet caused a substantial decrease in bone mineral density (-8%), which may be compounded by hindlimb unloading (-10%). Exogenous 1,25-D not only prevented the bone loss but also increased the bone mineral density to greater than the baseline level (+7%). EB1089 was less effective in preventing bone loss. Analysis of site and cell-specific effects of 1,25-D and EB1089 revealed that 1,25-D was more active than EB1089 in the intestine, the site of calcium absorption, and in inducing osteoclastogenesis and bone resorption whereas EB1089 was more effective in inducing osteoblast differentiation. These studies suggest that elevating circulating 1,25-D levels presumably increasing calcium absorption can counteract bone loss induced by disuse or microgravity with its associated reductions in circulating 1,25-D and decreased calcium absorption.

  14. SOUTH ELEVATION OF GOLD HILL MILL, LOOKING NORTH. THE PRIMARY ...

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

    SOUTH ELEVATION OF GOLD HILL MILL, LOOKING NORTH. THE PRIMARY ORE BIN IS A CENTER, WITH A JAW CRUSHER JUST TO THE RIGHT. A CONVEYOR (MISSING) WAS USED TO CARRY CRUSHED ORE UP AND INTO THE SECONDARY ORE BIN. THE STONE RAMP TO THE LEFT OF THE ORE BIN WAS USED TO DRIVE TRUCKS UP TO DUMPING LEVEL. - Gold Hill Mill, Warm Spring Canyon Road, Death Valley Junction, Inyo County, CA

  15. Caribbean mangroves adjust to rising sea level through biotic controls on change in soil elevation

    USGS Publications Warehouse

    McKee, K.L.; Cahoon, D.R.; Feller, Ilka C.

    2007-01-01

    Aim The long-term stability of coastal ecosystems such as mangroves and salt marshes depends upon the maintenance of soil elevations within the intertidal habitat as sea level changes. We examined the rates and processes of peat formation by mangroves of the Caribbean Region to better understand biological controls on habitat stability. Location Mangrove-dominated islands on the Caribbean coasts of Belize, Honduras and Panama were selected as study sites. Methods Biological processes controlling mangrove peat formation were manipulated (in Belize) by the addition of nutrients (nitrogen or phosphorus) to Rhizophora mangle (red mangrove), and the effects on the dynamics of soil elevation were determined over a 3-year period using rod surface elevation tables (RSET) and marker horizons. Peat composition and geological accretion rates were determined at all sites using radiocarbon-dated cores. Results The addition of nutrients to mangroves caused significant changes in rates of mangrove root accumulation, which influenced both the rate and direction of change in elevation. Areas with low root input lost elevation and those with high rates gained elevation. These findings were consistent with peat analyses at multiple Caribbean sites showing that deposits (up to 10 m in depth) were composed primarily of mangrove root matter. Comparison of radiocarbon-dated cores at the study sites with a sea-level curve for the western Atlantic indicated a tight coupling between peat building in Caribbean mangroves and sea-level rise over the Holocene. Main conclusions Mangroves common to the Caribbean region have adjusted to changing sea level mainly through subsurface accumulation of refractory mangrove roots. Without root and other organic inputs, submergence of these tidal forests is inevitable due to peat decomposition, physical compaction and eustatic sea-level rise. These findings have relevance for predicting the effects of sea-level rise and biophysical processes on tropical

  16. Clinical significance and diagnostic capacity of serum TK1, CEA, CA 19-9 and CA 72-4 levels in gastric and colorectal cancer patients.

    PubMed

    Ning, Shufang; Wei, Wene; Li, Jilin; Hou, Bingbing; Zhong, Jianhong; Xie, Yuxuan; Liu, Haizhou; Mo, Xianwei; Chen, Jiansi; Zhang, Litu

    2018-01-01

    Despite extensive progress in treatment for cancer in recent decades, the early diagnosis for gastric cancer (GC) and colorectal cancer (CRC) remains poor. In this study, we explore the diagnostic value of joint detection of thymidine kinase 1 (TK1), carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9) and carbohydrate antigen 72-4 (CA 72-4) in the diagnosis of GC and CRC, and to evaluated the relationship between TK1 expression and clinical pathological characteristics in the patients. Serum TK1, CA 19-9, CA 72-4 and CEA levels were measured in 169 patients with GC, 344 patients with CRC and 75 healthy controls using electro-chemiluminescence. The TK1 concentration was significantly higher in patients with cancer than in healthy controls and patients with clinical stage Ⅲ+Ⅳ had higher TK1 levels than clinical stage Ⅰ+Ⅱ ( P <0.05). The levels of TK1 is significantly associated with tumor stage, lymph node metastasis, distant metastasis, tumor differentiation and age ( P <0.05). When the tumor markers (TK1, CA 19-9 and CA 72-4) were detected respectively, the area under receiver operating characteristics curve (AUC) of TK1 for three cancers was the highest (0.823-0.895). However, the combination of AUC was higher than that for each tumor marker detected respectively (0.934-0.953), and the Hosmer-Lemeshow test showed an adequate model of calibration (P>0.05). Moreover, the AUCs varied significantly between the combination tests and single biomarker tests (Z test, P <0.01). In conclusion, serum TK1 may be an independent tumor marker for GC and CRC patients, and the combination of TK1, CA 19-9 and CA 72-4 and CEA performed even better. This study suggests that combination detection of four tumor markers may prove to be useful for the diagnosis of GC and CRC.

  17. [Prevalence of Elevated Lipoprotein (a) Levels in Patients < 60 Years of Age with Retinal Vein Occlusion].

    PubMed

    Kuhli-Hattenbach, C; Hellstern, P; Miesbach, W; Kohnen, T; Hattenbach, L-O

    2018-01-01

    The potential impact of elevated Lipoprotein (a) [Lp(a)] levels on retinal venous occlusive (RVO) diseases with regard to age and various risk factors has not been studied extensively. In a retrospective case-control study, thrombophilia data of 106 young patients (< 60 years at the time of the RVO or a previous thromboembolic event) with RVO and 76 healthy subjects were evaluated. Elevated Lp(a) plasma levels were significantly more prevalent among RVO patients (29.2 %) than among controls (9.2 %; p = 0.0009). Lp(a) levels were found to be significantly (p = 0.012) different between patients and controls. Moreover, we found that an unusual personal or family history of thromboembolism was a strong predictor of elevated Lp(a) (p = 0.03). We observed a significant correlation between elevated Lp(a) and other coagulation disorders (p = 0.005). Multivariate analysis showed that elevated lipoprotein(a) levels (OR: 3.5; p = 0.003) were an independent risk factor for the development of RVO. Elevated plasma levels of Lp(a) are associated with the development of RVO. Selective screening of young patients and subjects with a personal or family history of thromboembolism may be helpful in identifying RVO patients with elevated Lp(a). Georg Thieme Verlag KG Stuttgart · New York.

  18. Intestinal lymphangiectasia mimicking primary peritoneal carcinoma.

    PubMed

    Steines, Jennifer C; Larson, Joshua H; Wilkinson, Neal; Kirby, Patricia; Goodheart, Michael J

    2010-10-01

    Intestinal lymphangiectasia is an obstruction of the lymphatic system. We report on a patient with mesenteric adenopathy and an elevated CA125 level, which were suspicious for peritoneal carcinoma. Further evaluation and bowel resection identified intestinal lymphangiectasia. This disease should be considered in patients with mesenteric adenopathy and a small bowel mass. Copyright © 2010 Mosby, Inc. All rights reserved.

  19. Elevated systemic galectin-1 levels characterize HELLP syndrome.

    PubMed

    Schnabel, Annegret; Blois, Sandra M; Meint, Peter; Freitag, Nancy; Ernst, Wolfgang; Barrientos, Gabriela; Conrad, Melanie L; Rose, Matthias; Seelbach-Göbel, Birgit

    2016-04-01

    Galectin-1 (gal-1), a member of a family of conserved β-galactoside-binding proteins, has been shown to exert a key role during gestation. Though gal-1 is expressed at higher levels in the placenta from HELLP patients, it is still poorly understood whether systemic gal-1 levels also differ in HELLP patients. In the present study, we evaluated the systemic expression of gal-1, together with the angiogenic factors, placental growth factor (PlGF) and soluble fms-like tyrosine kinase 1 (sFlt-1) in conjunction with HELLP syndrome severity. Systemic levels of gal-1 and sFlt-1 were elevated in patients with both early- and late-onset HELLP syndrome as compared to healthy controls. In contrast, peripheral PlGF levels were decreased in early- and late-onset HELLP. A positive correlation between systemic gal-1 levels and sFlt-1/PlGF ratios was found in early onset HELLP patients. Our results show that HELLP syndrome is associated with increased circulating levels of gal-1; integrating systemic gal-1 measurements into the diagnostic analyses of pregnant women may provide more effective prediction of HELLP syndrome development. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  20. Elevated Choline-Containing Compound Levels in Rapid Cycling Bipolar Disorder.

    PubMed

    Cao, Bo; Stanley, Jeffrey A; Passos, Ives Cavalcante; Mwangi, Benson; Selvaraj, Sudhakar; Zunta-Soares, Giovana B; Soares, Jair C

    2017-10-01

    Previous studies have found increased levels of choline-containing compounds (ie, glycerophosphocholine plus phosphocholine (GPC+PC)) in bipolar disorder using in vivo proton magnetic resonance spectroscopy ( 1 H MRS), especially in bipolar I disorder (BD-I). Increased levels of GPC+PC suggest alterations in the membrane phospholipids metabolism in bipolar disorder. Rapid cycling (RC) bipolar disorder is considered as a severe course of bipolar disorder, but it is unclear whether rapid cycling bipolar disorder is linked to highly altered membrane phospholipid metabolism. The purpose of this study was to investigate whether the regional extent of elevated GPC+PC were greater in BD-I patients with rapid cycling compared to BD-I patients without rapid cycling and healthy controls. Using a multi-voxel 1 H MRS approach at 3 Tesla with high spatial resolution and absolute quantification, GPC+PC levels from the anterior cingulate cortex (ACC), caudate and putamen of 16 RC BD-I, 34 non-RC BD-I and 44 healthy controls were assessed. We found significantly elevated GPC+PC levels in ACC, putamen and caudate of RC BD-I patients compared to healthy controls (P<0.005) and in ACC compared to non-RC BD-I patients (P<0.05). These results suggest greater alteration of membrane phospholipid metabolisms in rapid cycling BD-I compared to non-rapid-cycling BD-I.

  1. MONOTERPENE LEVELS IN NEEDLES OF DOUGLAS-FIR EXPOSED TO ELEVATED CO2 AND TEMPERATURE

    EPA Science Inventory

    Levels of monoterpenes in current year needles of douglas-fir (Pseudotsuga menziesii (Mirb.) Franco) seedlings were measured at the conclusion of four years of exposure to ambient or elevated CO2 (+ 179 mmol.mol-1), and ambient or elevated temperature (+ 3.5 C). Eleven monoterpen...

  2. Renal hemodynamic response to galanin: importance of elevated plasma glucose.

    PubMed

    Premen, A J

    1989-12-01

    Although recent data point to a possible indirect role for galanin in modulating renal blood flow (RBF) and fluid homeostasis in experimental animals, there have been no systematic studies exploring the possible direct effects of the peptide on the mammalian kidney. We ascertained the RBF, glomerular filtration rate (GFR) and plasma glucose responses to direct intrarenal infusion of three progressively increasing doses of synthetic galanin in anesthetized dogs. A 50 ng/kg per min dose (n = 6) failed to affect RBF, GFR or arterial plasma glucose (APG). Yet, a 100 ng/kg per min dose elevated RBF and GFR by 13 and 14%, respectively, while concomitantly increasing APG by 38%. At 200 ng/kg per min, galanin elevated RBF and GFR by 32 and 33%, respectively, while elevating APG by 57%. Intrarenal infusion of glucose (12.5 mg/kg per min; n = 6), reproducing the percentage rise in glucose (62%) elicited by the highest dose of galanin, elevated RBF and GFR by 20 and 23%, respectively. These data indicate that the elevated plasma glucose level, stimulated by galanin infusion, may account for about 63 and 70% of the RBF and GFR responses, respectively, elicited by galanin infusion at the 200 ng dose. The factors mediating the remaining renal hyperemia and hyperfiltration await resolution.

  3. Consideration of vertical uncertainty in elevation-based sea-level rise assessments: Mobile Bay, Alabama case study

    USGS Publications Warehouse

    Gesch, Dean B.

    2013-01-01

    The accuracy with which coastal topography has been mapped directly affects the reliability and usefulness of elevationbased sea-level rise vulnerability assessments. Recent research has shown that the qualities of the elevation data must be well understood to properly model potential impacts. The cumulative vertical uncertainty has contributions from elevation data error, water level data uncertainties, and vertical datum and transformation uncertainties. The concepts of minimum sealevel rise increment and minimum planning timeline, important parameters for an elevation-based sea-level rise assessment, are used in recognition of the inherent vertical uncertainty of the underlying data. These concepts were applied to conduct a sea-level rise vulnerability assessment of the Mobile Bay, Alabama, region based on high-quality lidar-derived elevation data. The results that detail the area and associated resources (land cover, population, and infrastructure) vulnerable to a 1.18-m sea-level rise by the year 2100 are reported as a range of values (at the 95% confidence level) to account for the vertical uncertainty in the base data. Examination of the tabulated statistics about land cover, population, and infrastructure in the minimum and maximum vulnerable areas shows that these resources are not uniformly distributed throughout the overall vulnerable zone. The methods demonstrated in the Mobile Bay analysis provide an example of how to consider and properly account for vertical uncertainty in elevation-based sea-level rise vulnerability assessments, and the advantages of doing so.

  4. High-Intensity Targeted Screening for Elevated Blood Lead Levels Among Children in 2 Inner-City Chicago Communities

    PubMed Central

    Dignam, Timothy A.; Evens, Anne; Eduardo, Eduard; Ramirez, Shokufeh M.; Caldwell, Kathleen L.; Kilpatrick, Nikki; Noonan, Gary P.; Flanders, W. Dana; Meyer, Pamela A.; McGeehin, Michael A.

    2004-01-01

    Objectives. We assessed the prevalence of elevated blood lead levels (≥ 10 micrograms of lead per deciliter of blood), risk factors, and previous blood lead testing among children in 2 high-risk Chicago, Ill, communities. Methods. Through high-intensity targeted screening, blood lead levels were tested and risks were assessed among a representative sample of children aged 1 to 5 years who were at risk for lead exposure. Results. Of the 539 children who were tested, 27% had elevated blood lead levels, and 61% had never been tested previously. Elevated blood lead levels were associated with chipped exterior house paint. Conclusions. Most of the children who lived in these communities—where the prevalence for elevated blood lead levels among children was 12 times higher than the national prevalence—were not tested for lead poisoning. Our findings highlight the need for targeted community outreach that includes testing blood lead levels in accordance with the American Academy of Pediatrics’ recommendations. PMID:15514235

  5. Elevated cortisol levels in Cushing's disease are associated with cognitive decrements.

    PubMed

    Starkman, M N; Giordani, B; Berent, S; Schork, M A; Schteingart, D E

    2001-01-01

    The objective of this study was to use Cushing's disease as a unique human model to elucidate the cognitive deficits resulting from exposure to chronic stress-level elevations of endogenous cortisol. Forty-eight patients with a first episode of acute, untreated Cushing's disease and 38 healthy control subjects were studied. Scores for four of five verbal IQ subtests were significantly lower in patients with Cushing's disease; their scores were significantly lower for only one nonverbal performance IQ subtest (block design). Verbal, but not visual, learning and delayed recall at 30 minutes were significantly decreased among patients with Cushing's disease. Although verbal delayed recall was significantly lower in these patients, the retention index (percentage), which compares the amount of initially learned material to that recalled after the delay, was not significantly decreased. There was no significant association between depression scores and cognitive performance. A higher degree of cortisol elevation was associated with poorer performance on several subtests of learning, delayed recall, and visual-spatial ability. Chronically elevated levels of glucocorticoids have deleterious effects on particular domains of cognition. Verbal learning and other verbal functions seem more vulnerable than nonverbal functions. The results suggest that both the neocortex and hippocampus are affected.

  6. Iris Damage Is Associated With Elevated Cytokine Levels in Aqueous Humor.

    PubMed

    Aketa, Naohiko; Yamaguchi, Takefumi; Suzuki, Terumasa; Higa, Kazunari; Yagi-Yaguchi, Yukari; Satake, Yoshiyuki; Tsubota, Kazuo; Shimazaki, Jun

    2017-05-01

    To evaluate the association between iris damage and cytokine levels in the aqueous humor (AqH). A total of 201 AqH samples from 201 consecutive patients (mean age 73.7 ± 10.6) were collected at the beginning of corneal transplantation or cataract surgery. Iris damage of each case was assessed from preoperative slit-lamp findings based on its severity. The subjects were classified into three groups: eyes without iris damage (126 eyes), eyes with mild iris damage (51 eyes), and eyes with severe iris damage (24 eyes). The levels of cytokines (IL-1α, IL-1β, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-17a, interferon gamma-induced protein [IP]-10, monocyte chemotactic protein [MCP]-1, IFN-α, IFN-γ, macrophage inflammatory protein [MIP]-1α, MIP-1β, P-selectin, E-selectin, soluble intercellular adhesion molecule [sICAM]-1, TNF-α, and granulocyte-macrophage colony-stimulating factor [GM-CSF]) in AqH were measured by multiplex beads immunoassay. The levels of aqueous protein, IL-1α, IL-1β, IL-4, IL-6, IL-8, IL-10, IL-17A, MCP-1, TNF-α, E-selectin, P-selectin, and sICAM-1 in eyes with mild and severe iris damage were higher than in those without iris damage (P < 0.033). Multivariate analyses of clinical factors revealed that iris damage was associated with the history of complicated glaucoma, and the number of previous intraocular surgeries. The levels of AqH IL-6, IL-8, IL-13, MIP-1α, TNF-α, and sICAM-1 were significantly elevated in eyes with mild and severe iris damage in phakic eyes, and the levels of AqH IL-8 and sICAM-1 were significantly elevated in eyes with severe iris damage in pseudophakic eyes, compared with the eyes without iris damage (P < 0.045). Iris damage was associated with the elevation in the levels of aqueous protein and cytokines.

  7. Elevated levels of the mismatch repair protein PMS2 are associated with prostate cancer.

    PubMed

    Norris, Alixanna M; Woodruff, R D; D'Agostino, Ralph B; Clodfelter, Jill E; Scarpinato, Karin Drotschmann

    2007-02-01

    Defects in mismatch repair (MMR) proteins have been identified in various types of cancer. However, an association with prostate cancer has been controversial. Defective MMR results in genome instability with detrimental consequences that significantly contribute to tumorigenesis. This study determined alterations in key MMR protein levels in prostate cancer with the goal to identify prognostic markers. Prostatectomy samples were immunohistochemically stained and the relative presence or absence of key proteins MSH2, MLH1, and PMS2 determined. Cancer tissue of distinct grades was compared with the normal surrounding tissue. Microsatellite instability (MSI) in altered tissues was determined according to NCI guidelines. In contrast to reports that associate a lack of individual MMR proteins with tumorigenesis, a significant increase in PMS2 levels was identified in PIN lesions and prostate cancer tissue. This elevation in PMS2 was independent of changes in levels in its heterodimeric partner, MLH1. Prostate tumors with elevated levels of PMS2 were genetically unstable, which was corrected by MLH1 co-elevation. This is the first documentation of detrimental consequences associated with the increase in a MMR protein in human cancer. This study recognizes PMS2 elevation as a prognostic marker in pre-neoplastic and prostate cancer lesions. This result has significant implications for future diagnostic and treatment measures. (c) 2006 Wiley-Liss, Inc.

  8. Elevated Serum PSA is Associated With Human Herpesvirus 8 Infection and Increased Circulating Cytokine Levels in Men From Tobago.

    PubMed

    Henning, Jill D; Karamchandani, Jaideep M; Bonachea, Luis A; Bunker, Clareann H; Patrick, Alan L; Jenkins, Frank J

    2017-05-01

    Serum-prostate specific antigen (PSA) levels have been used for many years as a biomarker for prostate cancer. This usage is under scrutiny due to the fact that elevated PSA levels can be caused by other conditions such as benign prostatic hyperplasia and infections of or injury to the prostate. As a result, the identification of specific pathogens capable of increasing serum levels of PSA is important. A potential candidate responsible for elevated PSA is human herpesvirus 8 (HHV-8). We have reported previously that HHV-8 is capable of infecting and establishing a latent infection in the prostate. In this current study we test the hypothesis that HHV-8 infection is associated with elevated PSA levels. Circulating cytokine levels between men with elevated PSA and controls are also compared. HHV-8 serostatus was determined among men with elevated serum PSA (≥4 ng/ml; n = 168, no prostate cancer on biopsy) and age-matched controls (PSA <4 ng/ml; n = 234), Circulating cytokine levels were determined among a subset of each group (116 with elevated PSA and 85 controls). Men with an elevated serum PSA were significantly more likely to be HHV-8 seropositive (42.9%) than the age-matched cancer-free men (22.2%; OR 2.51; 95%CI 1.48-4.29, P = 00001). Comparison of circulating cytokine levels between men with elevated serum PSA and controls indicated that elevated serum PSA is associated with a pro-inflammatory response with a mixed Th1/Th2 response while HHV-8 infection was associated with significantly higher levels of IL12p70, IL-10, and IL-13 indicating a Th2 immune response. We found a significant association between HHV-8 infection and increased levels of serum PSA. In an age of patient-centered medicine, men with an elevated serum PSA should be considered for HHV-8 serology testing to determine if HHV-8 is responsible for the elevated PSA. Prostate 77: 617-624, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  9. 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

  10. Trace Element Partitioning Between low-Ca Pyroxene and Ultracalcic Liquids.

    NASA Astrophysics Data System (ADS)

    Pertermann, M.; Schmidt, M. W.; Pettke, T.

    2003-12-01

    Low-Ca pyroxene or pigeonite ( ˜0.25-0.35 Ca per formula unit, pfu) is an important residual phase during high temperature melting of refractory mantle (e.g., ankaramite formation). High-Ca cpx (>0.6-0.7 Ca pfu) may be residual to relatively low temperature melting of fertile mantle (MOR and OI), but the opx-cpx solvus narrows considerably at higher temperatures (>1330-1350° C), leading to coexisting opx and low-Ca cpx. Little is known about the trace element partitioning of such low-Ca cpx at upper mantle conditions. Our new partitioning experiments investigate the role of low-Ca cpx during melting of depleted peridotite. Nominally anhydrous experiments with graphite-lined Pt-capsules were conducted at 1.4 GPa and 1360-1370° C. The synthetic starting material is close in composition to an ultracalcic liquid saturated in opx+pigeonite+olivine+spinel. The experiments yielded assemblages of glass, low-Ca cpx, ol, and minor Cr-spinel; opx is absent. The low-Ca clinopyroxenes have 0.20 and 0.32 Ca pfu at 1370 and 1360° C, respectively, and tetrahedral Al of 0.046 and 0.067 pfu. The liquids have ˜50 wt% SiO2, ˜12.5 wt% CaO and CaO/Al2O3 of 1.44-1.54. Pyroxenes and glasses were analyzed for trace elements (La, Ce, Nd, Sm, Eu, Gd, Dy, Er Yb, Lu, Sc, Y, Sr, Zr, Hf, V, Cr, Mn, Co, Zn) by LA-ICP-MS using a 193 nm ArF excimer laser coupled to an Elan 6100 mass spectrometer. Ablation occurred in He, and ablation spot sizes were 15-30 μ m for minerals and 50 μ m for glasses. Trace element concentrations in pyroxenes were low for most 3+ and 4+ cations. This resulted in small mineral/melt partition coefficients (D-values), approximately an order of magnitude lower than those for high-Ca cpx associated with peridotite melting, thus making the low-Ca cpx partitioning behavior rather similar to the behavior of peridotitic opx. Cpx with 0.32 Ca pfu has slightly elevated D-values for 3+ cations when compared to the 0.20 Ca pfu cpx: DSc = 0.45, DY = 0.11, DSm = 0.054 and DYb

  11. Can preoperative and postoperative CA19-9 levels predict survival and early recurrence in patients with resectable hilar cholangiocarcinoma?

    PubMed

    Wang, Jun-Ke; Hu, Hai-Jie; Shrestha, Anuj; Ma, Wen-Jie; Yang, Qin; Liu, Fei; Cheng, Nan-Sheng; Li, Fu-Yu

    2017-07-11

    To investigate the predictive values of preoperative and postoperative serum CA19-9 levels on survival and other prognostic factors including early recurrence in patients with resectable hilar cholangiocarcinoma. In univariate analysis, increased preoperative and postoperative CA19-9 levels in the light of different cut-off points (37, 100, 150, 200, 400, 1000 U/ml) were significantly associated with poor survival outcomes, of which the cut-off point of 150 U/ml showed the strongest predictive value (both P < 0.001). Preoperative to postoperative increase in CA19-9 level was also correlated with poor survival outcome (P < 0.001). In multivariate analysis, preoperative CA19-9 level > 150 U/ml was significantly associated with lymph node metastasis (OR = 3.471, 95% CI 1.216-9.905; P = 0.020) and early recurrence (OR = 8.280, 95% CI 2.391-28.674; P = 0.001). Meanwhile, postoperative CA19-9 level > 150 U/ml was also correlated with early recurrence (OR = 4.006, 95% CI 1.107-14.459; P = 0.034). Ninety-eight patients who had undergone curative surgery for hilar cholangiocarcinoma between 1995 and 2014 in our institution were selected for the study. The correlations of preoperative and postoperative serum CA19-9 levels on the basis of different cut-off points with survival and various tumor factors were retrospectively analyzed with univariate and multivariate methods. In patients with resectable hilar cholangiocarcinoma, serum CA19-9 predict survival and early recurrence. Patients with increased preoperative and postoperative CA19-9 levels have poor survival outcomes and higher tendency of early recurrence.

  12. SAFETY AND SECURITY BUILDING, TRA614. ELEVATIONS. SECTIONS. TWO ROOF LEVELS. ...

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

    SAFETY AND SECURITY BUILDING, TRA-614. ELEVATIONS. SECTIONS. TWO ROOF LEVELS. BLAW-KNOX 3150-814-2, 3/1950. INL INDEX NO. 531-0614-00-098-100703, REV. 6. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  13. 41 CFR 102-80.125 - Who has the responsibility for determining the acceptability of each equivalent level of safety...

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... departments or other local authorities for use in developing pre-fire plans. ... Fire Prevention Equivalent Level of Safety Analysis § 102-80.125 Who has the responsibility for... acceptability must include a review of the fire protection engineer's qualifications, the appropriateness of the...

  14. 41 CFR 102-80.125 - Who has the responsibility for determining the acceptability of each equivalent level of safety...

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... departments or other local authorities for use in developing pre-fire plans. ... Fire Prevention Equivalent Level of Safety Analysis § 102-80.125 Who has the responsibility for... acceptability must include a review of the fire protection engineer's qualifications, the appropriateness of the...

  15. 41 CFR 102-80.125 - Who has the responsibility for determining the acceptability of each equivalent level of safety...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... departments or other local authorities for use in developing pre-fire plans. ... Fire Prevention Equivalent Level of Safety Analysis § 102-80.125 Who has the responsibility for... acceptability must include a review of the fire protection engineer's qualifications, the appropriateness of the...

  16. 41 CFR 102-80.125 - Who has the responsibility for determining the acceptability of each equivalent level of safety...

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... departments or other local authorities for use in developing pre-fire plans. ... Fire Prevention Equivalent Level of Safety Analysis § 102-80.125 Who has the responsibility for... acceptability must include a review of the fire protection engineer's qualifications, the appropriateness of the...

  17. 41 CFR 102-80.125 - Who has the responsibility for determining the acceptability of each equivalent level of safety...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... departments or other local authorities for use in developing pre-fire plans. ... Fire Prevention Equivalent Level of Safety Analysis § 102-80.125 Who has the responsibility for... acceptability must include a review of the fire protection engineer's qualifications, the appropriateness of the...

  18. Quality changes of highbush blueberries fruit stored in CA with different CO levels.

    PubMed

    Duarte, Carolina; Guerra, María; Daniel, Peter; Camelo, Andrés López; Yommi, Alejandra

    2009-01-01

    Quality changes of blueberries (Vacccinium corymbosum L. cv Brigitta) were evaluated during CA storage (0 degrees C) with different concentrations of CO(2) (5%, 10%, and 15%) combined with 5% O(2), respectively. Atmospheric air (20.9% O(2)+ 0.03% CO(2)) was used as control. From samples taken at 0, 24, and 48 d of storage, unmarketable fruits and weight loss were recorded as well as color (h), firmness (g), soluble solid content (%), titratable acidity (% citric acid), ratio, and the monomeric anthocyanin content (ppm). At each sampling time, additional units were kept for 3 d at 10 degrees C to simulate retail holding conditions. Irrespective of gas concentration, 0.9% of the initial fresh weight was lost after 48 d at 0 degrees C. CA fruit had better quality than control at the 24 d sampling but due to the high number of unmarketable fruits, this advantage was not observed at 48 d at 0 degrees C. After 24 d of storage, fruits for CA treatments were more firm and had better color, with higher anthocyanin and acidity levels. Soluble solid content showed no significant differences throughout the cold storage period. Residual effect of CA storage was observed at the retail holding condition yielding better firmness, acidity, and ratio. However, the CO(2) level tested increased the number of unmarketable fruit in long-term storage (48 d). Response of "Brigitta" blueberries to the different CO(2) levels studied was moderate and could be related to the high storage potential of this cultivar.

  19. Prognostic significance of preimmunotherapy serum CA27.29 (MUC-1) mucin level after active specific immunotherapy of metastatic adenocarcinoma patients.

    PubMed

    MacLean, G D; Reddish, M A; Longenecker, B M

    1997-01-01

    The TRUQUANT BR radioimmunoassay, which uses monoclonal antibody B27.29 to quantitate CA27.29 mucin antigen (MUC-1 gene product) in serum, has recently received Food and Drug Administration approval for predicting recurrent breast cancer in patients with stage II and III disease. The purpose of this study was to determine whether the new radioimmunoassay for serum MUC-1 has prognostic significance for patients with metastatic adenocarcinoma receiving active specific immunotherapy (ASI). Using 40 U/ml as the upper limit of "normal," patients with metastatic breast and ovarian cancer with a preimmunotherapy serum CA27.29 mucin > 40 U/ml (CA27.29 Hi patients) had a poorer survival than CA27.29 Lo patients (< or = 40 U/ml) after ASI. There was no significant correlation between preimmunotherapy CA27.29 serum levels and measurable tumor burden. The preimmunotherapy CA27.29 serum level was a predictor of poor survival of metastatic colorectal and pancreatic cancer patients independent of other prognostic factors. There seemed to be two populations of pancreatic cancer patients, separated at 60 U/ml serum CA27.29 (CA27.29 Hi versus Lo patients). A CA27.29 serum level of 22 U/ml separated patients with CA27.29 Hi vs. Lo colorectal cancer. Patients with CA27.29 Lo colorectal and pancreatic cancer survived longer after ASI compared with patients with CA27.29 Hi colorectal and pancreatic cancer, respectively. We suggest that various CA27.29 serum levels define poor prognosis patients (CA27.29 Hi secretors) versus good prognosis patients (CA27.29 Lo secretors) for different cancer types.

  20. Clinical Significance of Serum Interleukin-31 and Interleukin-33 Levels in Patients of Endometrial Cancer: A Case Control Study

    PubMed Central

    Zeng, Xi; Zhang, Zhu; Gao, Qian-Qian; Wang, Yan-Yun; Yu, Xiu-Zhang; Zhou, Bin; Xi, Ming-Rong

    2016-01-01

    Aims. Previous evidence has proved that interleukin-31 (IL-31) and interleukin-33 (IL-33) can be potential markers in some cancers' formulation. We aimed to determine the potential role of IL-31 and IL-33 in prognosis of endometrial cancer patients. Methods. Serum samples were collected from 160 patients with endometrial cancer and 160 healthy controls. The ELISA kits (Raybio® Systems) specific for human IL-31 and human IL-33 were used. Serum levels of tumor markers (CEA, CA-125, and CA19-9) were measured by chemiluminescence immunoassay. A two-side P value < 0.05 was indicated to be significant. Results. Serum levels of IL-31 and IL-33 in patients were significantly elevated compared to those of healthy controls. The interleukin levels were also related to clinical characteristics, including tumor stages, depth of invasion, and existence of node metastases and distant metastases. The sensitivity and specificity of IL-31 and IL-33 were higher than the counterparts of tumor markers, both separately and in combination of IL-31, IL-33, and the clinical markers. Conclusions. This report is the first one mentioning the possible association between serum IL-31 and IL-33 and endometrial cancer. With their sensitivity and specificity, the interleukins may be useful biomarkers for endometrial cancer's prognosis. PMID:27340318

  1. Evaluation of a childhood lead questionnaire in predicting elevated blood lead levels in a rural community.

    PubMed

    Muñiz, Marco A; Dundas, Robert; Mahoney, Martin C

    2003-01-01

    The accuracy of a lead screening questionnaire in predicting elevated blood lead levels was examined in a pediatric practice in a rural part of New York state. A retrospective chart review was used to collect data on children ages 9 to 24 months who presented for well-child visits. Children with both questionnaire and lead level results available in the chart were included in the study (n = 171). The mean blood lead level among all children was 1.6 microg/dl (median = 2.0 microg/dl, range 0 to 24 microg/dl). Four children (2.3%) had elevated lead levels (greater than 10 microg/dl), with levels for two of these children being greater than 20 microg/dl. Although our lead screening questionnaire was expanded from the standard 1991 CDC questionnaire by the inclusion of six additional items, it was not especially useful in predicting elevated blood lead levels above 10 microg/dl. However, the questionnaire exhibited some utility in predicting marked elevations in blood lead levels (over 20 microg/dl). Although results in other geographic areas might differ, the lead questionnaire may have value by enhancing parents' awareness of potential lead hazards in their children's environment and may prove to be more useful in areas of high risk to lead exposure.

  2. Conserved Regulation of p53 Network Dosage by MicroRNA–125b Occurs through Evolving miRNA–Target Gene Pairs

    PubMed Central

    Khaw, Swea Ling; Chin, Lingzi; Teh, Cathleen; Tay, Junliang; O'Day, Elizabeth; Korzh, Vladimir; Yang, Henry; Lal, Ashish; Lieberman, Judy; Lodish, Harvey F.; Lim, Bing

    2011-01-01

    MicroRNAs regulate networks of genes to orchestrate cellular functions. MiR-125b, the vertebrate homologue of the Caenorhabditis elegans microRNA lin-4, has been implicated in the regulation of neural and hematopoietic stem cell homeostasis, analogous to how lin-4 regulates stem cells in C. elegans. Depending on the cell context, miR-125b has been proposed to regulate both apoptosis and proliferation. Because the p53 network is a central regulator of both apoptosis and proliferation, the dual roles of miR-125b raise the question of what genes in the p53 network might be regulated by miR-125b. By using a gain- and loss-of-function screen for miR-125b targets in humans, mice, and zebrafish and by validating these targets with the luciferase assay and a novel miRNA pull-down assay, we demonstrate that miR-125b directly represses 20 novel targets in the p53 network. These targets include both apoptosis regulators like Bak1, Igfbp3, Itch, Puma, Prkra, Tp53inp1, Tp53, Zac1, and also cell-cycle regulators like cyclin C, Cdc25c, Cdkn2c, Edn1, Ppp1ca, Sel1l, in the p53 network. We found that, although each miRNA–target pair was seldom conserved, miR-125b regulation of the p53 pathway is conserved at the network level. Our results lead us to propose that miR-125b buffers and fine-tunes p53 network activity by regulating the dose of both proliferative and apoptotic regulators, with implications for tissue stem cell homeostasis and oncogenesis. PMID:21935352

  3. Northwest corner, showing arcade at ground level, and triple leaded ...

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

    Northwest corner, showing arcade at ground level, and triple leaded glass windows of bender room high on north elevation. - Stanford University Library, Stanford University, Palo Alto, Santa Clara County, CA

  4. Store-operated Ca2+ entry supports contractile function in hearts of hibernators

    PubMed Central

    Nakipova, Olga V.; Averin, Alexey S.; Evdokimovskii, Edward V.; Pimenov, Oleg Yu.; Kosarski, Leonid; Ignat’ev, Dmitriy; Anufriev, Andrey; Kokoz, Yuri M.; Reyes, Santiago; Terzic, Andre; Alekseev, Alexey E.

    2017-01-01

    Hibernators have a distinctive ability to adapt to seasonal changes of body temperature in a range between 37°C and near freezing, exhibiting, among other features, a unique reversibility of cardiac contractility. The adaptation of myocardial contractility in hibernation state relies on alterations of excitation contraction coupling, which becomes less-dependent from extracellular Ca2+ entry and is predominantly controlled by Ca2+ release from sarcoplasmic reticulum, replenished by the Ca2+-ATPase (SERCA). We found that the specific SERCA inhibitor cyclopiazonic acid (CPA), in contrast to its effect in papillary muscles (PM) from rat hearts, did not reduce but rather potentiated contractility of PM from hibernating ground squirrels (GS). In GS ventricles we identified drastically elevated, compared to rats, expression of Orai1, Stim1 and Trpc1/3/4/5/6/7 mRNAs, putative components of store operated Ca2+ channels (SOC). Trpc3 protein levels were found increased in winter compared to summer GS, yet levels of Trpc5, Trpc6 or Trpc7 remained unchanged. Under suppressed voltage-dependent K+, Na+ and Ca2+ currents, the SOC inhibitor 2-aminoethyl diphenylborinate (2-APB) diminished whole-cell membrane currents in isolated cardiomyocytes from hibernating GS, but not from rats. During cooling-reheating cycles (30°C–7°C–30°C) of ground squirrel PM, 2-APB did not affect typical CPA-sensitive elevation of contractile force at low temperatures, but precluded the contractility at 30°C before and after the cooling. Wash-out of 2-APB reversed PM contractility to control values. Thus, we suggest that SOC play a pivotal role in governing the ability of hibernator hearts to maintain their function during the transition in and out of hibernating states. PMID:28531217

  5. Divergence of seafloor elevation and sea level rise in coral reef ecosystems

    NASA Astrophysics Data System (ADS)

    Yates, Kimberly K.; Zawada, David G.; Smiley, Nathan A.; Tiling-Range, Ginger

    2017-04-01

    Coral reefs serve as natural barriers that protect adjacent shorelines from coastal hazards such as storms, waves, and erosion. Projections indicate global degradation of coral reefs due to anthropogenic impacts and climate change will cause a transition to net erosion by mid-century. Here, we provide a comprehensive assessment of the combined effect of all of the processes affecting seafloor accretion and erosion by measuring changes in seafloor elevation and volume for five coral reef ecosystems in the Atlantic, Pacific, and Caribbean over the last several decades. Regional-scale mean elevation and volume losses were observed at all five study sites and in 77 % of the 60 individual habitats that we examined across all study sites. Mean seafloor elevation losses for whole coral reef ecosystems in our study ranged from -0.09 to -0.8 m, corresponding to net volume losses ranging from 3.4 × 106 to 80.5 × 106 m3 for all study sites. Erosion of both coral-dominated substrate and non-coral substrate suggests that the current rate of carbonate production is no longer sufficient to support net accretion of coral reefs or adjacent habitats. We show that regional-scale loss of seafloor elevation and volume has accelerated the rate of relative sea level rise in these regions. Current water depths have increased to levels not predicted until near the year 2100, placing these ecosystems and nearby communities at elevated and accelerating risk to coastal hazards. Our results set a new baseline for projecting future impacts to coastal communities resulting from degradation of coral reef systems and associated losses of natural and socioeconomic resources.

  6. 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.

  7. Methamphetamine toxicity-induced calcineurin activation, nuclear translocation of nuclear factor of activated T-cells and elevation of cyclooxygenase 2 levels are averted by calpastatin overexpression in neuroblastoma SH-SY5Y cells.

    PubMed

    Chetsawang, Jirapa; Nudmamud-Thanoi, Sutisa; Phonchai, Ruchee; Abubakar, Zuroida; Govitrapong, Piyarat; Chetsawang, Banthit

    2018-06-23

    Methamphetamine (METH) is an addictive stimulant drug that has many negative consequences, including toxic effects to the brain. Recently, the induction of inflammatory processes has been identified as a potential contributing factor to induce neuronal cell degeneration. It has been demonstrated that the expression of inflammatory agents, such as cyclooxygenase 2 (COX-2), depends on the activation of calcineurin (CaN) and nuclear factor of activated T-cells (NFAT). Moreover, the excessive elevation in cytosolic Ca 2+ levels activates the cell death process, including calpain activation in neurons, which was diminished by the overexpression of the calpain inhibitor protein, calpastatin. However, it is unclear whether calpain mediates CaN-NFAT activation in the neurotoxic process. In the present study, we observed that the toxic high dose of METH-treated neuroblastoma SH-SY5Y cells significantly decreased cell viability but increased apoptotic cell death, the active cleaved form of calcineurin, the nuclear translocation of NFAT, and COX-2 levels. Nevertheless, these toxic effects were diminished in METH-treated calpastatin-overexpressing SH-SY5Y cells. These findings might emphasize the role of calpastatin against METH-induced toxicity by a mechanism related to calpain-dependent CaN-NFAT activation-induced COX-2 expression. Copyright © 2018. Published by Elsevier B.V.

  8. Adult Kawasaki's disease with myocarditis, splenomegaly, and highly elevated serum ferritin levels.

    PubMed

    Cunha, Burke A; Pherez, Francisco M; Alexiadis, Varvara; Gagos, Marios; Strollo, Stephanie

    2010-01-01

    erythema. We present a case of adult Kawasaki's disease with myocarditis and splenomegaly. The patient's myocarditis rapidly resolved, and he did not develop coronary artery aneurysms. In addition to splenomegaly, this case of adult Kawasaki's disease is remarkable because the patient had highly elevated serum ferritin levels of 944-1303 ng/mL; (normal<189 ng/mL). To the best of our knowledge, this is the first report of adult Kawasaki's disease with highly elevated serum ferritin levels. This is also the first report of splenomegaly in adult Kawasaki's disease. We conclude that Kawasaki's disease should be considered in the differential diagnosis in adult patients with rash/fever for> or =5 days with conjunctival suffusion, cervical adenopathy, swelling of the dorsum of the hands/feet, thrombocytosis and otherwise unexplained highly elevated ferritin levels. Copyright 2010 Elsevier Inc. All rights reserved.

  9. 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

  10. The Effects of Calcitonin on the Development of and Ca2+ Levels in Heat-shocked Bovine Preimplantation Embryos In Vitro

    PubMed Central

    KAMANO, Shumpei; IKEDA, Shuntaro; SUGIMOTO, Miki; KUME, Shinichi

    2014-01-01

    Intracellular calcium homeostasis is essential for proper cell function. We investigated the effects of heat shock on the development of and the intracellular Ca2+ levels in bovine preimplantation embryos in vitro and the effects of calcitonin (CT), a receptor-mediated Ca2+ regulator, on heat shock-induced events. Heat shock (40.5 C for 10 h between 20 and 30 h postinsemination) of in vitro-produced bovine embryos did not affect the cleavage rate; however, it significantly decreased the rates of development to the 5- to 8-cell and blastocyst stages as compared with those of the control cultured for the entire period at 38.5 C (P < 0.05). The relative intracellular Ca2+ levels at the 1-cell stage (5 h after the start of heat shock), as assessed by Fluo-8 AM, a fluorescent probe for Ca2+, indicated that heat shock significantly lowered the Ca2+ level as compared with the control level. Semiquantitative reverse transcription PCR and western blot analyses revealed the expression of CT receptor in bovine preimplantation embryos. The addition of CT (10 nM) to the culture medium ameliorated the heat shock-induced impairment of embryonic development beyond the 5- to 8-cell stage. The Ca2+ level in the heat-shocked embryos cultured with CT was similar to that of the control embryos, suggesting that heat shock lowers the Ca2+ level in fertilized embryos in vitro and that a lower Ca2+ level is implicated in heat shock-induced impairment of embryonic development. Intracellular Ca2+-mobilizing agents, e.g., CT, may effectively circumvent the detrimental effects of heat shock on early embryonic development. PMID:24899099

  11. West wing, west elevation, seen entirety from the pasture at ...

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

    West wing, west elevation, seen entirety from the pasture at the west edge of state park property. (recreation of HABS No. CA-38-P152-1). - Vallejo Adobe, Adobe Road at Casa Grande, Petaluma, Sonoma County, CA

  12. 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.

  13. The role of laparoscopy in the diagnosis and treatment of peritoneal carcinomatosis: a case report.

    PubMed Central

    Takizawa, B. T.; Shin, E. K.; Masters, L.; Lancelle, F.; Anaf, V.; Shahabi, S.

    2001-01-01

    A patient presented with deep venous thrombosis and an elevated CA-125 level, but normal pelvic ultrasound and abdominal and pelvic CT scans. Laparoscopy revealed diffuse carcinomatosis and a diagnosis of stage IIIc, poorly differentiated epithelial ovarian carcinoma was made. Laparoscopy may provide an alternative means of diagnosis when conventional imaging fails, and may facilitate the placement of catheters for subsequent intraperitoneal therapy. PMID:11393262

  14. 13. WEST ELEVATION, POWERHOUSE, WITH FIGURES AND AUTOMOBILES Historic photograph ...

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

    13. WEST ELEVATION, POWERHOUSE, WITH FIGURES AND AUTOMOBILES Historic photograph no. 1646, no date, held at Media Arts and Services Department, Pacific Gas & Electric Co., San Francisco, CA. - Centerville Hydroelectric System, Powerhouse, Butte Creek, Centerville, Butte County, CA

  15. Domain model for Ca2(+)-inactivation of Ca2+ channels at low channel density.

    PubMed Central

    Sherman, A; Keizer, J; Rinzel, J

    1990-01-01

    The "shell" model for Ca2(+)-inactivation of Ca2+ channels is based on the accumulation of Ca2+ in a macroscopic shell beneath the plasma membrane. The shell is filled by Ca2+ entering through open channels, with the elevated Ca2+ concentration inactivating both open and closed channels at a rate determined by how fast the shell is filled. In cells with low channel density, the high concentration Ca2+ "shell" degenerates into a collection of nonoverlapping "domains" localized near open channels. These domains form rapidly when channels open and disappear rapidly when channels close. We use this idea to develop a "domain" model for Ca2(+)-inactivation of Ca2+ channels. In this model the kinetics of formation of an inactivated state resulting from Ca2+ binding to open channels determines the inactivation rate, a mechanism identical with that which explains single-channel recordings on rabbit-mesenteric artery Ca2+ channels (Huang Y., J. M. Quayle, J. F. Worley, N. B. Standen, and M. T. Nelson. 1989. Biophys. J. 56:1023-1028). We show that the model correctly predicts five important features of the whole-cell Ca2(+)-inactivation for mouse pancreatic beta-cells (Plants, T. D. 1988. J. Physiol. 404:731-747) and that Ca2(+)-inactivation has only minor effects on the bursting electrical activity of these cells. PMID:2174274

  16. 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.

  17. Loss of carbonic anhydrase XII function in individuals with elevated sweat chloride concentration and pulmonary airway disease.

    PubMed

    Lee, Melissa; Vecchio-Pagán, Briana; Sharma, Neeraj; Waheed, Abdul; Li, Xiaopeng; Raraigh, Karen S; Robbins, Sarah; Han, Sangwoo T; Franca, Arianna L; Pellicore, Matthew J; Evans, Taylor A; Arcara, Kristin M; Nguyen, Hien; Luan, Shan; Belchis, Deborah; Hertecant, Jozef; Zabner, Joseph; Sly, William S; Cutting, Garry R

    2016-05-15

    Elevated sweat chloride levels, failure to thrive (FTT), and lung disease are characteristic features of cystic fibrosis (CF, OMIM #219700). Here we describe variants in CA12 encoding carbonic anhydrase XII in two pedigrees exhibiting CF-like phenotypes. Exome sequencing of a white American adult diagnosed with CF due to elevated sweat chloride, recurrent hyponatremia, infantile FTT and lung disease identified deleterious variants in each CA12 gene: c.908-1 G>A in a splice acceptor and a novel frameshift insertion c.859_860insACCT. In an unrelated consanguineous Omani family, two children with elevated sweat chloride, infantile FTT, and recurrent hyponatremia were homozygous for a novel missense variant (p.His121Gln). Deleterious CFTR variants were absent in both pedigrees. CA XII protein was localized apically in human bronchiolar epithelia and basolaterally in the reabsorptive duct of human sweat glands. Respiratory epithelial cell RNA from the adult proband revealed only aberrant CA12 transcripts and in vitro analysis showed greatly reduced CA XII protein. Studies of ion transport across respiratory epithelial cells in vivo and in culture revealed intact CFTR-mediated chloride transport in the adult proband. CA XII protein bearing either p.His121Gln or a previously identified p.Glu143Lys missense variant localized to the basolateral membranes of polarized Madin-Darby canine kidney (MDCK) cells, but enzyme activity was severely diminished when assayed at physiologic concentrations of extracellular chloride. Our findings indicate that loss of CA XII function should be considered in individuals without CFTR mutations who exhibit CF-like features in the sweat gland and lung. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  18. Synthesis of (125) I-lamivudine and (125) I-lamivudine-ursodeoxycholic acid codrug.

    PubMed

    Motaleb, M A; Abo-Kul, M; Ibrahim, Samy M; Saad, Shokry M; Arafat, Muhammad

    2016-09-01

    The preparation of (125) I-lamivudine ((125) I-3TC) and (125) I-lamivudine-ursodeoxycholic acid codrug ((125) I-3TC-UDCA), suitable for comparative biodistribution studies, is described. The synthesis of the unlabeled precursor 3TC-UDCA proceeds in an 11.6% yield, and the radiolabelling yields for (125) I-3TC and (125) I-3TC-UDCA were 89 and 92%, respectively. The final products are radiochemically pure (greater than 98%). Copyright © 2016 John Wiley & Sons, Ltd.

  19. Endocrine disrupting alkylphenols: structural requirements for their adverse effects on Ca2+ pumps, Ca2+ homeostasis & Sertoli TM4 cell viability.

    PubMed

    Michelangeli, Francesco; Ogunbayo, Oluseye A; Wootton, Laura L; Lai, Pei F; Al-Mousa, Fawaz; Harris, Robert M; Waring, Rosemary H; Kirk, Christopher J

    2008-11-25

    Alkylphenols such as nonylphenol are pollutants that are widely dispersed within our environment. They bio-accumulate within man, with levels in the muM concentration range reported in human tissues. These chemicals act as endocrine disruptors, having xenoestrogenic activity. More recently alkylphenols have also been shown to affect Ca2+ signalling pathways. Here we show that alkylphenols are potent inhibitors of sarcoplasmic-endoplasmic reticulum Ca2+-ATPase (SERCA) activity. For linear chain alkylphenols the potency of inhibition is related to chain length, with the IC50 values for inhibition ranging from 8 microM for 4-n-nonylphenol (C9) to 1.3 mM for 4-n-propylphenol (C3). Branched chain alkylphenols generally had lower potencies than their linear chain counterparts, however, good correlations for all alkylphenols were observed between their Ca2+ pump inhibition and hydrophobicity, molecular volume and flexibility, indicating that these parameters are all important factors. Alkylphenols cause abnormal elevations of intracellular [Ca2+] within TM4 Sertoli cells (cells involved in sperm maturation) depolarise their mitochondria and induce cell death in these cells, in an alkyl chain size-dependent manner.

  20. Vitamin D3-induced hypercalcemia increases carbon tetrachloride-induced hepatotoxicity through elevated oxidative stress in mice

    PubMed Central

    Usuda, Haruki; Miura, Nobuhiko; Fukuishi, Nobuyuki; Nonogaki, Tsunemasa; Onosaka, Satomi

    2017-01-01

    The aim of this study was to determine whether calcium potentiates acute carbon tetrachloride (CCl4) -induced toxicity. Elevated calcium levels were induced in mice by pre-treatment with cholecalciferol (vitamin D3; V.D3), a compound that has previously been shown to induce hypercalcemia in human and animal models. As seen previously, mice injected with CCl4 exhibited increased plasma levels of alanine aminotransferase, aspartate aminotransferase, and creatinine; transient body weight loss; and increased lipid peroxidation along with decreased total antioxidant power, glutathione, ATP, and NADPH. Pre-treatment of these animals with V.D3 caused further elevation of the values of these liver functional markers without altering kidney functional markers; continued weight loss; a lower lethal threshold dose of CCl4; and enhanced effects on lipid peroxidation and total antioxidant power. In contrast, exposure to V.D3 alone had no effect on plasma markers of liver or kidney damage or on total antioxidant power or lipid peroxidation. The potentiating effect of V.D3 was positively correlated with elevation of hepatic calcium levels. Furthermore, direct injection of CaCl2 also enhanced CCl4-induced hepatic injury. Since CaCl2 induced hypercalcemia transiently (within 3 h of injection), our results suggest that calcium enhances the CCl4-induced hepatotoxicity at an early stage via potentiation of oxidative stress. PMID:28448545

  1. Comparison of QTc and Troponin Levels in ST Elevation MIs Compared with Non-ST Elevation MIs.

    PubMed

    Henrie, Nathan; Harvell, Bryan; Ernst, Amy A; Weiss, Steven J; Oglesbee, Scott; Sarangarm, Dusadee; Hernandez, Lorenzo

    2017-03-01

    ST elevation myocardial infarctions (STEMIs) and non-ST elevation myocardial infarctions (NSTEMIs) have differences that can be important to differentiate. Our primary hypothesis was that corrected QT (QTc) duration and troponin I levels were higher in STEMIs compared with NSTEMIs. The objective of our study was to compare STEMIs with NSTEMIs for QTc duration and troponin levels. This was a retrospective case-control study of all STEMIs and a random sample of NSTEMIs during a 1-year period. STEMIs were retrieved by searching our electrocardiogram database for all of the cardiology-diagnosed STEMIs. NSTEMIs were found by selecting a randomized sample of all of the patients with a final discharge diagnosis of NSTEMI. Records and electrocardiograms were reviewed for initial troponin I levels and QTc duration. Data extractors were educated formally and a 5% sample was reevaluated by the other extractor as a reliability measure. Data analysis included χ 2 tests and parametric or nonparametric analysis, where appropriate. A logistic regression model was created with variables selected a priori for predictors of STEMIs compared with NSTEMIs. A total of 92 STEMIs and 111 NSTEMIs were evaluated, and interrater reliability showed 90% agreement. Patients with NSTEMIs had significantly longer QTc. Troponin I did not differ on univariate analysis. In a logistic model, Hispanics were more likely than whites to have a STEMI (adjusted odds ratio [AOR] 2.2, 95% confidence interval [CI] 1.09-4.5). An increase in troponin I of 1 was associated with a 7% increase in the AOR of a STEMI (AOR 1.7, 95% CI 1.03-1.12) and an increase in QTc by 10 was associated with a 13% decrease in the AOR of a STEMI (AOR 0.87, 95% CI 0.78-0.93). Patients with NSTEMIs had longer QTc intervals and lower troponin I levels than those with STEMIs.

  2. Elevated Serum Fibroblast Growth Factor 21 Levels in Patients With Hyperthyroidism.

    PubMed

    Xiao, Fangsen; Lin, Mingzhu; Huang, Peiying; Zeng, Jinyang; Zeng, Xin; Zhang, Huijie; Li, Xiaoying; Yang, Shuyu; Li, Zhibin; Li, Xuejun

    2015-10-01

    Recent evidence from animal studies indicates that fibroblast growth factor 21 (FGF21), an endocrine hormone that regulates glucose, lipid metabolism, and energy homeostasis, is regulated by T3. However, the role of FGF21 in hyperthyroid patients is unknown. The objective was to study serum FGF21 levels in hyperthyroid patients and the association of serum FGF21 levels with hyperthyroidism. This was a case-control study. A total of 119 hyperthyroid patients and 108 healthy subjects were recruited. Of them, 41 hyperthyroid patients received thionamide treatment for 3 months until euthyroidism was obtained. Serum FGF21 levels were determined using the ELISA method. Serum FGF21 levels were significantly elevated in hyperthyroid patients as compared with normal subjects [median 290.67 (interquartile range, 156.60-502.33) vs 228.10 (169.85.25-320.10) pg/mL; P < .001]. After thionamide treatment, serum FGF21 levels in hyperthyroid patients declined markedly from 249.10 (139.10-444.00) to 106.90 (38.70-196.15) pg/mL (P < .001). Logistic regression revealed that FGF21, basal metabolic rate, low-density lipoprotein cholesterol, and alanine transaminase were significantly associated with hyperthyroidism. With adjustment for potential confounders, serum FGF21 remained independently associated with hyperthyroidism, with an adjusted odds ratio of 3.123 (95% confidence interval, 1.306-7.468) (P = .010). Serum FGF21 levels were elevated in patients with hyperthyroidism and declined after thionamide treatment. And serum FGF21 level was independently associated with hyperthyroidism.

  3. Divergence of seafloor elevation and sea level rise in coral reef ecosystems

    USGS Publications Warehouse

    Yates, Kimberly K.; Zawada, David G.; Smiley, Nathan A.; Tiling-Range, Ginger

    2017-01-01

    Coral reefs serve as natural barriers that protect adjacent shorelines from coastal hazards such as storms, waves, and erosion. Projections indicate global degradation of coral reefs due to anthropogenic impacts and climate change will cause a transition to net erosion by mid-century. Here, we provide a comprehensive assessment of the combined effect of all of the processes affecting seafloor accretion and erosion by measuring changes in seafloor elevation and volume for five coral reef ecosystems in the Atlantic, Pacific, and Caribbean over the last several decades. Regional-scale mean elevation and volume losses were observed at all five study sites and in 77 % of the 60 individual habitats that we examined across all study sites. Mean seafloor elevation losses for whole coral reef ecosystems in our study ranged from −0.09 to −0.8 m, corresponding to net volume losses ranging from 3.4  ×  106 to 80.5  ×  106 m3 for all study sites. Erosion of both coral-dominated substrate and non-coral substrate suggests that the current rate of carbonate production is no longer sufficient to support net accretion of coral reefs or adjacent habitats. We show that regional-scale loss of seafloor elevation and volume has accelerated the rate of relative sea level rise in these regions. Current water depths have increased to levels not predicted until near the year 2100, placing these ecosystems and nearby communities at elevated and accelerating risk to coastal hazards. Our results set a new baseline for projecting future impacts to coastal communities resulting from degradation of coral reef systems and associated losses of natural and socioeconomic resources.

  4. Elevated extracellular calcium increases expression of bone morphogenetic protein-2 gene via a calcium channel and ERK pathway in human dental pulp cells

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

    Tada, Hiroyuki; Nemoto, Eiji, E-mail: e-nemoto@umin.ac.jp; Kanaya, Sousuke

    Dental pulp cells, which have been shown to share phenotypical features with osteoblasts, are capable of differentiating into odontoblast-like cells and generating a dentin-like mineral structure. Elevated extracellular Ca{sup 2+}Ca{sub o}{sup 2+} has been implicated in osteogenesis by stimulating the proliferation and differentiation of osteoblasts; however, the role of Ca{sub o}{sup 2+} signaling in odontogenesis remains unclear. We found that elevated Ca{sub o}{sup 2+} increases bone morphogenetic protein (BMP)-2 gene expression in human dental pulp cells. The increase was modulated not only at a transcriptional level but also at a post-transcriptional level, because treatment with Ca{sup 2+} increased the stabilitymore » of BMP-2 mRNA in the presence of actinomycin D, an inhibitor of transcription. A similar increase in BMP-2 mRNA level was observed in other human mesenchymal cells from oral tissue; periodontal ligament cells and gingival fibroblasts. However, the latter cells exhibited considerably lower expression of BMP-2 mRNA compared with dental pulp cells and periodontal ligament cells. The BMP-2 increase was markedly inhibited by pretreatment with an extracellular signal-regulated kinase (ERK) inhibitor, PD98059, and partially inhibited by the L-type Ca{sup 2+} channels inhibitor, nifedipine. However, pretreatment with nifedipine had no effect on ERK1/2 phosphorylation triggered by Ca{sup 2+}, suggesting that the Ca{sup 2+} influx from Ca{sup 2+} channels may operate independently of ERK signaling. Dental pulp cells do not express the transcript of Ca{sup 2+}-sensing receptors (CaSR) and only respond slightly to other cations such as Sr{sup 2+} and spermine, suggesting that dental pulp cells respond to Ca{sub o}{sup 2+} to increase BMP-2 mRNA expression in a manner different from CaSR and rather specific for Ca{sub o}{sup 2+} among cations.« less

  5. Characterization of stress-induced suppression of long-term potentiation in the hippocampal CA1 field of freely moving rats.

    PubMed

    Hirata, Riki; Togashi, Hiroko; Matsumoto, Machiko; Yamaguchi, Taku; Izumi, Takeshi; Yoshioka, Mitsuhiro

    2008-08-21

    Several lines of evidence have shown that exposure to stress impairs long-term potentiation (LTP) in the CA1 field of the hippocampus, but the detailed mechanisms for this effect remain to be clarified. The present study elucidated the synaptic mechanism of stress-induced LTP suppression in conscious, freely moving rats using electrophysiological approaches. Open field stress (i.e., novel environment stress) and elevated platform stress (i.e., uncontrollable stress) were employed. Basal synaptic transmission was significantly reduced during exposure to elevated platform stress but not during exposure to open field stress. LTP induction was blocked by elevated platform stress but not influenced by open field stress. Significant increases in serum corticosterone levels were observed in the elevated platform stress group compared with the open field stress group. Furthermore, LTP suppression induced by elevated platform stress was prevented by pretreatment with an anxiolytic drug diazepam (1 mg/kg, i.p.). These results suggest that stress-induced LTP suppression depends on the relative intensity of the stressor. The inhibitory synaptic response induced by an intense psychological stress, such as elevated platform stress, may be attributable to LTP impairment in the CA1 field of the hippocampus.

  6. Effect of Sustained Elevated Gastric pH Levels on Gefitinib Exposure.

    PubMed

    Tang, Weifeng; Tomkinson, Helen; Masson, Eric

    2017-09-01

    This open-label, randomized, phase 1 crossover study investigated the effect of elevated gastric pH level (>5) on the relative bioavailability and pharmacokinetic profile of the epidermal growth factor receptor tyrosine kinase inhibitor gefitinib. Healthy male volunteers (n = 26) were randomized to gefitinib 250 mg (fasted), either alone on day 1 (unmodified gastric pH) or 1 hour following the second of 2 oral doses of the H 2 -receptor antagonist ranitidine 450 mg (elevated gastric pH). After a 3-week washout period, volunteers crossed to the other treatment. The geometric least-squares (GLS) mean AUC 0-∞ and C max for gefitinib were reduced by 47% and 71%, respectively, under conditions of sustained elevated gastric pH; for both parameters, the 90%CI for the ratio of the GLS means lay below the prespecified lower limit. Median t max was delayed from 5 to 6 hours. Mean t 1/2 was similar under both gastric pH conditions. No serious adverse events were reported. The bioavailability of a single oral gefitinib 250-mg dose was reduced by approximately 50% when gefitinib was administered under conditions of sustained elevated gastric pH. © 2017, The American College of Clinical Pharmacology.

  7. In Situ Neutron Diffraction of Rare-Earth Phosphate Proton Conductors Sr/Ca-doped LaPO4 at Elevated Temperatures

    NASA Astrophysics Data System (ADS)

    Al-Wahish, Amal; Al-Binni, Usama; Bridges, C. A.; Huq, A.; Bi, Z.; Paranthaman, M. P.; Tang, S.; Kaiser, H.; Mandrus, D.

    Acceptor-doped lanthanum orthophosphates are potential candidate electrolytes for proton ceramic fuel cells. We combined neutron powder diffraction (NPD) at elevated temperatures up to 800° C , X-ray powder diffraction (XRD) and scanning electron microscopy (SEM) to investigate the crystal structure, defect structure, thermal stability and surface topography. NPD shows an average bond length distortion in the hydrated samples. We employed Quasi-Elastic Neutron Scattering (QENS) and electrochemical impedance spectroscopy (EIS) to study the proton dynamics of the rare-earth phosphate proton conductors 4.2% Sr/Ca-doped LaPO4. We determined the bulk diffusion and the self-diffusion coefficients. Our results show that QENS and EIS are probing fundamentally different proton diffusion processes. Supported by the U.S. Department of Energy.

  8. 4. VAL PARTIAL ELEVATION SHOWING LAUNCHER BRIDGE ON SUPPORTS, LAUNCHER ...

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

    4. VAL PARTIAL ELEVATION SHOWING LAUNCHER BRIDGE ON SUPPORTS, LAUNCHER SLAB, SUPPORT CARRIAGE, CONCRETE 'A' FRAME STRUCTURE AND CAMERA TOWER LOOKING SOUTHEAST. - Variable Angle Launcher Complex, Variable Angle Launcher, CA State Highway 39 at Morris Reservior, Azusa, Los Angeles County, CA

  9. Calcium feedback mechanisms regulate oscillatory activity of a TRP-like Ca2+ conductance in C. elegans intestinal cells

    PubMed Central

    Estevez, Ana Y; Strange, Kevin

    2005-01-01

    Inositol-1,4,5-trisphosphate (IP3)-dependent Ca2+ oscillations in Caenorhabditis elegans intestinal epithelial cells regulate the nematode defecation cycle. The role of plasma membrane ion channels in intestinal cell oscillatory Ca2+ signalling is unknown. We have shown previously that cultured intestinal cells express a Ca2+-selective conductance, IORCa, that is biophysically similar to TRPM7 currents. IORCa activates slowly and stabilizes when cells are patch clamped with pipette solutions containing 10 mm BAPTA and free Ca2+ concentrations of ∼17 nm. However, when BAPTA concentration is lowered to 1 mm, IORCa oscillates. Oscillations in channel activity induced simultaneous oscillations in cytoplasmic Ca2+ levels. Removal of extracellular Ca2+ inhibited IORCa oscillations, whereas readdition of Ca2+ to the bath caused a rapid and transient reactivation of the current. Experimental manoeuvres that elevated intracellular Ca2+ blocked current oscillations. Elevation of intracellular Ca2+ in the presence of 10 mm BAPTA to block IORCa oscillations led to a dose-dependent increase in the rate of current activation. At intracellular Ca2+ concentrations of 250 nm, current activation was transient. Patch pipette solutions buffered with 1–4 mm of either BAPTA or EGTA gave rise to similar patterns of IORCa oscillations. We conclude that changes in Ca2+ concentration close to the intracellular opening of the channel pore regulate channel activity. Low concentrations of Ca2+ activate the channel. As Ca2+ enters and accumulates near the pore mouth, channel activity is inhibited. Oscillating plasma membrane Ca2+ entry may play a role in generating intracellular Ca2+ oscillations that regulate the C. elegans defecation rhythm. PMID:15961418

  10. In vivo Ca2+ buffering capacity and microvascular oxygen pressures following muscle contractions in diabetic rat skeletal muscles: fiber-type specific effects.

    PubMed

    Eshima, Hiroaki; Poole, David C; Kano, Yutaka

    2015-07-15

    In Type 1 diabetes, skeletal muscle resting intracellular Ca(2+) concentration ([Ca(2+)]i) homeostasis is impaired following muscle contractions. It is unclear to what degree this behavior is contingent upon fiber type and muscle oxygenation conditions. We tested the hypotheses that: 1) the rise in resting [Ca(2+)]i evident in diabetic rat slow-twitch (type I) muscle would be exacerbated in fast-twitch (type II) muscle following contraction; and 2) these elevated [Ca(2+)]i levels would relate to derangement of microvascular partial pressure of oxygen (PmvO2 ) rather than sarcoplasmic reticulum dysfunction per se. Adult male Wistar rats were divided randomly into diabetic (DIA: streptozotocin ip) and healthy (CONT) groups. Four weeks later extensor digitorum longus (EDL, predominately type II fibers) and soleus (SOL, predominately type I fibers) muscle contractions were elicited by continuous electrical stimulation (120 s, 100 Hz). Ca(2+) imaging was achieved using fura 2-AM in vivo (i.e., circulation intact). DIA increased fatigability in EDL (P < 0.05) but not SOL. In recovery, SOL [Ca(2+)]i either returned to its resting baseline within 150 s (CONT 1.00 ± 0.02 at 600 s) or was not elevated in recovery at all (DIA 1.03 ± 0.02 at 600 s, P > 0.05). In recovery, EDL CONT [Ca(2+)]i also decreased to values not different from baseline (1.06 ± 0.01, P > 0.05) at 600 s. In marked contrast, EDL DIA [Ca(2+)]i remained elevated for the entire recovery period (i.e., 1.23 ± 0.03 at 600 s, P < 0.05). The inability of [Ca(2+)]i to return to baseline in EDL DIA was not associated with any reduction of SR Ca(2+)-ATPase (SERCA) 1 or SERCA2 protein levels (both increased 30-40%, P < 0.05). However, Pmv(O2) recovery kinetics were markedly slowed in EDL such that mean Pmv(O2) was substantially depressed (CONT 27.9 ± 2.0 vs. DIA 18.4 ± 2.0 Torr, P < 0.05), and this behavior was associated with the elevated [Ca(2+)]i. In contrast, this was not the case for SOL (P > 0.05) in that

  11. Elevation of endogenous anandamide impairs LTP, learning, and memory through CB1 receptor signaling in mice.

    PubMed

    Basavarajappa, Balapal S; Nagre, Nagaraja N; Xie, Shan; Subbanna, Shivakumar

    2014-07-01

    In rodents, many exogenous and endogenous cannabinoids, such as anandamide (AEA) and 2-arachidonyl glycerol (2-AG), have been shown to play an important role in certain hippocampal memory processes. However, the mechanisms by which endogenous AEA regulate this processes are not well understood. Here the effects of AEA on long-term potentiation (LTP), hippocampal-dependent learning and memory tasks, pERK1/2, pCaMKIV, and pCREB signaling events in both cannabinoid receptor type 1 (CB1R) wild-type (WT) and knockout (KO) mice were assessed following administration of URB597, an inhibitor of the fatty acid amide hydrolase (FAAH). Acute administration of URB597 enhanced AEA levels without affecting the levels of 2-AG or CB1R in the hippocampus and neocortex as compared to vehicle. In hippocampal slices, URB597 impaired LTP in CB1R WT but not in KO littermates. URB597 impaired object recognition, spontaneous alternation and spatial memory in the Y-maze test in CB1R WT mice but not in KO mice. Furthermore, URB597 enhanced ERK phosphorylation in WT without affecting total ERK levels in WT or KO mice. URB597 impaired CaMKIV and CREB phosphorylation in WT but not in KO mice. CB1R KO mice have a lower pCaMKIV/CaMKIV ratio and higher pCREB/CREB ratio as compared to WT littermates. Our results indicate that pharmacologically elevated AEA impair LTP, learning and memory and inhibit CaMKIV and CREB phosphorylation, via the activation of CB1Rs. Collectively, these findings also suggest that pharmacological elevation of AEA beyond normal concentrations is also detrimental for the underlying physiological responses. © 2014 Wiley Periodicals, Inc.

  12. Effects of elevated CO2 levels on root morphological traits and Cd uptakes of two Lolium species under Cd stress*

    PubMed Central

    Jia, Yan; Tang, Shi-rong; Ju, Xue-hai; Shu, Li-na; Tu, Shu-xing; Feng, Ren-wei; Giusti, Lorenzino

    2011-01-01

    This study was conducted to investigate the combined effects of elevated CO2 levels and cadmium (Cd) on the root morphological traits and Cd accumulation in Lolium multiflorum Lam. and Lolium perenne L. exposed to two CO2 levels (360 and 1000 μl/L) and three Cd levels (0, 4, and 16 mg/L) under hydroponic conditions. The results show that elevated levels of CO2 increased shoot biomass more, compared to root biomass, but decreased Cd concentrations in all plant tissues. Cd exposure caused toxicity to both Lolium species, as shown by the restrictions of the root morphological parameters including root length, surface area, volume, and tip numbers. These parameters were significantly higher under elevated levels of CO2 than under ambient CO2, especially for the number of fine roots. The increases in magnitudes of those parameters triggered by elevated levels of CO2 under Cd stress were more than those under non-Cd stress, suggesting an ameliorated Cd stress under elevated levels of CO2. The total Cd uptake per pot, calculated on the basis of biomass, was significantly greater under elevated levels of CO2 than under ambient CO2. Ameliorated Cd toxicity, decreased Cd concentration, and altered root morphological traits in both Lolium species under elevated levels of CO2 may have implications in food safety and phytoremediation. PMID:21462388

  13. Urinary Angiotensinogen Excretion Level Is Associated With Elevated Blood Pressure in the Normotensive General Population.

    PubMed

    Sato, Emiko; Wang, An Yi; Satoh, Michihiro; Nishikiori, Yoko; Oba-Yabana, Ikuko; Yoshida, Mai; Sato, Hiroshi; Ito, Sadayoshi; Hida, Wataru; Mori, Takefumi

    2018-05-07

    Inflammation, intrarenal renin-angiotensin system (RAS) activation, oxidative stress, and carbonyl stress have been postulated to play a fundamental role in controlling blood pressure. However, little is known about the association among renal RAS activation, carbonyl stress, and blood pressure elevation. We evaluated the relationship between blood pressure elevation and either renal RAS activity or carbonyl stress in the general population (N = 355) in Japan. To minimize the effect of antihypertensive drug therapy, we divided participants into 3 groups (normotensive, hypertensive-with-non-medication, and hypertensive-with-medication). Intrarenal RAS activity and carbonyl stress were indicated by the urinary angiotensinogen (AGT) and carbonyl compound excretion levels, respectively. The urinary AGT and carbonyl compound excretion levels were significantly associated with blood pressure. Using a stepwise multiple regression analysis, we found that the urinary AGT excretion levels were strongly associated with blood pressure elevation, compared with inflammation, oxidative stress, and carbonyl stress markers, in all groups. Urinary carbonyl compound excretion was significantly associated with blood pressure in only the hypertensive-without-medication group. Furthermore, blood pressure was significantly increased in these participants, and both the urinary AGT and carbonyl compound levels were high. The urinary AGT excretion levels were strongly associated with elevated blood pressure in normotensive people, and inappropriate renal RAS activity and carbonyl stress independently contributed to the development of hypertension. These findings suggest that RAS activation, particularly renal RAS activation exert a fundamental role in the pathogenesis of hypertension in the general population.

  14. Elevated ventricular wall stress disrupts cardiomyocyte t-tubule structure and calcium homeostasis.

    PubMed

    Frisk, Michael; Ruud, Marianne; Espe, Emil K S; Aronsen, Jan Magnus; Røe, Åsmund T; Zhang, Lili; Norseng, Per Andreas; Sejersted, Ole M; Christensen, Geir A; Sjaastad, Ivar; Louch, William E

    2016-10-01

    Invaginations of the cellular membrane called t-tubules are essential for maintaining efficient excitation-contraction coupling in ventricular cardiomyocytes. Disruption of t-tubule structure during heart failure has been linked to dyssynchronous, slowed Ca(2+) release and reduced power of the heartbeat. The underlying mechanism is, however, unknown. We presently investigated whether elevated ventricular wall stress triggers remodelling of t-tubule structure and function. MRI and blood pressure measurements were employed to examine regional wall stress across the left ventricle of sham-operated and failing, post-infarction rat hearts. In failing hearts, elevated left ventricular diastolic pressure and ventricular dilation resulted in markedly increased wall stress, particularly in the thin-walled region proximal to the infarct. High wall stress in this proximal zone was associated with reduced expression of the dyadic anchor junctophilin-2 and disrupted cardiomyocyte t-tubular structure. Indeed, local wall stress measurements predicted t-tubule density across sham and failing hearts. Elevated wall stress and disrupted cardiomyocyte structure in the proximal zone were also associated with desynchronized Ca(2+) release in cardiomyocytes and markedly reduced local contractility in vivo. A causative role of wall stress in promoting t-tubule remodelling was established by applying stretch to papillary muscles ex vivo under culture conditions. Loads comparable to wall stress levels observed in vivo in the proximal zone reduced expression of junctophilin-2 and promoted t-tubule loss. Elevated wall stress reduces junctophilin-2 expression and disrupts t-tubule integrity, Ca(2+) release, and contractile function. These findings provide new insight into the role of wall stress in promoting heart failure progression. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Cardiology.

  15. 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

  16. Influence of Cut-outs in Elevator on the Static Longitudinal Stability and on the Static Elevator Effect

    NASA Technical Reports Server (NTRS)

    Biechteler, Curt

    1934-01-01

    The rudder effect of a sport airplane at high angles of attack was to be improved. This made it necessary to make a cut-out in the center of the continuous elevator so as to enlarge the rudder downward. This cut-out which reduced the rudder area by 12.5 percent changed the static stability of the airplane as well as the elevator effect. Flight measurements showed the stability zone with locked elevator to be 1.8 percent less at full throttle and at idling to be 1.3 percent less than the mean wing chord. The effect of the cut-out on the control forces could not be determined owing to insufficient instrumental accuracy at the extremely low existing forces. The measurement of the static controllability resulting from the cut-out manifested an 18 percent drop in elevator effect at full throttle and a 10 to 20 percent drop at idling, depending on lift.

  17. Serum matrix metalloproteinase-3 levels are elevated in myasthenia gravis.

    PubMed

    Romi, Fredrik R; Gilhus, Nils Erik; Luckman, Steven P

    2008-03-01

    MMP-3 is capable of degrading a variety of proteins, including agrin, which plays a critical role in neuromuscular signalling by controlling acetylcholine receptor clustering. The degradation of agrin by MMP-3 may disrupt the neuromuscular junction leading to a failure of neuromuscular transmission and muscle weakness. We have therefore examined the levels of MMP-3 in 116 patients with myasthenia gravis (MG) and 90 healthy controls. A significant elevation in MMP-3 levels was observed in 10% of seronegative and 17% of seropositive MG patients, indicating that MMP-3 may play a pathogenic role in a proportion of MG patients.

  18. The other side of cardiac Ca2+ signaling: transcriptional control

    PubMed Central

    Domínguez-Rodríguez, Alejandro; Ruiz-Hurtado, Gema; Benitah, Jean-Pierre; Gómez, Ana M.

    2012-01-01

    Ca2+ is probably the most versatile signal transduction element used by all cell types. In the heart, it is essential to activate cellular contraction in each heartbeat. Nevertheless Ca2+ is not only a key element in excitation-contraction coupling (EC coupling), but it is also a pivotal second messenger in cardiac signal transduction, being able to control processes such as excitability, metabolism, and transcriptional regulation. Regarding the latter, Ca2+ activates Ca2+-dependent transcription factors by a process called excitation-transcription coupling (ET coupling). ET coupling is an integrated process by which the common signaling pathways that regulate EC coupling activate transcription factors. Although ET coupling has been extensively studied in neurons and other cell types, less is known in cardiac muscle. Some hints have been found in studies on the development of cardiac hypertrophy, where two Ca2+-dependent enzymes are key actors: Ca2+/Calmodulin kinase II (CaMKII) and phosphatase calcineurin, both of which are activated by the complex Ca2+/Calmodulin. The question now is how ET coupling occurs in cardiomyocytes, where intracellular Ca2+ is continuously oscillating. In this focused review, we will draw attention to location of Ca2+ signaling: intranuclear ([Ca2+]n) or cytoplasmic ([Ca2+]c), and the specific ionic channels involved in the activation of cardiac ET coupling. Specifically, we will highlight the role of the 1,4,5 inositol triphosphate receptors (IP3Rs) in the elevation of [Ca2+]n levels, which are important to locally activate CaMKII, and the role of transient receptor potential channels canonical (TRPCs) in [Ca2+]c, needed to activate calcineurin (Cn). PMID:23226134

  19. Systolic [Ca2+]i regulates diastolic levels in rat ventricular myocytes

    PubMed Central

    Sankaranarayanan, Rajiv; Kistamás, Kornél; Greensmith, David J.; Venetucci, Luigi A.

    2017-01-01

    Key points For the heart to function as a pump, intracellular calcium concentration ([Ca2+]i) must increase during systole to activate contraction and then fall, during diastole, to allow the myofilaments to relax and the heart to refill with blood.The present study investigates the control of diastolic [Ca2+]i in rat ventricular myocytes.We show that diastolic [Ca2+]i is increased by manoeuvres that decrease sarcoplasmic reticulum function. This is accompanied by a decrease of systolic [Ca2+]i such that the time‐averaged [Ca2+]i remains constant.We report that diastolic [Ca2+]i is controlled by the balance between Ca2+ entry and Ca2+ efflux during systole.The results of the present study identify a novel mechanism by which changes of the amplitude of the systolic Ca transient control diastolic [Ca2+]i. Abstract The intracellular Ca concentration ([Ca2+]i) must be sufficently low in diastole so that the ventricle is relaxed and can refill with blood. Interference with this will impair relaxation. The factors responsible for regulation of diastolic [Ca2+]i, in particular the relative roles of the sarcoplasmic reticulum (SR) and surface membrane, are unclear. We investigated the effects on diastolic [Ca2+]i that result from the changes of Ca cycling known to occur in heart failure. Experiments were performed using Fluo‐3 in voltage clamped rat ventricular myocytes. Increasing stimulation frequency increased diastolic [Ca2+]i. This increase of [Ca2+]i was larger when SR function was impaired either by making the ryanodine receptor leaky (with caffeine or ryanodine) or by decreasing sarco/endoplasmic reticulum Ca‐ATPase activity with thapsigargin. The increase of diastolic [Ca2+]i produced by interfering with the SR was accompanied by a decrease of the amplitude of the systolic Ca transient, such that there was no change of time‐averaged [Ca2+]i. Time‐averaged [Ca2+]i was increased by β‐adrenergic stimulation with isoprenaline and increased in a saturating

  20. 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.

  1. 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

  2. 15. Oblique view of southeast and northeast elevations following 1926 ...

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

    15. Oblique view of southeast and northeast elevations following 1926 alterations; photo date ca.1926; photo from collection of M.L. Days, Department of Community Development, Santa Barbara. - V.E. Wood Auto Building, 315 State Street, Santa Barbara, Santa Barbara County, CA

  3. 14. LOW OBLIQUE VIEW OF WEST ELEVATION, FROM OPPOSITE BANK ...

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

    14. LOW OBLIQUE VIEW OF WEST ELEVATION, FROM OPPOSITE BANK OF BUTTE CREEK Historic photograph no. 136, no date, held at Media Arts and Services Department, Pacific Gas & Electric Co., San Francisco, CA. - Centerville Hydroelectric System, Powerhouse, Butte Creek, Centerville, Butte County, CA

  4. Chronic Ca2+ influx through voltage-dependent Ca2+ channels enhance delayed rectifier K+ currents via activating Src family tyrosine kinase in rat hippocampal neurons.

    PubMed

    Yang, Yoon-Sil; Jeon, Sang-Chan; Kim, Dong-Kwan; Eun, Su-Yong; Jung, Sung-Cherl

    2017-03-01

    Excessive influx and the subsequent rapid cytosolic elevation of Ca 2+ in neurons is the major cause to induce hyperexcitability and irreversible cell damage although it is an essential ion for cellular signalings. Therefore, most neurons exhibit several cellular mechanisms to homeostatically regulate cytosolic Ca 2+ level in normal as well as pathological conditions. Delayed rectifier K + channels (I DR channels) play a role to suppress membrane excitability by inducing K + outflow in various conditions, indicating their potential role in preventing pathogenic conditions and cell damage under Ca 2+ -mediated excitotoxic conditions. In the present study, we electrophysiologically evaluated the response of I DR channels to hyperexcitable conditions induced by high Ca 2+ pretreatment (3.6 mM, for 24 hours) in cultured hippocampal neurons. In results, high Ca 2+ -treatment significantly increased the amplitude of I DR without changes of gating kinetics. Nimodipine but not APV blocked Ca 2+ -induced I DR enhancement, confirming that the change of I DR might be targeted by Ca 2+ influx through voltage-dependent Ca 2+ channels (VDCCs) rather than NMDA receptors (NMDARs). The VDCC-mediated I DR enhancement was not affected by either Ca 2+ -induced Ca 2+ release (CICR) or small conductance Ca 2+ -activated K + channels (SK channels). Furthermore, PP2 but not H89 completely abolished I DR enhancement under high Ca 2+ condition, indicating that the activation of Src family tyrosine kinases (SFKs) is required for Ca 2+ -mediated I DR enhancement. Thus, SFKs may be sensitive to excessive Ca 2+ influx through VDCCs and enhance I DR to activate a neuroprotective mechanism against Ca 2+ -mediated hyperexcitability in neurons.

  5. Elevation of CSF tumor necrosis factor alpha levels in new daily persistent headache and treatment refractory chronic migraine.

    PubMed

    Rozen, Todd; Swidan, Sahar Z

    2007-01-01

    To determine if patients with new daily persistent headache (NDPH) have elevated levels of tumor necrosis factor alpha (TNF alpha) in the CSF. NDPH is considered one of the most treatment resistant of all headache syndromes. This reflects a lack of understanding of its pathogenesis. As a certain percentage of NDPH patients have their headaches start after an infection, the possibility of a persistent state of systemic or CNS inflammation comes into question. TNF alpha is a proinflammatory cytokine involved in brain immune and inflammatory activities, as well as in pain initiation. The goal of this study was to look at TNF alpha levels in the CSF of NDPH patients, to determine if CNS inflammation may play some role in the pathogenesis of this condition. CSF TNF alpha levels were studied in 38 patients: 20 with NDPH and a control population of 16 patients with chronic migraine (CM), and 2 with post-traumatic headache (PT). CSF TNF alpha levels were elevated in 19 of 20 NDPH patients, 16 of 16 CM patients, and both PT patients. Serum TNF alpha levels were normal in most of the study subjects. An elevation of CSF TNF alpha levels was found in almost all NDPH patients and suggest a role for TNF alpha in the pathogenesis of this condition. Surprisingly, all CM and PT patients tested had elevated CSF TNF alpha levels. In most patients with elevated CSF levels, serum TNF alpha levels were normal. All of these syndromes may be manifestations of CNS inflammation. As most of the positive-tested patients showed minimal to no improvement during aggressive inpatient treatment, persistent elevation of CSF TNF alpha levels may be one of the causes of treatment refractory CDH.

  6. Dysregulated Zn2+ homeostasis impairs cardiac type-2 ryanodine receptor and mitsugumin 23 functions, leading to sarcoplasmic reticulum Ca2+ leakage.

    PubMed

    Reilly-O'Donnell, Benedict; Robertson, Gavin B; Karumbi, Angela; McIntyre, Connor; Bal, Wojciech; Nishi, Miyuki; Takeshima, Hiroshi; Stewart, Alan J; Pitt, Samantha J

    2017-08-11

    Aberrant Zn 2+ homeostasis is associated with dysregulated intracellular Ca 2+ release, resulting in chronic heart failure. In the failing heart a small population of cardiac ryanodine receptors (RyR2) displays sub-conductance-state gating leading to Ca 2+ leakage from sarcoplasmic reticulum (SR) stores, which impairs cardiac contractility. Previous evidence suggests contribution of RyR2-independent Ca 2+ leakage through an uncharacterized mechanism. We sought to examine the role of Zn 2+ in shaping intracellular Ca 2+ release in cardiac muscle. Cardiac SR vesicles prepared from sheep or mouse ventricular tissue were incorporated into phospholipid bilayers under voltage-clamp conditions, and the direct action of Zn 2+ on RyR2 channel function was examined. Under diastolic conditions, the addition of pathophysiological concentrations of Zn 2+ (≥2 nm) caused dysregulated RyR2-channel openings. Our data also revealed that RyR2 channels are not the only SR Ca 2+ -permeable channels regulated by Zn 2+ Elevating the cytosolic Zn 2+ concentration to 1 nm increased the activity of the transmembrane protein mitsugumin 23 (MG23). The current amplitude of the MG23 full-open state was consistent with that previously reported for RyR2 sub-conductance gating, suggesting that in heart failure in which Zn 2+ levels are elevated, RyR2 channels do not gate in a sub-conductance state, but rather MG23-gating becomes more apparent. We also show that in H9C2 cells exposed to ischemic conditions, intracellular Zn 2+ levels are elevated, coinciding with increased MG23 expression. In conclusion, these data suggest that dysregulated Zn 2+ homeostasis alters the function of both RyR2 and MG23 and that both ion channels play a key role in diastolic SR Ca 2+ leakage. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. Immunomodulatory Activity of Ganoderma atrum Polysaccharide on Purified T Lymphocytes through Ca2+/CaN and Mitogen-Activated Protein Kinase Pathway Based on RNA Sequencing.

    PubMed

    Xiang, Quan-Dan; Yu, Qiang; Wang, Hui; Zhao, Ming-Ming; Liu, Shi-Yu; Nie, Shao-Ping; Xie, Ming-Yong

    2017-07-05

    Our previous study has demonstrated that Ganoderma atrum polysaccharide (PSG-1) has immunomodulatory activity on spleen lymphocytes. However, how PSG-1 exerts its effect on purified lymphocytes is still obscure. Thus, this study aimed to investigate the immunomodulatory activity of PSG-1 on purified T lymphocytes and further elucidate the underlying mechanism based on RNA sequencing (RNA-seq). Our results showed that PSG-1 promoted T lymphocytes proliferation and increased the production of IL-2, IFN-γ, and IL-12. Meanwhile, RNA-seq analysis found 394 differentially expressed genes. KEGG pathway analysis identified 20 significant canonical pathways and seven biological functions. Furthermore, PSG-1 elevated intracellular Ca 2+ concentration and calcineurin (CaN) activity and raised the p-ERK, p-JNK, and p-p38 expression levels. T lymphocytes proliferation and the production of IL-2, IFN-γ, and IL-12 were decreased by the inhibitors of calcium channel and mitogen-activated protein kinases (MAPKs). These results indicated that PSG-1 possesses immunomodulatory activity on purified T lymphocytes, in which Ca 2+ /CaN and MAPK pathways play essential roles.

  8. Rapamycin (sirolimus) protects against hypoxic damage in primary heart cultures via Na+/Ca2+ exchanger activation.

    PubMed

    El-Ani, Dalia; Stav, Hagit; Guetta, Victor; Arad, Michael; Shainberg, Asher

    2011-07-04

    Rapamycin (sirolimus) is an antibiotic that inhibits protein synthesis through mammalian targeting of rapamycin (mTOR) signaling, and is used as an immunosuppressant in the treatment of organ rejection in transplant recipients. Rapamycin confers preconditioning-like protection against ischemic-reperfusion injury in isolated mouse heart cultures. Our aim was to further define the role of rapamycin in intracellular Ca(2+) homeostasis and to investigate the mechanism by which rapamycin protects cardiomyocytes from hypoxic damage. We demonstrate here that rapamycin protects rat heart cultures from hypoxic-reoxygenation (H/R) damage, as revealed by assays of lactate dehydrogenase (LDH) and creatine kinase (CK) leakage to the medium, by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) measurements, and desmin immunostaining. As a result of hypoxia, intracellular calcium levels ([Ca(2+)](i)) were elevated. However, treatment of heart cultures with rapamycin during hypoxia attenuated the increase of [Ca(2+)](i). Rapamycin also attenuated (45)Ca(2+) uptake into the sarcoplasmic reticulum (SR) of skinned heart cultures in a dose- and time-dependent manner. KB-R7943, which inhibits the "reverse" mode of Na(+)/Ca(2+) exchanger (NCX), protected heart cultures from H/R damage with or without the addition of rapamycin. Rapamycin decreased [Ca(2+)](i) following its elevation by extracellular Ca(2+) ([Ca(2+)](o)) influx, thapsigargin treatment, or depolarization with KCl. We suggest that rapamycin induces cardioprotection against hypoxic/reoxygenation damage in primary heart cultures by stimulating NCX to extrude Ca(2+) outside the cardiomyocytes. According to our findings, rapamycin preserves Ca(2+) homeostasis and prevents Ca(2+) overload via extrusion of Ca(2+) surplus outside the sarcolemma, thereby protecting the cells from hypoxic stress. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. Seawater Mg/Ca controls polymorph mineralogy of microbial CaCO3: a potential proxy for calcite-aragonite seas in Precambrian time.

    PubMed

    Ries, J B; Anderson, M A; Hill, R T

    2008-03-01

    A previously published hydrothermal brine-river water mixing model driven by ocean crust production suggests that the molar Mg/Ca ratio of seawater (mMg/Ca(sw)) has varied significantly (approximately 1.0-5.2) over Precambrian time, resulting in six intervals of aragonite-favouring seas (mMg/Ca(sw) > 2) and five intervals of calcite-favouring seas (mMg/Ca(sw) < 2) since the Late Archaean. To evaluate the viability of microbial carbonates as mineralogical proxy for Precambrian calcite-aragonite seas, calcifying microbial marine biofilms were cultured in experimental seawaters formulated over the range of Mg/Ca ratios believed to have characterized Precambrian seawater. Biofilms cultured in experimental aragonite seawater (mMg/Ca(sw) = 5.2) precipitated primarily aragonite with lesser amounts of high-Mg calcite (mMg/Ca(calcite) = 0.16), while biofilms cultured in experimental calcite seawater (mMg/Ca(sw) = 1.5) precipitated exclusively lower magnesian calcite (mMg/Ca(calcite) = 0.06). Furthermore, Mg/Ca(calcite )varied proportionally with Mg/Ca(sw). This nearly abiotic mineralogical response of the biofilm CaCO3 to altered Mg/Ca(sw) is consistent with the assertion that biofilm calcification proceeds more through the elevation of , via metabolic removal of CO2 and/or H+, than through the elevation of Ca2+, which would alter the Mg/Ca ratio of the biofilm's calcifying fluid causing its pattern of CaCO3 polymorph precipitation (aragonite vs. calcite; Mg-incorporation in calcite) to deviate from that of abiotic calcification. If previous assertions are correct that the physicochemical properties of Precambrian seawater were such that Mg/Ca(sw) was the primary variable influencing CaCO3 polymorph mineralogy, then the observed response of the biofilms' CaCO3 polymorph mineralogy to variations in Mg/Ca(sw), combined with the ubiquity of such microbial carbonates in Precambrian strata, suggests that the original polymorph mineralogy and Mg/Ca(calcite )of well

  10. 18. VIEW OF NORTH ELEVATION, FRANCIS TURBINE, WITH RHEOSTATS AND ...

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

    18. VIEW OF NORTH ELEVATION, FRANCIS TURBINE, WITH RHEOSTATS AND CONTROL PANEL IN BACKGROUND Historic photograph no. SC8730, 1913, curated in the Jon Kitchen Collection, Special Collections, Meriam Library, California State University, Chico, CA. - Centerville Hydroelectric System, Powerhouse, Butte Creek, Centerville, Butte County, CA

  11. Profound regulation of Na/K pump activity by transient elevations of cytoplasmic calcium in murine cardiac myocytes

    PubMed Central

    Lu, Fang-Min; Deisl, Christine; Hilgemann, Donald W

    2016-01-01

    Small changes of Na/K pump activity regulate internal Ca release in cardiac myocytes via Na/Ca exchange. We now show conversely that transient elevations of cytoplasmic Ca strongly regulate cardiac Na/K pumps. When cytoplasmic Na is submaximal, Na/K pump currents decay rapidly during extracellular K application and multiple results suggest that an inactivation mechanism is involved. Brief activation of Ca influx by reverse Na/Ca exchange enhances pump currents and attenuates current decay, while repeated Ca elevations suppress pump currents. Pump current enhancement reverses over 3 min, and results are similar in myocytes lacking the regulatory protein, phospholemman. Classical signaling mechanisms, including Ca-activated protein kinases and reactive oxygen, are evidently not involved. Electrogenic signals mediated by intramembrane movement of hydrophobic ions, such as hexyltriphenylphosphonium (C6TPP), increase and decrease in parallel with pump currents. Thus, transient Ca elevation and Na/K pump inactivation cause opposing sarcolemma changes that may affect diverse membrane processes. DOI: http://dx.doi.org/10.7554/eLife.19267.001 PMID:27627745

  12. 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

  13. Impact of elevated levels of atmospheric CO2 and herbivory on flavonoids of soybean (Glycine max Linnaeus).

    PubMed

    O'Neill, Bridget F; Zangerl, Arthur R; Dermody, Orla; Bilgin, Damla D; Casteel, Clare L; Zavala, Jorge A; DeLucia, Evan H; Berenbaum, May R

    2010-01-01

    Atmospheric levels of carbon dioxide (CO2) have been increasing steadily over the last century. Plants grown under elevated CO2 conditions experience physiological changes, particularly in phytochemical content, that can influence their suitability as food for insects. Flavonoids are important plant defense compounds and antioxidants that can have a large effect on leaf palatability and herbivore longevity. In this study, flavonoid content was examined in foliage of soybean (Glycine max Linnaeus) grown under ambient and elevated levels of CO2 and subjected to damage by herbivores in three feeding guilds: leaf skeletonizer (Popillia japonica Newman), leaf chewer (Vanessa cardui Linnaeus), and phloem feeder (Aphis glycines Matsumura). Flavonoid content also was examined in foliage of soybean grown under ambient and elevated levels of O3 and subjected to damage by the leaf skeletonizer P. japonica. The presence of the isoflavones genistein and daidzein and the flavonols quercetin and kaempferol was confirmed in all plants examined, as were their glycosides. All compounds significantly increased in concentration as the growing season progressed. Concentrations of quercetin glycosides were higher in plants grown under elevated levels of CO2. The majority of compounds in foliage were induced in response to leaf skeletonization damage but remained unchanged in response to non-skeletonizing feeding or phloem-feeding. Most compounds increased in concentration in plants grown under elevated levels of O3. Insects feeding on G. max foliage growing under elevated levels of CO2 may derive additional antioxidant benefits from their host plants as a consequence of the change in ratios of flavonoid classes. This nutritional benefit could lead to increased herbivore longevity and increased damage to soybean (and perhaps other crop plants) in the future.

  14. 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

  15. 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.

  16. Process for depositing I-125 onto a substrate used to manufacture I-125 sources

    DOEpatents

    McGovern, James J.; Olynyk, Joseph M.

    1988-01-01

    The invention relates to a process for depositing I-125 on a substrate which comprises contacting a predetermined surface area of substrate with Xe-125 gas, whereby the Xe-125 decays to I-125 and the I-125 in turn deposits as a solid on the surface of the substrate, the contact being for a time sufficient to deposit at least about 1 microcurie of I-125. I-125 is thereby deposited in a relatively uniform amount over the surface area of the substrate. The substrate is then assayed to determine how much I-125 has been deposited. The substrate is then divided into pieces of measured surface area, each piece therefore containing a measured amount of deposited I-125, and each piece can then be used in the manufacture of an I-125 source.

  17. APS: 125 Years of Progress of Physiology as a Scientific Discipline and a Profession

    ERIC Educational Resources Information Center

    Carroll, Robert G.; Frank, Martin; Ra'anan, Alice; Matyas, Marsha L.

    2013-01-01

    The Experimental Biology 2012 meeting in San Diego, CA, included events to celebrate the 125th anniversary of the founding of the American Physiological Society (APS) and reflect on the recent accomplishments of the society. Most of the APS activities in the past quarter century were guided by a series of strategic plans. Membership in the APS…

  18. Elevated Red Cell Distribution Width (RDW) Identifies Elevated Cardiovascular Disease Risk in Patients with HIV infection

    PubMed Central

    Al-Kindi, Sadeer G.; Kim, Chang H; Morris, Stephen R.; Freeman, Michael L.; Funderburg, Nicholas T.; Rodriguez, Benigno; McComsey, Grace A.; Dalton, Jarrod E.; Simon, Daniel I.; Lederman, Michael M.; Longenecker, Chris T.; Zidar, David A.

    2016-01-01

    Red cell distribution width (RDW) is linked to cardiovascular risk in the general population, an association that might be driven by inflammation. Whether this relationship holds for patients with Human Immunodeficiency Virus (HIV) infection has not been previously studied. Using a large clinical registry, we show that elevated RDW (>14.5%) is independently associated with increased risk of coronary artery disease (odds ratio (OR) 1.39 [1.25–1.55]), peripheral vascular disease (OR 1.41 [1.29–1.53]), myocardial infarction (1.43 [1.25–1.63]), heart failure (OR 2.23 [1.99–2.49]), and atrial fibrillation (OR 1.96 [1.64–2.33]). In conclusion, in the context of the inflammatory milieu that accompanies HIV infection, RDW remains a powerful marker of CV disease. PMID:27828877

  19. Influence of pre-, post-, and simultaneous perfusion of elevated calcium on the effect of ascending concentrations of lead on digoxin-induced cardiac arrest in isolated frog heart

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

    Krishnamoorthy, M.S.; Muthu, P.; Parthiban, N.

    1995-10-01

    Cardiotoxicity of lead, a ubiquitous environmental pollutant, has already been documented as a potentially lethal, although rarely recognized, complication of lead intoxication. Further, it has already been reported from this laboratory that lead acetate (LA) preperfusion potentiated cardiotoxicity of digoxin (DGN) in isolated frog heart preparation and that exposure to elevated calcium (elev. Ca{sup 2+}) prior to, and simultaneously with LA at 10{sup {minus}7} M concentration, attenuated this potentiation. As an extension of this work, it was considered of interest to study the effect of perfusion of elev. Ca{sup 2+} (6.5 mM) prior to, after and simultaneously with ascending concentrationsmore » of lead (10{sup {minus}9}, 10{sup {minus}7} and 10{sup {minus}5}M) on DGN induced cardiac arrest (CA) in isolated frog heart, since Pb{sup 2+} and Ca{sup 2+} ions are known to compete with each other for the same target sites at the cellular level, an instance of competitive mass action effect. 15 refs., 1 fig., 1 tab.« less

  20. Genetic variants influencing elevated myeloperoxidase levels increase risk of stroke.

    PubMed

    Phuah, Chia-Ling; Dave, Tushar; Malik, Rainer; Raffeld, Miriam R; Ayres, Alison M; Goldstein, Joshua N; Viswanathan, Anand; Greenberg, Steven M; Jagiella, Jeremiasz M; Hansen, Björn M; Norrving, Bo; Jimenez-Conde, Jordi; Roquer, Jaume; Pichler, Alexander; Enzinger, Christian; Montaner, Joan; Fernandez-Cadenas, Israel; Lindgren, Arne; Slowik, Agnieszka; Schmidt, Reinhold; Biffi, Alessandro; Rost, Natalia; Langefeld, Carl D; Markus, Hugh S; Mitchell, Braxton D; Worrall, Brad B; Kittner, Steven J; Woo, Daniel; Dichgans, Martin; Rosand, Jonathan; Anderson, Christopher D

    2017-10-01

    Primary intracerebral haemorrhage and lacunar ischaemic stroke are acute manifestations of progressive cerebral microvascular disease. Current paradigms suggest atherosclerosis is a chronic, dynamic, inflammatory condition precipitated in response to endothelial injury from various environmental challenges. Myeloperoxidase plays a central role in initiation and progression of vascular inflammation, but prior studies linking myeloperoxidase with stroke risk have been inconclusive. We hypothesized that genetic determinants of myeloperoxidase levels influence the development of vascular instability, leading to increased primary intracerebral haemorrhage and lacunar stroke risk. We used a discovery cohort of 1409 primary intracerebral haemorrhage cases and 1624 controls from three studies, an extension cohort of 12 577 ischaemic stroke cases and 25 643 controls from NINDS-SiGN, and a validation cohort of 10 307 ischaemic stroke cases and 29 326 controls from METASTROKE Consortium with genome-wide genotyping to test this hypothesis. A genetic risk score reflecting elevated myeloperoxidase levels was constructed from 15 common single nucleotide polymorphisms identified from prior genome-wide studies of circulating myeloperoxidase levels (P < 5 × 10-6). This genetic risk score was used as the independent variable in multivariable regression models for association with primary intracerebral haemorrhage and ischaemic stroke subtypes. We used fixed effects meta-analyses to pool estimates across studies. We also used Cox regression models in a prospective cohort of 174 primary intracerebral haemorrhage survivors for association with intracerebral haemorrhage recurrence. We present effects of myeloperoxidase elevating single nucleotide polymorphisms on stroke risk per risk allele, corresponding to a one allele increase in the myeloperoxidase increasing genetic risk score. Genetic determinants of elevated circulating myeloperoxidase levels were associated with both primary

  1. Elevated blood lead levels in refugee children--New Hampshire, 2003-2004.

    PubMed

    2005-01-21

    As a result of reductions in lead hazards and improved screening practices, blood lead levels (BLLs) in children aged 1-5 years are decreasing in the United States. However, the risk for elevated BLLs (> or =10 microg/dL) remains high for certain populations, including refugees. After the death of a Sudanese refugee child from lead poisoning in New Hampshire in 2000, the New Hampshire Department of Health and Human Services (NHDHHS) developed lead testing guidelines to screen and monitor refugee children. These guidelines recommend 1) capillary blood lead testing for refugee children aged 6 months-15 years within 3 months after arrival in New Hampshire, 2) follow-up venous testing of children aged <6 years within 3-6 months after initial screening, and 3) notation of refugee status on laboratory slips for first tests. In 2004, routine laboratory telephone reports of elevated BLLs to the New Hampshire Childhood Lead Poisoning Prevention Program (NHCLPPP) called attention to a pattern of elevated BLLs among refugee children. To develop prevention strategies, NHDHHS analyzed NHCLPPP and Manchester Health Department (MHD) data, focusing on the 37 African refugee children with elevated BLLs on follow-up for whom complete data were available. This report describes the results of that analysis, which indicated that 1) follow-up blood lead testing is useful to identify lead exposure that occurs after resettlement and 2) refugee children in New Hampshire older than those routinely tested might have elevated BLLs. Refugee children in all states should be tested for lead poisoning on arrival and several months after initial screening to assess exposure after resettlement.

  2. Influence of ER leak on resting cytoplasmic Ca2+ and receptor-mediated Ca2+ signalling in human macrophage.

    PubMed

    Layhadi, Janice A; Fountain, Samuel J

    2017-06-03

    Mechanisms controlling endoplasmic reticulum (ER) Ca 2+ homeostasis are important regulators of resting cytoplasmic Ca 2+ concentration ([Ca 2+ ] cyto ) and receptor-mediated Ca 2+ signalling. Here we investigate channels responsible for ER Ca 2+ leak in THP-1 macrophage and human primary macrophage. In the absence of extracellular Ca 2+ we employ ionomycin action at the plasma membrane to stimulate ER Ca 2+ leak. Under these conditions ionomycin elevates [Ca 2+ ] cyto revealing a Ca 2+ leak response which is abolished by thapsigargin. IP 3 receptors (Xestospongin C, 2-APB), ryanodine receptors (dantrolene), and translocon (anisomycin) inhibition facilitated ER Ca 2+ leak in model macrophage, with translocon inhibition also reducing resting [Ca 2+ ] cyto . In primary macrophage, translocon inhibition blocks Ca 2+ leak but does not influence resting [Ca 2+ ] cyto . We identify a role for translocon-mediated ER Ca 2+ leak in receptor-mediated Ca 2+ signalling in both model and primary human macrophage, whereby the Ca 2+ response to ADP (P2Y receptor agonist) is augmented following anisomycin treatment. In conclusion, we demonstrate a role of ER Ca 2+ leak via the translocon in controlling resting cytoplasmic Ca 2+ in model macrophage and receptor-mediated Ca 2+ signalling in model macrophage and primary macrophage. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Interactive effects of elevated temperature and CO2 levels on energy metabolism and biomineralization of marine bivalves Crassostrea virginica and Mercenaria mercenaria.

    PubMed

    Ivanina, Anna V; Dickinson, Gary H; Matoo, Omera B; Bagwe, Rita; Dickinson, Ashley; Beniash, Elia; Sokolova, Inna M

    2013-09-01

    The continuing increase of carbon dioxide (CO2) levels in the atmosphere leads to increases in global temperatures and partial pressure of CO2 (PCO2) in surface waters, causing ocean acidification. These changes are especially pronounced in shallow coastal and estuarine waters and are expected to significantly affect marine calcifiers including bivalves that are ecosystem engineers in estuarine and coastal communities. To elucidate potential effects of higher temperatures and PCO2 on physiology and biomineralization of marine bivalves, we exposed two bivalve species, the eastern oysters Crassostrea virginica and the hard clams Mercenaria mercenaria to different combinations of PCO2 (~400 and 800μatm) and temperatures (22 and 27°C) for 15weeks. Survival, bioenergetic traits (tissue levels of lipids, glycogen, glucose and high energy phosphates) and biomineralization parameters (mechanical properties of the shells and activity of carbonic anhydrase, CA) were determined in clams and oysters under different temperature and PCO2 regimes. Our analysis showed major inter-species differences in shell mechanical traits and bioenergetics parameters. Elevated temperature led to the depletion of tissue energy reserves indicating energy deficiency in both species and resulted in higher mortality in oysters. Interestingly, while elevated PCO2 had a small effect on the physiology and metabolism of both species, it improved survival in oysters. At the same time, a combination of high temperature and elevated PCO2 lead to a significant decrease in shell hardness in both species, suggesting major changes in their biomineralization processes. Overall, these studies show that global climate change and ocean acidification might have complex interactive effects on physiology, metabolism and biomineralization in coastal and estuarine marine bivalves. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Elevated blood lead levels from exposure via a radiator workshop.

    PubMed

    Treble, R G; Thompson, T S; Morton, D N

    1998-04-01

    Elevated lead levels were discovered in blood samples collected from family members where both the father and the mother worked in a radiator repair workshop. The father and mother were found to have blood lead levels of 2.0 and 0.5 mumol/L (41.7 and 10.4 micrograms/dL), respectively. The father's blood lead level was just below the Canadian occupational health and safety intervention level (2.5 mumol/L or 52.1 micrograms/dL). The two children had blood lead levels of 1.0 and 0.8 mumol/L (20.8 and 16.7 micrograms/dL), both of which are in excess of the recommended guideline for intervention in the case of children (0.5 mumol/L or 10.4 micrograms/dL). The exposure of the two children was possibly due to a combination of pathways including exposure at the workshop itself during visits and also the transportation of lead-containing dust to the home environment.

  5. Functional interaction of the SNARE protein NtSyp121 in Ca2+ channel gating, Ca2+ transients and ABA signalling of stomatal guard cells.

    PubMed

    Sokolovski, Sergei; Hills, Adrian; Gay, Robert A; Blatt, Michael R

    2008-03-01

    There is now growing evidence that membrane vesicle trafficking proteins, especially of the superfamily of SNAREs, are critical for cellular signalling in plants. Work from this laboratory first demonstrated that a soluble, inhibitory (dominant-negative) fragment of the SNARE NtSyp121 blocked K+ and Cl- channel responses to the stress-related hormone abscisic acid (ABA), but left open a question about functional impacts on signal intermediates, especially on Ca2+-mediated signalling events. Here, we report one mode of action for the SNARE mediated directly through alterations in Ca2+ channel gating and its consequent effects on cytosolic-free [Ca2+] ([Ca2+]i) elevation. We find that expressing the same inhibitory fragment of NtSyp121 blocks ABA-evoked stomatal closure, but only partially suppresses stomatal closure in the presence of the NO donor, SNAP, which promotes [Ca2+]i elevation independently of the plasma membrane Ca2+ channels. Consistent with these observations, Ca2+ channel gating at the plasma membrane is altered by the SNARE fragment in a manner effective in reducing the potential for triggering a rise in [Ca2+]i, and we show directly that its expression in vivo leads to a pronounced suppression of evoked [Ca2+]i transients. These observations offer primary evidence for the functional coupling of the SNARE with Ca2+ channels at the plant cell plasma membrane and, because [Ca2+]i plays a key role in the control of K+ and Cl- channel currents in guard cells, they underscore an important mechanism for SNARE integration with ion channel regulation during stomatal closure.

  6. Experimental tooth pain elevates substance P and matrix metalloproteinase-8 levels in human gingival crevice fluid.

    PubMed

    Avellán, Nina-Li; Sorsa, Timo; Tervahartiala, Taina; Forster, Clemens; Kemppainen, Pentti

    2008-02-01

    Tooth pain can induce a neurogenic inflammatory reaction in gingiva in association with local elevations of matrix metalloproteinase (MMP)-8, which is considered the major tissue destructive protease in gingival crevice fluid (GCF). The pro-inflammatory neuropeptides released by sensory nerves coordinate the activities of the immuno-effector cells and may influence the secretion of MMP-8. With this background, we studied whether experimental tooth pain can trigger changes in GCF levels of the neuropeptide substance P (SP) and MMP-8. The GCF SP levels of stimulated and non-stimulated teeth were analyzed for SP using a competitive enzyme immunoassay (EIA). The GCF MMP-8 levels were determined by quantitative immunofluorometric assay (IFMA). Painful stimulation of the upper central incisor caused significant elevations in GCF SP and MMP-8 levels of the stimulated tooth. At the same time, the GCF SP and MMP-8 levels of non-stimulated control teeth were unchanged. These data indicate that experimental tooth pain can induce local elevations of SP and MMP-8 levels in GCF simultaneously. This supports the possibility of a local neurogenic spread of inflammatory reactions from intrapulpal to surrounding periodontal tissues.

  7. Fungal and bacterial growth in floor dust at elevated relative humidity levels.

    PubMed

    Dannemiller, K C; Weschler, C J; Peccia, J

    2017-03-01

    Under sustained, elevated building moisture conditions, bacterial and fungal growth occurs. The goal of this study was to characterize microbial growth in floor dust at variable equilibrium relative humidity (ERH) levels. Floor dust from one home was embedded in coupons cut from a worn medium-pile nylon carpet and incubated at 50%, 80%, 85%, 90%, 95%, and 100% ERH levels. Quantitative PCR and DNA sequencing of ribosomal DNA for bacteria and fungi were used to quantify growth and community shifts. Over a 1-wk period, fungal growth occurred above 80% ERH. Growth rates at 85% and 100% ERH were 1.1 × 10 4 and 1.5 × 10 5 spore equivalents d -1 mg dust -1 , respectively. Bacterial growth occurred only at 100% ERH after 1 wk (9.0 × 10 4 genomes d -1 mg dust -1 ). Growth resulted in significant changes in fungal (P<.00001) and bacterial community structure (P<.00001) at varying ERH levels. Comparisons between fungal taxa incubated at different ERH levels revealed more than 100 fungal and bacterial species that were attributable to elevated ERH. Resuspension modeling indicated that more than 50% of airborne microbes could originate from the resuspension of fungi grown at ERH levels of 85% and above. © 2016 The Authors. Indoor Air published by John Wiley & Sons Ltd.

  8. Elevated red blood cell 2,3-diphosphoglycerate levels in black blood donors.

    PubMed

    Wallas, C H

    1978-01-01

    Mean levels of 2,3-diphosphoglycerate (DPG) were significantly increased in erythrocytes (RBC) from 43 nonanemic black blood donors (4.80 +/- 0.06 micromoles/l RBC) compared with 22 white donors 4.47 +/- 0.08 micromoles/l RBCs from eight of the 12 black donors with DPG levels greater than 5 micromoles/l RBC. Although a potentially hemolytic disorder could be defined in four (AS hemoglobin, beta-Thalassemia minor, G6PD deficiency), reticulocyte counts were normal. However, when RBCs from the subgroup were compared to RBCs from an additional 25 unselected white donors, the following suggested an abnormally large population of young RBCs in the subgroup: 1) normal or elevated RBC-ATP with normal serum phosphate level; 2) significantly increased activities of RBC age-dependent enzymes hexokinase (p less than 0.02), pyruvate kinase (p less than 0.05), and glutamicoxaloacetic transaminase (p less than 0.01), with normal activity of phosphoglycerate kinase, an age-independent enzyme; 3) decreased dense (older) RBCs as determined by sedimentation in phthalate esters. Since DPG is increased in young RBCs and falls as the RBC ages, loss of older relatively DPG depleted RBCs due to shortened survival could account for the elevated DPG levels seen in the subgroup.

  9. Analysis of lidar elevation data for improved identification and delineation of lands vulnerable to sea-level rise

    USGS Publications Warehouse

    Gesch, Dean B.

    2009-01-01

    The importance of sea-level rise in shaping coastal landscapes is well recognized within the earth science community, but as with many natural hazards, communicating the risks associated with sea-level rise remains a challenge. Topography is a key parameter that influences many of the processes involved in coastal change, and thus, up-to-date, high-resolution, high-accuracy elevation data are required to model the coastal environment. Maps of areas subject to potential inundation have great utility to planners and managers concerned with the effects of sea-level rise. However, most of the maps produced to date are simplistic representations derived from older, coarse elevation data. In the last several years, vast amounts of high quality elevation data derived from lidar have become available. Because of their high vertical accuracy and spatial resolution, these lidar data are an excellent source of up-to-date information from which to improve identification and delineation of vulnerable lands. Four elevation datasets of varying resolution and accuracy were processed to demonstrate that the improved quality of lidar data leads to more precise delineation of coastal lands vulnerable to inundation. A key component of the comparison was to calculate and account for the vertical uncertainty of the elevation datasets. This comparison shows that lidar allows for a much more detailed delineation of the potential inundation zone when compared to other types of elevation models. It also shows how the certainty of the delineation of lands vulnerable to a given sea-level rise scenario is much improved when derived from higher resolution lidar data.

  10. Mechanisms Underlying Endothelin-1 Level Elevations Caused by Excessive Fluoride Exposure.

    PubMed

    Sun, Liyan; Gao, Yanhui; Zhang, Wei; Liu, Xiaona; Li, Bingyun; Cui, Xiaohui; Sun, Dianjun

    2016-01-01

    To explore the mechanisms underlying endothelin-1 (ET-1) elevations induced by excessive fluoride exposure. We measured serum and bone fluoride ion content and plasma ET-1 levels and compared these parameters among different groups in an animal model. We also observed morphological changes in the aorta and endothelium of rabbits. In cell experiments, human umbilical vein endothelial cells (HUVECs) were treated with varying concentrations of NaF for 24h, with or without 10 µM U0126 pretreatment for 1 h. ET-1 levels in culture fluid and intracellular reactive oxygen species (ROS) levels, as well as ET1 gene, endothelin-converting enzyme-1 (ECE-1), extracellular signal-regulating kinase 1/2 (ERK1/2), pERK1/2 expression levels and RAS activation were measured and compared among the groups. Plasma ET-1 levels of rabbits increased significantly in fluorinated groups compared with those in the control group. The rabbit thoracic aortas became slightly hardened in fluorinated groups compared with those in the control group, and some vacuoles were present in the endothelial cell cytoplasm of the rabbits in fluorinated groups. In our cell experiments, ET1 gene and ECE-1 expression levels in HUVECs and ET-1 expression levels in the cell culture supernatants increased significantly in some experimental groups compared with those in the control group. These trends paralleled the changes in intracellular ROS levels, RAS activation, and the pERK1/2-to-ERK1/2 ratio. After U0126 was added, ECE-1 expression and ET-1 levels decreased significantly. Excessive fluoride exposure leads to characteristic endothelial damage (vacuoles), thoracic aorta hardening, and plasma ET-1 level elevations in rabbits. In addition, the ROS-RAS-MEK1/2-pERK1/2/ERK1/2 pathway plays a crucial-and at least partial-role in ET-1 over-expression, which is promoted by excessive fluoride exposure. © 2016 The Author(s) Published by S. Karger AG, Basel.

  11. Hydroxyhydroquinone, a by-product of coffee bean roasting, increases intracellular Ca2+ concentration in rat thymic lymphocytes.

    PubMed

    Kamae, Risa; Nojima, Shoko; Akiyoshi, Kenji; Setsu, Shoki; Honda, Sari; Masuda, Toshiya; Oyama, Yasuo

    2017-04-01

    Hydroxyhydroquinone (HHQ) is generated during coffee bean roasting. A cup of coffee contains 0.1-1.7 mg of HHQ. The actions of HHQ on mammalian DNA were examined because HHQ is a metabolite of benzene, which causes leukemia. Currently, information on the cellular actions of HHQ is limited. We examined the effects of sublethal levels of HHQ on the concentration of intracellular Ca 2+ in rat thymic lymphocytes by using a flow cytometric technique with fluorescent probes. HHQ at 10 μM or more significantly elevated intracellular Ca 2+ levels by increasing the membrane permeability of divalent cations, resulting in hyperpolarization via the activation of Ca 2+ -dependent K + channels. HHQ-induced changes in the intracellular Ca 2+ concentration and membrane potential may affect the cell functions of lymphocytes. HHQ-reduced coffee may be preferable in order to avoid the possible adverse effects of HHQ. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Nanodosimetry of (125)I Auger electrons.

    PubMed

    Bantsar, Aliaksandr; Pszona, Stanislaw

    2012-12-01

    The nanodosimetric description of the radiation action of Auger electrons on nitrogen targets of nanometric size is presented. Experimental microdosimetry at nanometer scale for Auger electrons has been accomplished with the set-up called Jet Counter. This consists of a pulse-operated valve which injects an expanding nitrogen jet into an interaction chamber where a gaseous sensitive volume of cylindrical shape is created. The ionization cluster size distributions (ICSD) created by Auger electrons emitted by (125)I while crossing a nanometer-sized volume have been measured. The ICSD for the sensitive volumes corresponding to 3 and 12 nm in diameter (in unit density 1 g/cm(3)) irradiated by electrons emitted by a (125)I source were collected and compared with the corresponding Monte Carlo (MC) simulation. The preliminary results of the experiments with Auger electrons of (125)I interacting with a nitrogen jet having nanometric size comparable to a deoxyribonucleic acid (DNA) and nucleosome, showing the discrete spectrum of ICSD with extended cluster size, are described. The presented paper describes for the first time the nanodosimetric experiments with Auger electrons emitted by (125)I. A set of the new descriptors of the radiation quality describing the radiation effect at nanometer level is proposed. The ICSD were determined for the first time for an Auger emitter of (125)I.

  13. Study on IL-2 and CA 15-3 level as combined biomarkers in monitoring chemotherapeutic response among invasive breast cancer patients

    NASA Astrophysics Data System (ADS)

    Hameed, Ahmed Muthanna Abdul; Hamid, Auni Fatin Abdul; Shahfiza Noor, Nurul; Appalanaido, Gokula Kumar; Bariyah Sahul Hamid, Shahrul

    2017-05-01

    In Malaysia, breast cancer is the most frequent type of disease among women. This study was designed to determine the clinical usefulness of carbohydrate antigen (CA 15-3) and interleukin 2 (IL-2) levels as combined biomarkers in monitoring breast cancer patient’s response to chemotherapy. Ethical approval was obtained to recruit patients with histologically confirmed invasive ductal carcinoma (IDC) attending Oncology Clinic at Advanced Medical and Dental Institute. Whole blood was collected from 10 IDC breast cancer patients’ pre and post primary chemotherapy. Plasma was separated from the whole blood to determine the CA 15-3 level and IL-2 level using enzyme-linked immunosorbent assay (ELISA) pre and post-treatment. In addition, the histological findings, tumour stage and other patients’ data were obtained from the medical record. Findings showed that IL-2 had borderline significant changes between pre- and post-chemotherapy (p = 0.074) whereas for CA 15-3, there was insignificant differences of CA 15-3 level between pre and post-chemotherapy (p > 0.05). It was noted that only CA 15-3 level had significant correlation with tumour size. This study demonstrates that IL-2 level requires further investigation in a larger sample size to correlate its potential use as combined biomarker with CA 15-3 in monitoring response to chemotherapy.

  14. Deformation processed Al/Ca nano-filamentary composite conductors for HVDC applications

    NASA Astrophysics Data System (ADS)

    Czahor, C. F.; Anderson, I. E.; Riedemann, T. M.; Russell, A. M.

    2017-07-01

    Efficient long-distance power transmission is necessary as the world continues to implement renewable energy sources, often sited in remote areas. Light, strong, high-conductivity materials are desirable for this application to reduce both construction and operational costs. In this study an Al/Ca (11.5% vol.) composite with nano-filamentary reinforcement was produced by powder metallurgy then extruded, swaged, and wire drawn to a maximum true strain of 12.7. The tensile strength increased exponentially as the filament size was reduced to the sub-micron level. In an effort to improve the conductor’s ability to operate at elevated temperatures, the deformation-processed wires were heat-treated at 260°C to transform the Ca-reinforcing filaments to Al2Ca. Such a transformation raised the tensile strength by as much as 28%, and caused little change in ductility, while the electrical conductivity was reduced by only 1% to 3%. Al/Al2Ca composites are compared to existing conductor materials to show how implementation could affect installation and performance.

  15. Low-Dose Ethanol Preconditioning Protects Against Oxygen-Glucose Deprivation/Reoxygenation-Induced Neuronal Injury By Activating Large Conductance, Ca2+-Activated K+ Channels In Vitro.

    PubMed

    Su, Fang; Guo, An-Chen; Li, Wei-Wei; Zhao, Yi-Long; Qu, Zheng-Yi; Wang, Yong-Jun; Wang, Qun; Zhu, Yu-Lan

    2017-02-01

    Increasing evidence suggests that low to moderate ethanol ingestion protects against the deleterious effects of subsequent ischemia/reperfusion; however, the underlying mechanism has not been elucidated. In the present study, we showed that expression of the neuronal large-conductance, Ca 2+ -activated K + channel (BK Ca ) α-subunit was upregulated in cultured neurons exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) compared with controls. Preconditioning with low-dose ethanol (10 mmol/L) increased cell survival rate in neurons subjected to OGD/R, attenuated the OGD/R-induced elevation of cytosolic Ca 2+ levels, and reduced the number of apoptotic neurons. Western blots revealed that ethanol preconditioning upregulated expression of the anti-apoptotic protein Bcl-2 and downregulated the pro-apoptotic protein Bax. The protective effect of ethanol preconditioning was antagonized by a BK Ca channel inhibitor, paxilline. Inside-out patches in primary neurons also demonstrated the direct activation of the BK Ca channel by 10 mmol/L ethanol. The above results indicated that low-dose ethanol preconditioning exerts its neuroprotective effects by attenuating the elevation of cytosolic Ca 2+ and preventing neuronal apoptosis, and this is mediated by BK Ca channel activation.

  16. Greek rheumatoid arthritis patients have elevated levels of antibodies against antigens from Proteus mirabilis.

    PubMed

    Christopoulos, Georgios; Christopoulou, V; Routsias, J G; Babionitakis, A; Antoniadis, C; Vaiopoulos, G

    2017-03-01

    Patients with rheumatoid arthritis (RA) from different ethnic groups present elevated levels of antibodies against Proteus mirabilis. This finding implicates P. mirabilis in the development of RA. The aim of this study was to investigate the importance of P. mirabilis in the etiopathogenesis of RA in Greek RA patients. In this study, 63 patients with RA and 38 healthy controls were included. Class-specific antibodies IgM, IgG, and IgA against three human cross-reactive and non-cross-reactive synthetic peptides from P. mirabilis-hemolysin (HpmB), urease C (UreC), and urease F (UreF)-were performed in all subjects, using the ELISA method. RA patients had elevated levels of IgM, IgG, and IgA antibodies against HpmB and UreC Proteus peptide which are significantly different compared to healthy controls: p = 0.005, p < 0.001, and p = 0.003 and p = 0.007, p = 0.002, and p < 0.001, correspondingly. Also, elevated levels of IgM, IgG, and IgA antibodies against the UreF Proteus peptide-which are non-cross-reactive with human tissue antigens-were observed and their significant difference compared to healthy controls (p = 0.007, p < 0.001, p < 0.001). Anti-peptide antibodies in RA patients showed a significant correlation with rheumatoid factors (Rf), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP), especially when patients were divided into subgroups according to the receiving treatment. Greek RA patients present elevated levels of antibodies against P. mirabilis antigenic epitopes, such as in North European populations, albeit Greek RA patients presenting the cross-reaction antigen in a low percentage. These results indicate that P. mirabilis through the molecular mimicry mechanism leads to inflammation and damage of the joints in RA.

  17. Tripeptidyl Peptidase II Regulates Sperm Function by Modulating Intracellular Ca2+ Stores via the Ryanodine Receptor

    PubMed Central

    Zhou, Yuchuan; Ru, Yanfei; Wang, Chunmei; Wang, Shoulin; Zhou, Zuomin; Zhang, Yonglian

    2013-01-01

    Recent studies have identified Ca2+ stores in sperm cells; however, it is not clear whether these Ca2+ stores are functional and how they are mobilized. Here, in vitro and in vivo, we determined that tripeptidyl peptidase II antagonists strongly activated the cAMP/PKA signaling pathway that drives sperm capacitation-associated protein tyrosine phosphorylation. We demonstrated that in the absence of Ca2+, TPIII antagonists elevated the intracellular Ca2+ levels in sperm, resulting in a marked improvement in sperm movement, capacitation, acrosome reaction, and the in vitro fertilizing ability. This antagonist-induced release of intracellular Ca2+ could be blocked by the inhibitors of ryanodine receptors (RyRs) which are the main intracellular Ca2+ channels responsible for releasing stored Ca2+. Consistent with these results, indirect immunofluorescence assay using anti-RyR antibodies further validated the presence of RyR3 in the acrosomal region of mature sperm. Thus, TPPII can regulate sperm maturation by modulating intracellular Ca2+ stores via the type 3 RyR. PMID:23818952

  18. The effect of oral contraception on cardiometabolic risk factors in women with elevated androgen levels.

    PubMed

    Krysiak, Robert; Gilowska, Małgorzata; Okopień, Bogusław

    2017-02-01

    In unselected reproductive-aged women, use of combined estrogen-progestin oral contraceptive pills has been linked with an increased risk of vascular disease. The aim of this study was to investigate the effect of oral contraception on cardiometabolic risk factors in a population of women with hyperandrogenism. The study included 16 untreated women with elevated testosterone levels and 15 matched healthy women who were then treated with oral contraceptive pills containing ethinyl estradiol (30μg) and drospirenone (3mg). Plasma lipids, glucose homeostasis markers, circulating levels of androgens, uric acid, high-sensitivity C-reactive protein (hsCRP), fibrinogen and homocysteine, as well as urinary albumin-to-creatinine ratio (UACR) were assessed at baseline and after 12 weeks of treatment. Compared to healthy women, women with elevated androgen levels showed increased plasma levels of hsCRP, fibrinogen and homocysteine, as well as a higher value of UACR. Oral contraception reduced androgen levels only in hyperandrogenic women. In healthy women, ethinyl estradiol plus drospirenone increased plasma levels of insulin, hsCRP, fibrinogen and homocysteine, while in women with elevated androgen levels their effect was limited only to a small increase in hsCRP. Our results suggest that a deteriorating effect of oral contraceptive pills containing ethinyl estradiol and drospirenone in hyperandrogenic women is weaker than in healthy young women and that ethinyl estradiol/drospirenone combination therapy may be safely used in the former group of patients. Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.

  19. Risk factors and consequences of maternal anaemia and elevated haemoglobin levels during pregnancy: a population-based prospective cohort study.

    PubMed

    Gaillard, Romy; Eilers, Paul H C; Yassine, Siham; Hofman, Albert; Steegers, Eric A P; Jaddoe, Vincent W V

    2014-05-01

    To determine sociodemographic and life style-related risk factors and trimester specific maternal, placental, and fetal consequences of maternal anaemia and elevated haemoglobin levels in pregnancy. In a population-based prospective cohort study of 7317 mothers, we measured haemoglobin levels in early pregnancy [gestational age median 14.4 weeks (inter-quartile-range 12.5-17.5)]. Anaemia (haemoglobin ≤11 g/dl) and elevated haemoglobin levels (haemoglobin ≥13.2 g/dl) were defined according to the WHO criteria. Maternal blood pressure, placental function and fetal growth were measured in each trimester. Data on gestational hypertensive disorders and birth outcomes was collected from hospitals. Older maternal age, higher body mass index, primiparity and European descent were associated with higher haemoglobin levels (P < 0.05). Elevated haemoglobin levels were associated with increased systolic and diastolic blood pressure throughout pregnancy (mean differences 5.1 mmHg, 95% confidence interval [CI] 3.8, 6.5 and 4.1 mmHg, 95% CI 3.0, 5.2, respectively) and with a higher risk of third trimester uterine artery notching (RR 1.3, 95% CI 1.0, 1.7). As compared with maternal normal haemoglobin levels, not anaemia, but elevated haemoglobin levels were associated with fetal head circumference, length, and weight growth restriction from third trimester onwards (P < 0.05). Elevated haemoglobin levels were associated with increased risks of gestational hypertensive disorders (RR 1.4, 95% CI 1.1, 1.8) and adverse birth outcomes (RR 1.4, 95% CI 1.1, 1.7). In a low-risk population, various sociodemographic and life style factors affect haemoglobin levels during pregnancy. Elevated haemoglobin levels are associated with increased risks of maternal, placental, and fetal complications. © 2014 John Wiley & Sons Ltd.

  20. Changes in wetland sediment elevation following major storms: implications for estimating trends in relative sea-level rise

    USGS Publications Warehouse

    Cahoon, D.R.

    2003-01-01

    Hurricanes can be important agents of geomorphic change in coastal marshes and mangrove forests. Hurricanes can cause large-scale redistribution of sediments within the coastal environment resulting in sedimentation, erosion, disruption of vegetated substrates, or some combination of these processes in coastal wetlands. It has been proposed that such sediment pulsing events are important at maintaining wetland sediment elevations in sediment-poor settings with high rates of relative sea-level rise, such as the Mississippi River Delta. But do these pulsing events result in a net gain in sediment elevation even when substantial amounts of sediment are deposited? Clearly sediment erosion and scour would result in a loss of elevation. But will a substantial sediment deposit on poorly consolidated sediments always result in a net gain in elevation? If the wetland vegetation is killed by wind, tidal surge, or the introduction of saline water, will there be a collapse of sediment elevation in the absence of root production and ongoing decomposition of root matter? During the past decade several wetlands where my colleagues and I have monitored sedimentation and elevation change have been struck by one to several hurricanes. This paper describes the range of sediment elevation responses to hurricane strikes, the suggested mechanisms driving those responses, the implications for estimating long-term trends in relative sea-level rise, and future research needs for improving our understanding of the role that major storms play in wetland sediment elevation dynamics. For many wetlands the change in sediment elevation was directly proportional to the amount of sediment deposited by the storm. But surprisingly, there was a loss of elevation in some wetlands with substantial sediment deposits. In these wetlands, the impact of the storm was either direct (sedimentation and compaction) or indirect (vegetation death), and the effect on sediment elevation was either permanent or

  1. Calreticulin reveals a critical Ca2+ checkpoint in cardiac myofibrillogenesis

    PubMed Central

    Li, Jian; Pucéat, Michel; Perez-Terzic, Carmen; Mery, Annabelle; Nakamura, Kimitoshi; Michalak, Marek; Krause, Karl-Heinz; Jaconi, Marisa E.

    2002-01-01

    Calreticulin (crt) is an ubiquitously expressed and multifunctional Ca2+-binding protein that regulates diverse vital cell functions, including Ca2+ storage in the ER and protein folding. Calreticulin deficiency in mice is lethal in utero due to defects in heart development and function. Herein, we used crt − / − embryonic stem (ES) cells differentiated in vitro into cardiac cells to investigate the molecular mechanisms underlying heart failure of knockout embryos. After 8 d of differentiation, beating areas were prominent in ES-derived wild-type (wt) embryoid bodies (EBs), but not in ES-derived crt − / − EBs, despite normal expression levels of cardiac transcription factors. Crt − / − EBs exhibited a severe decrease in expression and a lack of phosphorylation of ventricular myosin light chain 2 (MLC2v), resulting in an impaired organization of myofibrils. Crt − / − phenotype could be recreated in wt cells by chelating extracellular or cytoplasmic Ca2+ with EGTA or BAPTA, or by inhibiting Ca2+/calmodulin-dependent kinases (CaMKs). An imposed ionomycin-triggered cystolic-free Ca2+ concentration ([Ca2+]c) elevation restored the expression, phosphorylation, and insertion of MLC2v into sarcomeric structures and in turn the myofibrillogenesis. The transcription factor myocyte enhancer factor C2 failed to accumulate into nuclei of crt − / − cardiac cells in the absence of ionomycin-triggered [Ca2+]c increase. We conclude that the absence of calreticulin interferes with myofibril formation. Most importantly, calreticulin deficiency revealed the importance of a Ca2+-dependent checkpoint critical for early events during cardiac myofibrillogenesis. PMID:12105184

  2. Chronic hypervitaminosis D3 determines a decrease in C-cell numbers and calcitonin levels in rats.

    PubMed

    Martín-Lacave, I; Ramos, F; Utrilla, J C; Conde, E; Hevia, A; Fernández, R; Moreno, A M; Fernández-Santos, J M; Galera-Davidson, H

    1998-02-01

    Many papers have reported that chronic hypercalcemia induced either by large doses of vitamin D or by the administration of calcium or parathormone, produces hypertrophy and hyperplasia of C cells. However, more recent studies suggest that the effect of elevated calcium or 1.25(OH)2D3 concentration on the production of calcitonin may be more complex than previously suspected. To assess the validity of such a response an experimental model, where hypercalcemia was induced with vitamin D3 overdose, was designed. Male Wistar rats were administered vitamin D3 chronically (50,000 IU per 100 ml of drinking water with or without CaCl2). Serum calcium and calcitonin levels were determined. C cells were stained by immunohistochemistry using calcitonin and neuronal specific enolase (NSE) antibodies and their percentage was calculated by a morphometric analysis. We also investigated the ultrastructural characteristic of the C cells under experimental conditions. C cells did not have a proliferative response rather a decrease in their number was observed after 1 month of treatment with 25,000 IU of vitamin D3 (1.55 vs 2.43% in control animals) and 3 months with vitamin plus CaCl2 (2.27% vs 3.62% in control animals). In addition, no significant changes in serum calcitonin levels were observed during the experimental period. We conclude that rat C cells do not respond with hypertrophic and hyperplastic changes in a hypercalcemic state due to an intoxication with vitamin D3.

  3. Astrocytic Ca2+ responses in the spinal dorsal horn by noxious stimuli to the skin.

    PubMed

    Yoshihara, Kohei; Matsuda, Tsuyoshi; Kohro, Yuta; Tozaki-Saitoh, Hidetoshi; Inoue, Kazuhide; Tsuda, Makoto

    2018-05-03

    The role of astrocytes in the spinal dorsal horn (SDH) for sensory information processing under normal conditions is poorly understood. In this study, we investigated whether SDH astrocytes respond to noxious and innocuous stimuli to the skin of normal mice using in vivo two-photon Ca 2+ imaging under anesthesia. We found that noxious stimulation evoked by intraplantar formalin injection provoked an elevation in intracellular Ca 2+ levels in SDH astrocytes. By contrast, neither instantaneous noxious pinching nor innocuous stimuli (cooling or brushing) to the hindpaw elicited astrocytic Ca 2+ responses. Thus, SDH astrocytes could respond preferentially to a strong and/or sustained noxious stimulus. Copyright © 2018 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  4. Elevated CO2 facilitates C and N accumulation in a rice paddy ecosystem.

    PubMed

    Guo, Jia; Zhang, Mingqian; Wang, Xiaowen; Zhang, Weijian

    2015-03-01

    Elevated CO2 can stimulate wetland carbon (C) and nitrogen (N) exports through gaseous and dissolved pathways, however, the consequent influences on the C and N pools are still not fully known. Therefore, we set up a free-air CO2 enrichment experiment in a paddy field in Eastern China. After five year fumigation, we studied C and N in the plant-water-soil system. The results showed: (1) elevated CO2 stimulated rice aboveground biomass and N accumulations by 19.1% and 12.5%, respectively. (2) Elevated CO2 significantly increased paddy soil TOC and TN contents by 12.5% and 15.5%, respectively in the 0-15 cm layer, and 22.7% and 26.0% in the 15-30 cm soil layer. (3) Averaged across the rice growing period, elevated CO2 greatly increased TOC and TN contents in the surface water by 7.6% and 11.4%, respectively. (4) The TOC/TN ratio and natural δ15N value in the surface soil showed a decreasing trend under elevated CO2. The above results indicate that elevated CO2 can benefit C and N accumulation in paddy fields. Given the similarity between the paddies and natural wetlands, our results also suggest a great potential for long-term C and N accumulation in natural wetlands under future climate patterns. Copyright © 2015. Published by Elsevier B.V.

  5. East and west elevations. San Berardino Valley Union Junior College, ...

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

    East and west elevations. San Berardino Valley Union Junior College, Science Building. Also includes elevations and sections of chemistry department shelving. Howard E. Jones, Architect, San Bernardino, California. Sheet 4, Job no. 311. Scales 1/8 inch to the foot (elevations) and 1/2 inch t other foot (shelving). February 15, 1927. - San Bernardino Valley College, Life Science Building, 701 South Mount Vernon Avenue, San Bernardino, San Bernardino County, CA

  6. Evidence of a cellular immune response against sialyl-Tn in breast and ovarian cancer patients after high-dose chemotherapy, stem cell rescue, and immunization with Theratope STn-KLH cancer vaccine.

    PubMed

    Sandmaier, B M; Oparin, D V; Holmberg, L A; Reddish, M A; MacLean, G D; Longenecker, B M

    1999-01-01

    Seven ovarian and 33 breast high-risk stage II/III and stage IV cancer patients received high-dose chemotherapy followed by stem cell rescue. Thirty to 151 days after stem cell transplantation, the patients received their first immunotherapy treatment with Theratope STn-KLH cancer vaccine. Most patients developed increasing IgG anti-STn titers to a sustained peak after the fourth or fifth immunizations. Only one patient had elevated CA27.29 (MUC1 mucin) serum levels at trial entry. Five of the seven patients with preimmunotherapy elevated serum CA125 levels demonstrated decreasing CA125 levels during immunotherapy, consistent with an antitumor response. Evidence of STn antigen-specific T-cell proliferation was obtained from 17 of the 27 evaluable patients who received at least three immunotherapy treatments. Eleven of the 26 patients tested had evidence of an anti-STn TH1 antigen-specific T-cell response as determined by interferon-gamma, but not interleukin (IL)-4, production. After immunization, lytic activity of peripheral blood lymphocytes (PBLs) tested against a lymphokine activated killer (LAK)-sensitive cell line, a natural killer (NK)-sensitive cell line, and an STn-expressing cancer cell line (OVCAR) increased significantly. In vitro IL-2 treatment of the PBLs after vaccination greatly enhanced killing of the STn+ cancer cell line. Evidence of the development of OVCAR specific killing activity, over and above that seen due to LAK or NK killing, is presented. These studies provide the strongest evidence in humans of the development of an antitumor T-cell response after immunization with a cancer-associated carbohydrate antigen.

  7. Barrier island response to an elevated sea-level anomaly: Onslow Beach, North Carolina, USA

    NASA Astrophysics Data System (ADS)

    Theuerkauf, E. J.; Rodriguez, A. B.; Fegley, S. R.; Luettich, R.

    2012-12-01

    Variations in sea level over time scales ranging from hours to millennia influence coastal processes and evolution. At annual time scales, elevated sea-level anomalies produce coastal flooding and promote beach erosion. This study examines the coastal response of Onslow Beach, North Carolina to the summer 2009 East Coast sea-level anomaly. Onslow Beach is a 12-km-long wave-dominated barrier island with highly variable along-barrier morphology. The transgressive southern portion of the island is characterized by a narrow beach, low dunes, and multiple washover fans, while the regressive northern portion is characterized by a wide beach and continuous tall dunes. Hourly tide gauge data from adjacent NOAA stations (Beaufort and Wrightsville Beach) are used to determine the timing and extent of elevated water levels. The seasonal and longer term trends (relative sea level rise) are removed from both of the water level series and the sea-level anomaly is represented by a large residual between the observed and predicted water levels. Beach response is quantified using terrestrial laser scanning for morphology and from geoprobe cores to determine the maximum depth of erosion (MDOE). The mean high water (MHW) shoreline and dune toe are digitized from digital elevation models derived from the laser scans and analyzed using the Digital Shoreline Analysis System (DSAS). Landward (negative) movement of these contacts indicates erosion. Wave data collected from an Acoustic Wave and Current Meter (AWAC) located offshore of the southern end of Onslow Beach is used to characterize the wave regime throughout the study. Water level is elevated in the tide gauge data from June 2009 to March 2010. This sea-level anomaly corresponds with an increase in the maximum depth of erosion between 2009 and 2010. Landward movement of the MHW shoreline and the dunetoe increased during the period between September 2009 and May 2010 indicating an increase in beach erosion during the sea-level

  8. Bone turnover biomarkers in obese postmenopausal Saudi women with type-II diabetes mellitus.

    PubMed

    Alselami, Nada M; Noureldeen, Amani F H; Al-Ghamdi, Maryam A; Khan, Jalaluddin A; Moselhy, Said S

    2015-03-01

    There is a high prevalence of diabetes mellitus type-2 (T2DM) and osteoporosis are problems worldwide. In this study, we evaluated the correlation between T2DM and bone turnover in diabetic obese postmenopausal Saudi women. The present study included total of 65 T2-DM obese postmenopausal Saudi women, (36 uncontrolled, 29 controlled). The following serum biochemical parameters were evaluated [fasting blood glucose (FBG), total calcium (Ca), phosphorus (Pi), parathyroid hormone (PTH), 1,25-(OH)2 Vitamin D3, osteocalcin (OC), procollagen (PICP) and cathepsin k (Cath K)]. Serum OC levels were significantly decreased in diabetic obese postmenopausal group compared to their respective healthy group (P < 0.004). PICP and Cath K were significantly elevated in diabetic postmenopausal group compared to the healthy group (P < 0.024 & 0.001). A significant elevation in 1,25(OH)2 Vitamin D3, Ca and Pi levels in diabetic obese postmenopausal patients group compared to the healthy group. However, a non-significant changes was observed in serum PTH level between different groups. In this study, the changes in the biochemical parameters and bone turnover markers in obese women are strong risk factors for diabetes development that may contribute to osteopenia and osteoporosis. The study showed the strong effect of T2DM on biochemical markers of bone turnover in obese postmenopausal Saudi women.

  9. 1,25 Dihydroxyvitamin D circulating levels, calcitriol administration, and incidence of acute rejection, CMV infection, and polyoma virus infection in renal transplant recipients.

    PubMed

    Moscarelli, Luciano; Antognoli, Giulia; Buti, Elisa; Dervishi, Egrina; Fani, Filippo; Caroti, Leonardo; Tsalouchos, Aris; Romoli, Elena; Ghiandai, Giulia; Minetti, Enrico

    2016-10-01

    Observation that 1,25-Dihydroxyvitamin-D3 has an immunomodulatory effect on innate and adaptive immunity raises the possible effect on clinical graft outcome. Aim of this study was to evaluate the correlation of biopsy-proven acute rejection, CMV infection, BKV infection, with 1,25-Dihydroxyvitamin-D3 deficiency and the benefit of calcitriol supplementation before and during the transplantation. Risk factors and kidney graft function were also evaluated. All RTRs received induction therapy with basiliximab, cyclosporine, mycophenolic acid, and steroids. During the first year, the incidence of BPAR (4% vs 11%, P=.04), CMV infection (3% vs 9%, P=.04), and BKV infection (6% vs 19%, P=.04) was significantly lower in users compared to controls. By multivariate Cox regression analysis, 1,25-Dihydroxyvitamin-D3 deficiency and no calcitriol exposure were independent risk factors for BPAR (HR=4.30, P<.005 and HR=3.25, P<.05), for CMV infection (HR=2.33, P<.05 and HR=2.31, P=.001), and for BKV infection (HR=2.41, P<.05 and HR=2.45, P=.001). After one year, users had a better renal function: eGFR was 62.5±6.7 mL/min vs 51.4±7.6 mL/min (P<.05). Only one user developed polyomavirus-associated nephropathy vs 15 controls. Two users lost their graft vs 11 controls. 1,25(OH)2-D3 deficiency circulating levels increased the risk of BPAR, CMV infection, BKV infection after kidney transplantation. Administration of calcitriol is a way to obtain adequate 1,25(OH)2-D3 circulating levels. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Use of the MoCA in Detecting Early Alzheimer's Disease in a Spanish-Speaking Population with Varied Levels of Education

    PubMed Central

    Zhou, Yan; Ortiz, Freddy; Nuñez, Christopher; Elashoff, David; Woo, Ellen; Apostolova, Liana G.; Wolf, Sheldon; Casado, Maria; Caceres, Nenette; Panchal, Hemali; Ringman, John M.

    2015-01-01

    Background/Aims Performance on the Montreal Cognitive Assessment (MoCA) has been demonstrated to be dependent on the educational level. The purpose of this study was to identify how to best adjust MoCA scores and to identify MoCA items most sensitive to cognitive decline in incipient Alzheimer's disease (AD) in a Spanish-speaking population with varied levels of education. Methods We analyzed data from 50 Spanish-speaking participants. We examined the pattern of diagnosis-adjusted MoCA residuals in relation to education and compared four alternative score adjustments using bootstrap sampling. Sensitivity and specificity analyses were performed for the raw and each adjusted score. The interval reliability of the MoCA as well as item discrimination and item validity were examined. Results We found that with progressive compensation added for those with lower education, unexplained residuals decreased and education-residual association moved to zero, suggesting that more compensation was necessary to better adjust MoCA scores in those with a lower educational level. Cube copying, sentence repetition, delayed recall, and orientation were most sensitive to cognitive impairment due to AD. Conclusion A compensation of 3-4 points was needed for <6 years of education. Overall, the Spanish version of the MoCA maintained adequate psychometric properties in this population. PMID:25873930

  11. Elevated polyamines in urothelial cells from OAB subjects mediate oxotremorine-evoked rapid intracellular calcium rise and delayed acetylcholine release.

    PubMed

    Li, Mingkai; Sun, Yan; Tomiya, Noboru; Hsu, Yuchao; Chai, Toby C

    2013-08-15

    Increased polyamine signaling in bladder urothelial cells (BUC) may play a role in the pathophysiology of overactive bladder (OAB). We quantitated intracellular polyamine levels in cultured BUC from OAB and asymptomatic (NB) subjects. We assessed whether polyamines modulated rapid intracellular calcium ([Ca(2+)]i) changes and delayed acetylcholine (ACh) release evoked by oxotremorine (OXO, a muscarinic agonist). BUC were cultured from cystoscopic biopsies. High-performance liquid chromatography (HPLC) quantitated intracellular putrescine, spermidine, and spermine levels. Five-millimeter difluoromethylornithine (DFMO), and one-millimeter methylglyoxalbisguanylhydrazone (MGBG) treatments were used to deplete intracellular polyamines. Ten micrometers of OXO were used to increase [Ca(2+)]i levels (measured by fura 2 microfluorimetry) and trigger extracellular ACh release (measured by ELISA). Polyamine levels were elevated in OAB compared with NB BUC (0.5 ± 0.15 vs. 0.16 ± 0.03 nmol/mg for putrescine, 2.4 ± 0.21 vs. 1.01 ± 0.13 nmol/mg for spermidine, and 1.90 ± 0.27 vs. 0.86 ± 0.26 nmol/mg for spermine; P < 0.05 for all comparisons). OXO evoked greater [Ca(2+)]i rise in OAB (205.10 ± 18.82% increase over baseline) compared with in NB BUC (119.54 ± 13.01%; P < 0.05). After polyamine depletion, OXO evoked [Ca(2+)]i rise decreased in OAB and NB BUC to 43.40 ± 6.4