Science.gov

Sample records for abnormally high serum

  1. Abnormalities of serum calcium and magnesium

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Neonatal hypocalcemia is defined as a total serum calcium concentration of <7 mg/dL or an ionized calcium concentration of <4 mg/dL (1mmol/L). In very low birth weight (VLBW) infants, ionized calcium values of 0.8 to 1 mmol/L are common and not usually associated with clinical symptoms. In larger in...

  2. Interpretation of Serum Calcium in Patients with Abnormal Serum Proteins

    PubMed Central

    Payne, R. B.; Little, A. J.; Williams, R. B.; Milner, J. R.

    1973-01-01

    Two hundred consecutive specimens received in this laboratory for “liver function tests” showed a wide range of abnormal protein concentrations. Calcium concentration correlated closely with albumin (r = 0·867) but less closely with total protein (r = 0·682). A simple formula for adjusting calcium concentration was derived from the regression equation of calcium on albumin. Adjusted calcium = calcium - albumin + 4·0, where calcium is in mg/100 ml and albumin in g/100 ml. Low calcium concentrations were found in 49 (24·5%) and raised concentrations in six (3%) of the 200 blood specimens taken for liver function tests. After adjustment, the 95% limits of the observed range were identical with the 95% limits of the normal range determined in this laboratory. Unlike adjustments based on total protein or specific gravity, the adjustment on albumin in 39 specimens which showed hypergammaglobulinaemia on electrophoresis gave normal calcium concentrations. PMID:4758544

  3. Abnormal maternal serum alpha fetoprotein and pregnancy outcome.

    PubMed

    Zarzour, S J; Gabert, H A; Diket, A L; St Amant, M; Miller, J M

    1998-01-01

    The objective was to assess the occurrence of miscarriages, low birth weight, and karyotype abnormalities found with low and elevated maternal serum alpha-fetoprotein (MSAFP) among women who had genetic amniocentesis performed. A retrospective study of 2,159 women who had MSAFP analysis prior to amniocentesis was conducted. Pregnancy outcomes were obtained from record review and physicians follow-up. Limits of MSAFP used in analysis were <0.5 adjusted multiples of the median (MOM) (lower levels) and >2.0 MOM (upper levels). Autosomal trisomy was found in 1.6% with low, 0.9% normal, and 0.6% with elevated MSAFP values. Sex chromosome abnormalities were present only in patients with normal MSAFP, [45X (n = 6), 47XXY (n = 2), 69XXX]. Of five open neural tube defects, four had elevated MSAFP and one had a normal value. Omphalocele was identified in four patients, two with normal and two with elevated MSAFP. Gastroschisis was found in one low and one elevated MSAFP. Amniotic fluid alpha-fetoprotein (AFAFP) values did not correlate with MSAFP values. Patients with low MSAFP levels had a greater prevalence of abnormal karyotype (19 of 249, prevalence = 0.076) than patients with an elevated MSAFP level (2 or 166, prevalence = 0.012 OR (odds ratio) = 0.20 (P value = 0.024) when unadjusted for maternal age, and OR = 0.09 (P value = 0.001) when adjusted for maternal age. Spontaneous abortion occurred more often in patients with elevated (4 of 166, or 4%) than normal or low (20 of 1948, or 1%) values of MSAFP (odds ratio 4.32, P = 0.020 when adjusted for maternal age). Birth weight below 2,500 g was present less frequently with low or normal MSAFP (136 of 1,760, or 7.7%) than in elevated MSAFP (21 of 144 or 14.6%) (odds ratio 2.04, P = 0.005, unadjusted; and odds ratio = 2.32, P = 0.003, adjusted for maternal age). Female fetuses were present more often with low MSAFP (136 of 249, or 55%) than elevated levels 43% (71 of 164, or 43%; P = 0.024). We conclude that patients

  4. Effects of flaxseed consumption on systemic inflammation and serum lipid profile in hemodialysis patients with lipid abnormalities.

    PubMed

    Khalatbari Soltani, Saman; Jamaluddin, Rosita; Tabibi, Hadi; Mohd Yusof, Barakatun Nisak; Atabak, Shahnaz; Loh, Su-Peng; Rahmani, Leila

    2013-04-01

    Inflammation and lipid abnormalities are two important risk factors for cardiovascular disease in hemodialysis (HD) patients. The present study was designed to investigate the effects of flaxseed consumption on systemic inflammation and serum lipid profile in HD patients with lipid abnormalities. This was an unblinded, randomized clinical trial. Thirty HD patients with dyslipidemia (triglyceride >200 mg/dL and/or high-density lipoprotein-cholesterol (HDL-C) <40 mg/dL) were randomly assigned to either a flaxseed or control group. Patients in the flaxseed group received 40 g/day ground flaxseed for 8 weeks, whereas patients in the control group received their usual diet, without any flaxseed. At baseline and at the end of week 8, 7 mL of blood was collected after a 12- to 14-hour fast and serum concentrations of triglyceride, total cholesterol, low-density lipoprotein-cholesterol (LDL-C), HDL-C, and C-reactive protein (CRP) were measured. Serum concentrations of triglyceride (P < 0.01), total cholesterol (P < 0.01), LDL-C (P < 0.01), and CRP (P < 0.05) decreased significantly in the flaxseed group at the end of week 8 compared with baseline, whereas serum HDL-C showed a significant increase (P < 0.01). These changes in the flaxseed group were significant in comparison with the control group. The study indicates that flaxseed consumption improves lipid abnormalities and reduces systemic inflammation in HD patients with lipid abnormalities. PMID:22998533

  5. Abnormally high formation pressures, Potwar Plateau, Pakistan

    USGS Publications Warehouse

    Law, B.E.; Shah, S.H.A.; Malik, M.A.

    1998-01-01

    Abnormally high formation pressures in the Potwar Plateau of north-central Pakistan are major obstacles to oil and gas exploration. Severe drilling problems associated with high pressures have, in some cases, prevented adequate evaluation of reservoirs and significantly increased drilling costs. Previous investigations of abnormal pressure in the Potwar Plateau have only identified abnormal pressures in Neogene rocks. We have identified two distinct pressure regimes in this Himalayan foreland fold and thrust belt basin: one in Neogene rocks and another in pre-Neogene rocks. Pore pressures in Neogene rocks are as high as lithostatic and are interpreted to be due to tectonic compression and compaction disequilibrium associated with high rates of sedimentation. Pore pressure gradients in pre-Neogene rocks are generally less than those in Neogene rocks, commonly ranging from 0.5 to 0.7 psi/ft (11.3 to 15.8 kPa/m) and are most likely due to a combination of tectonic compression and hydrocarbon generation. The top of abnormally high pressure is highly variable and doesn't appear to be related to any specific lithologic seal. Consequently, attempts to predict the depth to the top of overpressure prior to drilling are precluded.

  6. Abnormality of circadian rhythm of serum melatonin and other biochemical parameters in fibromyalgia syndrome.

    PubMed

    Mahdi, Abbas Ali; Fatima, Ghizal; Das, Siddhartha Kumar; Verma, Nar Singh

    2011-04-01

    Fibromyalgia syndrome (FMS) is a complex chronic condition causing widespread pain and variety of other symptoms. It produces pain in the soft tissues located around joints throughout the body. FMS has unknown etiology and its pathophysiology is not fully understood. However, abnormality in circadian rhythm of hormonal profiles and cytokines has been observed in this disorder. Moreover, there are reports of deficiency of serotonin, melatonin, cortisol and cytokines in FMS patients, which are fully regulated by circadian rhythm. Melatonin, the primary hormone of the pineal gland regulates the body's circadian rhythm and normally its levels begin to rise in the mid-to-late evening, remain high for most of the night, and then decrease in the early morning. FMS patients have lower melatonin secretion during the hours of darkness than the healthy subjects. This may contribute to impaired sleep at night, fatigue during the day and changed pain perception. Studies have shown blunting of normal diurnal cortisol rhythm, with elevated evening serum cortisol level in patients with FMS. Thus, due to perturbed level of cortisol secretion several symptoms of FMS may occur. Moreover, disturbed cytokine levels have also been reported in FMS patients. Therefore, circadian rhythm can be an important factor in the pathophysiology, diagnosis and treatment of FMS. This article explores the circadian pattern of abnormalities in FMS patients, as this may help in better understanding the role of variation in symptoms of FMS and its possible relationship with circadian variations of melatonin, cortisol, cytokines and serotonin levels. PMID:21682138

  7. Cholangiolocellular carcinoma with rapid progression initially showing abnormally elevated serum alfa-fetoprotein.

    PubMed

    Yoh, Tomoaki; Kato, Tatsushi; Hirohata, Yoshiaki; Nakamura, Yuya; Nakayama, Hiroyuki; Okamura, Ryuji

    2016-08-01

    Cholangiolocellular carcinoma (CoCC) is a rare malignant liver tumor derived from hepatic progenitor cells, which exist in the canals of Hering. We encountered a case of CoCC with an extremely poor clinical course, initially showing abnormally elevated serum alfa-fetoprotein (AFP). A 72-year-old male presented with a liver tumor and abnormally elevated serum AFP levels (16,399 ng/ml). We preoperatively diagnosed hepatocellular carcinoma and performed extended right hepatectomy, after which the serum AFP levels remarkably decreased to 97 ng/ml. Postoperatively, the disease was pathologically diagnosed as CoCC. Furthermore, immunohistochemical pathological findings were alcian blue negative, cytokeratin (CK) 7 partially positive, CK19 positive, hepatocyte paraffin-1 negative, membranous negative for epithelial membrane antigen, and AFP negative. Fifty-five days later, intra- and extrahepatic recurrence developed, and the patient died 65 days after surgery. Although CoCCs show favorable outcomes, these characteristics of our case were not previously reported. It is necessary to accumulate more information on CoCC. PMID:27363839

  8. Serum vitamin A levels and associated abnormalities in patients on regular dialysis treatment.

    PubMed

    Werb, R; Clark, W F; Lindsay, R M; Jones, E O; Linton, A L

    1979-08-01

    Multivitamin preparations are commonly administered to regular dialysis treatment (RDT) patients. Serum Vitamin A was measured in 72 patients on RDT. Elevated serum Vitamin A levels (102.29 +/- 26.95 microgram/dl [3.57 +/- 0.94 mumoles/l]) were found in the dialysis population (normal 40.98 +/- 6.71 microgram/dl [1.43 +/- 0.23 mumoles/l]; P less than 0.0005). Serum Vitamin A levels increased with duration (months) of dialysis but not with frequency of dialysis (twice or thrice weekly). Patients taking a VitaminA-containing multivitamin preparation had higher serum Vitamin A levels than those on a non-Vitamin A supplemented diet. Bilaterally nephrectomized patients had the highest serum Vitamin A levels while patients with obstructive uropathy had the lowest levels. Serum Vitamin A levels did not correlate with symptoms of uremia. Positive correlations were found with serum levels of calcium, cholesterol and triglycerides. Patients receiving a Vitamin A supplement had higher serum cholesterol levels than non-supplemented patients. Vitamin A might be a factor in the high incidence of cardiovascular disease in RDT patients. We therefore advise discontinuing the long-term administration of Vitamin A-containing multivitamin supplements to patients on RDT. PMID:527272

  9. Abnormal high density lipoproteins in cerebrotendinous xanthomatosis

    SciTech Connect

    Shore, V.; Salen, G.; Cheng, F.W.; Forte, T.; Shefer, S.; Tint, G.S.

    1981-11-01

    The plasma lipoprotein profiles and high density lipoproteins (HDL) were characterized in patients with the genetic disease cerebrotendinous xanthomatosis (CTX). The mean HDL-cholesterol concentration in the CTX plasmas was 14.5 +/- 3.2 mg/dl, about one-third the normal value. The low HDL-cholesterol reflects a low concentration and an abnormal lipid composition of the plasma HDL. Relative to normal HDL, the cholesteryl esters are low, free cholesterol and phospholipids essentially normal, and triglycerides increased. The ratio of apoprotein (apo) to total cholesterol in the HDL of CTX was two to three times greater than normal. In the CTX HDL, the ratio of apoAI to apoAII was high, the proportion of apoC low, and a normally minor form of apoAI increased relative to other forms. The HDL in electron micrographs appeared normal morphologically and in particle size. The adnormalities in lipoprotein distribution profiles and composition of the plasma HDL result from metabolic defects that are not understood but may be linked to the genetic defect in bile acid synthesis in CTX. As a consequence, it is probable that the normal functions of the HDL, possibly including modulation of LDL-cholesterol uptake and the removal of excess cholesterol from peripheral tissues, are perturbed significantly in this disease.

  10. Transient neonatal hyperthyrotrophinaemia: a serum abnormality due to transplacentally acquired antibody to thyroid stimulating hormone.

    PubMed Central

    Lazarus, J H; John, R; Ginsberg, J; Hughes, I A; Shewring, G; Smith, B R; Woodhead, J S; Hall, R

    1983-01-01

    In a screening programme for neonatal hypothyroidism an otherwise healthy female infant was found to have a high concentration of thyroid stimulating hormone in a filter paper blood spot and in serum. A high concentration was also found in the maternal serum. Mother and baby were both biochemically euthyroid with normal serum thyroxine concentrations. The apparently high concentration of thyroid stimulating hormone in the mother was due to the presence of an IgG antibody that bound to human but not bovine thyroid stimulating hormone. Maternal serum inhibited the action of human thyroid stimulating hormone in an in vitro bioassay for the hormone. It is suggested that the baby acquired the antibody transplacentally, especially as the concentration of thyroid stimulating hormone subsequently fell. It is concluded that maternal serum should be assayed for thyroid stimulating hormone when a neonate is found to have a high concentration of the hormone and a normal concentration of thyroxine to establish the incidence of this finding and to avoid inappropriate replacement treatment. PMID:6402161

  11. Maternal serum leptin concentration during the second trimester of pregnancy: association with fetal chromosomal abnormalities.

    PubMed

    Rizos, Demetrios; Hassiakos, Demetrios; Grigori-Kostaraki, Panagiota; Sarandakou, Angeliki; Botsis, Demetrios; Salamalekis, Emmanuel

    2002-03-01

    Recent studies suggest that leptin, the product of the obese gene, is produced by the placenta during pregnancy. The present study addressed the question whether second trimester maternal serum leptin could be altered by fetal Down syndrome or Edwards syndrome. Maternal serum leptin concentrations were measured in 18 pregnancies complicated with Down syndrome, six pregnancies complicated with Edwards syndrome and 183 uncomplicated pregnancies during the second trimester of pregnancy. The present results demonstrate that leptin concentrations in uncomplicated pregnancies slightly decrease from the 16th week of pregnancy, reaching a minimum of 18.8 ng/ml around the 20th week, and then rapidly increase to 28.2 ng/ml by the 24th week. Leptin correlation with maternal body weight decreases from r=0.695 at 16-17 week of gestation to r=0.544 at >22 weeks of gestation. There was no significant difference between the mean MoMs of Down syndrome- (0.926) or Edwards syndrome- (0.960) affected pregnancies and normal pregnancies (1.002). A weak correlation (r=0.18, p<0.02) was observed between corrected leptin MoMs and human chorionic gonadotrophin (hCG) MoMs in normal pregnancies. It is assumed that around the 20th week of pregnancy placental leptin production is activated or at least is accelerated and it is added to the amount of leptin produced by maternal adipose tissue. Fetal Down syndrome or Edwards syndrome does not seem to alter maternal leptin concentration and therefore leptin cannot be used as a marker for these chromosomal abnormalities in the early second trimester of pregnancy. PMID:11920898

  12. Radioimmunoassay for detecting abnormal prealbumin in the serum for diagnosis of familial amyloidotic polyneuropathy (Japanese type)

    SciTech Connect

    Nakazato, M.; Kangawa, K.; Minamino, N.; Tawara, S.; Matsuo, H.; Araki, S.

    1984-07-31

    In the serum of a Japanese patient with familial amyloidotic polyneuropathy (FAP), we demonstrated the presence of a prealbumin variant using a single amino acid substitution of a methionine residue for a valine at position 30. We have developed a highly sensitive and specific method for quantitative analysis of the prealbumin variant in the sera of FAP patients by using radioimmunoassay for a nonapeptide corresponding to subsequence (22-30) of the prealbumin variant. This peptide is produced from the prealbumin variant by cyanogen bromide cleavage followed by tryptic digestion. The serum administration of the prealbumin variant in five Japanese FAP patients ranges from 1.0 mg/dl to 7.8 mg/dl, which is 100 times or even higher than normal animals. This method should be helpful for an early diagnosis of this hereditary disease. 6 references, 4 figures, 1 table.

  13. Abnormalities of serum potassium concentration in dialysis-associated hyperglycemia and their correction with insulin: review of published reports.

    PubMed

    Tzamaloukas, Antonios H; Ing, Todd S; Elisaf, Moses S; Raj, Dominic S C; Siamopoulos, Kostas C; Rohrscheib, Mark; Murata, Glen H

    2011-06-01

    The main difference between dialysis-associated hyperglycemia (DH) and diabetic ketoacidosis (DKA) or nonketotic hyperglycemia (NKH) occurring in patients with preserved renal function is the absence of osmotic diuresis in DH, which eliminates the need for large fluid and solute (including potassium) replacement. We analyzed published reports of serum potassium (K(+)) abnormalities and their treatment in DH. Hyperkalemia was often present at presentation of DH with higher frequency and severity than in hyperglycemic syndromes in patients with preserved renal function. The frequency and severity of hyperkalemia were higher in DH episodes with DKA than those with NKH in both hemodialysis and peritoneal dialysis. For DKA, the frequency and severity of hyperkalemia were similar in hemodialysis and peritoneal dialysis. For NKH, hyperkalemia was more severe and frequent in hemodialysis than in peritoneal dialysis. Insulin infusion corrected the hyperkalemia of DH in most cases. Additional measures for the management of hyperkalemia or modest potassium infusions for hypokalemia were needed in a few DH episodes. The predictors of the decrease in serum K(+) during treatment of DH with insulin included the starting serum K(+) level, the decreases in serum values of glucose concentration and tonicity, and the increase in serum total carbon dioxide level. DH represents a risk factor for hyperkalemia. Insulin infusion is the only treatment for hyperkalemia usually required. PMID:20827508

  14. Association of Serum Ferritin Level with Risk of Incident Abnormal Glucose Metabolism in Southwestern China: a Prospective Cohort Study.

    PubMed

    Zhou, Fangli; Zhao, Zhuoxian; Tian, Li; Zheng, Tianpeng; Gao, Yun; Chen, Tao; Yan, Fangfang; Tian, Haoming

    2016-01-01

    This prospective cohort study aimed to analyze the association between serum ferritin levels and the risk of abnormal glucose metabolism (AGM) in Southwestern Chinese population. The 383 subjects who are aged ≥20 years and free of AGM at baseline between in 2007 and in 2008 were included in Southwestern China, and their baseline serum ferritin levels were measured. Among these subjects, 140 subjects were developed into AGM during the follow-up (2008-2012). In logistic regression models, the relative risk in the top versus that in the lowest quartile of serum ferritin levels was 2.86 (p = 0.013) in females and 3.50 (p = 0.029) in males after adjusting the age, gender, family history of diabetes, current smoking, and alcohol; however, serum ferritin levels were not significantly associated with incident of AGM after controlling for metabolic factors (waist circumference, systolic pressure (SBP), triglyceride (TG), and homeostasis model assessment formula insulin resistance (HOMA-IR)). Elevated serum ferritin levels are associated with AGM but not an independent risk factor. PMID:26073512

  15. Abnormal physiological conditions in acute schizophrenic patients on emergency admission: dehydration, hypokalemia, leukocytosis and elevated serum muscle enzymes.

    PubMed

    Hatta, K; Takahashi, T; Nakamura, H; Yamashiro, H; Endo, H; Fujii, S; Fukami, G; Masui, K; Asukai, N; Yonezawa, Y

    1998-01-01

    This study investigated varieties and incidence of abnormal physiological conditions in acute schizophrenic patients on emergency. Laboratory data obtained prior to treatment from patients, admitted on an emergency basis during an 18-month period, were evaluated retrospectively, as well as demographics and clinical characteristics. Of 259 male acute schizophrenic patients (ICD-10: F2), 6.9% revealed dehydration, a third had hypokalemia and leukocytosis, and two thirds showed elevated serum muscle enzymes. These percentages were statistically significant compared with those of outpatients. In addition, the former three of these conditions in the F2 group were as frequent as those in alcohol and/or psychoactive substance abusers (ICD-10: F1) on emergency admission, although elevated serum muscle enzymes in the F2 group was less frequent than that in the F1 group. In order to prevent these abnormal physiological conditions from worsening and becoming life-threatening, one fourth of the F2 group [dehydration, 6.9%, severe hypokalemia (< 3.0 mEq/l), 2.3%, and markedly elevated serum muscle enzymes (creatine phosphokinase > 1000 IU/l), 16.5%] required medical management such as fluid therapy and various types of monitoring. In cases of a behavioral emergency, laboratory screening and monitoring of urinary output were essential. Due to their lack of cooperation, case history, physical examination, and initial vital signs did not contribute to detection of their medical condition. PMID:9810481

  16. Variation in the levels of pregnancy-specific beta-1-glycoprotein in maternal serum from chromosomally abnormal pregnancies.

    PubMed

    Graham, G W; Crossley, J A; Aitken, D A; Connor, J M

    1992-06-01

    Human pregnancy-specific beta-1-glycoprotein (SP1) was assayed retrospectively in stored maternal serum (MS) samples from 82 chromosomally abnormal pregnancies and 377 matched controls. The median MSSP1 concentration in 48 Down's syndrome pregnancies was significantly elevated at 1.17 multiples of the control median (MOM), and significantly reduced (0.5 MOM) in a group of eight cases of unbalanced translocations. There was no significant difference in median SP1 concentrations in cases of trisomy 18, trisomy 13, balanced translocations, or sex chromosome abnormalities. A comparison with human chorionic gonadotrophin results in the same series of samples indicates that SP1 is a less sensitive predictor of Down's syndrome pregnancies. PMID:1387478

  17. Serum levels of immunoglobulins (IgG, IgA, IgM) in a general adult population and their relationship with alcohol consumption, smoking and common metabolic abnormalities

    PubMed Central

    Gonzalez-Quintela, A; Alende, R; Gude, F; Campos, J; Rey, J; Meijide, L M; Fernandez-Merino, C; Vidal, C

    2008-01-01

    The present study investigated serum immunoglobulin (Ig) concentrations in relation to demographic factors, common habits (alcohol consumption and smoking) and metabolic abnormalities in an adult population-based survey including 460 individuals. Serum levels of interleukin (IL)-6, a marker of inflammation, were also determined. After adjusting for confounders, male sex was associated positively with IgA levels and negatively with IgM levels. Age was associated positively with IgA and IgG levels. Smoking was associated negatively with IgG levels. Heavy drinking was associated positively with IgA levels. Metabolic abnormalities (obesity and metabolic syndrome) were associated positively with IgA levels. Abdominal obesity and hypertriglyceridaemia were the components of metabolic syndrome associated most strongly with serum IgA. Heavy drinkers with metabolic syndrome showed particularly high serum IgA levels. Serum IL-6 levels were correlated positively with IgA and IgG concentrations. It is concluded that sex, age, alcohol consumption, smoking and common metabolic abnormalities should be taken into account when interpreting serum levels of IgA, IgG and IgM. PMID:18005364

  18. Dietary high-fat lard intake induces thyroid dysfunction and abnormal morphology in rats

    PubMed Central

    Shao, Shan-shan; Zhao, Yuan-fei; Song, Yong-feng; Xu, Chao; Yang, Jian-mei; Xuan, Shi-meng; Yan, Hui-li; Yu, Chun-xiao; Zhao, Meng; Xu, Jin; Zhao, Jia-jun

    2014-01-01

    Aim: Excess dietary fat intake can induce lipotoxicity in non-adipose tissues. The aim of this study was to observe the effects of dietary high-fat lard intake on thyroid in rats. Methods: Male Sprague-Dawley rats were fed a high-fat lard diet for 24 weeks, and then the rats were fed a normal control diet (acute dietary modification) or the high-fat lard diet for another 6 weeks. The serum lipid profile, total thyroxine (TT4), free thyroxine (FT4) and thyrotropin (TSH) levels were determined at the 12, 18, 24 and 30 weeks. High-frequency ultrasound scanning of the thyroid glands was performed at the 24 or 30 weeks. After the rats were sacrificed, the thyroid glands were collected for histological and immunohistochemical analyses. Results: The high-fat lard diet significantly increased triglyceride levels in both the serum and thyroid, and decreased serum TT4 and FT4 levels in parallel with elevated serum TSH levels. Ultrasonic imaging revealed enlarged thyroid glands with lowered echotexture and relatively heterogeneous features in the high-fat lard fed rats. The thyroid glands from the high-fat lard fed rats exhibited enlarged follicle cavities and flattened follicular epithelial cells under light microscopy, and dilated endoplasmic reticulum cisternae, twisted nuclei, fewer microvilli and secretory vesicles under transmission electron microscopy. Furthermore, the thyroid glands from the high-fat lard fed rats showed markedly low levels of thyroid hormone synthesis-related proteins TTF-1 and NIS. Acute dietary modification by withdrawal of the high-fat lard diet for 6 weeks failed to ameliorate the high-fat lard diet-induced thyroid changes. Conclusion: Dietary high-fat lard intake induces significant thyroid dysfunction and abnormal morphology in rats, which can not be corrected by short-term dietary modification. PMID:25263336

  19. ACE Reduces Metabolic Abnormalities in a High-Fat Diet Mouse Model

    PubMed Central

    Lee, Seong-Jong; Han, Jong-Min; Lee, Jin-Seok; Son, Chang-Gue; Im, Hwi-Jin; Jo, Hyun-Kyung; Yoo, Ho-Ryong; Kim, Yoon-Sik; Seol, In-Chan

    2015-01-01

    The medicinal plants Artemisia iwayomogi (A. iwayomogi) and Curcuma longa (C. longa) radix have been used to treat metabolic abnormalities in traditional Korean medicine and traditional Chinese medicine (TKM and TCM). In this study we evaluated the effect of the water extract of a mixture of A. iwayomogi and C. longa (ACE) on high-fat diet-induced metabolic syndrome in a mouse model. Four groups of C57BL/6N male mice (except for the naive group) were fed a high-fat diet freely for 10 weeks. Among these, three groups (except the control group) were administered a high-fat diet supplemented with ACE (100 or 200 mg/kg) or curcumin (50 mg/kg). Body weight, accumulation of adipose tissues in abdomen and size of adipocytes, serum lipid profiles, hepatic steatosis, and oxidative stress markers were analyzed. ACE significantly reduced the body and peritoneal adipose tissue weights, serum lipid profiles (total cholesterol and triglycerides), glucose levels, hepatic lipid accumulation, and oxidative stress markers. ACE normalized lipid synthesis-associated gene expressions (peroxisome proliferator-activated receptor gamma, PPARγ; fatty acid synthase, FAS; sterol regulatory element-binding transcription factor-1c, SREBP-1c; and peroxisome proliferator-activated receptor alpha, PPARα). The results from this study suggest that ACE has the pharmaceutical potential reducing the metabolic abnormalities in an animal model. PMID:26508977

  20. High incidence of MYC and BCL2 abnormalities in mantle cell lymphoma, although only MYC abnormality predicts poor survival

    PubMed Central

    Li, Chengwen; Zhong, Shizhen; Chen, Weiwei; Li, Zengjun; Xiong, Wenjie; Liu, Wei; Liu, Enbin; Cui, Rui; Ru, Kun; Zhang, Peihong; Xu, Yan; An, Gang; Lv, Rui; Qi, Junyuan; Wang, Jianxiang; Cheng, Tao; Qiu, Lugui

    2015-01-01

    The incidence and prognostic role of MYC and BCL2 rearrangements in mature B-cell lymphomas have been extensively studied, except the infrequent mantle cell lymphoma (MCL). Here, we analyzed the MYC and BCL2 abnormalities and other cytogenetic aberrations by fluorescence in situ hybridization (FISH) in 50 MCL patients with bone marrow involvement. Eighteen patients (36.0%) had MYC gains and/or amplifications, and twelve patients (24.0%) had BCL2 gains and/or amplifications. Among the 18 patients with MYC abnormality, four had simultaneous MYC translocations, but no BCL2 translocation was detected among patients with BCL2 abnormality. Only two patients (4.0%) had both MYC and BCL2 abnormalities. The patients with a MYC abnormality had a significantly higher tumor burden, a higher percentage of medium/high risk MIPI group and genomic instability compared to those without this abnormality. However, no significant difference was observed between patients with or without a BCL2 abnormality in terms of clinical and cytogenetic factors. Patients with a MYC abnormality had poorer progress-free survival (PFS) (9.0 vs. 48.0 months, p = .000) and overall survival (OS) (12.0 vs. 94.5 months, p = .000), but the presence of a BCL2 abnormality did not significantly influence either PFS or OS. In multivariate analysis, the MYC abnormality was the independent adverse factor for both PFS and OS, and intensive chemotherapy did not improve the outcome of these patients. Thus, the presence of a MYC but not BCL2 abnormality predicted the poor survival of MCL patients, and a new treatment strategy should be developed for these patients. PMID:26517511

  1. Maternal Early Pregnancy Serum Metabolomics Profile and Abnormal Vaginal Bleeding as Predictors of Placental Abruption: A Prospective Study

    PubMed Central

    Gelaye, Bizu; Sumner, Susan J.; McRitchie, Susan; Carlson, James E.; Ananth, Cande V.; Enquobahrie, Daniel A.; Qiu, Chunfang; Sorensen, Tanya K.; Williams, Michelle A.

    2016-01-01

    Background & Objective Placental abruption, an ischemic placental disorder, complicates about 1 in 100 pregnancies, and is an important cause of maternal and perinatal morbidity and mortality worldwide. Metabolomics holds promise for improving the phenotyping, prediction and understanding of pathophysiologic mechanisms of complex clinical disorders including abruption. We sought to evaluate maternal early pregnancy pre-diagnostic serum metabolic profiles and abnormal vaginal bleeding as predictors of abruption later in pregnancy. Methods Maternal serum was collected in early pregnancy (mean 16 weeks, range 15 to 22 weeks) from 51 abruption cases and 51 controls. Quantitative targeted metabolic profiles of serum were acquired using electrospray ionization liquid chromatography-mass spectrometry (ESI-LC-MS/MS) and the Absolute IDQ® p180 kit. Maternal sociodemographic characteristics and reproductive history were abstracted from medical records. Stepwise logistic regression models were developed to evaluate the extent to which metabolites aid in the prediction of abruption. We evaluated the predictive performance of the set of selected metabolites using a receiver operating characteristics (ROC) curve analysis and area under the curve (AUC). Results Early pregnancy vaginal bleeding, dodecanoylcarnitine/dodecenoylcarnitine (C12 / C12:1), and phosphatidylcholine acyl-alkyl C 38:1 (PC ae C38:1) strongly predict abruption risk. The AUC for these metabolites alone was 0.68, for early pregnancy vaginal bleeding alone was 0.65, and combined the AUC improved to 0.75 with the addition of quantitative metabolite data (P = 0.003). Conclusion Metabolomic profiles of early pregnancy maternal serum samples in addition to the clinical symptom, vaginal bleeding, may serve as important markers for the prediction of abruption. Larger studies are necessary to corroborate and validate these findings in other cohorts. PMID:27300725

  2. Abnormal serum gamma-glutamyltranspeptidase in alcoholics. Clues to its explanation.

    PubMed

    Frezza, M; Pozzato, G; Chiesa, L; Terpin, M; Barbone, F; Di Padova, C

    1989-02-01

    In order to investigate the reason for the elevation of serum gamma-glutamyltranspeptidase (GGT) after chronic alcohol consumption, the activity of this enzyme, together with the activities of aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase in serum (parameters of liver cell damage) and the excretion of D-glucaric acid (D-GA) in urine (parameter of microsomal enzymatic induction) were determined in 72 chronic alcoholics. Of these, 32 had no significant liver disease (1st group) and 40 had an overt liver disease varying from fatty liver to liver cirrhosis (2nd group). The GGT was elevated in only 62% of the patients of the first group, but in 95% of the second group. Of the latter group, patients with cirrhosis had significantly higher GGT mean levels than the patients with fatty liver. On the other hand, increased D-GA excretion was only found in 23% of the group 1 patients and in 44% of the group 2 patients. Moreover, in all patients there was a significant correlation between the values of GGT and aspartate aminotransferase, but not between GGT and D-GA. From these results, the GGT increase in chronic alcoholics, would seem to be better related to cellular damage than to enzymatic induction assessed on the basis of D-GA urinary excretion. PMID:2563572

  3. High Prevalence of Prothrombotic Abnormalities in Multifocal Osteonecrosis

    PubMed Central

    Peris, Pilar; Reverter, Joan Carles; Espinosa, Gerard; Martinez-Ferrer, Angeles; Monegal, Ana; Monteagudo, Juan; Tàssies, Dolors; Guañabens, Nuria

    2013-01-01

    Abstract Multifocal or multiple osteonecrosis (ON), defined by the involvement of 3 or more anatomic sites, is unusual, being observed in only 3%–10% of patients diagnosed with ON. We report the clinical characteristics of a cohort of 29 patients with multifocal ON from a single center and evaluate the prevalence of associated prothrombotic abnormalities in 26 of these patients. We conducted a retrospective study of all patients diagnosed with multifocal ON evaluated in our institution during the last 20 years. We recorded clinical manifestations and underlying diagnoses. A wide thrombophilic profile was performed, including antithrombin, protein C, protein S, lupus anticoagulant, anticardiolipin antibodies, activated protein C resistance, factor V Leiden, mutation G-20210-A of the prothrombin gene, and factor VIII. Coagulation test results were compared with those in a healthy control group and a group of patients with history of lower-extremity deep venous thrombosis. The mean age of the patients was 49.2 ± 15 years (range, 28–81 yr). The mean number of ON localizations per patient was 5.2 ± 2.3 (range, 3–11). Hips were the most commonly affected joint (82%), followed by knees (58%), shoulders (37%), and ankles (13%). Most patients had an underlying disease process, and 12 of 25 (48%) patients had coagulation test abnormalities. The most common alterations were high factor VIII levels and antiphospholipid antibody (aPL) positivity in 24% and 20% of cases, respectively. These abnormalities were more prevalent in patients with multifocal ON compared with patients in the control groups. Sixty-one percent of patients had a history of corticosteroid treatment. Patients with coagulation abnormalities had a higher number of ON localizations per patient (6.5 ± 2.7 vs. 3.88 ± 0.8; p = 0.002) and a higher prevalence of atypical ON localizations (25% vs. 0%; p = 0.05). In conclusion, in the present cohort of patients with multifocal ON, 48% of the patients had at

  4. Prognostic value of serum tumor abnormal protein in gastric cancer patients

    PubMed Central

    LAN, FENG; ZHU, MING; QI, QIUFENG; ZHANG, YAPING; LIU, YONGPING

    2016-01-01

    Aberrant glycosylation of protein occurs in nearly all types of cancers and has been confirmed to be associated with tumor progression, metastasis and the survival rate of patients. The present study aimed to explore the prognostic value of tumor abnormal protein (TAP) in gastric cancer patients. TAP was detected in the blood of 42 gastric cancer patients and 56 healthy volunteers by using the TAP testing kit. Univariate and multivariate Cox regression analysis were performed to evaluate the prognostic value of TAP. In total, 64.3% of gastric cancer patients were positive for TAP, and TAP was significantly correlated with poor prognosis [progression-free survival (PFS), 4.2 vs. 12.6 months; P=0.043]. TAP [hazard ratio (HR), 64.487; P<0.01), differentiation (HR, 17.279; P<0.01) and TNM stage (HR, 45.480; P<0.01) were found to be independent predictive factors for PFS. Furthermore, Kaplan-Meier curves indicated that TAP is associated with a reduced PFS in gastric cancer patients. The results of the present study therefore indicated that the TAP test has significant prognostic value for gastric cancer patients. PMID:27330802

  5. Viral load is associated with abnormal serum levels of micronutrients and glutathione and glutathione-dependent enzymes in genotype 3 HCV patients

    PubMed Central

    Razzaq, Zarish; Malik, Arif

    2014-01-01

    Background Oxidative stress in hepatitis C patients has been linked to hepatitis C virus. We verified this assumption in HCV genotype 3 patients by detecting the relationship between viral load and certain specific oxidative stress markers like Cu, Mn, Fe, Se, Zn and glutathione and glutathione-dependent enzymes. Method Subjects (n = 200, average age 24 years) with quantitative HCV RNA polymerase chain reaction-proven genotype 3 hepatitis C were simultaneously evaluated. Cu, Mn, Fe, Se and Zn serum levels were by using atomic absorption spectrophotometer. Internationally accepted methods were used for viral load quantification of glutathione, GR and Gpx serum levels. Result There was a significant correlation between HCV viral load and studied parameters. With the increase of viral load from mild group (200,000–1,000,000 copies/ml) to severe group (5,000,000–25,000,000 copies/ml) the serum levels of Cu, Mn, Zn, and Fe and glutathione reductase were found to be abnormally high. However, in severe viral load group serum concentration of Se and glutathione was less than the healthy controls. Conclusion As a significant correlation was detected between the study parameters in genotype 3 HCV patients, it is concluded that the studied micronutrients and glutathione and glutathione-dependent enzymes are the biomolecular targets of HCV to induce oxidative stress. General significance Constant monitoring and regulation of the recommended biomolecular targets of HCV can improve the plight of more than 170 million patients suffering from hepatitis C virus around the globe. PMID:26674880

  6. 1H-NMR Spectroscopy Revealed Mycobacterium tuberculosis Caused Abnormal Serum Metabolic Profile of Cattle

    PubMed Central

    Xiong, Xuekai; Hu, Xidan; Huang, Jiong; Xu, Zhiguang; Zhang, Xiansong; Hu, Changmin; Hu, Xueying; Guo, Aizhen; Wang, Yulan; Chen, Huanchun

    2013-01-01

    To re-evaluate virulence of Mycobacterium tuberculosis (M. tb) in cattle, we experimentally infected calves with M. tb andMycobacterium bovisvia intratracheal injection at a dose of 2.0×107 CFU and observed the animals for 33 weeks. The intradermal tuberculin test and IFN-γin vitro release assay showed that both M. tb and M. bovis induced similar responses. Immunohistochemical staining of pulmonary lymph nodes indicated that the antigen MPB83 of both M. tb and M. bovis were similarly distributed in the tissue samples. Histological examinations showed all of the infected groups exhibited neutrophil infiltration to similar extents. Although the infected cattle did not develop granulomatous inflammation, the metabolic profiles changed significantly, which were characterized by a change in energy production pathways and increased concentrations of N-acetyl glycoproteins. Glycolysis was induced in the infected cattle by decreased glucose and increased lactate content, and enhanced fatty acid β-oxidation was induced by decreased TG content, and decreased gluconeogenesis indicated by the decreased concentration of glucogenic and ketogenic amino acids promoted utilization of substances other than glucose as energy sources. In addition, an increase in acute phase reactive serum glycoproteins, together with neutrophil infiltration and increased of IL-1β production indicated an early inflammatory response before granuloma formation. In conclusion, this study indicated that both M. tb and M.bovis were virulent to cattle. Therefore, it is likely that cattle with M. tb infections would be critical to tuberculosis transmission from cattle to humans. Nuclear magnetic resonance was demonstrated to be an efficient method to systematically evaluate M. tb and M. bovi sinfection in cattle. PMID:24098654

  7. Relationship between paravascular abnormalities and foveoschisis in highly myopic patients

    PubMed Central

    Kamal-Salah, R; Morillo-Sanchez, M J; Rius-Diaz, F; Garcia-Campos, J M

    2015-01-01

    Purpose To describe the prevalence of paravascular abnormalities in highly myopic patients and its relationship with myopic foveoschisis (MF). Methods Cross-sectional study of 250 highly myopic eyes. All of the patients underwent a complete ophthalmologic examination that included optical coherence tomography . Results Optical coherence tomography images showed 170 eyes (68%) with paravascular microfolds (PM), 121 eyes (48.4%) presented paravascular retinal cysts (PC), and 35 eyes (14%) with paravascular lamellar holes . All the eyes with PCs had PMs. Out of the 250 eyes, 48 (19.2%) had paravascular retinoschisis (PR). All the eyes (100%) with PR had paravascular cysts and PMs. Sixteen eyes (6.4%) had foveoschis. The spherical equivalent (P<0.00), PR (P=0.01), and the presence of tractional structures (P<0.00) were associated with increased risk for foveoschsis in the multivariate study. Conclusions PMs were the lesions most often observed in the paravascular area in highly myopic eyes. MF would be a result of the action of different forces (intra- and extra-ocular forces), specially tractional structures, on precursor lesions (paravascular cyst and paravascular restinoschisis). Further studies are needed to confirm these results. PMID:25359287

  8. Abnormal Elastic and Vibrational Behaviors of Magnetite at High Pressures

    NASA Astrophysics Data System (ADS)

    Lin, Jung-Fu; Wu, Junjie; Zhu, Jie; Mao, Zhu; Said, Ayman H.; Leu, Bogdan M.; Cheng, Jinguang; Uwatoko, Yoshiya; Jin, Changqing; Zhou, Jianshi

    2014-09-01

    Magnetite exhibits unique electronic, magnetic, and structural properties in extreme conditions that are of great research interest. Previous studies have suggested a number of transitional models, although the nature of magnetite at high pressure remains elusive. We have studied a highly stoichiometric magnetite using inelastic X-ray scattering, X-ray diffraction and emission, and Raman spectroscopies in diamond anvil cells up to ~20 GPa, while complementary electrical conductivity measurements were conducted in a cubic anvil cell up to 8.5 GPa. We have observed an elastic softening in the diagonal elastic constants (C11 and C44) and a hardening in the off-diagonal constant (C12) at ~8 GPa where significant elastic anisotropies in longitudinal and transverse acoustic waves occur, especially along the [110] direction. An additional vibrational Raman band between the A1g and T2g modes was also detected at the transition pressure. These abnormal elastic and vibrational behaviors of magnetite are attributed to the occurrence of the octahedrally-coordinated Fe2+-Fe3+-Fe2+ ions charge-ordering along the [110] direction in the inverse spinel structure. We propose a new phase diagram of magnetite in which the temperature for the metal-insulator and distorted structural transitions decreases with increasing pressure while the charge-ordering transition occurs at ~8 GPa and room temperature.

  9. Abnormal Elastic and Vibrational Behaviors of Magnetite at High Pressures

    PubMed Central

    Lin, Jung-Fu; Wu, Junjie; Zhu, Jie; Mao, Zhu; Said, Ayman H.; Leu, Bogdan M.; Cheng, Jinguang; Uwatoko, Yoshiya; Jin, Changqing; Zhou, Jianshi

    2014-01-01

    Magnetite exhibits unique electronic, magnetic, and structural properties in extreme conditions that are of great research interest. Previous studies have suggested a number of transitional models, although the nature of magnetite at high pressure remains elusive. We have studied a highly stoichiometric magnetite using inelastic X-ray scattering, X-ray diffraction and emission, and Raman spectroscopies in diamond anvil cells up to ~20 GPa, while complementary electrical conductivity measurements were conducted in a cubic anvil cell up to 8.5 GPa. We have observed an elastic softening in the diagonal elastic constants (C11 and C44) and a hardening in the off-diagonal constant (C12) at ~8 GPa where significant elastic anisotropies in longitudinal and transverse acoustic waves occur, especially along the [110] direction. An additional vibrational Raman band between the A1g and T2g modes was also detected at the transition pressure. These abnormal elastic and vibrational behaviors of magnetite are attributed to the occurrence of the octahedrally-coordinated Fe2+-Fe3+-Fe2+ ions charge-ordering along the [110] direction in the inverse spinel structure. We propose a new phase diagram of magnetite in which the temperature for the metal-insulator and distorted structural transitions decreases with increasing pressure while the charge-ordering transition occurs at ~8 GPa and room temperature. PMID:25186916

  10. Abnormal elastic and vibrational behaviors of magnetite at high pressures.

    PubMed

    Lin, Jung-Fu; Wu, Junjie; Zhu, Jie; Mao, Zhu; Said, Ayman H; Leu, Bogdan M; Cheng, Jinguang; Uwatoko, Yoshiya; Jin, Changqing; Zhou, Jianshi

    2014-01-01

    Magnetite exhibits unique electronic, magnetic, and structural properties in extreme conditions that are of great research interest. Previous studies have suggested a number of transitional models, although the nature of magnetite at high pressure remains elusive. We have studied a highly stoichiometric magnetite using inelastic X-ray scattering, X-ray diffraction and emission, and Raman spectroscopies in diamond anvil cells up to ~20 GPa, while complementary electrical conductivity measurements were conducted in a cubic anvil cell up to 8.5 GPa. We have observed an elastic softening in the diagonal elastic constants (C11 and C44) and a hardening in the off-diagonal constant (C12) at ~8 GPa where significant elastic anisotropies in longitudinal and transverse acoustic waves occur, especially along the [110] direction. An additional vibrational Raman band between the A1g and T2g modes was also detected at the transition pressure. These abnormal elastic and vibrational behaviors of magnetite are attributed to the occurrence of the octahedrally-coordinated Fe(2+)-Fe(3+)-Fe(2+) ions charge-ordering along the [110] direction in the inverse spinel structure. We propose a new phase diagram of magnetite in which the temperature for the metal-insulator and distorted structural transitions decreases with increasing pressure while the charge-ordering transition occurs at ~8 GPa and room temperature. PMID:25186916

  11. Adult-onset multiple acyl CoA dehydrogenation deficiency associated with an abnormal isoenzyme pattern of serum lactate dehydrogenase.

    PubMed

    Sugai, Fuminobu; Baba, Kousuke; Toyooka, Keiko; Liang, Wen-Chen; Nishino, Ichizo; Yamadera, Misaki; Sumi, Hisae; Fujimura, Harutoshi; Nishikawa, Yoshiro

    2012-02-01

    We report a case of a 37 year-old male with multiple acyl-CoA dehydrogenation deficiency (MADD). The patient had suffered from exercise intolerance in his hip and thigh muscles for one year. Then, restriction of carbohydrates for a diet made his symptoms rapidly deteriorate. Blood test revealed compound heterozygosity for two novel missense mutations in the electron transfer flavoprotein dehydrogenase gene (ETFDH), and an abnormal LDH isoenzyme pattern: LDH-1 (60.0%) and LDH-2 (26.0%) predominated with abnormally elevated LDH-1/LDH-2 ratio (2.3), compared with muscle-derived LDH-5 (4.0%). Oral riboflavin treatment significantly improved his exercise intolerance and the LDH profile: LDH-1 (34.4%), LDH-2 (34.9%), LDH-5 (6.9%) and LDH-1/LDH-2 ratio (1.0). The abnormal LDH isoenzyme pattern may be one feature of adult-onset MADD selectively affecting type I muscle fibers with relatively high LDH-1 content. PMID:21907580

  12. Abnormally high expression of proteasomes in human leukemic cells.

    PubMed Central

    Kumatori, A; Tanaka, K; Inamura, N; Sone, S; Ogura, T; Matsumoto, T; Tachikawa, T; Shin, S; Ichihara, A

    1990-01-01

    Proteasomes are eukaryotic ring-shaped or cylindrical particles with multicatalytic protease activities. To clarify the involvement of proteasomes in tumorigenesis of human blood cells, we compared their expression in human hematopoietic malignant tumor cells with that in normal peripheral blood mononuclear cells. Immunohistochemical staining showed considerably increased concentrations of proteasomes in leukemic cells from the bone marrow of patients with various types of leukemia and the predominant localization of these proteasomes in the nuclei. Moreover, enzyme immunoassay and Northern blot analysis indicated that the concentrations of proteasomes and their mRNA levels were consistently much higher in a variety of malignant human hematopoietic cell lines than in resting peripheral lymphocytes and monocytes from healthy adults. Proteasome expression was also greatly increased in normal blood mononuclear cells during blastogenic transformation induced by phytohemagglutinin; their expression increased in parallel with induction of DNA synthesis and returned to the basal level with progress of the cell cycle. Thus, abnormally high expression of proteasomes may play an important role in transformation and proliferation of blood cells and in specific functions of hematopoietic tumor cells. Images PMID:2205851

  13. High prevalence of thyroid ultrasonographic abnormalities in primary aldosteronism.

    PubMed

    Armanini, Decio; Nacamulli, Davide; Scaroni, Carla; Lumachi, Franco; Selice, Riccardo; Fiore, Cristina; Favia, Gennaro; Mantero, Franco

    2003-11-01

    The study was performed to evaluate the prevalence of thyroid abnormalities detected by ultrasonography and, in particular, of multinodular nontoxic goiter in primary aldosteronism. We analyzed 80 consecutive of patients with primary hyperaldosteronism (40 with unilateral adenoma and 40 with idiopathic hyperaldosteronism) and 80 normotensive healthy controls, comparable for age, sex, iodine intake, and geographical area. Blood pressure, thyroid palpation, thyroid function, and ultrasonography were evaluated. The prevalence of ultrasonographic thyroid abnormalities was 60% in primary aldosteronism and 27% in controls (p < 0.0001). There was a statistically significant difference in prevalence of these abnormalities in unilateral adenoma and idiopathic hyperaldosteronism with respect to controls (p < 0.05 and p < 0.0001, respectively). The prevalence of multinodular nontoxic goiter in idiopathic hyperaldosteronism was higher than in controls (p < 0.001) and, in particular, in female patients. From these data it seems to be worth considering the existence of primary hyperaldosteronism in patients with multinodular goiter and hypertension. PMID:14665720

  14. Serum tumor necrosis factor alpha concentrations and clinical abnormalities in colostrum-fed and colostrum-deprived neonatal foals given endotoxin.

    PubMed

    Allen, G K; Green, E M; Robinson, J A; Garner, H E; Loch, W E; Walsh, D M

    1993-09-01

    We examined the effect of infusion of lipopolysaccharide (LPS) on serum tumor necrosis factor alpha (TNF alpha) concentration and clinical attitude in 2- 3-day-old colostrum-fed (CF) and colostrum-deprived (CD) foals. Eleven CF and 8 CD neonatal foals were given a bolus i.v. infusion of Escherichia coli O55:B5 lipopolysaccharide (0.5 microgram/kg of body weight) in sterile saline (0.9% NaCl) solution. Four CF and 2 CD foals were given saline solution alone. Serum IgG concentration and serum anti-LPS IgG(T) antibody titer were determined for each foal prior to infusion. A depression index was used to score clinical abnormalities. Serum TNF alpha concentration was estimated by use of an in vitro cytotoxicity bioassay that used WEHI 164 clone 13 cells as targets. The cytotoxic serum factor was identified as TNF alpha by immunoprecipitation with caprine antisera raised against the 15 NH2-terminal amino acids of human TNF alpha. Tumor necrosis factor alpha was not detected in any preinfusion serum samples nor in any samples from foals given saline solution alone. Serum TNF alpha concentration increased in all LPS-infused foals and peaked between 60 and 90 minutes after infusion. Serum TNF alpha concentrations, expressed as mean percentage of peak serum TNF alpha concentration, persisted longer in CD foals given LPS than in CF foals given LPS. All LPS-infused foals displayed clinical signs of endotoxemia, but mean depression index scores of the CF and CD foals given LPS were not significantly different at any time. Serum TNF alpha concentrations were correlated with depression index scores in both LPS-infused groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8239125

  15. Acetyl-L-carnitine and lipoic acid improve mitochondrial abnormalities and serum levels of liver enzymes in a mouse model of nonalcoholic fatty liver disease.

    PubMed

    Kathirvel, Elango; Morgan, Kengathevy; French, Samuel W; Morgan, Timothy R

    2013-11-01

    Mitochondrial abnormalities are suggested to be associated with the development of nonalcoholic fatty liver. Liver mitochondrial content and function have been shown to improve in oral feeding of acetyl-L-carnitine (ALC) to rodents. Carnitine is involved in the transport of acyl-coenzyme A across the mitochondrial membrane to be used in mitochondrial β-oxidation. We hypothesized that oral administration ALC with the antioxidant lipoic acid (ALC + LA) would benefit nonalcoholic fatty liver. To test our hypothesis, we fed Balb/C mice a standard diet (SF) or SF with ALC + LA or high-fat diet (HF) or HF with ALC + LA for 6 months. Acetyl-L-carnitine and LA were dissolved at 0.2:0.1% (wt/vol) in drinking water, and mice were allowed free access to food and water. Along with physical parameters, insulin resistance (blood glucose, insulin, glucose tolerance), liver function (alanine transaminase [ALT], aspartate transaminase [AST]), liver histology (hematoxylin and eosin), oxidative stress (malondialdehyde), and mitochondrial abnormalities (carbamoyl phosphate synthase 1 and electron microscopy) were done. Compared with SF, HF had higher body, liver, liver-to-body weight ratio, white adipose tissue, ALT, AST, liver fat, oxidative stress, and insulin resistance. Coadministration of ALC + LA to HF animals significantly improved the mitochondrial marker carbamoyl phosphate synthase 1 and the size of the mitochondria in liver. Alanine transaminase and AST levels were decreased. In a nonalcoholic fatty liver mice model, ALC + LA combination improved liver mitochondrial content, size, serum ALT, and AST without significant changes in oxidative stress, insulin resistance, and liver fat accumulation. PMID:24176233

  16. 14 CFR 91.144 - Temporary restriction on flight operations during abnormally high barometric pressure conditions.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... during abnormally high barometric pressure conditions. 91.144 Section 91.144 Aeronautics and Space... flight operations during abnormally high barometric pressure conditions. (a) Special flight restrictions. When any information indicates that barometric pressure on the route of flight currently exceeds...

  17. 14 CFR 91.144 - Temporary restriction on flight operations during abnormally high barometric pressure conditions.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... during abnormally high barometric pressure conditions. 91.144 Section 91.144 Aeronautics and Space... flight operations during abnormally high barometric pressure conditions. (a) Special flight restrictions. When any information indicates that barometric pressure on the route of flight currently exceeds...

  18. 14 CFR 91.144 - Temporary restriction on flight operations during abnormally high barometric pressure conditions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... during abnormally high barometric pressure conditions. 91.144 Section 91.144 Aeronautics and Space... flight operations during abnormally high barometric pressure conditions. (a) Special flight restrictions. When any information indicates that barometric pressure on the route of flight currently exceeds...

  19. 14 CFR 91.144 - Temporary restriction on flight operations during abnormally high barometric pressure conditions.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... during abnormally high barometric pressure conditions. 91.144 Section 91.144 Aeronautics and Space... flight operations during abnormally high barometric pressure conditions. (a) Special flight restrictions. When any information indicates that barometric pressure on the route of flight currently exceeds...

  20. 14 CFR 91.144 - Temporary restriction on flight operations during abnormally high barometric pressure conditions.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... during abnormally high barometric pressure conditions. 91.144 Section 91.144 Aeronautics and Space... flight operations during abnormally high barometric pressure conditions. (a) Special flight restrictions. When any information indicates that barometric pressure on the route of flight currently exceeds...

  1. Bilateral cataract and high serum ferritin: a new dominant genetic disorder?

    PubMed Central

    Bonneau, Dominique; Winter-Fuseau, Isabelle; Loiseau, Marie-Noëlle; Amati, Patrizia; Berthier, Michel; Oriot, Denis; Beaumont, Carole

    1995-01-01

    This paper reports the cosegregation in a three generation pedigree of dominantly inherited cataract with an abnormally high level of serum ferritin. In this family, circulating L ferritin was raised in all subjects affected by cataract independently of iron overload. We suggest that a disorder of ferritin metabolism could be a new genetic disorder leading to lens opacity. Cataract-hyperferritaemia syndrome could also be a new contiguous gene syndrome involving the L ferritin gene and the gene coding for the lens membrane protein (MP19), which both map to the same region of chromosome 19q. PMID:8558554

  2. Method of curved surface abnormal holes vision measurement based on high precision turntable

    NASA Astrophysics Data System (ADS)

    Lyu, Laipeng; Bi, Chao; Fang, Jianguo; Zhu, Yong; Wang, Liping

    2015-10-01

    For solving the difficult problem that there is no effective way to measure abnormal holes located at blade erection loop of aero-engine case, an image measurement system based on high precision air-bearing turntable is established in this paper. The issue that monocular vision can't measure curved surface has overcome by using high precision turntable to make sure high positioning accuracy of the surface abnormal holes and high-resolution microscope lens which is used to image local tiny features. Besides, an algorithm of determining the boundary points of a trailing edge on the contour of abnormal hole is proposed to achieve a rapid fitting and accuracy. After experiments and analysis, results show that the system can be used to measure local tiny features on curved surfaces validly and efficiently.

  3. Highly sensitive bovine serum albumin biosensor based on liquid crystal

    NASA Astrophysics Data System (ADS)

    Sharma, Vikash; Kumar, Ajay; Ganguly, Prasun; Biradar, A. M.

    2014-01-01

    A highly sensitive liquid crystal (LC) based bovine serum albumin (BSA) protein biosensor is designed. A uniform homeotropic alignment of nematic LC was observed in BSA free substrate which changed into homogeneous in presence of BSA. The change in the LC orientation is found to depend strongly on BSA concentration. This change in the LC alignment is attributed to the modification in the surface conditions which is verified by contact angle measurements. We have detected an ultra low concentration (0.5 μg/ml) of BSA. The present study demonstrates the utilization of LC in the realization of high sensitivity biosensors.

  4. Time Orientation in the Positive and Negative Free Phantasies of Mildly Abnormal Versus Normal High School Males

    ERIC Educational Resources Information Center

    Rychlak, Joseph F.

    1973-01-01

    This study contrasts a group of mildly'' abnormal high school males with matched normals in a two-session free phantasy procedure. Mildly abnormal boys phantasized more negative contents than normal boys. Normal boys projected more positive phantasies into the future than mildly abnormal boys. A logical learning theory'' embracing the…

  5. An Algorithm for the Segmentation of Highly Abnormal Hearts Using a Generic Statistical Shape Model.

    PubMed

    Alba, Xenia; Pereanez, Marco; Hoogendoorn, Corne; Swift, Andrew J; Wild, Jim M; Frangi, Alejandro F; Lekadir, Karim

    2016-03-01

    Statistical shape models (SSMs) have been widely employed in cardiac image segmentation. However, in conditions that induce severe shape abnormality and remodeling, such as in the case of pulmonary hypertension (PH) or hypertrophic cardiomyopathy (HCM), a single SSM is rarely capable of capturing the anatomical variability in the extremes of the distribution. This work presents a new algorithm for the segmentation of severely abnormal hearts. The algorithm is highly flexible, as it does not require a priori knowledge of the involved pathology or any specific parameter tuning to be applied to the cardiac image under analysis. The fundamental idea is to approximate the gross effect of the abnormality with a virtual remodeling transformation between the patient-specific geometry and the average shape of the reference model (e.g., average normal morphology). To define this mapping, a set of landmark points are automatically identified during boundary point search, by estimating the reliability of the candidate points. With the obtained transformation, the feature points extracted from the patient image volume are then projected onto the space of the reference SSM, where the model is used to effectively constrain and guide the segmentation process. The extracted shape in the reference space is finally propagated back to the original image of the abnormal heart to obtain the final segmentation. Detailed validation with patients diagnosed with PH and HCM shows the robustness and flexibility of the technique for the segmentation of highly abnormal hearts of different pathologies. PMID:26552082

  6. Abnormal Pap Smear and Diagnosis of High-Grade Vaginal Intraepithelial Neoplasia: A Retrospective Cohort Study.

    PubMed

    Sopracordevole, Francesco; Mancioli, Francesca; Clemente, Nicolò; De Piero, Giovanni; Buttignol, Monica; Giorda, Giorgio; Ciavattini, Andrea

    2015-10-01

    The aim of this study was to analyze the correlation between the first diagnosis of high-grade Vaginal Intraepithelial Neoplasia (HG-VaIN: VaIN 2-VaIN 3) and the cytological abnormalities on the referral pap smear.All the women with histological diagnosis of HG-VaIN consecutively referred to the Gynecological Oncology Unit of the Aviano National Cancer Institute (Aviano, Italy) from January 1991 to April 2014 and with a pap smear performed in the 3 months before the diagnosis were considered, and an observational cohort study was performed.A total of 87 women with diagnosis of HG-VaIN were identified. Major cytological abnormalities (HSIL and ASC-H) on the referral pap smear were significantly more frequent than lesser abnormalities (ASC-US and LSIL) in postmenopausal women (64.9% vs 36.7%, P = 0.02) and in women with a previous diagnosis of HPV-related cervical preinvasive or invasive lesions (70.5% vs 39.5%, P = 0.01). Diagnosis of VaIN 3 was preceded by major cytological abnormalities in most of the cases (72.7% vs 27.3%, P < 0.001).The diagnosis of HG-VaIN can be preceded by different abnormalities on referral pap smear. Major abnormalities are usually reported in postmenopausal women and in women with previous cervical HPV-related disease. However, ASC-US or LSIL do not exclude HG-VaIN, especially VaIN2. An accurate examination of the whole vaginal walls (or vaginal vault) must be performed in all the women who underwent colposcopy for an abnormal pap smear, and a biopsy of all suspicious areas is mandatory. PMID:26496321

  7. Erythrocyte echinocytosis in liver disease. Role of abnormal plasma high density lipoproteins.

    PubMed Central

    Owen, J S; Brown, D J; Harry, D S; McIntyre, N; Beaven, G H; Isenberg, H; Gratzer, W B

    1985-01-01

    Echinocytes were frequently found in patients with liver disease when their blood was examined in wet films, but rarely detected in dried, stained smears. When normal erythrocytes (discocytes) were incubated with physiologic concentrations of the abnormal high density lipoproteins (HDL) from some jaundiced patients, echinocytosis developed within seconds. Other plasma fractions were not echinocytogenic. There was a close correlation between the number of echinocytes found in vivo and the ability of the corresponding HDL to induce discocyte-echinocyte transformation. On incubation with normal HDL, echinocytes generated in vitro rapidly reverted to a normal shape, and echinocytes from patients showed a similar trend. Echinocytosis occurred without change in membrane cholesterol content, as did its reversal, and was not caused by membrane uptake of lysolecithin or bile acids. Abnormal, echinocytogenic HDL showed saturable binding to approximately 5,000 sites per normal erythrocyte with an association constant of 10(8) M-1. Nonechinocytogenic patient HDL and normal HDL showed only nonsaturable binding. Several minor components of electrophoretically separated erythrocyte membrane proteins bound the abnormal HDL; pretreatment of the cells with trypsin or pronase reduced or eliminated binding. Echinocytosis by abnormal HDL required receptor occupancy, rather than transfer of constituents to or from the membrane, because cells reversibly prefixed in the discoid shape by wheat germ agglutinin, and then exposed to abnormal HDL, did not become echinocytes when the HDL and lectin were successively removed. Binding did not cause dephosphorylation of spectrin. We conclude that the echinocytes of liver disease are generated from discocytes by abnormal HDL, and we infer that the shape change is mediated by cell-surface receptors for abnormal HDL molecules. Images PMID:4077979

  8. Abnormal Heart Rate Turbulence Predicts Cardiac Mortality in Low, Intermediate and High Risk Older Adults

    PubMed Central

    Stein, Phyllis K.; Barzilay, Joshua I.

    2011-01-01

    Introduction We examined whether heart rate turbulence (HRT) adds to traditional risk factors for cardiac mortality in older adults at low, intermediate and high risk. Methods and Results N=1298, age ≥65 years, with 24-hour Holter recordings were studied. HRT, which quantifies heart rate response to ventricular premature contractions, was categorized as: both turbulence onset (TO) and turbulence slope (TS) normal; TO abnormal; TS abnormal; or both abnormal. Independent risks for cardiac mortality associated with HRT or, for comparison, elevated C-reactive protein (CRP) (>3.0 mg/L), were calculated using Cox regression analysis adjusted for traditional cardiovascular disease risk factors and stratified by the presence of no, isolated subclinical (i.e., intermediate risk) or clinical CVD. Having both TS and TO abnormal compared to both normal was associated with cardiac mortality in the low risk group [HR 7.9, 95% CI 2.8–22.5, (p<0.001)]. In the high and intermediate risk groups, abnormal TS and TO ([HR 2.2, 95% CI 1.5–4.0, p=0.016] and [HR 2.7, 95% CI 1.2–5.9, p=0.012]), respectively, were also significantly associated with cardiac mortality. In contrast, elevated CRP was associated with increased cardiac mortality risk only in low risk individuals [HR 2.5, 95% CI 1.3–5.1, p=0.009]. In the low risk group, the c-statistic was 0.706 for the base model, 0.725 for the base model with CRP, and 0.767 for the base model with HRT. Conclusions Abnormal HRT independently adds to risk stratification of low, intermediate and high risk individuals but appears to add especially to the stratification of those considered at low risk. PMID:21134026

  9. Primary colon cancer with a high serum PIVKA-II level

    PubMed Central

    Kato, Kazuya; Iwasaki, Yoshiaki; Taniguchi, Masahiko; Onodera, Kazuhiko; Matsuda, Minoru; Kawakami, Takako; Higuchi, Mineko; Kato, Kimitaka; Kato, Yurina; Furukawa, Hiroyuki

    2014-01-01

    Introduction Protein induced by vitamin K absence/antagonist-II (PIVKA-II) is an abnormal protein, and several reports have demonstrated the efficacy of PIVKA-II in the diagnosis of hepatocellular carcinoma (HCC). We report an extremely rare case of adenocarcinoma of the colon with a high serum PIVKA-II level. Presentation of Case A 95-year-old woman presented with right lower quadrant pain and appetite loss. An abdominal computed tomography scan and ultrasonography showed an ascending colon tumor and multiple metastatic tumors in the liver. The serum level of PIVKA-II was extremely high, 11,900 ng/mL. Colonoscopic examination revealed a tumor accompanied by an ulcer in the ascending colon, which was highly suspicious for malignancy. Multiple biopsies showed well-differentiated adenocarcinoma of the colon, which was evaluated as colon cancer, stage IV. PIVKA-II-productive colon cancer was confirmed. Chemotherapy with TS-1 was administered. The patient died 3 months after initial admission. Discussion The expression of PIVKA-II was detected in non-cancer areas, with non-specific expression observed in plasma cells in our case. There might be some possibility that hepatoid differentiation exists in other regions of the colon tumor or in the liver tumor, parenchymal cells or lung metastases, which were composed of PIVKA-II-positive and AFP-negative cells. Conclusion To the best of our knowledge, high serum levels of PIVKA-II resulting from colon adenocarcinoma have not been reported previously. We report this rare case together with a review of the literature. PMID:25528035

  10. Effect of high fluoride and high fat on serum lipid levels and oxidative stress in rabbits.

    PubMed

    Sun, Liyan; Gao, Yanhui; Zhang, Wei; Liu, Hui; Sun, Dianjun

    2014-11-01

    The purpose of this study was to explore the effects of high fluoride and high fat on triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), total antioxidant capacity (T-AOC), lipid peroxide (LPO) and malondialdehyde (MDA) in rabbits. A factorial experimental design was used, with two factors (fluoride and fat) and three levels. Seventy-two male rabbits were randomly assigned into nine groups according to initial weight and serum lipid levels. The rabbits were fed with basic feed, moderate fat feed or high fat feed and drank tap water, fluoridated water at levels of 50 and 100mgfluorion/L freely. Biological materials were collected after 5 months, and serum lipid, T-AOC, LPO, and MDA levels were then measured. Using these data, the separate and interactive effects of high fluoride and high fat were analyzed. High fluoride and high fat both increased serum levels of TC, HDL-C and LDL-C significantly (P<0.05), and there was also a synergistic effect between high fluoride and high fat (P<0.05). High fluoride and high fat had different effects on TG levels: high fat significantly increased TG levels (P<0.01) whereas high fluoride had nothing to do with TG levels (P>0.05). High fat significantly elevated LPO and MDA levels and lowered T-AOC levels in serum (P<0.05). Similarly, high fluoride significantly increased LPO and MDA levels in serum (P<0.05). However, there was no interactive effect between high fat and high fluoride on these indexes. In summary, high fluoride and high fat increased serum TC and LDL-C levels individually and synergistically, and this would cause and aggravate hypercholesterolemia in rabbits. At the same time, high fluoride and high fat both made the accumulation of product of oxidative stress in experimental animals. PMID:25461561

  11. High Serum SHBG Predicts Incident Vertebral Fractures in Elderly Men

    PubMed Central

    Vandenput, Liesbeth; Mellström, Dan; Kindmark, Andreas; Johansson, Helena; Lorentzon, Mattias; Leung, Jason; Redlund‐Johnell, Inga; Rosengren, Björn E; Karlsson, Magnus K; Wang, Yi‐Xiang; Kwok, Timothy

    2016-01-01

    ABSTRACT Previous prospective cohort studies have shown that serum levels of sex steroids and sex hormone‐binding globulin (SHBG) associate with nonvertebral fracture risk in men. The predictive value of sex hormones and SHBG for vertebral fracture risk specifically is, however, less studied. Elderly men (aged ≥65 years) from Sweden and Hong Kong participating in the Osteoporotic Fractures in Men (MrOS) study had baseline estradiol and testosterone analyzed by gas chromatography–mass spectrometry (GC‐MS) and SHBG by immunoradiometric assay (IRMA). Incident clinical vertebral fractures (n = 242 cases) were evaluated in 4324 men during an average follow‐up of 9.1 years. In a subsample of these men (n = 2256), spine X‐rays were obtained at baseline and after an average follow‐up of 4.3 years to identify incident radiographic vertebral fractures (n = 157 cases). The likelihood of incident clinical and radiographic vertebral fractures was estimated by Cox proportional hazards models and logistic regression models, respectively. Neither serum estradiol (hazard ratio [HR] per SD increase = 0.93, 95% confidence interval [CI] 0.80–1.08) nor testosterone (1.05, 0.91–1.21) predicted incident clinical vertebral fractures in age‐adjusted models in the combined data set. High serum SHBG, however, associated with increased clinical vertebral fracture risk (1.24, 1.12–1.37). This association remained significant after further adjustment for FRAX with or without bone mineral density (BMD). SHBG also associated with increased incident radiographic vertebral fracture risk (combined data set; odds ratio [OR] per SD increase = 1.23, 95% CI 1.05–1.44). This association remained significant after adjustment for FRAX with or without BMD. In conclusion, high SHBG predicts incident clinical and radiographic vertebral fractures in elderly men and adds moderate information beyond FRAX with BMD for vertebral fracture risk prediction. © 2015 The

  12. IgG4-related tubulointerstitial nephritis associated with only lymphadenopathy and without elevated serum IgG4 or renal imaging abnormalities: a case report and literature review.

    PubMed

    Qiao, Xi; Wang, Lihua; Wang, Chen; Gao, Lifang; Yao, Shulei; Wu, Liran; Zhang, Xiaoqin

    2015-01-01

    IgG4-related tubulointerstitial nephritis (IgG4-TIN) is the most common renal manifestation of IgG4-related kidney disease (IgG4-RKD) and may cause acute or chronic renal dysfunction. Imaging often shows heterogeneous densities in the kidneys, such as a mass or multiple nodules. Serology usually demonstrates high levels of serum IgG4 and total IgG. Most patients have other organs involvement by IgG4 related disease. Although lymphadenopathy is frequently observed in patients with IgG4-TIN, it is rarely presented as the only extrarenal lesion. Herein, we present a rare case of IgG4-TIN associated with only lymphadenopathy and without elevated serum IgG4 or renal imaging abnormalities. A 61-year-old Chinese man was admitted to our hospital with seven months history of generalized lymphadenopathy and five months history of renal dysfunction. His renal imaging was normal. He had no current or previous clinical, radiographic, and/or histologic evidence of other organ involvement except for the lymphadenopathy. Renal biopsy indicated plasma cell-rich TIN with an increased number of IgG4-positive plasma cells and storiform fibrosis. Repeated lymph nodes biopsy revealed IgG4-related lymphadenopathy. However, he did not have elevated serum IgG4 or total IgG levels. Oral prednisone therapy improved his renal function and lymphadenopathy. These findings supported our final diagnosis of IgG4-TIN. Clinicians should be aware of this condition and steroid therapy should be considered for such patients. An early diagnosis and appropriate therapy can induce remission and preserve renal function. PMID:26770608

  13. Significance of abnormal serum binding of insulin-like growth factor II in the development of hypoglycemia in patients with non-islet-cell tumors.

    PubMed Central

    Daughaday, W H; Kapadia, M

    1989-01-01

    We reported that serum and tumor from a hypoglycemic patient with a fibrosarcoma contained insulin-like growth factor II (IGF-II), mostly in a large molecular form designated "big IGF-II." We now describe two additional patients with non-islet-cell tumor with hypoglycemia (NICTH) whose sera contained big IGF-II. Removal of the tumor eliminated most of the big IGF-II from the sera of two patients. Because specific IGF-binding proteins modify the bioactivity of IGFs, the sizes of the endogenous IGF-binding protein complexes were determined after neutral gel filtration through Saphadex G-200. Normally about 75% of IGFs are carried as a ternary complex of 150 kDa consisting of IGF, a growth hormone (GH)-dependent IGF-binding protein, and an acid-labile complexing component. The three patients with NICTH completely lacked the 150-kDa complex. IGF-II was present as a 60-kDa complex with variable contributions of smaller complexes. In the immediate postoperative period, a 110-kDa complex appeared rather than the expected 150-kDa complex. Abnormal IGF-II binding may be important in NICTH because the 150-kDa complexes cross the capillary membrane poorly. The smaller complexes present in our patients' sera would be expected to enter interstitial fluid readily, and a 4- to 5-fold increase in the fraction of IGFs reaching the target cells would result. PMID:2771956

  14. Significance of abnormal serum binding of insulin-like growth factor II in the development of hypoglycemia in patients with non-islet-cell tumors

    SciTech Connect

    Daughaday, W.H.; Kapadia, M. )

    1989-09-01

    The authors reported that serum and tumor from a hypoglycemic patient with a fibrosarcoma contained insulin-like growth factor II (IGF-II), mostly in a large molecular form designated big IGF-II. They now describe two additional patients with non-islet-cell tumor with hypoglycemia (NICTH) whose sera contained big IGF-II. Removal of the tumor eliminated most of the big IGF-II from the sera of two patients. Because specific IGF-binding proteins modify the bioactivity of IGFs, the sizes of the endogenous IGF-binding protein complexes were determined after neutral gel filtration through Sephadex G-200. Normally about 75% of IGFs are carried as a ternary complex of 150 kDa consisting of IGF, a growth hormone (GH)-dependent IGF-binding protein, and an acid-labile complexing component. The three patients with NICTH completely lacked the 150-kDa complex. IGF-II was present as a 60-kDa complex with variable contributions of smaller complexes. In the immediate postoperative period, a 110-kDa complex appeared rather than the expected 150-kDa complex. Abnormal IGF-II binding may be important in NICTH because the 150-kDa complexes cross the capillary membrane poorly. The smaller complexes present in our patients' sera would be expected to enter interstitial fluid readily, and a 4- to 5-fold increase in the fraction of IGFs reaching the target cells would result.

  15. Phenotyping structural abnormalities in mouse embryos using high-resolution episcopic microscopy

    PubMed Central

    Weninger, Wolfgang J.; Geyer, Stefan H.; Martineau, Alexandrine; Galli, Antonella; Adams, David J.; Wilson, Robert; Mohun, Timothy J.

    2014-01-01

    The arrival of simple and reliable methods for 3D imaging of mouse embryos has opened the possibility of analysing normal and abnormal development in a far more systematic and comprehensive manner than has hitherto been possible. This will not only help to extend our understanding of normal tissue and organ development but, by applying the same approach to embryos from genetically modified mouse lines, such imaging studies could also transform our knowledge of gene function in embryogenesis and the aetiology of developmental disorders. The International Mouse Phenotyping Consortium is coordinating efforts to phenotype single gene knockouts covering the entire mouse genome, including characterising developmental defects for those knockout lines that prove to be embryonic lethal. Here, we present a pilot study of 34 such lines, utilising high-resolution episcopic microscopy (HREM) for comprehensive 2D and 3D imaging of homozygous null embryos and their wild-type littermates. We present a simple phenotyping protocol that has been developed to take advantage of the high-resolution images obtained by HREM and that can be used to score tissue and organ abnormalities in a reliable manner. Using this approach with embryos at embryonic day 14.5, we show the wide range of structural abnormalities that are likely to be detected in such studies and the variability in phenotypes between sibling homozygous null embryos. PMID:25256713

  16. Does high serum uric acid level cause aspirin resistance?

    PubMed

    Yildiz, Bekir S; Ozkan, Emel; Esin, Fatma; Alihanoglu, Yusuf I; Ozkan, Hayrettin; Bilgin, Murat; Kilic, Ismail D; Ergin, Ahmet; Kaftan, Havane A; Evrengul, Harun

    2016-06-01

    In patients with coronary artery disease (CAD), though aspirin inhibits platelet activation and reduces atherothrombotic complications, it does not always sufficiently inhibit platelet function, thereby causing a clinical situation known as aspirin resistance. As hyperuricemia activates platelet turnover, aspirin resistance may be specifically induced by increased serum uric acid (SUA) levels. In this study, we thus investigated the association between SUA level and aspirin resistance in patients with CAD. We analyzed 245 consecutive patients with stable angina pectoris (SAP) who in coronary angiography showed more than 50% occlusion in a major coronary artery. According to aspirin resistance, two groups were formed: the aspirin resistance group (Group 1) and the aspirin-sensitive group (Group 2). Compared with those of Group 2, patients with aspirin resistance exhibited significantly higher white blood cell counts, neutrophil counts, neutrophil-to-lymphocyte ratios, SUA levels, high-sensitivity C-reactive protein levels, and fasting blood glucose levels. After multivariate analysis, a high level of SUA emerged as an independent predictor of aspirin resistance. The receiver-operating characteristic analysis provided a cutoff value of 6.45 mg/dl for SUA to predict aspirin resistance with 79% sensitivity and 65% specificity. Hyperuricemia may cause aspirin resistance in patients with CAD and high SUA levels may indicate aspirin-resistant patients. Such levels should thus recommend avoiding heart attack and stroke by adjusting aspirin dosage. PMID:26656902

  17. Nicotine in Combination With a High-Fat Diet Causes Intramyocellular Mitochondrial Abnormalities in Male Mice

    PubMed Central

    Sinha-Hikim, Indrani; Friedman, Theodore C.; Shin, Chang-Sung; Lee, Desean; Ivey, Rasheed

    2014-01-01

    Smoking is a major risk factor for diabetes, cardiovascular disease, and nonalcoholic fatty liver disease. The health risk associated with smoking can be exaggerated by obesity. We hypothesize that nicotine when combined with a high-fat diet (HFD) can also cause ectopic lipid accumulation in skeletal muscle, similar to recently observed hepatic steatosis. Adult C57BL6 male mice were fed a normal chow diet or HFD and received twice-daily ip injections of nicotine (0.75 mg/kg body weight) or saline for 10 weeks. Transmission electron microscopy of the gastrocnemius muscle revealed substantial intramyocellular lipid accumulation in close association with intramyofibrillar mitochondria along with intramyofibrillar mitochondrial swelling and vacuolization in nicotine-treated mice on an HFD compared with mice on an HFD treated with saline. These abnormalities were reversed by acipimox, an inhibitor of lipolysis. Mechanistically, the detrimental effect of nicotine plus HFD on skeletal muscle was associated with significantly increased oxidative stress, plasma free fatty acid, and muscle triglyceride levels coupled with inactivation of AMP-activated protein kinase and activation of its downstream target, acetyl-coenzyme A-carboxylase. We conclude that 1) greater oxidative stress together with inactivation of AMP-activated protein kinase mediates the effect of nicotine on skeletal muscle abnormalities in diet-induced obesity and 2) adipose tissue lipolysis is an important contributor of muscle steatosis and mitochondrial abnormalities. PMID:24424058

  18. High serum circulating telopeptide type I in multinodular goiter.

    PubMed

    Loviselli, A; Rizzolo, E; Mastinu, R; Velluzzi, F; Secci, G; Taberlet, A; Mariotti, S

    2003-06-01

    Recently, concentrations of serum carboxy-terminal-1-telopeptide (ICTP), a marker of bone collagen resorption, were found to be more sensitive than sex hormone-binding globulin (SHBG) in identifying peripheral overexposure to thyroid hormones in exogenous subclinical hyperthyroidism. The aim of the present study was to assess serum ICTP and SHBG in multinodular goiter with (pretoxic goiter) or without biochemical evidence of endogenous subclinical hyperthyroidism. Forty-five women affected by multinodular goiter were enrolled in this study. They were subdivided into two groups: group 1, consisting of 27 patients affected by pretoxic goiter; group 2, consisting of 18 patients affected by non toxic goiter; group 3, consisting of thirty-six euthyroid women matched with the other groups for age and lifestyle. In group 1, serum ICTP (mean +/- SD: 5.8 +/- 2.9 microg/l) concentrations were significantly higher when compared either to group 2 (3.6 +/- 1.2 microg/l; p < 0.02) or controls (2.7 +/- 0.7 microg/l; p < 0.0001); serum ICTP concentrations were also slightly but significantly higher in patients of group 2 compared to controls (p < 0.003). In contrast, mean serum SHBG concentrations did not show any difference among the three groups. No significant correlation was found between serum TSH and ICTP concentrations, while a weak positive correlation (p < 0.05) was only found between serum FT 3 and ICTP concentrations when data from the two patient groups were analyzed together. Moreover, when we subdivided patients into pre- and postmenopausal patients, we observed that SHBG but not ICTP serum concentrations were influenced by estrogenic status. In summary, the measurement of serum ICTP seems to be more suitable than SHBG for identifying those with a higher degree of peripheral thyroid hormone exposure in women affected by endogenous subclinical hyperthyroidism. PMID:12920662

  19. Mathematical impairment associated with high-contrast abnormalities in change detection and magnocellular visual evoked response.

    PubMed

    Jastrzebski, Nicola R; Crewther, Sheila G; Crewther, David P

    2015-10-01

    The cause of developmental dyscalculia, a specific deficit in acquisition of arithmetic skills, particularly of enumeration, has never been investigated with respect to the patency of the visual magnocellular system. Here, the question of dysfunction of the afferent magnocellular cortical input and its dorsal stream projections was tested directly using nonlinear analysis of the visual evoked potential (VEP) and through the psychophysical ability to rapidly detect visual change. A group of young adults with self-reported deficiencies of arithmetical ability, showed marked impairment in magnitude estimation and enumeration performance-though not in lexical decision reaction times when compared with an arithmetically capable group controlled for age and handedness. Multifocal nonlinear VEPs were recorded at low (24 %) and high (96 %) contrast. First- and second-order VEP kernels were comparable between groups at low contrast, but not at high contrast. The mathematically impaired group showed an abnormal lack of contrast saturation in the shortest latency first-order peak (N60) and a delayed P100 positivity in the first slice of the second-order kernel. Both features have previously been argued to be physiological markers of magnocellular function. Mathematically impaired participants also performed worse on a gap paradigm change detection for digit task showing increased reaction times for high-contrast stimuli but not for low-contrast stimuli compared with controls. The VEP results give direct evidence of abnormality in the occipital processing of magnocellular information in those with mathematical impairment. The anomalous high visual contrast physiological and psychophysical performance suggests an abnormality in the inhibitory processes that normally result in saturation of contrast gain in the magnocellular system. PMID:26195163

  20. Abnormal high surface heat flow caused by the Emeishan mantle plume

    NASA Astrophysics Data System (ADS)

    Jiang, Qiang; Qiu, Nansheng; Zhu, Chuanqing

    2016-04-01

    It is commonly believed that increase of heat flow caused by a mantle plume is small and transient. Seafloor heat flow data near the Hawaiian hotspot and the Iceland are comparable to that for oceanic lithosphere elsewhere. Numerical modeling of the thermal effect of the Parana large igneous province shows that the added heat flow at the surface caused by the magmatic underplating is less than 5mW/m2. However, the thermal effect of Emeishan mantle plume (EMP) may cause the surface hear-flow abnormally high. The Middle-Late Emeishan mantle plume is located in the western Yangtze Craton. The Sichuan basin, to the northeast of the EMP, is a superimposed basin composed of Paleozoic marine carbonate rocks and Mesozoic-Cenozoic terrestrial clastic rocks. The vitrinite reflectance (Ro) data as a paleogeothermal indicator records an apparent change of thermal regime of the Sichuan basin. The Ro profiles from boreholes and outcrops which are close to the center of the basalt province exhibit a 'dog-leg' style at the unconformity between the Middle and Upper Permian, and they show significantly higher gradients in the lower subsection (pre-Middle Permian) than the Upper subsection (Upper Permian to Mesozoic). Thermal history inversion based on these Ro data shows that the lower subsection experienced a heat flow peak much higher than that of the upper subsection. The abnormal heat flow in the Sichuan basin is consistent with the EMP in temporal and spatial distribution. The high-temperature magmas from deep mantle brought heat to the base of the lithosphere, and then large amount of heat was conducted upwards, resulting in the abnormal high surface heat flow.

  1. Abnormal effective connectivity and psychopathological symptoms in the psychosis high-risk state

    PubMed Central

    Schmidt, André; Smieskova, Renata; Simon, Andor; Allen, Paul; Fusar-Poli, Paolo; McGuire, Philip K.; Bendfeldt, Kerstin; Aston, Jacqueline; Lang, Undine E.; Walter, Marc; Radue, Ernst-Wilhelm; Riecher-Rössler, Anita; Borgwardt, Stefan J.

    2014-01-01

    Background Recent evidence has revealed abnormal functional connectivity between the frontal and parietal brain regions during working memory processing in patients with schizophrenia and first-episode psychosis. However, it still remains unclear whether abnormal frontoparietal connectivity during working memory processing is already evident in the psychosis high-risk state and whether the connection strengths are related to psychopathological outcomes. Methods Healthy controls and antipsychotic-naive individuals with an at-risk mental state (ARMS) performed an n-back working memory task while undergoing functional magnetic resonance imaging. Effective connectivity between frontal and parietal brain regions during working memory processing were characterized using dynamic causal modelling. Results Our study included 19 controls and 27 individuals with an ARMS. In individuals with an ARMS, we found significantly lower task performances and reduced activity in the right superior parietal lobule and middle frontal gyrus than in controls. Furthermore, the working memory–induced modulation of the connectivity from the right middle frontal gyrus to the right superior parietal lobule was significantly reduced in individuals with an ARMS, while the extent of this connectivity was negatively related to the Brief Psychiatric Rating Scale total score. Limitations The modest sample size precludes a meaningful subgroup analysis for participants with a later transition to psychosis. Conclusion This study demonstrates that abnormal frontoparietal connectivity during working memory processing is already evident in individuals with an ARMS and is related to psychiatric symptoms. Thus, our results provide further insight into the pathophysiological mechanisms of the psychosis high-risk state by linking functional brain imaging, computational modelling and psychopathology. PMID:24506946

  2. A high-capacity hydrophobic adsorbent for human serum albumin.

    PubMed

    Belew, M; Peterson, E A; Porath, J

    1985-12-01

    A simple method, based on salting out hydrophobic interaction chromatography, for the efficient removal of trace amounts of serum albumin from partially purified protein preparations is described. The method is also successfully applied for the purification of albumin from Cohn fraction IV, a by-product obtained from the commercial fractionation of human serum proteins by the ethanol precipitation procedure. About 70% of the adsorbed albumin can be eluted by buffer of low ionic strength and can thus be lyophilized directly, if required. The adsorbent can be used for several cycles of adsorption and desorption without affecting its selectivity or capacity. Its adsorption properties and capacity for serum albumin are compared with those of the commercially available adsorbent Blue Sepharose CL-6B. PMID:3879424

  3. Normal and abnormal evolution of argon metastable density in high-density plasmas

    SciTech Connect

    Seo, B. H.; Kim, J. H.; You, S. J.

    2015-05-15

    A controversial problem on the evolution of Ar metastable density as a function of electron density (increasing trend versus decreasing trend) was resolved by discovering the anomalous evolution of the argon metastable density with increasing electron density (discharge power), including both trends of the metastable density [Daltrini et al., Appl. Phys. Lett. 92, 061504 (2008)]. Later, by virtue of an adequate physical explanation based on a simple global model, both evolutions of the metastable density were comprehensively understood as part of the abnormal evolution occurring at low- and high-density regimes, respectively, and thus the physics behind the metastable evolution has seemed to be clearly disclosed. In this study, however, a remarkable result for the metastable density behavior with increasing electron density was observed: even in the same electron density regime, there are both normal and abnormal evolutions of metastable-state density with electron density depending on the measurement position: The metastable density increases with increasing electron density at a position far from the inductively coupled plasma antenna but decreases at a position close to the antenna. The effect of electron temperature, which is spatially nonuniform in the plasma, on the electron population and depopulation processes of Argon metastable atoms with increasing electron density is a clue to understanding the results. The calculated results of the global model, including multistep ionization for the argon metastable state and measured electron temperature, are in a good agreement with the experimental results.

  4. Left-Hemispheric Microstructural Abnormalities in Children With High Functioning Autism Spectrum Disorder

    PubMed Central

    Peterson, Daniel; Mahajan, Rajneesh; Crocetti, Deana; Mejia, Amanda; Mostofsky, Stewart

    2014-01-01

    Current theories of the neurobiological basis of Autism Spectrum Disorder (ASD) posit an altered pattern of connectivity in large-scale brain networks. Here we used Diffusion Tensor Imaging to investigate the microstructural properties of the white matter that mediates inter-regional connectivity in 36 high-functioning children with ASD (HF-ASD), as compared to 37 controls. By employing an atlas-based analysis using LDDMM registration, a widespread, but left-lateralized pattern of abnormalities was revealed. The Mean Diffusivity (MD) of water in the white matter of HF-ASD children was significantly elevated throughout the left hemisphere, particularly in the outer-zone cortical white matter. Across diagnostic groups there was a significant effect of age on left hemisphere MD, with a similar reduction in MD during childhood in both TD and HF-ASD children. The increased MD in children with HF-ASD suggests hypomyelination, and may reflect increased short-range cortico-cortical connections subsequent to early white matter overgrowth. These findings also highlight left hemispheric connectivity as relevant to the pathophysiology of ASD, and indicate that the spatial distribution of microstructural abnormalities in HF-ASD is widespread, and left-lateralized. This altered left-hemispheric connectivity may contribute to deficits in communication and praxis observed in ASD. PMID:25256103

  5. Cefaclor pharmacokinetic parameters: serum concentrations determined by a new high-performance liquid chromatographic technique.

    PubMed

    Rotschafer, J C; Crossley, K B; Lesar, T S; Zaske, D; Miller, K

    1982-01-01

    Pharmacokinetic parameters of cefaclor were studied in eight patients after an oral dose of 250 mg. Serum samples were obtained before and on 19 occasions after oral administration. Cefaclor serum concentrations were determined by a new high-performance liquid chromatographic technique. PMID:7081972

  6. The integrated method to select drilling muds for abnormally high pressure formations

    NASA Astrophysics Data System (ADS)

    Khorev, V. S.; Dmitriev, A. Yu; Boyko, I. A.; Kayumova, N. S.; Rakhimov, T. R.

    2016-03-01

    The article describes the method for choosing a drilling mud for drilling abnormally high pressure formations. A carefully selected drilling mud formulation would not only enhance an array of interrelated fluid properties, but also minimize the impact on the pay zones when the drill bit first penetrates the pay. To ensure a better assessment of drilling mud impact on the pay zone, it is reasonable to carry out the study focused on the analysis of technological parameters, involving filtration, acid and drilling mud tests, as well as formation damage analysis. This would enable evaluating the degree of mudding off, reservoirs acid fracturing effect and the risks of pipe sticking at significant depth. The article presents the results of the above-described study with regard to the currently used drilling mud and new experimental formulations developed at National Research Tomsk Polytechnic University (Drilling Mud and Cement Slurry Laboratory).

  7. High-Flux Hemodialysis and High-Volume Hemodiafiltration Improve Serum Calcification Propensity

    PubMed Central

    Dekker, Marijke; Pasch, Andreas; van der Sande, Frank; Konings, Constantijn; Bachtler, Matthias; Dionisi, Mauro; Meier, Matthias; Kooman, Jeroen; Canaud, Bernard

    2016-01-01

    Background Calciprotein particles (CPPs) may play an important role in the calcification process. The calcification propensity of serum (T50) is highly predictive of all-cause mortality in chronic kidney disease patients. Whether T50 is therapeutically improvable, by high-flux hemodialysis (HD) or hemodiafiltration (HDF), has not been studied yet. Methods We designed a cross-sectional single center study, and included stable prevalent in-center dialysis patients on HD or HDF. Patients were divided into two groups based on dialysis modality, were on a thrice-weekly schedule, had a dialysis vintage of > 3 months and vascular access providing a blood flow rate > 300 ml/min. Calcification propensity of serum was measured by the time of transformation from primary to secondary CPP (T50 test), by time-resolved nephelometry. Results We included 64 patients, mean convective volume was 21.7L (SD 3.3L). In the pooled analysis, T50 levels increased in both the HD and HDF group with pre- and post-dialysis (mean (SD)) of 244(64) - 301(57) and 253(55) - 304(61) min respectively (P = 0.43(HD vs. HDF)). The mean increase in T50 was 26.29% for HD and 21.97% for HDF patients (P = 0.61 (HD vs. HDF)). The delta values (Δ) of calcium, phosphate and serum albumin were equal in both groups. Baseline T50 was negatively correlated with phosphate, and positively correlated with serum magnesium and fetuin-A. The ΔT50 was mostly influenced by Δ phosphate (r = -0.342; P = 0.002 HD and r = -0.396; P<0.001 HDF) in both groups. Conclusions HD and HDF patients present with same baseline T50 calcification propensity values pre-dialysis. Calcification propensity is significantly improved during both HD and HDF sessions without significant differences between both modalities. PMID:27064679

  8. Network Mechanisms Generating Abnormal and Normal Hippocampal High-Frequency Oscillations: A Computational Analysis1,2,3

    PubMed Central

    Gliske, Stephen; Catoni, Nicholas

    2015-01-01

    Abstract High-frequency oscillations (HFOs) are an intriguing potential biomarker for epilepsy, typically categorized according to peak frequency as either ripples (100–250 Hz) or fast ripples (>250 Hz). In the hippocampus, fast ripples were originally thought to be more specific to epileptic tissue, but it is still very difficult to distinguish which HFOs are caused by normal versus pathological brain activity. In this study, we use a computational model of hippocampus to investigate possible network mechanisms underpinning normal ripples, pathological ripples, and fast ripples. Our results unify several prior findings regarding HFO mechanisms, and also make several new predictions regarding abnormal HFOs. We show that HFOs are generic, emergent phenomena whose characteristics reflect a wide range of connectivity and network input. Although produced by different mechanisms, both normal and abnormal HFOs generate similar ripple frequencies, underscoring that peak frequency is unable to distinguish the two. Abnormal ripples are generic phenomena that arise when input to pyramidal cells overcomes network inhibition, resulting in high-frequency, uncoordinated firing. In addition, fast ripples transiently and sporadically arise from the precise conditions that produce abnormal ripples. Lastly, we show that such abnormal conditions do not require any specific network structure to produce coherent HFOs, as even completely asynchronous activity is capable of producing abnormal ripples and fast ripples in this manner. These results provide a generic, network-based explanation for the link between pathological ripples and fast ripples, and a unifying description for the entire spectrum from normal ripples to pathological fast ripples. PMID:26146658

  9. High frequency of p53/MDM2/p14ARF pathway abnormalities in relapsed neuroblastoma

    PubMed Central

    Carr-Wilkinson, Jane; O' Toole, Kieran; Wood, Katrina M.; Challen, Christine C.; Baker, Angela G.; Board, Julian R.; Evans, Laura; Cole, Michael; Cheung, Nai-Kong V.; Boos, Joachim; Köhler, Gabriele; Leuschner, Ivo; Pearson, Andrew D.J.; Lunec, John; Tweddle, Deborah A.

    2010-01-01

    Purpose: Most neuroblastomas initially respond to therapy but many relapse with chemoresistant disease. p53 mutations are rare in diagnostic neuroblastomas, but we have previously reported inactivation of the p53/MDM2/p14ARF pathway in 9/17 (53%) neuroblastoma cell lines established at relapse. Hypothesis: Inactivation of the p53/MDM2/p14ARF pathway develops during treatment and contributes to neuroblastoma relapse. Methods: Eighty-four neuroblastomas were studied from 41 patients with relapsed neuroblastoma including 38 paired neuroblastomas at different stages of therapy. p53 mutations were detected by automated sequencing, p14ARF methylation and deletion by methylation-specific PCR and duplex PCR respectively, and MDM2 amplification by fluorescent in-situ hybridisation. Results: Abnormalities in the p53 pathway were identified in 20/41(49%) cases. Downstream defects due to inactivating missense p53 mutations were identified in 6/41 (15%) cases, 5 following chemotherapy and/or at relapse and 1 at diagnosis, post chemotherapy and relapse. The presence of a p53 mutation was independently prognostic for overall survival (hazard ratio 3.4, 95% confidence interval 1.2, 9.9; p = 0.02). Upstream defects were present in 35% cases: MDM2 amplification in 3 cases, all at diagnosis & relapse and p14ARF inactivation in 12/41 (29%) cases: 3 had p14ARF methylation, 2 after chemotherapy, and 9 had homozygous deletions, 8 at diagnosis and relapse. Conclusions: These results show that a high proportion of neuroblastomas which relapse have an abnormality in the p53 pathway. The majority have upstream defects suggesting that agents which reactivate wild-type p53 would be beneficial, in contrast to those with downstream defects where p53 independent therapies are indicated. PMID:20145180

  10. Association between Serum Interleukin-17A Level and High-Altitude Deacclimatization Syndrome

    PubMed Central

    He, Binfeng; Li, Hongli; Hu, Mingdong; Dong, Weijie; Wei, Zhenghua; Li, Jin; Yao, Wei; Guo, Xiaolan

    2016-01-01

    High-altitude deacclimatization syndrome (HADAS) is emerging as a severe public health issue that threatens the quality of life of individuals who return to lower altitude from high altitude. In this study, we measured serum levels of SOD, MDA, IL-17A, IL-10, TNF-α, and HADAS score in HADAS subjects at baseline and 50th and 100th days and to evaluate the relationship between interleukins, including IL-17A, and HADAS. Our data showed that and the serum IL-17A levels and HADAS score decreased over time in the HADAS group, and serum IL-17A levels were significantly higher in the HADAS group at baseline and 50th day compared with controls (p < 0.05). Furthermore, baseline serum levels of MDA and TNF-α were significantly higher, while SOD and IL-10 levels were lower in HADAS subjects compared with controls (p < 0.05). It is interesting that serum levels of IL-17A were clearly interrelated with HADAS incidence and severity (p < 0.05). ROC curve analysis showed that combined serum IL-17A and IL-10 levels were a better predictor of HADAS incidence than serum levels of IL-17A or IL-10 alone. These data suggest that serum levels of IL-17A are a novel predictive index of HADAS. PMID:27190491

  11. Abnormal high-Q modes of coupled stadium-shaped microcavities.

    PubMed

    Ryu, Jung-Wan; Lee, Soo-Young; Kim, Inbo; Choi, Muhan; Hentschel, Martina; Kim, Sang Wook

    2014-07-15

    It is well known that the strongly deformed microcavity with fully chaotic ray dynamics cannot support high-Q modes due to its fast chaotic diffusion to the critical line of refractive emission. Here, we investigate how the Q factor is modified when two chaotic cavities are coupled, and show that some modes, whose Q factor is about 10 times higher than that of the corresponding single cavity, can exist. These abnormal high-Q modes are the result of an optimal combination of coupling and cavity geometry. As an example, in the coupled stadium-shaped microcavities, the mode pattern extends over both cavities such that it follows a whispering-gallery-type mode at both ends, whereas a big coupling spot forms at the closest contact of the two microcavities. The pattern of such a "rounded bow tie" mode allows the mode to have a high-Q factor. This mode pattern minimizes the leakage of light at both ends of the microcavities as the pattern at both ends is similar to the whispering gallery mode. PMID:25121685

  12. Isolation and Characterization of an Abnormal High Density Lipoprotein in Tangier Disease

    PubMed Central

    Assmann, Gerd; Herbert, Peter N.; Fredrickson, Donald S.; Forte, Trudy

    1977-01-01

    The nature of the high density lipoproteins has been investigated in five patients homozygous for Tangier disease (familial high density lipoprotein deficiency). It has been established that Tangier high density lipoproteins, as isolated by ultracentrifugation, are morphologically heterogenous and contain several proteins (Apo B, albumin, and Apo A-II). An abnormal lipoprotein has been isolated from the d = 1.063-1.21 g/ml ultracentrifugal fraction by agarose-column chromatography which contains apoprotein A-II as the sole protein constituent. In negative-stain electron microscopy, these lipoproteins appeared as spherical particles 55-75 Å in diameter. By a variety of criteria (immunochemical, polyacrylamide electrophoresis, amino acid composition, and fluorescence measurements), apoprotein A-I the major apoprotein of normal high density lipoproteins and the C apoproteins were absent from this lipoprotein. As demonstrated by 125I very low density lipoprotein incubation experiments with Tangier plasma, C apoproteins did not associate with lipoproteins of d = 1.063-1.21 g/ml. Tangier apoprotein A-II, isolated to homogeneity by delipidation of the apoprotein A-II-containing lipoprotein or Sephadex G-200 guanidine-HCl chromatography of the d = 1.063-1.21 g/ml fraction, was indistinguishable from control apoprotein A-II with respect to amino acid composition and migration of tryptic peptides in urea-polyacrylamide electrophoresis. The ability of Tangier apoprotein A-II to bind phospholipid was demonstrated by in vitro reconstitution experiments and morphological and chemical analysis of lipid-protein complexes. It is concluded that normal high density lipoproteins, as defined by polypeptide composition and morphological appearance, are absent from Tangier plasma and that as a consequence, the impairment of C apoprotein metabolism contributes to the hypertriglyceridemia and fasting chylomicronemia observed in these patients. Images PMID:194920

  13. Abnormal Adrenal Responsiveness and Angiotensin II Dependency in High Renin Essential Hypertension

    PubMed Central

    Dluhy, Robert G.; Bavli, Sam Z.; Leung, Frank K.; Solomon, Harold S.; Moore, Thomas J.; Hollenberg, Norman K.; Williams, Gordon H.

    1979-01-01

    Adrenal responsiveness to angiotensin II (AII) and the diastolic blood pressure responses to saralasin were studied in 19 patients with high renin essential hypertension (HREH) on a 10-meq Na+/100 meq K+ diet. The increment in plasma renin activity (PRA) between supine and upright positions was used as an estimate of the acute stimulation of the adrenal gland by endogenous AII; the normal increment in plasma aldosterone divided by the increment in PRA was >3.8. 7 of 19 had abnormal upright posture responses with significantly greater mean PRA increments (24±6 ng/ml per h) and significantly smaller plasma aldosterone increments 47 ± 16 ng/dl) (P < 0.036) compared to the increments observed in HREH patients with normal adrenal responsiveness (PRA = 15 ± 1 ng/ml per h; plasma aldosterone = 87 ± 17 ng/dl). When AII was infused at doses of 0.1-3 ng/kg per min, only patients with normal posture responses had normal plasma aldosterone increments; plasma aldosterone levels failed to significantly increase even at the highest infusion rate in the patients with the abnormal upright posture responses. The AII competitive inhibitor, saralasin (0.3-30 μg/kg per min) was then infused to study the occurrence of angiotensinogenic hypertension in both HREH subgroups. The mean decline in diastolic blood pressure to saralasin in the subnormal adrenal responsive patients (−15 ± 3 mm Hg) was significantly greater than in the normal adrenal responsive group (−3 ± 2 mm Hg) (P < 0.02). It is concluded that patients with HREH are not a homogeneous population; approximately one-third have AII-dependent hypertension. In these patients, the mechanism responsible for the elevated renin and blood pressure could be a compensatory increase secondary to decreased adrenal responsiveness to AII. In the remainder, the high PRA levels have little, if any, causal role in the pathogenesis of the hypertension but could reflect a marker of other pathophysiologic processes. PMID:500810

  14. High serum creatinine nonlinearity: a renal vital sign?

    PubMed

    Palant, Carlos E; Chawla, Lakhmir S; Faselis, Charles; Li, Ping; Pallone, Thomas L; Kimmel, Paul L; Amdur, Richard L

    2016-08-01

    Patients with chronic kidney disease (CKD) may have nonlinear serum creatinine concentration (SC) trajectories, especially as CKD progresses. Variability in SC is associated with renal failure and death. However, present methods for measuring SC variability are unsatisfactory because they blend information about SC slope and variance. We propose an improved method for defining and calculating a patient's SC slope and variance so that they are mathematically distinct, and we test these methods in a large sample of US veterans, examining the correlation of SC slope and SC nonlinearity (SCNL) and the association of SCNL with time to stage 4 CKD (CKD4) and death. We found a strong correlation between SCNL and rate of CKD progression, time to CKD4, and time to death, even in patients with normal renal function. We therefore argue that SCNL may be a measure of renal autoregulatory dysfunction that provides an early warning sign for CKD progression. PMID:27194712

  15. Reproductive and behavioral abnormalities in tree swallows with high levels of PCB contamination

    SciTech Connect

    McCarty, J.; Secord, A.; Tillitt, D.

    1995-12-31

    Tree Swallows (Tachycineta bicolor) breeding along the Hudson River forage extensively on PCB contaminated insects that emerge from the river. The authors studied the reproductive ecology and behavior of tree swallows breeding at several sites along the Hudson River. These sites vary in the severity of PCB contamination. PCB levels in both eggs and chicks were found to be among the highest ever reported in this species, with concentrations comparable to those found in aquatic organisms in the Hudson River. In 1994 reproductive success at PCB contaminated sites was significantly impaired, relative to other sites in New York. Reduced reproductive success was largely attributed to high levels of nest abandonment during incubation and reduced hatchability of eggs. Growth and development of nestlings was not significantly impaired. Abnormal nest building behavior was also noted in 1994, and this was studied in detail in 1995. Nests from contaminated areas are significantly smaller than those at a nearby reference site and at other sites in New York. The authors suggest that the reduced reproductive outputs at these sites are, in large part, a result of effects on the behavior of incubating females. The population-level implications of these patterns are unknown.

  16. Identification of novel serum peptide biomarkers for high-altitude adaptation: a comparative approach

    PubMed Central

    Yang, Juan; Li, Wenhua; Liu, Siyuan; Yuan, Dongya; Guo, Yijiao; Jia, Cheng; Song, Tusheng; Huang, Chen

    2016-01-01

    We aimed to identify serum biomarkers for screening individuals who could adapt to high-altitude hypoxia at sea level. HHA (high-altitude hypoxia acclimated; n = 48) and HHI (high-altitude hypoxia illness; n = 48) groups were distinguished at high altitude, routine blood tests were performed for both groups at high altitude and at sea level. Serum biomarkers were identified by comparing serum peptidome profiling between HHI and HHA groups collected at sea level. Routine blood tests revealed the concentration of hemoglobin and red blood cells were significantly higher in HHI than in HHA at high altitude. Serum peptidome profiling showed that ten significantly differentially expressed peaks between HHA and HHI at sea level. Three potential serum peptide peaks (m/z values: 1061.91, 1088.33, 4057.63) were further sequence identified as regions of the inter-α trypsin inhibitor heavy chain H4 fragment (ITIH4 347–356), regions of the inter-α trypsin inhibitor heavy chain H1 fragment (ITIH1 205–214), and isoform 1 of fibrinogen α chain precursor (FGA 588–624). Expression of their full proteins was also tested by ELISA in HHA and HHI samples collected at sea level. Our study provided a novel approach for identifying potential biomarkers for screening people at sea level who can adapt to high altitudes. PMID:27150491

  17. Identification of novel serum peptide biomarkers for high-altitude adaptation: a comparative approach.

    PubMed

    Yang, Juan; Li, Wenhua; Liu, Siyuan; Yuan, Dongya; Guo, Yijiao; Jia, Cheng; Song, Tusheng; Huang, Chen

    2016-01-01

    We aimed to identify serum biomarkers for screening individuals who could adapt to high-altitude hypoxia at sea level. HHA (high-altitude hypoxia acclimated; n = 48) and HHI (high-altitude hypoxia illness; n = 48) groups were distinguished at high altitude, routine blood tests were performed for both groups at high altitude and at sea level. Serum biomarkers were identified by comparing serum peptidome profiling between HHI and HHA groups collected at sea level. Routine blood tests revealed the concentration of hemoglobin and red blood cells were significantly higher in HHI than in HHA at high altitude. Serum peptidome profiling showed that ten significantly differentially expressed peaks between HHA and HHI at sea level. Three potential serum peptide peaks (m/z values: 1061.91, 1088.33, 4057.63) were further sequence identified as regions of the inter-α trypsin inhibitor heavy chain H4 fragment (ITIH4 347-356), regions of the inter-α trypsin inhibitor heavy chain H1 fragment (ITIH1 205-214), and isoform 1 of fibrinogen α chain precursor (FGA 588-624). Expression of their full proteins was also tested by ELISA in HHA and HHI samples collected at sea level. Our study provided a novel approach for identifying potential biomarkers for screening people at sea level who can adapt to high altitudes. PMID:27150491

  18. Identification of novel serum peptide biomarkers for high-altitude adaptation: a comparative approach

    NASA Astrophysics Data System (ADS)

    Yang, Juan; Li, Wenhua; Liu, Siyuan; Yuan, Dongya; Guo, Yijiao; Jia, Cheng; Song, Tusheng; Huang, Chen

    2016-05-01

    We aimed to identify serum biomarkers for screening individuals who could adapt to high-altitude hypoxia at sea level. HHA (high-altitude hypoxia acclimated; n = 48) and HHI (high-altitude hypoxia illness; n = 48) groups were distinguished at high altitude, routine blood tests were performed for both groups at high altitude and at sea level. Serum biomarkers were identified by comparing serum peptidome profiling between HHI and HHA groups collected at sea level. Routine blood tests revealed the concentration of hemoglobin and red blood cells were significantly higher in HHI than in HHA at high altitude. Serum peptidome profiling showed that ten significantly differentially expressed peaks between HHA and HHI at sea level. Three potential serum peptide peaks (m/z values: 1061.91, 1088.33, 4057.63) were further sequence identified as regions of the inter-α trypsin inhibitor heavy chain H4 fragment (ITIH4 347–356), regions of the inter-α trypsin inhibitor heavy chain H1 fragment (ITIH1 205–214), and isoform 1 of fibrinogen α chain precursor (FGA 588–624). Expression of their full proteins was also tested by ELISA in HHA and HHI samples collected at sea level. Our study provided a novel approach for identifying potential biomarkers for screening people at sea level who can adapt to high altitudes.

  19. High prevalence of anterolateral ligament abnormalities in magnetic resonance images of anterior cruciate ligament-injured knees.

    PubMed

    Claes, Steven; Bartholomeeusen, Stijn; Bellemans, Johan

    2014-03-01

    The purpose of this study was to identify the newly described anterolateral ligament of the human knee on magnetic resonance imaging and to describe its eventual radiological abnormalities in anterior cruciate ligament-injured subjects. A retrospective cohort study on a series of consecutive subjects undergoing anterior cruciate ligament reconstructive surgery was performed. The MR images of 206 included knees were studied and the status of the anterolateral ligament status was judged to be either "non-visualized", "normal" or "abnormal". Of all the visualized anterolateral ligaments, 44 (21.3%) were considered uninjured, while 162 (78.8%) knees demonstrated radiological ALL abnormalities. The majority of ALL abnormalities were situated in the distal part of the ligament (77.8%). In conclusion, the anterolateral ligament can be identified on classic knee magnetic resonance images. Although anterior cruciate ligament injured subjects often demonstrated associated anterolateral ligament lesions, further research is needed in order to establish the clinical relevance of these highly frequent radiological abnormalities. PMID:24873084

  20. Classification Accuracy of Serum Apo A-I and S100B for the Diagnosis of Mild Traumatic Brain Injury and Prediction of Abnormal Initial Head Computed Tomography Scan

    PubMed Central

    Blyth, Brian J.; He, Hua; Mookerjee, Sohug; Jones, Courtney; Kiechle, Karin; Moynihan, Ryan; Wojcik, Susan M.; Grant, William D.; Secreti, LaLainia M.; Triner, Wayne; Moscati, Ronald; Leinhart, August; Ellis, George L.; Khan, Jawwad

    2013-01-01

    Abstract The objective of the current study was to determine the classification accuracy of serum S100B and apolipoprotein (apoA-I) for mild traumatic brain injury (mTBI) and abnormal initial head computed tomography (CT) scan, and to identify ethnic, racial, age, and sex variation in classification accuracy. We performed a prospective, multi-centered study of 787 patients with mTBI who presented to the emergency department within 6 h of injury and 467 controls who presented to the outpatient laboratory for routine blood work. Serum was analyzed for S100B and apoA-I. The outcomes were disease status (mTBI or control) and initial head CT scan. At cutoff values defined by 90% of controls, the specificity for mTBI using S100B (0.899 [95% confidence interval (CI): 0.78–0.92]) was similar to that using apoA-I (0.902 [0.87–0.93]), and the sensitivity using S100B (0.252 [0.22–0.28]) was similar to that using apoA-I (0.249 [0.22–0.28]). The area under the receiver operating characteristic curve (AUC) for the combination of S100B and apoA-I (0.738, 95% CI: 0.71, 0.77), however, was significantly higher than the AUC for S100B alone (0.709, 95% CI: 0.68, 0.74, p=0.001) and higher than the AUC for apoA-I alone (0.645, 95% CI: 0.61, 0.68, p<0.0001). The AUC for prediction of abnormal initial head CT scan using S100B was 0.694 (95%CI: 0.62, 0.77) and not significant for apoA-I. At a S100B cutoff of <0.060 μg/L, the sensitivity for abnormal head CT was 98%, and 22.9% of CT scans could have been avoided. There was significant age and race-related variation in the accuracy of S100B for the diagnosis of mTBI. The combined use of serum S100B and apoA-I maximizes classification accuracy for mTBI, but only S100B is needed to classify abnormal head CT scan. Because of significant subgroup variation in classification accuracy, age and race need to be considered when using S100B to classify subjects for mTBI. PMID:23758329

  1. Do Abnormal Serum Lipid Levels Increase the Risk of Chronic Low Back Pain? The Nord-Trøndelag Health Study

    PubMed Central

    Heuch, Ingrid; Heuch, Ivar; Hagen, Knut; Zwart, John-Anker

    2014-01-01

    Background Cross-sectional studies suggest associations between abnormal lipid levels and prevalence of low back pain (LBP), but it is not known if there is any causal relationship. Objective The objective was to determine, in a population-based prospective cohort study, whether there is any relation between levels of total cholesterol, high density lipoprotein (HDL) cholesterol and triglycerides and the probability of experiencing subsequent chronic (LBP), both among individuals with and without LBP at baseline. Methods Information was collected in the community-based HUNT 2 (1995–1997) and HUNT 3 (2006–2008) surveys of an entire Norwegian county. Participants were 10,151 women and 8731 men aged 30–69 years, not affected by chronic LBP at baseline, and 3902 women and 2666 men with LBP at baseline. Eleven years later the participants indicated whether they currently suffered from chronic LBP. Results Among women without LBP at baseline, HDL cholesterol levels were inversely associated and triglyceride levels positively associated with the risk of chronic LBP at end of follow-up in analyses adjusted for age only. Adjustment for the baseline factors education, work status, physical activity, smoking, blood pressure and in particular BMI largely removed these associations (RR: 0.96, 95% CI: 0.85–1.07 per mmol/l of HDL cholesterol; RR: 1.16, 95% CI: 0.94–1.42 per unit of lg(triglycerides)). Total cholesterol levels showed no associations. In women with LBP at baseline and men without LBP at baseline weaker relationships were observed. In men with LBP at baseline, an inverse association with HDL cholesterol remained after complete adjustment (RR: 0.83, 95% CI: 0.72–0.95 per mmol/l). Conclusion Crude associations between lipid levels and risk of subsequent LBP in individuals without current LBP are mainly caused by confounding with body mass. However, an association with low HDL levels may still remain in men who are already affected and possibly experience a

  2. Tea Dietary Fiber Improves Serum and Hepatic Lipid Profiles in Mice Fed a High Cholesterol Diet.

    PubMed

    Guo, Wenxin; Shu, Yang; Yang, Xiaoping

    2016-06-01

    Tea dietary fiber (TDF) was prepared from tea residues and modified to get cellulose-modified TDF (CTDF) by cellulase or micronized TDF (MTDF) by ultrafine grinding. The in vitro lipid-binding capacities of the three fibers and their effects on serum and hepatic lipid profiles in mice fed a high cholesterol diet were evaluated. The results showed that the three fibers had excellent lipid-binding capacities, and the cholesterol- and sodium cholate-binding capacities of CTDF and MTDF were significantly higher than those of TDF. Animal studies showed that, compared to model control, the three fibers significantly decreased mice average daily gain, gain: feed, and liver index, reduced total cholesterol (TC), triglyceride, and low density lipoprotein-cholesterol of serum and liver, increased serum and hepatic high density lipoprotein-cholesterol to TC ratio, and promoted the excretion of fecal lipids, and they also significantly increased the activities of superoxide dismutase and glutathione peroxidase of serum and liver, and decreased lipid peroxidation; moreover, the effects of CTDF and MTDF were better than that of TDF. It was concluded that the three fibers could improve serum and hepatic lipid profiles in mice fed a high cholesterol diet and the mechanism of action might be due to the promotion of fecal excretion of lipids through their lipid-binding ability and the inhibition of lipid peroxidation. These findings suggest that tea dietary fiber has the potential to be used as a functional ingredient to control cardiovascular disease. PMID:27040277

  3. Stable isotope dilution ultra-high performance liquid chromatography-tandem mass spectrometry quantitative profiling of tryptophan-related neuroactive substances in human serum and cerebrospinal fluid.

    PubMed

    Hényková, Eva; Vránová, Hana Přikrylová; Amakorová, Petra; Pospíšil, Tomáš; Žukauskaitė, Asta; Vlčková, Magdaléna; Urbánek, Lubor; Novák, Ondřej; Mareš, Jan; Kaňovský, Petr; Strnad, Miroslav

    2016-03-11

    Many compounds related to L-tryptophan (L-TRP) have interesting biological or pharmacological activity, and their abnormal neurotransmission seems to be linked to a wide range of neurodegenerative and psychiatric diseases. A high-throughput method based on ultra-high performance liquid chromatography connected to electrospray tandem mass spectrometry (UHPLC-ESI-MS/MS) was developed for the quantitative analysis of L-TRP and 16 of its metabolites in human serum and cerebrospinal fluid (CSF), representing both major and minor routes of L-TRP catabolism. The combination of a fast LC gradient with selective tandem mass spectrometry enabled accurate analysis of almost 100 samples in 24h. The standard isotope dilution method was used for quantitative determination. The method's lower limits of quantification for serum and cerebrospinal fluid ranged from 0.05 to 15nmol/L and 0.3 to 45nmol/L, respectively. Analytical recoveries ranged from 10.4 to 218.1% for serum and 22.1 to 370.0% for CSF. The method's accuracy ranged from 82.4 to 128.5% for serum matrix and 90.7 to 127.7% for CSF matrix. All intra- and inter-day coefficients of variation were below 15%. These results demonstrate that the new method is capable of quantifying endogenous serum and CSF levels of a heterogeneous group of compounds spanning a wide range of concentrations. The method was used to determine the physiological levels of target analytes in serum and CSF samples from 18 individuals, demonstrating its reliability and potential usefulness in large-scale epidemiological studies. PMID:26879452

  4. Determination of myoglobin in human serum by high-performance liquid chromatography with chemiluminescence detection.

    PubMed

    Maltsev, V G; Zimina, T M; Khvatov, A B; Belenkii, B G

    1987-04-24

    A highly sensitive method for the determination of myoglobin in serum is described, based on high-performance size-exclusion chromatography with chemiluminescence detection. Serum proteins are separated according to their molecular masses on columns packed with TSK-SW gel and those containing haem are detected selectively by post-column chemiluminescence reaction with luminol using a conventional fluorimetric detector. The method is rapid (30 min) and sufficiently sensitive for the diagnosis of myocardial infarction. The minimum detectable myoglobin concentration is 10 ng/ml. PMID:3597641

  5. High Goblet Cell Count Is Inversely Associated with Ploidy Abnormalities and Risk of Adenocarcinoma in Barrett’s Esophagus

    PubMed Central

    Sanchez, Carissa A.; Liu, Karen; Fong, Pui Yee; Li, Xiaohong; Cowan, David S.; Rabinovitch, Peter S.; Reid, Brian J.; Blount, Patricia L.

    2015-01-01

    Purpose Goblet cells may represent a potentially successful adaptive response to acid and bile by producing a thick mucous barrier that protects against cancer development in Barrett's esophagus (BE). The aim of this study was to determine the relationship between goblet cells (GC) and risk of progression to adenocarcinoma, and DNA content flow cytometric abnormalities, in BE patients. Experimental Design Baseline mucosal biopsies (N=2988) from 213 patients, 32 of whom developed cancer during the follow up period, enrolled in a prospective dynamic cohort of BE patients were scored in a blinded fashion, for the total number (#) of GC, mean # of GC/crypt (GC density), # of crypts with ≥ 1 GC, and the proportion of crypts with ≥1 GC, in both dysplastic and non-dysplastic epithelium separately. The relationship between these four GC parameters and DNA content flow cytometric abnormalities and adenocarcinoma outcome was compared, after adjustment for age, gender, and BE segment length. Results High GC parameters were inversely associated with DNA content flow cytometric abnormalities, such as aneuploidy, ploidy >2.7N, and an elevated 4N fraction > 6%, and with risk of adenocarcinoma. However, a Kaplan-Meier analysis showed that the total # of GC and the total # crypts with ≥1 GC were the only significant GC parameters (p<0.001 and 0.003, respectively). Conclusions The results of this study show, for the first time, an inverse relationship between high GC counts and flow cytometric abnormalities and risk of adenocarcinoma in BE. Further studies are needed to determine if GC depleted foci within esophageal columnar mucosa are more prone to neoplastic progression or whether loss of GC occurs secondary to underlying genetic abnormalities. PMID:26230607

  6. An evaluation of serum high density lipoproteins-phospholipids.

    PubMed

    Ide, H; Tsuji, M; Shimada, M; Kondo, T; Fujiya, S; Asanuma, Y; Agishi, Y

    1988-07-01

    Phospholipids in high density lipoproteins (HDL) is being used as a negative risk indicator of atherosclerosis. Phospholipids in HDL may not demonstrate the actual level of HDL-phospholipids when determined by the precipitation or ultracentrifugal methods, because HDL fractions contain very high density lipoproteins (VHDL) and albumin. In the present study, the true level of phospholipids in HDL was estimated using high performance liquid chromatography (HPLC), and it was compared with the level of phospholipids in HDL determined by the precipitation method. Sera from 18 healthy subjects were used as materials. In the HPLC method, the HDL fraction was extracted making sure that it contained no free albumin, which is albumin not bound to phospholipids. The HDL fraction was separated into subfractions. It was found that phospholipids in the VHDL fraction make a 20.2 +/- 7.3% (mean +/- S.D.) part of the total HDL-phospholipids. A large part of the VHDL fraction was constituted of albumin-bound phospholipids. A significant correlation was observed between HDL-phospholipids determined by the precipitation method, which contain albumin, and the actual HDL fraction phospholipids determined by HPLC, which do not contain VHDL (r = 0.903, p less than 0.01). These results suggest that HDL-phospholipids values determined by the precipitation method give useful clinical data. PMID:3176021

  7. Gastric Cancer with a Very High Serum CA 19-9 Level.

    PubMed

    Kato, Kazuya; Taniguchi, Masahiko; Kawakami, Takako; Nagase, Atsushi; Matsuda, Minoru; Onodea, Kazuhiko; Yamaguchi, Hidenori; Higuchi, Mineko; Furukawa, Hiroyuki

    2011-01-01

    Carbohydrate antigen 19-9 (CA 19-9) is a sensitive marker for pancreatic and hepatobiliary malignancies. The highest frequency of elevated serum CA 19-9 levels is found among patients with pancreatic cancer. CA 19-9 has recently been demonstrated to be a marker of digestive tract malignancies. We report the case of a patient with a gastric cancer and a very high serum CA 19-9 level. During laparotomy, a large mass was found in the antrum. A distal gastrectomy with D2 dissection of the lymph nodes was performed. Histological examination, including immunohistochemistry, revealed an adenocarcinoma of the stomach producing CA 19-9. To the best of our knowledge, no patient with an extremely high serum CA 19-9 level resulting from a gastric adenocarcinoma has been reported previously. PMID:21577374

  8. CHARACTERIZATION OF DRUG INTERACTIONS WITH SERUM PROTEINS BY USING HIGH-PERFORMANCE AFFINITY CHROMATOGRAPHY

    PubMed Central

    Hage, David S.; Anguizola, Jeanethe; Barnaby, Omar; Jackson, Abby; Yoo, Michelle J.; Papastavros, Efthimia; Pfaunmiller, Erika; Sobansky, Matt; Tong, Zenghan

    2011-01-01

    The binding of drugs with serum proteins can affect the activity, distribution, rate of excretion, and toxicity of pharmaceutical agents in the body. One tool that can be used to quickly analyze and characterize these interactions is high-performance affinity chromatography (HPAC). This review shows how HPAC can be used to study drug-protein binding and describes the various applications of this approach when examining drug interactions with serum proteins. Methods for determining binding constants, characterizing binding sites, examining drug-drug interactions, and studying drug-protein dissociation rates will be discussed. Applications that illustrate the use of HPAC with serum binding agents such as human serum albumin, α1-acid glycoprotein, and lipoproteins will be presented. Recent developments will also be examined, such as new methods for immobilizing serum proteins in HPAC columns, the utilization of HPAC as a tool in personalized medicine, and HPAC methods for the high-throughput screening and characterization of drug-protein binding. PMID:21395530

  9. Ameliorative effects of boron on serum profile in buffalo (Bubalus bubalis) fed high fluoride ration.

    PubMed

    Bharti, Vijay K; Gupta, Meenakshi; Lall, D

    2008-02-01

    An experiment was undertaken to evaluate the protective role of boron on the serum profile of buffalo calves fed a high fluoride ration. Twelve male Murrah buffalo (Bubalus bubalis) calves of 6-8 months age, divided into three groups of four calves in each, were fed basal diets and supplemented with sodium fluoride (NaF, 60 ppm) alone or in combination with borax (Na2B4O7.10H2O, 140 ppm) for 90 days. Boron (B) was added in the ration as borax to make @140 ppm boron (elemental B) on DM basis in treatment II. Dietary F caused a significant (p<0.05) depressing effect on serum Ca and Zn on day 90 which was improved with B supplementation. However, serum Fe and Cu did not show any significant change on F or F+B supplementation. The serum ALP and phosphorus level were increased significantly (p<0.05) on F feeding but declined significantly (p<0.05) when B was fed. The findings suggested beneficial effect of boron on serum minerals and ALP in buffalo calves fed high fluoride ration. PMID:18422253

  10. Microfluidic system for high-throughput immunoglobulin-E analysis from clinical serum samples.

    PubMed

    Zheng, Lulu; Fu, Yongfeng; Jiang, Xiran; Man, Suqin; Ran, Wei; Feng, Meng; Liu, Sixiu; Cheng, Xunjia; Sui, Guodong

    2015-10-01

    Rapid and high-throughput analytical techniques for IgE that requires a small serum amount are very important, especially for pediatric patients. In these patients, blood is collected from veins, which is painful compared to fingertip blood collection. Herein, a novel microfluidic system capable of high-throughput parallel analyses of allergen-specific IgE from small amounts of patient serum was successfully developed. A six-plex immunoassay was constructed within a microfluidic chip, and the entire system was validated using samples from clinical patients. Major antigens from house dust mite (Dermatophagoides farinae and Blomia tropicalis), cat (Felis domesticus), fungus (Cladosporium herbarum), ragweed (Humulus japonicas), and tree pollen (Platanus acerifolia) were used as analysis targets. Sample consumption decreased to <0.05 µL compared with the 480µL serum consumption by fluoroenzyme immunoassay (UniCAP system Pharmacia Diagnostics AB, Uppsala, Sweden), the 50 µL serum consumption by enzyme-linked immune sorbent assay (ELISA), or the 1.5 µL serum consumption by conventional protein chip analysis. Analysis duration, reagent cost, and total cost for each measurement were also considerably decreased. The assay showed good accuracy and sensitivity toward the clinical samples. A significant correlation of allergen-specific IgE levels was found among the microfluidic assay, UniCAP system, and ELISA. PMID:26078132

  11. Serum amyloid A changes high density lipoprotein's cellular affinity. A clue to serum amyloid A's principal function.

    PubMed

    Kisilevsky, R; Subrahmanyan, L

    1992-06-01

    The affinity of high density lipoproteins (HDL), or HDL carrying serum amyloid A (HDL/SAA), for hepatocytes or peritoneal macrophages was examined, as part of an investigation exploring the principal function of SAA and how this may be related to amyloidogenesis. The binding results in conjunction with SAA's existence primarily on HDL during inflammation, and HDL's known "reverse cholesterol transport" function suggest a clear role for SAA in the afferent arm of the reverse cholesterol transport pathway during the process of inflammation. The presence of SAA reduced HDL's affinity for normal hepatocytes by a factor of 2. In contrast, HDL/SAA had a 3- to 4-fold higher affinity for macrophages than HDL alone. Furthermore, the number of binding sites for HDL/SAA increased on macrophages during inflammation, while decreasing on hepatocytes. The net effect was a significant shift in HDL cholesterol carrying capacity towards the macrophage. Competition experiments demonstrated that HDL/SAA is only half as effective as HDL in inhibiting radiolabeled HDL binding to macrophages. This is in keeping with the reduced apolipoprotein A-1 content in HDL/SAA. Strikingly, although HDL contains twice as much apolipoprotein A-1 as HDL/SAA, it is only one-tenth as effective as HDL/SAA in inhibiting radiolabeled HDL/SAA binding to macrophages. The latter results suggest that there is a specific SAA binding site on macrophages. PMID:1602745

  12. Meiotic abnormalities

    SciTech Connect

    1993-12-31

    Chapter 19, describes meiotic abnormalities. These include nondisjunction of autosomes and sex chromosomes, genetic and environmental causes of nondisjunction, misdivision of the centromere, chromosomally abnormal human sperm, male infertility, parental age, and origin of diploid gametes. 57 refs., 2 figs., 1 tab.

  13. Furosemide Pharmacokinetics in Adult Rats become Abnormal with an Adverse Intrauterine Environment and Modulated by a Post-Weaning High-Fat Diet.

    PubMed

    DuBois, Barent N; Pearson, Jacob; Mahmood, Tahir; Thornburg, Kent; Cherala, Ganesh

    2016-06-01

    Adult individuals born with intrauterine growth restriction (IUGR) have physiological maladaptations that significantly increase risk of chronic disease. We suggested that such abnormalities in organ function would alter pharmacokinetics throughout life, exacerbated by environmental mismatch. Pregnant and lactating rats were fed either a purified control diet (18% protein) or low-protein diet (9% protein) to produce IUGR offspring. Offspring were weaned onto either laboratory chow (11% fat) or high-fat diet (45% fat). Adult offspring (5 months old) were dosed with furosemide (10 mg/kg i.p.) and serum and urine collected. The overall exposure profile in IUGR males was significantly reduced due to a ~35% increase in both clearance and volume of distribution. Females appeared resistant to the IUGR phenotype. The effects of the high-fat diet trended in the opposite direction to that of IUGR, with increased drug exposure due to decreases in both clearance (31% males, 46% females) and volume of distribution (24% males, 44% females), with a 10% longer half-life in both genders. The alterations in furosemide pharmacokinetics and pharmacodynamics were explained by changes in the expression of renal organic anion transporters 1 and 3, and sodium-potassium-chloride cotransporter-2. In summary, this study suggests that IUGR and diet interact to produce subpopulations with similar body-weights but dissimilar pharmacokinetic profiles; this underlines the limitation of one-size-fits-all dosing which does not account for physiological differences in body composition resulting from IUGR and diet. PMID:26550796

  14. Inversion of the western Pacific subtropical high dynamic model and analysis of dynamic characteristics for its abnormality

    NASA Astrophysics Data System (ADS)

    Hong, M.; Zhang, R.; Li, J. X.; Ge, J. J.; Liu, K. F.

    2013-02-01

    Based on time series data of 500 hPa potential field from NCEP/NCAR (National Center for Environmental Forecast of American/National Center for Atmospheric Research), a novel consideration of empirical orthogonal function (EOF) time-space separation and dynamic system reconstruction for time series is introduced. This method consists of two parts: first, the dynamical model inversion and model parameter optimization are carried out on the EOF time coefficient series using the genetic algorithm (GA), and, second, a nonlinear dynamic model representing the subtropical high (SH) activity and its abnormality is established. The SH activity and its abnormal mechanism is studied using the developed dynamical model. Results show that the configuration and diversification of the SH equilibriums have good correspondence with the actual short-medium term abnormal activity of the SH. Change of SH potential field brought by the combination of equilibriums is more complex than that by mutation, and their exhibition patterns are different. The mutation behavior from high-value to low-value equilibriums of the SH in summer corresponds with the southward drop of the SH in the observed weather process. The combination behavior of the two steady equilibriums corresponds with disappearance of the "double-ridge" phenomenon of the SH. Dynamical mechanisms of these phenomena are explained.

  15. High consumption of pulses is associated with lower risk of abnormal glucose metabolism in women in Mauritius

    PubMed Central

    Wennberg, M.; Söderberg, S.; Uusitalo, U.; Tuomilehto, J.; Shaw, J. E.; Zimmet, P. Z.; Kowlessur, S.; Pauvaday, V.; Magliano, D. J.

    2014-01-01

    Aims To investigate if consumption of pulses was associated with a reduced risk of developing abnormal glucose metabolism, increases in body weight and increases in waist circumference in a multi-ethnic cohort in Mauritius. Methods Population-based surveys were performed in Mauritius in 1992 and in 1998. Pulse consumption was estimated from a food frequency questionnaire in 1992 and outcomes were measured in 1998. At both time points, anthropometry was undertaken and an oral glucose tolerance test was performed. Results Mauritian women with the highest consumption of pulses (highest tertile) had a reduced risk of developing abnormal glucose metabolism [odds ratio 0.52; 95% CI 0.27, 0.99) compared with those with the lowest consumption, and also after multivariable adjustments. In women, a high consumption of pulses was associated with a smaller increase in BMI. Conclusions High consumption of pulses was associated with a reduced risk of abnormal glucose metabolism and a smaller increase in BMI in Mauritian women. Promotion of pulse consumption could be an important dietary intervention for the prevention of Type 2 diabetes and obesity in Mauritius and should be examined in other populations and in clinical trials. PMID:25346062

  16. High prevalence of cardiovascular and respiratory abnormalities in advanced, intensively treated (transplanted) myeloma: The case for ‘late effects’ screening and preventive strategies

    PubMed Central

    Samuelson, Clare; O'Toole, Laurence; Boland, Elaine; Greenfield, Diana; Ezaydi, Yousef; Ahmedzai, Sam H.; Snowden, John A.

    2016-01-01

    Objectives: Modern management of myeloma has significantly improved survival, with increasing numbers of patients living beyond a decade. However, little is known about the long-term cardiovascular and respiratory status of intensively treated and multiply relapsed survivors. Methods: We performed detailed cardiovascular and respiratory evaluations in patients with intensively treated, advanced but stable myeloma. All patients had received at least two lines of treatment, including at least one haematopoietic stem cell transplantation procedure, but had stable, controlled disease and were off active treatment at the time of evaluation. Results: Thirty-two patients with a median duration of 6 years (range 2–12) from original diagnosis of myeloma and three lines (range 2–6) of treatment were evaluated. Despite normal physical examination in the majority, there was a high prevalence of sub-clinical cardiac and respiratory dysfunction, reflected by abnormalities of electrocardiography (45%), echocardiography (50%), serum N-terminal pro-B-type natriuretic peptide level (NT-pro-BNP, 50%), and pulmonary function testing (45%). NT-pro-BNP level correlated negatively with quality of life (P = 0.012) and positively with serum ferritin (P = 0.027). Dyspnoea score correlated with BMI (P = 0.001). Risk factors for cardiovascular disease (obesity, hypertension, hyperlipidaemia, and hyperinsulinaemia) were common. Discussion: Even in the absence of overt clinical features, the majority of intensively treated long-term survivors of myeloma have established cardiovascular and/or respiratory dysfunction, above levels expected in the general population of a similar age. Conclusion: This study supports routine screening and lifestyle modification combined with primary and secondary preventive strategies to reduce cardiovascular and respiratory disease and to preserve quality of life in transplanted myeloma patients. PMID:27077780

  17. Heterogenetiy of glucocorticoid binders: a high affinity triamcinolone acetonide binder in bovine serum.

    PubMed

    Do, Y; Feldman, D

    1980-11-01

    While investigating glucocorticoid-binding proteins in bovine tissues, a new binder was found in fresh bovine serum which exhibited high affinity for certain synthetic glucocorticoids. This serum binder was characterized using [3H]triamcinolone acetonide (TA) as the ligand. On sucrose gradients, the [3H]TA peak sedimented at 8S, which was easily distinguishable from the [3H]cortisol-transcortin peak at 4S. Unlike the tissue receptor, which showed ionically dependent transformation from 8S in equilibrium or formed from 4S, the serum binder sedimented at 8S in both hypo- and hypertonic gradients. Binding properties were evaluated employing sephadex G-50 chromatography to separate bound from free steroid. Scatchard analysis of specific [3H]TA binding data revealed a straight line. The apparent equilibrium dissociation constant (Kd) was 7.8 +/- 0.7 X 10(-8) M, and the binding capacity was 772 +/- 70 fmol/mg serum protein. Hormonal specificity was determined by a competitive binding assay and revealed the following sequence: TA (100%) > betamethasone (47%) > triamcinolone (33%) > dexamethasone (2%) = cortisol = progesterone; aldosterone, estradiol, and testosterone exhibited negligible competitive activity. The serum binder was very stable, withstanding heating to 37 C for 60 min and long term storage in the frozen state. However, binding was significantly destroyed by trypsin. The binder was absent from fresh samples of chicken, mouse, rat, rabbit, dog, monkey, and human sera and frozen horse and porcine sera, but was clearly present in commercially available frozen calf, fetal calf, and lamb sera. At this time, we are unable to define the function of this binder, although its existence in both ovine and bovine sera suggests a possible role in ruminants. However, since bovine serum is routinely employed in tissue culture studies, the presence of this glucocorticoid binder might significantly influence many experiments. PMID:6775927

  18. Abnormally Low or High Ankle-Brachial Index Is Associated with Proliferative Diabetic Retinopathy in Type 2 Diabetic Mellitus Patients

    PubMed Central

    Chen, Szu-Chia; Hsiao, Pi-Jung; Huang, Jiun-Chi; Lin, Kun-Der; Hsu, Wei-Hao; Lee, Yu-Li; Lee, Mei-Yueh; Chang, Jer-Ming; Shin, Shyi–Jang

    2015-01-01

    Although some studies have reported that low ankle-brachial index (ABI) is associated with diabetic retinopathy (DR) in diabetic patients, it remains controversial as to which stage of DR. The aim of this study is to assess whether peripheral artery disease (PAD), indicated by abnormally low or high ABI, is associated with different stages of DR in patients with type 2 diabetes mellitus (DM), and further evaluate the risk factors. A total of 2001 (858 men and 1143 women) patients with type 2 DM who underwent ABI measurement in an outpatient clinic were enrolled. PAD was defined as ABI < 0.9 or ≧ 1.3 in either leg. DR was classified as non-DR, nonproliferative DR and proliferative DR stages. The clinical data were analyzed and the risk factors for abnormal ABI were determined by multivariate logistic regression analysis. The prevalence of ABI < 0.9 or ≧ 1.3 was 3.0%. Multivariate forward logistic regression analysis identified proliferative DR (vs. non-DR) was associated with abnormal ABI (odds ratio, 1.718; 95% confidence interval, 1.152 to 2.562; p = 0.008), but nonproliferative DR was not. Furthermore, the presence of coronary artery disease, cerebrovascular disease, declining renal function and patients without diuretics use were associated with abnormal ABI in patients with proliferative DR. Our study in patients of type 2 DM demonstrated that PAD was associated with proliferative DR. We emphasize the recommendation of performing the ABI test in this population at risk. PMID:26230390

  19. Congenital Abnormalities

    MedlinePlus

    ... serious health problems (e.g. Down syndrome ). Single-Gene Abnormalities Sometimes the chromosomes are normal in number, ... blood flow to the fetus impair fetal growth. Alcohol consumption and certain drugs during pregnancy significantly increase ...

  20. Craniofacial Abnormalities

    MedlinePlus

    ... of the skull and face. Craniofacial abnormalities are birth defects of the face or head. Some, like cleft ... palate, are among the most common of all birth defects. Others are very rare. Most of them affect ...

  1. Walking abnormalities

    MedlinePlus

    ... include: Arthritis of the leg or foot joints Conversion disorder (a psychological disorder) Foot problems (such as a ... injuries. For an abnormal gait that occurs with conversion disorder, counseling and support from family members are strongly ...

  2. Chromosome Abnormalities

    MedlinePlus

    ... decade, newer techniques have been developed that allow scientists and doctors to screen for chromosomal abnormalities without using a microscope. These newer methods compare the patient's DNA to a normal DNA ...

  3. Nail abnormalities

    MedlinePlus

    Nail abnormalities are problems with the color, shape, texture, or thickness of the fingernails or toenails. ... Fungus or yeast cause changes in the color, texture, and shape of the nails. Bacterial infection may ...

  4. HIGH SERUM PCBs ARE ASSOCIATED WITH ELEVATION OF SERUM LIPIDS AND CARDIOVASCULAR DISEASE IN A NATIVE AMERICAN POPULATION

    PubMed Central

    Goncharov, Alexey; Haase, Richard F.; Santiago-Rivera, Azara; Morse, Gayle; McCaffrey, Robert J.; Rej, Robert; Carpenter, David O.

    2008-01-01

    We have investigated the relationships among the concentration of total serum polychlorinated biphenyls (PCBs), various PCB congener groupings, and three pesticides to total serum lipids in humans with and without self-reported cardiovascular disease. Blood samples were obtained from 335 adult Akwesasne Mohawks, and were analyzed for 101 PCB congeners, mirex, DDE, and hexachlorobenzene (HCB), as well as serum triglycerides and cholesterol. Structural equation modeling, following the definition of latent variables by means of confirmatory factor analysis, was used to analyze the relationships between serum lipids with PCBs and heart disease. There were significant associations among PCBs, lipids, age, and body mass index (BMI), a fact which justified the application of the structural equation model. Gender of the participant was unrelated to any of the remaining study variables. The results of this study are consistent with a model in which age is considered as both an exogenous explanatory variable and a biological driving mechanism for the acquisition of PCBs. Moreover, the results of this study are consistent with the conclusion that PCBs, acting through P450 enzymes, are directly responsible for increased synthesis of cholesterol and triglycerides, substances known to be major risk factors for cardiovascular disease. PMID:18054906

  5. High-throughput assay for measuring monoclonal antibody self-association and aggregation in serum.

    PubMed

    Li, Xiaoning; Geng, Steven B; Chiu, Mark L; Saro, Dorina; Tessier, Peter M

    2015-03-18

    Subcutaneous delivery is one of the preferred administration routes for therapeutic monoclonal antibodies (mAbs). High antibody dosing requirements and small injection volumes necessitate formulation and delivery of highly concentrated mAb solutions. Such elevated antibody concentrations can lead to undesirable solution behaviors such as mAb self-association and aggregation, which are relatively straightforward to detect using various biophysical methods because of the high purity and concentration of antibody formulations. However, the biophysical properties of mAbs in serum can also impact antibody activity, but these properties are less well understood because of the difficulty characterizing mAbs in such a complex environment. Here we report a high-throughput assay for directly evaluating mAb self-association and aggregation in serum. Our approach involves immobilizing polyclonal antibodies specific for human mAbs on gold nanoparticles, and then using these conjugates to capture human antibodies at a range of subsaturating to saturating mAb concentrations in serum. Antibody aggregation is detected at subsaturating mAb concentrations via blue-shifted plasmon wavelengths due to the reduced efficiency of capturing mAb aggregates relative to monomers, which reduces affinity cross-capture of mAbs by multiple conjugates. In contrast, antibody self-association is detected at saturating mAb concentrations via red-shifted plasmon wavelengths due to attractive interparticle interactions between immobilized mAbs. The high-throughput nature of this assay along with its compatibility with unusually dilute mAb solutions (0.1-10 μg per mL) should make it useful for identifying antibody candidates with high serum stability during early antibody discovery. PMID:25714504

  6. Proteomics tools reveal startlingly high amounts of oxytocin in plasma and serum.

    PubMed

    Brandtzaeg, Ole Kristian; Johnsen, Elin; Roberg-Larsen, Hanne; Seip, Knut Fredrik; MacLean, Evan L; Gesquiere, Laurence R; Leknes, Siri; Lundanes, Elsa; Wilson, Steven Ray

    2016-01-01

    The neuropeptide oxytocin (OT) is associated with a plethora of social behaviors, and is a key topic at the intersection of psychology and biology. However, tools for measuring OT are still not fully developed. We describe a robust nano liquid chromatography-mass spectrometry (nanoLC-MS) platform for measuring the total amount of OT in human plasma/serum. OT binds strongly to plasma proteins, but a reduction/alkylation (R/A) procedure breaks this bond, enabling ample detection of total OT. The method (R/A + robust nanoLC-MS) was used to determine total OT plasma/serum levels to startlingly high concentrations (high pg/mL-ng/mL). Similar results were obtained when combining R/A and ELISA. Compared to measuring free OT, measuring total OT can have advantages in e.g. biomarker studies. PMID:27528413

  7. Proteomics tools reveal startlingly high amounts of oxytocin in plasma and serum

    PubMed Central

    Brandtzaeg, Ole Kristian; Johnsen, Elin; Roberg-Larsen, Hanne; Seip, Knut Fredrik; MacLean, Evan L.; Gesquiere, Laurence R.; Leknes, Siri; Lundanes, Elsa; Wilson, Steven Ray

    2016-01-01

    The neuropeptide oxytocin (OT) is associated with a plethora of social behaviors, and is a key topic at the intersection of psychology and biology. However, tools for measuring OT are still not fully developed. We describe a robust nano liquid chromatography-mass spectrometry (nanoLC-MS) platform for measuring the total amount of OT in human plasma/serum. OT binds strongly to plasma proteins, but a reduction/alkylation (R/A) procedure breaks this bond, enabling ample detection of total OT. The method (R/A + robust nanoLC-MS) was used to determine total OT plasma/serum levels to startlingly high concentrations (high pg/mL-ng/mL). Similar results were obtained when combining R/A and ELISA. Compared to measuring free OT, measuring total OT can have advantages in e.g. biomarker studies. PMID:27528413

  8. High VEGF serum values are associated with locoregional spread of gastroenteropancreatic neuroendocrine tumors (GEP-NETs).

    PubMed

    Cigrovski Berković, Maja; Čačev, Tamara; Catela Ivković, Tina; Marout, Jasminka; Ulamec, Monika; Zjačić-Rotkvić, Vanja; Kapitanović, Sanja

    2016-04-15

    Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are highly vascularized neoplasms, capable of synthethisizing VEGF-A, a key mediator of angiogenesis. In pancreatic neuroendocrine tumors (pNETs) VEGF expression is higher in benign and low-grade tumors and associated with good prognosis (neuroendocrine paradox) while the VEGF role in gastrointestinal NETs (GI-NETs) is still unclear. In this study, we examined the VEGF-1154A/G polymorphism in 145 GEP-NET patients and 150 controls. Next, we measured VEGF serum levels and VEGF tumor protein expression, comparing it with Ki67 and tumor grade. Patients' VEGF serum levels were compared with VEGF -1145A/G genotypes and metastatic status as well as with chromogranin A (CgA) and 5-hydroxyindolacetic acid (5-HIAA) in case of GI-NET patients. In this study GEP-NET patients had elevated VEGF serum values when compared to healthy controls (p = 0.0013). VEGF-1145G allele correlated with higher VEGF serum levels (p = 0.002). Patients with metastatic tumors had higher VEGF serum values when compared to patients without metastases (p = 0.033), and highest levels were observed in case of lymph node metastases (p = 0.008). VEGF-1145G allele was more frequent in non-functional GI-NET patients than in healthy controls (p = 0.041). CgA was superior to VEGF in tumor detection, while VEGF was superior to 5-HIAA. A correlation was observed between VEGF immunohistochemical staining and Ki-67 (p = 0.028). Tumours with weaker VEGF protein expression were more aggressive than tumours with stronger VEGF expression, confirming a "neuroendocrine paradox" in GI-NETs. Our results suggest the role of VEGF in GI-NETs locoregional spread. PMID:26805636

  9. High Serum Irisin Level as an Independent Predictor of Diabetes Mellitus

    PubMed Central

    Huh, Ji Hye; Ahn, Song Vogue; Choi, Jung Hye; Koh, Sang Baek; Chung, Choon Hee

    2016-01-01

    Abstract Irisin, a novel exercise-induced myokine, has been suggested to regulate energy homeostasis and insulin sensitivity. However, it remains unclear whether circulating irisin plays a role in the development of DM in human. We investigated the possible association between circulating irisin levels and incident DM in a 2.6-year longitudinal study of a population-based cohort comprised of rural Korean subjects. We conducted a longitudinal study within the Korean Genome and Epidemiology Study on Atherosclerosis Risk of Rural Areas in the Korean General Population (KoGES-ARIRANG) study from November 2005 to January 2008. Cases (n=85) were patients with incident DM during the follow-up period and controls (n = 85) were matched to incident DM cases based on sex and age at baseline. The relative risk of serum irisin/adiponectin level for incident DM was analyzed using conditional logistic regression analysis. Baseline irisin_ENREF_1 levels were significantly higher in subjects who developed DM than in subjects who did not. The serum irisin level was positively associated with glycated hemoglobin (HbA1c) and postprandial glucose. Irisin was negatively associated with adiponectin (R = –0.189, P = 0.014). After adjustment for potential confounders, including body mass index, the odds ratios [95% confidence intervals] for incident DM increased in a graded manner as the serum irisin level increased (Quartile 1 vs Quartile 2 vs Quartile 3 vs Quartile 4 = 1 vs 0.80 [0.28–2.35] vs 3.33 [1.11–10.00] vs 4.10 [1.35–12.44], respectively), whereas the odds ratios for incident DM decreased in a graded manner as the serum adiponectin level increased. High serum irisin was independently associated with the development of DM, indicating that irisin may be a useful predictor of DM in Korean adults. PMID:27281072

  10. A biosensor of high-density lipoprotein of human serum on a liquid crystal and polymer composite film

    NASA Astrophysics Data System (ADS)

    Lin, Yi-Hsin; Chang, Kai-Han; Chu, Wei-Lin; Tsou, Yu-Shih; Wu, Li-Ching; Li, Chien-Feng

    2013-10-01

    A biosensor for the concentration of high-density lipoprotein (HDL) in human serum on a liquid crystal and polymer composite film (LCPCF) is demonstrated. The sensing mechanism is based on a polar-polar interaction between orientation of LC directors and HDL in human serum. The concentration of polar HDL in human serum affects the orientations of LC directors at the interface between LCPCF and the human serum. In addition, the surface free energy of LCPCF changes with the applied voltage due to the electrically tunable orientations of LC directors anchored among the polymer grains of LCPCF. As a result, the droplet motion of human serum on LCPCF under applied voltages can sense the concentration of HDL in human serum.

  11. Mapping of Genetic Abnormalities of Primary Tumours from Metastatic CRC by High-Resolution SNP Arrays

    PubMed Central

    Sayagués, José María; Fontanillo, Celia; Abad, María del Mar; González-González, María; Sarasquete, María Eugenia; del Carmen Chillon, Maria; Garcia, Eva; Bengoechea, Oscar; Fonseca, Emilio; Gonzalez-Diaz, Marcos; De Las Rivas, Javier

    2010-01-01

    Background For years, the genetics of metastatic colorectal cancer (CRC) have been studied using a variety of techniques. However, most of the approaches employed so far have a relatively limited resolution which hampers detailed characterization of the common recurrent chromosomal breakpoints as well as the identification of small regions carrying genetic changes and the genes involved in them. Methodology/Principal Findings Here we applied 500K SNP arrays to map the most common chromosomal lesions present at diagnosis in a series of 23 primary tumours from sporadic CRC patients who had developed liver metastasis. Overall our results confirm that the genetic profile of metastatic CRC is defined by imbalanced gains of chromosomes 7, 8q, 11q, 13q, 20q and X together with losses of the 1p, 8p, 17p and 18q chromosome regions. In addition, SNP-array studies allowed the identification of small (<1.3 Mb) and extensive/large (>1.5 Mb) altered DNA sequences, many of which contain cancer genes known to be involved in CRC and the metastatic process. Detailed characterization of the breakpoint regions for the altered chromosomes showed four recurrent breakpoints at chromosomes 1p12, 8p12, 17p11.2 and 20p12.1; interestingly, the most frequently observed recurrent chromosomal breakpoint was localized at 17p11.2 and systematically targeted the FAM27L gene, whose role in CRC deserves further investigations. Conclusions/Significance In summary, in the present study we provide a detailed map of the genetic abnormalities of primary tumours from metastatic CRC patients, which confirm and extend on previous observations as regards the identification of genes potentially involved in development of CRC and the metastatic process. PMID:21060790

  12. High quality topic extraction from business news explains abnormal financial market volatility.

    PubMed

    Hisano, Ryohei; Sornette, Didier; Mizuno, Takayuki; Ohnishi, Takaaki; Watanabe, Tsutomu

    2013-01-01

    Understanding the mutual relationships between information flows and social activity in society today is one of the cornerstones of the social sciences. In financial economics, the key issue in this regard is understanding and quantifying how news of all possible types (geopolitical, environmental, social, financial, economic, etc.) affects trading and the pricing of firms in organized stock markets. In this article, we seek to address this issue by performing an analysis of more than 24 million news records provided by Thompson Reuters and of their relationship with trading activity for 206 major stocks in the S&P US stock index. We show that the whole landscape of news that affects stock price movements can be automatically summarized via simple regularized regressions between trading activity and news information pieces decomposed, with the help of simple topic modeling techniques, into their "thematic" features. Using these methods, we are able to estimate and quantify the impacts of news on trading. We introduce network-based visualization techniques to represent the whole landscape of news information associated with a basket of stocks. The examination of the words that are representative of the topic distributions confirms that our method is able to extract the significant pieces of information influencing the stock market. Our results show that one of the most puzzling stylized facts in financial economies, namely that at certain times trading volumes appear to be "abnormally large," can be partially explained by the flow of news. In this sense, our results prove that there is no "excess trading," when restricting to times when news is genuinely novel and provides relevant financial information. PMID:23762258

  13. High Quality Topic Extraction from Business News Explains Abnormal Financial Market Volatility

    PubMed Central

    Hisano, Ryohei; Sornette, Didier; Mizuno, Takayuki; Ohnishi, Takaaki; Watanabe, Tsutomu

    2013-01-01

    Understanding the mutual relationships between information flows and social activity in society today is one of the cornerstones of the social sciences. In financial economics, the key issue in this regard is understanding and quantifying how news of all possible types (geopolitical, environmental, social, financial, economic, etc.) affects trading and the pricing of firms in organized stock markets. In this article, we seek to address this issue by performing an analysis of more than 24 million news records provided by Thompson Reuters and of their relationship with trading activity for 206 major stocks in the S&P US stock index. We show that the whole landscape of news that affects stock price movements can be automatically summarized via simple regularized regressions between trading activity and news information pieces decomposed, with the help of simple topic modeling techniques, into their “thematic” features. Using these methods, we are able to estimate and quantify the impacts of news on trading. We introduce network-based visualization techniques to represent the whole landscape of news information associated with a basket of stocks. The examination of the words that are representative of the topic distributions confirms that our method is able to extract the significant pieces of information influencing the stock market. Our results show that one of the most puzzling stylized facts in financial economies, namely that at certain times trading volumes appear to be “abnormally large,” can be partially explained by the flow of news. In this sense, our results prove that there is no “excess trading,” when restricting to times when news is genuinely novel and provides relevant financial information. PMID:23762258

  14. Serum biomarker profile associated with high bone turnover and BMD in postmenopausal women.

    PubMed

    Bhattacharyya, Sudeepa; Siegel, Eric R; Achenbach, Sara J; Khosla, Sundeep; Suva, Larry J

    2008-07-01

    Early diagnosis of the onset of osteoporosis is key to the delivery of effective therapy. Biochemical markers of bone turnover provide a means of evaluating skeletal dynamics that complements static measurements of BMD by DXA. Conventional clinical measurements of bone turnover, primarily the estimation of collagen and its breakdown products in the blood or urine, lack both sensitivity and specificity as a reliable diagnostic tool. As a result, improved tests are needed to augment the use of BMD measurements as the principle diagnostic modality. In this study, the serum proteome of 58 postmenopausal women with high or low/normal bone turnover (training set) was analyzed by surface enhanced laser-desorption/ionization time-of-flight mass spectrometry, and a diagnostic fingerprint was identified using a variety of statistical and machine learning tools. The diagnostic fingerprint was validated in a separate distinct test set, consisting of serum samples from an additional 59 postmenopausal women obtained from the same Mayo cohort, with a gap of 2 yr. Specific protein peaks that discriminate between postmenopausal patients with high or low/normal bone turnover were identified and validated. Multiple supervised learning approaches were able to classify the level of bone turnover in the training set with 80% sensitivity and 100% specificity. In addition, the individual protein peaks were also significantly correlated with BMD measurements in these patients. Four of the major discriminatory peaks in the diagnostic profile were identified as fragments of interalpha-trypsin-inhibitor heavy chain H4 precursor (ITIH4), a plasma kallikrein-sensitive glycoprotein that is a component of the host response system. These data suggest that these serum protein fragments are the serum-borne reflection of the increased osteoclast activity, leading to the increased bone turnover that is associated with decreasing BMD and presumably an increased risk of fracture. In conjunction with the

  15. High concentrations of haptocorrin interfere with routine measurement of cobalamins in human serum and milk. A problem and its solution.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Human milk and occasional serum samples contain high concentrations of unsaturated haptocorrin (apoHC), which may influence measurement of cobalamins (Cbl). Methods: Cbl in serum samples spiked with increasing amounts of apoHC were measured employing the Centaur, Cobas and Architect anal...

  16. Maternal high-fat hypercaloric diet during pregnancy results in persistent metabolic and respiratory abnormalities in offspring

    PubMed Central

    Griffiths, Pamela S.; Walton, Cheryl; Samsell, Lennie; Perez, Miriam K.; Piedimonte, Giovanni

    2016-01-01

    Background: We have shown in a previous population-based study significant correlation between childhood asthma and early abnormalities of lipid and glucose metabolism. This study's specific aim was to determine whether maternal nutrition in pregnancy affects postnatal metabolic and respiratory outcomes in the offspring. Methods: On gestation day 1, dams were switched from standard chow to either high-fat hypercaloric diet or control diet. Terminal experiments were performed on newborn and weanling offspring of dams fed the study diet during gestation and lactation, and on adult offspring maintained on the same diet as their mother. Results: Pups born from high-fat hypercaloric diet (HFD) dams developed metabolic abnormalities persistent throughout development. Cytokine expression analysis of lung tissues from newborns born to HFD dams revealed a strong proinflammatory pattern. Gene expression of neurotrophic factors and receptors was upregulated in lungs of weanlings born to HFD dams, and this was associated to higher respiratory system resistance and lower compliance at baseline, as well as hyperreactivity to aerosolized methacholine. Furthermore, HFD dams delivered pups prone to develop more severe disease after respiratory syncytial virus (RSV) infection. Conclusion: Maternal nutrition in pregnancy is a critical determinant of airway inflammation and hyperreactivity in offspring and also increases risk for bronchiolitis independent from prepregnancy nutrition. PMID:26539661

  17. Serum testosterone levels and excessive erythrocytosis during the process of adaptation to high altitudes

    PubMed Central

    Gonzales, Gustavo F

    2013-01-01

    Populations living at high altitudes (HAs), particularly in the Peruvian Andes, are characterized by a mixture of subjects with erythrocytosis (16 g dl−121 g dl−1). Elevated haemoglobin values (EE) are associated with chronic mountain sickness, a condition reflecting the lack of adaptation to HA. According to current data, native men from regions of HA are not adequately adapted to live at such altitudes if they have elevated serum testosterone levels. This seems to be due to an increased conversion of dehydroepiandrosterone sulphate (DHEAS) to testosterone. Men with erythrocytosis at HAs show higher serum androstenedione levels and a lower testosterone/androstenedione ratio than men with EE, suggesting reduced 17beta-hydroxysteroid dehydrogenase (17beta-HSD) activity. Lower 17beta-HSD activity via Δ4-steroid production in men with erythrocytosis at HA may protect against elevated serum testosterone levels, thus preventing EE. The higher conversion of DHEAS to testosterone in subjects with EE indicates increased 17beta-HSD activity via the Δ5-pathway. Currently, there are various situations in which people live (human biodiversity) with low or high haemoglobin levels at HA. Antiquity could be an important adaptation component for life at HA, and testosterone seems to participate in this process. PMID:23524530

  18. Immobilization of Bovine Serum Albumin Upon Multiwall Carbon Nanotube for High Speed Humidity Sensing Application.

    PubMed

    Bhattacharya, Sankhya; Sasmal, Milan

    2016-01-01

    We present a high-speed humidity sensor based on immobilization of bovine serum albumin upon multiwall carbon nanotube (IBC). A simple and versatile drop casting technique was employed to make the humidity sensor using novel material IBC at room temperature. IBC was synthesized using easy solution process technique. The working principle of the IBC humidity sensor depends upon the variation of output current or conductance with the exposure of different humidity level. Humidity sensing properties of our device is explained on the basis of charge transfer from water molecules to IBC and bovine serum albumin to multiwall carbon nanotube (MWCNT). Our sensor exhibits faster response time around 1.2 s and recovery time 1.5 s respectively. PMID:26841403

  19. EUROarray human papillomavirus (HPV) assay is highly concordant with other commercial assays for detection of high-risk HPV genotypes in women with high grade cervical abnormalities.

    PubMed

    Cornall, A M; Poljak, M; Garland, S M; Phillips, S; Machalek, D A; Tan, J H; Quinn, M A; Tabrizi, S N

    2016-06-01

    The purpose of this study was to evaluate the performance of the EUROIMMUN EUROArray HPV genotyping assay against the Roche Cobas 4800, Roche HPV Amplicor, Roche Linear Array and Qiagen Hybrid Capture 2 assays in the detection of high-risk HPV (HR-HPV) from liquid based cervical cytology samples collected from women undergoing follow-up for abnormal cervical cytology results. Cervical specimens from 404 women undergoing management of high-grade cytological abnormality were evaluated by EUROarray HPV for detection of HR-HPV genotypes and prediction of histologically-confirmed cervical intraepithelial neoplasia grade 2 or higher (≥CIN2). The results were compared to Hybrid Capture 2, Cobas 4800 HPV, Amplicor and Linear Array HPV. Positivity for 14 HR-HPV types was 80.0 % for EUROarray (95 % CI; 75.7-83.8 %). Agreement (κ, 95 % CI) between the EUROarray and other HPV tests for detection of HR-HPV was good to very good [Hybrid Capture κ = 0.62 (0.54-0.71); Cobas κ = 0.81 (0.74-0.88); Amplicor κ = 0.68 (0.60-0.77); Linear Array κ = 0.77 (0.70-0.85)]. For detection of HR-HPV, agreement with EUROarray was 87.90 % (Hybrid Capture), 93.58 % (Cobas), 92.84 % (Amplicor) and 92.59 % (Linear Array). Detection of HR-HPV was not significantly different between EUROarray and any other test (p < 0.001). EUROarray was concordant with other assays evaluated for detection of high-risk HPV and showed sensitivity and specificity for detection of ≥ CIN2 of 86 % and 71 %, respectively. PMID:27048314

  20. Quantitative determination of fluoxetine in human serum by high performance thin layer chromatography.

    PubMed

    Mennickent, Sigrid; Fierro, Ricardo; Vega, Mario; De Diego, Marta; Godoy, C Gloria

    2010-07-01

    A high performance thin layer chromatographic method was developed and validated for the quantification of fluoxetine in human serum. Fluoxetine was extracted by liquid-liquid extraction method with diethyl ether as extraction solvent. Imipramine was used as internal standard. The chromatographic separation was achieved on precoated silica gel F 254 high performance thin layer chromatographic plates using a mixture of toluene/acetic acid glacial (4:5 v/v) as mobile phase. 4-Dimethylamino-azobenzene-4-sulphonyl chloride was used as derivatization reagent. Densitometric detection was done at 272 nm. The method was linear between 12.5 and 87.5 ng/spot, corresponding to 0.05 and 0.35 ng/microL of fluoxetine in human serum after extraction process and applying 25 microL to the chromatographic plates. The method correlation coefficient was 0.999. The intra-assay and inter-assay precisions, expressed as the RSD, were in the range of 0.70-2.01% (n=3) and 0.81-3.90% (n=9), respectively. The LOD was 0.23 ng, and the LOQ was 0.70 ng. The method proved be accurate, with a recovery between 94.75 and 98.95%, with a RSD not higher than 3.61% and was selective for the active principle tested. This method was successfully applied to quantify fluoxetine in patient serum samples. In conclusion, the method is useful for quantitative determination of fluoxetine in human serum. PMID:20533339

  1. 'Abnormal' angle response curves of TW/Rs for near zero tilt and high tilt channeling implants

    SciTech Connect

    Guo Baonian; Gossmann, Hans-Joachim; Toh, Terry; Colombeau, Benjamin; Todorov, Stan; Sinclair, Frank; Shim, Kyu-Ha; Henry, Todd

    2012-11-06

    Angle control has been widely accepted as the key requirement for ion implantation in semiconductor device processing. From an ion implanter point of view, the incident ion direction should be measured and corrected by suitable techniques, such as XP-VPS for the VIISta implanter platform, to ensure precision ion placement in device structures. So called V-curves have been adopted to generate the wafer-based calibration using channeling effects as the Si lattice steer ions into a channeling direction. Thermal Wave (TW) or sheet resistance (Rs) can be used to determine the minimum of the angle response curve. Normally it is expected that the TW and Rs have their respective minima at identical angles. However, the TW and Rs response to the angle variations does depend on factors such as implant species, dose, and wafer temperature. Implant damage accumulation effects have to be considered for data interpretation especially for some 'abnormal' V-curve data. In this paper we will discuss some observed 'abnormal' angle responses, such as a) TW/Rs reverse trend for Arsenic beam, 2) 'W' shape of Rs Boron, and 3) apparent TW/Rs minimum difference for high tilt characterization, along with experimental data and TCAD simulations.

  2. TSLP Expression and High Serum TSLP Level Indicate a Poor Prognosis in Gastric Cancer Patients

    PubMed Central

    Watanabe, Joji; Saito, Hiroaki; Miyatani, Kozo; Ikeguchi, Masahide; Umekita, Yoshihisa

    2015-01-01

    Background Thymic stromal lymphopoietin (TSLP) plays an important role in promoting tumor survival, by manipulating the immune response and angiogenesis. However, the clinical significance of TSLP in gastric cancer is unclear. Methods Immunohistochemistry was used to investigate TSLP expression in non-cancerous gastric mucosa and gastric cancer tissue from patients with gastric cancer. Serum TSLP levels were measured using an enzyme-linked immunosorbent assay. Results Tumors with TSLP expression were significantly larger than those without TSLP expression. TSLP expression was observed more frequently in advanced (T2/T3/T4) than in early (T1) gastric cancer and in stage 3/4 than in stage 1/2. Lymph node metastasis, liver metastasis, positive peritoneal lavage cytology, lymphatic invasion, and vascular invasion occurred significantly more often in TSLP-expressing than in non-expressing tumors. The prognosis of patients with TSLP-positive tumors was significantly worse than that of patients with TSLP-negative tumors. Patients with high serum TSLP concentrations also had a significantly worse prognosis than those with low concentrations. Multivariate analysis identified serum TSLP level as an independent prognostic indicator. Conclusion TSLP is closely related to the progression of gastric cancer and may predict survival in these patients. PMID:26538800

  3. Serum Paraoxonase 1 Activity Is Associated with Fatty Acid Composition of High Density Lipoprotein

    PubMed Central

    Boshtam, Maryam; Pourfarzam, Morteza; Ani, Mohsen; Naderi, Gholam Ali; Basati, Gholam; Mansourian, Marjan; Dinani, Narges Jafari; Asgary, Seddigheh; Abdi, Soheila

    2013-01-01

    Introduction. Cardioprotective effect of high density lipoprotein (HDL) is, in part, dependent on its related enzyme, paraoxonase 1 (PON1). Fatty acid composition of HDL could affect its size and structure. On the other hand, PON1 activity is directly related to the structure of HDL. This study was designed to investigate the association between serum PON1 activity and fatty acid composition of HDL in healthy men. Methods. One hundred and forty healthy men participated in this research. HDL was separated by sequential ultracentrifugation, and its fatty acid composition was analyzed by gas chromatography. PON1 activity was measured spectrophotometrically using paraxon as substrate. Results. Serum PON1 activity was directly correlated with the amount of stearic acid and dihomo-gamma-linolenic acid (DGLA). PON1/HDL-C was directly correlated with the amount of miristic acid, stearic acid, and DGLA and was inversely correlated with total amount of ω6 fatty acids of HDL. Conclusion. The fatty acid composition of HDL could affect the activity of its associated enzyme, PON1. As dietary fats are the major determinants of serum lipids and lipoprotein composition, consuming some special dietary fatty acids may improve the activity of PON1 and thereby have beneficial effects on health. PMID:24167374

  4. A highly sensitive colorimetric determination of serum zinc using water-soluble pyridylazo dye.

    PubMed

    Makino, T; Saito, M; Horiguchi, D; Kina, K

    1982-03-26

    A colorimetric method for precise and accurate determination of zinc in serum is presented. Only 0.3 ml of sample is necessary, because of the use of a new, highly sensitive reagent, 2-(5-bromo-2-pyridylazo)-5-(N-n-propyl-N-3-sulfopropylamino)-phenol (epsilon 554nm = 1.3 X 10(5) 1 . mol-1 . cm-1), which is water-soluble and has long-term stability. Interference of iron and copper in serum can be removed by co-precipitation of the iron fluoride complex with trichloroacetic acid precipitated proteins and the copper dithiocarboxy sarcosine complex, respectively. Within-run and day-to-day precision (CV) are in the range of 0.3-3.5% and 1.9-3.1%, respectively, depending on the serum zinc content. A good correlation (r = 0.98, p less than 0.05) was obtained between this method and atomic absorption spectrometry. In contrast to previous colorimetric methods, the present method does not involve heating, extraction with organic solvents, or a cyanide masking system. PMID:7067132

  5. Analysis of Lidocaine Interactions with Serum Proteins Using High-Performance Affinity Chromatography

    PubMed Central

    Soman, Sony; Yoo, Michelle J.; Jang, Yoon Jeong; Hage, David S.

    2010-01-01

    High-performance affinity chromatography was used to study binding by the drug lidocaine to human serum albumin (HSA) and α1–acid glycoprotein (AGP). AGP had strong binding to lidocaine, with an association equilibrium constant (Ka) of 1.1-1.7 × 105 M-1 at 37 °C and pH 7.4. Lidocaine had weak-to-moderate binding to HSA, with a Ka in the range of 103 to 104 M-1. Competitive experiments with site selective probes showed that lidocaine was interacting with Sudlow site II of HSA and the propranolol site of AGP. These results agree with previous observations in the literature and provide a better quantitative understanding of how lidocaine binds to these serum proteins and is transported in the circulation. This study also demonstrates how HPAC can be used to examine the binding of a drug with multiple serum proteins and provide detailed information on the interaction sites and equilibrium constants that are involved in such processes. PMID:20138813

  6. Effects of serum amyloid A on the structure and antioxidant ability of high-density lipoprotein.

    PubMed

    Sato, Megumi; Ohkawa, Ryunosuke; Yoshimoto, Akira; Yano, Kouji; Ichimura, Naoya; Nishimori, Madoka; Okubo, Shigeo; Yatomi, Yutaka; Tozuka, Minoru

    2016-08-01

    Serum amyloid A (SAA) levels increase during acute and chronic inflammation and are mainly associated with high-density lipoprotein (HDL). In the present study, we investigated the effect of SAA on the composition, surface charge, particle size and antioxidant ability of HDL using recombinant human SAA (rhSAA) and HDL samples from patients with inflammation. We confirmed that rhSAA bound to HDL3 and released apolipoprotein A-I (apoA-I) from HDL without an apparent change in particle size. Forty-one patients were stratified into three groups based on serum SAA concentrations: Low (SAA ≤ 8 μg/ml), Middle (8 < SAA ≤ 100 μg/ml) and High (SAA > 100 μg/ml). The ratios of apoA-I to total protein mass, relative cholesterol content and negative charge of HDL samples obtained from patients with high SAA levels were lower than that for samples from patients with low SAA levels. Various particle sizes of HDL were observed in three groups regardless of serum SAA levels. Antioxidant ability of rhSAA, evaluated as the effect on the formation of conjugated diene in low-density lipoprotein (LDL) induced by oxidation using copper sulfate, was higher than that of apoA-I. Consistent with this result, reconstituted SAA-containing HDL (SAA-HDL) indicated higher antioxidant ability compared with normal HDL. Furthermore, HDL samples obtained from High SAA group patients also showed the highest antioxidant ability among the three groups. Consequently, SAA affects the composition and surface charge of HDL by displacement of apoA-I and enhances its antioxidant ability. PMID:27422844

  7. Effects of serum amyloid A on the structure and antioxidant ability of high-density lipoprotein

    PubMed Central

    Sato, Megumi; Ohkawa, Ryunosuke; Yoshimoto, Akira; Yano, Kouji; Ichimura, Naoya; Nishimori, Madoka; Okubo, Shigeo; Yatomi, Yutaka; Tozuka, Minoru

    2016-01-01

    Serum amyloid A (SAA) levels increase during acute and chronic inflammation and are mainly associated with high-density lipoprotein (HDL). In the present study, we investigated the effect of SAA on the composition, surface charge, particle size and antioxidant ability of HDL using recombinant human SAA (rhSAA) and HDL samples from patients with inflammation. We confirmed that rhSAA bound to HDL3 and released apolipoprotein A-I (apoA-I) from HDL without an apparent change in particle size. Forty-one patients were stratified into three groups based on serum SAA concentrations: Low (SAA ≤ 8 μg/ml), Middle (8 < SAA ≤ 100 μg/ml) and High (SAA > 100 μg/ml). The ratios of apoA-I to total protein mass, relative cholesterol content and negative charge of HDL samples obtained from patients with high SAA levels were lower than that for samples from patients with low SAA levels. Various particle sizes of HDL were observed in three groups regardless of serum SAA levels. Antioxidant ability of rhSAA, evaluated as the effect on the formation of conjugated diene in low-density lipoprotein (LDL) induced by oxidation using copper sulfate, was higher than that of apoA-I. Consistent with this result, reconstituted SAA-containing HDL (SAA-HDL) indicated higher antioxidant ability compared with normal HDL. Furthermore, HDL samples obtained from High SAA group patients also showed the highest antioxidant ability among the three groups. Consequently, SAA affects the composition and surface charge of HDL by displacement of apoA-I and enhances its antioxidant ability. PMID:27422844

  8. Approach to the evaluation of a patient with an increased serum osmolal gap and high-anion-gap metabolic acidosis.

    PubMed

    Kraut, Jeffrey A; Xing, Shelly Xiaolei

    2011-09-01

    An increase in serum osmolality and serum osmolal gap with or without high-anion-gap metabolic acidosis is an important clue to exposure to one of the toxic alcohols, which include methanol, ethylene glycol, diethylene glycol, propylene glycol, or isopropanol. However, the increase in serum osmolal gap and metabolic acidosis can occur either together or alone depending on several factors, including baseline serum osmolal gap, molecular weight of the alcohol, and stage of metabolism of the alcohol. In addition, other disorders, including diabetic or alcoholic ketoacidosis, acute kidney injury, chronic kidney disease, and lactic acidosis, can cause high-anion-gap metabolic acidosis associated with an increased serum osmolal gap and therefore should be explored in the differential diagnosis. It is essential for clinicians to understand the value and limitations of osmolal gap to assist in reaching the correct diagnosis and initiating appropriate treatment. In this teaching case, we present a systematic approach to diagnosing high serum osmolality and increased serum osmolal gap with or without high-anion-gap metabolic acidosis. PMID:21794966

  9. Distinct Patterns of Grey Matter Abnormality in High-Functioning Autism and Asperger's Syndrome

    ERIC Educational Resources Information Center

    McAlonan, Grainne M.; Suckling, John; Wong, Naikei; Cheung, Vinci; Lienenkaemper, Nina; Cheung, Charlton; Chua, Siew E.

    2008-01-01

    Background: Autism exists across a wide spectrum and there is considerable debate as to whether children with Asperger's syndrome, who have normal language milestones, should be considered to comprise a subgroup distinct other from high-functioning children with autism (HFA), who have a history of delayed language development. Magnetic resonance…

  10. Gene Transfection in High Serum Levels: Case Studies with New Cholesterol Based Cationic Gemini Lipids

    PubMed Central

    Misra, Santosh K.; Biswas, Joydeep; Kondaiah, Paturu; Bhattacharya, Santanu

    2013-01-01

    Background Six new cationic gemini lipids based on cholesterol possessing different positional combinations of hydroxyethyl (-CH2CH2OH) and oligo-oxyethylene -(CH2CH2O)n- moieties were synthesized. For comparison the corresponding monomeric lipid was also prepared. Each new cationic lipid was found to form stable, clear suspensions in aqueous media. Methodology/Principal Findings To understand the nature of the individual lipid aggregates, we have studied the aggregation properties using transmission electron microscopy (TEM), dynamic light scattering (DLS), zeta potential measurements and X-ray diffraction (XRD). We studied the lipid/DNA complex (lipoplex) formation and the release of the DNA from such lipoplexes using ethidium bromide. These gemini lipids in presence of a helper lipid, 1, 2-dioleoyl phophatidyl ethanol amine (DOPE) showed significant enhancements in the gene transfection compared to several commercially available transfection agents. Cholesterol based gemini having -CH2-CH2-OH groups at the head and one oxyethylene spacer was found to be the most effective lipid, which showed transfection activity even in presence of high serum levels (50%) greater than Effectene, one of the potent commercially available transfecting agents. Most of these geminis protected plasmid DNA remarkably against DNase I in serum, although the degree of stability was found to vary with their structural features. Conclusions/Significance -OH groups present on the cationic headgroups in combination with oxyethylene linkers on cholesterol based geminis, gave an optimized combination of new genera of gemini lipids possessing high transfection efficiency even in presence of very high percentage of serum. This property makes them preferential transfection reagents for possible in vivo studies. PMID:23861884

  11. Peritoneal Malignant Mesothelioma with Epithelioid Type, Demonstrating High Serum and Ascitic KL-6 Levels: Immunohistochemical Analyses

    PubMed Central

    Nahar, Saifun; Nakamoto, Manabu; Hokama, Akira; Kobashigawa, Chiharu; Kaida, Masatoshi; Kinjo, Tetsu; Hirata, Tetsuo; Kinjo, Nagisa; Saio, Masanao; Yoshimi, Naoki; Ohtsuki, Yuji; Fujita, Jiro

    2015-01-01

    We report a case of KL-6 producing peritoneal malignant mesothelioma. A 56-year-old woman was referred to our hospital on November 2005 with severe abdominal distention. Peritoneal malignant mesothelioma with epithelioid type was diagnosed by clinical symptoms, laboratory investigations, imaging studies, and immunohistochemical examination of known tumor markers. In addition, high serum and ascitic KL-6 levels were observed and the immunostaining of the tumor for KL-6 was evident. We thus consider KL-6 to be a potential novel marker for peritoneal malignant mesothelioma with epithelioid type. PMID:26500734

  12. Peritoneal Malignant Mesothelioma with Epithelioid Type, Demonstrating High Serum and Ascitic KL-6 Levels: Immunohistochemical Analyses.

    PubMed

    Nahar, Saifun; Nakamoto, Manabu; Hokama, Akira; Kobashigawa, Chiharu; Kaida, Masatoshi; Kinjo, Tetsu; Hirata, Tetsuo; Kinjo, Nagisa; Saio, Masanao; Yoshimi, Naoki; Ohtsuki, Yuji; Fujita, Jiro

    2015-09-01

    We report a case of KL-6 producing peritoneal malignant mesothelioma. A 56-year-old woman was referred to our hospital on November 2005 with severe abdominal distention. Peritoneal malignant mesothelioma with epithelioid type was diagnosed by clinical symptoms, laboratory investigations, imaging studies, and immunohistochemical examination of known tumor markers. In addition, high serum and ascitic KL-6 levels were observed and the immunostaining of the tumor for KL-6 was evident. We thus consider KL-6 to be a potential novel marker for peritoneal malignant mesothelioma with epithelioid type. PMID:26500734

  13. A case of hypocomplementaemic urticarial vasculitis with a high serum level of rheumatoid factor.

    PubMed

    Ashida, Atsuko; Murata, Hiroshi; Ohashi, Atsuko; Ogawa, Eisaku; Uhara, Hisashi; Okuyama, Ryuhei

    2013-08-01

    We report a case of hypocomplementaemic urticarial vasculitis with an elevated serum rheumatoid factor level. Hypocomplementaemic urticarial vasculitis is an immune complex-mediated disease characterised by urticarial eruptions. High levels of rheumatoid factor may be associated with hypocomplementaemia due to the consumption of complement, because the rheumatoid factor can form immune complexes with immunoglobulin. It is necessary to pay attention to the amounts of complement in cases of urticarial eruptions with elevated rheumatoid factor level. The eruptions were relieved with a combination of prednisolone and colchicine. PMID:23905981

  14. Body mass index, serum total cholesterol, and risk of gastric high-grade dysplasia

    PubMed Central

    Huang, Ya-Kai; Kang, Wei-Ming; Ma, Zhi-Qiang; Liu, Yu-Qin; Zhou, Li; Yu, Jian-Chun

    2016-01-01

    Abstract Obesity is related to an increased risk of gastric cardia cancer. However, the influences of excess body weight and serum total cholesterol on the risk of gastric high-grade dysplasia have not been fully characterized. A case–control study was conducted to explore the relationships between body mass index (BMI), serum total cholesterol level, and the risk of gastric high-grade dysplasia in Chinese adults. A total of 893 consecutive patients with gastric high-grade dysplasia (537 men and 356 women) and 902 controls (543 men and 359 women) were enrolled from January 2000 to October 2015. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated, and a multivariate analysis was conducted. After adjusting for age, alcohol consumption, smoking status, family history of gastric cancer or esophageal cancer, and serum total cholesterol level, a BMI ranging from 27.5 to 29.9 was significantly related to an increased risk of gastric high-grade dysplasia in both men (adjusted OR = 1.87, 95% CI = 1.24–2.81) and women (adjusted OR = 2.72, 95% CI = 1.44–5.16). The 2 highest BMI categories (27.5–29.9 and ≥30.0) were identified as risk factors for gastric cardia high-grade dysplasia in both men (BMI = 27.5–29.9: adjusted OR = 1.78, 95% CI = 1.02–3.10; BMI ≥ 30.0: adjusted OR = 2.54, 95% CI = 1.27–5.08) and women (BMI = 27.5–29.9: adjusted OR = 2.88, 95% CI = 1.27–6.55; BMI ≥ 30.0: adjusted OR = 2.77, 95% CI = 1.36–5.64), whereas only a BMI ranging from 27.5 to 29.9 was a risk factor for gastric noncardia high-grade dysplasia in both men (adjusted OR = 1.98, 95% CI = 1.25–3.14) and women (adjusted OR = 2.88, 95% CI = 1.43–5.81). In addition, higher serum total cholesterol was associated with an increased risk of gastric noncardia high-grade dysplasia (adjusted OR = 1.83, 95% CI = 1.25–2.69) in women. Increased BMI was associated with an increased risk

  15. Identification of a Proteinaceous Component in the Leaf of Moringa Oleifera lam. with Effects on High Serum Creatinine.

    PubMed

    Sahoo, S; Raghavendra, K M; Biswas, S

    2014-01-01

    Moringa oleifera Lam. has been an important plant in the history of mankind, both for its nutritional and medicinal uses. Apart from bactericidal effects, the parts of this plant have been effectively used in the treatment of circulatory, respiratory, endocrine, digestive as well as neural disorders. Till date, though, there has been no reported activity of the involvement of any proteinaceous extract from M. oleifera on high levels of serum creatinine. To address this issue, blood samples with high levels of serum creatinine (2 mg/dl and above) were treated with leaf extract from M. oleifera. The crude extract was partially purified initially and eventually purified to completion as well. All these proteinaceous fractions were used to treat samples with high levels of serum creatinine as mentioned above. While the treatment of serum sample having high creatinine with crude extract and partially purified protein fractions showed a decrease of approximately 20% in the levels of serum creatinine over a period of 24 h, the samples treated with purified protein fraction reduced the serum creatinine level by 50%. In light of the fact that increased level of serum creatinine levels have adverse downstream effects on the heart, lungs and other organs, this communication assumes significance because it suggests a way of reducing the level of serum creatinine as an emergency measure. Further, the identification and characterisation of this proteinaceous component and possible in vivo experiments would provide a major tool for the treatment of downstream complications associated with increased serum creatinine via a new sources, albeit a natural one. PMID:24799742

  16. Identification of a Proteinaceous Component in the Leaf of Moringa Oleifera lam. with Effects on High Serum Creatinine

    PubMed Central

    Sahoo, S.; Raghavendra, K. M.; Biswas, S.

    2014-01-01

    Moringa oleifera Lam. has been an important plant in the history of mankind, both for its nutritional and medicinal uses. Apart from bactericidal effects, the parts of this plant have been effectively used in the treatment of circulatory, respiratory, endocrine, digestive as well as neural disorders. Till date, though, there has been no reported activity of the involvement of any proteinaceous extract from M. oleifera on high levels of serum creatinine. To address this issue, blood samples with high levels of serum creatinine (2 mg/dl and above) were treated with leaf extract from M. oleifera. The crude extract was partially purified initially and eventually purified to completion as well. All these proteinaceous fractions were used to treat samples with high levels of serum creatinine as mentioned above. While the treatment of serum sample having high creatinine with crude extract and partially purified protein fractions showed a decrease of approximately 20% in the levels of serum creatinine over a period of 24 h, the samples treated with purified protein fraction reduced the serum creatinine level by 50%. In light of the fact that increased level of serum creatinine levels have adverse downstream effects on the heart, lungs and other organs, this communication assumes significance because it suggests a way of reducing the level of serum creatinine as an emergency measure. Further, the identification and characterisation of this proteinaceous component and possible in vivo experiments would provide a major tool for the treatment of downstream complications associated with increased serum creatinine via a new sources, albeit a natural one. PMID:24799742

  17. High Fat Diet Produces Brain Insulin Resistance, Synaptodendritic Abnormalities and Altered Behavior in Mice

    PubMed Central

    Arnold, Steven E.; Lucki, Irwin; Brookshire, Bethany R.; Carlson, Gregory C.; Browne, Carolyn A.; Kazi, Hala; Bang, Sookhee; Choi, Bo-Ran; Chen, Yong; McMullen, Mary F.; Kim, Sangwon F.

    2014-01-01

    Insulin resistance and other features of the metabolic syndrome are increasingly recognized for their effects on cognitive health. To ascertain mechanisms by which this occurs, we fed mice a very high fat diet (60% kcal by fat) for 17 days or a moderate high fat diet (HFD, 45% kcal by fat) for 8 weeks and examined changes in brain insulin signaling responses, hippocampal synaptodendritic protein expression, and spatial working memory. Compared to normal control diet mice, cerebral cortex tissues of HFD mice were insulin-resistant as evidenced by failed activation of Akt, S6 and GSK3β with ex-vivo insulin stimulation. Importantly, we found that expression of brain IPMK, which is necessary for mTOR/Akt signaling, remained decreased in HFD mice upon activation of AMPK. HFD mouse hippocampus exhibited increased expression of serine-phosphorylated insulin receptor substrate 1 (IRS1-pS616), a marker of insulin resistance, as well as decreased expression of PSD-95, a scaffolding protein enriched in post-synaptic densities, and synaptopodin, an actin-associated protein enriched in spine apparatuses. Spatial working memory was impaired as assessed by decreased spontaneous alternation in a T-maze. These findings indicate that HFD is associated with telencephalic insulin resistance and deleterious effects on synaptic integrity and cognitive behaviors. PMID:24686304

  18. Behavioral and neurochemical abnormalities after exposure to low doses of high-energy iron particles.

    PubMed

    Hunt, W A; Joseph, J A; Rabin, B M

    1989-01-01

    Exposure of rats to high-energy iron particles (600 MeV/amu) has been found to alter behavior after doses as low as 10 rads. The performance of a task that measures upper body strength was significantly degraded after irradiation. In addition, an impairment in the regulation of dopamine release in the caudate nucleus (a motor center in the brain), lasting at least 6 months, was also found and correlated with the performance deficits. A general indication of behavioral toxicity and an index of nausea and emesis, the conditioned taste aversion, was also evident. The sensitivity to iron particles was 10-600 times greater than to gamma photons. These results suggest that behavioral and neurobiological damage may be a consequence of exposure to low doses of heavy particles and that this possibility should be extensively studied. PMID:11537313

  19. Behavioral and neurochemical abnormalities after exposure to low doses of high-energy iron particles

    NASA Astrophysics Data System (ADS)

    Hunt, Walter A.; Joseph, James A.; Rabin, Bernard M.

    Exposure of rats to high-energy iron particles (600 MeV/amu) has been found to alter behavior after doses as low as 10 rads. The performance of a task that measures upper body strength was significantly degraded after irradiation. In addition, an impairment in the regulation of dopamine release in the caudate nucleus (a motor center in the brain), lasting at least 6 months, was also found and correlated with the performance deficits. A general indication of behavioral toxicity and an index of nausea and emesis, the conditioned taste aversion, was also evident. The sensitivity to iron particles was 10-600 times greater than to gamma photons. These results suggest that behavioral and neurobiological damage may be a consequence of exposure to low doses of heavy particles and that this possibility should be extensively studied.

  20. Current source imaging for high spatial resolution magnetocardiography in normal and abnormal rat cardiac muscles

    NASA Astrophysics Data System (ADS)

    Uchida, S.; Iramina, K.; Goto, K.; Ueno, S.

    2000-05-01

    The purpose of our study was to identify the current source produced by acute ischemia and infarction. We measured magnetocardiograms (MCG) and electrocardiograms (ECG) of five male rats using a high-resolution dc superconducting quantum interference device gradiometer in a magnetically shielded room after performing coronary artery occlusion. The spatial resolution of the detecting magnetic field of our system is higher than the typical system, thus permitting the measurement of magnetic fields in small animals. Distribution of the magnetic fields B(t) and distribution of |rot B(t)|, which corresponded to the distribution of the current source, were imaged by 12-channel MCGs. As a result, the distribution of current source changes in the affected area of the myocardium during the ST segment, and amplitude of the peak significantly increased after occlusion. Our system can be used to help clarify the mechanism of the ST shift related to severe heart disease.

  1. Behavioral and neurochemical abnormalities after exposure to low doses of high-energy iron particles

    SciTech Connect

    Hunt, W.A.; Joseph, J.A.; Rabin, B.M.

    1989-01-01

    Exposure of rats to high-energy iron particles (600 MeV/amu) has been found to alter behavior after doses as low as 10 rads. The performance of a task that measures upper body strength was significantly degraded after irradiation. In addition, an impairment in the regulation of dopamine release in the caudate nucleus (a motor center in the brain), lasting at least 6 months, was also found and correlated with the performance deficits. A general indication of behavioral toxicity and an index of nausea and emesis, the conditioned taste aversion, was also evident. The sensitivity to iron particles was 10-600 times greater than to gamma photons. These results suggest that behavioral and neurobiological damage may be a consequence of exposure to low doses of heavy particles and that this possibility should be extensively studied.

  2. A study of the abnormal lipoproteins in abetalipoproteinemia.

    PubMed Central

    Scanu, A M; Aggerbeck, L P; Kruski, A W; Lim, C T; Kayden, H J

    1974-01-01

    The serum lipoproteins of five patients with abetalipoproteinemia (ABL) were separated by ultracentrifugation and then analyzed either intact or after delipidation. In accord with previous findings, all of the patients lacked serum particles with the characteristics of normal low-density lipoproteins (LDL) and of the LDL apoprotein as assessed by immunochemical methods. Each patient exhibited on every examination an abnormal particle, "LDL", which had the flotational properties of LDL, the polypeptide makeup of high-density lipoproteins HDL, the spectral and morphological characteristics of neither LDL nor HDL, and a relatively low content of cholesteryl esters. The HDL were abnormal in having a marked decrease in their total plasma content, an altered proportion of the subclasses HDL2 and HDL3, and a peculiar polypeptide distribution, comprising both normal and additional components, usually not seen in normal controls. The patients also exhibited a decrease of plasma lecithin-cholesterol acyl transferase (LCAT) activity which probably accounted for the low content of cholesteryl esters in both "LDL" and HDL, and in turn for the unusual appearance of "LDL" on electron microscopy. It is concluded that ABL is a disorder affecting all serum lipoprotein classes. Whether the abetalipoproteinemia previously described and noted in the current studies is related to or independent of the abnormalities observed in the other lipoproteins was not established. How the deficiency of LCAT activity, observed in all patients studied, contributed to some of the observed structural lipoprotein abnormalities also remained undetermined. Images PMID:11344558

  3. High Doses of Bone Morphogenetic Protein 2 Induce Structurally Abnormal Bone and Inflammation In Vivo

    PubMed Central

    Zara, Janette N.; Siu, Ronald K.; Zhang, Xinli; Shen, Jia; Ngo, Richard; Lee, Min; Li, Weiming; Chiang, Michael; Chung, Jonguk; Kwak, Jinny; Wu, Benjamin M.; Ting, Kang

    2011-01-01

    The major Food and Drug Association–approved osteoinductive factors in wide clinical use are bone morphogenetic proteins (BMPs). Although BMPs can promote robust bone formation, they also induce adverse clinical effects, including cyst-like bone formation and significant soft tissue swelling. In this study, we evaluated multiple BMP2 doses in a rat femoral segmental defect model and in a minimally traumatic rat femoral onlay model to determine its dose-dependent effects. Results of our femoral segmental defect model established a low BMP2 concentration range (5 and 10 μg/mL, total dose 0.375 and 0.75 μg in 75 μg total volume) unable to induce defect fusion, a mid-range BMP2 concentration range able to fuse the defect without adverse effects (30 μg/mL, total dose 2.25 μg in 75 μg total volume), and a high BMP2 concentration range (150, 300, and 600 μg/mL, total dose 11.25, 22.5, and 45 μg in 75 μg total volume) able to fuse the defect, but with formation of cyst-like bony shells filled with histologically confirmed adipose tissue. In addition, compared to control, 4 mg/mL BMP2 also induced significant tissue inflammatory infiltrates and exudates in the femoral onlay model that was accompanied by increased numbers of osteoclast-like cells at 3, 7, and 14 days. Overall, we consistently reproduced BMP2 side effects of cyst-like bone and soft tissue swelling using high BMP2 concentration approaching the typical human 1500 μg/mL. PMID:21247344

  4. High doses of bone morphogenetic protein 2 induce structurally abnormal bone and inflammation in vivo.

    PubMed

    Zara, Janette N; Siu, Ronald K; Zhang, Xinli; Shen, Jia; Ngo, Richard; Lee, Min; Li, Weiming; Chiang, Michael; Chung, Jonguk; Kwak, Jinny; Wu, Benjamin M; Ting, Kang; Soo, Chia

    2011-05-01

    The major Food and Drug Association-approved osteoinductive factors in wide clinical use are bone morphogenetic proteins (BMPs). Although BMPs can promote robust bone formation, they also induce adverse clinical effects, including cyst-like bone formation and significant soft tissue swelling. In this study, we evaluated multiple BMP2 doses in a rat femoral segmental defect model and in a minimally traumatic rat femoral onlay model to determine its dose-dependent effects. Results of our femoral segmental defect model established a low BMP2 concentration range (5 and 10 μg/mL, total dose 0.375 and 0.75 μg in 75 μg total volume) unable to induce defect fusion, a mid-range BMP2 concentration range able to fuse the defect without adverse effects (30 μg/mL, total dose 2.25 μg in 75 μg total volume), and a high BMP2 concentration range (150, 300, and 600 μg/mL, total dose 11.25, 22.5, and 45 μg in 75 μg total volume) able to fuse the defect, but with formation of cyst-like bony shells filled with histologically confirmed adipose tissue. In addition, compared to control, 4 mg/mL BMP2 also induced significant tissue inflammatory infiltrates and exudates in the femoral onlay model that was accompanied by increased numbers of osteoclast-like cells at 3, 7, and 14 days. Overall, we consistently reproduced BMP2 side effects of cyst-like bone and soft tissue swelling using high BMP2 concentration approaching the typical human 1500 μg/mL. PMID:21247344

  5. Sasa quelpaertensis leaf extract improves high fat diet-induced lipid abnormalities and regulation of lipid metabolism genes in rats.

    PubMed

    Kim, Jina; Kim, Yoo-Sun; Lee, Hyun Ah; Lim, Ji Ye; Kim, Mina; Kwon, Oran; Ko, Hee-Chul; Kim, Se-Jae; Shin, Jae-Ho; Kim, Yuri

    2014-05-01

    Sasa quelpaertensis is a bamboo leaf that is only grown on Jeju Island in South Korea. It is used as a bamboo tea that is consumed for therapeutic purposes, particularly for its anti-diabetic, diuretic, and anti-inflammatory effects. This study investigated the effect of S. quelpaertensis leaf extract (SQE) on high fat-induced lipid abnormalities and regulation of lipid metabolism-related gene expressions in rats. SQE supplementation significantly decreased the levels of plasma triglycerides, total cholesterol, and low-density lipoprotein cholesterol as well as the atherogenic index. SQE restored levels of plasma high-density lipoprotein cholesterol, which were lowered by a high fat diet. Plasma and cardiac resistin levels were also significantly decreased by SQE supplementation. In adipose tissue, mRNA levels of CAAT/enhancer-binding protein β (C/EBPβ) were suppressed in the SQE group. SQE supplementation decreased the accumulation of lipid droplets, inflammatory cell infiltrations, levels of triglycerides, and total lipids in the liver and effectively down-regulated expression of sterol regulatory element binding protein-1 (SREBP-1), fatty acid synthetase (FAS), and uncoupling protein 2 (UCP-2). These results suggest that SQE may be a potential treatment for high fat-related disorders by improving lipid profiles and modulating lipid metabolism. PMID:24738745

  6. A tyrosinase with an abnormally high tyrosine hydroxylase/dopa oxidase ratio.

    PubMed

    Hernández-Romero, Diana; Sanchez-Amat, Antonio; Solano, Francisco

    2006-01-01

    The sequencing of the genome of Ralstonia solanacearum[Salanoubat M, Genin S, Artiguenave F, et al. (2002) Nature 415, 497-502] revealed several genes that putatively code for polyphenol oxidases (PPOs). This soil-borne pathogenic bacterium withers a wide range of plants. We detected the expression of two PPO genes (accession numbers NP_518458 and NP_519622) with high similarity to tyrosinases, both containing the six conserved histidines required to bind the pair of type-3 copper ions at the active site. Generation of null mutants in those genes by homologous recombination mutagenesis and protein purification allowed us to correlate each gene with its enzymatic activity. In contrast with all tyrosinases so far studied, the enzyme NP_518458 shows higher monophenolase than o-diphenolase activity and its initial activity does not depend on the presence of l-dopa cofactor. On the other hand, protein NP_519622 is an enzyme with a clear preference to oxidize o-diphenols and only residual monophenolase activity, behaving as a catechol oxidase. These catalytic characteristics are discussed in relation to two other characteristics apart from the six conserved histidines. One is the putative presence of a seventh histidine which interacts with the carboxy group on the substrate and controls the preference for carboxylated and decarboxylated substrates. The second is the size of the residue isosteric with the aromatic F261 reported in sweet potato catechol oxidase which acts as a gate to control accessibility to CuA at the active site. PMID:16403014

  7. Diastolic Dysfunction Induced by a High-Fat Diet Is Associated with Mitochondrial Abnormality and Adenosine Triphosphate Levels in Rats

    PubMed Central

    Kang, Ki-Woon; Kim, Ok-Soon; Chin, Jung Yeon; Kim, Won Ho; Park, Sang Hyun; Choi, Yu Jeong; Shin, Jong Ho; Jung, Kyung Tae; Lim, Do-Seon

    2015-01-01

    Background Obesity is well-known as a risk factor for heart failure, including diastolic dysfunction. However, this mechanism in high-fat diet (HFD)-induced obese rats remain controversial. The purpose of this study was to investigate whether cardiac dysfunction develops when rats are fed with a HFD for 10 weeks; additionally, we sought to investigate the association between mitochondrial abnormalities, adenosine triphosphate (ATP) levels and cardiac dysfunction. Methods We examined myocardia in Wistar rats after 10 weeks of HFD (45 kcal% fat, n=6) or standard diet (SD, n=6). Echocardiography, histomorphologic analysis, and electron microscopy were performed. The expression levels of mitochondrial oxidative phosphorylation (OXPHOS) subunit genes, peroxisome-proliferator-activated receptor γ co-activator-1α (PGC1α) and anti-oxidant enzymes were assessed. Markers of oxidative stress damage, mitochondrial DNA copy number and myocardial ATP level were also examined. Results After 10 weeks, the body weight of the HFD group (349.6±22.7 g) was significantly higher than that of the SD group (286.8±14.9 g), and the perigonadal and epicardial fat weights of the HFD group were significantly higher than that of the SD group. Histomorphologic and electron microscopic images were similar between the two groups. However, in the myocardium of the HFD group, the expression levels of OXPHOS subunit NDUFB5 in complex I and PGC1α, and the mitochondrial DNA copy number were decreased and the oxidative stress damage marker 8-hydroxydeoxyguanosine was increased, accompanied by reduced ATP levels. Conclusion Diastolic dysfunction was accompanied by the mitochondrial abnormality and reduced ATP levels in the myocardium of 10 weeks-HFD-induced rats. PMID:26790384

  8. High resolution protein electrophoresis of 100 paired canine cerebrospinal fluid and serum.

    PubMed

    Behr, Sébastien; Trumel, Cathy; Cauzinille, Laurent; Palenché, Florence; Braun, Jean-Pierre

    2006-01-01

    This study was performed to investigate the diagnostic relevance of cerebrospinal fluid (CSF) high resolution electrophoresis. The laboratory technique was applied to 100 paired samples of canine CSF and serum, with paired samples tested during the same analytical run, as recommended in human medicine. Ninety four of the dogs had a neurological disease and 6 healthy dogs served as a control group. A strong linear correlation between CSF total protein concentration and the albumin quota (AQ) was found in the control group and in the inflammatory (infectious or noninfectious), neoplastic, and miscellaneous groups: AQ = 0.015 CSF total protein--0.102, r = 0.990. This correlation suggests that an increased CSF total protein concentration can be an indicator of blood brain barrier dysfunction. The highest median AQ value was found in the aseptic suppurative meningitis group, but no statistical differences were found between this and the other groups. The AQ, calculated with this technique, did not provide any additional information. Moreover, although unexpected, the electrophoretic profiles were not characteristic of any particular disease. In conclusion, this study did not confirm high resolution electrophoresis of paired CSF and serum samples to be a valuable ancillary diagnostic tool for canine neurological diseases. PMID:16734104

  9. Evaluation of Serum Homocysteine, High-Sensitivity CRP, and RBC Folate in Patients with Alopecia Areata

    PubMed Central

    Yousefi, Maryam; Namazi, Mohammad Reza; Rahimi, Hoda; Younespour, Shima; Ehsani, Amir Houshang; Shakoei, Safoura

    2014-01-01

    Introduction: Alopecia areata (AA) is a common type of hair loss with an autoimmune basis. As the role of homocysteine (Hcys), folate, and CRP has been considered in some autoimmune diseases. Objectives: To evaluate homocysteine, folate and CRP level in AA. Methods: This study was performed on 29 patients who had AA for at least 6 months affecting more than 20% of scalp, and 32 healthy controls. Levels of serum Hcys, blood high-sensitivity CRP, and RBC folate were measured in all subjects. Results: The mean level of RBC folate was significantly lower in the patient group than that in controls (P < 0.001). Also, the level of RBC folate was significantly lower in patients with extensive forms of disease (alopecia totalis/alopecia universalis) in comparison with more localized form (patchy hair loss) (P < 0.05). Patients with higher “Severity of Alopecia Total” (SALT) score had lower RBC folate, as well. Serum Hcys and blood high-sensitivity CRP levels did not show a significant difference in two groups. Conclusion: Patients with alopecia areata have lower level of RBC folate which is in negative correlation with both severity and extension of AA. PMID:25484412

  10. High Serum IgG4 Concentrations in Patients with Hashimoto's Thyroiditis.

    PubMed

    Popławska-Kita, Anna; Kościuszko-Zdrodowska, Maria; Siewko, Katarzyna; Telejko, Beata; Hryniewicka, Justyna; Milewski, Robert; Abdelrazek, Saeid Soleman; Szelachowska, Małgorzata; Górska, Maria

    2015-01-01

    Purpose. Since recent reports suggest that Hashimoto thyroiditis (HT) may be associated with IgG4-related disease, we aimed to find out whether the measurement of serum IgG4 allows for the identification of distinct types of HT, with different clinical, sonographic, and serologic characteristics. Methods. The group studied consisted of 53 patients with HT and 28 healthy individuals who underwent thyroid ultrasonography and body composition analysis. Serum concentrations of IgG4, TSH, anti-peroxidase antibodies (TPOAb), anti-TSH receptor antibodies, TNF-α, TGF-β1, Fas Ligand, TRAIL, and chemokines (CXCL9, CXCL11, and CXCL10) were measured by ELISA or radioimmunoassay. Results. The group with IgG4 level >135 IU/ml accounted for 32.5% of the patients. The signs of fibrosis were present in 27.0% of the high-IgG4 patients and in 9.1% of the normal-IgG4 group. The patients with elevated IgG4 required higher doses of L-thyroxine and had significantly lower level of TPOAb (P=0.02) than the non-IgG4-HT individuals and higher TNF-α level in comparison with the controls (P=0.01). Conclusions. Our results suggest that the measurement of serum IgG4 allows for an identification of patients with more rapid progression of HT, requiring higher doses of L-thyroxine. Low TPOAb level and the absence of coexisting autoimmune diseases may suggest distinct pathomechanism of this type of thyroiditis. PMID:25784936

  11. Isotopic and Hydrogeochemical Studies on Abnormally High Ammonium of Natural Origin in A Coastal Aquifer-aquitard System

    NASA Astrophysics Data System (ADS)

    Wang, Y.; Jiao, J. J.; Cherry, J.

    2010-12-01

    Excessive nitrogen concentration in water bodies is regarded as an environmental contamination because of its possible harm to human bodies and significant ecological effects. Previous studies commonly concerned on elevated nitrogen in water of anthropogenic origins, such as agricultural, domestic, sewage and industrial discharges, because people realize that it is necessary to manage negative influences of human being to the natural environment. Understanding contamination sources of nitrogen is crucial for both waste discharge management and pollutants cleanup. This study was aimed to 1) understand the spatial distribution of abnormally high ammonium groundwater in the Quaternary basalt aquifer in the Pearl River Delta (PRD), China; 2) to distinguish sources of recharge to the basalt aquifer; and 3) to identify the origin of the ammonium in the aquitard and aquifer system. Total 40 boreholes were drilled, and approximately 1000 deposit samples from the aquitard and over 200 groundwater samples from the Quaternary basalt aquifer were collected. A cluster of 7 piezometers was installed in Minzhong Town to study the hydraulic relationships between the aquitard and the basalt aquifer. The results demonstrated that the greater groundwater ammonium concentrations were preserved in the aquifer buried deeper. The ammonium concentration up to 390 mg/L was observed in the basalt sand and gravel Pleistocene aquifer of 20-50m deep, and this is the greatest concentration ever reported for natural groundwater globally. The Quaternary aquitard, which contained abundant sedimentary organic matter and was mainly composed of silt and clay, provided a strict anaerobic environment for sedimentary organic matter mineralization and ammonium preservation. Ammonium concentrations in the aquifer were predominantly controlled by the aquitard ammonium content. This naturally occurring abnormally high ammonium in the Quaternary sediments is areally extensive (over 1600 km2). Great

  12. The determination of inorganic sulphate in serum and synovial fluid by high performance ion chromatography.

    PubMed

    Kock, R; Schneider, H; Delvoux, B; Greiling, H

    1997-09-01

    A method for the determination of inorganic sulphate based on high performance ion chromatography is presented. The separation was performed on an anion-exchange column with a 1.8 mmol/l sodium carbonate/ 1.7 mmol/l sodium hydrogen carbonate-buffer, pH 10.35. Conductivity of the eluate was monitored after suppression of the background conductivity caused by the eluent-buffer. Serum and synovial fluid samples were prepared by ultrafiltration through membranes with a molecular mass cutoff of M(r) 10,000. The viscosity of the synovial fluids was reduced by treatment with hyaluronate lyase before ultrafiltration. The method showed a linear response for sulphate concentrations between 0.5 and 1000 mumol/l. The limit of detection was 1 mumol/l for aqueous standards. For serum the coefficient of variation within-run was 2.3%-2.4%, the coefficient of variation between days 2.9%-3.1%. For synovial fluids the coefficient of variation within-run was 3.1%-3.4%, the coefficient of variation between days 4.6%-5.7%. Standard recovery experiments performed by spiking pools of human sera containing low sulphate concentrations with sulphate concentrations between 5 mumol/l and 40 mumol/l showed recoveries between 98.9% and 100.6%. The corresponding experiments with pools of synovial fluids showed recoveries of 98.3% to 100.9%. As determined from 127 serum samples the reference range for sulphate was 262 mumol/l-420 mumol/l, with a mean value of 314 mumol/l. No dependence on age or sex was observed. The sulphate concentration in 36 synovial fluids from knees affected by inflammatory processes showed a mean value of 424 mumol/l and a standard deviation of 70 mumol/l. In 41 synovial fluids from knees affected by chronic degeneration joint disease, the sulphate concentrations were statistically significantly lower, with a mean of 374 mumol/l and a standard deviation of 58 mumol/l. The concentrations of sulphate in the synovial fluids were statistically significantly higher than those in

  13. Serum Dickkopf-1 Level in Postmenopausal Females: Correlation with Bone Mineral Density and Serum Biochemical Markers

    PubMed Central

    Fouda, Neveen; Abbas, Amal Ahmed

    2013-01-01

    Objective. To assess serum level of Dickkopf-1 in postmenopausal females and its correlation with bone mineral density and serum biochemical markers. Methods. Bone densitometry, serum Dickkopf-1, calcium, phosphorus, and alkaline phosphatase were done in sixty postmenopausal females. Patients were divided according to T score into osteoporosis (group I), osteopenia (group II), and normal bone mineral density that served as controls. Results. There was highly significant increase in serum Dickkopf-1 levels in postmenopausal females with abnormal T score versus controls (P < 0.001). Serum DKK-1 levels correlated negatively with both lumbar T score (r = −0.69, P < 0.001) and femur T score (r = −0.64, P < 0.001) and correlated positively with duration of menopause (r = 0.61, P < 0.001), while there was no significant correlation between serum levels of either calcium, phosphorus or alkaline phosphatase, and both serum Dickkopf-1 levels and the level of bone mineral density (P > 0.05). Conclusion. Postmenopausal females may suffer from osteoporosis as evidenced by bone densitometry. Postmenopausal women with significantly increased serum Dickkopf-1 had more significant osteoporosis. Prolonged duration of menopause and increased serum Dickkopf-1 are important risk factors for the development and severity of osteoporosis. PMID:23878759

  14. Tuna extract reduces serum uric acid in gout-free subjects with insignificantly high serum uric acid: A randomized controlled trial

    PubMed Central

    Kubomura, Daiki; Yamada, Masanori; Masui, Ayano

    2016-01-01

    Long-term reduction of serum urate levels is vital in the treatment of gout. However, it is difficult to convince gout-free individuals of the necessity of treatment as few appropriate over-the-counter remedies and dietary supplements are available. Therefore, the present study aimed to investigate the antihyperuricemic efficacy and safety of a tuna extract containing the imidazole compounds to evaluate its potential as a functional food ingredient. A randomized, 4-week, double-blind, placebo-controlled study was conducted. A total of 48 male gout-free subjects with insignificantly high serum uric acid were randomly assigned to low- and high-dose tuna extract groups or a placebo group. The efficacy of the extract was assessed by measuring serum uric acid levels. Furthermore, a safety assessment was performed by physical parameters, hematology, blood biochemistry and urinalysis. The results indicated that the uric acid level was decreased at week 4 during the intervention in the tuna extract groups (low and high dose, −0.23 and −0.34 mg/dl, respectively) compared to the placebo group (−0.07 mg/dl). At week 4 after the intervention, a significant reduction in uric acid levels (−0.41 mg/dl; P<0.05) was observed in the high-dose tuna extract group compared with the placebo group (+0.11 mg/dl). No dose-related adverse events were observed during and following the intervention. Therefore, the present results suggest that oral administration of tuna extract containing the imidazole compounds has hypouricemic activity with no undesirable side effects. PMID:27446553

  15. Serum Response Factor Protects Retinal Ganglion Cells Against High-Glucose Damage.

    PubMed

    Cao, Yan; Wang, Liang; Zhao, Junhong; Zhang, Hongbing; Tian, Ying; Liang, Houcheng; Ma, Qiang

    2016-06-01

    Serum response factor (SRF), which encodes the MADS-box family of related proteins, is a common transcription factor related to the expression of genes associated with cell survival. However, SRF's role in retinal ganglion cells (RGCs) after high-glucose injury remains unclear. In this study, we investigate the protective role of SRF after high-glucose injury and its underlying mechanism. The in vitro RGC model subjected to high glucose was established by employing a 50 mmol/L glucose culture environment. As detected by real-time quantitative PCR and Western blot, SRF was significantly upregulated in RGCs treated with high glucose. Overexpression of SRF significantly promoted survival among RGCs exposed to high glucose and inhibited RGC apoptosis. Knockdown of SRF exerted an inverse effect. Moreover, SRF upregulation enhanced expression of an antioxidant protein, nuclear factor erythroid 2-related factor (Nrf2), via control of the Fos-related antigen 1 (Fra-1). SRF upregulation also affected RGC survival after high-glucose treatment. Our findings showed that overexpression of SRF promoted survival of RGCs after high-glucose injury by regulating Fra-1 and Nrf2. PMID:26803311

  16. Oral cancer screening: serum Raman spectroscopic approach

    NASA Astrophysics Data System (ADS)

    Sahu, Aditi K.; Dhoot, Suyash; Singh, Amandeep; Sawant, Sharada S.; Nandakumar, Nikhila; Talathi-Desai, Sneha; Garud, Mandavi; Pagare, Sandeep; Srivastava, Sanjeeva; Nair, Sudhir; Chaturvedi, Pankaj; Murali Krishna, C.

    2015-11-01

    Serum Raman spectroscopy (RS) has previously shown potential in oral cancer diagnosis and recurrence prediction. To evaluate the potential of serum RS in oral cancer screening, premalignant and cancer-specific detection was explored in the present study using 328 subjects belonging to healthy controls, premalignant, disease controls, and oral cancer groups. Spectra were acquired using a Raman microprobe. Spectral findings suggest changes in amino acids, lipids, protein, DNA, and β-carotene across the groups. A patient-wise approach was employed for data analysis using principal component linear discriminant analysis. In the first step, the classification among premalignant, disease control (nonoral cancer), oral cancer, and normal samples was evaluated in binary classification models. Thereafter, two screening-friendly classification approaches were explored to further evaluate the clinical utility of serum RS: a single four-group model and normal versus abnormal followed by determining the type of abnormality model. Results demonstrate the feasibility of premalignant and specific cancer detection. The normal versus abnormal model yields better sensitivity and specificity rates of 64 and 80% these rates are comparable to standard screening approaches. Prospectively, as the current screening procedure of visual inspection is useful mainly for high-risk populations, serum RS may serve as a useful adjunct for early and specific detection of oral precancers and cancer.

  17. Oral cancer screening: serum Raman spectroscopic approach.

    PubMed

    Sahu, Aditi K; Dhoot, Suyash; Singh, Amandeep; Sawant, Sharada S; Nandakumar, Nikhila; Talathi-Desai, Sneha; Garud, Mandavi; Pagare, Sandeep; Srivastava, Sanjeeva; Nair, Sudhir; Chaturvedi, Pankaj; Murali Krishna, C

    2015-11-01

    Serum Raman spectroscopy (RS) has previously shown potential in oral cancer diagnosis and recurrence prediction. To evaluate the potential of serum RS in oral cancer screening, premalignant and cancer-specific detection was explored in the present study using 328 subjects belonging to healthy controls, premalignant, disease controls, and oral cancer groups. Spectra were acquired using a Raman microprobe. Spectral findings suggest changes in amino acids, lipids, protein, DNA, and β-carotene across the groups. A patient-wise approach was employed for data analysis using principal component linear discriminant analysis. In the first step, the classification among premalignant, disease control (nonoral cancer), oral cancer, and normal samples was evaluated in binary classification models. Thereafter, two screening-friendly classification approaches were explored to further evaluate the clinical utility of serum RS: a single four-group model and normal versus abnormal followed by determining the type of abnormality model. Results demonstrate the feasibility of premalignant and specific cancer detection. The normal versus abnormal model yields better sensitivity and specificity rates of 64 and 80%; these rates are comparable to standard screening approaches. Prospectively, as the current screening procedure of visual inspection is useful mainly for high-risk populations, serum RS may serve as a useful adjunct for early and specific detection of oral precancers and cancer. PMID:26580700

  18. [Effects of high- and low-intensity training on cardiorespiratory system and serum lipids].

    PubMed

    Yanagibori, R; Aoki, K; Suzuki, Y; Gunji, A

    1991-08-01

    The differences between the effects of high- and low-intensity exercise training on cardiorespiratory system and serum lipid levels were examined under conditions in which the total work load was same. Twenty-two healthy, untrained female students, aged 18 to 24 years, participated in the 8-week training experiment. Two training groups exercised on bicycle ergometers 4-5d/wk for 8 wk with high-intensity (H: 70% VO2 max 13 min/session; N = 8) or in low-intensity (L: 36% VO2 max 33 min/session; N = 8). The control group (C: N = 6) continued its sedentary life style. Data of 6 students (H: N = 2, L: N = 2, C: N = 2) were excluded from the analysis, because they did not carry out their duties. The results of this study were as follows; 1) Aerobic capacity increased in both training groups. 2) After training, both heart rates and oxygen uptake during submaximal work loads significantly decreased in group H, but only heart rates significantly decreased in group L. 3) Heart rates with a same oxygen-uptake load during submaximal work seemed to increase in group H, but significantly decreased in group L. 4) The mechanical efficiency during the submaximal work load significantly increased in group H, but not in group L. 5) DBP and MBP during the submaximal work load in group L significantly decreased compared with those before the training. SBP with a same oxygen-uptake load during submaximal work increased in group H, but decreased in group L. 6) Rate pressure products both at rest and during submaximal exercise decreased significantly in group L. 7) Serum lipid levels remained in all groups. These results suggested that when the amount of exercise is the same, low-intensity exercise training with 35% VO2 max was more effective to increase endurance capacity and was safer than high-intensity exercise training. PMID:1956126

  19. Diagnostic accuracy of myocardial deformation indices for detecting high risk coronary artery disease in patients without regional wall motion abnormality

    PubMed Central

    Rostamzadeh, Alireza; Shojaeifard, Maryam; Rezaei, Yousef; Dehghan, Kasra

    2015-01-01

    Background: The prediction of coronary artery disease (CAD) by conventional echocardiographic measurements is principally based on the estimation of ejection fraction and regional wall motion abnormality (RWMA). This study aimed to determine whether strain echocardiography of left ventricle measured by velocity vector imaging (VVI) method could detect patients with a high-risk CAD. Methods: In a prospective study, a total of 119 consecutive patients who were assessed for eligibility were categorized into three groups: (1) without CAD as normal (n=59), (2) 1- or 2-vessel disease as low-risk (n=29), and (3) left main and/or 3-vessel disease as high-risk (n=31). The peaks of systolic strain and strain rate from 18 curves of apical views were averaged as global longitudinal strain and strain rate (GLS and GLSR), respectively; the 6 systolic peaks of strain and strain rate at base- and mid-ventricular of short axis views were averaged as mean radial strain rate (MRSR). Results: GLS, GLSR, and basal MRSR of left ventricle were significantly lower in the high-risk group (P=0.047, P=0.004 and P=0.030, respectively). Receiver operating characteristics curve showed that the optimal values of GLS, GLSR, and basal MRSR for detecting the severe CAD were -17%, -1 s-1, and 1.45 s-1 with the sensitivities of 77%, 71%, and 71% and the specificities of 63%, 67%, and 62%, respectively. Conclusion: Decrements in the GLS, GLSR, and basal MRSR of the left ventricle can detect the high-risk CAD cases among patients without RWMA at rest. PMID:26309603

  20. Quantitative proteomic analysis for high-throughput screening of differential glycoproteins in hepatocellular carcinoma serum

    PubMed Central

    Gao, Hua-Jun; Chen, Ya-Jing; Zuo, Duo; Xiao, Ming-Ming; Li, Ying; Guo, Hua; Zhang, Ning; Chen, Rui-Bing

    2015-01-01

    Objective Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths. Novel serum biomarkers are required to increase the sensitivity and specificity of serum screening for early HCC diagnosis. This study employed a quantitative proteomic strategy to analyze the differential expression of serum glycoproteins between HCC and normal control serum samples. Methods Lectin affinity chromatography (LAC) was used to enrich glycoproteins from the serum samples. Quantitative mass spectrometric analysis combined with stable isotope dimethyl labeling and 2D liquid chromatography (LC) separations were performed to examine the differential levels of the detected proteins between HCC and control serum samples. Western blot was used to analyze the differential expression levels of the three serum proteins. Results A total of 2,280 protein groups were identified in the serum samples from HCC patients by using the 2D LC-MS/MS method. Up to 36 proteins were up-regulated in the HCC serum, whereas 19 proteins were down-regulated. Three differential glycoproteins, namely, fibrinogen gamma chain (FGG), FOS-like antigen 2 (FOSL2), and α-1,6-mannosylglycoprotein 6-β-N-acetylglucosaminyltransferase B (MGAT5B) were validated by Western blot. All these three proteins were up-regulated in the HCC serum samples. Conclusion A quantitative glycoproteomic method was established and proven useful to determine potential novel biomarkers for HCC. PMID:26487969

  1. High versus low vancomycin serum trough regimen for Gram-positive infections: a meta-analysis.

    PubMed

    Meng, Long; Fang, Yun; Chen, Yongfei; Zhu, Huaijun; Long, Rui

    2015-08-01

    This study aimed to evaluate the impact of high vancomycin serum trough concentrations (≧15 mg/l) on clinical outcomes and nephrotoxicity among adult subjects. We searched MEDLINE, Cochrane Library, and CNKI systematically. A total of 17 studies were included. Meta-analysis found that high trough group showed no significant difference comparing to low trough group in treatment failure [relative risk (RR) 0·91, 95% confidence interval (CI) 0·67-1·24; P = 0·57] and all-cause mortality (RR 1·14, 95% CI 0·81-1·59; P = 0·46). However, the high trough concentrations were associated with lower treatment failure in bacteremia subgroup (RR 0·72, 95% CI 0·59-0·88; P = 0·001). High trough concentrations were associated with an increased risk of vancomycin-induced nephrotoxicity (RR 2·06, 95% CI 1·52-2·79; P<0·00001). Our meta-analysis indicates that high trough concentrations were not significantly superior to low trough concentrations in lowering treatment failure and mortality. Moreover, high trough concentrations significantly increased the risk of nephrotoxicity. PMID:24641266

  2. Effects of moderate-dose versus high-dose trimethoprim on serum creatinine and creatinine clearance and adverse reactions.

    PubMed Central

    Naderer, O; Nafziger, A N; Bertino, J S

    1997-01-01

    The effects of a 10-day course of moderate-dose (10 mg/kg/day) or high-dose (20 mg/kg/day) trimethoprim therapy on serum creatinine, measured creatinine clearance, urinary creatinine excretion, and serum folate were studied in 20 healthy volunteers. Serum creatinine concentrations increased significantly during trimethoprim therapy, began to decrease near day 10, and returned to baseline during the washout phase at both dosage levels. At the same time, measured creatinine clearance and urine creatinine changed in the opposite direction. No clinical or statistical differences were noted between changes in the moderate- versus the high-dose phases. Serum folate concentration decreases during high-dose trimethoprim therapy were statistically significant. Adverse drug reactions in the two groups were statistically different during the first study period, with the high-dose group having a 75% incidence rate and the moderate-dose group having an 11% incidence rate (P < 0.02). Serum creatinine, measured creatinine clearance, and urinary creatinine excretion demonstrated statistically, but not clinically, significant changes during trimethoprim therapy. In addition, high-dose trimethoprim caused significantly more adverse drug reactions than moderate-dose trimethoprim in normal volunteers. PMID:9371351

  3. Abnormal functional specialization within medial prefrontal cortex in high-functioning autism: a multi-voxel similarity analysis

    PubMed Central

    Meuwese, Julia D.I.; Towgood, Karren J.; Frith, Christopher D.; Burgess, Paul W.

    2009-01-01

    Multi-voxel pattern analyses have proved successful in ‘decoding’ mental states from fMRI data, but have not been used to examine brain differences associated with atypical populations. We investigated a group of 16 (14 males) high-functioning participants with autism spectrum disorder (ASD) and 16 non-autistic control participants (12 males) performing two tasks (spatial/verbal) previously shown to activate medial rostral prefrontal cortex (mrPFC). Each task manipulated: (i) attention towards perceptual versus self-generated information and (ii) reflection on another person's mental state (‘mentalizing'versus ‘non-mentalizing’) in a 2 × 2 design. Behavioral performance and group-level fMRI results were similar between groups. However, multi-voxel similarity analyses revealed strong differences. In control participants, the spatial distribution of activity generalized significantly between task contexts (spatial/verbal) when examining the same function (attention/mentalizing) but not when comparing different functions. This pattern was disrupted in the ASD group, indicating abnormal functional specialization within mrPFC, and demonstrating the applicability of multi-voxel pattern analysis to investigations of atypical populations. PMID:19174370

  4. Abnormal functional specialization within medial prefrontal cortex in high-functioning autism: a multi-voxel similarity analysis.

    PubMed

    Gilbert, Sam J; Meuwese, Julia D I; Towgood, Karren J; Frith, Christopher D; Burgess, Paul W

    2009-04-01

    Multi-voxel pattern analyses have proved successful in 'decoding' mental states from fMRI data, but have not been used to examine brain differences associated with atypical populations. We investigated a group of 16 (14 males) high-functioning participants with autism spectrum disorder (ASD) and 16 non-autistic control participants (12 males) performing two tasks (spatial/verbal) previously shown to activate medial rostral prefrontal cortex (mrPFC). Each task manipulated: (i) attention towards perceptual versus self-generated information and (ii) reflection on another person's mental state ('mentalizing'versus 'non-mentalizing') in a 2 x 2 design. Behavioral performance and group-level fMRI results were similar between groups. However, multi-voxel similarity analyses revealed strong differences. In control participants, the spatial distribution of activity generalized significantly between task contexts (spatial/verbal) when examining the same function (attention/mentalizing) but not when comparing different functions. This pattern was disrupted in the ASD group, indicating abnormal functional specialization within mrPFC, and demonstrating the applicability of multi-voxel pattern analysis to investigations of atypical populations. PMID:19174370

  5. High frequency of low serum levels of vitamin 12 among patients attending Jordan University Hospital.

    PubMed

    Barghouti, F F; Younes, N A; Halaseh, L J; Said, T T; Ghraiz, S M

    2009-01-01

    This study aimed to estimate the status of serum vitamin B12 level in patients attending Jordan University Hospital in Amman, and to examine the relationship with demographic data, chronic illness, dietary habits, haematological parameters and symptoms related to vitamin B12 levels. A total of 838 patients completed a questionnaire and gave blood samples; 44.6% were vitamin B12 deficient (< 180 pg/mL) and 34.2% had hypovitaminosis (180-300 pg/mL). Vitamin B12 deficiency was associated with memory impairment, low meat intake and strict vegetarian (vegan) diets. The high frequency of low vitamin B12 warrants the development of a strategy to correct this problem in Jordan. PMID:20187536

  6. [Serial determinations of serum oxytocinase and ultrasonic biparietal cephalometry in normal and high-risk pregnancies].

    PubMed

    Mansani, F E; Serventi, G; Verrelli, D; Condemi, V; Ferrari, F

    1975-01-01

    The value of sonor biparietal cephalometry and serum oxytocinase that we have obtained with weekly simultaneous determinations in 14 females with normal pregnancy and in 5 with pathological pregnancy, from 24th to 39th week, show a statical positive relation. Serum oxitocinase determination against hormonal tests of the phetoplancental function (urinary oestriol, pregnandiol, serum HCS, ecc.) give advantages: it is the easyer, faster and less espandove determination. Therefore we think that it is helpful to determin togheter serial values of sonar biparietal cephalometry and serum oxytocinase to anticipate the endouterine fetal growth retardation. PMID:1212272

  7. Predictors of High Serum Casein Antibody Levels among Malnourished Infants and Young Children with Congenital Heart Disease

    PubMed Central

    El-Alameey, Inas R.; Ahmed, Hanaa H.; Monir, Zeinab M.; Rabah, Thanaa M.; Gawad, Ayman M. Abdel

    2015-01-01

    BACKGROUND: Factors predictive of growth retardation and malnutrition in patients with congenital heart disease remain unclear. OBJECTIVES: This study aimed to measure antibody response to bovine casein through assessing serum casein antibody levels in malnourished patients three year or younger with CHD, and to determine its relationship to gastrointestinal symptoms, anthropometric measures, and laboratory data. SUBJECTS AND METHODS: This cross sectional case control study was conducted in sixty patients with CHD aged 4 to 72 months. They were subdivided into thirty patients with cyanotic and thirty patients with acyanotic CHD compared with thirty apparently healthy children. RESULTS: On comparison with controls, patients showed highly significant lower anthropometric measures, calcium, iron, hemoglobin levels, and higher serum levels of casein antibody, total iron binding capacity, and alkaline phoshatase activity (P<0.000). Serum levels of casein antibody showed significantly positive correlations with serum total iron binding capacity and alkaline phosphatase activities and negatively correlated with the age at onset of symptoms, anthropometric measures, serum calcium, and iron levels. CONCLUSION: Serum casein antibody levels play a significant role in the pathogenesis of malnutrition. Encouragement of breast feeding and avoidance of early cow’s milk consumption could prevent the development of antibody response to bovine casein.

  8. Association of a high normalized protein catabolic rate and low serum albumin level with carpal tunnel syndrome in hemodialysis patients.

    PubMed

    Huang, Wen-Hung; Hsu, Ching-Wei; Weng, Cheng-Hao; Yen, Tzung-Hai; Lin, Jui-Hsiang; Lee, Meng

    2016-06-01

    Carpal tunnel syndrome (CTS) is the most common mononeuropathy in patients with end-stage renal disease (ESRD). The association between chronic inflammation and CTS in hemodialysis (HD) patients has rarely been investigated. HD patients with a high normalized protein catabolic rate (nPCR) and low serum albumin level likely have adequate nutrition and inflammation. In this study, we assume that a low serum albumin level and high nPCR is associated with CTS in HD patients. We recruited 866 maintenance hemodialysis (MHD) patients and divided them into 4 groups according to their nPCR and serum albumin levels: (1) nPCR <1.2 g/kg/d and serum albumin level <4 g/dL; (2) nPCR ≥1.2 g/kg/d and serum albumin level <4 g/dL; (3) nPCR <1.2 g/kg/d and serum albumin level ≥4 g/dL; and (4) nPCR ≥1.2 g/kg/d and serum albumin level ≥4 g/dL. After adjustment for related variables, HD duration and nPCR ≥1.2 g/kg/d and serum albumin level <4 g/dL were positively correlated with CTS. By calculating the area under the receiver-operating characteristic curve, we calculated that the nPCR and HD duration cut-off points for obtaining the most favorable Youden index were 1.29 g/kg/d and 7.5 years, respectively. Advance multivariate logistic regression analysis revealed that in MHD patients, nPCR ≥1.29 g/kg/d and serum albumin <4 g/dL, and also HD duration >7.5 years were associated with CTS. A high nPCR and low serum albumin level, which likely reflect adequate nutrition and inflammation, were associated with CTS in MHD patients. PMID:27368039

  9. Association of a high normalized protein catabolic rate and low serum albumin level with carpal tunnel syndrome in hemodialysis patients

    PubMed Central

    Huang, Wen-Hung; Hsu, Ching-Wei; Weng, Cheng-Hao; Yen, Tzung-Hai; Lin, Jui-Hsiang; Lee, Meng

    2016-01-01

    Abstract Carpal tunnel syndrome (CTS) is the most common mononeuropathy in patients with end-stage renal disease (ESRD). The association between chronic inflammation and CTS in hemodialysis (HD) patients has rarely been investigated. HD patients with a high normalized protein catabolic rate (nPCR) and low serum albumin level likely have adequate nutrition and inflammation. In this study, we assume that a low serum albumin level and high nPCR is associated with CTS in HD patients. We recruited 866 maintenance hemodialysis (MHD) patients and divided them into 4 groups according to their nPCR and serum albumin levels: (1) nPCR <1.2 g/kg/d and serum albumin level <4 g/dL; (2) nPCR ≥1.2 g/kg/d and serum albumin level <4 g/dL; (3) nPCR <1.2 g/kg/d and serum albumin level ≥4 g/dL; and (4) nPCR ≥1.2 g/kg/d and serum albumin level ≥4 g/dL. After adjustment for related variables, HD duration and nPCR ≥1.2 g/kg/d and serum albumin level <4 g/dL were positively correlated with CTS. By calculating the area under the receiver-operating characteristic curve, we calculated that the nPCR and HD duration cut-off points for obtaining the most favorable Youden index were 1.29 g/kg/d and 7.5 years, respectively. Advance multivariate logistic regression analysis revealed that in MHD patients, nPCR ≥1.29 g/kg/d and serum albumin <4 g/dL, and also HD duration >7.5 years were associated with CTS. A high nPCR and low serum albumin level, which likely reflect adequate nutrition and inflammation, were associated with CTS in MHD patients. PMID:27368039

  10. Reduction of low- and high-grade cervical abnormalities associated with high uptake of the HPV bivalent vaccine in Scotland

    PubMed Central

    Pollock, K G J; Kavanagh, K; Potts, A; Love, J; Cuschieri, K; Cubie, H; Robertson, C; Cruickshank, M; Palmer, T J; Nicoll, S; Donaghy, M

    2014-01-01

    Background: In Scotland, a national HPV immunisation programme began in 2008 for 12- to 13-year olds, with a catch-up campaign from 2008 to 2011 for those under the age of 18. To monitor the impact of HPV immunisation on cervical disease at the population level, a programme of national surveillance was established. Methods: We analysed colposcopy data from a cohort of women born between 1988 and 1992 who entered the Scottish Cervical Screening Programme (SCSP) and were aged 20–21 in 2008–2012. Results: By linking datasets from the SCSP and colposcopy services, we observed a significant reduction in diagnoses of cervical intraepithelial neoplasia 1 (CIN 1; RR 0.71, 95% CI 0.58 to 0.87; P=0.0008), CIN 2 (RR 0.5, 95% CI 0.4 to 0.63; P<0.0001) and CIN 3 (RR 0.45, 95% CI 0.35 to 0.58; P<0.0001) for women who received three doses of vaccine compared with unvaccinated women. Conclusions: To our knowledge, this is one of the first studies to show a reduction of low- and high-grade CIN associated with high uptake of the HPV bivalent vaccine at the population level. These data are very encouraging for countries that have achieved high HPV vaccine uptake. PMID:25180766

  11. In Vitro Assessment of Serum-Saline Ratios for Fluid Simulator Testing of Highly Modular Spinal Implants With Articulating Surfaces

    PubMed Central

    Khandha, Ashutosh; Malcolmson, George; Timm, JP

    2008-01-01

    and lower bounds of predictive implant debris generation modeling, where saline represents a worst-case scenario and as little as 20% serum masks all weight loss completely in highly modular articulating implants. Clinical Relevance Clinical Relevance = 5 (Oxford Centre for Evidence-based Medicine Levels of Evidence). Study findings are limited to a greater understanding of the science associated with predictive wear testing of articulating spinal implants. PMID:25802619

  12. Development of Gel-Filter Method for High Enrichment of Low-Molecular Weight Proteins from Serum

    PubMed Central

    Chen, Lingsheng; Zhai, Linhui; Li, Yanchang; Li, Ning; Zhang, Chengpu; Ping, Lingyan; Chang, Lei; Wu, Junzhu; Li, Xiangping; Shi, Deshun; Xu, Ping

    2015-01-01

    The human serum proteome has been extensively screened for biomarkers. However, the large dynamic range of protein concentrations in serum and the presence of highly abundant and large molecular weight proteins, make identification and detection changes in the amount of low-molecular weight proteins (LMW, molecular weight ≤ 30kDa) difficult. Here, we developed a gel-filter method including four layers of different concentration of tricine SDS-PAGE-based gels to block high-molecular weight proteins and enrich LMW proteins. By utilizing this method, we identified 1,576 proteins (n = 2) from 10 μL serum. Among them, 559 (n = 2) proteins belonged to LMW proteins. Furthermore, this gel-filter method could identify 67.4% and 39.8% more LMW proteins than that in representative methods of glycine SDS-PAGE and optimized-DS, respectively. By utilizing SILAC-AQUA approach with labeled recombinant protein as internal standard, the recovery rate for GST spiked in serum during the treatment of gel-filter, optimized-DS, and ProteoMiner was 33.1 ± 0.01%, 18.7 ± 0.01% and 9.6 ± 0.03%, respectively. These results demonstrate that the gel-filter method offers a rapid, highly reproducible and efficient approach for screening biomarkers from serum through proteomic analyses. PMID:25723528

  13. High serum testosterone levels during postpartum period are associated with postpartum depression.

    PubMed

    Aswathi, A; Rajendiren, Soundravally; Nimesh, Archana; Philip, R Ravi; Kattimani, Shivanand; Jayalakshmi, D; Ananthanarayanan, P H; Dhiman, Pooja

    2015-10-01

    In view of the reported cases of mood disorders that occur in mothers following childbirth and believing that sex steroid hormones contribute to mood and behavioral changes, this study has been aimed to explore the role of sex steroid hormones as an etiological factor for postpartum depression (PPD). This study was conducted at JIPMER, Puducherry, India between January 2010 and 2011. 103 women were recruited in the study after childbirth, out of which 62 women who were believed to be suffering from PPD were categorized as cases and the remaining 41 with no mood changes as controls, using Edinburgh Postpartum Depression Scale (EPDS) (cases had EPDS score ≥10 at 24-28h, controls had score <10 at 24-48h postpartum). The hormones estimated in these two groups included estradiol, progesterone and testosterone, and their levels were compared between these two groups. A significantly high testosterone levels were observed in cases with PPD at 24-28h when compared to controls. Estradiol and progesterone levels did not show significant difference between cases and controls. ROC analysis done at 24-28h showed that testosterone levels beyond 42.71ng/mL predict the development of PPD with 79% sensitivity, 63% specificity, 68% positive predictive value, 74% negative predictive value with AUC being 0.708. This study shows that there is an association between persistent high serum testosterone level in women following childbirth and PPD. PMID:26372084

  14. Effect of digoxin on serum and urinary cation changes on acute induction to high altitude

    SciTech Connect

    Ohri, V.C.; Chatterji, J.C.; Sachdev, Y.R.; Das, B.K.; Akhtar, M.; Tiwari, S.C.; Bhattacharji, P.; Behl, A.; Dutta, S.K.

    1984-04-01

    Forty subjects each were rapidly inducted by road to altitudes of 3200 and 3771 meters (m). Half of subjects at each altitude were maintained on digoxin and the other half received placebos. The digoxin group showed higher serum potassium at both altitudes. Serum sodium remained unaltered. When compared to control groups, urinary volume changes were less marked in the digoxin group. Similarly, the alterations in calcium and magnesium in serum and urine at 3771 m were less pronounced. However, none of these changes in the digoxin groups were statistically significant when compared with control groups. 21 references.

  15. High-performance liquid chromatography-tandem mass spectrometry validation of medroxyprogesterone acetate in products of pork origin and serum.

    PubMed

    Giannetti, Luigi; Barchi, Daniela; Fiorucci, Fulvia; Gennuso, Elisa; Sanna, Patrizia; Pallagrosi, Marco; Neri, Bruno

    2005-08-01

    Different extraction and purification methods are described here to determine medroxyprogesterone acetate (MPA) in pork meat and serum. Spiked samples are investigated over the concentration range of MPA 0.5-20 ng/g. Pork meat tissues are subjected to extraction using organic solvent, and pork serum is simply diluted with acetate buffer. Clean-up is performed using solid-phase extraction on a C18 cartridge, and MPA is eluted with ethanol. Aliquots are injected into a high-performance liquid chromatography-mass spectrometry system. MPA content is determined on the basis of m/z 387-327 and 387-123 transitions. PMID:16176642

  16. Crevicular Fluid and Serum Concentrations of Progranulin and High Sensitivity CRP in Chronic Periodontitis and Type 2 Diabetes

    PubMed Central

    Priyanka, N.; Kumari, Minal; Kalra, Nitish; Arjun, P.; Naik, Savitha B.; Pradeep, A. R.

    2013-01-01

    Introduction. This study was designed to correlate the serum and gingival crevicular fluid (GCF) levels of progranulin (PGRN) and high sensitivity C-reactive protein (hs CRP) in chronic periodontitis and type 2 diabetes mellitus (DM). Design. PGRN and hs CRP levels were estimated in 3 groups: healthy, chronic periodontitis, and type 2 DM with chronic periodontitis. Results. The mean PGRN and hs CRP concentrations in serum and GCF were the highest for group 3 followed by group 2 and the least in group 1. Conclusion. PGRN and hs CRP may be biomarkers of the inflammatory response in type 2 DM and chronic periodontitis. PMID:24191130

  17. Association of high viral load and abnormal liver function with high aflatoxin B1–albumin adduct levels in HIV-positive Ghanaians: preliminary observations

    PubMed Central

    Jolly, P.E.; Shuaib, F.M.; Jiang, Y.; Preko, P.; Baidoo, J.; Stiles, J.K.; Wang, J.-S.; Phillips, T.D.; Williams, J.H.

    2012-01-01

    We examined the association between certain clinical factors and aflatoxin B1–albumin adduct (AF-ALB) levels in HIV-positive people. Plasma samples collected from 314 (155 HIV-positive and 159 HIV-negative) people were tested for AF-ALB levels, viral load, CD4+ T-cell count, liver function profile, malaria parasitaemia, and hepatitis B and C virus infections. HIV-positive participants were divided into high and low groups based on their median AF-ALB of 0.93 pmol mg−1 albumin and multivariable logistic and linear regression methods used to assess relationships between clinical conditions and AF-ALB levels. Multivariable logistic regression showed statistically significant increased odds of having higher HIV viral loads (OR=2.84; 95% CI=1.17–7.78) and higher direct bilirubin levels (OR=5.47; 95% CI=1.03–22.85) among HIV-positive participants in the high AF-ALB group. There were also higher levels of total bilirubin and lower levels of albumin in association with high AF-ALB. Thus, aflatoxin exposure may contribute to high viral loads and abnormal liver function in HIV-positive people and so promote disease progression. PMID:21749228

  18. Associations between sexually transmitted infections, high-risk human papillomavirus infection, and abnormal cervical Pap smear results in OB/GYN outpatients

    PubMed Central

    Kim, Tae Jin

    2016-01-01

    Objective This study aimed to examine the meaning and usefulness of sexually transmitted infection (STI) test when caring for patients who have abnormal cervical cytology and/or positive high-risk human papillomavirus (HPV) DNA test results. Methods Among patients who underwent liquid-based cervical cytology and HPV DNA tests at the Obstetrics and Gynecology outpatient clinic, 800 patients who showed abnormal cervical cytology were compared with 200 patients in the control group. Both groups were simultaneously tested via multiplex real-time polymerase chain reaction for seven types of STI-causative microorganisms. Results The positive rate of high-risk HPV infection in total STIs positive group was 1.47 times higher than that of total STIs negative group. The probability of a cytological diagnosis of a grade equal to or higher than atypical squamous cells-cannot exclude high grade squamous intraepithelial lesion (ASC-H) was significantly higher in patients testing positive for total STIs (1.46 times), Chlamydia trachomatis (3.21 times), or Mycoplasma genitalicum (3.58 times) than in those testing negative. The total STIs positive rate was significantly higher for those having a cytological diagnosis of a grade equal to or higher than atypical squamous cells of undetermined significance (ASC-US) when high-risk HPV test result was negative. Conclusion Correlations were present not only between STIs and high-risk HPV infection but also between abnormal cervical cytology and STIs. Therefore, additional evaluation of STIs will be helpful to appropriately diagnose and treat patients with abnormal cervical cytology, positive results on high-risk HPV DNA test, or a cytological diagnosis of ASC-US despite negative high-risk HPV DNA test result. PMID:27329197

  19. High Serum Thyrotropin Levels Are Associated with Current But Not with Incident Hypertension

    PubMed Central

    Tiller, Daniel; Meisinger, Christa; Agger, Carsten; Nauck, Matthias; Rettig, Rainer; Hofman, Albert; Jørgensen, Torben; Linneberg, Allan; Witteman, Jacqueline C.M.; Franco, Oscar H.; Greiser, Karin H.; Werdan, Karl; Döring, Angela; Kluttig, Alexander; Stricker, Bruno H.C.; Völzke, Henry

    2013-01-01

    Background Recent data from a population-based study in children and adolescents suggest that serum thyrotropin (TSH) levels are associated with arterial blood pressure and hypertension. These results are in agreement with some but not all population-based studies in adults. Discrepancies in results might be explained by drug intake, different iodine supplies, and sizes of populations investigated. In addition, it is not clear whether an association between TSH and hypertension exists longitudinally or only cross-sectionally. Thus, our aim was to investigate cross-sectional and longitudinal associations between thyroid function and arterial blood pressure in a large consortium of cohort studies in adults. Methods Data from five population-based studies were pooled resulting in 17,023 individuals being available for cross-sectional and 10,048 individuals for longitudinal analyses. Associations of baseline TSH with baseline blood pressure or hypertension were analyzed by multivariable median or logistic regression models. Multivariable median or Poisson regression models were used to investigate associations of baseline TSH with five-year change in arterial blood pressure or incident hypertension. Results There was a cross-sectional positive association of TSH with arterial blood pressure (p<0.001) and hypertension (odds ratio [OR]=1.76 [confidence interval (CI) 1.24–2.50], p=0.002). Likewise, hypothyroidism was associated with systolic (β=1.1 [CI 0.1–2.1], p=0.040) and diastolic blood pressure (β=1.4 [CI 0.7–2.0], p<0.001). TSH, however, was not consistently associated with a five-year change in blood pressure or incident hypertension. Conclusions High serum TSH levels were associated with current hypertension and blood pressure but not with a five-year change in blood pressure and incident hypertension. This argues for only a short-term effect of thyroid hormone levels on arterial blood pressure or a spurious association that needs further evaluation in

  20. Studies of drug interactions with glycated human serum albumin by high-performance affinity chromatography

    PubMed Central

    Matsuda, Ryan; Kye, So-Hwang; Anguizola, Jeanethe; Hage, David S.

    2015-01-01

    Diabetes is a health condition associated with elevated levels of glucose in the bloodstream and affects 366 million people worldwide. Type II diabetes is often treated with sulfonylurea drugs, which are known to bind tightly in blood to the transport protein human serum albumin (HSA). One consequence of the elevated levels of glucose in diabetes is the non-enzymatic glycation of proteins such as HSA. Several areas of HSA are now known to be affected by glycation-related modifications, which may in turn affect the binding of sulfonylurea drugs and other solutes to this protein. This review discusses some recent studies that have examined these changes in drug-protein binding by employing high-performance affinity chromatography (HPAC). A description of the theoretical and experimental techniques that were used in these studies is given. The information on drug interactions with glycated HSA, as obtained through this method, is also summarized. In addition, the potential advantages of this approach in the areas of biointeraction analysis and personalized medicine are considered. PMID:26526139

  1. Studies of drug interactions with glycated human serum albumin by high-performance affinity chromatography.

    PubMed

    Matsuda, Ryan; Kye, So-Hwang; Anguizola, Jeanethe; Hage, David S

    2014-08-01

    Diabetes is a health condition associated with elevated levels of glucose in the bloodstream and affects 366 million people worldwide. Type II diabetes is often treated with sulfonylurea drugs, which are known to bind tightly in blood to the transport protein human serum albumin (HSA). One consequence of the elevated levels of glucose in diabetes is the non-enzymatic glycation of proteins such as HSA. Several areas of HSA are now known to be affected by glycation-related modifications, which may in turn affect the binding of sulfonylurea drugs and other solutes to this protein. This review discusses some recent studies that have examined these changes in drug-protein binding by employing high-performance affinity chromatography (HPAC). A description of the theoretical and experimental techniques that were used in these studies is given. The information on drug interactions with glycated HSA, as obtained through this method, is also summarized. In addition, the potential advantages of this approach in the areas of biointeraction analysis and personalized medicine are considered. PMID:26526139

  2. Carbohydrate composition of serum low and high density lipoproteins of nonhuman primate species.

    PubMed

    Pargaonkar, P S; Radhakrishnamurthy, B; Srinivasan, S R; Berenson, G S

    1977-01-01

    1. Carbohydrate composition of serum low and high density lipoproteins obtained from 5 nonhuman primate species (chimpanzee, patas, baboon, rhesus, and spider) and humans was studied. 2. Individual lipoproteins were isolated from pooled sera of each species by ultracentrifugal flotation between the densities 1.019-1.063 for LDL-2; 1.063-1.12 for HDL-2; and 1.12-1.21 for HDL-3. After delipidation, sialic acid, fucose, glucosamine, mannose, galactose, and glucose were determined on apo LDL-2, apo HDL-2, and apo HDL-3. 3. Glucosamine, galactose, and mannose constituted a major component of the sugars in apo LDL-2, with similar relative proportions in all species. Sialic acid, fucose, and glucose formed a minor component, the proportions of which varied greatly among the species. 4. Unlike apo LDL-2, sialic acid, fucose, and glucosamine constituted the bulk of the sugars in apo HDL-2 and apo HDL-3. Mannose, galactose, and glucose were minor components, with galactose predominating. 5. Qualitative differences were observed in electrophoretic mobilities of apo HDL-2 and apo HDL-3 on polyacrylamide gel. One faster moving band was unique to chimpanzee. 6. Intraspecies differences in the content of sialic acid and fucose of apolipoproteins may be related to lipoprotein metabolism and species susceptibility (or resistance) to either spontaneous or diet-induced atherosclerosis. PMID:233783

  3. High rates of serum Se deficiency among HIV and HCV infected and uninfected drug users in Buenos Aires, Argentina

    PubMed Central

    Sheehan, Heidi B; Benetucci, Jorge; Muzzio, Estela; Redini, Liliana; Naveira, Jorge; Segura, Marcela; Weissenbacher, Mercedes; Tang, Alice M

    2012-01-01

    Objective To describe the prevalence and correlates of low serum Se and determine whether HIV, hepatitis C virus (HCV) and/or types of drugs used are associated with serum Se in a cohort of infected and uninfected drug users. Design Independent correlates of low serum Se levels based on data collected from food recalls, physical exams, and clinical status questionnaires were identified using multivariate analysis. Setting Buenos Aires, Argentina Subjects A total of 205 (25 females and 180 males) former and current drug users Results Drug users had an average serum Se level of 69.8±32.8 μg/dl, and 82% were considered deficient (< 85μg/l). Multivariate analyses found that HIV and/or HCV infection had lower mean Se compared to healthy, uninfected drug users (HIV/HCV co-infection: −25.3 μg/l (SE =7.6, p=0.001); HIV alone: −28.9 μg/l (SE=6.9, p<0.001); HCV alone −19.4 μg/l (SE = 7.1, p=0.006). Current and previous drug use was associated with higher serum Se. Cigarette smoking and heavy alcohol consumption were not found to be associated with Se status. Conclusions Low serum Se levels are highly prevalent among drug users in Buenos Aires, Argentina. Se supplementation and/or dietary interventions may be warranted in drug users who are at high risk of HIV and/or HCV infection. PMID:21740621

  4. A reversed-phase high performance liquid chromatography method for quantification of methotrexate in cancer patients serum.

    PubMed

    Li, Yuan-dong; Li, Yan; Liang, Ning-sheng; Yang, Fan; Kuang, Zhi-peng

    2015-10-01

    A simple, rapid and sensitive reversed-phase high performance liquid chromatography (HPLC) method has been developed for the determination of methotrexate in human serum. After deproteinization of the serum with 40% silver nitrate solution, methotrexate and internal standard (IS) were separated on a reversed-phase column with a mobile phase consisting of 10mM sodium phosphate buffer (pH6.40)-methanol (78:22%, v/v) and ultraviolet detection at 310nm. The linearity is evaluated by a calibration curve in the concentration range of 0.05-10.0μg/mL and presented a correlation coefficient of 0.9995. The absolute recoveries were 97.52±3.9% and 96.87±3.7% for methotrexate and ferulic acid (internal standard), respectively. The intra- and inter-day precision were less 6.19 and 5.89%, respectively (n=6). The limit of quantitation was 0.02μg/mL and the limit of detection was 0.006μg/mL. The complete analysis was achieved less than 10min with no interference from endogenous components or 22 examined drugs. This method was validated by using serum samples from high-dose methotrexate treated patients with osteosarcoma, breast cancer, acute leukemia and lymphoma. The method was demonstrated to be a simple, rapid and reliable approach in quantification of methotrexate in serum samples from patients with high-dose methotrexate therapy. PMID:26319303

  5. High and abnormal forms of aggression in rats with extremes in trait anxiety--involvement of the dopamine system in the nucleus accumbens.

    PubMed

    Beiderbeck, Daniela I; Reber, Stefan O; Havasi, Andrea; Bredewold, Remco; Veenema, Alexa H; Neumann, Inga D

    2012-12-01

    A better neurobiological understanding of high and abnormal aggression based on adequate animal models is essential for novel therapy and prevention. Selective breeding of rats for extremes in anxiety-related behavior resulted in two behavioral phenotypes with high and abnormal forms of aggression. Rats bred for low anxiety-related behavior (LAB) consistently show highest levels of aggression and little social investigation in the resident-intruder (RI) test, compared with non-selected low-aggressive (NAB) rats. High anxiety-related (HAB) rats also show higher levels of aggression than NAB rats, but to a lesser extent than LAB rats. Accordingly, extremes in inborn anxiety in both directions are linked to an increased aggression level. Further, both LAB and HAB, but not NAB males, display abnormal aggression (attacks towards vulnerable body parts, females or narcotized males), which is particularly prominent in LABs. Also, only in LAB rats, the nucleus accumbens (NAc) was found to be strongly activated in response to the RI test as reflected by increased c-fos and zif268 mRNA expression, and higher local dopamine release compared with NAB males, without differences in local dopamine receptor binding. Consequently, local pharmacological manipulation by infusion of an anesthetic (lidocaine, 20 μg/μl) or a dopamine D2 (haloperidol, 10 ng/μl), but not D1 (SCH-23390 10 ng/μl), receptor antagonist significantly reduced high aggression in LAB rats. Thus, LAB rats are an adequate model to study high and abnormal aggression. In LAB males, this is likely to be linked to hyper-activation of the reward system, as found in psychopathic patients. Specifically, activation of the accumbal dopamine system is likely to underlie the high aggression observed in LAB rats. PMID:22608548

  6. Age and sensory processing abnormalities predict declines in encoding and recall of temporally manipulated speech in high-functioning adults with ASD.

    PubMed

    Mayer, Jennifer L; Heaton, Pamela F

    2014-02-01

    While temporal and perceptual processing abnormalities, identified in a number of electrophysiological and brain imaging studies of individuals with (ASD), are likely to impact on speech perception, surprisingly little is known about the behavioral outcomes of such abnormalities. It has been hypothesized that rapid temporal processing deficits may be linked to impaired language development through interference with acoustic information during speech perception. The present study aimed to investigate the impact of temporal changes on encoding and recall of speech, and the associated cognitive, clinical, and behavioral correlates in adults with ASD. Research carried out with typically developing (TD) adults has shown that word recall diminishes as the speed of speech increases, and it was predicted that the magnitude of this effect would be far greater in those with ASD because of a preexisting rapid temporal processing deficit. Nineteen high-functioning adults with ASD, and age- and intelligence-matched TD controls performed verbatim recall of temporally manipulated sentences. Reduced levels of word recall in response to increases in presentation speed were observed, and this effect was greater in the older participants in the ASD group than in the control group. This is the first study to show that both sensory abnormalities and aging impact on speech encoding in ASD. Auditory processing deficits in ASD may be indicative of an association with the sensory abnormalities and social and communication impairments characterizing the disorder. PMID:24106132

  7. Is abnormal non-high-density lipoprotein cholesterol a gender-specific predictor for metabolic syndrome in patients with schizophrenia taking second-generation antipsychotics?

    PubMed

    Lin, Esther Ching-Lan; Shao, Wen-Chuan; Yang, Hsin-Ju; Yen, Miaofen; Lee, Sheng-Yu; Wu, Pei-Chun; Lu, Ru-Band

    2015-02-01

    Evidence supports an association between metabolic syndrome (MetS) and schizophrenia. However, specific risk factors for MetS and gender differences in patients with schizophrenia taking second-generation antipsychotics (SGAs) have not been well explored. A cross-sectional cohort of 329 Han Chinese patients was recruited in a psychiatric hospital in central Taiwan. Using the definitions of the International Diabetes Federation for Chinese, the prevalence of MetS was 23.7% (men: 25.7%; women: 21.2%). Logistic regression analyses showed that patients with a BMI ≥ 24 and an abnormal non-high-density lipoprotein cholesterol (non-HDL-C) were significantly (p < 0.001) more likely to develop MetS. A BMI ≥ 24 was a significant risk factor in men (OR: 6.092, p < 0.001) and women (OR: 5.886, p < 0.001). An abnormal non-HDL-C was a significant specific risk factor for men with MetS (OR: 4.127, p < 0.001), but not for women. This study supports a greater prevalence of MetS in patients with schizophrenia taking SGAs than in the general population. Abnormal BMI and non-HDL-C were significantly associated with developing MetS, and an abnormal non-HDL-C was a specific risk factor for men. Future development of specific interventions and regular monitoring for MetS is imperative for early identification and prevention. PMID:25034455

  8. Relationship between High Serum Cystatin C Levels and the Risk of Gestational Diabetes Mellitus

    PubMed Central

    Li, Huaping; Huang, Yajuan; Liu, Fang; Tao, Minfang; Jia, Weiping

    2016-01-01

    Aims Serum cystatin C (CysC) has recently been shown to be associated with the incidence of type 2 diabetes mellitus (T2DM) and progression to the pre-diabetic state. The aim of this study was to explore the relationship between serum CysC and the risk of gestational diabetes mellitus (GDM) in Chinese pregnant women. Methods This cross-sectional study consisted of 400 pregnant women including111 with GDM and 289 with normal glucose tolerance at 24–28 weeks of gestation. The subjects were further divided into four groups according to the CysC quartiles, and their clinical characteristics were compared. The serum CysC concentration was measured using immunoturbidimetry and the degree of insulin resistance was assessed by the homeostasis model assessment of insulin resistance (HOMA-IR). Results Serum CysC levels were significantly higher in pregnant women with GDM than in the healthy pregnant women[1.0(0.8–1.8) vs 0.7(0.6–1.0), P<0.01). The Spearman’s correlation analysis showed that serum CysC was positively associated with HOMA-IR(r = 0.118, P<0.05) and the occurrence of GDM(r = 0.348, P<0.01). The pregnant women were divided into quartiles according to their serum CysC concentrations. Compared to the first quartile, pregnant women in Q2 (OR, 2.441; P = 0.025), Q3 (OR, 3.383; P = 0.001) and Q4 (OR, 5.516; P<0.001) had higher risk of GDM after adjusted for age, BMI, HbA1c and HOMA-IR. Further, with a rise in the serum CysC, there was an increasing trend in the HOMA-IR levels (P<0.05). A binary logistic regression analysis after adjusting for other confounding variables revealed a significant and independent association between serum CysC and GDM [OR = 14.269; 95% confidence interval, 4.977–40.908, P<0.01].The receiver operating characteristic curve analysis revealed that the optimal cutoff point for serum CysC to indicate GDM was 0.95mg/L. Conclusions Serum CysC is significantly and independently associated with insulin resistance and GDM. It may be a

  9. Patients with MCI and N400 or P600 abnormalities are at very high risk for conversion to dementia

    PubMed Central

    Olichney, J.M.; Taylor, J.R.; Gatherwright, J.; Salmon, D.P.; Bressler, A.J.; Kutas, M.; Iragui-Madoz, V.J.

    2011-01-01

    Objective We sought cognitive event-related potential (ERP) biomarkers of disease progression and subsequent conversion to dementia in mild cognitive impairment (MCI). Background Two ERP components, the P600 and N400, are sensitive to abnormal episodic/declarative memory and semantic processing. When congruous category-exemplars are repeated, smaller P600s (relative to initial presentation) are normally elicited. Repetitions of semantically incongruous words yield smaller N400 amplitude. In mild Alzheimer disease (AD), abnormalities of both the N400 and P600 repetition effects are present, suggesting a wide-spread failure of synaptic plasticity. Methods Patients with amnestic MCI (n = 32) were longitudinally studied annually with an ERP paradigm in which semantically congruous (50%) and incongruous target words are repeated 10 to 140 seconds after initial presentation. ERP data were analyzed to contrast MCI-to-AD converters (within 3 years) vs nonconverters, using split-plot analyses of variance. Results A statistically significant P600 congruous word repetition effect was found only in the nonconverter group (F = 9.9, p = 0.005 vs MCI converters). This effect correlated with verbal memory measures. Repetition of incongruous words produced a significant N400 amplitude attenuation (across right-hemisphere sites) in nonconverters, but not in converters. Patients with MCI with abnormal/reduced N400 or P600 word repetition effects had an 87 to 88% likelihood of dementia within 3 years while those with normal/spared N400 and P600 repetition effects had only an 11 to 27% likelihood. Conclusions Abnormalities of the P600 or N400 in mild cognitive impairment are associated with an increased risk of subsequent conversion to Alzheimer disease (AD). These event-related potential components may offer useful biomarkers for the detection and staging of very early AD. PMID:18077800

  10. REG4 Is Highly Expressed in Mucinous Ovarian Cancer: A Potential Novel Serum Biomarker.

    PubMed

    Lehtinen, Laura; Vesterkvist, Pia; Roering, Pia; Korpela, Taina; Hattara, Liisa; Kaipio, Katja; Mpindi, John-Patrick; Hynninen, Johanna; Auranen, Annika; Davidson, Ben; Haglund, Caj; Iljin, Kristiina; Grenman, Seija; Siitari, Harri; Carpen, Olli

    2016-01-01

    Preoperative diagnostics of ovarian neoplasms rely on ultrasound imaging and the serum biomarkers CA125 and HE4. However, these markers may be elevated in non-neoplastic conditions and may fail to identify most non-serous epithelial cancer subtypes. The objective of this study was to identify histotype-specific serum biomarkers for mucinous ovarian cancer. The candidate genes with mucinous histotype specific expression profile were identified from publicly available gene-expression databases and further in silico data mining was performed utilizing the MediSapiens database. Candidate biomarker validation was done using qRT-PCR, western blotting and immunohistochemical staining of tumor tissue microarrays. The expression level of the candidate gene in serum was compared to the serum CA125 and HE4 levels in a patient cohort of prospectively collected advanced ovarian cancer. Database searches identified REG4 as a potential biomarker with specificity for the mucinous ovarian cancer subtype. The specific expression within epithelial ovarian tumors was further confirmed by mRNA analysis. Immunohistochemical staining of ovarian tumor tissue arrays showed distinctive cytoplasmic expression pattern only in mucinous carcinomas and suggested differential expression between benign and malignant mucinous neoplasms. Finally, an ELISA based serum biomarker assay demonstrated increased expression only in patients with mucinous ovarian cancer. This study identifies REG4 as a potential serum biomarker for histotype-specific detection of mucinous ovarian cancer and suggests serum REG4 measurement as a non-invasive diagnostic tool for postoperative follow-up of patients with mucinous ovarian cancer. PMID:26981633

  11. REG4 Is Highly Expressed in Mucinous Ovarian Cancer: A Potential Novel Serum Biomarker

    PubMed Central

    Lehtinen, Laura; Vesterkvist, Pia; Roering, Pia; Korpela, Taina; Hattara, Liisa; Kaipio, Katja; Mpindi, John-Patrick; Hynninen, Johanna; Auranen, Annika; Davidson, Ben; Haglund, Caj; Iljin, Kristiina; Grenman, Seija; Siitari, Harri; Carpen, Olli

    2016-01-01

    Preoperative diagnostics of ovarian neoplasms rely on ultrasound imaging and the serum biomarkers CA125 and HE4. However, these markers may be elevated in non-neoplastic conditions and may fail to identify most non-serous epithelial cancer subtypes. The objective of this study was to identify histotype-specific serum biomarkers for mucinous ovarian cancer. The candidate genes with mucinous histotype specific expression profile were identified from publicly available gene-expression databases and further in silico data mining was performed utilizing the MediSapiens database. Candidate biomarker validation was done using qRT-PCR, western blotting and immunohistochemical staining of tumor tissue microarrays. The expression level of the candidate gene in serum was compared to the serum CA125 and HE4 levels in a patient cohort of prospectively collected advanced ovarian cancer. Database searches identified REG4 as a potential biomarker with specificity for the mucinous ovarian cancer subtype. The specific expression within epithelial ovarian tumors was further confirmed by mRNA analysis. Immunohistochemical staining of ovarian tumor tissue arrays showed distinctive cytoplasmic expression pattern only in mucinous carcinomas and suggested differential expression between benign and malignant mucinous neoplasms. Finally, an ELISA based serum biomarker assay demonstrated increased expression only in patients with mucinous ovarian cancer. This study identifies REG4 as a potential serum biomarker for histotype-specific detection of mucinous ovarian cancer and suggests serum REG4 measurement as a non-invasive diagnostic tool for postoperative follow-up of patients with mucinous ovarian cancer. PMID:26981633

  12. High serum selenium levels are associated with increased risk for diabetes mellitus independent of central obesity and insulin resistance

    PubMed Central

    Lu, Chia-Wen; Chang, Hao-Hsiang; Yang, Kuen-Cheh; Kuo, Chia-Sheng; Lee, Long-Teng; Huang, Kuo-Chin

    2016-01-01

    Objective Selenium is an essential micronutrient for human health. Although many observational and interventional studies have examined the associations between selenium and diabetes mellitus, the findings were inconclusive. This study aimed to investigate the relationship between serum selenium levels and prevalence of diabetes, and correlated the relationship to insulin resistance and central obesity. Research design and methods This was a hospital-based case–control study of 847 adults aged more than 40 years (diabetes: non-diabetes =1:2) in Northern Taiwan. Serum selenium was measured by an inductively coupled plasma-mass spectrometer. The association between serum selenium and diabetes was examined using multivariate logistic regression analyses. Results After adjusting for age, gender, current smoking, current drinking, and physical activity, the ORs (95% CI, p value) of having diabetes in the second (Q2), third (Q3), and fourth (Q4) selenium quartile groups were 1.24 (95% CI 0.78 to 1.98, p>0.05), 1.90 (95% CI 1.22 to 2.97, p<0.05), and 5.11 (95% CI 3.27 to 8.00, p<0.001), respectively, compared with the first (Q1) quartile group. Further adjustments for waist circumference and homeostatic model assessment-insulin resistance (HOMA-IR) largely removed the association of serum selenium levels with diabetes but not in the highest quartile (compared with Q1, Q3: 1.57, 95% CI 0.91 to 2.70, Q4: 3.79, 95% CI 2.17 to 6.32). Conclusions We found that serum selenium levels were positively associated with prevalence of diabetes. This is the first human study to link insulin resistance and central obesity to the association between selenium and diabetes. Furthermore, the association between selenium and diabetes was independent of insulin resistance and central obesity at high serum selenium levels. The mechanism behind warrants further confirmation. PMID:27547419

  13. Fatty liver and hepatic function for residents with markedly high serum PCDD/Fs levels in Taiwan.

    PubMed

    Lee, Ching-Chang; Yao, Yei-Jen; Chen, Hsiu-Ling; Guo, Yue-Liang; Su, Huey-Jen

    2006-03-01

    This study was designed to examine the associations between serum polychtorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) levels and adverse hepatic-related health outcomes. Residents living in the vicinity of a closed pentachlorophenol (PCP) manufacturing factory (exposure area) and other areas nearby (control area) were identified from prior investigation of serum PCDD/Fs measurements. A total of 85 subjects were recruited for the study, 52 from exposure area and 33 from control, respectively. Average level of serum PCDD/Fs was 80.1 6 50.9 pg WHO-TEQ/g lipid for those residing in exposure area, and 25.5 6 18.2 in control area. Statistically higher odds ratio (ORs) for fatty liver and gamma-glutamyltransferase (GGT) activity was found in subjects with higher serum PCDD/Fs levels and high body mass index (BMI) as compared to those with lower PCDD/Fs levels and less BMI. Data suggest that dioxin exposure and high lipid content affect the prevalence of fatty liver in exposed subjects. Future study should be directed to prevent continuous exposure to environmental PCDD/Fs from the defunct PCP factory, and to characterize prospectively, with a larger study sample size, the potential long-term consequences on hepatic function associated with contaminant exposure. PMID:16455615

  14. Serum levels of brain-derived neurotrophic factor in alcohol-dependent patients receiving high-dose baclofen.

    PubMed

    Geisel, Olga; Hellweg, Rainer; Müller, Christian A

    2016-06-30

    The neurotrophin brain-derived neurotrophic factor (BDNF) has been suggested to be involved in the development and maintenance of addictive and other psychiatric disorders. Also, interactions of γ-aminobutyric acid (GABA)-ergic compounds and BDNF have been reported. The objective of this study was to investigate serum levels of BDNF over time in alcohol-dependent patients receiving individually titrated high-dose treatment (30-270mg/d) with the GABA-B receptor agonist baclofen or placebo for up to 20 weeks. Serum levels of BDNF were measured in patients of the baclofen/placebo group at baseline (t0), 2 weeks after reaching individual high-dose of baclofen/placebo treatment (t1) and after termination of study medication (t2) in comparison to carefully matched healthy controls. No significant differences in serum levels of BDNF between the baclofen and the placebo group or healthy controls were found at t0, t1, or at t2. Based on these findings, it seems unlikely that baclofen exerts a direct effect on serum levels of BDNF in alcohol-dependent patients. Future studies are needed to further explore the mechanism of action of baclofen and its possible relationship to BDNF in alcohol use disorders. PMID:27107672

  15. Morphological abnormalities in elasmobranchs.

    PubMed

    Moore, A B M

    2015-08-01

    A total of 10 abnormal free-swimming (i.e., post-birth) elasmobranchs are reported from The (Persian-Arabian) Gulf, encompassing five species and including deformed heads, snouts, caudal fins and claspers. The complete absence of pelvic fins in a milk shark Rhizoprionodon acutus may be the first record in any elasmobranch. Possible causes, including the extreme environmental conditions and the high level of anthropogenic pollution particular to The Gulf, are briefly discussed. PMID:25903257

  16. Measurement of serum total glycerides and free glycerol by high-performance liquid chromatography.

    PubMed

    Li, Hongxia; Dong, Jun; Chen, Wenxiang; Wang, Shu; Guo, Hanbang; Man, Yong; Mo, Peisheng; Li, Jianzhai

    2006-09-01

    Serum levels of total glycerides and free glycerol are important indices of lipid metabolism and cardiovascular disease risk. Convenient enzymatic methods of measurement have been available, but they are susceptible to interference. Situations exist in both research and clinical laboratories in which more specific and precise methods are needed. We developed HPLC methods for the measurement of serum total glycerides and free glycerol. For total glycerides, serum was mixed with an internal standard (1,2,4-butanetriol) and treated with alcoholic sodium hydroxide to hydrolyze glycerides to glycerol. After deproteinization with tungstic acid, the glycerol was benzoylated with an optimized Schotten-Baumann reaction and analyzed by HPLC. For free glycerol, serum was equilibrated with the internal standard and deproteinized with tungstic acid to remove the glycerides. The glycerol was benzoylated and analyzed as for total glycerol. Various factors were investigated, and no significant sources of interference were detected. The total coefficients of variation ranged from 0.7% to 2.0% for total glycerides and from 1.7% to 3.2% for free glycerol. The analytical recoveries ranged from 98.5% to 101.6%. In conclusion, simple and reliable HPLC methods for serum total glycerides and free glycerol have been developed. The methods may also be used for the analyses of glycerol or glycerides in other biological samples. PMID:16788212

  17. Consumption of a high-fat meal containing cheese compared with a vegan alternative lowers postprandial C-reactive protein in overweight and obese individuals with metabolic abnormalities: a randomised controlled cross-over study.

    PubMed

    Demmer, Elieke; Van Loan, Marta D; Rivera, Nancy; Rogers, Tara S; Gertz, Erik R; German, J Bruce; Zivkovic, Angela M; Smilowitz, Jennifer T

    2016-01-01

    Dietary recommendations suggest decreased consumption of SFA to minimise CVD risk; however, not all foods rich in SFA are equivalent. To evaluate the effects of SFA in a dairy food matrix, as Cheddar cheese, v. SFA from a vegan-alternative test meal on postprandial inflammatory markers, a randomised controlled cross-over trial was conducted in twenty overweight or obese adults with metabolic abnormalities. Individuals consumed two isoenergetic high-fat mixed meals separated by a 1- to 2-week washout period. Serum was collected at baseline, and at 1, 3 and 6 h postprandially and analysed for inflammatory markers (IL-6, IL-8, IL-10, IL-17, IL-18, TNFα, monocyte chemotactic protein-1 (MCP-1)), acute-phase proteins C-reactive protein (CRP) and serum amyloid-A (SAA), cellular adhesion molecules and blood lipids, glucose and insulin. Following both high-fat test meals, postprandial TAG concentrations rose steadily (P < 0·05) without a decrease by 6 h. The incremental AUC (iAUC) for CRP was significantly lower (P < 0·05) in response to the cheese compared with the vegan-alternative test meal. A treatment effect was not observed for any other inflammatory markers; however, for both test meals, multiple markers significantly changed from baseline over the 6 h postprandial period (IL-6, IL-8, IL-18, TNFα, MCP-1, SAA). Saturated fat in the form of a cheese matrix reduced the iAUC for CRP compared with a vegan-alternative test meal during the postprandial 6 h period. The study is registered at clinicaltrials.gov under NCT01803633. PMID:27313852

  18. Optimization of human serum albumin monoliths for chiral separations and high-performance affinity chromatography.

    PubMed

    Pfaunmiller, Erika L; Hartmann, Mahli; Dupper, Courtney M; Soman, Sony; Hage, David S

    2012-12-21

    Various organic-based monoliths were prepared and optimized for immobilization of the protein human serum albumin (HSA) as a binding agent for chiral separations and high-performance affinity chromatography. These monoliths contained co-polymers based on glycidyl methacrylate (GMA) and ethylene glycol dimethacrylate (EDMA) or GMA and trimethylolpropane trimethacrylate (TRIM). A mixture of cyclohexanol and 1-dodecanol was used as the porogen, with the ratio of these solvents being varied along with the polymerization temperature to generate a library of monoliths. These monoliths were used with both the Schiff base and epoxy immobilization methods and measured for their final content of HSA. Monoliths showing the highest protein content were further evaluated in chromatographic studies using R/S-warfarin and d/l-tryptophan as model chiral solutes. A 2.6-2.7-fold increase in HSA content was obtained in the final monoliths when compared to similar HSA monoliths prepared according to the literature. The increased protein content made it possible for the new monoliths to provide higher retention and/or two-fold faster separations for the tested solutes when using 4.6mm i.d.× 50 mm columns. These monoliths were also used to create 4.6mm i.d.× 10 mm HSA microcolumns that could separate the same chiral solutes in only 1.5-6.0 min. The approaches used in this study could be extended to the separation of other chiral solutes and to the optimization of organic monoliths for use with additional proteins as binding agents. PMID:23010249

  19. Optimization of human serum albumin monoliths for chiral separations and high-performance affinity chromatography

    PubMed Central

    Pfaunmiller, Erika L.; Hartmann, Mahli; Dupper, Courtney M.; Soman, Sony; Hage, David S.

    2012-01-01

    Various organic-based monoliths were prepared and optimized for immobilization of the protein human serum albumin (HSA) as a binding agent for chiral separations and high-performance affinity chromatography. These monoliths contained co-polymers based on glycidyl methacrylate (GMA) and ethylene glycol dimethacrylate (EDMA) or GMA and trimethylolpropane trimethacrylate (TRIM). A mixture of cyclohexanol and 1-dodecanol was used as the porogen, with the ratio of these solvents being varied along with the polymerization temperature to generate a library of monoliths. These monoliths were used with both the Schiff base and epoxy immobilization methods and measured for their final content of HSA. Monoliths showing the highest protein content were further evaluated in chromatographic studies using R/S-warfarin and d/l-tryptophan as model chiral solutes. A 2.6–2.7-fold increase in HSA content was obtained in the final monoliths when compared to similar HSA monoliths prepared according to the literature. The increased protein content made it possible for the new monoliths to provide higher retention and/or two-fold faster separations for the tested solutes when using 4.6 mm i.d. × 50 mm columns. These monoliths were also used to create 4.6 mm i.d. × 10 mm HSA microcolumns that could separate the same chiral solutes in only 1.5–6.0 min. The approaches used in this study could be extended to the separation of other chiral solutes and to the optimization of organic monoliths for use with additional proteins as binding agents. PMID:23010249

  20. Highly sensitive detection of bovine serum albumin based on the aggregation of triangular silver nanoplates

    NASA Astrophysics Data System (ADS)

    Zhang, Ling Ling; Ma, Fang Fang; Kuang, Yang Fang; Cheng, Shu; Long, Yun Fei; Xiao, Qiu Guo

    2016-02-01

    A simple, fast and highly sensitive spectrophotometric method for the determination of bovine serum albumin (BSA) has been developed based on the interactions between triangular silver nanoplates (TAgNPs) and BSA in the presence of Britton-Robison buffer solution (BR). Particularly, the wavelength of absorption maximum (λmax) of TAgNPs is red shifted in the presence of BSA together with Britton-Robinson buffer solution (BR, pH = 2.56), and the color of the solution changed from blue to light blue. This may be due to the interactions between BSA molecules on the surface of TAgNPs through electrostatic forces, hydrogen bonds, hydrophobic effects and van der Waals forces at pH 2.56, which leads to the aggregation of TAgNPs. The determination of BSA was achieved by measuring the change of λmax corresponding to localized surface plasmon resonance (LSPR) from UV-visible spectrophotometry. It was found that the shift value in the wavelength of absorption maximum (Δλ, the difference in absorption maxima of the TAgNPs/BSA/BR mixture and the TAgNPs/BR mixture) was proportionate to the concentration of BSA in the range of 1.0 ng mL- 1 to 100.0 ng mL- 1 with the correlation coefficient of r = 0.9969. The detection limit (3 σ/k) for BSA was found to be as low as 0.5 ng mL- 1.

  1. Serum YKL-40 is a marker of prognosis and disease status in high-grade gliomas.

    PubMed

    Iwamoto, Fabio M; Hottinger, Andreas F; Karimi, Sasan; Riedel, Elyn; Dantis, Jocelynn; Jahdi, Maryam; Panageas, Katherine S; Lassman, Andrew B; Abrey, Lauren E; Fleisher, Martin; DeAngelis, Lisa M; Holland, Eric C; Hormigo, Adília

    2011-11-01

    The objective of this study was to evaluate whether longitudinal levels of serum YKL-40 correlate with disease status or survival in adults with gliomas. Patients with histologically confirmed gliomas were eligible for this longitudinal study. Serum samples were collected prospectively and concurrently with MRI scans at multiple time points during the course of the disease. YKL-40 levels determined by ELISA were correlated with radiographic disease status and survival. We performed a multivariate survival analysis including well-known prognostic factors such as age, performance status, and extent of surgical resection. Three hundred and forty-three patients with gliomas (41 low-grade, 105 anaplastic, and 197 glioblastoma) were accrued. Two-year survival from registration was 29% for glioblastomas, 62% for anaplastic gliomas, and 83% for low-grade gliomas. A total of 1740 serum samples were collected, and 95.6% of samples had matching MRI scans. Serum YKL-40 level was significantly lower in patients with no radiographic disease compared with patients with radiographic disease in both the anaplastic glioma (P= .0008) and the glioblastoma (P= .0006) cohorts. Serum levels of YKL-40 in patients with low-grade gliomas were not associated with radiographic disease status. Increases in YKL-40 were independently associated with worse survival in anaplastic gliomas (hazard ratio [HR] = 1.4, P= .01) and glioblastomas (HR = 1.4, P< .0001). Longitudinal increases in serum YKL-40 are associated with increased risk of death in patients with glioblastomas and anaplastic gliomas. YKL-40 is also a putative indicator of disease status in these patients. PMID:21831900

  2. Serum YKL-40 is a marker of prognosis and disease status in high-grade gliomas†

    PubMed Central

    Iwamoto, Fabio M.; Hottinger, Andreas F.; Karimi, Sasan; Riedel, Elyn; Dantis, Jocelynn; Jahdi, Maryam; Panageas, Katherine S.; Lassman, Andrew B.; Abrey, Lauren E.; Fleisher, Martin; DeAngelis, Lisa M.; Holland, Eric C.; Hormigo, Adília

    2011-01-01

    The objective of this study was to evaluate whether longitudinal levels of serum YKL-40 correlate with disease status or survival in adults with gliomas. Patients with histologically confirmed gliomas were eligible for this longitudinal study. Serum samples were collected prospectively and concurrently with MRI scans at multiple time points during the course of the disease. YKL-40 levels determined by ELISA were correlated with radiographic disease status and survival. We performed a multivariate survival analysis including well-known prognostic factors such as age, performance status, and extent of surgical resection. Three hundred and forty-three patients with gliomas (41 low-grade, 105 anaplastic, and 197 glioblastoma) were accrued. Two-year survival from registration was 29% for glioblastomas, 62% for anaplastic gliomas, and 83% for low-grade gliomas. A total of 1740 serum samples were collected, and 95.6% of samples had matching MRI scans. Serum YKL-40 level was significantly lower in patients with no radiographic disease compared with patients with radiographic disease in both the anaplastic glioma (P= .0008) and the glioblastoma (P= .0006) cohorts. Serum levels of YKL-40 in patients with low-grade gliomas were not associated with radiographic disease status. Increases in YKL-40 were independently associated with worse survival in anaplastic gliomas (hazard ratio [HR] = 1.4, P= .01) and glioblastomas (HR = 1.4, P< .0001). Longitudinal increases in serum YKL-40 are associated with increased risk of death in patients with glioblastomas and anaplastic gliomas. YKL-40 is also a putative indicator of disease status in these patients. PMID:21831900

  3. Oral high-dose medroxyprogesterone acetate (MPA) treatment: cortisol/MPA serum profiles in relation to breast cancer regression.

    PubMed

    Mahlke, M; Grill, H J; Knapstein, P; Wiegand, U; Pollow, K

    1985-01-01

    Medroxyprogesterone acetate (MPA), a potent synthetic progestin, has been widely used in the hormonal treatment of advanced breast cancer, but presently with varying dose schedules. The availability of a sensitive RIA-method for determination of serum MPA has stimulated the research on MPA serum levels in patients after repeated MPA administration. The aim of this study was to assay blood level profiles of MPA as well as of cortisol during repeated high-dose orally administered MPA. 34 patients with metastatic breast cancer were enrolled in this study. 12 patients died already within the first 4 weeks of MPA treatment due to multiple metastases. The dosage regimen based on the daily oral administration of 1,000 mg MPA suspension. During MPA treatment, a decrease of cortisol serum levels was observed in nearly all patients. Within the observation time of 8 months out of 22 evaluable cases 18.2% responded to the therapy (complete and partial response). No change was observed in 36.4% and progression in 45.5% of the patients. Within the remission (complete and partial) group, a good correlation between constant MPA serum levels above 150 ng/ml and remission was observed. But in the groups with no change and progression no such correlation could be observed. PMID:4000617

  4. Highly sensitive detection of HER2 extracellular domain (ECD) in the serum of breast cancer patients by piezoelectric microcantilevers (PEMS)

    PubMed Central

    Loo, LiNa; Capobianco, Joseph A.; Wu, Wei; Gao, Xiaotong; Shih, Wan Y.; Shih, Wei-Heng; Pourrezaei, Kambiz; Robinson, Matthew K.; Adams, Gregory P.

    2011-01-01

    Rapid and sensitive detection of serum tumor biomarkers are needed to monitor cancer patients for disease progression. Highly sensitive piezoelectric microcantilever sensors (PEMS) offer an attractive tool for biomarker detection, however their utility in the complex environment encountered in serum has yet to be determined. As a proof of concept, we have functionalized PEMS with antibodies that specifically bind to HER2, a biomarker (antigen) that is commonly overexpressed in the blood of breast cancer patients. The function and sensitivity of these anti-HER2 PEMS biosensors was initially assessed using recombinant HER2 spiked into human serum. Their ability to detect native HER2 present in the serum of breast cancer patients was then determined. We have found that the anti-HER2 PEMS were able to accurately detect both recombinant and naturally occurring HER2 at clinically relevant levels (>2 ng/ml). This indicates that PEMS-based biosensors provide a potentially effective tool for biomarker detection. PMID:21449604

  5. Determination and Pharmacokinetic Study of Pirfenidone in Rat Serum by High-Performance Thin-Layer Chromatography.

    PubMed

    Thorat, Sonali G; Chikhale, Rupesh V

    2016-08-01

    A rapid, sensitive and selective high-performance thin-layer chromatography (HPTLC) method was developed and validated for the determination and pharmacokinetics of pirfenidone in rat serum. One-step protein precipitation by methanol is reported, and serum samples were separated by HPTLC using a simple mobile phase of toluene-methanol in the ratio of 8:2. The retardation factor of pirfenidone in the serum sample was 0.45 with the detection performed at 315 nm. The calibration curve was linear over the range of 100-1,200 ng/spot with a lower limit of quantitation of 40 ng/spot. The mean recovery of pirfenidone in serum was in the range of 70.6-75.8%, and intra-day and inter-day precision were both <14.1%. This method was successfully applied to the pharmacokinetic study of pirfenidone in rats on oral administration of the drug at a dose of 15.0 mg/kg. PMID:27406123

  6. Highly Specific Detection of Myostatin Prodomain by an Immunoradiometric Sandwich Assay in Serum of Healthy Individuals and Patients

    PubMed Central

    Widera, Christian; Gottlieb, Jens; Vogel, Arndt; Schmidt, Sebastian; Brandes, Gudrun; Heuft, Hans-Gert; Lichtinghagen, Ralf; Kempf, Tibor; Wollert, Kai C.; Bauersachs, Johann; Heineke, Joerg

    2013-01-01

    Background Myostatin is a muscle derived factor that functions as a negative regulator of skeletal muscle growth. Induction of myostatin expression was observed in rodent models of muscle wasting and in cachectic patients with cancer or pulmonary disease. Therefore, there is an increasing interest to use serum myostatin as a biomarker. Methods We established an immunoradiometric sandwich assay (IRMA), which uses a commercially available chicken polyclonal, affinity purified antibody directed against human myostatin prodomain. We determined the serum concentrations of myostatin prodomain in 249 healthy individuals as well as 169 patients with heart failure, 53 patients with cancer and 44 patients with chronic pulmonary disease. Results The IRMA had a detection limit of 0.7ng/ml, an intraassay imprecision of ≤14.1% and an interassay imprecision of ≤ 18.9%. The specificity of our assay was demonstrated by size exclusion chromatography, detection of myostatin by Western-blotting and a SMAD-dependent transcriptional-reporter assay in the signal-rich serum fractions, as well as lack of interference by unspecific substances like albumin, hemoglobin or lipids. Myostatin prodomain was stable at room temperature and resistant to freeze-thaw cycles. Apparently healthy individuals over the age of 55 had a median myostatin prodomain serum concentration of 3.9ng/ml (25th-75th percentiles, 2-7ng/ml) and we could not detect increased levels in patients with stable chronic heart failure or cancer related weight loss. In contrast, we found strongly elevated concentrations of myostatin prodomain (median 26.9ng/ml, 25th-75th percentiles, 7-100ng/ml) in the serum of underweight patients with chronic pulmonary disease. Conclusions We established a highly specific IRMA for the quantification of myostatin prodomain concentration in human serum. Our assay could be useful to study myostatin as a biomarker for example in patients with chronic pulmonary disease, as we detected highly

  7. Abnormal pressure in hydrocarbon environments

    USGS Publications Warehouse

    Law, B.E.; Spencer, C.W.

    1998-01-01

    Abnormal pressures, pressures above or below hydrostatic pressures, occur on all continents in a wide range of geological conditions. According to a survey of published literature on abnormal pressures, compaction disequilibrium and hydrocarbon generation are the two most commonly cited causes of abnormally high pressure in petroleum provinces. In young (Tertiary) deltaic sequences, compaction disequilibrium is the dominant cause of abnormal pressure. In older (pre-Tertiary) lithified rocks, hydrocarbon generation, aquathermal expansion, and tectonics are most often cited as the causes of abnormal pressure. The association of abnormal pressures with hydrocarbon accumulations is statistically significant. Within abnormally pressured reservoirs, empirical evidence indicates that the bulk of economically recoverable oil and gas occurs in reservoirs with pressure gradients less than 0.75 psi/ft (17.4 kPa/m) and there is very little production potential from reservoirs that exceed 0.85 psi/ft (19.6 kPa/m). Abnormally pressured rocks are also commonly associated with unconventional gas accumulations where the pressuring phase is gas of either a thermal or microbial origin. In underpressured, thermally mature rocks, the affected reservoirs have most often experienced a significant cooling history and probably evolved from an originally overpressured system.

  8. Genotype Distribution of Human Papillomavirus among Women with Cervical Cytological Abnormalities or Invasive Squamous Cell Carcinoma in a High-Incidence Area of Esophageal Carcinoma in China

    PubMed Central

    Wang, Yuanyuan; Wang, Shaohong; Shen, Jinhui; Peng, Yanyan; Chen, Lechuan; Mai, Ruiqin

    2016-01-01

    Data of HPV genotype including 16 high-risk HPV (HR-HPV) and 4 low-risk HPV from 38,397 women with normal cytology, 1341 women with cervical cytology abnormalities, and 223 women with ISCC were retrospectively evaluated by a hospital-based study. The prevalence of high-risk HPV (HR-HPV) was 6.51%, 41.83%, and 96.86% in women with normal cytology, cervical cytology abnormalities, and ISCC, respectively. The three most common HPV types were HPV-52 (1.76%), HPV-16 (1.28%), and HPV-58 (0.97%) in women with normal cytology, whereas the most prevalent HPV type was HPV-16 (16.85%), followed by HPV-52 (9.55%) and HPV-58 (7.83%) in women with cervical cytology abnormalities. Specifically, HPV-16 had the highest frequency in ASC-H (24.16%, 36/149) and HSIL (35.71%, 110/308), while HPV-52 was the most common type in ASC-US (8.28%, 53/640) and LSIL (16.80%, 41/244). HPV-16 (75.78%), HPV18 (10.31%), and HPV58 (9.87%) were the most common types in women with ISCC. These data might contribute to increasing the knowledge of HPV epidemiology and providing the guide for vaccine selection for women in Shantou. PMID:27610364

  9. Genotype Distribution of Human Papillomavirus among Women with Cervical Cytological Abnormalities or Invasive Squamous Cell Carcinoma in a High-Incidence Area of Esophageal Carcinoma in China.

    PubMed

    Wang, Yuanyuan; Wang, Shaohong; Shen, Jinhui; Peng, Yanyan; Chen, Lechuan; Mai, Ruiqin; Zhang, Guohong

    2016-01-01

    Data of HPV genotype including 16 high-risk HPV (HR-HPV) and 4 low-risk HPV from 38,397 women with normal cytology, 1341 women with cervical cytology abnormalities, and 223 women with ISCC were retrospectively evaluated by a hospital-based study. The prevalence of high-risk HPV (HR-HPV) was 6.51%, 41.83%, and 96.86% in women with normal cytology, cervical cytology abnormalities, and ISCC, respectively. The three most common HPV types were HPV-52 (1.76%), HPV-16 (1.28%), and HPV-58 (0.97%) in women with normal cytology, whereas the most prevalent HPV type was HPV-16 (16.85%), followed by HPV-52 (9.55%) and HPV-58 (7.83%) in women with cervical cytology abnormalities. Specifically, HPV-16 had the highest frequency in ASC-H (24.16%, 36/149) and HSIL (35.71%, 110/308), while HPV-52 was the most common type in ASC-US (8.28%, 53/640) and LSIL (16.80%, 41/244). HPV-16 (75.78%), HPV18 (10.31%), and HPV58 (9.87%) were the most common types in women with ISCC. These data might contribute to increasing the knowledge of HPV epidemiology and providing the guide for vaccine selection for women in Shantou. PMID:27610364

  10. Increased cancer cell proliferation in prostate cancer patients with high levels of serum folate

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Introduction: A recent clinical trial revealed that folic acid supplementation is associated with an increased incidence of prostate cancer (1). The present study evaluates serum and prostate tissue folate levels in men with prostate cancer, compared to histologically normal prostate glands from can...

  11. High Serum Irisin Level as an Independent Predictor of Diabetes Mellitus: A Longitudinal Population-Based Study.

    PubMed

    Huh, Ji Hye; Ahn, Song Vogue; Choi, Jung Hye; Koh, Sang Baek; Chung, Choon Hee

    2016-06-01

    Irisin, a novel exercise-induced myokine, has been suggested to regulate energy homeostasis and insulin sensitivity. However, it remains unclear whether circulating irisin plays a role in the development of DM in human. We investigated the possible association between circulating irisin levels and incident DM in a 2.6-year longitudinal study of a population-based cohort comprised of rural Korean subjects.We conducted a longitudinal study within the Korean Genome and Epidemiology Study on Atherosclerosis Risk of Rural Areas in the Korean General Population (KoGES-ARIRANG) study from November 2005 to January 2008. Cases (n=85) were patients with incident DM during the follow-up period and controls (n = 85) were matched to incident DM cases based on sex and age at baseline. The relative risk of serum irisin/adiponectin level for incident DM was analyzed using conditional logistic regression analysis.Baseline irisin_ENREF_1 levels were significantly higher in subjects who developed DM than in subjects who did not. The serum irisin level was positively associated with glycated hemoglobin (HbA1c) and postprandial glucose. Irisin was negatively associated with adiponectin (R = -0.189, P = 0.014). After adjustment for potential confounders, including body mass index, the odds ratios [95% confidence intervals] for incident DM increased in a graded manner as the serum irisin level increased (Quartile 1 vs Quartile 2 vs Quartile 3 vs Quartile 4 = 1 vs 0.80 [0.28-2.35] vs 3.33 [1.11-10.00] vs 4.10 [1.35-12.44], respectively), whereas the odds ratios for incident DM decreased in a graded manner as the serum adiponectin level increased.High serum irisin was independently associated with the development of DM, indicating that irisin may be a useful predictor of DM in Korean adults. PMID:27281072

  12. Serum amyloid A1 levels and amyloid deposition following a high-fat diet challenge in transgenic mice overexpressing hepatic serum amyloid A1.

    PubMed

    Jang, Woo Young; Jeong, Jain; Kim, Seonggon; Kang, Min-Cheol; Sung, Yong Hun; Choi, Minjee; Park, Si Jun; Kim, Myoung Ok; Kim, Sung Hyun; Ryoo, Zae Young

    2016-06-01

    Serum amyloid A (SAA) is an acute-phase response protein in the liver, and SAA1 is the major precursor protein involved in amyloid A amyloidosis. This amyloidosis has been reported as a complication in chronic inflammatory conditions such as arthritis, lupus, and Crohn's disease. Obesity is also associated with chronic, low-grade inflammation and sustained, elevated levels of SAA1. However, the contribution of elevated circulating SAA1 to metabolic disturbances and their complications is unclear. Furthermore, in several recent studies of transgenic (TG) mice overexpressing SAA1 that were fed a high-fat diet (HFD) for a relatively short period, no relationship was found between SAA1 up-regulation and metabolic disturbances. Therefore, we generated TG mice overexpressing SAA1 in the liver, challenged these mice with an HFD, and investigated the influence of elevated SAA1 levels. Sustained, elevated levels of SAA1 were correlated with metabolic parameters and local cytokine expression in the liver following 16 weeks on the HFD. Moreover, prolonged consumption (52 weeks) of the HFD was associated with impaired glucose tolerance and elevated SAA1 levels and resulted in systemic SAA1-derived amyloid deposition in the kidney, liver, and spleen of TG mice. Thus, we concluded that elevated SAA1 levels under long-term HFD exposure result in extensive SAA1-derived amyloid deposits, which may contribute to the complications associated with HFD-induced obesity and metabolic disorders. PMID:27218680

  13. Relationship between high-mobility group box 1 overexpression in ovarian cancer tissue and serum: a meta-analysis

    PubMed Central

    Wang, Haipeng; Li, Zengjun; Sun, Yanlai; Xu, Zhongfa; Han, Jianjun; Song, Bao; Song, Wentao; Qin, Chen; Yin, Lei

    2015-01-01

    Objective To implement a meta-analysis to investigate the relationship between high-mobility group box 1 (HMGB1) overexpression in the tissue and serum of ovarian cancer patients, and to evaluate its prognostic significance. Methods Searches were made of China National Knowledge Infrastructure, EMBASE, WanFang, PubMed, MEDLINE, and Web of Science databases up to August 2015, with no language or style restrictions. Reference lists of related studies were also carefully reviewed to identify additional articles. Results The literature search identified a total of 12 relevant studies on HMGB1 expression for inclusion in the meta-analysis: seven in ovarian tumor tissue, four in ovarian tumor patient serum, and one in both tissue and serum. HMGB1 protein levels in ovarian cancer tissues were notably higher than those in normal ovarian tissues with no evidence of heterogeneity between studies (RD=0.64, 95% confidence interval (CI): 0.57–0.70, Z=18.70, P<0.00001, I2=15%), and also higher than those in benign tumor tissues with no evidence of heterogeneity between studies (RD=0.52, 95% CI: 0.43–0.61, Z=11.14, P<0.00001, I2=0). Serum HMGB1 levels were similarly significantly higher in ovarian cancer patients than those with benign tumors or normal ovaries. Pooled mean differences of HMGB1 in ovarian cancer patients compared with patients with benign tumors or normal ovaries were 99.32 with 95% CI: 67.82–130.81, Z=6.18, P<0.00001, and 95.34 with 95% CI: 62.11–128.57, Z=5.62, P<0.0001. The pooled relative risk of ovarian cancer with high vs low HMGB1 expression levels was 1.40 with 95% CI: 1.09–1.79, Z=2.66, P=0.008, heterogeneity I2=50%. Conclusion This meta-analysis suggested that HMGB1 levels in both tissue and serum of ovarian cancer patients were significantly higher than those of benign tumor and normal ovarian samples. High serum or tissue HMGB1 expression may therefore be an effective molecular marker for ovarian benign or malignant tumor diagnosis and

  14. Palpable pediatric thyroid abnormalities – diagnostic pitfalls necessitate a high index of clinical suspicion: a case report

    PubMed Central

    Klopper, Joshua P; McDermott, Michael T

    2007-01-01

    A 12-year-old girl presented with a 4 year history of an enlarged, firm thyroid gland. On exam, her thyroid was firm and fixed and an enlarged cervical lymph node was palpable as well. Though a thyroid ultrasound prior to referral was read as thyroiditis, clinical suspicion for thyroid carcinoma mandated continued investigation. The diagnosis of papillary thyroid cancer was established and her workup revealed lymph node metastases as well as a tremendous burden of pulmonary metastases. Pediatric thyroid cancer is extremely rare, but often presents with aggressive disease. Palpable thyroid abnormalities in an individual under 20-years-old should be viewed with suspicion and should be thoroughly investigated to rule out malignancy even in the face of negative diagnostic procedures. Though pediatric papillary thyroid cancer often presents with loco-regional and even distant metastatic disease, mortality rates in follow-up for as long as 20 years are very favorable. PMID:17587454

  15. [An acute severe heat stroke patient showing abnormal diffuse high intensity of the cerebellar cortex in diffusion weighted image: a case report].

    PubMed

    Fujioka, Yusuke; Yasui, Keizo; Hasegawa, Yasuhiro; Takahashi, Akira; Sobue, Gen

    2009-10-01

    A 47-year-old man was admitted to the hospital because of general convulsion, loss of consciousness and hyperthermia. A diagnosis of acute heat stroke was made clinically and neuroradiologically. As the consciousness level ameliorated, he developed severe abulia and mutism, then cerebellar ataxic syndrome (viz. truncal ataxia, hypermetria, ataxic speech and nystagmus). An MRI (diffusion weighted image; DWI) disclosed abnormal diffuse high signal intensity of the cerebellar cortex with reduced apparent diffusion coefficient (ADC). Two months later after the onset, truncal ataxia and dysarthria significantly improved, while dysmetria of the extremities rather worsened. At that time, the abnormal signal intensity of the cerebellar cortex disappeared, and the cerebellum became atrophic. The cerebellar blood flow was significantly decreased on brain SPECT (99mTc-ECD). The abnormal DWI signal intensity of the cerebellar cortex in the present patient may represent the cytotoxic edema of Purkinje cells resulting from heat stroke-related hyperthermia It is essential to repeat MRI examination for cerebellar pathology and to obtain better insight into sequelae in patients with acute heat stroke. Protirelin tartrate seemed to be valid for improvement of abulia in the present patient. Further study is indicated. PMID:19999144

  16. Quantification of the DNA content of structurally abnormal X chromosomes and X chromosome aneuploidy using high resolution bivariate flow karyotyping.

    PubMed

    Trask, B; van den Engh, G; Nussbaum, R; Schwartz, C; Gray, J

    1990-01-01

    Quantification of the Hoechst and chromomycin A3 fluorescence intensities of mitotic human chromosomes isolated from karyotypically normal and abnormal cells was performed with a dual beam flow cytometer. The resultant flow karyotypes contain information about the relative DNA content and base composition of chromosomes and their relative frequencies in the mitotic cell sample. The relative copy number of X and Y chromosomes was determined for 38 normal males and females and 6 cell lines with X or Y chromosome aneuploidy. Flow karyotype diagnoses corresponded with conventional cytogenetic results in all cases. We show that chromosome DNA content can be derived from peak position in Hoechst vs. chromomycin flow karyotypes. These values are linearly related to propidium iodide staining intensity as measured with flow cytometry and to the binding of gallocyanin chrome alum to phosphate groups as measured with slide-based scanning photometry. Cell lines with deleted or dicentric X chromosomes ranging in length from 0.53 to 1.95 times normal were analyzed by using flow cytometry. The measured difference in DNA content between a normal X and each of the structurally abnormal chromosomes was linearly correlated to the difference predicted from cytogenetics and/or probe analyses. Deletions of 3-5 Mb, which were at and below the detection limits of conventional cytogenetics, could be quantified by flow karyotyping in individuals with X-linked diseases such as Duchenne muscular dystrophy, choroideremia, and ocular albinism/ichthyosis. The results show that the use of flow karyotyping to quantify the size of restricted regions of the genome can complement conventional cytogenetics and other physical mapping techniques in the study of genetic disorders. PMID:2106419

  17. Krill oil supplementation lowers serum triglycerides without increasing low-density lipoprotein cholesterol in adults with borderline high or high triglyceride levels.

    PubMed

    Berge, Kjetil; Musa-Veloso, Kathy; Harwood, Melody; Hoem, Nils; Burri, Lena

    2014-02-01

    The aim of the study was to explore the effects of 12 weeks daily krill oil supplementation on fasting serum triglyceride (TG) and lipoprotein particle levels in subjects whose habitual fish intake is low and who have borderline high or high fasting serum TG levels (150-499 mg/dL). We hypothesized that Krill oil lowers serum TG levels in subjects with borderline high or high fasting TG levels. To test our hypothesis 300 male and female subjects were included in a double-blind, randomized, multi-center, placebo-controlled study with five treatment groups: placebo (olive oil) or 0.5, 1, 2, or 4 g/day of krill oil. Serum lipids were measured after an overnight fast at baseline, 6 and 12 weeks. Due to a high intra-individual variability in TG levels, data from all subjects in the four krill oil groups were pooled to increase statistical power, and a general time- and dose-independent one-way analysis of variance was performed to assess efficacy. Relative to subjects in the placebo group, those administered krill oil had a statistically significant calculated reduction in serum TG levels of 10.2%. Moreover, LDL-C levels were not increased in the krill oil groups relative to the placebo group. The outcome of the pooled analysis suggests that krill oil is effective in reducing a cardiovascular risk factor. However, owing to the individual fluctuations of TG concentrations measured, a study with more individual measurements per treatment group is needed to increase the confidence of these findings. PMID:24461313

  18. Analysis of serum immune markers in seropositive and seronegative rheumatoid arthritis and in high-risk seropositive arthralgia patients

    PubMed Central

    Chalan, Paulina; Bijzet, Johan; van den Berg, Anke; Kluiver, Joost; Kroesen, Bart-Jan; Boots, Annemieke M. H.; Brouwer, Elisabeth

    2016-01-01

    Presence of autoantibodies precedes development of seropositive rheumatoid arthritis (SP RA) and seropositive arthralgia patients (SAP) are at risk of developing RA. The aims of the study are to identify additional serum immune markers discriminating between SP and seronegative (SN) RA, and markers identifying high-risk SAP. Sera from SAP (n = 27), SP RA (n = 22), SN RA (n = 11) and healthy controls (n = 20) were analyzed using the Human Cytokine 25-Plex Panel. Selected markers were validated in independent cohorts of SP RA (n = 35) and SN RA (n = 12) patients. Eleven of 27 SAP developed RA within 8 months (median follow-up time, range 1–32 months), and their baseline serum markers were compared to 16 non-progressing SAP. SAP and SP RA patients showed a marked overlap in their systemic immune profiles, while SN RA showed a distinct immune profile. Three of 4 markers discriminating between SP and SN RA (IL-1β, IL-15 and Eotaxin, but not CCL5) were similarly modulated in independent cohorts. SAP progressing to RA showed trends for increases in IL-5, MIP-1β, IL-1RA and IL-12 compared to non-progressing SAP. ROC analysis showed that serum IL-5 most accurately discriminated between the two SAP groups (AUC > 0.8), suggesting that baseline IL-5 levels may aid the identification of high-risk SAP. PMID:27189045

  19. Analysis of serum immune markers in seropositive and seronegative rheumatoid arthritis and in high-risk seropositive arthralgia patients.

    PubMed

    Chalan, Paulina; Bijzet, Johan; van den Berg, Anke; Kluiver, Joost; Kroesen, Bart-Jan; Boots, Annemieke M H; Brouwer, Elisabeth

    2016-01-01

    Presence of autoantibodies precedes development of seropositive rheumatoid arthritis (SP RA) and seropositive arthralgia patients (SAP) are at risk of developing RA. The aims of the study are to identify additional serum immune markers discriminating between SP and seronegative (SN) RA, and markers identifying high-risk SAP. Sera from SAP (n = 27), SP RA (n = 22), SN RA (n = 11) and healthy controls (n = 20) were analyzed using the Human Cytokine 25-Plex Panel. Selected markers were validated in independent cohorts of SP RA (n = 35) and SN RA (n = 12) patients. Eleven of 27 SAP developed RA within 8 months (median follow-up time, range 1-32 months), and their baseline serum markers were compared to 16 non-progressing SAP. SAP and SP RA patients showed a marked overlap in their systemic immune profiles, while SN RA showed a distinct immune profile. Three of 4 markers discriminating between SP and SN RA (IL-1β, IL-15 and Eotaxin, but not CCL5) were similarly modulated in independent cohorts. SAP progressing to RA showed trends for increases in IL-5, MIP-1β, IL-1RA and IL-12 compared to non-progressing SAP. ROC analysis showed that serum IL-5 most accurately discriminated between the two SAP groups (AUC > 0.8), suggesting that baseline IL-5 levels may aid the identification of high-risk SAP. PMID:27189045

  20. Quantitative analysis of human serum corticosterone by high-performance liquid chromatography coupled to electrospray ionization mass spectrometry.

    PubMed

    Ghulam, A; Kouach, M; Racadot, A; Boersma, A; Vantyghem, M C; Briand, G

    1999-04-30

    An original method based upon high-performance liquid chromatography coupled to electrospray ionization mass spectrometry has been developed for corticosterone (B) quantification in human serum. After extraction by diethyl ether using triamcinolone (T) as an internal standard, solutes are separated on a C18 microbore column (250 X 1.0 mm, I.D.), using acetonitrile-water-formic acid (40:59.9:0.1, v/v/v) as the mobile phase (flow-rate 40 microl/min). Detection is performed on an API 1 single quadrupole mass spectrometer equipped with a ESI interface and operated in positive ionization mode. Corticosterone quantifications were realized by computing peak area ratios (B/T) of the serum extracts analyzed in SIM mode (m/z 347 and m/z 395 for B and T. respectively), and comparing them with the calibration curve (r=0.998). PMID:10360442

  1. Serum protein electrophoresis by using high-resolution agarose gel in clinically healthy and Aspergillus species-infected falcons.

    PubMed

    Kummrow, Maya; Silvanose, Christudas; Di Somma, Antonio; Bailey, Thomas A; Vorbrüggen, Susanne

    2012-12-01

    Serum protein electrophoresis has gained importance in avian medicine during the past decade. Interpretation of electrophoretic patterns should be based on species-specific reference intervals and the electrophoresis gel system. In this study, serum protein electrophoresis by using high-resolution agarose gels was performed on blood samples collected from 105 falcons, including peregrine falcons (Falco peregrinus), gyrfalcons (Falco rusticolus), saker falcons (Falco cherrug), red-naped shaheens (Falco pelegrinoides babylonicus), and hybrid falcons, that were submitted to the Dubai Falcon Hospital (Dubai, United Arab Emirates) between 2003 and 2006. Reference values were established in clinically healthy birds and compared with values from falcons infected with Aspergillus species (n = 32). Falcons with confirmed aspergillosis showed significantly lower prealbumin values, which is a novel finding. Prealbumin has been documented in many avian species, but further investigation is required to illuminate the diagnostic significance of this negative acute-phase protein. PMID:23409432

  2. [Thymoma with extensive coagulative necrosis and high serum level of CYFRA 21-1; report of a case].

    PubMed

    Himuro, Naoya; Minakata, Takao; Oshima, Yutaka; Tomita, Yuri; Kataoka, Daisuke; Kadokura, Mitsutaka

    2014-12-01

    A 73-year-old woman complained of right chest discomfort. Chest X-ray during the follow-up for rheumatoid arthritis showed a mediastinal tumor. Chest computed tomography (CT) and magnetic resonance imaging (MRI) showed a 65-mm tumor in the right anterior mediastinum. A blood test showed high serum levels of CYFRA 21-1(29.8 ng/ml), white blood cells( WBC 10,800/µl), and C-reactive protein(CRP 16.1 mg/dl). Subsequently, inflammatory reactions improved, and the thymic tumor was resected. Histopathologically, the tumor was a type B2 thymoma with extensive coagulative necrosis. After resection, the serum CYFRA 21-1 level returned to the normal range. PMID:25434553

  3. /sup 67/Ga citrate scanning and serum angiotensin converting enzyme levels in sarcoidosis

    SciTech Connect

    Gupta, R.G.; Bekerman, C.; Sicilian, L.; Oparil, S.; Pinsky, S.M.; Szidon, J.P.

    1982-09-01

    /sup 67/Ga citrate scans and serum angiotensin converting enzyme (ACE) levels were obtained in 54 patients with sarcoidosis and analyzed in relation to clinical manifestations. /sup 67/Ga scans were abnormal in 97% of patients with clinically active disease (n . 30) and in 71% of patients with inactive disease (n . 24). Serum ACE levels were abnormally high (2 standard deviations above the control mean) in 73% of patients with clinically active disease and in 54% of patients with inactive disease. Serum ACE levels correlated significantly with /sup 67/Ga uptake score (r..436; p less than .005). The frequency of abnormal /sup 67/Ga scans and elevated serum ACE levels suggests that inflammatory activity with little or no clinical expression is common in sarcoidosis. Abnormal /sup 67/Ga scans were highly sensitive (97%) but had poor specificity (29%) to clinical disease activity. The accuracy of negative prediction of clinical activity by normal scans (87%) was better than the accuracy of positive prediction of clinical activity by abnormal scans (63%). /sup 67/Ga scans can be used to support the clinical indentification of inactive sacoidosis.

  4. Gallium 67 citrate scanning and serum angiotensin converting enzyme levels in sarcoidosis

    SciTech Connect

    Gupta, R.G.; Bekerman, C.; Sicilian, L.; Oparil, S.; Pinsky, S.M.; Szidon, J.P.

    1982-09-01

    Gallium 67 citrate scans and serum angiotension converting enzyme (ACE) levels were obtained in 54 patients with sarcoidosis and analyzed in relation to clinical manifestation. /sup 67/Ga scans were abnormal in 97% of patients with clinically active disease (n = 30) and in 71% of patients with inactive disease (n = 24). Serum ACE levels were abnormally high (2 standard deviations above the control mean) in 73% of patients with clinically active disease and in 54% of patients with inactive disease. Serum ACE levels correlated significantly with /sup 67/Ga uptake score (r = .436; p < .005). The frequency of abnormal /sup 67/Ga scans and elevated serum ACE levels suggests that inflammatory activity with little or no clinical expression is common in sarcoidosis. Abnormal /sup 67/Ga scans were highly sensitive (97%) but had poor specificity (29%) to clinical disease activity. The accuracy of negative prediction of clinical activity by normal scans (87%) was better than the accuracy of positive prediction of clinical activity by abnormal scans (63%). /sup 67/Ga scans can be used to support the clinical identification of inactive sarcoidosis.

  5. High serum levels of soluble CD40-L in patients with undifferentiated nasopharyngeal carcinoma: pathogenic and clinical relevance

    PubMed Central

    Caggiari, Laura; Guidoboni, Massimo; Vaccher, Emanuela; Barzan, Luigi; Franchin, Giovanni; Gloghini, Annunziata; Martorelli, Debora; Zancai, Paola; Bortolin, Maria Teresa; Mazzucato, Mario; Serraino, Diego; Carbone, Antonino; De Paoli, Paolo; Dolcetti, Riccardo

    2007-01-01

    Background Engagement of CD40 promotes survival of undifferentiated nasopharyngeal carcinoma (UNPC) cells and similar effects are induced by the EBV oncoprotein LMP-1 that is expressed in a fraction of cases. Considering that CD40 may be activated also by the soluble isoform of CD40L (sCD40L), we investigated the serum levels of sCD40L in a series of 61 UNPC patients from Italy, a non-endemic area for this disease. Results At diagnosis, serum samples of UNPC patients contained significantly higher levels of sCD40L than age-matched healthy controls (p < 0.001). High levels of sCD40L (i.e., >18 ng/ml) were more frequently found in patients <40 years of age (p = 0.03) and with distant metastases at presentation (p = 0.03). Serum levels of sCD40L were inversely associated with the expression of the EBV oncoprotein LMP-1 (p = 0.03), which mimics a constitutively activated CD40. The amount of sCD40L decreased in a fraction of patients treated with local radiotherapy alone. Moreover, CD40L+ lymphoid cells admixed to neoplastic UNPC cells were detected in cases with high serum levels of sCD40L, suggesting that sCD40L is probably produced within the tumor mass. Conclusion sCD40L may contribute to CD40 activation in UNPC cells, particularly of LMP-1-negative cases, further supporting the crucial role of CD40 signalling in the pathogenesis of UNPC. sCD40L levels may be useful to identify UNPC patients with occult distant metastases at presentation. PMID:17331231

  6. Serum uric acid is associated with increased risk of idiopathic venous thromboembolism in high HDL-C population: A case-control study

    PubMed Central

    YU, MIAO; LING, KEN; TENG, YUNFEI; LI, QIN; MEI, FEI; LI, YIQING; OUYANG, CHENXI

    2016-01-01

    Many studies have indicated that metabolic disorders are positively correlated with idiopathic venous thromboembolism (VTE), whereas the risk factor serum uric acid (SUA) for idiopathic VTE has yet to be investigated. In this retrospective case-control study, 276 idiopathic VTE patients and 536 gender- and age-matched control subjects were included. The subjects in the case and control groups exhibiting common known VTE risk factors and the patients with a first VTE onset in one month were excluded. For the control group, primary and secondary VTE patients were excluded. High-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, total cholesterol, fasting blood glucose, and current smoking were significantly associated with idiopathic VTE in the univariate analysis. Hyperuricemia was detected in 56/276 (20.29%) idiopathic patients compared with 71/536 (13.25%) in the control group. HDL-C was considered the most prominent interactive factor for SUA in idiopathic VTE by the interaction analysis. After testing for the interaction terms, SUA was closely associated with idiopathic VTE in the high HDL-C population (P=0.0026 for interaction), while there was no such correlation in the low HDL-C group. The results indicated no obvious correlation between triglyceride and hypertension to idiopathic VTE. In conclusion, SUA is closely associated with an increased risk of idiopathic VTE in the high HDL-C population. The abnormality of SUA may act as an important linkage between atherosclerosis and idiopathic VTE through HDL-C. PMID:27284315

  7. Blockade of Extracellular High-Mobility Group Box 1 Attenuates Systemic Inflammation and Coagulation Abnormalities in Rats with Acute Traumatic Coagulopathy

    PubMed Central

    Xu, Lin; Zhao, Kun; Shen, Xiao; Fan, Xin-xin; Ding, Kai; Liu, Ren-min; Wang, Feng

    2016-01-01

    Background As an extracellularly released mediator, high-mobility group box 1 (HMGB1) initiates sterile inflammation following severe trauma. Serum HMGB1 levels correlate well with acute traumatic coagulopathy (ATC) in trauma patients, which is independently associated with higher mortality. We investigated the involvement of HMGB1 in ATC through blocking extracellular HMGB1. Material/Methods The ATC model was induced by polytrauma and hemorrhage in male Sprague-Dawley rats, which were randomly assigned to sham, ATC, and ATCH (ATC with HMGB1 blockade) groups. Thrombelastography (TEG) was performed to monitor changes in coagulation function. Serum levels of HMGB1, TNF-α, and IL-6 were measured, as well as lung levels of HMGB1 and nuclear factor (NF)-κB and expression of receptor for advanced glycation end-products (RAGE). Results Compared with the sham group, HMGB1 increased the serum levels of TNF-α and IL-6, whereas HMGB1 blockade inhibited the induction of TNF-α and IL-6. HMGB1 also induced elevated serum soluble P-selectin and fibrinolysis markers plasmin-antiplasmin complex, which both were reduced by HMGB1 blockade. Thrombelastography revealed the hypocoagulability status in the ATC group, which was attenuated by anti-HMGB1 antibody. Furthermore, the lung level of NF-κB and expression of RAGE were decreased by anti-HMGB1 antibody, suggesting the role of RAGE/NF-κB pathway in ATC. Conclusions HMGB1 blockade can attenuate inflammation and coagulopathy in ATC rats. Anti-HMGB1 antibody might exert protective effects partly through the RAGE/NF-κB pathway. Thus, HMGB1 has potential as a therapeutic target in ATC. PMID:27436061

  8. High serum carotenoids are associated with lower risk for developing elevated serum alanine aminotransferase among Japanese subjects: the Mikkabi cohort study.

    PubMed

    Sugiura, Minoru; Nakamura, Mieko; Ogawa, Kazunori; Ikoma, Yoshinori; Yano, Masamichi

    2016-04-01

    Many recent studies have shown that antioxidant vitamins and/or carotenoids may reduce liver disease, but this association has not been well established with thorough longitudinal cohort studies. The objective of this study was to longitudinally investigate whether serum carotenoids at baseline are associated with the risk of developing elevated serum alanine aminotransferase (ALT) among Japanese subjects. We conducted a follow-up study of 1073 males and females aged between 30 and 79 years at baseline from the Mikkabi prospective cohort study. Those who participated in the baseline study and completed follow-up surveys were examined longitudinally. Exclusions included excessive alcohol consumption (≥60 g alcohol/d), hepatitis B and C and having a history of medication use for liver disease. A cohort of 213 males and 574 females free of elevated serum ALT (>30 IU/ml) at baseline was studied. Over a mean follow-up period of 7·4 (sd 3·1) years, thirty-one males and forty-nine females developed new elevated serum ALT. After adjustments for confounders, the hazard ratios for elevated serum ALT in the highest tertiles of basal serum β-carotene, β-cryptoxanthin and total provitamin A carotenoids against the lowest tertiles were 0·43 (95 % CI 0·22, 0·81), 0·51 (CI 0·27, 0·94) and 0·52 (CI 0·28, 0·97), respectively. For α-carotene and lycopene, borderline reduced risks were also observed; however, these were not significant. Our results further support the hypothesis that antioxidant carotenoids, especially provitamin A carotenoids, might help prevent earlier pathogenesis of non-alcoholic liver disease in Japanese subjects. PMID:26916997

  9. Differentiated quantification of human bile acids in serum by high-performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Burkard, Ines; von Eckardstein, Arnold; Rentsch, Katharina M

    2005-11-01

    Determination of quantitative changes in the pattern of serum bile acids is important for the monitoring of diseases affecting bile acid metabolism. A sensitive and specific high-performance liquid chromatography (HPLC)-MS/MS method was developed for the differentiated quantification of unconjugated as well as glycine- and taurine-conjugated cholic, chenodeoxycholic (CDCA), deoxycholic (DCA), ursodeoxycholic (UDCA) and lithocholic acid (LCA) in serum samples. After solid-phase extraction and reversed-phase HPLC separation, detection of the conjugated bile acids was performed using electrospray ionization (ESI)-MS/MS and selected reaction monitoring mode, whereas unconjugated bile acids were determined by ESI-MS and selected ion monitoring mode. The within-day and between-day coefficients of variation were below 7% for all bile acids and the recovery rates of the extraction procedure were between 84.9 and 105%. The developed method was applied to a group of 21 healthy volunteers and preliminary reference intervals in serum were established. In patients with drug-induced cholestasis, an elevation of primary bile acids has been shown. PMID:16182619

  10. Quantification of phylloquinone and menaquinones in feces, serum, and food by high-performance liquid chromatography-mass spectrometry.

    PubMed

    Karl, J Philip; Fu, Xueyan; Dolnikowski, Gregory G; Saltzman, Edward; Booth, Sarah L

    2014-07-15

    Vitamin K, comprising phylloquinone (PK) and menaquinones (MKn), is a family of vitamers found in multiple biological and environmental matrices. Advancing emerging evidence for novel and distinct physiologic roles of these vitamers in human health and disease necessitates sensitive and selective methods for quantifying PK and MKn in these matrices. We developed a novel method employing high-performance liquid chromatography-mass spectrometry with atmospheric pressure chemical ionization (LC-APCI-MS) for simultaneous quantification of 11 vitamin K vitamers that can be applied in feces, serum and food. Minimal detectable concentrations of vitamin K vitamers ranged from 1 pmol/g to 30 pmol/g. Limits of quantification ranged from 5 pmol/g to 90 pmol/g. Inter-assay and intra-assay variations were <17% and <8%, respectively, in food, and <12% and <8%, respectively, in feces. Recovery exceeded 80% for all vitamers in both food and feces. The method successfully quantified PK and MKn concentrations in rat chow, feces and serum. In summary, this LC-APCI-MS method provides a sensitive and selective tool for quantifying vitamin K vitamers in feces, serum and food. This method can be applied in human and animal studies examining the role of vitamin K vitamers derived from the diet and gut bacteria synthesis in health and disease. PMID:24956079

  11. Method development and validation for ultra-high-pressure LC/MS/MS determination of hop prenylflavonoids in human serum.

    PubMed

    Yuan, Yang; Qiu, Xi; Nikolic, Dejan; Dahl, Jeffrey H; van Breemen, Richard B

    2012-01-01

    Hops (Humulus lupulus L.) are used in the brewing of beer, and hop extracts containing prenylated compounds, such as xanthohumol (XN) and 8-prenylnaringenin (8-PN), are under investigation as dietary supplements for cancer chemoprevention and the management of hot flashes in menopausal women. To facilitate clinical studies of hop safety and efficacy, a selective, sensitive, and fast ultra-high-pressure LC (UHPLC) tandem MS method was developed and validated for the simultaneous determination of the hop prenylflavonoids XN, isoxanthohumol (IX), 6-prenylnaringenin (6-PN), and 8-PN in human serum. The analytical method requires 300 microL of human serum, which is processed using liquid-liquid extraction. UHPLC separation was carried out in 2.5 min with gradient elution using an RP C18 column containing 1.6 pm particle size packing material. Prenylflavonoids were measured using negative ion electrospray MS with collision-induced dissociation and selected reaction monitoring. The method was validated and showed good accuracy and precision with an LOQ of 0.50 ng/mL for XN (1.4 nM) and 1.0 ng/mL for 6-PN, 8-PN (2.94 nM), and IX (2.82 nM) in serum. PMID:23451393

  12. Cross-sectional study of serum parathyroid hormone level in high-risk pregnancies as compared to nonpregnant control

    PubMed Central

    Sharma, J. B.; Sharma, Subhadra; Usha, B. R.; Yadav, Manisha; Kumar, Sunesh; Mukhopadhyay, A. K.

    2016-01-01

    Objectives: To note the value of serum parathyroid hormone (PTH) levels in normal and high-risk pregnancies (HRP) in patients attending antenatal visits at All India Institute of Medical Sciences (AIIMS). Materials and Methods: This is a cross-sectional study where a total of 282 patients attending Gynecology Outpatient Department at AIIMS, New Delhi were recruited. Among the 282 subjects, 251 were pregnant, and 31 were controls. The serum was tested for serum PTH levels using Beckman coulter access 2 immunoassay. Results: The median value of PTH level in pregnant women was 31.6 pg/ml with range being 0.8–505.5 pg/ml in contrast to 45.9 pg/ml with range being 19–102.7 pg/ml in nonpregnant female. This difference was statistically significant (P = 0.0012). There was no significant difference in median level of PTH in different age group. Although the median PTH levels were lower in second trimester (25.25 pg/ml) than in first trimester (35.5 pg/ml) and in third trimester (32.4 pg/ml), the difference was not statistically significant. There was no significant difference in PTH level in HRP (median value – 31.6 pg/ml) as compared to low-risk pregnancies (31.5 pg/ml). Conclusion: Serum PTH levels are significantly lower during pregnancy as compared to nonpregnant state. However, age, parity, and HRP did not alter PTH level during pregnancy. PMID:26904475

  13. High Maternal Serum Estradiol Levels Induce Dyslipidemia in Human Newborns via a Hepatic HMGCR Estrogen Response Element

    PubMed Central

    Meng, Ye; Lv, Ping-Ping; Ding, Guo-Lian; Yu, Tian-Tian; Liu, Ye; Shen, Yan; Hu, Xiao-Ling; Lin, Xian-Hua; Tian, Shen; Lv, Min; Song, Yang; Guo, Meng-Xi; Ke, Zhang-Hong; Xu, Hong; Sheng, Jian-Zhong; Shi, Feng-Tao; Huang, He-Feng

    2015-01-01

    While the intrauterine environment is essential for the health of offspring, the impact of high maternal serum estradiol (E2) on lipid metabolism in offspring and the mechanisms are unknown. We found that ovarian stimulation (OS) could result in high E2 levels in women throughout pregnancy. Strikingly, their newborns showed elevated total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels that were positively related with E2 in newborns. In vitro, E2 dose-dependently stimulated TC and LDL-C secretion, and increased expression of the cholesterol synthesis rate-limiting enzyme 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) in HepG2 cells and mouse fetal hepatocytes. In vivo, high maternal E2 was detected and fetal livers also showed significantly higher HMGCR expression in an OS mouse model. Notably, an estrogen response element (ERE) was identified in the HMGCR promoter, indicating that high maternal serum E2 could up-regulate HMGCR expression in fetal hepatocytes via an ERE that in turn induces elevated levels of TC and LDL-C in offspring. Conclusion: OS can induce a high maternal E2 environment, which up-regulates HMGCR expression in fetal hepatocytes via an ERE in the promoter, and induces elevated levels of TC and LDL-C in newborns that may be related to increased risk of metabolic disease in adulthood. PMID:25961186

  14. Abnormal Head Position

    MedlinePlus

    ... cause. Can a longstanding head turn lead to any permanent problems? Yes, a significant abnormal head posture could cause permanent ... occipitocervical synostosis and unilateral hearing loss. Are there any ... postures? Yes. Abnormal head postures can usually be improved depending ...

  15. Urine - abnormal color

    MedlinePlus

    ... straw-yellow. Abnormally colored urine may be cloudy, dark, or blood-colored. Causes Abnormal urine color may ... red blood cells, or mucus in the urine. Dark brown but clear urine is a sign of ...

  16. Prostate cancer biomarker discovery using high performance mass spectral serum profiling.

    PubMed

    Oh, Jung Hun; Lotan, Yair; Gurnani, Prem; Rosenblatt, Kevin P; Gao, Jean

    2009-10-01

    Prostate-specific antigen (PSA) is the most widely used serum biomarker for early detection of prostate cancer (PCA). Nevertheless, PSA level can be falsely elevated due to prostatic enlargement, inflammation or infection, which limits the PSA test specificity. The objective of this study is to use a machine learning approach for the analysis of mass spectrometry data to discover more reliable biomarkers that distinguish PCA from benign specimens. Serum samples from 179 prostate cancer patients and 74 benign patients were analyzed. These samples were processed using ProXPRESSION Biomarker Enrichment Kits (PerkinElmer). Mass spectra were acquired using a prOTOF 2000 matrix-assisted laser desorption/ionization orthogonal time-of-flight (MALDI-O-TOF) mass spectrometer. In this study, we search for potential biomarkers using our feature selection method, the Extended Markov Blanket (EMB). From the new marker selection algorithm, a panel of 26 peaks achieved an accuracy of 80.7%, a sensitivity of 83.5%, a specificity of 74.4%, a positive predictive value (PPV) of 87.9%, and a negative predictive value (NPV) of 68.2%. On the other hand, when PSA alone was used (with a cutoff of 4.0ng/ml), a sensitivity of 66.7%, a specificity of 53.6%, a PPV of 73.5%, and a NPV of 45.4% were obtained. PMID:19423179

  17. A multiplexed targeted assay for high-throughput quantitative analysis of serum methylamines by ultra performance liquid chromatography coupled to high resolution mass spectrometry.

    PubMed

    Kadar, Hanane; Dubus, Justine; Dutot, Jérémie; Hedjazi, Lyamine; Srinivasa, Suman; Fitch, Kathleen V; Grinspoon, Steven K; Nicholson, Jeremy K; Dumas, Marc-Emmanuel; Gauguier, Dominique

    2016-05-01

    Methylamines are biologically-active metabolites present in serum and urine samples, which play complex roles in metabolic diseases. Methylamines can be detected by proton nuclear magnetic resonance (NMR), but specific methods remain to be developed for their routine assay in human serum in clinical settings. Here we developed and validated a novel reliable "methylamine panel" method for simultaneous quantitative analysis of trimethylamine (TMA), its major detoxification metabolite trimethylamine-N-oxide (TMAO), and precursors choline, betaine and l-carnitine in human serum using Ultra Performance Liquid Chromatography (UPLC) coupled to High Resolution Mass Spectrometry (HRMS). Metabolite separation was carried out on a HILIC stationary phase. For all metabolites, the assay was linear in the range of 0.25-12.5 μmol/L and enabled to reach limit of detection of about 0.10 μmol/L. Relative standard deviations were below 16% for the three levels of concentrations. We demonstrated the strong reliability and robustness of the method, which was applied to serum samples from healthy individuals to establish the range of concentrations of the metabolites and their correlation relationships and detect gender differences. Our data provide original information for implementing in a clinical environment a MS-based diagnostic method with potential for targeted metabolic screening of patients at risk of cardiometabolic diseases. PMID:27036856

  18. Longxuetongluo Capsule Improves Erythrocyte Function against Lipid Peroxidation and Abnormal Hemorheological Parameters in High Fat Diet-Induced ApoE−/− Mice

    PubMed Central

    Zheng, Jiao; Liu, Binglin; Lun, Qixing; Yao, Weijuan; Zhao, Yunfang; Xiao, Wei; Huang, Wenzhe; Wang, Yonghua; Li, Jun; Tu, Pengfei

    2016-01-01

    Chinese dragon's blood, the red resin of Dracaena cochinchinensis, one of the renowned traditional medicines, has been used to facilitate blood circulation and disperse blood stasis for thousands of years. Phenolic compounds are considered to be responsible for its main biological activities. In this study, total phenolic compounds of Chinese dragon's blood were made into capsule (Longxuetongluo Capsule, LTC) and their effects on the abnormal hemorheological properties were examined by high fat diet (HFD) induced ApoE−/− mice. Compared to the model group, LTC recovered the abnormal hemorheological parameters in HFD-induced ApoE−/− mice by reducing whole blood viscosity (WBV) at high rate and improving erythrocyte function. In conclusion, LTC could ameliorate erythrocyte deformability and osmotic fragility through the reduction of lipid peroxidation on plasma and erythrocyte membranes in HFD-induced ApoE−/− mice, which supported the traditional uses of Chinese dragon's blood as an effective agent for improving blood microcirculation in hypercholesterolemia. PMID:26649134

  19. Relationships (II) of International Classification of High-resolution Computed Tomography for Occupational and Environmental Respiratory Diseases with ventilatory functions indices for parenchymal abnormalities

    PubMed Central

    TAMURA, Taro; SUGANUMA, Narufumi; HERING, Kurt G.; VEHMAS, Tapio; ITOH, Harumi; AKIRA, Masanori; TAKASHIMA, Yoshihiro; HIRANO, Harukazu; KUSAKA, Yukinori

    2015-01-01

    The International Classification of High-Resolution Computed Tomography (HRCT) for Occupational and Environmental Respiratory Diseases (ICOERD) is used to screen and diagnose respiratory illnesses. Using univariate and multivariate analysis, we investigated the relationship between subject characteristics and parenchymal abnormalities according to ICOERD, and the results of ventilatory function tests (VFT). Thirty-five patients with and 27 controls without mineral-dust exposure underwent VFT and HRCT. We recorded all subjects’ occupational history for mineral dust exposure and smoking history. Experts independently assessed HRCT using the ICOERD parenchymal abnormalities (Items) grades for well-defined rounded opacities (RO), linear and/or irregular opacities (IR), and emphysema (EM). High-resolution computed tomography showed that 11 patients had RO; 15 patients, IR; and 19 patients, EM. According to the multiple regression model, age and height had significant associations with many indices ventilatory functions such as vital capacity, forced vital capacity, and forced expiratory volume in 1 s (FEV1). The EM summed grades on the upper, middle, and lower zones of the right and left lungs also had significant associations with FEV1 and the maximum mid-expiratory flow rate. The results suggest the ICOERD notation is adequate based on the good and significant multiple regression modeling of ventilatory function with the EM summed grades. PMID:25810443

  20. High serum phosphate concentration as the result of smoking might underlie the lower risk of Parkinson's disease.

    PubMed

    Håglin, L

    2015-09-01

    Epidemiological studies have found a negative association between cigarette smoking and Parkinson's disease (PD): PD patients are approximately 50% less likely to have smoked cigarettes than age- and sex-matched controls. In both women and men, the PD protection effect of smoking may be explained by higher levels of phosphate in serum (S-P) and triglycerides (S-TG) in smokers compared to non-smokers. That is, the protecting effect from smoking could be mediated by either a high S-P or high S-TG levels. I suggest that higher S-P as the result of smoking may be associated with intracellular depletion of Pi in skeletal muscle and that this depletion of Pi is associated with increased availability of phosphate for the brain. This increased phosphate availability would protect against PD, as oxidative phosphorylation in the mitochondria is a central and persistent phenomenon in the pathogenesis cascade of PD. Phosphate is necessary for energy production in the form of creatine phosphate (CP) and adenosine-tri-phosphate (ATP) in the brain and skeletal muscle. As such, hypophosphatemia increases risk of cell death. In some clinical instances, this energy depletion may pre-dispose to dopamine neuron death. Mitochondrial dysfunction is associated with the generation of oxidative stress and mediates the induction of apoptosis. Studies with NMR spectroscopy reveal that an energy deficit in brain cells is a strong mark for PD although this differed for men and women. Compared to women, men had lower serum phosphate and ATP levels in the brain (about 15% lower). In addition to sex differences, age, stress, and malnutrition may cause low serum phosphate levels, a situation that could contribute to the lack of energy available to the brain and the risk of PD. As hypophosphatemia is present in overnutrition and has an inverse relation with a high BMI, both obesity and malnutrition are considered to be presumptive risk factor for PD. PMID:26206759

  1. Identification and mapping of linear antibody epitopes in human serum albumin using high-density Peptide arrays.

    PubMed

    Hansen, Lajla Bruntse; Buus, Soren; Schafer-Nielsen, Claus

    2013-01-01

    We have recently developed a high-density photolithographic, peptide array technology with a theoretical upper limit of 2 million different peptides per array of 2 cm(2). Here, we have used this to perform complete and exhaustive analyses of linear B cell epitopes of a medium sized protein target using human serum albumin (HSA) as an example. All possible overlapping 15-mers from HSA were synthesized and probed with a commercially available polyclonal rabbit anti-HSA antibody preparation. To allow for identification of even the weakest epitopes and at the same time perform a detailed characterization of key residues involved in antibody binding, the array also included complete single substitution scans (i.e. including each of the 20 common amino acids) at each position of each 15-mer peptide. As specificity controls, all possible 15-mer peptides from bovine serum albumin (BSA) and from rabbit serum albumin (RSA) were included as well. The resulting layout contained more than 200.000 peptide fields and could be synthesized in a single array on a microscope slide. More than 20 linear epitope candidates were identified and characterized at high resolution i.e. identifying which amino acids in which positions were needed, or not needed, for antibody interaction. As expected, moderate cross-reaction with some peptides in BSA was identified whereas no cross-reaction was observed with peptides from RSA. We conclude that high-density peptide microarrays are a very powerful methodology to identify and characterize linear antibody epitopes, and should advance detailed description of individual specificities at the single antibody level as well as serologic analysis at the proteome-wide level. PMID:23894373

  2. Hypertension, Abnormal Cholesterol, and High Body Mass Index among Non-Hispanic Asian Adults: United States, 2011-2012

    MedlinePlus

    ... high total cholesterol among non-Hispanic Asian adults did not differ by sex, age, education, or foreign- ... Figure 3 ). The prevalence of high total cholesterol did not differ significantly by sex, age, education, or ...

  3. Subacute cognitive deterioration with high serum anti-thyroid peroxidase antibodies: two cases and a plea for pragmatism.

    PubMed

    Segers, Kurt; Braconnier, Philippe; Corazza, Francis; Divano, Luisa; Mabrouk, Asmaa; Robberecht, Jean; Surquin, Murielle

    2013-09-01

    Autoimmune encephalopathy is a rare but potentially reversible cause of cognitive deterioration and neuropsychiatric disturbances. We describe two older female patients with subacute cognitive decline and marked neuropsychiatric disturbances in the presence of high serum anti-thyroid peroxidase antibodies and with normal dosage of free thyroxine 4. One patient recovered almost completely after oral corticotherapy. Differential diagnosis and the role of biomarkers, in particular, are discussed. We support a pragmatic approach involving a short empirical therapeutic trial with intravenous or oral corticoids; this should be considered in all patients with subacute encephalopathy and with laboratory arguments for an underlying autoimmune aetiology. PMID:25913766

  4. Sailing between Scylla and Charybdis: the high serum K-low dialysate K quandary.

    PubMed

    Labriola, Laura; Jadoul, Michel

    2014-01-01

    In HD patients, the optimal choice of dialysate K concentration is of paramount importance. Recent large observational studies have documented an association between low dialysate K concentration (< 2 or even <3 mEq/L) and a higher risk of sudden death. In this review, we first briefly discuss the available data concerning the link between hypokalemia and negative outcomes in non-CKD populations, especially after an acute myocardial infarction or in congestive heart failure. We next review the pathophysiology of the arrhythmogenic effect related to K fluxes during HD and discuss the dialytic strategies aiming at making potassium fall more gradual and thus at reducing the electrical disturbances triggered by the HD session. We conclude with practical recommendations regarding the optimal choice of K bath and the importance of more frequent monitoring of serum K in some clinical scenarios. PMID:24824161

  5. High fasting serum insulin level due to autoantibody interference in insulin immunoassay discloses autoimmune insulin syndrome: a case report.

    PubMed

    Lamy, Pierre-Jean; Sault, Corinne; Renard, Eric

    2016-08-01

    Insulin-antibodies are a cause of misleading results in insulin immunoassays. They may also mediate deleterious blood glucose variations. A patient presented with overtiredness, recurrent episodes of sweating, dizziness and fainting fits. A fasting serum insulin assay performed on a Modular platform (Modular analytic E170, Roche Diagnostic, Meylan, France) showed a highly elevated value of 194.7 mIU/L, whereas on the same sample glucose and C-peptide levels were normal. Other immunometric insulin assays were performed, as well as antibodies anti-insulin radiobinding assay (RBA) and gel filtration chromatography (GFC). While complementary insulin assays yielded closer to normal fasting levels, the free insulin concentration assessed after PEG precipitation was 14.0 mIU/L and the RBA was positive. GFC revealed that most of the insulin was complexed with a 150 kDa molecule, corresponding to an immunoglobulin G (IgG). A high fasting serum insulin level in a patient with neuroglucopenic symptoms was related to a high insulin-antibody level, suggesting an insulin autoimmune syndrome. PMID:27492703

  6. Greater Cognitive Decline with Aging among Elders with High Serum Concentrations of Organochlorine Pesticides

    PubMed Central

    Kim, Se-A; Lee, Yu-Mi; Lee, Ho-Won; Jacobs, David R; Lee, Duk-Hee

    2015-01-01

    Although cognitive decline is very common in elders, age-related cognitive decline substantially differs among elders and the determinants of the differences in age-related cognitive decline are unclear. We investigated our hypothesis that the association between age and cognition was stronger in those with higher serum concentrations of organochlorine (OC) pesticides, common persistent and strongly lipophilic neurotoxic chemicals. Participants were 644 elders aged 60-85, participating in the National Health and Nutrition Examination Survey 1999-2002. Six OC pesticides (p,p'-dichlorodiphenyltrichloroethane (DDT), p,p'-dichlorodipenyldichloroethylene (DDE), β-hexachlorocyclohexane, trans-nonachlor, oxychlordane, and heptachlor epoxide) were evaluated. “Lower cognitive function” was defined as having a low Digit-Symbol Substitution Test (DSST) score (<25th percentile of DSST score, cutpoint 28 symbols substituted). Higher levels of β-hexachlorocyclohexane, trans-nonachlor, oxychlordane, and heptachlor epoxide modified the associations between age and lower cognitive function (Pinteraction<0.01, 0.03, <0.01, and 0.02, respectively). Elders in the 3rd tertile of these chemicals demonstrated a greater risk of lower cognitive function with aging, compared to those in the combined 1st and 2nd tertiles. Among those with highest OC pesticides (3rd tertile), the odds ratio for the risk of lower cognitive function was about 6 to 11 for the highest quintile of age (80-85 years) vs. the first quintile of age (60-63 years), while the association between age and lower cognitive function became flatter in those with lower OC pesticides (combined 1st and 2nd tertiles). Both DDT and DDE showed no interaction, with lower DSST scores for higher age irrespective of serum concentrations of DDT or DDE. Even though DSST score measures only one aspect of cognition, several OC pesticides modified aging-related prevalence of low cognitive score, a finding which should be evaluated in

  7. Effect of dietary supplementation of Bacillus subtilis B10 on biochemical and molecular parameters in the serum and liver of high-fat diet-induced obese mice* #

    PubMed Central

    Lei, Kai; Li, Ya-li; Wang, Yang; Wen, Jing; Wu, Hong-zhao; Yu, Dong-you; Li, Wei-fen

    2015-01-01

    While a high-fat diet (HFD) is assumed to be related to fat-mediated oxidative stress decreasing antioxidant enzyme activity, probiotics are believed to have positive effects on the regulation of HFD-induced obesity as well as lipid metabolism, energy homeostasis, and anti-oxidation. Because Bacillus subtilis B10 has beneficial effects on the abnormal lipid metabolism and the oxidative stress in HFD-induced obese mice, ICR mice were randomly assigned into an HFD group and the HFD was supplemented with 0.1% (w/w) Bacillus subtilis B10 (HFD+B10 group). Thereafter, 30-d treatments were run, and then hepatic lipid level and antioxidant status were measured. The expression of genes related to lipid metabolism and oxidative stress in the liver was determined by reverse-transcription quantitative polymerase chain reaction (RT-qPCR). We found that HFD-induced obese mice treated with B10 showed a decrease in weight gain, serum glucose activity as well as hepatic triglyceride (TG), glutamic oxaloacetic transaminase (GOT), and glutamic pyruvic transaminase (GPT) activities. In addition, the gene expressions of antioxidant genes, glutathione reductase (GR), xanthine oxidase (XO), heat-shock protein 90 (Hsp90), and lipid synthesis gene 3β-hydroxysteroid-∆24 reductase (DHCR24) in the HFD+B10 group were down-regulated, suggesting alleviation of oxidative stress, while the lipolysis gene 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), energy metabolism gene peroxisome proliferator-activated receptor α (PPARα) and the gene encoding tumor-suppressor protein p53 were up-regulated. The regulatory and positive effect of dietary supplementation of probiotic B10 suggests that it has a beneficial effect on the homeostasis of the lipid metabolism and on alleviating oxidative stress in HFD-induced obese mice. PMID:26055910

  8. Holding thermal receipt paper and eating food after using hand sanitizer results in high serum bioactive and urine total levels of bisphenol A (BPA).

    PubMed

    Hormann, Annette M; Vom Saal, Frederick S; Nagel, Susan C; Stahlhut, Richard W; Moyer, Carol L; Ellersieck, Mark R; Welshons, Wade V; Toutain, Pierre-Louis; Taylor, Julia A

    2014-01-01

    Bisphenol A (BPA) is an endocrine disrupting environmental contaminant used in a wide variety of products, and BPA metabolites are found in almost everyone's urine, suggesting widespread exposure from multiple sources. Regulatory agencies estimate that virtually all BPA exposure is from food and beverage packaging. However, free BPA is applied to the outer layer of thermal receipt paper present in very high (∼20 mg BPA/g paper) quantities as a print developer. Not taken into account when considering thermal paper as a source of BPA exposure is that some commonly used hand sanitizers, as well as other skin care products, contain mixtures of dermal penetration enhancing chemicals that can increase by up to 100 fold the dermal absorption of lipophilic compounds such as BPA. We found that when men and women held thermal receipt paper immediately after using a hand sanitizer with penetration enhancing chemicals, significant free BPA was transferred to their hands and then to French fries that were eaten, and the combination of dermal and oral BPA absorption led to a rapid and dramatic average maximum increase (Cmax) in unconjugated (bioactive) BPA of ∼7 ng/mL in serum and ∼20 µg total BPA/g creatinine in urine within 90 min. The default method used by regulatory agencies to test for hazards posed by chemicals is intra-gastric gavage. For BPA this approach results in less than 1% of the administered dose being bioavailable in blood. It also ignores dermal absorption as well as sublingual absorption in the mouth that both bypass first-pass liver metabolism. The elevated levels of BPA that we observed due to holding thermal paper after using a product containing dermal penetration enhancing chemicals have been related to an increased risk for a wide range of developmental abnormalities as well as diseases in adults. PMID:25337790

  9. Holding Thermal Receipt Paper and Eating Food after Using Hand Sanitizer Results in High Serum Bioactive and Urine Total Levels of Bisphenol A (BPA)

    PubMed Central

    Hormann, Annette M.; vom Saal, Frederick S.; Nagel, Susan C.; Stahlhut, Richard W.; Moyer, Carol L.; Ellersieck, Mark R.; Welshons, Wade V.; Toutain, Pierre-Louis; Taylor, Julia A.

    2014-01-01

    Bisphenol A (BPA) is an endocrine disrupting environmental contaminant used in a wide variety of products, and BPA metabolites are found in almost everyone’s urine, suggesting widespread exposure from multiple sources. Regulatory agencies estimate that virtually all BPA exposure is from food and beverage packaging. However, free BPA is applied to the outer layer of thermal receipt paper present in very high (∼20 mg BPA/g paper) quantities as a print developer. Not taken into account when considering thermal paper as a source of BPA exposure is that some commonly used hand sanitizers, as well as other skin care products, contain mixtures of dermal penetration enhancing chemicals that can increase by up to 100 fold the dermal absorption of lipophilic compounds such as BPA. We found that when men and women held thermal receipt paper immediately after using a hand sanitizer with penetration enhancing chemicals, significant free BPA was transferred to their hands and then to French fries that were eaten, and the combination of dermal and oral BPA absorption led to a rapid and dramatic average maximum increase (Cmax) in unconjugated (bioactive) BPA of ∼7 ng/mL in serum and ∼20 µg total BPA/g creatinine in urine within 90 min. The default method used by regulatory agencies to test for hazards posed by chemicals is intra-gastric gavage. For BPA this approach results in less than 1% of the administered dose being bioavailable in blood. It also ignores dermal absorption as well as sublingual absorption in the mouth that both bypass first-pass liver metabolism. The elevated levels of BPA that we observed due to holding thermal paper after using a product containing dermal penetration enhancing chemicals have been related to an increased risk for a wide range of developmental abnormalities as well as diseases in adults. PMID:25337790

  10. Highly sensitive and selective measurement of underivatized methylmalonic acid in serum and plasma by liquid chromatography-tandem mass spectrometry.

    PubMed

    Yuan, Chao; Gabler, Jessica; El-Khoury, Joe M; Spatholt, Regina; Wang, Sihe

    2012-07-01

    Methylmalonic acid (MMA) is a functional biomarker of vitamin B12 deficiency. Measurement of plasma MMA is challenging due to its small molecular weight and hydrophilic nature. Several liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods have been developed for measuring plasma MMA. However, these methods involve lengthy sample preparation, long chromatographic run time, inadequate sensitivity, or interference from succinic acid (SA). Here we report a novel LC-MS/MS method for quantitation of underivatized MMA in serum or heparinized plasma with high sensitivity and selectivity. Sample preparation involved only strong anion exchange solid phase extraction. The extract was purified by online turbulent flow and analyzed on an Organic Acids column. MS/MS analysis was performed in negative electrospray mode, and the analytical time was 6 min. The use of ion ratio confirmation in combination with chromatographic resolution from SA greatly enhanced the selectivity. No interference was observed. This method was linear from 26.2 to 26,010.0 nM with an accuracy of 98-111 %. Total coefficient of variation was less than 4.6 % for three concentration levels tested. Comparison with a reference laboratory LC-MS/MS method using leftover patient serum specimens (n = 48) showed a mean bias of -2.3 nM (-0.61 %) with a Deming regression slope of 1.016, intercept of -6.6 nM, standard error of estimate of 25.3 nM, and a correlation coefficient of 0.9945. In conclusion, this LC-MS/MS method offers highly sensitive and selective quantitation of MMA in serum and plasma with simple sample preparation. PMID:22618327

  11. Serum-circulating miRNAs predict neuroblastoma progression in mouse model of high-risk metastatic disease

    PubMed Central

    Ramraj, Satish Kumar; Aravindan, Sheeja; Somasundaram, Dinesh Babu; Herman, Terence S.; Natarajan, Mohan; Aravindan, Natarajan

    2016-01-01

    Background Circulating miRNAs have momentous clinical relevance as prognostic biomarkers and in the progression of solid tumors. Recognizing novel candidates of neuroblastoma-specific circulating miRNAs would allow us to identify potential prognostic biomarkers that could predict the switch from favorable to high-risk metastatic neuroblastoma (HR-NB). Results Utilizing mouse models of favorable and HR-NB and whole miRnome profiling, we identified high serum levels of 34 and low levels of 46 miRNAs in animals with HR-NB. Preferential sequence homology exclusion of mouse miRNAs identified 25 (11 increased; 14 decreased) human-specific prognostic marker candidates, of which, 21 were unique to HR-NB. miRNA QPCR validated miRnome profile. Target analysis defined the candidate miRNAs' signal transduction flow-through and demonstrated their converged roles in tumor progression. miRNA silencing studies verified the function of select miRNAs on the translation of at least 14 target proteins. Expressions of critical targets that correlate tumor progression in tissue of multifarious organs identify the orchestration of HR-NB. Significant (>10 fold) increase in serum levels of miR-381, miR-548h, and miR-580 identify them as potential prognostic markers for neuroblastoma progression. Conclusion For the first time, we identified serum-circulating miRNAs that predict the switch from favorable to HR-NB and, further imply that these miRNAs could play a functional role in tumor progression. PMID:26921195

  12. Pregnancy-associated serum N-glycome changes studied by high-throughput MALDI-TOF-MS.

    PubMed

    Jansen, Bas C; Bondt, Albert; Reiding, Karli R; Lonardi, Emanuela; de Jong, Coen J; Falck, David; Kammeijer, Guinevere S M; Dolhain, Radboud J E M; Rombouts, Yoann; Wuhrer, Manfred

    2016-01-01

    Pregnancy requires partial suppression of the immune system to ensure maternal-foetal tolerance. Protein glycosylation, and especially terminal sialic acid linkages, are of prime importance in regulating the pro- and anti-inflammatory immune responses. However, little is known about pregnancy-associated changes of the serum N-glycome and sialic acid linkages. Using a combination of recently developed methods, i.e. derivatisation that allows the distinction between α2,3- and α2,6-linked sialic acids by high-throughput MALDI-TOF-MS and software-assisted data processing, we analysed the serum N-glycome of a cohort of 29 healthy women at 6 time points during and after pregnancy. A total of 77 N-glycans were followed over time, confirming in part previous findings while also revealing novel associations (e.g. an increase of FA2BG1S1(6), FA2G1S1(6) and A2BG2S2(6) with delivery). From the individual glycans we calculated 42 derived traits. With these, an increase during pregnancy and decrease after delivery was observed for both α2,3- and α2,6-linked sialylation. Additionally, a difference in the recovery speed after delivery was observed for α2,3- and α2,6-linked sialylation of triantennary glycans. In conclusion, our new high-throughput workflow allowed the identification of novel plasma glycosylation changes with pregnancy. PMID:27075729

  13. Pregnancy-associated serum N-glycome changes studied by high-throughput MALDI-TOF-MS

    PubMed Central

    Jansen, Bas C.; Bondt, Albert; Reiding, Karli R.; Lonardi, Emanuela; de Jong, Coen J.; Falck, David; Kammeijer, Guinevere S. M.; Dolhain, Radboud J. E. M.; Rombouts, Yoann; Wuhrer, Manfred

    2016-01-01

    Pregnancy requires partial suppression of the immune system to ensure maternal-foetal tolerance. Protein glycosylation, and especially terminal sialic acid linkages, are of prime importance in regulating the pro- and anti-inflammatory immune responses. However, little is known about pregnancy-associated changes of the serum N-glycome and sialic acid linkages. Using a combination of recently developed methods, i.e. derivatisation that allows the distinction between α2,3- and α2,6-linked sialic acids by high-throughput MALDI-TOF-MS and software-assisted data processing, we analysed the serum N-glycome of a cohort of 29 healthy women at 6 time points during and after pregnancy. A total of 77 N-glycans were followed over time, confirming in part previous findings while also revealing novel associations (e.g. an increase of FA2BG1S1(6), FA2G1S1(6) and A2BG2S2(6) with delivery). From the individual glycans we calculated 42 derived traits. With these, an increase during pregnancy and decrease after delivery was observed for both α2,3- and α2,6-linked sialylation. Additionally, a difference in the recovery speed after delivery was observed for α2,3- and α2,6-linked sialylation of triantennary glycans. In conclusion, our new high-throughput workflow allowed the identification of novel plasma glycosylation changes with pregnancy. PMID:27075729

  14. Supplementation of broccoli or Bifidobacterium longum-fermented broccoli suppresses serum lipid peroxidation and osteoclast differentiation on alveolar bone surface in rats fed a high-cholesterol diet.

    PubMed

    Tomofuji, Takaaki; Ekuni, Daisuke; Azuma, Tetsuji; Irie, Koichiro; Endo, Yasumasa; Yamamoto, Tatsuo; Ishikado, Atsushi; Sato, Takehiko; Harada, Kayo; Suido, Hirohisa; Morita, Manabu

    2012-04-01

    High-cholesterol diet enhances osteoclastic activity on alveolar bone by increasing serum lipid peroxidation. We hypothesized that supplementation with dietary antioxidants, such as found in broccoli and its fermented products, might suppress increases in serum lipid peroxidation, contributing to the inhibition of osteoclastic activity after high-cholesterol diet intake. The purpose of the present study was to investigate the effects of broccoli and fermented broccoli consumption on serum lipid peroxidation and osteoclast differentiation in alveolar bone of rats fed a high-cholesterol diet. In this 12-week study, rats were divided into 4 groups (n = 6/group): a control group (fed regular diet) and 3 experimental groups (fed a high-cholesterol [1% wt/wt] diet, or a high-cholesterol diet supplemented with either broccoli powder [5% wt/wt] or Bifidobacterium longum-fermented broccoli powder [5% wt/wt]). Serum hexanoyl-lysine (HEL) levels were measured as a parameter of lipid peroxidation. The number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts in alveolar bone was enumerated to evaluate osteoclast differentiation. When compared with regular diet, the high-cholesterol diet increased serum HEL levels and resulted in a higher number of TRAP-positive osteoclasts at 12 weeks. The high-cholesterol diet supplemented with broccoli or B. longum-fermented broccoli showed lower levels of serum HEL and fewer TRAP-positive osteoclasts than the high-cholesterol diet at 12 weeks. In conclusion, consumption of broccoli, or its fermented product, inhibited the effects of a high-cholesterol diet on osteoclast differentiation in rat alveolar bone by suppressing serum lipid peroxidation. PMID:22575044

  15. WDR1 and CLNK gene polymorphisms correlate with serum glucose and high-density lipoprotein levels in Tibetan gout patients.

    PubMed

    Lan, Bing; Chen, Peng; Jiri, Mutu; He, Na; Feng, Tian; Liu, Kai; Jin, Tianbo; Kang, Longli

    2016-03-01

    Current evidence suggests heredity and metabolic syndrome contributes to gout progression. Specifically, the WDR1 and CLNK genes may play a role in gout progression in European ancestry populations. However, no studies have focused on Chinese populations, especially Tibetan individuals. This study aims to determine whether variations in these two genes correlate with gout-related indices in Chinese-Tibetan gout patients. Eleven single-nucleotide polymorphisms in the WDR1 and CLNK genes were detected in 319 Chinese-Tibetan gout patients and 318 controls. We used one-way analysis of variance to evaluate the polymorphisms' effects on gout based on mean serum levels of metabolism indicators, such as albumin, glucose (GLU), triglycerides, cholesterol, high-density lipoproteins (HDL-C), creatinine, and uric acid, from fasting venous blood samples. All p values were Bonferroni corrected. Polymorphisms of the WDR1 and CLNK genes affected multiple risk factors for gout development. Significant differences in serum GLU levels were detected between different genotypic groups with WDRI polymorphisms rs4604059 (p = 0.005) and rs12498927 (p = 0.005). In addition, significant differences in serum HDL-C levels were detected between different genotypic groups with the CLNK polymorphism rs2041215 (p = 0.001). Polymorphisms of CLNK also affected levels of albumin, triglycerides, and creatinine. This study is the first to investigate and identify positive correlations between WDR1 and CLNK gene polymorphisms in Chinese-Tibetan populations. Our findings provide significant evidence for the effect of genetic polymorphisms on gout-related factors in Chinese-Tibetan populations. PMID:26438387

  16. A Serum Vitamin D Level <25nmol/L Pose High Tuberculosis Risk: A Meta-Analysis

    PubMed Central

    Yang, Wen; Gu, Xiaoling; Liang, Wenjun; Yao, Yanwen; Song, Yong

    2015-01-01

    Background Low serum Vitamin D is considered to be associated with tuberculosis while the “dangerous” level was not clear. The aim of this study was to identify the association between tuberculosis and serum Vitamin D levels via synthesis of available evidence. Methods A search of EMBASE, Medline, ISI Web of knowledge, and Pubmed was conducted. The number of subjects of tuberculosis and no-tuberculosis groups in four Vitamin D range. Meta-analyses were performed and presented by odds ratios (ORs) and corresponding 95% confidence intervals (CIs). Results A total of 15 studies involving 1440 cases and 2558 controls were included. A significantly increased risk of tuberculosis was found in two ranges: ≤ 12.5 nmol/L: pooled OR = 4.556, 95% CI = 2.200-9.435; 13-25 nmol/L: pooled OR = 3.797, 95% CI = 1.935-7.405. No statistically significant risk of tuberculosis was found in the range of 26–50 nmol/L (pooled OR = 1.561, 95% CI =0.997-2.442). In range 51–75 nmol/L, no positive association was found (pooled OR =1.160, 95% CI = 0.708-1.900). Conclusions This study found that a serum Vitamin D level ≤ 25 nmol/L was significantly associated with an increased risk of tuberculosis while the range of 51–75 nmol/L was not. The range 26-50nmol/L posed potential high tuberculosis risk. Future large-scale, well-designed studies are needed to verify these results. PMID:25938683

  17. Elevated Serum MicroRNA Levels Associate with Absence of High-Grade Prostate Cancer in a Retrospective Cohort

    PubMed Central

    Mihelich, Brittany L.; Maranville, Joseph C.; Nolley, Rosalie; Peehl, Donna M.; Nonn, Larisa

    2015-01-01

    To reduce treatment of indolent prostate cancer (PCa), biomarkers are needed to improve identification of patients with a low-risk of having aggressive disease. Over-treatment of these patients occurs because of uncertainty in the aggressiveness of the entire tumor based on the biopsies, which do not accurately sample multifocal tumors. Circulating microRNAs (miRNAs) are stable serum markers and differential miRNA levels occur in men with PCa. The goal of this study was to identify circulating miRNAs that were associated with aggressive or indolent PCa. We measured circulating miRNAs in 150 patients prior to surgery and compared the miRNA levels to the pathology of the entire radical prostatectomy specimen. For this study we used an exceptionally well-characterized cohort of patients who had benign prostatic hyperplasia (BPH), low-grade or high-grade PCa. Low-grade was defined as patients with 100% Gleason grade 3 tumor as determined by step-wise sectioning. High-grade PCa patients had 30-90% Gleason grade 4+5 in the tumor. BPH patients had at least two biopsies negative for PCa. Twenty one miRNAs were selected for analysis. The miRNAs were quantified by RT-qPCR and analyzed by logistic regression. High levels of 14 miRNAs were exclusively present in the serum from patients with low-grade PCa or BPH, compared to men with high-grade PCa who had consistently low levels. The expression levels of the 14 miRNAs were combined into a “miR Score” which had a negative predictive value (NPV) of 0.939 to predict absence of high-grade PCa among PCa and BPH patients. Biochemical recurrence (BCR) was known for the PCa patients and a combined “miR Risk Score” accurately classified a subset of patients with low risk of BCR (NPV 0.941). In summary, measurement of serum miRNAs may have pre-surgical utility in combination with clinical risk calculators to identify patients with low risk of harboring aggressive PCa. PMID:25874774

  18. Abnormal Functional Specialization within Medial Prefrontal Cortex in High-Functioning Autism: A Multi-Voxel Similarity Analysis

    ERIC Educational Resources Information Center

    Gilbert, Sam J.; Meuwese, Julia D. I.; Towgood, Karren J.; Frith, Christopher D.; Burgess, Paul W.

    2009-01-01

    Multi-voxel pattern analyses have proved successful in "decoding" mental states from fMRI data, but have not been used to examine brain differences associated with atypical populations. We investigated a group of 16 (14 males) high-functioning participants with autism spectrum disorder (ASD) and 16 non-autistic control participants (12 males)…

  19. Eye movement abnormalities.

    PubMed

    Moncayo, Jorge; Bogousslavsky, Julien

    2012-01-01

    Generation and control of eye movements requires the participation of the cortex, basal ganglia, cerebellum and brainstem. The signals of this complex neural network finally converge on the ocular motoneurons of the brainstem. Infarct or hemorrhage at any level of the oculomotor system (though more frequent in the brain-stem) may give rise to a broad spectrum of eye movement abnormalities (EMAs). Consequently, neurologists and particularly stroke neurologists are routinely confronted with EMAs, some of which may be overlooked in the acute stroke setting and others that, when recognized, may have a high localizing value. The most complex EMAs are due to midbrain stroke. Horizontal gaze disorders, some of them manifesting unusual patterns, may occur in pontine stroke. Distinct varieties of nystagmus occur in cerebellar and medullary stroke. This review summarizes the most representative EMAs from the supratentorial level to the brainstem. PMID:22377853

  20. Prevalence of High-Risk Human Papillomavirus (HR-HPV) Genotypes and Multiple Infections in Cervical Abnormalities from Northern Xinjiang, China

    PubMed Central

    Du, Jingyun; Jiang, Jianjun; Jia, Xuesong; Chen, Chuangfu; Wang, Yuanzhi

    2016-01-01

    Multiple human papillomavirus (HPV) genotypes often coexist within the cervical epithelia and are frequently detected together in various grades of the cervical neoplasia. To date, only a few reports exist on multiple HPV infections of HPV in Xinjiang Uygur Autonomous Region (XUAR). In the present study, we investigated the prevalence of High-Risk HPV (HR-HPV) genotypes and multiple infections. Cervical cytology samples were collected from 428 women who presented cervical abnormalities. Genotyping of HPV was performed by polymerase chain reaction–sequencing based typing (PCR-SBT) using consensus primers and specific primers. Of them, 166 samples were positive for HPV according to PCR results using the consensus primers. These samples contained cervical abnormalities enriched with inflammation (n = 107), cervical intraepithelial neoplasia (CIN) I (n = 19), CINII-III (n = 9) and cervical cancer (n = 31). Of the 166 HPV positive samples as determined by PCR analysis, 151 were further typed by PCR-SBT using 19 pairs of genotype-specific primers. Using this method, 17 different HR-HPV genotypes were identified. The most frequently observed HPV genotypes were HPV16 (44.0%, 73/166), 53 (28.9%, 48/166), 52 (25.3%, 42/166), 58 (22.3%, 37/166) and 35 (17.5%, 29/166). The proportions of single and multiple infections in the HPV-positive specimens were 34.9% and 65.1%, respectively. Multiple HPV types were most prevalent in the inflammatory state (63.0%), followed by cervical cancer (24.1%), CINI (11.1%), and CINII-III (1.9%). The results of our data analyses suggested that i) multiple HPV infection is not necessarily correlated with the severity of cervical abnormalities; and ii) among the multiple HPV infections, double infections combined with HPV16 is the most common. In addition, L1 full-length sequences of the top five high-risk HPV genotypes were amplified and sequenced. According to the L1 sequence of the epidemic genotypes that were amplified, we found that these

  1. Performance characteristics of bioassay, radioenzymatic assay, homogeneous enzyme immunoassay, and high-performance liquid chromatographic determination of serum gentamicin

    SciTech Connect

    Delaney, C.J.; Opheim, K.E.; Smith, A.L.; Plorde, J.J.

    1982-01-01

    We compared the accuracy, precision, and between-method error of the microbiological assay, the radioenzymatic assay, the homogeneous enzyme immunoassay, and the high-performance liquid chromatographic assay for the quantitation of gentamicin in serum. Precision and accuracy were evaluated by reference samples prepared to contain 0.0 to 32.7 micrograms of gentamicin per ml. Correlations between the methods utilized patient sera with gentamicin concentrations ranging from 0.6 to 13.3 micrograms/ml. All methods were reliable within acceptable limits for routine clinical use; intermethod correlation coefficients exceeded 0.96. Relative to the microbiological assay, the alternative methods offer the advantage of rapid analysis. The elapsed times for acquiring data on a set of 10 specimens under routine operating conditions were 0.5 h by the enzyme immunoassay, 4 h by the radioenzymatic assay, 5 h by the high-performance liquid chromatographic assay, and 10 h by the microbiological assay.

  2. Performance characteristics of bioassay, radioenzymatic assay, homogeneous enzyme immunoassay, and high-performance liquid chromatographic determination of serum gentamicin.

    PubMed Central

    Delaney, C J; Opheim, K E; Smith, A L; Plorde, J J

    1982-01-01

    We compared the accuracy, precision, and between-method error of the microbiological assay, the radioenzymatic assay, the homogeneous enzyme immunoassay, and the high-performance liquid chromatographic assay for the quantitation of gentamicin in serum. Precision and accuracy were evaluated by reference samples prepared to contain 0.0 to 32.7 micrograms of gentamicin per ml. Correlations between the methods utilized patient sera with gentamicin concentrations ranging from 0.6 to 13.3 micrograms/ml. All methods were reliable within acceptable limits for routine clinical use; intermethod correlation coefficients exceeded 0.96. Relative to the microbiological assay, the alternative methods offer the advantage of rapid analysis. The elapsed times for acquiring data on a set of 10 specimens under routine operating conditions were 0.5 h by the enzyme immunoassay, 4 h by the radioenzymatic assay, 5 h by the high-performance liquid chromatographic assay, and 10 h by the microbiological assay. PMID:7044297

  3. Vescalagin from Pink Wax Apple [Syzygium samarangense (Blume) Merrill and Perry] Alleviates Hepatic Insulin Resistance and Ameliorates Glycemic Metabolism Abnormality in Rats Fed a High-Fructose Diet.

    PubMed

    Huang, Da-Wei; Chang, Wen-Chang; Wu, James Swi-Bea; Shih, Rui-Wen; Shen, Szu-Chuan

    2016-02-10

    This study investigates the ameliorative effect of vescalagin (VES) isolated from Pink wax apple fruit on hepatic insulin resistance and abnormal carbohydrate metabolism in high-fructose diet (HFD)-induced hyperglycemic rats. The results show that in HFD rats, VES significantly reduced the values of the area under the curve for glucose in an oral glucose tolerance test and the homeostasis model assessment of insulin resistance index. VES significantly enhanced the activity of hepatic antioxidant enzymes while reducing thiobarbituric acid-reactive substances in HFD rats. Western blot assay revealed that VES reduced hepatic protein expression involved in inflammation pathways while up-regulating expression of hepatic insulin signaling-related proteins. Moreover, VES up-regulated the expression of hepatic glycogen synthase and hepatic glycolysis-related proteins while down-regulating hepatic gluconeogenesis-related proteins in HFD rats. This study suggests some therapeutic potential of VES in preventing the progression of diabetes mellitus. PMID:26800576

  4. Liver- and bone-derived isoenzymes of alkaline phosphatase in serum as determined by high-performance affinity chromatography.

    PubMed

    Anderson, D J; Branum, E L; O'Brien, J F

    1990-02-01

    To separate liver and bone alkaline phosphatase (ALP) isoenzymes in human serum, we used high-performance affinity chromatography (HPAC) on a column of wheat-germ lectin conjugated to 7-microns-diameter silica particles and an eluent containing N-acetyl-D-glucosamine (NAG). On-line spectrophotometric detection of ALP involved pumping diethanolamine-buffered p-nitrophenyl phosphate solution post-column. Bone and liver isoenzymes could be separated into two peaks with only 10% overlap when an exponential gradient was used. A linear-step gradient separated 80.9% of liver ALP and 91.6% of bone ALP in two distinct peaks. True bone and liver ALP peak areas for the linear-step gradient were determined by using correction factors, because each peak contained a co-eluted portion of the other ALP isoenzyme. The detection limit improved 10-fold over those of other techniques for ALP isoenzymes, owing to the relatively large sample that could be applied to the column. Correlation with a urea-inactivation procedure was reasonable for patients' serum samples (r = 0.98 and 0.79 for liver ALP and bone ALP, respectively). PMID:2302767

  5. High performance liquid chromatographic measurement of iothalamate in human serum and urine for evaluation of glomerular filtration rate.

    PubMed

    Bi, Daoqin; Leary, Kevin J; Weitz, Julie A; Cherstniakova, Svetlana A; Reil, Michael A; Roy, Michael J; Cantilena, Louis R

    2007-09-01

    A simple and sensitive HPLC-UV assay was developed for the measurement of iothalamate (IOT) in human serum and urine. Chromatographic separation was achieved using an embedded-carbamate-group bonded RP18 column and mobile phase consisting of 50 mM monobasic sodium phosphate and methanol (90:10, v/v) without the addition of ion-pair reagents. The assay demonstrated a high analytical reliability within the IOT concentration range of 1-150 microg/ml in serum and 25-1500 microg/ml in urine. The relative standard deviations (RSDs) for intra- and inter-day analysis were less than 5.1% in all cases. This method has been used for the evaluation of glomerular filtration rate (GFR) in subjects participating in a phase I clinical trial of a novel antimalarial medicine. The average baseline GFR was 100.41+/-19.99 ml/min/1.73 m(2) in 119 healthy volunteers. The assay may also allow the simultaneous measurements of p-aminohippuric acid (PAH), N-acetyl PAH (aPAH), and IOT with some modification. PAH, IOT, aPAH, and beta-hydroxyethyl-theophylline internal standard peaks appeared approximately at 2.5, 3.7, 5.9, and 11.8 min, respectively, in an isocratic run. PMID:17599846

  6. The importance of low serum levels of high-density lipoprotein cholesterol (HDL-C) as a cardiovascular risk factor.

    PubMed

    Espinosa-Larrañaga, Francisco; Vejar-Jalaf, Margarita; Medina-Santillán, Roberto

    2005-10-01

    In order to discuss and establish a joint position on the treatment of low serum levels of high-density lipoprotein cholesterol (HDL-C), a group of experts involved in the care of people with dyslipidaemia and at risk of cardiovascular disease met in Miami, Florida, U.S., on 5th and 6th March 2005. The experts came from the Latin American countries Argentina, Brazil, Chile, Colombia, Ecuador, Guatemala, Mexico and Venezuela and had at least five years of experience in the care of patients with dyslipidaemia and low HDL-C. The main objective of the meeting was to discuss and propose a treatment for low serum HDL-C levels as a cardiovascular risk factor in patients and to create a group of useful recommendations in this regard, applicable to the daily clinical practice of physicians dealing with patients with dyslipidaemia and cardiovascular disease. This document describes the methodology developed to obtain these recommendations and presents the results of this academic meeting. PMID:16342610

  7. Is the serum amyloid A protein in acute phase plasma high density lipoprotein the precursor of AA amyloid fibrils?

    PubMed Central

    Baltz, M L; Rowe, I F; Caspi, D; Turnell, W G; Pepys, M B

    1986-01-01

    Serum amyloid A protein (SAA), an apolipoprotein of high density lipoprotein (HDL), is generally considered to be the precursor of AA protein, which forms the fibrils in reactive systemic amyloidosis in man and animals. This view is based on amino acid sequence identity between AA and the amino-terminal portion of SAA. However, in extensive and well-controlled studies of experimentally induced murine AA amyloidosis, we were unable to demonstrate a direct precursor-product relationship between SAA, in SAA-rich HDL preparations from acute phase or amyloidotic mouse or human serum, and AA protein in the amyloid deposits. This raises the possibility that SAA in its usual form, as an apolipoprotein of HDL synthesized during the acute phase response, may not be the major precursor of AA fibrils. The amyloidogenic forms of circulating SAA molecules may not be isolated during the preparation of HDL. Alternatively, particularly in the light of recent evidence that SAA mRNA is expressed in many different tissues throughout the body of appropriately stimulated animals, amyloidogenic SAA may be derived from sources other than the liver cells in which SAA-rich HDL is synthesized. PMID:3105937

  8. High dose flaxseed oil supplementation may affect fasting blood serum glucose management in human type 2 diabetics.

    PubMed

    Barre, Douglas E; Mizier-Barre, Kazimiera A; Griscti, Odette; Hafez, Kevin

    2008-01-01

    Type 2 diabetes is characterized partially by elevated fasting blood serum glucose and insulin concentrations and the percentage of hemoglobin as HbA1c. It was hypothesized that each of blood glucose and its co-factors insulin and HbA1c and would show a more favorable profile as the result of flaxseed oil supplementation. Patients were recruited at random from a population pool responding to a recruitment advertisement in the local newspaper and 2 area physicians. Completing the trial were 10 flaxseed oil males, 8 flaxseed oil females, 8 safflower (placebo) oil males and 6 safflower oil females. Patients visited on two pre-treatment occasions each three months apart (visits 1 and 2). At visit 2 subjects were randomly assigned in double blind fashion and in equal gender numbers to take flaxseed oil or safflower oil for three further months until visit 3. Oil consumption in both groups was approximately 10 g/d. ALA intake in the intervention group was approximately 5.5 g/d. Power was 0.80 to see a difference of 1 mmol of glucose /L using 12 subjects per group with a p < 0.05. Flaxseed oil had no impact on fasting blood serum glucose, insulin or HbA1c levels. It is concluded that high doses of flaxseed oil have no effect on glycemic control in type 2 diabetics. PMID:18391475

  9. Tooth - abnormal shape

    MedlinePlus

    Hutchinson incisors; Abnormal tooth shape; Peg teeth; Mulberry teeth; Conical teeth ... The appearance of normal teeth varies, especially the molars. ... conditions. Specific diseases can affect tooth shape, tooth ...

  10. Tooth - abnormal shape

    MedlinePlus

    Hutchinson incisors; Abnormal tooth shape; Peg teeth; Mulberry teeth; Conical teeth ... from many different conditions. Specific diseases can affect tooth shape, tooth color, time of appearance, or absence ...

  11. MULTISCREEN SERUM ANALYSIS OF HIGHLY SENSITIZED RENAL DIALYSIS PATIENTS FOR ANTIBODIES TOWARD PUBLIC AND PRIVATE CLASS I HLA DETERMINANTS

    PubMed Central

    Duquesnoy, Rene J.; White, Linda T.; Fierst, Janet W.; Vanek, Marian; Banner, Barbara F.; Iwaki, Yuichi; Starzl, Thomas E.

    2010-01-01

    A multi screen serum analysis program has been developed that permits a determination of antibody specificity for the vast majority of highly sensitized patients awaiting transplantation. This program is based on a 2 × 2 table analysis of correlations between serum reactivity with an HLA-typed cell panel and incorporates two modifications. One implements the concept of public HLA determinants based on the serologic crossreactivity among class I HLA antigens. The other modification derives from the premise that most highly sensitized patients maintain the same PRA and antibody profiles over many months and even years. Monthly screening results for patients with persistent PRA values can therefore be combined for analysis. For 132 of 150 highly sensitized patients with >50% PRA, this multiscreen serum analysis program yielded information about antibody specificity toward public and private class I HLA determinants. The vast majority of patients (108 of 112) with PRA values between 50 and 89% showed antibody specificity generally toward one, two, or three public markers and/or the more common private HLA-A, B antigens. For 24 of 38 patients with >90% PRA, it was possible to define one or few HLA-specific antibodies. The primary objective of the multiscreen program was to develop an algorithm about computer-predicted acceptable and unacceptable donor HLA-A, B antigens for patients with preformed antibodies. A retrospective analysis of kidney transplants into 89 highly sensitized patients has demonstrated that allografts with unacceptable HLA-A, B mismatches had significantly lower actuarial survival rates than those with acceptable mismatches (P = 0.01). This was shown for both groups of 32 primary transplants (44% vs. 67% after 1 year) and 60 retransplants (50% vs. 68%). Also, serum creatinine levels were significantly higher in patients with unacceptable class I mismatches (3.0 vs. 8.4 mg% [P = 0.007] after 2 weeks; 3.9 vs. 9.1 mg% [P = 0.014] after 4 weeks

  12. Serum phenylalanine screening

    MedlinePlus

    ... The test detects abnormally high levels of an amino acid called phenylalanine. ... body lacks a substance needed to breakdown the amino acid phenylalanine. If PKU is not detected early, increasing ...

  13. Abnormalities in carbohydrate and lipid metabolisms in high-fructose dietfed insulin-resistant rats: amelioration by Catharanthus roseus treatments.

    PubMed

    Rasineni, Karuna; Bellamkonda, Ramesh; Singareddy, Sreenivasa Reddy; Desireddy, Saralakumari

    2013-09-01

    High intake of dietary fructose has been shown to exert a number of adverse metabolic effects in humans and experimental animals. The present study was proposed to elucidate the effect of Catharanthus roseus (C. roseus) leaf powder treatment on alterations in carbohydrate and lipid metabolisms in rats fed with high-fructose diet. Male Wistar rats of body weight around 180 g were divided into four groups, two of these groups (groups C and C+CR) were fed with standard pellet diet and the other two groups (groups F and F+CR) were fed with high-fructose (66 %) diet. C. roseus leaf powder suspension in water (100 mg/kg body weight/day) was administered orally to group C+CR and group F+CR. At the end of a 60-day experimental period, biochemical parameters related to carbohydrate and lipid metabolisms were assayed. C. roseus treatment completely prevented the fructose-induced increased body weight, hyperglycemia, and hypertriglyceridemia. Hyperinsulinemia and insulin resistance observed in group F was significantly decreased with C. roseus treatment in group F+CR. The alterations observed in the activities of enzymes of carbohydrate and lipid metabolisms and contents of hepatic tissue lipids in group F rats were significantly restored to near normal values by C. roseus treatment in group F+CR. In conclusion, our study demonstrates that C. roseus treatment is effective in preventing fructose-induced insulin resistance and hypertriglyceridemia while attenuating the fructose-induced alterations in carbohydrate and lipid metabolisms. This study suggests that the plant can be used as an adjuvant for the prevention and/or management of insulin resistance and disorders related to it. PMID:23334857

  14. Breathing abnormalities in sleep in achondroplasia.

    PubMed Central

    Waters, K A; Everett, F; Sillence, D; Fagan, E; Sullivan, C E

    1993-01-01

    Overnight sleep studies were performed in 20 subjects with achondroplasia to document further the respiratory abnormalities present in this group. Somatosensory evoked potentials (SEPs) were recorded in 19 of the subjects to screen for the presence of brainstem abnormalities, which are one of the potential aetiological mechanisms. Fifteen children aged 1 to 14 years, and five young adults, aged 20 to 31 years were included. All had upper airway obstruction and 15 (75%) had a pathological apnoea index (greater than five per hour). Other sleep associated respiratory abnormalities, including partial obstruction, central apnoea, and abnormal electromyographic activity of accessory muscles of respiration, also showed a high prevalence. SEPs were abnormal in eight (42%), but there was no correlation between abnormal SEPs and apnoea during sleep, either qualitatively or quantitatively. A high prevalence of both sleep related respiratory abnormalities and abnormal SEPs in young subjects with achondroplasia was demonstrated. However, the sleep related respiratory abnormalities do not always result in significant blood gas disturbances or correlate with abnormal SEPs in this group. PMID:8215519

  15. Electrocardiographic abnormalities and dyslipidaemic syndrome in children with sickle cell anaemia

    PubMed Central

    Adegoke, Samuel Ademola; Okeniyi, John Akintunde Oladotun; Akintunde, Adeseye Abiodun

    2016-01-01

    Summary Background Lipid and electrocardiographic (ECG) abnormalities have been reported in adults with sickle cell anaemia (SCA) and may reflect underlying structural and/ or functional damage. However, the relationship between ECG and lipid abnormalities among children with sickle cell disease is not fully understood. Objectives To compare the steady-state lipid and ECG abnormalities in children with SCA to the controls and examine the hypothesis that lipid abnormalities are closely related to electrocardiographic abnormalities, and therefore are a reflection of cardiac damage among these children. Methods: Clinical, laboratory and ECG profiles of 62 children with SCA and 40 age- and gender-matched haemoglobin AA controls were compared. The influence of clinical characteristics, lipids profiles, markers of haemolysis, and renal and hepatic dysfunction on ECG pattern in children with SCA was then determined. Results The patients had lower average diastolic and mean arterial blood pressure, total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels than the controls, (p = 0.001, 0.002, 0.000 and 0.000, respectively). The mean triglyceride level was significantly higher (p < 0.001), while high-density lipoprotein cholesterol (HDL-C) levels were comparable (p = 0.858). The cases were about six times more likely to have left ventricular hypertrophy than the controls (OR = 6.4, 95% CI = 2.7–15.6, p = 0.000). Haematocrit level had a negative correlation with QTC (r = –0.3, p = 0.016) and QT intervals (r = – 0.3, p = 0.044). Triglyceride levels had a positive correlation with the PR interval (r = 0.3, p = 0.012), while serum alanine transferase (ALT) concentrations had an inverse correlation with PR interval (r = –0.3, p = 0.015). There was no statistical difference in the sociodemographic and clinical characteristics of the SCA children with or without ECG abnormalities. However, the mean triglyceride and serum ALT levels in those with ECG

  16. Neuroanatomic and cognitive abnormalities in attention-deficit/hyperactivity disorder in the era of 'high definition' neuroimaging.

    PubMed

    Baroni, Argelinda; Castellanos, F Xavier

    2015-02-01

    The ongoing release of the Human Connectome Project (HCP) data is a watershed event in clinical neuroscience. By attaining a quantum leap in spatial and temporal resolution within the framework of a twin/sibling design, this open science resource provides the basis for delineating brain-behavior relationships across the neuropsychiatric landscape. Here we focus on attention-deficit/hyperactivity disorder (ADHD), which is at least partly continuous across the population, highlighting constructs that have been proposed for ADHD and which are included in the HCP phenotypic battery. We review constructs implicated in ADHD (reward-related processing, inhibition, vigilant attention, reaction time variability, timing and emotional lability) which can be examined in the HCP data and in future 'high definition' clinical datasets. PMID:25212469

  17. Neuroanatomic and Cognitive Abnormalities in Attention-Deficit/Hyperactivity Disorder in the Era of “High Definition” Neuroimaging

    PubMed Central

    Baroni, Argelinda; Castellanos, F. Xavier

    2014-01-01

    The ongoing release of the Human Connectome Project (HCP) data is a watershed event in clinical neuroscience. By attaining a quantum leap in spatial and temporal resolution within the framework of a twin/sibling design, this open science resource provides the basis for delineating brain-behavior relationships across the neuropsychiatric landscape. Here we focus on attention-deficit/hyperactivity disorder (ADHD), which is at least partly continuous across the population, highlighting constructs that have been proposed for ADHD and which are included in the HCP phenotypic battery. We review constructs implicated in ADHD (reward-related processing, inhibition, vigilant attention, reaction time variability, timing and emotional lability) which can be examined in the HCP data and in future “high definition” clinical datasets. PMID:25212469

  18. Abnormally High Content of Free Glucosamine Residues Identified in a Preparation of Commercially Available Porcine Intestinal Heparan Sulfate.

    PubMed

    Mulloy, Barbara; Wu, Nian; Gyapon-Quast, Frederick; Lin, Lei; Zhang, Fuming; Pickering, Matthew C; Linhardt, Robert J; Feizi, Ten; Chai, Wengang

    2016-07-01

    Heparan sulfate (HS) polysaccharides are ubiquitous in animal tissues as components of proteoglycans, and they participate in many important biological processes. HS carbohydrate chains are complex and can contain rare structural components such as N-unsubstituted glucosamine (GlcN). Commercially available HS preparations have been invaluable in many types of research activities. In the course of preparing microarrays to include probes derived from HS oligosaccharides, we found an unusually high content of GlcN residue in a recently purchased batch of porcine intestinal mucosal HS. Composition and sequence analysis by mass spectrometry of the oligosaccharides obtained after heparin lyase III digestion of the polysaccharide indicated two and three GlcN in the tetrasaccharide and hexasaccharide fractions, respectively. (1)H NMR of the intact polysaccharide showed that this unusual batch differed strikingly from other HS preparations obtained from bovine kidney and porcine intestine. The very high content of GlcN (30%) and low content of GlcNAc (4.2%) determined by disaccharide composition analysis indicated that N-deacetylation and/or N-desulfation may have taken place. HS is widely used by the scientific community to investigate HS structures and activities. Great care has to be taken in drawing conclusions from investigations of structural features of HS and specificities of HS interaction with proteins when commercial HS is used without further analysis. Pending the availability of a validated commercial HS reference preparation, our data may be useful to members of the scientific community who have used the present preparation in their studies. PMID:27295282

  19. Abnormally High Content of Free Glucosamine Residues Identified in a Preparation of Commercially Available Porcine Intestinal Heparan Sulfate

    PubMed Central

    2016-01-01

    Heparan sulfate (HS) polysaccharides are ubiquitous in animal tissues as components of proteoglycans, and they participate in many important biological processes. HS carbohydrate chains are complex and can contain rare structural components such as N-unsubstituted glucosamine (GlcN). Commercially available HS preparations have been invaluable in many types of research activities. In the course of preparing microarrays to include probes derived from HS oligosaccharides, we found an unusually high content of GlcN residue in a recently purchased batch of porcine intestinal mucosal HS. Composition and sequence analysis by mass spectrometry of the oligosaccharides obtained after heparin lyase III digestion of the polysaccharide indicated two and three GlcN in the tetrasaccharide and hexasaccharide fractions, respectively. 1H NMR of the intact polysaccharide showed that this unusual batch differed strikingly from other HS preparations obtained from bovine kidney and porcine intestine. The very high content of GlcN (30%) and low content of GlcNAc (4.2%) determined by disaccharide composition analysis indicated that N-deacetylation and/or N-desulfation may have taken place. HS is widely used by the scientific community to investigate HS structures and activities. Great care has to be taken in drawing conclusions from investigations of structural features of HS and specificities of HS interaction with proteins when commercial HS is used without further analysis. Pending the availability of a validated commercial HS reference preparation, our data may be useful to members of the scientific community who have used the present preparation in their studies. PMID:27295282

  20. [Serum mesothelin dosages in follow-up of previously exposed workers].

    PubMed

    Foddis, R; Vivaldi, A; Filiberti, R; Puntoni, R; Mutti, L; Ambrosino, N; Chella, A; Guglielmi, G; Gattini, V; Buselli, R; Perretta, S; Cristaudo, A

    2007-01-01

    High dosages of Serum Mesothelin have been demonstrated to be significantly associated to Pleural Malignant Mesothelioma. We recently demonstrated that Serum Mesothelin may be clinically helpful both for diagnostic and prognostic purposes, with the best cut-off corresponding to 1 nM. We also discovered that high levels of Serum Mesothelin are significantly associated to Lung Cancer. The usefulness of this marker in secondary prevention has been suggested, though never demonstrated. We therefore started a long-term prospective cohort study including previously asbestos-exposed workers. These subjects periodically underwent both radiological tests and serum mesothelin dosages. As a mid-term goal of this longitudinal study we decided to check the variability of mesothelin dosages, comparing baseline and follow-up values, as well as the possible correlation with age, duration of exposure, smoking, any abnormality of respiratory functional tests (RFT) and/or radiological tests. At baseline, Mesothelin mean value was 0.66 +/- 0.4 (range 0.08-2.2 nM). Both age (p = 0.04) and abnormal thoracic TC (p = 0.04) were significantly correlated with increased serum mesothelin levels and increasing age. No association was found between baseline mesothelin levels and duration of asbestos exposure (p = 0.5), smoking habits (p = 0.2), abnormal RFT, DLCO (carbon monoxide diffusing capacity) or thoracic X-ray. No significant variation was observed between mesothelin values at baseline and at follow-up (p = 0.2). PMID:18409716

  1. High-Throughput Serum 25-Hydroxy Vitamin D Testing with Automated Sample Preparation.

    PubMed

    Stone, Judy

    2016-01-01

    Serum from bar-coded tubes, and then internal standard, are pipetted to 96-well plates with an 8-channel automated liquid handler (ALH). The first precipitation reagent (methanol:ZnSO4) is added and mixed with the 8-channel ALH. A second protein precipitating agent, 1 % formic acid in acetonitrile, is added and mixed with a 96-channel ALH. After a 4-min delay for larger precipitates to settle to the bottom of the plate, the upper 36 % of the precipitate/supernatant mix is transferred with the 96-channel ALH to a Sigma Hybrid SPE(®) plate and vacuumed through for removal of phospholipids and precipitated proteins. The filtrate is collected in a second 96-well plate (collection plate) which is foil-sealed, placed in the autosampler (ALS), and injected into a multiplexed LC-MS/MS system running AB Sciex Cliquid(®) and MPX(®) software. Two Shimadzu LC stacks, with multiplex timing controlled by MPX(®) software, inject alternately to one AB Sciex API-5000 MS/MS using positive atmospheric pressure chemical ionization (APCI) and a 1.87 min water/acetonitrile LC gradient with a 2.1 × 20 mm, 2.7 μm, C18 fused core particle column (Sigma Ascentis Express). LC-MS/MS through put is ~44 samples/h/LC-MS/MS system with dual-LC channel multiplexing. Plate maps are transferred electronically from the ALH and reformatted into LC-MS/MS sample table format using the Data Innovations LLC (DI) Instrument Manager middleware application. Before collection plates are loaded into the ALS, the plate bar code is manually scanned to download the sample table from the DI middleware to the LC-MS/MS. After acquisition-LC-MS/MS data is analyzed with AB Sciex Multiquant(®) software using customized queries, and then results are transferred electronically via a DI interface to the LIS. 2500 samples/day can be extracted by two analysts using four ALHs in 4-6 h. LC-MS/MS analysis of those samples on three dual-channel LC multiplexed LC-MS/MS systems requires 19-21 h and data analysis can be

  2. Brain abnormalities in high-risk violent offenders and their association with psychopathic traits and criminal recidivism.

    PubMed

    Leutgeb, V; Leitner, M; Wabnegger, A; Klug, D; Scharmüller, W; Zussner, T; Schienle, A

    2015-11-12

    Measures of psychopathy have been proved to be valuable for risk assessment in violent criminals. However, the neuronal basis of psychopathy and its contribution to the prediction of criminal recidivism is still poorly understood. We compared structural imaging data from 40 male high-risk violent offenders and 37 non-delinquent healthy controls via voxel-based morphometry. Psychopathic traits and risk of violence recidivism were correlated with gray matter volume (GMV) of regions of interest previously shown relevant for criminal behavior. Relative to controls, criminals showed less GMV in the prefrontal cortex (PFC) and more GMV in cerebellar regions and basal ganglia structures. Within criminals, we found a negative correlation between prefrontal GMV and psychopathy. Additionally, there was a positive correlation between cerebellar GMV and psychopathy as well as risk of recidivism for violence. Moreover, GMVs of the basal ganglia and supplementary motor area (SMA) were positively correlated with anti-sociality. GMV of the amygdala was negatively correlated with dynamic risk for violence recidivism. In contrast, GMV of (para)limbic areas (orbitofrontal cortex, insula) was positively correlated with anti-sociality and risk of violence recidivism. The current investigation revealed that in violent offenders deviations in GMV of the PFC as well as areas involved in the motor component of impulse control (cerebellum, basal ganglia, SMA) are differentially related to psychopathic traits and the risk of violence recidivism. The results might be valuable for improving existing risk assessment tools. PMID:26362887

  3. Brain white matter abnormality in a newborn infant with congenital adrenal hyperplasia.

    PubMed

    Kaga, Akimune; Saito-Hakoda, Akiko; Uematsu, Mitsugu; Kamimura, Miki; Kanno, Junko; Kure, Shigeo; Fujiwara, Ikuma

    2013-10-01

    Several studies have described brain white matter abnormalities on magnetic resonance imaging (MRI) in children and adults with congenital adrenal hyperplasia (CAH), while the brain MRI findings of newborn infants with CAH have not been clarified. We report a newborn boy with CAH who presented brain white matter abnormality on MRI. He was diagnosed as having salt-wasting CAH with a high 17-OHP level at neonatal screening and was initially treated with hydrocortisone at 8 days of age. On day 11 after birth, he had a generalized tonic seizure. No evidence of serum electrolyte abnormalities was observed. Brain MRI revealed white matter abnormalities that consisted of bilateral small diffuse hyperintensities on T1-weighted images with slightly low intensity on T2-weighted images in the watershed area. Several factors associated with brain white matter abnormalities in adults with CAH, such as increasing age, hypertension, diabetes and corticosteroid replacement, were not applicable. Although the cause of the phenomenon in this case is unclear, brain white matter abnormality could be observed in newborn infants with CAH as well as in adult patients. PMID:24170965

  4. Pre-Treatment Serum C-Reactive Protein Level Is An Independent Risk Factor for Development of Nephrotoxicity in Patients Receiving High-Dose Vancomycin.

    PubMed

    He, Juan; Mao, En-Qiang; Jing, Feng; Jiang, Hui-Ting; Yang, Wan-Hua; Chen, Er-Zhen

    2016-01-01

    High-dose vancomycin treatment increases the likelihood of vancomycin-related nephrotoxicity. C-reactive protein (CRP) is a sensitive marker of systemic inflammation. In this study, we evaluated the pre-treatment serum CRP level as a risk factor of the development of nephrotoxicity in patients receiving high total daily doses (>2.5 g) of vancomycin. Data extracted from medical records for 174 patients who received total daily doses of >2.5 g of intravenous vancomycin for a minimum of 48 h and had their serum CRP level and erythrocyte sedimentation rate tested within 24 h before vancomycin treatment were subject to final analyses. Univariate analyses showed that patients who developed nephrotoxicity during vancomycin treatment had significantly higher median vancomycin serum concentration, duration of vancomycin treatment, and the serum CRP level within 24 h before vancomycin treatment than the non-nephrotoxicity group. Multivariate logistic regression analysis showed that after adjustment for potential confounders, median vancomycin serum concentration, duration of treatment, serum CRP level within 24 h before vancomycin treatment, and nephrotoxic medication were found significantly associated with the development of nephrotoxicity. This was confirmed by multivariate hazard ratio analysis after adjustment for potential confounders. In conclusion, this study provides the first evidence supporting the fact that the serum CRP level within 24 h before vancomycin treatment is an independent risk factor for the development of nephrotoxicity in patients receiving total daily doses of >2.5 g of vancomycin. Therefore, the serum CRP level within 24 h before vancomycin treatment could be a potential biomarker or prognostic factor for the development of vancomycin nephrotoxicity. PMID:26919511

  5. Abnormalities in myo-inositol metabolism associated with type 2 diabetes in mice fed a high-fat diet: benefits of a dietary myo-inositol supplementation.

    PubMed

    Croze, Marine L; Géloën, Alain; Soulage, Christophe O

    2015-06-28

    We previously reported that a chronic supplementation with myo-inositol (MI) improved insulin sensitivity and reduced fat accretion in mice. We then tested the potency of such dietary intervention in the prevention of insulin resistance in C57BL/6 male mouse fed a high-fat diet (HFD). In addition, some abnormalities in inositol metabolism were reported to be associated with insulin resistance in several animal and human studies. We then investigated the presence of such anomalies (i.e. inosituria and an inositol intra-tissue depletion) in this diet-induced obesity (DIO) mouse model, as well as the potential benefit of a MI supplementation for inositol intra-tissue deficiency correction. HFD (60 % energy from fat) feeding was associated with inosituria and inositol intra-tissue depletion in the liver and kidneys. MI supplementation (0·58 mg/g per d) restored inositol pools in kidneys (partially) and liver (fully). HFD feeding for 4 months induced ectopic lipid redistribution to liver and muscles, fasting hyperglycaemia and hyperinsulinaemia, insulin resistance and obesity that were not prevented by MI supplementation, despite a significant improvement in insulin sensitivity parameter K insulin tolerance test and a reduction in white adipose tissue (WAT) mass ( - 17 %, P< 0·05). MI supplementation significantly reduced fatty acid synthase activity in epididymal WAT, which might explain its beneficial, but modest, effect on WAT accretion in HFD-fed mice. Finally, we found some abnormalities in inositol metabolism in association with a diabetic phenotype (i.e. insulin resistance and fasting hyperglycaemia) in a DIO mouse model. Dietary MI supplementation was efficient in the prevention of inositol intra-tissue depletion, but did not prevent insulin resistance or obesity efficiently in this mouse model. PMID:25990651

  6. Structurally abnormal human autosomes

    SciTech Connect

    1993-12-31

    Chapter 25, discusses structurally abnormal human autosomes. This discussion includes: structurally abnormal chromosomes, chromosomal polymorphisms, pericentric inversions, paracentric inversions, deletions or partial monosomies, cri du chat (cat cry) syndrome, ring chromosomes, insertions, duplication or pure partial trisomy and mosaicism. 71 refs., 8 figs.

  7. Fatty acid composition in serum correlates with that in the liver and non-alcoholic fatty liver disease activity scores in mice fed a high-fat diet.

    PubMed

    Wang, Xing-He; Li, Chun-Yan; Muhammad, Ishfaq; Zhang, Xiu-Ying

    2016-06-01

    In this study, we investigated the correlation between the serum fatty acid composition and hepatic steatosis, inflammation, hepatocellular ballooning scores, and liver fatty acids composition in mice fed a high-fat diet. Livers were collected for non-alcoholic fatty liver disease score analysis. Fatty acid compositions were analysed by gas chromatography. Correlations were determined by Pearson correlation coefficient. Exposed to a high-fat diet, mice developed fatty liver disease with varying severity without fibrosis. The serum fatty acid variation became more severe with prolonged exposure to a high-fat diet. This variation also correlated significantly with the variation in livers, with the types of fatty acids corresponding to liver steatosis, inflammation, and hepatocellular ballooning scores. Results of this study lead to the following hypothesis: the extent of serum fatty acid variation may be a preliminary biomarker of fatty liver disease caused by high-fat intake. PMID:27179602

  8. Alpha slow-moving high-density-lipoprotein subfraction in serum of a patient with radiation enteritis and peritoneal carcinosis

    SciTech Connect

    Peynet, J.; Legrand, A.; Messing, B.; Thuillier, F.; Rousselet, F.

    1989-04-01

    An alpha slow-moving high-density-lipoprotein (HDL) subfraction was seen in a patient presenting with radiation enteritis and peritoneal carcinosis, who was given long-term cyclic parenteral nutrition. This subfraction, observed in addition to normal HDL, was precipitated with low-density lipoproteins (LDL) and very-low-density lipoproteins (VLDL) by sodium phosphotungstate-magnesium chloride. The patient's serum lipoproteins were analyzed after fractionation by density gradient ultracentrifugation. The alpha slow-moving HDL floated in the ultracentrifugation subfractions with densities ranging from 1.028 to 1.084 kg/L, and their main apolipoproteins included apolipoprotein E in addition to apolipoprotein A-I. These HDL were larger than HDL2. The pathogenesis of this unusual HDL subfraction is hypothesized.

  9. High-performance liquid chromatographic determination of loracarbef, a potential metabolite, cefaclor and cephalexin in human plasma, serum and urine.

    PubMed

    Kovach, P M; Lantz, R J; Brier, G

    1991-06-14

    A high-performance liquid chromatographic (HPLC) method is reported for the determination of a new carbacephem antibiotic, loracarbef, a hydroxylated analogue, and two cephalosporins, cefaclor and cephalexin, in plasma, serum, and urine. The antibiotics are extracted from plasma by means of C18 solid-phase cartridges. Urine samples are diluted with water and directly injected on the HPLC system. The HPLC system utilizes a Supelcosil LC-18-DB (250 mm x 4.6 mm I.D.) reversed-phase column and ultraviolet detection at 265 nm. The limit of quantitation is 0.5 micrograms/ml for each compound. Excellent correlation of plasma concentrations is shown between results determined by HPLC and those obtained by microbiological agar-well diffusion assays. Stability studies of loracarbef in human plasma show the antibiotic to be stable for at least 24 h at room temperature and for at least twelve months at -20 degrees C. PMID:1918240

  10. Comparative analysis of conjugated bile acids in human serum using high-performance liquid chromatography and capillary electrophoresis.

    PubMed

    Lee, B L; New, A L; Ong, C N

    1997-12-19

    This paper describes the analysis of conjugated bile acids in human serum using reversed-phase high-performance liquid chromatography (HPLC) and micellar electrokinetic capillary electrophoresis (CE). Samples of healthy subjects and patients with different hepatic diseases were pretreated with a simple preparation procedure using a solid-phase extraction technique. The optimal analytical conditions of both chromatographic methods were investigated for the convenience and reliability for routine analysis. Both HPLC and CE methods were found to be reliable and compatible. The recoveries of nine bile acid conjugates using both methods were generally >85% and reproducibility >90%. The day-to-day variation of retention time was <5% for HPLC, while the variation of migration time for CE was <3%. Although the detection limit of the HPLC method (1 nmol/ml) was five times more sensitive than that of the CE method, the CE method was considered to be more time and cost effective. PMID:9518169

  11. Norepinephrine stimulates progesterone production in highly estrogenic bovine granulosa cells cultured under serum-free, chemically defined conditions

    PubMed Central

    2012-01-01

    Background Since noradrenergic innervation was described in the ovarian follicle, the actions of the intraovarian catecholaminergic system have been the focus of a variety of studies. We aimed to determine the gonadotropin-independent effects of the catecholamine norepinephrine (NE) in the steroid hormone profile of a serum-free granulosa cell (GC) culture system in the context of follicular development and dominance. Methods Primary bovine GCs were cultivated in a serum-free, chemically defined culture system supplemented with 0.1% polyvinyl alcohol. The culture features were assessed by hormone measurements and ultrastructural characteristics of GCs. Results GCs produced increasing amounts of estradiol and pregnenolone for 144h and maintained ultrastructural features of healthy steroidogenic cells. Progesterone production was also detected, although it significantly increased only after 96h of culture. There was a highly significant positive correlation between estradiol and pregnenolone production in high E2-producing cultures. The effects of NE were further evaluated in a dose–response study. The highest tested concentration of NE (10 (−7) M) resulted in a significant increase in progesterone production, but not in estradiol or pregnenolone production. The specificity of NE effects on progesterone productio n was further investigated by incubating GCs with propranolol (10 (−8) M), a non-selective beta-adrenergic antagonist. Conclusions The present culture system represents a robust model to study the impact of intrafollicular factors, such as catecholamines, in ovarian steroidogenesis and follicular development. The results of noradrenergic effects in the steroidogenesis of GC have implications on physiological follicular fate and on certain pathological ovarian conditions such as cyst formation and anovulation. PMID:23171052

  12. Purified human pancreatic duct cell culture conditions defined by serum-free high-content growth factor screening.

    PubMed

    Hoesli, Corinne A; Johnson, James D; Piret, James M

    2012-01-01

    The proliferation of pancreatic duct-like CK19+ cells has implications for multiple disease states including pancreatic cancer and diabetes mellitus. The in vitro study of this important cell type has been hampered by their limited expansion compared to fibroblast-like vimentin+ cells that overgrow primary cultures. We aimed to develop a screening platform for duct cell mitogens after depletion of the vimentin+ population. The CD90 cell surface marker was used to remove the vimentin+ cells from islet-depleted human pancreas cell cultures by magnetic-activated cell sorting. Cell sorting decreased CD90+ cell contamination of the cultures from 34±20% to 1.3±0.6%, yielding purified CK19+ cultures with epithelial morphology. A full-factorial experimental design was then applied to test the mitogenic effects of bFGF, EGF, HGF, KGF and VEGF. After 6 days in test conditions, the cells were labelled with BrdU, stained and analyzed by high-throughput imaging. This screening assay confirmed the expected mitogenic effects of bFGF, EGF, HGF and KGF on CK19+ cells and additionally revealed interactions between these factors and VEGF. A serum-free medium containing bFGF, EGF, HGF and KGF led to CK19+ cell expansion comparable to the addition of 10% serum. The methods developed in this work should advance pancreatic cancer and diabetes research by providing effective cell culture and high-throughput screening platforms to study purified primary pancreatic CK19+ cells. PMID:22442738

  13. High throughput LC-MS/MS method for the simultaneous analysis of multiple vitamin D analytes in serum.

    PubMed

    Jenkinson, Carl; Taylor, Angela E; Hassan-Smith, Zaki K; Adams, John S; Stewart, Paul M; Hewison, Martin; Keevil, Brian G

    2016-03-01

    Recent studies suggest that vitamin D-deficiency is linked to increased risk of common human health problems. To define vitamin D 'status' most routine analytical methods quantify one particular vitamin D metabolite, 25-hydroxyvitamin D3 (25OHD3). However, vitamin D is characterized by complex metabolic pathways, and simultaneous measurement of multiple vitamin D metabolites may provide a more accurate interpretation of vitamin D status. To address this we developed a high-throughput liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to analyse multiple vitamin D analytes, with particular emphasis on the separation of epimer metabolites. A supportive liquid-liquid extraction (SLE) and LC-MS/MS method was developed to quantify 10 vitamin D metabolites as well as separation of an interfering 7α-hydroxy-4-cholesten-3-one (7αC4) isobar (precursor of bile acid), and validated by analysis of human serum samples. In a cohort of 116 healthy subjects, circulating concentrations of 25-hydroxyvitamin D3 (25OHD3), 3-epi-25-hydroxyvitamin D3 (3-epi-25OHD3), 24,25-dihydroxyvitamin D3 (24R,25(OH)2D3), 1,25-dihydroxyvitamin D3 (1α,25(OH)2D3), and 25-hydroxyvitamin D2 (25OHD2) were quantifiable using 220μL of serum, with 25OHD3 and 24R,25(OH)2D3 showing significant seasonal variations. This high-throughput LC-MS/MS method provides a novel strategy for assessing the impact of vitamin D on human health and disease. PMID:26874878

  14. Ability of Serum Glial Fibrillary Acidic Protein, Ubiquitin C-Terminal Hydrolase-L1, and S100B To Differentiate Normal and Abnormal Head Computed Tomography Findings in Patients with Suspected Mild or Moderate Traumatic Brain Injury.

    PubMed

    Welch, Robert D; Ayaz, Syed I; Lewis, Lawrence M; Unden, Johan; Chen, James Y; Mika, Valerie H; Saville, Ben; Tyndall, Joseph A; Nash, Marshall; Buki, Andras; Barzo, Pal; Hack, Dallas; Tortella, Frank C; Schmid, Kara; Hayes, Ronald L; Vossough, Arastoo; Sweriduk, Stephen T; Bazarian, Jeffrey J

    2016-01-15

    Head computed tomography (CT) imaging is still a commonly obtained diagnostic test for patients with minor head injury despite availability of clinical decision rules to guide imaging use and recommendations to reduce radiation exposure resulting from unnecessary imaging. This prospective multicenter observational study of 251 patients with suspected mild to moderate traumatic brain injury (TBI) evaluated three serum biomarkers' (glial fibrillary acidic protein [GFAP], ubiquitin C-terminal hydrolase-L1 [UCH-L1] and S100B measured within 6 h of injury) ability to differentiate CT negative and CT positive findings. Of the 251 patients, 60.2% were male and 225 (89.6%) had a presenting Glasgow Coma Scale score of 15. A positive head CT (intracranial injury) was found in 36 (14.3%). UCH-L1 was 100% sensitive and 39% specific at a cutoff value >40 pg/mL. To retain 100% sensitivity, GFAP was 0% specific (cutoff value 0 pg/mL) and S100B had a specificity of only 2% (cutoff value 30 pg/mL). All three biomarkers had similar values for areas under the receiver operator characteristic curve: 0.79 (95% confidence interval; 0.70-0.88) for GFAP, 0.80 (0.71-0.89) for UCH-L1, and 0.75 (0.65-0.85) for S100B. Neither GFAP nor UCH-L1 curve values differed significantly from S100B (p = 0.21 and p = 0.77, respectively). In our patient cohort, UCH-L1 outperformed GFAP and S100B when the goal was to reduce CT use without sacrificing sensitivity. UCH-L1 values <40 pg/mL could potentially have aided in eliminating 83 of the 215 negative CT scans. These results require replication in other studies before the test is used in actual clinical practice. PMID:26467555

  15. Ability of Serum Glial Fibrillary Acidic Protein, Ubiquitin C-Terminal Hydrolase-L1, and S100B To Differentiate Normal and Abnormal Head Computed Tomography Findings in Patients with Suspected Mild or Moderate Traumatic Brain Injury

    PubMed Central

    Ayaz, Syed I.; Lewis, Lawrence M.; Unden, Johan; Chen, James Y.; Mika, Valerie H.; Saville, Ben; Tyndall, Joseph A.; Nash, Marshall; Buki, Andras; Barzo, Pal; Hack, Dallas; Tortella, Frank C.; Schmid, Kara; Hayes, Ronald L.; Vossough, Arastoo; Sweriduk, Stephen T.; Bazarian, Jeffrey J.

    2016-01-01

    Abstract Head computed tomography (CT) imaging is still a commonly obtained diagnostic test for patients with minor head injury despite availability of clinical decision rules to guide imaging use and recommendations to reduce radiation exposure resulting from unnecessary imaging. This prospective multicenter observational study of 251 patients with suspected mild to moderate traumatic brain injury (TBI) evaluated three serum biomarkers' (glial fibrillary acidic protein [GFAP], ubiquitin C-terminal hydrolase-L1 [UCH-L1] and S100B measured within 6 h of injury) ability to differentiate CT negative and CT positive findings. Of the 251 patients, 60.2% were male and 225 (89.6%) had a presenting Glasgow Coma Scale score of 15. A positive head CT (intracranial injury) was found in 36 (14.3%). UCH-L1 was 100% sensitive and 39% specific at a cutoff value >40 pg/mL. To retain 100% sensitivity, GFAP was 0% specific (cutoff value 0 pg/mL) and S100B had a specificity of only 2% (cutoff value 30 pg/mL). All three biomarkers had similar values for areas under the receiver operator characteristic curve: 0.79 (95% confidence interval; 0.70–0.88) for GFAP, 0.80 (0.71–0.89) for UCH-L1, and 0.75 (0.65–0.85) for S100B. Neither GFAP nor UCH-L1 curve values differed significantly from S100B (p = 0.21 and p = 0.77, respectively). In our patient cohort, UCH-L1 outperformed GFAP and S100B when the goal was to reduce CT use without sacrificing sensitivity. UCH-L1 values <40 pg/mL could potentially have aided in eliminating 83 of the 215 negative CT scans. These results require replication in other studies before the test is used in actual clinical practice. PMID:26467555

  16. High Uric Acid (UA) Negatively Affects Serum Tartrate-Resistant Acid Phosphatase 5b (TRACP 5b) Immunoassay

    PubMed Central

    Wu, Zhi-Qi; Zhang, Yan; Xie, Erfu; Song, Wei-Juan; Yang, Rui-Xia; Yan, Cheng-Jing; Zhang, Bing-Feng; Xu, Hua-Guo

    2016-01-01

    Background Bone metastases often occur in the majority of patients with advanced cancer, such as prostate cancer, lung cancer and breast cancer. Serum tartrate-resistant acid phosphatase 5b (TRACP 5b), a novel bone resorption marker, has been used gradually in the clinics as a specific and sensitive marker of bone resorption for the early diagnosis of cancer patients with bone metastasis. Here, we reported that high concentrations of uric acid (UA) lead to decrease of TRACP 5b levels and determined whether TRACP 5b level was associated with UA in interference experiment. Methods A total of 77 patients with high concentrations of UA and 77 healthy subjects were tested to evaluate the differences in their TRACP 5b levels. Serial dilutions of UA were respectively spiked with a known concentration of TRACP 5b standard sample, then Serum TRACP 5b was detected by using bone TRAP® Assay. A correction equation was set to eliminate UA-derived TRACP 5b false-decrease. The effect of this correction was evaluated in high-UA individuals. Results The average TRACP level of the high-UA individuals (1.47± 0.62 U/L) was significantly lower than that of the healthy subjects (2.62 ± 0.63 U/L) (t-test, p<0.0001). The UA correction equation derived: ΔTRACP 5b = -1.9751lgΔUA + 3.7365 with an R2 = 0.98899. Application of the UA correction equation resulted in a statistically non-significant difference in TRACP 5b values between the healthy subjects and high-UA individuals (p = 0.24). Conclusions High UA concentrations can falsely decrease TRACP 5b levels due to a method-related systematic error. To avoid misdiagnoses or inappropriate therapeutic decisions, increased attention should be paid to UA interference, when TRACP 5b is used for early diagnosis of cancer patients with bone metastasis, evaluation of the aggressiveness of osteosarcoma or prediction of survival in prostate cancer and breast cancer with bone metastases. PMID:26800211

  17. Absence of cytoglobin promotes multiple organ abnormalities in aged mice

    PubMed Central

    Thuy, Le Thi Thanh; Van Thuy, Tuong Thi; Matsumoto, Yoshinari; Hai, Hoang; Ikura, Yoshihiro; Yoshizato, Katsutoshi; Kawada, Norifumi

    2016-01-01

    Cytoglobin (Cygb) was identified in hepatic stellate cells (HSCs) and pericytes of all organs; however, the effects of Cygb on cellular functions remain unclear. Here, we report spontaneous and age-dependent malformations in multiple organs of Cygb−/− mice. Twenty-six percent of young Cygb−/− mice (<1 year old) showed heart hypertrophy, cystic disease in the kidney or ovary, loss of balance, liver fibrosis and lymphoma. Furthermore, 71.3% (82/115) of aged Cygb−/− mice (1–2 years old) exhibited abnormalities, such as heart hypertrophy and cancer development in multiple organs; by contrast, 5.8% (4/68) of aged wild-type (WT) mice had abnormalities (p < 0.0001). Interestingly, serum and urine analysis demonstrated that the concentration of nitric oxide metabolites increased significantly in Cygb−/− mice, resulting in an imbalance in the oxidative stress and antioxidant defence system that was reversed by NG-monomethyl-L-arginine treatment. A senescent phenotype and evidence of DNA damage were found in primary HSCs and the liver of aged Cygb−/− mice. Moreover, compared with HSC+/+, HSC−/− showed high expression of Il-6 and chemokine mRNA when cocultured with mouse Hepa 1–6 cells. Thus, the absence of Cygb in pericytes provokes organ abnormalities, possibly via derangement of the nitric oxide and antioxidant defence system and through accelerated cellular senescence. PMID:27146058

  18. Association between serum levels of high sensitive C-reactive protein and inflammation activity in chronic gastritis patients.

    PubMed

    Rahmani, Asghar; Moradkhani, Atefeh; Hafezi Ahmadi, Mohammad Reza; Jafari Heirdarlo, Ali; Abangah, Ghobad; Asadollahi, Khairollah; Sayehmiri, Kourosh

    2016-05-01

    Background Gastritis is an important premalignant lesion and recent studies suggested a production of inflammatory cytokine-like C-reactive protein during gastritis. This study aimed to determine any relationship between high sensitive C-reactive protein (hs-CRP) and inflammation activity among patients with gastritis. Methods Demographic and clinical variables of participants were collected by a validated questionnaire. Using histology of the gastric mucosa, Helicobacter pylori status was investigated and serum concentrations of hs-CRP were measured among dyspeptic patients. Correlation between hs-CRP serum levels and inflammation activities was evaluated by logistic regression analysis. The relation between active inflammation and other variables was evaluated by logic link function model. Results Totally 239 patients (56.6% female) were analysed. The prevalence of mild, moderate and severe inflammation activities was 66.5%, 23.8% and 9.6% respectively. Mean ± SD of hs-CRP among men and women were 2.85 ± 2.84 mg/dl and 2.80 ± 4.80 mg/dl (p = 0.047) respectively. Mean ± SD of hs-CRP among patients with H. pylori infection, gland atrophy, metaplasia and dysplasia were 2.83 ± 3.80 mg/dl, 3.52 ± 5.1 mg/dl, 2.22 ± 2.3 mg/dl and 5.3 ± 5.04 mg/dl respectively. Relationship between hs-CRP and inflammation activities (p < 0.01) was significant. A significant relationship between dysplasia and hs-CRP (p < 0.04) was revealed. A significant relationship between age and hs-CRP was detected (p < 0.05). Conclusion Although serum hs-CRP is not a specific biomarker for gastritis, elevated hs-CRP levels may be considered as a predictive marker of changes in gastric mucosa and a promising therapeutic target for patients with gastritis. PMID:26758551

  19. High Levels of Serum DPP-4 Activity Are Associated with Low Bone Mineral Density in Obese Postmenopausal Women

    PubMed Central

    2016-01-01

    Background Dipeptidyl peptidase 4/CD26 (DPP-4) is a widely expressed cell surface serine protease. DPP-4 inhibitors, one of common anti-diabetic agents play a protective role in bone metabolism in recent studies. A soluble form of DPP-4 is found in serum, and exhibits DPP-4 enzymatic activity. However, the physiological role of serum or soluble DPP-4 and its relationship with DPP-4 enzymatic function remain poorly understood. The aims of current study were to determine the association between serum DPP-4 activity and bone mineral density (BMD) in postmenopausal women. Methods We recruited data and serum samples from 124 consecutive healthy postmenopausal women aged >50 years. We divided study subjects into obese (body mass index [BMI] ≥25 kg/m2) and non-obese (BMI <25 kg/m2) postmenopausal women and examined the correlation between serum DPP-4 activity and clinical variables in each groups. Results A total of 124 postmenopausal women was enrolled, with a mean age of 59.9±7.1 years. The mean BMI of the study patients was 24.4±2.8 kg/m2. Regarding bone turnover markers, serum DPP-4 activity was positively correlated with serum calcium concentrations, intact parathyroid hormone, and serum C-telopeptide levels in all of the study subjects. However, there was no association between serum DPP-4 activity and BMD in the spine or femoral neck in all of the study subjects. Serum DPP-4 activity was negatively correlated (R=−0.288, P=0.038) with BMD of the spine in obese postmenopausal women. Conclusion This study demonstrated for the first time that serum soluble DPP-4 activity was negatively correlated with BMD in obese postmenopausal women. PMID:26676330

  20. Analysis of naltrexone and its metabolite 6-beta-naltrexol in serum with high-performance liquid chromatography

    PubMed Central

    2012-01-01

    Background Naltrexone has been proven to be an effective treatment option for the treatment of alcohol dependency. In this article we introduce a reliable and simple method developed for the simultaneous determination of naltrexone and 6-β-naltrexol in human serum by using high-performance liquid chromatography (HPLC). Findings Liquid-liquid extraction with butyl acetate from basic solutions (pH 9) was chosen for extraction with nalorphine as an internal standard (IS). Analytes were back-extracted from organic solvent into perchloric acid. The acid extract was chromatographed by HPLC with a reverse-phase ODS-column and electrochemical detector. The mobile phase was a NaH2PO4-solution with acetonitrile as an organic modifier and octanesulphonic acid and tetraethylammonium hydrogen sulphate as ion-pair reagents. The recovery of the extraction method was 48% for naltrexone and 75% for 6-β-naltrexol. The limit of quantification was 5.0 ng/ml for naltrexone and 1.0 ng/ml for 6-β-naltrexol. The analysed concentrations of naltrexone differed from the theoretic concentrations by 0.7 to 2.3% and those of 6-β-naltrexol by 2.6%. The relative standard deviation of within-day assay was from 0.9 to 5.7% for naltrexone and from 0.8 to 4.2% for 6-β-naltrexol; for the between-day assay it was 5.7% and 4.2%, respectively. Conclusions Our results indicate that the developed method is suitable for determination of naltrexone and 6-β-naltrexol in human serum. PMID:22894733

  1. Analysis of glipizide binding to normal and glycated human serum albumin by high-performance affinity chromatography.

    PubMed

    Matsuda, Ryan; Li, Zhao; Zheng, Xiwei; Hage, David S

    2015-07-01

    In diabetes, the elevated levels of glucose in the bloodstream can result in the nonenzymatic glycation of proteins such as human serum albumin (HSA). This type of modification has been shown to affect the interactions of some drugs with HSA, including several sulfonylurea drugs that are used to treat type II diabetes. This study used high-performance affinity chromatography (HPAC) to examine the interactions of glipizide (i.e., a second-generation sulfonylurea drug) with normal HSA or HSA that contained various levels of in vitro glycation. Frontal analysis indicated that glipizide was interacting with both normal and glycated HSA through two general groups of sites: a set of relatively strong interactions and a set of weaker interactions with average association equilibrium constants at pH 7.4 and 37 °C in the range of 2.4-6.0 × 10(5) and 1.7-3.7 × 10(4) M(-1), respectively. Zonal elution competition studies revealed that glipizide was interacting at both Sudlow sites I and II, which were estimated to have affinities of 3.2-3.9 × 10(5) and 1.1-1.4 × 10(4) M(-1). Allosteric effects were also noted to occur for this drug between the tamoxifen site and the binding of R-warfarin at Sudlow site I. Up to an 18% decrease in the affinity for glipizide was observed at Sudlow site I ongoing from normal HSA to glycated HSA, while up to a 27% increase was noted at Sudlow site II. This information should be useful in indicating how HPAC can be used to investigate other drugs that have complex interactions with proteins. These results should also be valuable in providing a better understanding of how glycation may affect drug-protein interactions and the serum transport of drugs such as glipizide during diabetes. PMID:25912461

  2. Identification and quantification of bleomycin in serum and tumor tissue by liquid chromatography coupled to high resolution mass spectrometry.

    PubMed

    Kosjek, Tina; Krajnc, Anja; Gornik, Tjasa; Zigon, Dusan; Groselj, Ales; Sersa, Gregor; Cemazar, Maja

    2016-11-01

    Bleomycin is a cytotoxic antibiotic available as a compost of structurally strongly related glycopeptides, which is in vivo found chelated with several metals. Its pharmacotherapy has merely been based on experimental dose - response data, whereas its biodistribution and pharmacokinetics remain fundamentally unknown. This is reasoned by an absence of a specific and sensitive mass spectrometry-based analytical method for its determination in biological tissues. We herein reveal the results of our study on the mass spectrometric behavior of two main bleomycin fractions A2 and B2, including their metal complexes, particularly the predominant copper chelates. In the electrospray ion source bleomycin forms double charged species, where for the metal-free fraction A2 and its copper complex m/z 707.76 and m/z 707.21 are seen, respectively. Hence, the second isotopic ion of the chelate (m/z 707.71) nearly coincides with the first isotopic ion of the metal-free fraction. This phenomenon can only be followed by high-resolution mass spectrometry, and is considered the plausible reason, why the attempts to determine bleomycin with mass spectrometry have been so scarce. The presented paper further describes a sensitive and selective liquid chromatography - mass spectrometry analytical method for determination of bleomycin in serum and tumor tissues. This newly developed method was employed for bleomycin pharmacokinetic studies in serum and tumors of laboratory animals. Additionally, the method was employed for determination of bleomycin pharmacokinetic parameters in elderly patients in order to determine the effective therapeutic window of electrochemotherapy with bleomycin. PMID:27591601

  3. The V227A polymorphism at the PPARA locus is associated with serum lipid concentrations and modulates the association between dietary polyunsaturated fatty acid intake and serum high density lipoprotein concentrations in Chinese women.

    PubMed

    Chan, Edmund; Tan, Chuen Seng; Deurenberg-Yap, Mabel; Chia, Kee Seng; Chew, Suok Kai; Tai, E Shyong

    2006-08-01

    Peroxisome proliferators activated receptor alpha (PPARalpha) regulates the transcription of several proteins involved in human lipoprotein metabolism. We screened the PPARA locus for polymorphisms in 20 unrelated subjects from each of three ethnic groups (Chinese, Malays and Asian Indians). Only the V227A polymorphism was observed. We genotyped 4248 subjects (2899 Chinese, 761 Malay and 588 Asian Indians) and found allele frequencies for the A227 allele of 0.04 in Chinese, 0.006 in Malays and 0.003 in Asian Indians. We examined the associations between this polymorphism and serum lipid concentrations in Chinese. In women, but not in men, the presence of the A227 allele was associated with lower serum concentrations of total cholesterol [5.38mmol/l (95%CI: 5.22-5.54) versus 5.21mmol/l (95%CI: 4.99-5.43), p=0.047] and triglycerides [1.19mmol/l (95%CI: 1.10-1.28) versus 1.09mmol/l (95%CI: 0.98-1.21), p=0.048]. We also found that the V227A polymorphism modulates the association between dietary polyunsaturated fatty acid intake and serum high density lipoprotein concentration (p-value for interaction=0.049). Our findings implicate PPARalpha in the lipid lowering associated with diets high in PUFA and suggests that genetic variation at the PPARA locus may determine the lipid response to changes in PUFA intake. PMID:16288935

  4. High-throughput sequencing enhanced phage display enables the identification of patient-specific epitope motifs in serum

    PubMed Central

    Christiansen, Anders; Kringelum, Jens V.; Hansen, Christian S.; Bøgh, Katrine L.; Sullivan, Eric; Patel, Jigar; Rigby, Neil M.; Eiwegger, Thomas; Szépfalusi, Zsolt; Masi, Federico de; Nielsen, Morten; Lund, Ole; Dufva, Martin

    2015-01-01

    Phage display is a prominent screening technique with a multitude of applications including therapeutic antibody development and mapping of antigen epitopes. In this study, phages were selected based on their interaction with patient serum and exhaustively characterised by high-throughput sequencing. A bioinformatics approach was developed in order to identify peptide motifs of interest based on clustering and contrasting to control samples. Comparison of patient and control samples confirmed a major issue in phage display, namely the selection of unspecific peptides. The potential of the bioinformatic approach was demonstrated by identifying epitopes of a prominent peanut allergen, Ara h 1, in sera from patients with severe peanut allergy. The identified epitopes were confirmed by high-density peptide micro-arrays. The present study demonstrates that high-throughput sequencing can empower phage display by (i) enabling the analysis of complex biological samples, (ii) circumventing the traditional laborious picking and functional testing of individual phage clones and (iii) reducing the number of selection rounds. PMID:26246327

  5. A fluorescence-based high throughput assay for the determination of small molecule–human serum albumin protein binding

    PubMed Central

    McCallum, Megan M.; Pawlak, Alan J.; Shadrick, William R.; Simeonov, Anton; Jadhav, Ajit; Yasgar, Adam; Maloney, David J.; Arnold, Leggy A.

    2014-01-01

    Herein, we describe the development of a fluorescence-based high throughput assay to determine the small molecule binding towards human serum albumin (HSA). This innovative competition assay is based on the use of a novel fluorescent small molecule Red Mega 500 with unique spectroscopic and binding properties. The commercially available probe displays a large fluorescence intensity difference between the protein-bound and protein-unbound state. The competition of small molecules for HSA binding in the presence of probe resulted in low fluorescence intensities. The assay was evaluated with the LOPAC small molecule library of 1280 compounds identifying known high protein binders. The small molecule competition of HSA–Red Mega 500 binding was saturable at higher compound concentrations and exhibited IC50 values between 3–24 μM. The compound affinity towards HSA was confirmed by isothermal titration calorimetry indicating that the new protein binding assay is a valid high throughput assay to determine plasma protein binding. PMID:24390461

  6. High-Throughput Analysis of Serum Antigens Using Sandwich ELISAs on Microarrays

    SciTech Connect

    Servoss, Shannon; Gonzalez, Rachel M.; Varnum, Susan M.; Zangar, Richard C.

    2009-05-11

    Enzyme-linked immunosorbent assay (ELISA) microarrays promise to be a powerful tool for the detection and validation of disease biomarkers. ELISA microarrays are capable of simultaneous detection of many proteins using a small sample volume. Although there are many potential pitfalls to the use of ELISA microarrays, these can be avoided by careful planning of experiments. In this chapter we describe a high-throughput protocol for processing ELISA microarrays that will result in reliable and reproducible data.

  7. "Jeopardy" in Abnormal Psychology.

    ERIC Educational Resources Information Center

    Keutzer, Carolin S.

    1993-01-01

    Describes the use of the board game, Jeopardy, in a college level abnormal psychology course. Finds increased student interaction and improved application of information. Reports generally favorable student evaluation of the technique. (CFR)

  8. Abnormal Uterine Bleeding

    MedlinePlus

    ... Abnormal uterine bleeding is any bleeding from the uterus (through your vagina) other than your normal monthly ... or fibroids (small and large growths) in the uterus can also cause bleeding. Rarely, a thyroid problem, ...

  9. Abnormal Uterine Bleeding FAQ

    MedlinePlus

    ... as cancer of the uterus, cervix, or vagina • Polycystic ovary syndrome How is abnormal bleeding diagnosed? Your health care ... before the fetus can survive outside the uterus. Polycystic Ovary Syndrome: A condition characterized by two of the following ...

  10. Highly absorptive curcumin reduces serum atherosclerotic low-density lipoprotein levels in patients with mild COPD

    PubMed Central

    Funamoto, Masafumi; Sunagawa, Yoichi; Katanasaka, Yasufumi; Miyazaki, Yusuke; Imaizumi, Atsushi; Kakeya, Hideaki; Yamakage, Hajime; Satoh-Asahara, Noriko; Komiyama, Maki; Wada, Hiromichi; Hasegawa, Koji; Morimoto, Tatsuya

    2016-01-01

    Purpose COPD is mainly caused by tobacco smoking and is associated with a high frequency of coronary artery disease. There is growing recognition that the inflammation in COPD is not only confined to the lungs but also involves the systemic circulation and can impact nonpulmonary organs, including blood vessels. α1-antitrypsin–low-density lipoprotein (AT-LDL) complex is an oxidatively modified LDL that accelerates atherosclerosis. Curcumin, one of the best-investigated natural products, is a powerful antioxidant. However, the effects of curcumin on AT-LDL remain unknown. We hypothesized that Theracurmin®, a highly absorptive curcumin with improved bioavailability using a drug delivery system, ameliorates the inflammatory status in subjects with mild COPD. Patients and methods This is a randomized, double-blind, parallel-group study. Subjects with stages I–II COPD according to the Japanese Respiratory Society criteria were randomly assigned to receive 90 mg Theracurmin® or placebo twice a day for 24 weeks, and changes in inflammatory parameters were evaluated. Results There were no differences between the Theracurmin® and placebo groups in terms of age, male/female ratio, or body mass index in 39 evaluable subjects. The percent changes in blood pressure and hemoglobin A1c and LDL-cholesterol, triglyceride, or high-density lipoprotein-cholesterol levels after treatment were similar for the two groups. However, the percent change in the AT-LDL level was significantly (P=0.020) lower in the Theracurmin® group compared with the placebo group. Conclusion Theracurmin® reduced levels of atherosclerotic AT-LDL, which may lead to the prevention of future cardiovascular events in mild COPD subjects. PMID:27616885

  11. Dietary factors associated with high serum ferritin levels in postmenopausal women with the Fifth Korea National Health and Nutrition Examination Survey (KNHANES V), 2010-2012

    PubMed Central

    Ju, Se Young

    2016-01-01

    BACKGROUND/OBJECTIVES Serum ferritin levels are significantly increased after menopause and greatly affect women's health. The aim of this study was to investigate the dietary and non-dietary factors associated with high ferritin levels in postmenopausal women. SUBJECTS/METHODS Among adult women in 2010-2012, qualified postmenopausal women (n = 3880) were separated into quartiles of serum ferritin. The variable differences among the quartiles of ferritin were determined using either procsurvey chi-square test (χ2-test) among categorical variables, or GLM (Generalized Linear Model) among continuous variables. The odds ratio for high ferritin in relation to dietary factors was also determined using procsurvery logistic analysis. RESULTS Age, obesity, drinking habit, and blood glucose levels were found to be significant indicators of high serum ferritin level after adjusting for all confounding factors. Among the food groups, grain, milk, vegetable, and seaweed intakes were significantly associated with high ferritin levels, but after adjusting for all confounding factors, only grains and vegetables remained significant factors. Among the nutrient groups, calcium, vitamin A, and vitamin C intake were significant factors, but after adjustment, none of the nutrient groups analyzed were associated with a high risk of ferritin. CONCLUSION Age, obesity, drinking habit, and glucose levels, as well as inadequate intakes of grains and vegetables, were found to be significantly associated with high serum ferritin levels in postmenopausal Korean women. PMID:26865920

  12. [Immunohistochemical Analysis of Krebs von den Lungen-6 (KL-6) Expression in Lung Tissue in Primary Lung Cancer Patients with High Serum KL-6 Levels].

    PubMed

    Yatsuyanagi, Eiji; Sato, Kazuhiro; Sato, Keisuke

    2015-09-01

    We investigated sialylated carbohydrate antigen( Krebs von den Lungen-6:KL-6) expression in lung tissue and correlation between the expression and serum KL-6 level in the patients with primary lung cancer. Thirty-four primary lung cancer patients with high serum KL-6 levels( >500 U/ml) were evaluated. A coexistence of interstitial pneumonia (IP) was histopathologically evaluated and an immunohistochemical staining using a mouse anti-human KL-6 antibody (mKL-6) was performed. A multiple regression analysis was also caluculated using a serum KL-6 level as a target variable and the histopathological and immunohistochemical factors (KL-6 expression in cancer tissue and IP tissue, coexistence of IP, tumor size, pathological staging) as descriptive variables. Twenty-two patients (64.7%) were histopathologically concomitant with IP. Cancer tissues were positively stained by mKL-6 in 32 patients (94.1%). Among them, 20 patients were concomitant with IP and all of their cancer tissues were more strongly stained by mKL-6 than IP tissues. Although considerable high rate of lung cancer patients might express the KL-6 in the cancer tissue, we could not reveal the relationship between the expression and serum KL-6 level by a multiple regression analysis. For revealing the mechanism of elevating serum KL-6 level in the patients with lung cancer, more detailed and powerful study is thought to be needed. PMID:26329623

  13. Serum 25-hydroxyvitamin D and CD4+CD25(+high) FoxP3+ Regulatory T cell as Predictors of Severity of Bronchial Asthma in Children.

    PubMed

    Ismail, Ahlam M; Aly, Sanaa S; Fayed, Hanan M; Ahmed, Samar S

    2015-01-01

    Bronchial asthma (BA) is one of the common chronic diseases of childhood. Vitamin D deficiency has been associated with BA. Suppressor regulatory T cells (Treg) are important for the induction, maintenance of immunological tolerance to allergens. This study assessed serum 25-hydroxyvitamin D (vitamin D) and the percentages of CD4+CD25+(high) Foxp3+ Treg, in peripheral blood, as predictors of asthma severity and level of clinical control. The study enrolled 72 children divided equally between asthmatic children (AC) and age and sex matched controls. Diagnostic criteria and level of asthma severity followed the Global Initiative for Asthma guidelines. Serum vitamin D was determined by an immunoassay and the percentages of CD4+CD25+ig Foxp3+ Treg by flow cytometry. Serum vitamin D level and percentage of CD4+CD25+(high) Treg were lower in AC compared to controls (P < 0.001) whereas Fox p3 expression was higher in AC compared to controls, P < 0.001. Serum vitamin D levels were lower in severe asthma compared to mild and moderate forms (P = 0.008) and in uncontrolled attacks compared to partially or completely controlled children. No difference in percentage of Treg in relation to asthma severity and clinical control was observed. Since AC has decreased serum vitamin D with inverse relationship between its levels and asthma severity, we conclude that it can be used to predict severity of asthma. PMID:26415368

  14. Chromosomal Abnormalities and Schizophrenia

    PubMed Central

    BASSETT, ANNE S.; CHOW, EVA W.C.; WEKSBERG, ROSANNA

    2011-01-01

    Schizophrenia is a common and serious psychiatric illness with strong evidence for genetic causation, but no specific loci yet identified. Chromosomal abnormalities associated with schizophrenia may help to understand the genetic complexity of the illness. This paper reviews the evidence for associations between chromosomal abnormalities and schizophrenia and related disorders. The results indicate that 22q11.2 microdeletions detected by fluorescence in-situ hybridization (FISH) are significantly associated with schizophrenia. Sex chromosome abnormalities seem to be increased in schizophrenia but insufficient data are available to indicate whether schizophrenia or related disorders are increased in patients with sex chromosome aneuploidies. Other reports of chromosomal abnormalities associated with schizophrenia have the potential to be important adjuncts to linkage studies in gene localization. Advances in molecular cytogenetic techniques (i.e., FISH) have produced significant increases in rates of identified abnormalities in schizophrenia, particularly in patients with very early age at onset, learning difficulties or mental retardation, or dysmorphic features. The results emphasize the importance of considering behavioral phenotypes, including adult onset psychiatric illnesses, in genetic syndromes and the need for clinicians to actively consider identifying chromosomal abnormalities and genetic syndromes in selected psychiatric patients. PMID:10813803

  15. Abnormal uterine bleeding.

    PubMed

    Whitaker, Lucy; Critchley, Hilary O D

    2016-07-01

    Abnormal uterine bleeding (AUB) is a common and debilitating condition with high direct and indirect costs. AUB frequently co-exists with fibroids, but the relationship between the two remains incompletely understood and in many women the identification of fibroids may be incidental to a menstrual bleeding complaint. A structured approach for establishing the cause using the Fédération International de Gynécologie et d'Obstétrique (FIGO) PALM-COEIN (Polyp, Adenomyosis, Leiomyoma, Malignancy (and hyperplasia), Coagulopathy, Ovulatory disorders, Endometrial, Iatrogenic and Not otherwise classified) classification system will facilitate accurate diagnosis and inform treatment options. Office hysteroscopy and increasing sophisticated imaging will assist provision of robust evidence for the underlying cause. Increased availability of medical options has expanded the choice for women and many will no longer need to recourse to potentially complicated surgery. Treatment must remain individualised and encompass the impact of pressure symptoms, desire for retention of fertility and contraceptive needs, as well as address the management of AUB in order to achieve improved quality of life. PMID:26803558

  16. Extracellular Matrix Abnormalities in Schizophrenia

    PubMed Central

    Berretta, Sabina

    2011-01-01

    Emerging evidence points to the involvement of the brain extracellular matrix (ECM) in the pathophysiology of schizophrenia (SZ). Abnormalities affecting several ECM components, including Reelin and chondroitin sulfate proteoglycans (CSPGs), have been described in subjects with this disease. Solid evidence supports the involvement of Reelin, an ECM glycoprotein involved in corticogenesis, synaptic functions and glutamate NMDA receptor regulation, expressed prevalently in distinct populations of GABAergic neurons, which secrete it into the ECM. Marked changes of Reelin expression in SZ have typically been reported in association with GABA-related abnormalities in subjects with SZ and bipolar disorder. Recent findings from our group point to substantial abnormalities affecting CSPGs, a main ECM component, in the amygdala and entorhinal cortex of subjects with schizophrenia, but not bipolar disorder. Striking increases of glial cells expressing CSPGs were accompanied by reductions of perineuronal nets, CSPG- and Reelin-enriched ECM aggregates enveloping distinct neuronal populations. CSPGs developmental and adult functions, including neuronal migration, axon guidance, synaptic and neurotransmission regulation are highly relevant to the pathophysiology of SZ. Together with reports of anomalies affecting several other ECM components, these findings point to the ECM as a key component of the pathology of SZ. We propose that ECM abnormalities may contribute to several aspects of the pathophysiology of this disease, including disrupted connectivity and neuronal migration, synaptic anomalies and altered GABAergic, glutamatergic and dopaminergic neurotransmission. PMID:21856318

  17. Serum sickness

    MedlinePlus

    ... passive immunization. It gives you immediate, but temporary, protection while your body develops an active immune response against the toxin or germ. During serum sickness, the immune system falsely identifies a protein in antiserum as a ...

  18. Vitamin B(12) Immunoassay on Roche Elecsys 2010: Effects of High Excess Concentration of Serum Vitamin B(12) in CKD Patients on Parenteral Administration.

    PubMed

    Basu, Surupa; Chaudhuri, Subimal

    2011-10-01

    Vitamin B(12) being water soluble is excreted in the urine when administered in excess. The probability of finding an abnormally excess serum concentration would be almost surreal. We report a peculiar clinical situation that may impact the vitamin B(12) immunoassay on the Roche Elecsys 2010 due to excess analyte concentration. In separate episodes (Feb and June 2010), the Biochemistry laboratory of a tertiary-care hospital, Kolkata, India, encountered two critically ill patients with background chronic kidney disease (CKD), low urine output, and on cyanocoabalamin supplementation, who had serum vitamin B(12) concentrations far exceeding expected values; even post dialysis. The B(12) assays (pmol/l) were performed using electrochemiluminiscence immunoassay on Roche Elecsys 2010, the assay validity confirmed by concomitant quality control runs. The immunoassays failed to deliver results, flagged with "signal level below limit". Biotin therapy was ruled out as a possible interferent. In the first episode, re-assay of a repeat draw yielded same outcome; outsourcing on Immulite provided concentration of >738 pmol/l. Serial dilution gave result of >29520 pmol/l on Elecsys 2010. In the second, we gained from past experience. Vitamin B(12) concentration >59040 pmol/l was conveyed to the treating nephrologist the very day. The B(12) immunoassay on the Elecsys 2010 employs sequential incubation steps for competitive binding that is compromised in the event of abnormally excess B(12) concentration in patient sera akin to the prozone effect. This knowledge may be beneficial while assaying sera of CKD patients to avoid financial loss due unnecessary repeats and delay in turnaround time. PMID:23024480

  19. Long-Term Administration of High-Fat Diet Corrects Abnormal Bone Remodeling in the Tibiae of Interleukin-6-Deficient Mice.

    PubMed

    Feng, Wei; Liu, Bo; Liu, Di; Hasegawa, Tomoka; Wang, Wei; Han, Xiuchun; Cui, Jian; Yimin; Oda, Kimimitsu; Amizuka, Norio; Li, Minqi

    2016-01-01

    In this study, we aimed to evaluate the influence of diet-induced obesity on IL-6 deficiency-induced bone remodeling abnormality. Seven-week-old IL-6(-/-) mice and their wild type (WT) littermates were fed a standard diet (SD) or high-fat diet (HFD) for 25 weeks. Lipid formation and bone metabolism in mice tibiae were investigated by histochemical analysis. Both IL-6(-/-) and WT mice fed the HFD showed notable body weight gain, thickened cortical bones, and adipose accumulation in the bone marrow. Notably, the HFD normalized the bone phenotype of IL-6(-/-) mice to that of their WT counterpart, as characterized by a decrease in bone mass and the presence of an obliquely arranged, plate-like morphology in the trabecular bone. Alkaline phosphatase and osteocalcin expressions were attenuated in both genotypes after HFD feeding, especially for the IL-6(-/-) mice. Meanwhile, tartrate-resistant acid phosphatase staining was inhibited, osteoclast apoptosis rate down-regulated (revealed by TUNEL assay), and the proportion of cathepsin K (CK)-positive osteoclasts significantly increased in IL-6(-/-) mice on a HFD as compared with IL-6(-/-) mice on standard chow. Our results demonstrate that HFD-induced obesity reverses IL-6 deficiency-associated bone metabolic disorders by suppressing osteoblast activity, upregulating osteoclastic activity, and inhibiting osteoclast apoptosis. PMID:26416243

  20. High-Moisture Diet for Laboratory Rats: Complete Blood Counts, Serum Biochemical Values, and Intestinal Enzyme Activity

    NASA Technical Reports Server (NTRS)

    Battles, August H.; Knapka, Joseph T.; Stevens, Bruce R.; Lewis, Laura; Lang, Marie T.; Gruendel, Douglas J.

    1991-01-01

    Rats were fed an irradiated high-moisture diet (KSC-25) with or without access to a water bottle. Physiologic values were compared between these two groups and a group of rats fed a purified diet. Hematologic and serum biochemical values, urine specific gravity, and intestinal enzyme activities were determined from samples collected from the three groups of rats. Sprague Dawley rats (n=32) fed the irradiated high-moisture diet with or without a water bottle were the test animals. Rats (n=16) fed an irradiated purified diet and water provided via a water bottle were the control group. The purified diet formulation, modified AIN-76A, is a commonly used purified diet for laboratory rodents. All rats remained alert and healthy throughout the study. A comparison of the physiologic values of rats in this study with reported normal values indicated that all of the rats in the study were in good health. Significant differences (P less than 0.05) of the physiologic values from each rat group are reported.

  1. Precision high-throughput proton NMR spectroscopy of human urine, serum, and plasma for large-scale metabolic phenotyping.

    PubMed

    Dona, Anthony C; Jiménez, Beatriz; Schäfer, Hartmut; Humpfer, Eberhard; Spraul, Manfred; Lewis, Matthew R; Pearce, Jake T M; Holmes, Elaine; Lindon, John C; Nicholson, Jeremy K

    2014-10-01

    Proton nuclear magnetic resonance (NMR)-based metabolic phenotyping of urine and blood plasma/serum samples provides important prognostic and diagnostic information and permits monitoring of disease progression in an objective manner. Much effort has been made in recent years to develop NMR instrumentation and technology to allow the acquisition of data in an effective, reproducible, and high-throughput approach that allows the study of general population samples from epidemiological collections for biomarkers of disease risk. The challenge remains to develop highly reproducible methods and standardized protocols that minimize technical or experimental bias, allowing realistic interlaboratory comparisons of subtle biomarker information. Here we present a detailed set of updated protocols that carefully consider major experimental conditions, including sample preparation, spectrometer parameters, NMR pulse sequences, throughput, reproducibility, quality control, and resolution. These results provide an experimental platform that facilitates NMR spectroscopy usage across different large cohorts of biofluid samples, enabling integration of global metabolic profiling that is a prerequisite for personalized healthcare. PMID:25180432

  2. Long-Term In Vitro Degradation of a High-Strength Brushite Cement in Water, PBS, and Serum Solution

    PubMed Central

    Ajaxon, Ingrid; Öhman, Caroline; Persson, Cecilia

    2015-01-01

    Bone loss and fractures may call for the use of bone substituting materials, such as calcium phosphate cements (CPCs). CPCs can be degradable, and, to determine their limitations in terms of applications, their mechanical as well as chemical properties need to be evaluated over longer periods of time, under physiological conditions. However, there is lack of data on how the in vitro degradation affects high-strength brushite CPCs over longer periods of time, that is, longer than it takes for a bone fracture to heal. This study aimed at evaluating the long-term in vitro degradation properties of a high-strength brushite CPC in three different solutions: water, phosphate buffered saline, and a serum solution. Microcomputed tomography was used to evaluate the degradation nondestructively, complemented with gravimetric analysis. The compressive strength, chemical composition, and microstructure were also evaluated. Major changes from 10 weeks onwards were seen, in terms of formation of a porous outer layer of octacalcium phosphate on the specimens with a concomitant change in phase composition, increased porosity, decrease in object volume, and mechanical properties. This study illustrates the importance of long-term evaluation of similar cement compositions to be able to predict the material's physical changes over a relevant time frame. PMID:26587540

  3. Development and validation of an high-performance liquid chromatography-diode array detector method for the simultaneous determination of six phenolic compounds in abnormal savda munziq decoction

    PubMed Central

    Tian, Shuge; Liu, Wenxian; Liu, Feng; Zhang, Xuejia; Upur, Halmuart

    2015-01-01

    Aims: Given the high-effectiveness and low-toxicity of abnormal savda munziq (ASMQ), its herbal formulation has long been used in traditional Uyghur medicine to treat complex diseases, such as cancer, diabetes, and cardiovascular diseases. Settings and Design: ASMQ decoction by reversed-phase high-performance liquid chromatography coupled with a diode array detector was successfully developed for the simultaneous quality assessment of gallic acid, protocatechuic acid, caffeic acid, rutin, rosmarinic acid, and luteolin. The six phenolic compounds were separated on an Agilent TC-C18 reversed-phase analytical column (4.6 × 250 mm, 5 μm) by gradient elution using 0.3% aqueous formic acid (v/v) and 0.3% methanol formic acid (v/v) at 1.0 mL/min. Materials and Methods: The plant material was separately ground and mixed at the following ratios (10): Cordia dichotoma (10.6), Anchusa italic (10.6), Euphorbia humifusa (4.9), Adiantum capillus-veneris (4.9), Ziziphus jujube (4.9), Glycyrrhiza uralensis (7.1), Foeniculum vulgare (4.9), Lavandula angustifolia (4.9), Dracocephalum moldavica L. (4.9), and Alhagi pseudoalhagi (42.3). Statistical Analysis Used: The precisions of all six compounds were <0.60%, and the average recoveries ranged from 99.39% to 104.85%. Highly significant linear correlations were found between component concentrations and specific chromatographic peak areas (R2 > 0.999). Results: The proposed method was successfully applied to determine the levels of six active components in ASMQ. Conclusions: Given the simplicity, precision, specificity, and sensitivity of the method, it can be utilized as a quality control approach to simultaneously determining the six phenolic compounds in AMSQ. PMID:25709227

  4. Identification of high-density lipoprotein in serum to determine anti-cancer efficacy of doxorubicin in HeLa cells.

    PubMed

    Yung, B Y; Bor, A M

    1992-04-01

    The cytotoxic effects of doxorubicin (DOX) and daunorubicin (DAU) on HeLa cells cultured under different serum conditions were analyzed by the "nucleophosmin translocation" assay using immunofluorescence. Bright nucleolar fluorescence was observed in untreated cells. A shift from nucleolar to nuclear fluorescence was observed with increasing doses of DOX or DAU, with longer incubation times. A lesser degree of nucleophosmin translocation from nucleoli to nucleoplasm was observed in serum-deprived cells under the same DOX or DAU treatment. These results correlated well with those of cell-growth-reversibility and colony-formation studies, showing decreased inhibitory effects of growth on cells cultured in medium without serum. Furthermore, cells cultured in medium supplemented with the lipoprotein-free serum responded to DOX in a similar way to cells cultured without serum. High-density lipoprotein (HDL) and low-density lipoprotein (LDL) were then added to the lipoprotein-free serum. Cells cultured in medium with the HDL-supplemented, serum showed increased sensitivity to DOX. Inhibition of cell growth and colony formation was observed in such HDL-supplemented cells upon DOX treatment (30 min). LDL, on the other hand, did not show an increase in the anti-cancer response. These results suggested that the variation in response of cells to DOX anti-cancer treatment under different growth conditions may be due to their varied concentrations of HDL. "Nucleophosmin translocation", which is useful for monitoring and ensuring the efficacy of the drug during anti-cancer treatment, provides an improved potential for successful chemotherapy. PMID:1555894

  5. Exposure to Hypoxia at High Altitude (5380 m) for 1 Year Induces Reversible Effects on Semen Quality and Serum Reproductive Hormone Levels in Young Male Adults.

    PubMed

    He, Jiang; Cui, Jianhua; Wang, Rui; Gao, Liang; Gao, Xiaokang; Yang, Liu; Zhang, Qiong; Cao, Jinjun; Yu, Wuzhong

    2015-09-01

    This study investigated the effect of hypoxia at high altitude on the semen quality and the serum reproductive hormone levels in male adults. A total of 52 male soldiers were enrolled in this cohort study. They were exposed to hypoxia at high altitude (5380 m) for 12 months when undergoing a service. After exposure, they were followed up for 6 months. The samples of semen and peripheral blood were collected at 1 month before exposure (M0), 6 months of exposure (M6), 12 months of exposure (M12), and 6 months after exposure (M18). The semen quality was assessed with computer-assisted analysis system, and the serum levels of reproductive hormones, including prolactin (PRL), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone were analyzed by ELISA. Compared with those at M0, total sperm count, sperm density, motility, survival rate, and serum levels of LH, PRL and testosterone were significantly decreased, whereas the liquefaction time was significantly prolonged and serum FSH level was significantly increased at M6 (p<0.05). At M12, total sperm count and sperm density increased, whereas sperm motility, survival rate, and the liquefaction time further decreased. Sperm velocities, progression ratios, and lateral head displacements were also decreased. Serum FSH level decreased while serum LH, PRL, and testosterone levels increased. Compared with those at M6, the changes in these detected parameters of semen and hormone at M12 were significant (p<0.05). At M18, all these detected parameters except testosterone level returned to levels comparable to those before exposure. In conclusion, hypoxia at high altitude causes adverse effects on semen quality and reproductive hormones, and these effects are reversible. PMID:26288097

  6. Effect of High Intensity Interval and Continuous Swimming Training on Body Mass Adiposity Level and Serum Parameters in High-Fat Diet Fed Rats.

    PubMed

    da Rocha, Guilherme L; Crisp, Alex H; de Oliveira, Maria R M; da Silva, Carlos A; Silva, Jadson O; Duarte, Ana C G O; Sene-Fiorese, Marcela; Verlengia, Rozangela

    2016-01-01

    This study aimed to investigate the effects of interval and continuous training on the body mass gain and adiposity levels of rats fed a high-fat diet. Forty-eight male Sprague-Dawley rats were randomly divided into two groups, standard diet and high-fat diet, and received their respective diets for a period of four weeks without exercise stimuli. After this period, the animals were randomly divided into six groups (n = 8): control standard diet (CS), control high-fat diet (CH), continuous training standard diet (CTS), continuous training high-fat diet (CTH), interval training standard diet (ITS), and interval training high-fat diet (ITH). The interval and continuous training consisted of a swimming exercise performed over eight weeks. CH rats had greater body mass gain, sum of adipose tissues mass, and lower serum high density lipoprotein values than CS. The trained groups showed lower values of feed intake, caloric intake, body mass gain, and adiposity levels compared with the CH group. No significant differences were observed between the trained groups (CTS versus ITS and CTH versus ITH) on body mass gains and adiposity levels. In conclusion, both training methodologies were shown to be effective in controlling body mass gain and adiposity levels in high-fat diet fed rats. PMID:26904718

  7. Effect of High Intensity Interval and Continuous Swimming Training on Body Mass Adiposity Level and Serum Parameters in High-Fat Diet Fed Rats

    PubMed Central

    da Rocha, Guilherme L.; Crisp, Alex H.; de Oliveira, Maria R. M.; da Silva, Carlos A.; Silva, Jadson O.; Duarte, Ana C. G. O.; Sene-Fiorese, Marcela; Verlengia, Rozangela

    2016-01-01

    This study aimed to investigate the effects of interval and continuous training on the body mass gain and adiposity levels of rats fed a high-fat diet. Forty-eight male Sprague-Dawley rats were randomly divided into two groups, standard diet and high-fat diet, and received their respective diets for a period of four weeks without exercise stimuli. After this period, the animals were randomly divided into six groups (n = 8): control standard diet (CS), control high-fat diet (CH), continuous training standard diet (CTS), continuous training high-fat diet (CTH), interval training standard diet (ITS), and interval training high-fat diet (ITH). The interval and continuous training consisted of a swimming exercise performed over eight weeks. CH rats had greater body mass gain, sum of adipose tissues mass, and lower serum high density lipoprotein values than CS. The trained groups showed lower values of feed intake, caloric intake, body mass gain, and adiposity levels compared with the CH group. No significant differences were observed between the trained groups (CTS versus ITS and CTH versus ITH) on body mass gains and adiposity levels. In conclusion, both training methodologies were shown to be effective in controlling body mass gain and adiposity levels in high-fat diet fed rats. PMID:26904718

  8. The role of serum C-reactive protein measured by high-sensitive method in thyroid disease.

    PubMed

    Czarnywojtek, Agata; Owecki, Maciej; Zgorzalewicz-Stachowiak, Małgorzata; Woliński, Kosma; Szczepanek-Parulska, Ewelina; Budny, Bartłomiej; Florek, Ewa; Waligórska-Stachura, Joanna; Miechowicz, Izabela; Bączyk, Maciej; Sawicka, Nadia; Dhir, Sumit; Ruchała, Marek

    2014-12-01

    The aim of this study was the evaluation of serum C-reactive protein (CRP) concentration as a marker of the inflammatory state in many different thyroid diseases and its dependence on the stage and duration of disease. We conducted a retrospective analysis of 444 randomly selected patients with different kinds of thyroid disease (106 men and 338 women, ranging 18-72 years of age; mean 56.2 ± 5.0 years; median 52 years). Group 1 (G1) comprised 250 patients with hyperthyroidism. Group 2 (G2) consisted of 72 euthyroid patients. Group 3 (G3) consisted of 122 patients with hypothyroidism. Free T4, free T3, and thyrotropin (TSH) levels were measured using the electrochemiluminescent method. Human serum thyroglobulin autoantibodies (Tg-Abs), thyroperoxidase autoantibodies (TPO-Abs), and autoantibodies against the thyrotropin receptor (TSHR-Abs) levels were measured by radioimmunoassay. The high-sensitive CRP (Hs-CRP) level (reference range <3 mg/L) was determined with a highly sensitive latex-based immunoassay. The mean value of Hs-CRP in G1 was 3.6 ± 2.8 mg/L, in G2 2.5 ± 1.5 mg/L and in G3 5.9 ± 5.8 mg/L. Hs-CRP (in mg/L) medians, interquartile and the total ranges in G1 were 3.0 (2.0 [0.1-21.0] 4.0); in G2: 2.3 [1.8 (0.2-9.2) 3.2]; and in G3: 4.3 [2.2 (0.3-31.5) 7.8]. We found statistically significant differences (Kruskal-Wallis test) in serum Hs-CRP values between G1 and G2 (P = 0.007), G1 and G3 (P = 0.001), G2 and G3 (P < 0.001). In G1, statistically significant correlation was confirmed between Hs-CRP and Tg-Abs (r = -0.22, P = 0.0016), CRP and TPO-Abs (r = -0.26, P < 0.001), and also between Hs-CRP and TSHR-Abs (r = -0.18, P = 0.02). In the remaining cases, differences between Hs-CRP and TSH levels (r = -0.09, P = 0.16) were not statistically significant. In G2, no statistically significant correlation was observed: Hs-CRP and Tg-Abs (r = -0.18, P = 0.13), Hs-CRP and TPO-Abs (r = -0.17, P = 0.15), Hs-CRP and TSH (r = 0.01, P = 0.91), Hs-CRP and TSHR-Abs (r

  9. Development and optimization of ultra-high performance supercritical fluid chromatography mass spectrometry method for high-throughput determination of tocopherols and tocotrienols in human serum.

    PubMed

    Pilařová, Veronika; Gottvald, Tomáš; Svoboda, Pavel; Novák, Ondřej; Benešová, Karolína; Běláková, Sylvie; Nováková, Lucie

    2016-08-31

    The goal of this study was to develop an effective supercritical fluid chromatography method using single quadrupole MS for analysis of all isomeric forms of vitamin E. Finally, two fast and effective methods, the high resolution one and the high speed one, for the determination of 8 vitamin E isomers in human serum were developed. Rapid high-throughput liquid-liquid extraction was selected as a sample preparation step. Sample pretreatment of 100 μL human serum was consisted of protein precipitation with 200 μL ethanol and liquid-liquid extraction by 400 μL hexane/dichloromethane (80/20, v/v). The separation was performed on BEH 2-EP (3.0 × 100 mm, 1.7 μm) stationary phase, using isocratic elution with carbon dioxide and 10 mM ammonium formate in methanol in the ratio 98:2 for high resolution method with run time 4.5 min and in the ratio 95:5 for high speed method, where the run time was 2.5 min. The method development included optimization of key parameters: the choice of the suitable stationary phase and the composition of mobile phase, where an influence of various modifiers, their ratio and additives were tested, and optimization of fine tunning parameters including BPR pressure, flow-rate and column temperature. Quantification of all isomeric forms was performed using SIM (single ion monitoring) experiments in ESI positive ion mode. Both high speed and high resolution chromatographic methods were validated in terms of precision, accuracy, range, linearity, LOD, LOQ and matrix effects using the same LLE procedure. The high resolution method provided more sensitive results (LOD: 0.017-0.083 μg mL(-1)) and better linearity (r(2) > 0.9930) than the high speed one (LOD: 0.083-0.25 μg mL(-1), r(2) > 0.9877) at the cost of double time of analysis. PMID:27506367

  10. Application of high-performance thin-layer chromatography for the detection of organophosphorus insecticides in human serum after acute poisoning.

    PubMed

    Futagami, K; Narazaki, C; Kataoka, Y; Shuto, H; Oishi, R

    1997-12-19

    We developed a rapid and simple method for identifying 25 commonly used organophosphorus insecticides in human serum using high-performance thin-layer chromatography (HPTLC). These organophosphates were separated on plates with three different developing systems within 6-18 min and detected by means of ultraviolet radiation and coloring reactions with 4-(4-nitrobenzyl)pyridine-tetraethylenepentamine reagent (NT reagent) or palladium chloride reagent (PdCl2 reagent). Each organophosphate was accurately identified by means of the R(F) x 100 value and the spot color in three systems. The detection limits of dichlorvos, fenitrothion, malathion, methidathion, parathion and trichlorfon in serum by the liquid-liquid extraction method were 1.1, 0.12, 0.12, 0.05, 0.6 and 0.1 microg/ml, respectively. These sensitivities may be sufficient to detect those organophosphates in patient serum after acute poisoning. PMID:9518173

  11. Abnormal thyroid function tests in children on ethionamide treatment.

    PubMed

    Thee, S; Zöllner, E W; Willemse, M; Hesseling, A C; Magdorf, K; Schaaf, H S

    2011-09-01

    Ethionamide (ETH) treatment may cause hypothyroidism. Clinical data, serum thyroid stimulating hormone (TSH) and free thyroxine (fT4) levels were retrospectively assessed in 137 children receiving anti-tuberculosis treatment including ETH. Abnormal thyroid function tests (TFTs) were recorded in 79 (58%) children: elevated serum TSH and suppressed fT4 (n = 30), isolated elevated serum TSH (n = 20), isolated low serum fT4 (n = 28) and isolated low TSH (n = 1). The risk for biochemical hypothyroidism was higher for children on regimens including para-aminosalicylic acid and in human immunodeficiency virus infected children. TFT abnormalities are frequent in children on ETH and are mainly due to primary hypothyroidism or euthyroid sick syndrome. PMID:21943844

  12. High preoperative serum globulin in rectal cancer treated with neoadjunctive chemoradiation therapy is a risk factor for poor outcome

    PubMed Central

    Li, Qingguo; Meng, Xianke; Liang, Lei; Xu, Ye; Cai, Guoxiang; Cai, Sanjun

    2015-01-01

    An elevated serum albumin (ALB) and albumin/globulin ratio (AGR) has been reported to be associated with a favorable prognosis for certain malignancies; however, little is known about the prognostic significance of globulin (GLB) in rectal cancer treated with neoadjuvant chemoradiation therapy (NCRT). The purpose of this study was to evaluate whether GLB analysis could predict the prognosis of patients received NCRT. A retrospective cohort of 293 locally advanced rectal cancer patients receiving NCRT followed by radical surgery was recruited between January 2006 and December 2012 at Fudan University Shanghai Cancer Center. Levels for preoperative GLB and ALB were obtained and used to calculate the AGR. Survival analysis was used to evaluate the predictive value of GLB. X-tile program determined 28.50, 36.20 and 1.20 as optimal cut-off value for GLB, ALB and AGR in terms of survival. Univariate and multivariate analysis revealed that low GLB levels were significantly associated with favorable rectal cancer-specific survival (RCSS) (P < 0.05). Conversely, low ALB levels were associated with a significantly worse RCSS (P = 0.010). Collectively, high preoperative GLB level was a significantly unfavorable factor for rectal cancer patients treated with NCRT. This easily obtained variable may serve as a valuable marker to predict the outcomes of such patient population. PMID:26609491

  13. Unbiased analysis by high throughput sequencing of the viral diversity in fetal bovine serum and trypsin used in cell culture.

    PubMed

    Gagnieur, Léa; Cheval, Justine; Gratigny, Marlène; Hébert, Charles; Muth, Erika; Dumarest, Marine; Eloit, Marc

    2014-05-01

    Fetal bovine serum (FBS) and trypsin are reagents used in cell culture and have been the source of viral contamination of pharmaceutical products. We performed high throughput sequencing (HTS) of two pools of commercial batches of FBS and three commercial batches of trypsin. Taxonomies were assigned by comparing sequences of contigs and singletons to the entire NCBI nucleic acid and protein databases. The same major viral species were evidenced between batches of a given reagent but the proportion of viral reads among total reads varied markedly between samples (from 0.002% to 22.7%). In FBS, the sequences found were mainly from bovine viral diarrhea virus (BVDV) 1 to 3 and bovine parvovirus 3 (BPV3). The BVDV sequences derived from FBS showed only minor discrepancies with primers generally used for the screening of BVDV. Viral sequences in trypsin were mainly from porcine circovirus type 2. Other known viral sequences at lower read counts and potential new viral species (bovine parvovirus and bovine pegivirus) were evidenced. The load of some known and new viruses detected by HTS could be quantified by qPCR. Results of HTS provide a framework for evaluating the pertinence of control measures including the design of PCRs, bioassays and inactivation procedures. PMID:24661556

  14. High serum levels of proinflammatory markers during epileptogenesis. Can omega-3 fatty acid administration reduce this process?

    PubMed

    Gouveia, Telma Luciana Furtado; Vieira de Sousa, Paula Viviane; de Almeida, Sandro Soares; Nejm, Mariana Bocca; Vieira de Brito, Joíse Marques; Cysneiros, Roberta Monterazzo; de Brito, Marlon Vilela; Salu, Bruno Ramos; Oliva, Maria Luiza Vilela; Scorza, Fúlvio Alexandre; Naffah-Mazzacoratti, Maria da Graça

    2015-10-01

    During the epileptogenic process, several events may occur, such as an important activation of the immune system in the central nervous system. The response to seizure activity results in an inflammation in the brain as well as in the periphery. Moreover, CRP and cytokines may be able to interact with numerous ligands in response to cardiac injury caused by sympathetic stimulation in ictal and postictal states. Based on this, we measured the serum levels of C-reactive protein (CRP) and cytokines during acute, silent, and chronic phases of rats submitted to the pilocarpine model of epilepsy. We have also analyzed the effect of a chronic treatment of these rats with omega-3 fatty acid in CRP and cytokine levels, during an epileptic focus generation. C-reactive protein and cytokines such as IL-1β, IL-6, and TNF-α presented high concentration in the blood of rats, even well after the occurrence of SE. We found reduced levels of CRP and all proinflammatory cytokines in the blood of animals with chronic seizures, treated with omega-3, when compared with those treated with vehicle solution. Taken together, our results strongly suggest that the omega-3 is an effective treatment to prevent SUDEP occurrence due to its capability to act as an anti-inflammatory compound, reducing the systemic inflammatory parameters altered by seizures. PMID:26318793

  15. Preparation of carbon quantum dots with a high quantum yield and the application in labeling bovine serum albumin

    NASA Astrophysics Data System (ADS)

    Liu, Pengpeng; Zhang, Changchang; Liu, Xiang; Cui, Ping

    2016-04-01

    An economic and green approach of manufacturing carbon quantum dots (CQDs) with a high quantum yield (denoted with HQY-CQDs) and the application in labeling bovine serum albumin (BSA) were described in detail in this work. Firstly, the cheap resources of citric acid and glycine were pyrolysed in drying oven for preparing the CQDs. Then the product was immersed in tetrahydrofuran for 8 h. HQY-CQDs were obtained by removing tetrahydrofuran from the supernate and were evaluated that they possessed a much higher quantum yield compared with that without dealing with tetrahydrofuran and a wonderful photo-bleaching resistance. Such HQY-CQDs could be functionalized by N-hydroxysuccinimide and successively combined with BSA covalently. Thus fluorescent labeling on BSA was realized. The HQY-CQDs were demonstrated with transmission electron microscopy and the chemical modification with N-hydroxysuccinimide was proved by infrared and X-ray photoelectron spectra. Labeling BSA with the HQY-CQDs was confirmed by gel electrophoresis and fluorescence imaging.

  16. Rapid Screening of Drug-Protein Binding Using High-Performance Affinity Chromatography with Columns Containing Immobilized Human Serum Albumin

    PubMed Central

    Li, Ying-Fei; Zhang, Xiao-Qiong; Hu, Wei-Yu; Li, Zheng; Liu, Ping-Xia; Zhang, Zhen-Qing

    2013-01-01

    For drug candidates, a plasma protein binding (PPB) more than 90% is more meaningful and deserves further investigation in development. In the study, a high-performance liquid chromatography method employing column containing immobilized human serum albumin (HSA) to screen in vitro PPB of leading compounds was established and successfully applied to tested compounds. Good correlation (a coefficient correlation of 0.96) was attained between the reciprocal values (X) of experimentally obtained retention time of reference compounds eluted through HSA column and the reported PPB values (Y) with a correlation equation of Y = 92.03 − 97.01X. The method was successfully applied to six test compounds, and the result was confirmed by the conventional ultrafiltration technique, and both yielded equal results. However, due to the particular protein immobilized to column, the method cannot be applied for all compounds and should be exploited judiciously based on the value of the logarithmic measure of the acid dissociation constant (pKa) as per the requirement. If α1-acid glycoprotein and other plasma proteins could be immobilized like HSA with their actual ratio in plasma to column simultaneously, the result attained using immobilized column may be more accurate, and the method could be applied to more compounds without pKa limitation. PMID:23607050

  17. Correlation of serum triglyceride and its reduction by omega-3 fatty acids with lipid transfer activity and the neutral lipid compositions of high-density and low-density lipoproteins.

    PubMed

    Pownall, H J; Brauchi, D; Kilinç, C; Osmundsen, K; Pao, Q; Payton-Ross, C; Gotto, A M; Ballantyne, C M

    1999-04-01

    Serum triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) concentrations are inversely correlated and mechanistically linked by means of lipid transfer activities. Phospholipid transfer activity (PLTA) moves phospholipids among serum lipoproteins; cholesteryl ester transfer activity (CETA), which exchanges cholesteryl esters (CE) and TG among lipoproteins, is stimulated by nonesterified fatty acids (NEFA). The aims of this study were (a) to develop a quantitative model that correlates the neutral lipid (NL = CE + TG) compositions of HDL and LDL with serum TG concentration; (b) identify the serum lipid determinants of CETA and PLTA, and; (c) identify the effects of serum TG reductions on the neutral lipid compositions of HDL and LDL, serum NEFA concentrations, and on PLTA and CETA. These aims were addressed in 40 hypertriglyceridemic subjects before and after treatment with an 85% concentrate of omega-3 fatty acids (Omacor) and in 16 untreated normolipidemic subjects. In vivo, the NL compositions of LDL and HDL were described by a mathematical model having the form of adsorption isotherms: HDL - (TG/NL) = (0.90 +/- 0.07) serum TG/(7.0 +/- 1.2 mmol/l + serum TG) and LDL - (TG/NL) = (0.65 +/- 0.08) serum TG/(4.9 +/- 1.5 mmol/l + serum TG). Reduction of serum TG was associated with reductions in HDL - (TG/NL), serum NEFA concentration, and serum CETA but not PLTA. These data suggest that both hypertriglyceridemia and the attendant elevated serum CETA but not PLTA are determinants of HDL and LDL composition and structure and that serum TG concentrations are good predictors of the NL compositions of HDL and LDL. PMID:10217357

  18. Post-translationally Abnormal Collagens of Prolyl 3-Hydroxylase-2 Null Mice Offer a Pathobiological Mechanism for the High Myopia Linked to Human LEPREL1 Mutations*

    PubMed Central

    Hudson, David M.; Joeng, Kyu Sang; Werther, Rachel; Rajagopal, Abbhirami; Weis, MaryAnn; Lee, Brendan H.; Eyre, David R.

    2015-01-01

    Myopia, the leading cause of visual impairment worldwide, results from an increase in the axial length of the eyeball. Mutations in LEPREL1, the gene encoding prolyl 3-hydroxylase-2 (P3H2), have recently been identified in individuals with recessively inherited nonsyndromic severe myopia. P3H2 is a member of a family of genes that includes three isoenzymes of prolyl 3-hydroxylase (P3H), P3H1, P3H2, and P3H3. Fundamentally, it is understood that P3H1 is responsible for converting proline to 3-hydroxyproline. This limited additional knowledge also suggests that each isoenzyme has evolved different collagen sequence-preferred substrate specificities. In this study, differences in prolyl 3-hydroxylation were screened in eye tissues from P3h2-null (P3h2n/n) and wild-type mice to seek tissue-specific effects due the lack of P3H2 activity on post-translational collagen chemistry that could explain myopia. The mice were viable and had no gross musculoskeletal phenotypes. Tissues from sclera and cornea (type I collagen) and lens capsule (type IV collagen) were dissected from mouse eyes, and multiple sites of prolyl 3-hydroxylation were identified by mass spectrometry. The level of prolyl 3-hydroxylation at multiple substrate sites from type I collagen chains was high in sclera, similar to tendon. Almost every known site of prolyl 3-hydroxylation in types I and IV collagen from P3h2n/n mouse eye tissues was significantly under-hydroxylated compared with their wild-type littermates. We conclude that altered collagen prolyl 3-hydroxylation is caused by loss of P3H2. We hypothesize that this leads to structural abnormalities in multiple eye tissues, but particularly sclera, causing progressive myopia. PMID:25645914

  19. Changes in serum calcium, phosphorus, and magnesium levels in captive ruminants affected by diet manipulation.

    PubMed

    Miller, Michele; Weber, Martha; Valdes, Eduardo V; Neiffer, Donald; Fontenot, Diedre; Fleming, Gregory; Stetter, Mark

    2010-09-01

    A combination of low serum calcium (Ca), high serum phosphorus (P), and low serum magnesium (Mg) has been observed in individual captive ruminants, primarily affecting kudu (Tragelaphus strepsiceros), eland (Taurotragus oryx), nyala (Tragelaphus angasii), bongo (Tragelaphus eurycerus), and giraffe (Giraffa camelopardalis). These mineral abnormalities have been associated with chronic laminitis, acute tetany, seizures, and death. Underlying rumen disease secondary to feeding highly fermentable carbohydrates was suspected to be contributing to the mineral deficiencies, and diet changes that decreased the amount of starch fed were implemented in 2003. Serum chemistry values from before and after the diet change were compared. The most notable improvement after the diet change was a decrease in mean serum P. Statistically significant decreases in mean serum P were observed for the kudu (102.1-66.4 ppm), eland (73.3-58.4 ppm), and bongo (92.1-64.2 ppm; P < 0.05). Although not statistically significant, mean serum P levels also decreased for nyala (99.3-86.8 ppm) and giraffe (82.6-68.7 ppm). Significant increases in mean serum Mg were also observed for kudu (15.9-17.9 ppm) and eland (17.1-19.7 ppm). A trend toward increased serum Mg was also observed in nyala, bongo, and giraffe after the diet change. No significant changes in mean serum Ca were observed in any of the five species evaluated, and Ca was within normal ranges for domestic ruminants. The mean Ca:P ratio increased to greater than one in every species after the diet change, with kudu, eland, and bongo showing a statistically significant change. The results of this study indicate that the diet change had a generally positive effect on serum P and Mg levels. PMID:20945636

  20. A link between high serum levels of human chorionic gonadotrophin and chorionic expression of its mature functional receptor (LHCGR) in Down's syndrome pregnancies

    PubMed Central

    Banerjee, Subhasis; Smallwood, Alan; Chambers, Anne E; Papageorghiou, Aris; Loosfelt, Hugues; Spencer, Kevin; Campbell, Stuart; Nicolaides, Kypros

    2005-01-01

    Human chorionic gonadotrophin (hCG) is released from placental trophoblasts and is involved in establishing pregnancy by maintaining progesterone secretion from the corpus luteum. Serum hCG is detected in the maternal circulation within the first 2–3 wks of gestation and peaks at the end of the first trimester before declining. In Down's syndrome (DS) pregnancies, serum hCG remains significantly high compared to gestation age-matched uncompromised pregnancies. It has been proposed that increased serum hCG levels could be due to transcriptional hyper-activation of the CGB (hCG beta) gene, or an increased half life of glycosylated hCG hormone, or both. Another possibility is that serum hCG levels remain high due to reduced availability of the hormone's cognate receptor, LHCGR, leading to lack of hormone utilization. We have tested this hypothesis by quantifying the expression of the hCG beta (CGB) RNA, LHCGR RNA and LHCGR proteins in chorionic villous samples. We demonstrate that chorionic expression of hCG beta (CGB) mRNA directly correlates with high serum hCG levels. The steady-state synthesis of LHCGR mRNA (exons 1–5) in DS pregnancies was significantly higher than that of controls, but the expression of full-length LHCGR mRNA (exons 1–11) in DS was comparable to that of uncompromised pregnancies. However, the synthesis of high molecular weight mature LHCGR proteins was significantly reduced in DS compared to uncompromised pregnancies, suggesting a lack of utilization of circulating hCG in DS pregnancies. PMID:15969756

  1. Association Between Serum Concentrations of Hypoxia Inducible Factor Responsive Proteins and Excessive Erythrocytosis in High Altitude Peru

    PubMed Central

    Painschab, Matthew S.; Malpartida, Gary E.; Dávila-Roman, Victor G.; Gilman, Robert H.; Kolb, Todd M.; León-Velarde, Fabiola; Miranda, J. Jaime

    2015-01-01

    Abstract Painschab, Matthew S., Gary E. Malpartida, Victor G. Davila-Roman, Robert H. Gilman, Todd M. Kolb, Fabiola Leon-Velarde, J. Jaime Miranda, and William Checkley. Association between serum concentrations of hypoxia inducible factor responsive proteins and excessive erythrocytosis in high altitude Peru. High Alt Med Biol 16:26–33, 2015.—Long-term residence at high altitude is associated with the development of chronic mountain sickness (CMS), which is characterized by excessive erythrocytosis (EE). EE occurs under chronic hypoxia, and a strongly selected mutation in hypoxia-inducible factor 2α (HIF2A) has been found in native Tibetans that correlates with having a normal hemoglobin at high altitude. We sought to evaluate differences in plasma levels of four HIF-responsive proteins in 20 participants with EE (hemoglobin >21 g/dL in men and >19 in women) and in 20 healthy, age- and sex-matched participants without EE living at high altitude in Puno, Peru. We performed ELISA to measure plasma levels of the four HIF-responsive proteins: vascular endothelial growth factor (VEGF), soluble VEGF receptor 1 (sVEGF-R1), endothelin-1, and erythropoietin. As a secondary aim, we evaluated the association between HIF-responsive proteins and echocardiography-estimated pulmonary artery systolic pressure (PASP) in a subset of 26 participants. sVEGF-R1 was higher in participants with vs. without EE (mean 107 pg/mL vs. 90 pg/mL; p=0.007). Although plasma concentrations of endothelin-1, VEGF, and erythropoietin were higher in participants with vs. without EE, they did not achieve statistical significance (all p>0.25). Both sVEGF-R1 (p=0.04) and erythropoietin (p=0.04) were positively associated with PASP after adjustment for age, sex, and BMI. HIF-responsive proteins may play a pathophysiological role in altitude-related, chronic diseases but our results did not show consistent changes in all measured HIF-responsive proteins. Larger studies are needed to evaluate for

  2. Relationship between Serum Ferritin Levels and Dyslipidemia in Korean Adolescents

    PubMed Central

    Kim, Young-Eun; Roh, Yong-Kyun; Ju, Sang-Yhun; Yoon, Yeo-Joon; Nam, Ga-Eun; Nam, Hyo-Yun; Choi, Jun-Seok; Lee, Jong-Eun; Sang, Jung-Eun; Han, Kyungdo

    2016-01-01

    Background Ferritin is associated with various cardiometabolic risk factors such as dyslipidemia, hypertension, obesity, and insulin resistance in adults. We aimed to study the association between serum ferritin levels and dyslipidemia in adolescents, because dyslipidemia is considered an important modifiable cardiovascular risk factor in the young. Methods We analyzed 1,879 subjects (1,026 boys and 853 girls) from the 2009–2010 Korean National Health and Nutrition Examination Survey IV. Subjects were categorized into quartiles according to their lipid parameters, which were classified according to age and gender. Those in the highest quartile groups for total cholesterol, low-density lipoprotein cholesterol (LDL-C), and triglyceride concentrations were diagnosed as having dyslipidemia. Those in the lowest quartile for high-density lipoprotein cholesterol (HDL-C) values were diagnosed with abnormal levels. Results In boys, total cholesterol, LDL-C, and triglyceride concentrations were significantly correlated with serum ferritin levels. In both boys and girls, serum ferritin levels were negatively associated with HDL-C values, even after adjusting for all covariates. Furthermore, there was no significant correlation between serum ferritin levels and total cholesterol, LDL, and triglyceride concentrations in girls. Conclusion Serum ferritin levels were significantly associated with major dyslipidemia parameters, more prominently in boys than in girls, and this association represents a cardiometabolic risk factor. PMID:27070153

  3. Biophoton emission from blood serum of diabetic patients

    NASA Astrophysics Data System (ADS)

    Van Wijk, R.; Wiegant, F. A. C.; Popp, Fritz A.; Storms, G. E. M. G.

    1994-12-01

    The concept that free radicals mediate vascular abnormalities in diabetes has been debated. This study examines the relationship between serum free radical activity and glycaemic regulation. A cross-sectional assessment is presented of the chemiluminescence of blood serum, long term glycaemic control (HbAlc, fructosamine) and blood glucose concentrations in patients with type-1 (n equals 114) and patients with type-2 (n equals 112) diabetes. The average value of serum chemiluminescence of type-1 patients is higher than that of type-2 patients (p equals 0.014). Spectral analysis suggests that different sources of free radical activity are responsible in different ratios for chemiluminescence in type-1 and type-2 sera. Serum chemiluminescence values of type-1 patients strongly correspond with blood glucose levels (p < 0.001). Chemiluminescence values were higher, although not significant (p equals 0.082) in the 'poorly' controlled group characterized by high values of HbAlc and/or fructosamine in comparision with the group of 'good' glycaemic control with lower values of HbAlc and/or fructosamine. Serum chemeluminescence values of type-2 patients neither correspond to their long tern glycaemic status nor to their blood glucose levels. It is concluded that changes in glucose metabolism and changes in chemiluminescence are coordinated for type-1 but not for type-2 patients. This strongly indicates the relevance of ther free radical connection to diabetes type-1 complications.

  4. No effects of low and high consumption of dairy products and calcium supplements on body composition and serum lipids in Puerto Rican obese adults

    PubMed Central

    Palacios, Cristina; Bertrán, José J.; Ríos, Ruth E.; Soltero, Sandra

    2013-01-01

    Objective Epidemiologic studies have shown that a high calcium intake is related to lower body weight, fat, and serum lipids in obese individuals. However, clinical studies have shown inconclusive results. The present study was conducted to determine if dairy or calcium supplementation alters body composition or serum lipids in Puerto Rican obese adults without dietary energy restriction or exercise. Methods A 21-wk randomized clinical trial was conducted in 30 obese adults, aged 21–50 y, with usual calcium intakes <700 mg/d. Subjects were randomly assigned to the following: high dairy (~1300 mg/d of calcium from dairy products by substituting foods); high calcium (~1300 mg/d of calcium; ~700 mg/d from diet and 600 mg/d from a supplement); or placebo. Subjects were asked to continue their established dietary intake (except for the high dairy group) and their physical activity during the study. Body weight was measured monthly; body fat, bone, and serum lipids (total cholesterol, high-density lipoprotein, low-density lipoprotein, and triacylglycerol) were measured at baseline and at 21 wk. Pairwise differences in study endpoints among the groups were assessed using ANOVA and post-hoc analysis. Results Grand mean calcium intake was 1200 ± 370 (median 1187) mg/d in the high dairy group, 1171 ± 265 (median 1165) mg/d in the high calcium group, and 668 ± 273 (median 691) mg/d in the control group, which was significantly lower compared to the two treatment groups (P < 0.001). There were no significant group effects in any of the outcome variables. Conclusion A high dairy or calcium diet alone did not alter body composition or serum lipids profile in a sample of Puerto Rican obese adults. PMID:20579848

  5. [Clinical evaluation for abnormalities of bone and mineral metabolism in ESKD].

    PubMed

    Yano, Shozo

    2016-09-01

    In patients with end-stage kidney disease(ESKD), bone disorders are characterized by cortical porosity and by abnormal turnover of bone metabolism:adynamic(low turnover)bone disease and high turnover bone due to various degrees of secondary hyperparathyroidism. Abnormalities of bone metabolism are generally assessed by interview, X-ray, bone mineral density(BMD), serum phosphorus, calcium, and parathyroid hormone levels, and bone metabolic markers. Recent clinical studies have demonstrated that high turnover bone representing elevated bone metabolic markers and low BMD are independent risks of bone fractures as well as mortality among this population. Treatment of bone disorders in ESKD patients should be aiming at the normalization of mineral metabolism and the maintenance and/or improvement of BMD. PMID:27561341

  6. Associations between the human intestinal microbiota, Lactobacillus rhamnosus GG and serum lipids indicated by integrated analysis of high-throughput profiling data.

    PubMed

    Lahti, Leo; Salonen, Anne; Kekkonen, Riina A; Salojärvi, Jarkko; Jalanka-Tuovinen, Jonna; Palva, Airi; Orešič, Matej; de Vos, Willem M

    2013-01-01

    Accumulating evidence indicates that the intestinal microbiota regulates our physiology and metabolism. Bacteria marketed as probiotics confer health benefits that may arise from their ability to affect the microbiota. Here high-throughput screening of the intestinal microbiota was carried out and integrated with serum lipidomic profiling data to study the impact of probiotic intervention on the intestinal ecosystem, and to explore the associations between the intestinal bacteria and serum lipids. We performed a comprehensive intestinal microbiota analysis using a phylogenetic microarray before and after Lactobacillus rhamnosus GG intervention. While a specific increase in the L. rhamnosus-related bacteria was observed during the intervention, no other changes in the composition or stability of the microbiota were detected. After the intervention, lactobacilli returned to their initial levels. As previously reported, also the serum lipid profiles remained unaltered during the intervention. Based on a high-resolution microbiota analysis, intake of L. rhamnosus GG did not modify the composition of the intestinal ecosystem in healthy adults, indicating that probiotics confer their health effects by other mechanisms. The most prevailing association between the gut microbiota and lipid profiles was a strong positive correlation between uncultured phylotypes of Ruminococcus gnavus-group and polyunsaturated serum triglycerides of dietary origin. Moreover, a positive correlation was detected between serum cholesterol and Collinsella (Coriobacteriaceae). These associations identified with the spectrometric lipidome profiling were corroborated by enzymatically determined cholesterol and triglyceride levels. Actinomycetaceae correlated negatively with triglycerides of highly unsaturated fatty acids while a set of Proteobacteria showed negative correlation with ether phosphatidylcholines. Our results suggest that several members of the Firmicutes, Actinobacteria and

  7. Abnormalities of the IgA immune system in members of unrelated pedigrees from patients with IgA nephropathy.

    PubMed Central

    Schena, F P; Scivittaro, V; Ranieri, E; Sinico, R; Benuzzi, S; Di Cillo, M; Aventaggiato, L

    1993-01-01

    In the last few years many investigators have reported the recurrence of primary IgA nephropathy (IgAN) or the presence of persistent microhaematuria and/or proteinuria in family members of patients with IgAN. Our study was undertaken to investigate the relevance of abnormalities in the regulation of the IgA and IgM immune system in microhaematuric and asymptomatic family members of IgAN patients. Fifty-four out of 120 members of nine unrelated pedigrees were examined by urinalysis; polymeric IgA (pIgA), IgA rheumatoid factor (IgARF), IgA1-IgG immune complexes (IgA 1-IgG IC) and IgA 1-IgM IC, and other immunoglobulins were measured in serum samples. Moreover, we studied the production of immunoglobulins, pIgA and IgARF by peripheral blood mononuclear cells (PBMC) in basal conditions and after pokeweed mitogen (PWM) stimulation. Our data demonstrate that persistent microhaematuria was present in 24% of relatives. High serum levels of IgA, mainly pIgA and IgARF, IgA 1-IgG IC and IgA 1-IgM IC occurred in 66% of relatives. Abnormal spontaneous production of IgA by PBMC and after PWM stimulation was present in 64% of family members. Interestingly, high serum levels of IgM and abnormal production of this immunoglobulin by PBMC were observed in relatives. However, the immunological abnormalities did not correlate in any way with the presence of urinary abnormalities such as microhaematuria, which was most likely determined by an underlying glomerular alteration. PMID:8467558

  8. Crystallographic analysis reveals the structural basis of the high-affinity binding of iophenoxic acid to human serum albumin

    PubMed Central

    2011-01-01

    Background Iophenoxic acid is an iodinated radiocontrast agent that was withdrawn from clinical use because of its exceptionally long half-life in the body, which was due in part to its high-affinity binding to human serum albumin (HSA). It was replaced by Iopanoic acid, which has an amino rather than a hydroxyl group at position 3 on the iodinated benzyl ring and, as a result, binds to albumin with lower affinity and is excreted more rapidly from the body. To understand how iophenoxic acid binds so tightly to albumin, we wanted to examine the structural basis of its interaction with HSA. Results We have determined the co-crystal structure of HSA in complex with iophenoxic acid at 2.75 Å resolution, revealing a total of four binding sites, two of which - in drugs sites 1 and 2 on the protein - are likely to be occupied at clinical doses. High-affinity binding of iophenoxic acid occurs at drug site 1. The structure reveals that polar and apolar groups on the compound are involved in its interactions with drug site 1. In particular, the 3-hydroxyl group makes three hydrogen bonds with the side-chains of Tyr 150 and Arg 257. The mode of binding to drug site 2 is similar except for the absence of a binding partner for the hydroxyl group on the benzyl ring of the compound. Conclusions The HSA-iophenoxic acid structure indicates that high-affinity binding to drug site 1 is likely to be due to extensive desolvation of the compound, coupled with the ability of the binding pocket to provide a full set of salt-bridging or hydrogen bonding partners for its polar groups. Consistent with this interpretation, the structure also suggests that the lower-affinity binding of iopanoic acid arises because replacement of the 3-hydroxyl by an amino group eliminates hydrogen bonding to Arg 257. This finding underscores the importance of polar interactions in high-affinity binding to albumin. PMID:21501503

  9. Case report on an infant presenting with hypoglycemia, and milky serum

    PubMed Central

    Gupta, Yogesh Kumar; Prasad, Anushre; Kini, Pushpa; Naik, Prashant; Choprra, Deepti; Prabhu, Krishnananda

    2012-01-01

    A 4-month-old male baby who presented in a moribund condition with seizures was found to have hepatomegaly, hypoglycemia and milky serum. Serum triglycerides were markedly elevated (3 168 mg/dL) with cholesterol being 257 mg/dL and high density lipoprotein levels were low (19 mg/dL). The possibility of glycogen storage disease type I was considered in the diagnosis. Infants with glycogen storage disease type I may present like sepsis. The association of hepatomegaly, hypoglycemia and abnormal lipid profile stated above should alert the physician to consider glycogen storage disease type I in the diagnosis. PMID:23569924

  10. Liver Enzymes Abnormalities among Highly Active Antiretroviral Therapy Experienced and HAART Naïve HIV-1 Infected Patients at Debre Tabor Hospital, North West Ethiopia: A Comparative Cross-Sectional Study

    PubMed Central

    Tulu, Ketema Tafess; Zegeye, Amtatachew Moges; Wubante, Amarech Asratie

    2016-01-01

    Liver disease has emerged as the most common non-AIDS-related cause of death in HIV patients. However, there is limited data regarding this condition including our setting in Ethiopia. Hence, liver enzyme abnormalities among highly active antiretroviral therapy (HAART) experienced and HAART naïve patients were assessed in this study. A total of 164 HAART experienced and 164 HAART naïve patients were studied. Blood specimen was collected to determine alanine aminotransferase (ALT) and aspartate aminotransferase (AST), CD4 count, and viral hepatitis. The prevalence of liver enzyme abnormality was 20.1% and 22.0% among HAART experienced and HAART naïve patients, respectively. The HAART experienced patients had higher mean ALT than HAART naïve patients (P = 0.002). Viral hepatitis (AOR = 6.02; 95% CI = 1.87–19.39), opportunistic infections (AOR = 2.91; 95% CI = 1.04–8.19), current CD4 count <200 cells/mm3 (AOR = 2.16; 95% CI = 1.06–4.39), and male sex (AOR = 1.83; 95% CI = 1.001–3.33) were associated with elevated ALT and/or AST. In conclusion, liver enzyme abnormalities were high in both HAART experienced and HAART naïve HIV-1 infected patients. Hence, monitoring and management of liver enzyme abnormalities in HIV-1 infected patients are important in our setting. PMID:27493798

  11. Apolipoprotein AI Deficiency Inhibits Serum Opacity Factor Activity against Plasma High Density Lipoprotein via a Stabilization Mechanism

    PubMed Central

    Rosales, Corina; Patel, Niket; Gillard, Baiba K.; Yelamanchili, Dedipya; Yang, Yaliu; Courtney, Harry S.; Santos, Raul D.; Gotto, Antonio M.; Pownall, Henry J.

    2016-01-01

    The reaction of Streptococcal serum opacity factor (SOF) against plasma high-density lipoproteins (HDL) produces a large cholesteryl ester-rich microemulsion (CERM), a smaller neo HDL that is apolipoprotein (apo) AI-poor, and lipid-free apo AI. SOF is active vs. both human and mouse plasma HDL. In vivo injection of SOF into mice reduces plasma cholesterol ~40% in 3 hours while forming the same products observed in vitro, but at different ratios. Previous studies supported the hypothesis that labile apo AI is required for the SOF reaction vs. HDL. Here we further tested that hypothesis by studies of SOF against HDL from apo AI-null mice. When injected into apo AI-null mice, SOF reduced plasma cholesterol ~35% in three hours. The reaction of SOF vs. apo AI-null HDL in vitro produced a CERM and neo HDL, but no lipid-free apo. Moreover, according to the rate of CERM formation, the extent and rate of the SOF reaction vs. apo AI-null mouse HDL was less than that against wild-type (WT) mouse HDL. Chaotropic perturbation studies using guanidine hydrochloride showed that apo AI-null HDL was more stable than WT HDL. Human apo AI added to apo AI-null HDL was quantitatively incorporated, giving reconstituted HDL. Both SOF and guanidine hydrochloride displaced apo AI from the reconstituted HDL. These results support the conclusion that apo AI-null HDL is more stable than WT HDL because it lacks apo AI, a labile protein that is readily displaced by physico-chemical and biochemical perturbations. Thus, apo AI-null HDL is less SOF-reactive than WT HDL. The properties of apo AI-null HDL can be partially restored to those of WT HDL by the spontaneous incorporation of human apo AI. It remains to be determined what other HDL functions are affected by apo AI deletion. PMID:25790332

  12. Bovine serum albumin nanospheres synchronously encapsulating "gold selenium/gold" nanoparticles and photosensitizer for high-efficiency cancer phototherapy.

    PubMed

    Yu, Cong; Wo, Fangjie; Shao, Yuxiang; Dai, Xiangyun; Chu, Maoquan

    2013-03-01

    Gold nanostructures have generated significant attention in biomedical areas because of their major role in cancer photothermal therapeutics. In order to conveniently combine gold nanostructures and drugs into one nanocomposite, Au2Se/Au core-shell nanostructures with strong near-infrared-absorbing properties were synthesized using a simple method and embedded inside bovine serum albumin (BSA) nanospheres by using a spray dryer equipped with an ultrasonic atomizer followed by thermal denaturation. The nanospheres with narrow size distribution mainly ranging from 450 to 600 nm were obtained. The Au2Se/Au-loaded BSA nanospheres (1 mg) adsorbed at least 0.01 mg of water-insoluble zinc phthalocyanine (ZnPc) photosensitizer. After irradiation with a 655-nm laser (20 min), the temperature of the Au2Se/Au-loaded BSA nanospheres [200 μL, 2 mg/mL, BSA/Au2Se/Au 10:1 (w/w)] increased by over 20 °C from the initial temperature of 24.82 ± 0.15 °C, and the release of ZnPc was improved compared with a corresponding sample without irradiation. After being incubated with cancer cells (human esophageal carcinoma Eca-109), the nanospheres exhibited photothermal and photodynamic therapy with a synergistic effect upon laser irradiation. This work provides novel Au2Se/Au-loaded polymer nanospheres prepared by a high-efficiency strategy for incorporating drugs for improving the efficiency in killing cancer cells. PMID:23322252

  13. Prophylaxis with human serum butyrylcholinesterase protects Göttingen minipigs exposed to a lethal high-dose of sarin vapor.

    PubMed

    Saxena, Ashima; Hastings, Nicholas B; Sun, Wei; Dabisch, Paul A; Hulet, Stanley W; Jakubowski, Edward M; Mioduszewski, Robert J; Doctor, Bhupendra P

    2015-08-01

    Serum-derived human butyrylcholinesterase (Hu BChE) is a stoichiometric bioscavenger that is being developed as a potential prophylactic nerve agent countermeasure. Previously, we reported the prophylactic efficacy of Hu BChE in Göttingen minipigs against a whole-body exposure to 4.1mg/m(3) of sarin (GB) vapor, which produced lethality over 60min. Since the toxicity of nerve agent is concentration-dependent, in the present study, we investigated the toxic effects of an almost 3-fold higher rate of GB vapor exposure and the ability of Hu BChE to protect minipigs against this exposure. Male minipigs were subjected to: (1) air exposure; (2) GB vapor exposure; or (3) pretreatment with 7.5mg/kg of Hu BChE by i.m. injection, 24h prior to whole-body exposure to 11.4mg/m(3) of GB vapor for 10min. Electrocardiogram, electroencephalogram, and pupil size were monitored throughout exposure. Blood drawn before and throughout exposure was analyzed for blood gases, electrolytes, metabolites, acetylcholinesterase and BChE activities, and amount of GB bound to red blood cells and plasma. A novel finding was that saline-treated animals exposed to GB vapor did not develop any seizures, but manifested a variety of cardiac and whole blood toxic signs and rapidly died due to respiratory failure. Strikingly, pre-treatment with 7.5mg/kg of Hu BChE not only prevented lethality, but also avoided all cardiac toxic signs manifested in the non-treated cohort. Thus, Hu BChE alone can serve as an effective prophylactic countermeasure versus a lethal high-dose exposure to GB vapor. PMID:26145887

  14. Streptococcal serum opacity factor increases the rate of hepatocyte uptake of human plasma high-density lipoprotein cholesterol.

    PubMed

    Gillard, Baiba K; Rosales, Corina; Pillai, Biju K; Lin, Hu Yu; Courtney, Harry S; Pownall, Henry J

    2010-11-16

    Serum opacity factor (SOF), a virulence determinant of Streptococcus pyogenes, converts plasma high-density lipoproteins (HDL) to three distinct species: lipid-free apolipoprotein (apo) A-I, neo HDL, a small discoidal HDL-like particle, and a large cholesteryl ester-rich microemulsion (CERM) that contains the cholesterol esters (CE) of up to ∼400000 HDL particles and apo E as its major protein. Similar SOF reaction products are obtained with HDL, total plasma lipoproteins, and whole plasma. We hypothesized that hepatic uptake of CERM-CE via multiple apo E-dependent receptors would be faster than that of HDL-CE. We tested our hypothesis using human hepatoma cells and lipoprotein receptor-specific Chinese hamster ovary (CHO) cells. The uptake of [(3)H]CE by HepG2 and Huh7 cells from HDL after SOF treatment, which transfers >90% of HDL-CE to CERM, was 2.4 and 4.5 times faster, respectively, than from control HDL. CERM-[(3)H]CE uptake was inhibited by LDL and HDL, suggestive of uptake by both the LDL receptor (LDL-R) and scavenger receptor class B type I (SR-BI). Studies in CHO cells specifically expressing LDL-R and SR-BI confirmed CERM-[(3)H]CE uptake by both receptors. RAP and heparin inhibit CERM-[(3)H]CE but not HDL-[(3)H]CE uptake, thereby implicating LRP-1 and cell surface proteoglycans in this process. These data demonstrate that SOF treatment of HDL increases the rate of CE uptake via multiple hepatic apo E receptors. In so doing, SOF might increase the level of hepatic disposal of plasma cholesterol in a way that is therapeutically useful. PMID:20879789

  15. Apolipoprotein AI deficiency inhibits serum opacity factor activity against plasma high density lipoprotein via a stabilization mechanism.

    PubMed

    Rosales, Corina; Patel, Niket; Gillard, Baiba K; Yelamanchili, Dedipya; Yang, Yaliu; Courtney, Harry S; Santos, Raul D; Gotto, Antonio M; Pownall, Henry J

    2015-04-14

    The reaction of Streptococcal serum opacity factor (SOF) against plasma high-density lipoproteins (HDL) produces a large cholesteryl ester-rich microemulsion (CERM), a smaller neo HDL that is apolipoprotein (apo) AI-poor, and lipid-free apo AI. SOF is active versus both human and mouse plasma HDL. In vivo injection of SOF into mice reduces plasma cholesterol ∼40% in 3 h while forming the same products observed in vitro, but at different ratios. Previous studies supported the hypothesis that labile apo AI is required for the SOF reaction vs HDL. Here we further tested that hypothesis by studies of SOF against HDL from apo AI-null mice. When injected into apo AI-null mice, SOF reduced plasma cholesterol ∼35% in 3 h. The reaction of SOF vs apo AI-null HDL in vitro produced a CERM and neo HDL, but no lipid-free apo. Moreover, according to the rate of CERM formation, the extent and rate of the SOF reaction versus apo AI-null mouse HDL were less than that against wild-type (WT) mouse HDL. Chaotropic perturbation studies using guanidine hydrochloride showed that apo AI-null HDL was more stable than WT HDL. Human apo AI added to apo AI-null HDL was quantitatively incorporated, giving reconstituted HDL. Both SOF and guanidine hydrochloride displaced apo AI from the reconstituted HDL. These results support the conclusion that apo AI-null HDL is more stable than WT HDL because it lacks apo AI, a labile protein that is readily displaced by physicochemical and biochemical perturbations. Thus, apo AI-null HDL is less SOF-reactive than WT HDL. The properties of apo AI-null HDL can be partially restored to those of WT HDL by the spontaneous incorporation of human apo AI. It remains to be determined what other HDL functions are affected by apo AI deletion. PMID:25790332

  16. High serum androstenedione levels correlate with impaired memory in the surgically menopausal rat: a replication and new findings

    PubMed Central

    Camp, Bryan W.; Gerson, Julia E.; Tsang, Candy Wing S.; Villa, Stephanie R.; Acosta, Jazmin I.; Braden, B. Blair; Hoffman, Ann N.; Conrad, Cheryl D.; Bimonte-Nelson, Heather A.

    2012-01-01

    After natural menopause in women, androstenedione becomes the primary hormone secreted by the residual follicle-depleted ovaries. In two independent studies, in rodents that had undergone ovarian follicular depletion, we found that higher endogenous serum androstenedione levels correlated with increased working memory errors. This led to the hypothesis that higher androstenedione levels impair memory. The current study directly tested this hypothesis, examining the cognitive effects of exogenous androstenedione administration in rodents. Middle-aged ovariectomized rats received vehicle or one of two doses of androstenedione. Rats were tested on a spatial working and reference memory maze battery including the water-radial arm maze, Morris water maze (MM) and delay match-to-sample task. Androstenedione at the highest dose impaired reference memory as well as the ability to maintain performance as memory demand was elevated. This was true for both high temporal demand memory retention of one item of spatial information, as well as the ability to handle multiple items of spatial working memory information. We measured glutamic acid decarboxylase (GAD) protein in multiple brain regions to determine whether the gamma-aminobutyric acid (GABA) system relates to androstenedione-induced memory impairments. Results showed that higher entorhinal cortex GAD levels were correlated with worse MM performance, irrespective of androstenedione treatment. These findings suggest that androstenedione, the main hormone produced by the follicle-depleted ovary, is detrimental to working memory, reference memory and memory retention. Furthermore, while spatial reference memory performance might be related to the GABAergic system, it does not appear to be altered with androstenedione administration. PMID:22758646

  17. Apoptosis-related deregulation of proteolytic activities and high serum levels of circulating nucleosomes and DNA in blood correlate with breast cancer progression

    PubMed Central

    2011-01-01

    Background As cell-free circulating DNA exists predominantly as mono- and oligonucleosomes, the focus of the current study was to examine the interplay of circulating nucleosomes, DNA, proteases and caspases in blood of patients with benign and malignant breast diseases. Methods The concentrations of cell-free DNA and nucleosomes as well as the protease and caspase activities were measured in serum of patients with benign breast disease (n = 20), primary breast cancer (M0, n = 31), metastatic breast cancer (M1, n = 32), and healthy individuals (n = 28) by PicoGreen, Cell Death Detection ELISA, Protease Fluorescent Detection Kit and Caspase-Glo®3/7 Assay, respectively. Results Patients with benign and malignant tumors had significantly higher levels of circulating nucleic acids in their blood than healthy individuals (p = 0.001, p = 0.0001), whereas these levels could not discriminate between benign and malignant lesions. Our analyses of all serum samples revealed significant correlations of circulating nucleosome with DNA concentrations (p = 0.001), nucleosome concentrations with caspase activities (p = 0.008), and caspase with protease activities (p = 0.0001). High serum levels of protease and caspase activities associated with advanced tumor stages (p = 0.009). Patients with lymph node-positive breast cancer had significantly higher nucleosome levels in their blood than node-negative patients (p = 0.004). The presence of distant metastases associated with a significant increase in serum nucleosome (p = 0.01) and DNA levels (p = 0.04), and protease activities (p = 0.008). Conclusion Our findings demonstrate that high circulating nucleic acid concentrations in blood are no indicators of a malignant breast tumor. However, the observed changes in apoptosis-related deregulation of proteolytic activities along with the elevated serum levels of nucleosomes and DNA in blood are linked to breast cancer progression. PMID:21211028

  18. Right Liver Lobe Hypoplasia and Related Abnormalities

    PubMed Central

    Alicioglu, Banu

    2015-01-01

    Summary Background Hypoplasia and agenesis of the liver lobe is a rare abnormality. It is associated with biliary system abnormalities, high location of the right kidney, and right colon interposition. These patients are prone to gallstones, portal hypertension and possible surgical complications because of anatomical disturbance. Case Report Magnetic resonance imaging features of a rare case of hypoplasia of the right lobe of the liver in a sigmoid cancer patient are presented. Conclusions Hypoplasia of the right liver should not be confused with liver atrophy; indeed, associations with other coexistent abnormalities are also possible. Awareness and familiarity with these anomalies are necessary to avoid fatal surgical and interventional complications. PMID:26634012

  19. Large-Scale Glycomics of Livestock: Discovery of Highly Sensitive Serum Biomarkers Indicating an Environmental Stress Affecting Immune Responses and Productivity of Holstein Dairy Cows.

    PubMed

    Rehan, Ibrahim F; Ueda, Koichiro; Mitani, Tomohiro; Amano, Maho; Hinou, Hiroshi; Ohashi, Tetsu; Kondo, Seiji; Nishimura, Shin-Ichiro

    2015-12-01

    Because various stresses strongly influence the food productivity of livestock, biomarkers to indicate unmeasurable environmental stress in domestic animals are of increasing importance. Thermal comfort is one of the basic principles of dairy cow welfare that enhances productivity. To discover sensitive biomarkers that monitor such environmental stresses in dairy cows, we herein performed, for the first time, large-scale glycomics on 336 lactating Holstein cow serum samples over 9 months between February and October. Glycoblotting combined with MALDI-TOF/MS and DMB/HPLC allowed for comprehensive glycomics of whole serum glycoproteins. The results obtained revealed seasonal alterations in serum N-glycan levels and their structural characteristics, such as an increase in high-mannose type N-glycans in spring, the occurrence of di/triantennary complex type N-glycans terminating with two or three Neu5Gc residues in summer and autumn, and N-glycans in winter dominantly displaying Neu5Ac. A multivariate analysis revealed a correlation between the serum expression levels of these season-specific glycoforms and productivity. PMID:26595672

  20. A highly sensitive "turn-on" fluorescent sensor for the detection of human serum proteins based on the size exclusion of the polyacrylamide gel.

    PubMed

    Xu, Shenghao; Liu, Pingping; Lu, Xin; Zhang, Jing; Huang, Lingyun; Hua, Wenhao; He, Dacheng; Ouyang, Jin

    2014-02-01

    A highly sensitive "turn-on" fluorescent sensor based on the size exclusion of the polyacrylamide gel was developed for the on-gels detection of human serum proteins after PAGE. The possible mechanism of this fluorescence sensor was illustrated and validated by utilizing five kinds of colloidal silver nanoparticles with different particle size distribution and six kinds of polyacrylamide gels with different pore size. It was attributed to that silver nanoparticles (<5 nm in diameter) had been selectively absorbed into the gel and formed the small silver nanoclusters, resulting in the red fluorescence. Using this new technique for the detection of human serum proteins after PAGE, a satisfactory sensitivity was achieved and some relatively low-abundance proteins (e.g. zinc-alpha-2-glycoprotein), which are the significant proteinic markers of certain diseases can be easily detected, but not with traditional methods. Furthermore, it was also successfully applied to distinguish between serums from hepatoma patient and healthy people. As a new protein detection technique, the colloidal silver nanoparticles based "turn-on" fluorescent sensor offers a rapid, economic, low background, and sensitive way for direct detection of human serum proteins, showing available potential and significance in the development of nanobiotechnology and proteome research. PMID:24150987

  1. Red-Backed Vole Brain Promotes Highly Efficient In Vitro Amplification of Abnormal Prion Protein from Macaque and Human Brains Infected with Variant Creutzfeldt-Jakob Disease Agent

    PubMed Central

    Nemecek, Julie; Nag, Nabanita; Carlson, Christina M.; Schneider, Jay R.; Heisey, Dennis M.; Johnson, Christopher J.; Asher, David M.; Gregori, Luisa

    2013-01-01

    Rapid antemortem tests to detect individuals with transmissible spongiform encephalopathies (TSE) would contribute to public health. We investigated a technique known as protein misfolding cyclic amplification (PMCA) to amplify abnormal prion protein (PrPTSE) from highly diluted variant Creutzfeldt-Jakob disease (vCJD)-infected human and macaque brain homogenates, seeking to improve the rapid detection of PrPTSE in tissues and blood. Macaque vCJD PrPTSE did not amplify using normal macaque brain homogenate as substrate (intraspecies PMCA). Next, we tested interspecies PMCA with normal brain homogenate of the southern red-backed vole (RBV), a close relative of the bank vole, seeded with macaque vCJD PrPTSE. The RBV has a natural polymorphism at residue 170 of the PrP-encoding gene (N/N, S/S, and S/N). We investigated the effect of this polymorphism on amplification of human and macaque vCJD PrPTSE. Meadow vole brain (170N/N PrP genotype) was also included in the panel of substrates tested. Both humans and macaques have the same 170S/S PrP genotype. Macaque PrPTSE was best amplified with RBV 170S/S brain, although 170N/N and 170S/N were also competent substrates, while meadow vole brain was a poor substrate. In contrast, human PrPTSE demonstrated a striking narrow selectivity for PMCA substrate and was successfully amplified only with RBV 170S/S brain. These observations suggest that macaque PrPTSE was more permissive than human PrPTSE in selecting the competent RBV substrate. RBV 170S/S brain was used to assess the sensitivity of PMCA with PrPTSE from brains of humans and macaques with vCJD. PrPTSE signals were reproducibly detected by Western blot in dilutions through 10-12 of vCJD-infected 10% brain homogenates. This is the first report showing PrPTSE from vCJD-infected human and macaque brains efficiently amplified with RBV brain as the substrate. Based on our estimates, PMCA showed a sensitivity that might be sufficient to detect PrPTSE in vCJD-infected human

  2. Red-backed vole brain promotes highly efficient in vitro amplification of abnormal prion protein from macaque and human brains infected with variant Creutzfeldt-Jakob disease agent.

    USGS Publications Warehouse

    Nemecek, Julie; Nag, Nabanita; Carlson, Christina M.; Schneider, Jay R.; Heisey, Dennis M.; Johnson, Christopher J.; Asher, David M.; Gregori, Luisa

    2013-01-01

    Rapid antemortem tests to detect individuals with transmissible spongiform encephalopathies (TSE) would contribute to public health. We investigated a technique known as protein misfolding cyclic amplification (PMCA) to amplify abnormal prion protein (PrPTSE) from highly diluted variant Creutzfeldt-Jakob disease (vCJD)-infected human and macaque brain homogenates, seeking to improve the rapid detection of PrPTSE in tissues and blood. Macaque vCJD PrPTSE did not amplify using normal macaque brain homogenate as substrate (intraspecies PMCA). Next, we tested interspecies PMCA with normal brain homogenate of the southern red-backed vole (RBV), a close relative of the bank vole, seeded with macaque vCJD PrPTSE. The RBV has a natural polymorphism at residue 170 of the PrP-encoding gene (N/N, S/S, and S/N). We investigated the effect of this polymorphism on amplification of human and macaque vCJD PrPTSE. Meadow vole brain (170N/N PrP genotype) was also included in the panel of substrates tested. Both humans and macaques have the same 170S/S PrP genotype. Macaque PrPTSE was best amplified with RBV 170S/S brain, although 170N/N and 170S/N were also competent substrates, while meadow vole brain was a poor substrate. In contrast, human PrPTSE demonstrated a striking narrow selectivity for PMCA substrate and was successfully amplified only with RBV 170S/S brain. These observations suggest that macaque PrPTSE was more permissive than human PrPTSE in selecting the competent RBV substrate. RBV 170S/S brain was used to assess the sensitivity of PMCA with PrPTSE from brains of humans and macaques with vCJD. PrPTSE signals were reproducibly detected by Western blot in dilutions through 10-12 of vCJD-infected 10% brain homogenates. This is the first report showing PrPTSE from vCJD-infected human and macaque brains efficiently amplified with RBV brain as the substrate. Based on our estimates, PMCA showed a sensitivity that might be sufficient to detect PrPTSE in v

  3. Chromosome abnormalities in glioma

    SciTech Connect

    Li, Y.S.; Ramsay, D.A.; Fan, Y.S.

    1994-09-01

    Cytogenetic studies were performed in 25 patients with gliomas. An interesting finding was a seemingly identical abnormality, an extra band on the tip of the short arm of chromosome 1, add(1)(p36), in two cases. The abnormality was present in all cells from a patient with a glioblastoma and in 27% of the tumor cells from a patient with a recurrent irradiated anaplastic astrocytoma; in the latter case, 7 unrelated abnormal clones were identified except 4 of those clones shared a common change, -Y. Three similar cases have been described previously. In a patient with pleomorphic astrocytoma, the band 1q42 in both homologues of chromosome 1 was involved in two different rearrangements. A review of the literature revealed that deletion of the long arm of chromosome 1 including 1q42 often occurs in glioma. This may indicate a possible tumor suppressor gene in this region. Cytogenetic follow-up studies were carried out in two patients and emergence of unrelated clones were noted in both. A total of 124 clonal breakpoints were identified in the 25 patients. The breakpoints which occurred three times or more were: 1p36, 1p22, 1q21, 1q25, 3q21, 7q32, 8q22, 9q22, 16q22, and 22q13.

  4. [Congenital foot abnormalities].

    PubMed

    Delpont, M; Lafosse, T; Bachy, M; Mary, P; Alves, A; Vialle, R

    2015-03-01

    The foot may be the site of birth defects. These abnormalities are sometimes suspected prenatally. Final diagnosis depends on clinical examination at birth. These deformations can be simple malpositions: metatarsus adductus, talipes calcaneovalgus and pes supinatus. The prognosis is excellent spontaneously or with a simple orthopedic treatment. Surgery remains outstanding. The use of a pediatric orthopedist will be considered if malposition does not relax after several weeks. Malformations (clubfoot, vertical talus and skew foot) require specialized care early. Clubfoot is characterized by an equine and varus hindfoot, an adducted and supine forefoot, not reducible. Vertical talus combines equine hindfoot and dorsiflexion of the forefoot, which is performed in the midfoot instead of the ankle. Skew foot is suspected when a metatarsus adductus is resistant to conservative treatment. Early treatment is primarily orthopedic at birth. Surgical treatment begins to be considered after walking age. Keep in mind that an abnormality of the foot may be associated with other conditions: malposition with congenital hip, malformations with syndromes, neurological and genetic abnormalities. PMID:25524290

  5. Serum Parathyroid Hormone Is a New Potential Risk Factor in Multiple Myeloma

    PubMed Central

    Won, Eun-Jeong; Kim, Hye-Ran; Choi, Hyun-Jung; Park, Hye-Ri; Shin, Jong-Hee; Suh, Soon-Pal; Ryang, Dong-Wook; Shin, Myung-Geun

    2014-01-01

    We hypothesized that serum PTH might be associated with various clinicopathological parameters in multiple myeloma (MM). So we investigated the implications of serum PTH in MM patients and the relationship with other risk factors of MM. A total of 115 patients who were newly diagnosed with MM were enrolled. Serum PTH level was 24.7 ± 34.9 (ranged 0.0–284.1) pg/mL. Serum levels of IgG, IgM, FLC-lambda, albumin, and LDH were in positive correlation with serum PTH. Compared to non-high PTH (<68.3 pg/mL) group, the hazard ratio (HR) for overall survival was higher for group with high PTH level (≥68.3 pg/mL) (HR, 1.710). Furthermore, the patient group with high PTH level showed inferior progression-free survival than non-high PTH group (P = 0.056). Interestingly, subgroup analysis showed that serum PTH level at diagnosis was associated with risk factors and clinical outcome in MM patients, especially in complete remission group, transplantation cases, ISS stage II cases, and cases without chromosome abnormality. In conclusion, this study showed that blood PTH level in MM at diagnosis was associated with risk factors and clinical outcome in MM patients. PMID:24967406

  6. Concentration Study of High Sensitive C - reactive Protein and some Serum Trace Elements in Patients with Benign and Malignant Breast Tumor

    PubMed Central

    Abdollahi, Alireza; Ali-Bakhshi, Abbas; Farahani, Zahra

    2015-01-01

    Background : Breast cancer is the most common invasive cancer in females worldwide. It accounts for 16% of all female cancers and 22.9% of invasive cancers in women. 18.2% of all cancer deaths worldwide including both males and females are from breast cancer. In this study we compared few serum elements in patients with benign and malignant breast tumor to find any related prognostic and predictive value. Subjects and Methods: A case-control study was carried out in a hospital (Tehran - Iran) in 2012. Target population was divided in 2 groups; subjects with benign and malignant breast tumors. We did preoperative hematological test. Five milliliter fasting blood vein was collected, centrifuged in 3000 g for 15 minutes to obtain serum. We measured serum Calcium (Ca), Phosphorus (P), Magnesium (Mg), Zinc (Zn), and high sensitive-CRP, analyzed statistically and compared recorded elements in 2 groups by software package SPSS version 16. The level of significant was considered P < 0.05. Results: Of 87 women, 49 cases with benign breast disease (group A) and 38 cases with breast cancer (group B) entered our study. Serum concentration of Ca, mg, and P in group A were higher than group B, however these differences were not significant. We found no significant correlation between serum Zn and type of tumor in our patients. On the other hand, a significant elevation in hs-CRP in patient with breast cancer was seen (P Value=.000). Conclusion : Our results have shown similar concentration of Ca, Mg, Zn, P and completely different hs-CRP concentration in patients with benign and malignant breast disease. PMID:26865928

  7. Serum chemerin and high-sensitivity C reactive protein as markers of subclinical atherosclerosis in Egyptian patients with type 2 diabetes

    PubMed Central

    Lachine, Nagwa A.; Elnekiedy, Abdel Aziz; Megallaa, Magdy Helmy; Khalil, Gihane I.; Sadaka, Mohamed A.; Rohoma, Kamel H.; Kassab, Heba S.

    2016-01-01

    Context: Chemerin is one of the adipokines that regulate fat metabolism. High-sensitivity C-reactive protein (hs-CRP) may be considered as a cardiovascular risk predictor. Measuring intima-media thickness of the CCA (C-IMT) is a well-evidenced tool for the detection of early stages of atherosclerosis. We aimed here to study both serum chemerin and hs-CRP as markers of subclinical atherosclerosis in Egyptian patients with type 2 diabetes, who are angiographically free of coronary artery disease (CAD). Subjects and methods: This cross-sectional study was conducted on 180 subjects divided into two groups: Group A included 90 type 2 diabetic patients without CAD and group B including 90 nondiabetic control subjects. All study subjects were having normal coronary angiography. Serum chemerin, homeostasis model assessment for insulin resistance (HOMA-IR), glycated haemoglobin (HbA1c), lipid profile, hs-CRP as well as C-IMT were assessed in all study subjects. Results: There was a statistically significant difference between the 2 groups regarding serum chemerin level, HOMA-IR, hs-CRP and C-IMT; being higher in the diabetic patients than in the control group (p = 0.006, 0.024, 0.040 and <0.001, respectively). There was positive correlation between serum chemerin level and waist-to-hip ratio (WHR), HOMA-IR, hs-CRP and C-IMT. Carotid intima-media thickness was positively correlated with patients’ WHR, blood pressure, HbA1c, diabetes duration as well as hs-CRP, and negatively correlated with ankle-brachial index (ABI). Linear regression analysis showed that HbA1c, serum chemerin and hs-CRP were independently affecting C-IMT. Serum hs-CRP was positively correlated with HbA1c and HOMA-IR (p = 0.006 and 0.032, respectively), and negatively correlated with HDL-cholesterol level (p = 0.018). Conclusion: Both serum chemerin and hs-CRP could be considered as markers of subclinical atherosclerosis, and hence, may be utilized for the early detection of macrovascular disease, in

  8. Abnormal pressures as hydrodynamic phenomena

    USGS Publications Warehouse

    Neuzil, C.E.

    1995-01-01

    So-called abnormal pressures, subsurface fluid pressures significantly higher or lower than hydrostatic, have excited speculation about their origin since subsurface exploration first encountered them. Two distinct conceptual models for abnormal pressures have gained currency among earth scientists. The static model sees abnormal pressures generally as relict features preserved by a virtual absence of fluid flow over geologic time. The hydrodynamic model instead envisions abnormal pressures as phenomena in which flow usually plays an important role. This paper develops the theoretical framework for abnormal pressures as hydrodynamic phenomena, shows that it explains the manifold occurrences of abnormal pressures, and examines the implications of this approach. -from Author

  9. Wild rice ( Zizania latifolia (Griseb) Turcz) improves the serum lipid profile and antioxidant status of rats fed with a high fat/cholesterol diet.

    PubMed

    Zhang, Hong; Cao, Pei; Agellon, Luis B; Zhai, Cheng-Kai

    2009-12-01

    The diet consumed by urban residents in modern China has become rich in saturated fats and cholesterol. In addition, the diet is high in carbohydrates from white rice and processed wheat starch. The aim of the present study was to determine the effects of replacing white rice and processed wheat starch with wild rice (WR) as the chief source of dietary carbohydrates. Rats fed with the diet patterned after the diet consumed by city residents of modern China showed elevated serum lipid levels comparable with rats consuming a high fat/cholesterol diet known to induce hyperlipidaemia in this species. Meanwhile, rats consuming the city diet with WR as the carbohydrate source suppressed the increase in serum TAG and total cholesterol, and the decrease in HDL cholesterol level. In addition, the rats fed the WR diet suppressed the build-up of oxidative stress by improving antioxidant capacity, increasing superoxide dismutase activity and reducing malondialdehyde concentration, both in the serum and liver. These findings illustrate that WR is effective in suppressing hyperlipidaemia and oxidative stress in rats even when the diet consumed is high in fat and cholesterol. PMID:19631021

  10. Abnormal hepatic function and splenomegaly on the newly diagnosed acute leukemia patients.

    PubMed

    Sharma Poudel, B; Karki, L

    2007-01-01

    To evaluate the liver function, splenomegaly and related factors in the newly diagnosed acute leukemia patients. One hundred of fifty eight acute leukemia patients admitted in our hospital from March 2003 to April 2006 were studied. The related factors such as peripheral WBC count, bone marrow blasts, peripheral blasts, sex, age, AML, ALL affecting the liver function and splenomegaly were evaluated. Sixty two (39.24%) patients presented with splenomegaly. Twelve (7.59%) patients presented with hepatomegaly. Serum ALT was elevated in 54 (34.17%) patients. Similarly, serum AST, GGT, ALP, and Direct bilirubin were elevated in 26 (16.45%), 32 (20.25%), 20 (12.65%), and 22 (13.92%) patients, respectively. Low serum albumin was found in 40 (25.31%) patients. PT was prolonged in 62 (39.24%) patients. Statistical study shows that there is a relation between high WBC counts and elevated serum ALT (P<0.05) and high WBC counts and splenomegaly (P<0.05). Acute leukemia patients with leukocytosis are more prone to develop abnormal liver function and splenomegaly. PMID:18340367

  11. Feeling Abnormal: Simulation of Deviancy in Abnormal and Exceptionality Courses.

    ERIC Educational Resources Information Center

    Fernald, Charles D.

    1980-01-01

    Describes activity in which student in abnormal psychology and psychology of exceptional children classes personally experience being judged abnormal. The experience allows the students to remember relevant research, become sensitized to the feelings of individuals classified as deviant, and use caution in classifying individuals as abnormal.…

  12. Serum Bisphenol A Level in Boys with Cryptorchidism: A Step to Male Infertility?

    PubMed Central

    Komarowska, Marta Diana; Hermanowicz, Adam; Czyzewska, Urszula; Milewski, Robert; Matuszczak, Ewa; Miltyk, Wojciech; Debek, Wojciech

    2015-01-01

    Cryptorchidism is the most common congenital birth defect in boys and affects about 2–4% full-term male neonates. Its etiology is multifactorial. Purpose. To evaluate the serum bisphenol A (BPA) levels in boys with cryptorchidism and healthy boys and to assess the risk of environmental exposure to BPA using the authors' questionnaire. The data were acquired from a study on boys with cryptorchidism (n = 98) and a control group (n = 57). Prior to surgery, all patients had BPA serum levels evaluated. The size, position, rigidity of the testis, and abnormality of the epididymis of the undescended testis were assessed. Parents also completed a questionnaire on the risks of exposure to BPA in everyday life. Results. The testes in both groups were similar in size. The turgor of the undescended testis in the group of boys with cryptorchidism was decreased. Free serum BPA level in cryptorchid boys and in the control group was not statistically significant (p > 0.05). The conjugated serum BPA level in cryptorchid boys and in the control group was statistically significant (p ≤ 0.05). Total serum BPA level in cryptorchid boys and in the control group was statistically significant (p < 0.05). Serum total BPA level was related with a positive answer about problems with conception (p < 0.02). Conclusion. Our study indicated that high serum BPA was associated with cryptorchidism. PMID:26491444

  13. High serum adiponectin levels predict incident falls among middle-aged and older adults: a prospective cohort study

    PubMed Central

    Huang, Cong; Momma, Haruki; Niu, Kaijun; Chujo, Masahiko; Otomo, Atsushi; Cui, Yufei; Nagatomi, Ryoichi

    2016-01-01

    Background and objective: adiponectin is an adipocyte-derived hormone with anti-obesity and anti-diabetic properties. However, higher circulating adiponectin levels are related to poor muscle function and physical disability, which suggests a potential link between adiponectin and risk of falls. Nevertheless, no direct association between circulating adiponectin levels and incident fall risk has been reported. Therefore, this study aimed to investigate the relationship between serum adiponectin levels and incident falls in a population of middle-aged and older adults. Design: a prospective cohort study. Setting: Oroshisho Center in Sendai City, Japan. Subjects: Japanese adults who were ≥45 years old (n = 430). Measurements: serum adiponectin levels were measured at baseline, and the subjects were divided into sex-specific tertiles. Data regarding a history of falls were collected via participant recall using a self-reported questionnaire. Incident falls were defined as falls that were experienced by people without a history of falls at baseline. Results: during the 2-year follow-up, 15.6% (67/430) of the subjects experienced an incident fall. In the univariate logistic regression analysis, incident falls were significantly more frequent across the increasing sex-specific serum adiponectin tertiles (P for trend = 0.008). Adjusted odds ratios (95% confidence interval) for incident falls were 2.31 (1.07–4.98) in the middle tertile and 3.61 (1.63–7.99) in the highest tertile; this risk was significantly higher than that for the lowest adiponectin tertile (P for trend = 0.002). Conclusions: the findings of this prospective cohort study indicate that higher serum adiponectin levels may be a predictor of incident falls. PMID:27013505

  14. A high-performance liquid chromatographic method for the determination of hypoxanthine, xanthine, uric acid and allantoin in serum.

    PubMed

    Kock, R; Delvoux, B; Greiling, H

    1993-05-01

    A method was developed for the simultaneous determination of hypoxanthine, xanthine, uric acid and allantoin based on isocratic reversed-phase chromatography. This HPLC-method additionally allows the direct determination with UV-detection of inosine-5'-phosphate, uridine, thymine, orotic acid, allopurinol and oxipurinol, besides hypoxanthine, xanthine and uric acid in the same chromatographic run. Allantoin elutes in this system near the void volume and a fraction is collected covering the retention time range for this substance. After hydrolysis allantoin is converted to glyoxylate-2,4-dinitrophenylhydrazone, rechromatographed and detected at 360 nm. The coefficient of variation for this method does not exceed 5.0% for a serum concentration of 0.3 mumol/l hypoxanthine and is not greater than 5.3% for a xanthine concentration of 0.3 mumol/l serum. Recoveries were 90-110% for both hypoxanthine and xanthine. The determination of uric acid had an imprecision and inaccuracy not exceeding 1.45% in the concentration range of 103-568 mumol/l. Due to the more complex procedure required for the determination of allantoin, the coefficient of variation between days was 13.6% for a sample containing 0.8 mumol/l allantoin and the recoveries for this analyte were in the range of 86-93%. Reference ranges (mean +/- SD) determined on 171 serum samples from healthy adults were 12.7 +/- 6.6 mumol/l for hypoxanthine, 3.3 +/- 1.4 mumol/l for xanthine, and 15.7 +/- 7.9 mumol/l for allantoin. No significant age or sex dependence was observed. Uric acid concentrations were 320 +/- 55 mumol/l serum for men and 206 +/- 55 mumol/l for women. PMID:8357939

  15. Abnormal human sex chromosome constitutions

    SciTech Connect

    1993-12-31

    Chapter 22, discusses abnormal human sex chromosome constitution. Aneuploidy of X chromosomes with a female phenotype, sex chromosome aneuploidy with a male phenotype, and various abnormalities in X chromosome behavior are described. 31 refs., 2 figs.

  16. Exercises to Improve Gait Abnormalities

    MedlinePlus

    ... Home About iChip Articles Directories Videos Resources Contact Exercises to Improve Gait Abnormalities Home » Article Categories » Exercise and Fitness Font Size: A A A A Exercises to Improve Gait Abnormalities Next Page The manner ...

  17. Prognostic role of serum concentrations of high-sensitivity C-reactive protein in patients with metastatic colorectal cancer: results from the ITACa trial.

    PubMed

    Casadei Gardini, Andrea; Carloni, Silvia; Scarpi, Emanuela; Maltoni, Paolo; Dorizzi, Romolo M; Passardi, Alessandro; Frassineti, Giovanni Luca; Cortesi, Pietro; Giannini, Maria Benedetta; Marisi, Giorgia; Amadori, Dino; Lucchesi, Alessandro

    2016-03-01

    Serum levels of C-reactive protein are (CRP) higher in patients with neoplastic conditions and numerous studies have been performed to clarify the etiologic and prognostic role of the high-sensitivity CRP (hs-CRP) in cancer. Our study was conducted on patients enrolled in the prospective randomized "Italian Trial in Advanced Colorectal Cancer (ITACa)" to assess hs-CRP levels and their impact on overall survival (OS) and progression-free survival (PFS). Serum samples from 132 ITACa patients were collected at baseline and 2 months after starting first-line chemotherapy. The supernatant was immediately transferred to cryovials and stored at -80°C. After thawing, hs-CRP was measured with the Cobas c501 analyzer. High levels of hs-CRP (≥ 13.1 mg/L) were associated with poorer median PFS (p < 0.0001) and OS (p < 0.0001) than low hs-CRP levels (< 13.1 mg/L). hs-CRP values in 107 patients were evaluated again after 2 months of therapy, revealing that patients with low hs-CRP levels in both baseline and second serum samples had the best median PFS and OS. Our study confirms the prognostic value of hs-CRP in patients with metastatic colorectal carcinoma. PMID:26848624

  18. Prognostic role of serum concentrations of high-sensitivity C-reactive protein in patients with metastatic colorectal cancer: results from the ITACa trial

    PubMed Central

    Scarpi, Emanuela; Maltoni, Paolo; Dorizzi, Romolo M.; Passardi, Alessandro; Frassineti, Giovanni Luca; Cortesi, Pietro; Giannini, Maria Benedetta; Marisi, Giorgia; Amadori, Dino; Lucchesi, Alessandro

    2016-01-01

    Serum levels of C-reactive protein are (CRP) higher in patients with neoplastic conditions and numerous studies have been performed to clarify the etiologic and prognostic role of the high-sensitivity CRP (hs-CRP) in cancer. Our study was conducted on patients enrolled in the prospective randomized “Italian Trial in Advanced Colorectal Cancer (ITACa)” to assess hs-CRP levels and their impact on overall survival (OS) and progression-free survival (PFS). Serum samples from 132 ITACa patients were collected at baseline and 2 months after starting first-line chemotherapy. The supernatant was immediately transferred to cryovials and stored at −80°C. After thawing, hs-CRP was measured with the Cobas c501 analyzer. High levels of hs-CRP (≥ 13.1 mg/L) were associated with poorer median PFS (p < 0.0001) and OS (p < 0.0001) than low hs-CRP levels (< 13.1 mg/L). hs-CRP values in 107 patients were evaluated again after 2 months of therapy, revealing that patients with low hs-CRP levels in both baseline and second serum samples had the best median PFS and OS. Our study confirms the prognostic value of hs-CRP in patients with metastatic colorectal carcinoma. PMID:26848624

  19. High-dose atorvastatin causes a rapid sustained increase in human serum PCSK9 and disrupts its correlation with LDL cholesterol.

    PubMed

    Welder, Greg; Zineh, Issam; Pacanowski, Michael A; Troutt, Jason S; Cao, Guoqing; Konrad, Robert J

    2010-09-01

    Proprotein convertase subtilisin kexin type 9 (PCSK9) is a key regulator of serum LDL-cholesterol (LDL-C) levels. PCSK9 is secreted by the liver into the plasma and binds the hepatic LDL receptor (LDLR), causing its subsequent degradation. We first demonstrated that a moderate dose of atorvastatin (40 mg) increases PCSK9 serum levels, suggesting why increasing statin doses may have diminished efficacy with regard to further LDL-C lowering. Since that initial observation, at least two other groups have reported statin-induced PCSK9 increases. To date, no analysis of the effect of high-dose atorvastatin (80 mg) on PCSK9 over time has been conducted. Therefore, we studied the time course of atorvastatin (80 mg) in human subjects. We measured PCSK9 and lipid levels during a 2-week lead-in baseline period and every 4 weeks thereafter for 16 weeks. We observed that atorvastatin (80 mg) caused a rapid 47% increase in serum PCSK9 at 4 weeks that was sustained throughout 16 weeks of dosing. Importantly, while PCSK9 levels were highly correlated with total cholesterol (TC), LDL-C, and triglyceride (TG) levels at baseline, atorvastatin (80 mg) completely abolished all of these correlations. Together, these results further suggest an explanation for why increasing doses of statins fail to achieve proportional LDL-C lowering. PMID:20525997

  20. A simple, accurate, time-saving and green method for the determination of 15 sulfonamides and metabolites in serum samples by ultra-high performance supercritical fluid chromatography.

    PubMed

    Zhang, Yuan; Zhou, Wei-E; Li, Shao-Hui; Ren, Zhi-Qin; Li, Wei-Qing; Zhou, Yu; Feng, Xue-Song; Wu, Wen-Jie; Zhang, Feng

    2016-02-01

    An analytical method based on ultra-high performance supercritical fluid chromatography (UHPSFC) with photo-diode array detection (PDA) has been developed to quantify 15 sulfonamides and their N4-acetylation metabolites in serum. Under the optimized gradient elution conditions, it took only 7min to separate all 15 sulfonamides and the critical pairs of each parent drug and metabolite were completely separated. Variables affecting the UHPSFC were optimized to get a better separation. The performance of the developed method was evaluated. The UHPSFC method allowed the baseline separation and determination of 15 sulfonamides and metabolites with limit of detection ranging from 0.15 to 0.35μg/mL. Recoveries between 90.1 and 102.2% were obtained with satisfactory precision since relative standard deviations were always below 3%. The proposed method is simple, accurate, time-saving and green, it is applicable to a variety of sulfonamides detection in serum samples. PMID:26780846

  1. Simultaneous detection and quantitation of highly water-soluble herbicides in serum using ion-pair liquid chromatography-tandem mass spectrometry.

    PubMed

    Wang, Kuang-Chuan; Chen, Shih-Ming; Hsu, Jung-Fa; Cheng, Sheaw-Guey; Lee, Ching-Kuo

    2008-12-15

    We report the simultaneous screening of highly polar, water-soluble, and less-volatile herbicides, including glyphosate, glufosinate, paraquat, and diquat, in serum using liquid chromatography-mass spectrometry. The herbicides were separated by solid-phase extraction using a Strata-XC cartridge. A heptafluorobutyric acid solution was chosen as the mobile phase for ion-pair liquid chromatography. Mass spectrometry was used for analysis and was optimized for operation in the positive mode for all analytes. The serum specimens were screened for the presence of the herbicides at the following concentrations: 5 ng/mL for glyphosate, 2 ng/mL for glufosinate, 1 ng/mL for diquat, and 5 ng/mL for paraquat. This is the first report on the simultaneous detection of these compounds. PMID:19022710

  2. Serum high expression of miR-214 and miR-135b as novel predictor for myeloma bone disease development and prognosis

    PubMed Central

    Hao, Mu; Zang, Meirong; Zhao, Lei; Deng, Shuhui; Xu, Yan; Qi, Fang; An, Gang; Qin, Yu; Sui, Weiwei; Li, Fei; Yang, Wenjuan; Li, Zengjun; Yi, Shuhua; Zou, Dehui; Zhan, Fenghuang; Qiu, Lugui

    2016-01-01

    Multiple myeloma (MM) originates from malignant plasma cells, leading to multiple destructive lytic bone lesions that occur in more than 80% of MM patients. MicroRNAs have been reported to be involved in development of bone lesions in MM. However, the circulating microRNA as diagnostic and prognostic biomarkers for bone lesions has not been elucidated yet. In this study, we identified differentially expressed miRNAs that are potentially involved in myeloma-related bone disease in serum of MM patients. MiR-214 and miR-135b was shown to be increased in serum of MM patients with bone lesions. Serum level of miR-214 and miR-135b was highly correlated with the severity of lytic bone lesions and demonstrated as a diagnostic tool for identifying bone diseases based on results of a receiver operating characteristic analysis (ROC). In addition, patients with high levels of serum miR-214 had a dismal survival with significantly shortened progression free survival (PFS) and overall survival (OS). Interestingly, bisphosphonates treatment significantly extended PFS and OS in patients with higher level of miR-214 comparing to patients without bisphosphonates treatment. Taken together, our findings revealed the significance of circulating miR-214 and miR-135b levels in detection of bone disease and in prediction of prognosis of patients with multiple myeloma, suggesting its potential clinical applications. The result of this study also set the foundation for searching more circulating miRNA as biomarker for tumor bone lesions. PMID:26995755

  3. High-Density Peptide Microarray Analysis of IgG Autoantibody Reactivities in Serum and Cerebrospinal Fluid of Multiple Sclerosis Patients.

    PubMed

    Hecker, Michael; Fitzner, Brit; Wendt, Matthias; Lorenz, Peter; Flechtner, Kristin; Steinbeck, Felix; Schröder, Ina; Thiesen, Hans-Jürgen; Zettl, Uwe Klaus

    2016-04-01

    Intrathecal immunoglobulin G (IgG) synthesis and oligoclonal IgG bands in cerebrospinal fluid (CSF) are hallmarks of multiple sclerosis (MS), but the antigen specificities remain enigmatic. Our study is the first investigating the autoantibody repertoire in paired serum and CSF samples from patients with relapsing-remitting MS (RRMS), primary progressive MS (PPMS), and other neurological diseases by the use of high-density peptide microarrays. Protein sequences of 45 presumed MS autoantigens (e.g.MOG, MBP, and MAG) were represented on the microarrays by overlapping 15mer peptides. IgG reactivities were screened against a total of 3991 peptides, including also selected viral epitopes. The measured antibody reactivities were highly individual but correlated for matched serum and CSF samples. We found 54 peptides to be recognized significantly more often by serum or CSF antibodies from MS patients compared with controls (pvalues <0.05). The results for RRMS and PPMS clearly overlapped. However, PPMS patients presented a broader peptide-antibody signature. The highest signals were detected for a peptide mapping to a region of the Epstein-Barr virus protein EBNA1 (amino acids 392-411), which is homologous to the N-terminal part of human crystallin alpha-B. Our data confirmed several known MS-associated antigens and epitopes, and they delivered additional potential linear epitopes, which await further validation. The peripheral and intrathecal humoral immune response in MS is polyspecific and includes antibodies that are also found in serum of patients with other diseases. Further studies are required to assess the pathogenic relevance of autoreactive and anti-EBNA1 antibodies as well as their combinatorial value as biomarkers for MS. PMID:26831522

  4. Vitamin D and Risk of Neuroimaging Abnormalities

    PubMed Central

    Littlejohns, Thomas J.; Kos, Katarina; Henley, William E.; Lang, Iain A.; Annweiler, Cedric; Beauchet, Olivier; Chaves, Paulo H. M.; Kestenbaum, Bryan R.; Kuller, Lewis H.; Langa, Kenneth M.; Lopez, Oscar L.; Llewellyn, David J.

    2016-01-01

    Vitamin D deficiency has been linked with an increased risk of incident all-cause dementia and Alzheimer’s disease. The aim of the current study was to explore the potential mechanisms underlying these associations by determining whether low vitamin D concentrations are associated with the development of incident cerebrovascular and neurodegenerative neuroimaging abnormalities. The population consisted of 1,658 participants aged ≥65 years from the US-based Cardiovascular Health Study who were free from prevalent cardiovascular disease, stroke and dementia at baseline in 1992–93. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were determined by liquid chromatography-tandem mass spectrometry from blood samples collected at baseline. The first MRI scan was conducted between 1991–1994 and the second MRI scan was conducted between 1997–1999. Change in white matter grade, ventricular grade and presence of infarcts between MRI scan one and two were used to define neuroimaging abnormalities. During a mean follow-up of 5.0 years, serum 25(OH)D status was not significantly associated with the development of any neuroimaging abnormalities. Using logistic regression models, the multivariate adjusted odds ratios (95% confidence interval) for worsening white matter grade in participants who were severely 25(OH)D deficient (<25 nmol/L) and deficient (≥25–50 nmol/L) were 0.76 (0.35–1.66) and 1.09 (0.76–1.55) compared to participants with sufficient concentrations (≥50 nmol/L). The multivariate adjusted odds ratios for ventricular grade in participants who were severely 25(OH)D deficient and deficient were 0.49 (0.20–1.19) and 1.12 (0.79–1.59) compared to those sufficient. The multivariate adjusted odds ratios for incident infarcts in participants who were severely 25(OH)D deficient and deficient were 1.95 (0.84–4.54) and 0.73 (0.47–1.95) compared to those sufficient. Overall, serum vitamin D concentrations could not be shown to be associated with

  5. Vitamin D and Risk of Neuroimaging Abnormalities.

    PubMed

    Littlejohns, Thomas J; Kos, Katarina; Henley, William E; Lang, Iain A; Annweiler, Cedric; Beauchet, Olivier; Chaves, Paulo H M; Kestenbaum, Bryan R; Kuller, Lewis H; Langa, Kenneth M; Lopez, Oscar L; Llewellyn, David J

    2016-01-01

    Vitamin D deficiency has been linked with an increased risk of incident all-cause dementia and Alzheimer's disease. The aim of the current study was to explore the potential mechanisms underlying these associations by determining whether low vitamin D concentrations are associated with the development of incident cerebrovascular and neurodegenerative neuroimaging abnormalities. The population consisted of 1,658 participants aged ≥65 years from the US-based Cardiovascular Health Study who were free from prevalent cardiovascular disease, stroke and dementia at baseline in 1992-93. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were determined by liquid chromatography-tandem mass spectrometry from blood samples collected at baseline. The first MRI scan was conducted between 1991-1994 and the second MRI scan was conducted between 1997-1999. Change in white matter grade, ventricular grade and presence of infarcts between MRI scan one and two were used to define neuroimaging abnormalities. During a mean follow-up of 5.0 years, serum 25(OH)D status was not significantly associated with the development of any neuroimaging abnormalities. Using logistic regression models, the multivariate adjusted odds ratios (95% confidence interval) for worsening white matter grade in participants who were severely 25(OH)D deficient (<25 nmol/L) and deficient (≥25-50 nmol/L) were 0.76 (0.35-1.66) and 1.09 (0.76-1.55) compared to participants with sufficient concentrations (≥50 nmol/L). The multivariate adjusted odds ratios for ventricular grade in participants who were severely 25(OH)D deficient and deficient were 0.49 (0.20-1.19) and 1.12 (0.79-1.59) compared to those sufficient. The multivariate adjusted odds ratios for incident infarcts in participants who were severely 25(OH)D deficient and deficient were 1.95 (0.84-4.54) and 0.73 (0.47-1.95) compared to those sufficient. Overall, serum vitamin D concentrations could not be shown to be associated with the development of

  6. Spirometric abnormalities among welders

    SciTech Connect

    Rastogi, S.K.; Gupta, B.N.; Husain, T.; Mathur, N.; Srivastava, S. )

    1991-10-01

    A group of manual welders age group 13-60 years having a mean exposure period of 12.4 {plus minus} 1.12 years were subjected to spirometry to evaluate the prevalence of spirometric abnormalities. The welders showed a significantly higher prevalence of respiratory impairment than that observed among the unexposed controls as a result of exposure to welding gases which comprised fine particles of lead, zinc, chromium, and manganese. This occurred despite the lower concentration of the pollutants at the work place. In the expose group, the smoking welders showed a prevalence of respiratory impairment significantly higher than that observed in the nonsmoking welders. The results of the pulmonary function tests showed a predominantly restrictive type of pulmonary impairment followed by a mixed ventilatory defect among the welders. The effect of age on pulmonary impairment was not discernible. Welders exposed for over 10 years showed a prevalence of respiratory abnormalities significantly higher than those exposed for less than 10 years. Smoking also had a contributory role.

  7. Serum lactate dehydrogenase levels at presentation in stage IV non-small cell lung cancer: predictive value of metastases and relation to survival outcomes.

    PubMed

    Lee, Dong Soo; Park, Kyung Ran; Kim, Seung Joon; Chung, Mi Joo; Lee, Yun Hee; Chang, Ji Hyun; Kang, Jin Hyoung; Hong, Sook Hee; Kim, Myung Sin; Kim, Yeon Sil

    2016-01-01

    This study aimed to evaluate the clinical correlations between serum lactate dehydrogenase (LDH) levels and tumor characteristics and to investigate the prognostic impact of serum LDH levels in advanced non-small cell lung cancer (NSCLC). A total of 394 patients were included in the present study between June 2007 and January 2013. All eligible patients had serum LDH levels available before treatment, and whole-body metastatic extent was measured using whole-body metastatic scores, as determined by 18(F)-fludeoxyglucose positron emission tomography scans from 1 to 7 as the sum of each metastatic region. The diagnostic cutoff value for an abnormal serum LDH level was 450 IU/L. The median serum LDH level was 477 IU/L (range, 113-2850), and 224 (56.9 %) patients had abnormal serum LDH levels. The serum LDH levels showed no significant associations with age, gender, histology, tumor differentiation, and smoking history. However, the proportion of patients with abnormal serum LDH levels was statistically significantly higher in the high total metastatic score group (scores 3-7) than in the low total metastatic score group (scores 1-2) (65.3 vs 50.4 %, p = 0.001). In a multivariate survival analysis, age (p = 0.001), gender (p = 0.001), histology (p = 0.003), tumor differentiation (p = 0.001), Eastern Cooperative Oncology Group (ECOG) performance status (p = 0.001), LDH levels (p = 0.046), and treatment factors (p = 0.001) proved to be independent prognostic factors for survival outcomes. The results of this study suggest that the serum LDH levels at presentation may be significantly correlated with whole-body tumor extent and might independently but modestly prognosticate OS in stage IV NSCLC. PMID:26240025

  8. High Incidence of Progressive Postnatal Cerebellar Enlargement in Costello Syndrome: Brain Overgrowth Associated with HRAS Mutations as the Likely Cause of Structural Brain and Spinal Cord Abnormalities

    PubMed Central

    Gripp, Karen W.; Hopkins, Elisabeth; Doyle, Daniel; Dobyns, William B.

    2010-01-01

    Costello syndrome is a rasopathy caused by germline mutations in the proto-oncogene HRAS. Its presentation includes failure-to-thrive with macrocephaly, characteristic facial features, hypertrophic cardiomyopathy, papillomata, malignant tumors, and cognitive impairment. In a systematic review we found absolute or relative macrocephaly (100%), ventriculomegaly (50%), and other abnormalities on brain and spinal cord imaging studies in 27/28 individuals. Posterior fossa crowding with cerebellar tonsillar herniation (CBTH) was noted in 27/28 (96%), and in 10/17 (59%) with serial studies posterior fossa crowding progressed. Sequelae of posterior fossa crowding and CBTH included hydrocephalus requiring shunt or ventriculostomy (25%), Chiari 1 malformation (32%) and syrinx formation (25%). Our data reveal macrocephaly with progressive frontal bossing and CBTH, documenting an ongoing process rather than a static congenital anomaly. Comparison of images obtained in young infants to subsequent studies demonstrated postnatal development of posterior fossa crowding. This process of evolving megalencephaly and cerebellar enlargement is in keeping with mouse model data, delineating abnormal genesis of neurons and glia, resulting in an increased number of astrocytes and enlarged brain volume. In Costello syndrome and macrocephaly-capillary malformation syndrome disproportionate brain growth is the main factor resulting in postnatal CBTH and Chiari 1 malformation. PMID:20425820

  9. Lack of Evidence for Regional Brain Volume or Cortical Thickness Abnormalities in Youths at Clinical High Risk for Psychosis: Findings From the Longitudinal Youth at Risk Study.

    PubMed

    Klauser, Paul; Zhou, Juan; Lim, Joseph K W; Poh, Joann S; Zheng, Hui; Tng, Han Ying; Krishnan, Ranga; Lee, Jimmy; Keefe, Richard S E; Adcock, R Alison; Wood, Stephen J; Fornito, Alex; Chee, Michael W L

    2015-11-01

    There is cumulative evidence that young people in an "at-risk mental state" (ARMS) for psychosis show structural brain abnormalities in frontolimbic areas, comparable to, but less extensive than those reported in established schizophrenia. However, most available data come from ARMS samples from Australia, Europe, and North America while large studies from other populations are missing. We conducted a structural brain magnetic resonance imaging study from a relatively large sample of 69 ARMS individuals and 32 matched healthy controls (HC) recruited from Singapore as part of the Longitudinal Youth At-Risk Study (LYRIKS). We used 2 complementary approaches: a voxel-based morphometry and a surface-based morphometry analysis to extract regional gray and white matter volumes (GMV and WMV) and cortical thickness (CT). At the whole-brain level, we did not find any statistically significant difference between ARMS and HC groups concerning total GMV and WMV or regional GMV, WMV, and CT. The additional comparison of 2 regions of interest, hippocampal, and ventricular volumes, did not return any significant difference either. Several characteristics of the LYRIKS sample like Asian origins or the absence of current illicit drug use could explain, alone or in conjunction, the negative findings and suggest that there may be no dramatic volumetric or CT abnormalities in ARMS. PMID:25745033

  10. Spontaneous remission of acute myeloid leukemia relapse after hematopoietic cell transplantation in a high-risk patient with 11q23/MLL abnormality.

    PubMed

    Hudecek, Michael; Bartsch, Kristina; Jäkel, Nadja; Heyn, Simone; Pfannes, Roald; Al-Ali, Haifa Kathrin; Cross, Michael; Pönisch, Wolfram; Gerecke, Ulrich; Edelmann, Jeanett; Ittel, Thomas; Niederwieser, Dietger

    2008-01-01

    A 35-year-old female patient was diagnosed with acute myeloid leukemia with multiple genetic aberrations [48 XX, del(3)(q21), +6, t(11;15)(q23;q15), +21] including an 11q23/MLL abnormality. The patient achieved a complete remission after one induction chemotherapy cycle. After three courses of consolidation, a matched unrelated hematopoietic cell transplantation (HCT) was performed. Following an upper respiratory tract infection 7 years after transplant, her blood counts declined to leukocytes of 1 x 10(9)/l, platelets of 51 x 10(9)/l and hemoglobin of 7.5 g/dl. A bone marrow aspirate revealed 55% leukemic blasts carrying the unfavorable genetic aberrations seen at initial diagnosis (11q23/MLL). In the absence of any disease-specific treatment, the leukemic blasts cleared from the bone marrow within 6 days after diagnosis of relapse and peripheral blood counts returned to normal. Molecular analysis of the 11q23/MLL rearrangement was used to evaluate minimal residual disease, which became undetectable in repetitive FISH analyses. This is the first report of spontaneous remission in a patient with initially a multiaberrant leukemic cell clone and a proven 11q23/MLL abnormality at relapse after HCT. PMID:18367831

  11. High intake of fatty fish, but not of lean fish, affects serum concentrations of TAG and HDL-cholesterol in healthy, normal-weight adults: a randomised trial.

    PubMed

    Hagen, Ingrid V; Helland, Anita; Bratlie, Marianne; Brokstad, Karl A; Rosenlund, Grethe; Sveier, Harald; Mellgren, Gunnar; Gudbrandsen, Oddrun A

    2016-08-01

    The aim of the present study was to examine whether high intake of lean or fatty fish (cod and farmed salmon, respectively) by healthy, normal-weight adults would affect risk factors of type 2 diabetes and CVD when compared with lean meat (chicken). More knowledge is needed concerning the potential health effects of high fish intake (>300 g/week) in normal-weight adults. In this randomised clinical trial, thirty-eight young, healthy, normal-weight participants consumed 750 g/week of lean or fatty fish or lean meat (as control) for 4 weeks at dinner according to provided recipes to ensure similar ways of preparations and choices of side dishes between the groups. Energy and macronutrient intakes at baseline and end point were similar in all groups, and there were no changes in energy and macronutrient intakes within any of the groups during the course of the study. High intake of fatty fish, but not lean fish, significantly reduced TAG and increased HDL-cholesterol concentrations in fasting serum when compared with lean meat intake. When compared with lean fish intake, fatty fish intake increased serum HDL-cholesterol. No differences were observed between lean fish, fatty fish and lean meat groups regarding fasting and postprandial glucose regulation. These findings suggest that high intake of fatty fish, but not of lean fish, could beneficially affect serum concentrations of TAG and HDL-cholesterol, which are CVD risk factors, in healthy, normal-weight adults, when compared with high intake of lean meat. PMID:27363518

  12. Abnormal ferrite in hyper-eutectoid steels

    SciTech Connect

    Chairuangsri, T.; Edmonds, D.V.

    2000-04-19

    The microstructural characteristics of ultra-high carbon hyper-eutectoid Fe-C and Fe-C-Cu experimental steels have been examined after isothermal transformation in a range just beneath the eutectoid temperature. Particular attention was paid to the formation of so-called abnormal ferrite, which refers to coarse ferrite grains which can form, in hyper-eutectoid compositions, on the pro-eutectoid cementite before the pearlite reaction occurs. Thus it is confirmed that the abnormal ferrite is not a result of pearlite coarsening, but of austenite decomposition before the conditions for coupled growth of pearlite are established. The abnormal ferrite formed on both allotriomorphic and Widmanstaetten forms of pro-eutectoid cementite, and significantly, it was observed that the pro-eutectoid cementite continued to grow, despite being enclosed by the abnormal ferrite. Under certain conditions this could lead to the eventual formation of substantially reduced amounts of pearlite. Thus, a model for carbon redistribution that allows the proeutectoid cementite to thicken concurrently with the abnormal ferrite is presented. The orientation relationships between the abnormal ferrite and pro-eutectoid cementite were also determined and found to be close to those which have been reported between pearlitic ferrite and pearlitic cementite.

  13. Prevalence of asymptomatic urinary abnormalities among adolescents.

    PubMed

    Fouad, Mohamed; Boraie, Maher

    2016-05-01

    To determine the prevalence of asymptomatic urinary abnormalities in adolescents, first morning clean mid-stream urine specimens were obtained from 2500 individuals and examined by dipstick and light microscopy. Adolescents with abnormal screening results were reexamined after two weeks and those who had abnormal results twice were subjected to systemic clinical examination and further clinical and laboratory investigations. Eight hundred and three (32.1%) individuals had urinary abnormalities at the first screening, which significantly decreased to 345 (13.8%) at the second screening, (P <0.001). Hematuria was the most common urinary abnormalities detected in 245 (9.8%) adolescents who had persistent urine abnormalities; 228 (9.1%) individuals had non glomerular hematuria. The hematuria was isolated in 150 (6%) individuals, combined with leukocyturia in 83 (3.3%) individuals, and combined with proteinuria in 12 (0.5%) individuals. Leukocyturia was detected in 150 (6%) of all studied adolescents; it was isolated in 39 (1.6%) individuals and combined with proteinuria in 28 (1.1%) of them. Asymptomatic bacteriuria was detected in 23 (0.9%) of all studied adolescents; all the cases were females. Proteinuria was detected in 65 (2.6%) of all the studied adolescents; 45 (1.8%) individuals had <0.5 g/day and twenty (0.8%) individuals had 0.5-3 g/day. Asymptomatic urinary abnormalities were more common in males than females and adolescents from rural than urban areas (P <0.01) and (P <0.001), respectively. The present study found a high prevalence of asymptomatic urinary abnormalities among adolescents in our population. PMID:27215241

  14. An improvement in the attaching capability of cryopreserved human hepatocytes by a proteinaceous high molecule, sericin, in the serum-free solution.

    PubMed

    Miyamoto, Yoshitaka; Teramoto, Naozumi; Hayashi, Shuji; Enosawa, Shin

    2010-01-01

    The methodology of cryopreservation of human hepatocytes remains unsatisfactory. Even when the viability of thawed cells is tolerable, the cells often lose the attaching capability to a culture dish, resulting in the cells' inability to survive. Previously, we described the effectiveness of maltose on the attachment of hepatocytes. This article demonstrates that a silk-derived high molecular protein, sericin, improves the cell-attaching capability in the serum-free freezing medium. When human hepatocytes [initial viability: 60.9 ± 3.1% (mean ± SD, n = 3)] were frozen with serum-free Dulbecco's modified Eagle medium (DMEM) containing 10% dimethyl sulfoxide (DMSO), the viability was 29.4 ± 3.2% and the cell-attaching capability 20.4 ± 4.1%. On the other hand, DMEM containing 10% DMSO and 1% sericin increased the values to 45.0 ± 0.8% and 26.2 ± 3.2%. Moreover, the addition of 0.1 mol/L maltose to the sericin-containing medium improved to 42.2 ± 3.2% and 51.1 ± 1.0%, as we demonstrated in a previous report. The present results indicated that sericin combined with maltose is a novel additive in the serum-free freezing medium for human hepatocytes. PMID:20525438

  15. Sustained high levels of serum leptin rather than IL-6 observed in patients with postpartum thyroiditis during their first postpartum year.

    PubMed

    Guo, Huiling; Liu, Xiu; Li, Chenyang; Li, Yushu; Sang, Miao; Shan, Zhongyan; Teng, Weiping; Guan, Haixia

    2014-11-01

    The purpose of the study is to explore the roles of leptin and interleukin-6 (IL-6) during the first postpartum year in the occurrence and development of postpartum thyroiditis (PPT). We retrospectively collected serum samples from 57 PPT patients consisting of 34 overt PPT (O-PPT) and 23 subclinical PPT (S-PPT) in addition to 37 healthy postpartum women at four postpartum time points, i.e., 3-day and 3, 6, 12-month postpartum. Serum leptin and IL-6 levels were measured by radioimmunoassay and ELISA assay, respectively. Leptin level and leptin/BMI (LEP/BMI) ratio were higher in PPT patients than in control during the first postpartum year, but were not significantly different between O-PPT and S-PPT. However, a similar trend but did not reach significant difference in IL-6 level was observed during the postpartum period in PPT patients and control women. We conclude that a sustained high level of serum leptin after delivery may be involved in the pathogenesis of PPT. IL-6 does not contribute to the development of PPT. PMID:24573491

  16. Fluorocarbon-bonded magnetic mesoporous microspheres for the analysis of perfluorinated compounds in human serum by high-performance liquid chromatography coupled to tandem mass spectrometry.

    PubMed

    Liu, Xiaodan; Yu, Yingjia; Li, Yan; Zhang, Haiying; Ling, Jin; Sun, Xueni; Feng, Jianan; Duan, Gengli

    2014-09-24

    We report herein an extraction method for the analysis of perfluorinated compounds in human serum based on magnetic core-mesoporous shell microspheres with decyl-perfluorinated interior pore-walls (Fe3O4@mSiO2-F17). Thanks to the unique properties of the Fe3O4@mSiO2-F17 microspheres, macromolecules like proteins could be easily excluded from the mesoporous channels due to size exclusion effect, and perfluorinated compounds (PFCs) in protein-rich biosamples such as serum could thus be directly extracted with the fluorocarbon modified on the channel wall without any other pretreatment procedure. The PFCs adsorbed Fe3O4@mSiO2-F17 microspheres could then be simply and rapidly isolated by using a magnet, followed by being identified and quantified by LC-MS/MS (high-performance liquid chromatography coupled to tandem mass spectrometry). Five perfluorinatedcarboxylic acids (C6, C8-C11) and perfluorooctane sulfonate (PFOS) were selected as model analytes. In order to achieve the best extraction efficiency, some important factors including the amount of Fe3O4@mSiO2-F17 microspheres added, adsorption time, type of elution solvent, eluting solvent volume and elution time were investigated. The ranges of the LOD were 0.02-0.05 ng mL(-1) for the six PFCs. The recovery of the optimized method varies from 83.13% to 92.42% for human serum samples. PMID:25172813

  17. Two doses of parenterally administered split influenza virus vaccine elicited high serum IgG concentrations which effectively limited viral shedding upon challenge in mice.

    PubMed

    Hovden, A-O; Cox, R J; Madhun, A; Haaheim, L R

    2005-10-01

    We have previously found that whole influenza virus vaccine induced a more rapid and stronger humoral response, particularly after the first dose of vaccine, than split virus vaccine in mice. In this study, we have evaluated the protective efficacy of whole and split influenza virus vaccines in mice using a nonlethal upper respiratory tract challenge model. We have also investigated the immunological correlates associated with no or very little viral shedding after viral challenge. Vaccination resulted in reduced viral shedding and shortened the duration of infection by at least 2 days. After one dose of vaccine, whole virus vaccine generally resulted in less viral shedding than split virus vaccine. In contrast, two doses of split virus vaccine, particularly the highest vaccine strengths of 15 and 30 microg HA, most effectively limited viral replication and these mice had high concentrations of prechallenge influenza-specific serum IgG. The vaccine formulation influenced the IgG2a/IgG1 ratio, and this IgG subclass profile was maintained upon challenge to some extent, although it did not influence the level of viral shedding. The concentration of postvaccination serum IgG showed an inverse relationship with the level of viral shedding after viral challenge. Therefore, serum IgG is an important factor in limiting viral replication in the upper respiratory tract upon challenge of an antigenically similar virus. PMID:16253121

  18. Determination of aluminum in the human serum of a dialysis patient by ion-pair reversed-phase partition high-performance liquid chromatography.

    PubMed

    Kaneko, E; Hoshino, H; Yotsuyanagi, T; Gunji, N; Sato, M; Kikuta, T; Yuasa, M

    1991-10-15

    An ion-pair reversed-phase partition high-performance liquid chromatography-spectrophotometric method is described for the determination of aluminum in human serum, based on its complexation with 2,2'-dihydroxyazobenzene. The chelate is separated on C18-bonded silica packing by using an aqueous methanol mobile phase containing tetrabutylammonium bromide and is detected with 0.005 AU full-scale at 510 nm. The proposed system offers a simple, sensitive, and selective method. The detection limits defined as twice the standard deviation of the blank signal, are 0.2 micrograms L-1 in pure solution and 6 micrograms L-1 in serum. The sample solution is prepared from 0.4 mL of serum after protein precipitation with hydrochloric acid and methanol. There was good agreement between the values obtained by this method and graphite furnace atomic absorption spectrophotometry. The aluminum concentrations in 121 patients on hemodialysis were 6-201 micrograms L-1. PMID:1759707

  19. A new mammalian host cell with enhanced survival enables completely serum-free development of high-level protein production cell lines.

    PubMed

    Rossi, Diane L; Rossi, Edmund A; Goldenberg, David M; Chang, Chien-Hsing

    2011-01-01

    With over 25 monoclonal antibodies (mAbs) currently approved and many more in development, there is considerable interest in gaining improved productivity by increasing cell density and enhancing cell survival of production cell lines. In addition, high costs and growing safety concerns with use of animal products have made the availability of serum-free cell lines more appealing. We elected to transfect the myeloma cell line Sp2/0-Ag14 with Bcl2-EEE, the constitutively active phosphomimetic mutant of Bcl2, for extended cell survival. After adaptation of the initial transfectants to serum-independent growth, a clone with superior growth properties, referred to as SpESF, was isolated and further subjected to iterative rounds of stressful growth over a period of 4 months. The effort resulted in the selection of a promising clone, designated SpESFX-10, which was shown to exhibit robust growth and resist apoptosis induced by sodium butyrate or glutamine deprivation. The advantage of SpESFX-10 as a host for generating mAb-production cell lines was demonstrated by its increased transfection efficiency, culture longevity, and mAb productivity, as well as by the feasibility of accomplishing the entire cell line development process, including transfection, subcloning, and cryopreservation, in the complete absence of serum. PMID:21473000

  20. Comparative Study of Tomato and Tomato Paste Supplementation on the Level of Serum Lipids and Lipoproteins Levels in Rats Fed With High Cholesterol

    PubMed Central

    Khayat Nouri, Mir Hadi; Namvaran Abbas Abad, Ali

    2013-01-01

    Background Hypercholesterolemia is one of the risk factors of cardiovascular diseases. Increased blood cholesterol affects general health and increases mortality due to cardiovascular disease. Poor nutrition increases LDL cholesterol and decreases LDL receptor activities in the liver. Scientists have shown that consumption of antioxidants can reduce hypercholesterolemia and proved benefits of fruit and vegetables. Tomato reduces oxidative stress by increasing serum total antioxidant level. Objectives This study compared the tomato and tomato paste supplementation on the level of serum lipids and lipoproteins in rats fed with high cholesterol. Materials and Methods In this study, four male rat groups (10 rats per group) were used. Control group received basal diet, second group received basal diet and 2% cholesterol (Chol), third and fourth groups received basal diet, 2% cholesterol tomato and tomato paste respectively (20 percent of the diet) for a month. Then serum TC, LDL, HDL and TG were measured. Results Results showed that in Chol group, all lipids increased significantly (P < 0.05) except HDL compared to the control group. Tomato and tomato paste supplementation decreased TC, LDL and TG concentration significantly (P < 0.05) compared to Chol group. Tomato paste had the higher effect on lipids decreasing than tomato. Conclusions Decreases of TC, LDL and TG may be related to tomato antioxidant effect. This course in human required more investigations. PMID:24082999

  1. Expression of the High Affinity IgE Receptor by Neutrophils of Individuals with Allergic Asthma is Both Minimal and Insensitive to Regulation by Serum IgE

    PubMed Central

    Mora, Juanita; Riggs, Emily K.; Fu, Jun; MacGlashan, Donald W.; Fox, Susan A.; Yu, Byung; Tobin, Mary C.; Thomas, Larry L.

    2009-01-01

    We evaluated the hypothesis that serum IgE regulates neutrophil FcεRI expression in the same manner as described for other FcεRI+ cells. FcεRI expression by neutrophils of 40 asthma subjects and 20 control subjects did not correlate with serum IgE levels, whereas FcεRI expression by basophils of the same subjects showed a highly significant correlation. The level of FcεRI expression by neutrophils of both asthma and control subjects was approximately 1% of that for basophil FcεRI expression. IgE+ neutrophils were minimally detectable, and FcεRI α subunit was not detected in Western blots of neutrophil membranes and cytosol. The neutrophil FcεRI did not support anti-IgE stimulated superoxide release or IgE-induced increase in neutrophil survival. We conclude that FcεRI expression by neutrophils of both asthma patients and control individuals is minimal at best and that, if present, neutrophil FcεRI expression, unlike that of other human FcεRI+ cells, is not regulated by serum IgE. PMID:19359220

  2. Development of a high-throughput LC/APCI-MS method for the determination of thirteen phytoestrogens including gut microbial metabolites in human urine and serum.

    PubMed

    Wyns, Ciska; Bolca, Selin; De Keukeleire, Denis; Heyerick, Arne

    2010-04-15

    The investigation into the potential usefulness of phytoestrogens in the treatment of menopausal symptoms requires large-scale clinical trials that involve rapid, validated assays for the characterization and quantification of the phytoestrogenic precursors and their metabolites in biological matrices, as large interindividual differences in metabolism and bioavailability have been reported. Consequently, a new sensitive high-performance liquid chromatography-mass spectrometry method (HPLC-MS) for the quantitative determination of thirteen phytoestrogens including their most important gut microbial metabolites (genistein, daidzein, equol, dihydrodaidzein, O-desmethylangolensin, coumestrol, secoisolariciresinol, matairesinol, enterodiol, enterolactone, isoxanthohumol, xanthohumol and 8-prenylnaringenin) in human urine and serum within one single analytical run was developed. The method uses a simple sample preparation procedure consisting of enzymatic deconjugation followed by liquid-liquid extraction (LLE) or solid-phase extraction (SPE) for urine or serum, respectively. The phytoestrogens and their metabolites are detected with a single quadrupole mass spectrometer using atmospheric pressure chemical ionization (APCI), operating both in the positive and the negative mode. This bioanalytical method has been fully validated and proved to allow an accurate and precise quantification of the targeted phytoestrogens and their metabolites covering the lower parts-per-billion range for the measurement of relevant urine and serum levels following ingestion of phytoestrogen-rich dietary supplements. PMID:20299290

  3. Serum-derived exosomes from mice with highly metastatic breast cancer transfer increased metastatic capacity to a poorly metastatic tumor.

    PubMed

    Gorczynski, Reginald M; Erin, Nuray; Zhu, Fang

    2016-02-01

    Altered interaction between CD200 and CD200R represents an example of "checkpoint blockade" disrupting an effective, tumor-directed, host response in murine breast cancer cells. In CD200R1KO mice, long-term cure of EMT6 breast cancer, including metastatic spread to lung and liver, was achieved in BALB/c mice. The reverse was observed with 4THM tumors, an aggressive, inflammatory breast cancer, with increased tumor metastasis in CD200R1KO. We explored possible explanations for this difference. We measured the frequency of circulating tumor cells (CTCs) in peripheral blood of tumor bearers, as well as lung/liver and draining lymph nodes. In some cases mice received infusions of exosomes from nontumor controls, or tumor bearers, with/without additional infusions of anticytokine antibodies. The measured frequency of circulating tumor cells (CTCs) in peripheral blood was equivalent in the two models in WT and CD200R1KO mice. Increased metastasis in EMT6 tumor bearers was seen in vivo following adoptive transfer of serum, or serum-derived exosomes, from 4THM tumor bearers, an effect which was attenuated by anti-IL-6, and anti-IL-17, but not anti-TNFα, antibody. Anti-IL-6 also attenuated enhanced migration of EMT6 cells in vitro induced by 4THM serum or exosomes, or recombinant IL-6. Exosome cytokine proteomic profiles responses in 4THM and EMT6 tumor-bearing mice were regulated by CD200:CD200R interactions, with attenuation of both IL-6 and IL-17 in 4THM CD200(tg) mice, and enhanced levels in 4THM CD200R1KO mice. We suggest these cytokines act on the microenvironment at sites within the host, and/or directly on tumor cells themselves, to increase metastatic potential. PMID:26725371

  4. Application of high-performance liquid chromatography combined with ultra-sensitive thermal lens spectrometric detection for simultaneous biliverdin and bilirubin assessment at trace levels in human serum.

    PubMed

    Martelanc, Mitja; Žiberna, Lovro; Passamonti, Sabina; Franko, Mladen

    2016-07-01

    We present the applicability of a new ultra-sensitive analytical method for the simultaneous determination of biliverdin and bilirubin in human serum. The method comprises isocratic reversed-phase (RP) C18 high-performance liquid chromatography (HPLC) and thermal lens spectrometric detection (TLS) based on excitation by a krypton laser emission line at 407nm. This method enables the separation of IX-α biliverdin and IX-α bilirubin in 11min with limit of detection (LOD) and limit of quantitation (LOQ) for biliverdin of 1.2nM and 3nM, and 1nM and 2.8nM for bilirubin, respectively. In addition, a step-gradient elution was set up, by changing the mobile phase composition, in order to further enhance the sensitivity for bilirubin determination with LOD and LOQ of 0.5nM and 1.5nM, respectively. In parallel, an isocratic HPLC-DAD method was developed for benchmarking against HPLC-TLS methods. The LOD and LOQ for biliverdin were 6nM and 18nM, and 2.5nM and 8nM for bilirubin, respectively. Additionally, both isocratic methods were applied for measuring biliverdin and free bilirubin in human serum samples (from 2 male and 2 female healthy donors). Combining isocratic HPLC method with TLS detector was crucial for first ever biliverdin determination in serum together with simultaneous free bilirubin determination. We showed for the first time the concentration ratio of free bilirubin versus unbound biliverdin in human serum samples. PMID:27154653

  5. Two high performance liquid chromatographic methods for the determination of alpha-tocopherol in serum compared to isotope dilution-gas chromatography-mass spectrometry.

    PubMed

    Kock, R; Seitz, S; Delvoux, B; Greiling, H

    1997-05-01

    Two high performance liquid chromatographic methods (HPLC) with isocratic reversed-phase separation are presented for the determination of alpha-tocopherol (vitamin E) in serum. In the first method alpha-tocopherol acetate is used as internal standard, detection of absorbance is performed at 284 nm. In the second method tocol is used as internal standard, detection of fluorescence is performed with an excitation wavelength of 292 nm and emission wavelength of 325 nm. Both methods require a liquid-liquid extraction as sample preparation. The results of both HPLC methods have been tested by method comparison for n = 25 serum samples versus an isotope dilution-gas chromatography-mass spectrometry (ID-GC-MS) method using alpha-tocopherol-d6 as internal standard. The imprecision within-run was lower than 2.5% for the UV method and lower than 1% for the fluorescence method for both standards and serum pools. The between-run imprecision, obtained for serum pools, was below 5% for the UV method and not higher than 1.5% for the fluorescence method and not higher 1.8% for the ID-GC-MS. Recovery experiments performed by spiking pool sera with alpha-tocopherol showed recoveries between 98.5% and 100.6% for all methods studied. The result of the method comparison was a coefficient of correlation of r = 0.998 for the HPLC method with fluorescence detection to the ID-GC-MS reference method and a coefficient of correlation of r = 0.981 for the HPLC method with UV detection to the ID-GC-MS reference method. Both methods presented are useful for the analysis of alpha-tocopherol in patient samples. If detection of fluorescence is used, imprecision and inaccuracy of the HPLC method are comparable to the ID-GC-MS chosen as reference method. PMID:9189742

  6. High-mobility group box-1 protein and keratin-18, circulating serum proteins informative of acetaminophen-induced necrosis and apoptosis in vivo.

    PubMed

    Antoine, Daniel J; Williams, Dominic P; Kipar, Anja; Jenkins, Rosalind E; Regan, Sophie L; Sathish, Jean G; Kitteringham, Neil R; Park, B Kevin

    2009-12-01

    Drug-induced hepatotoxicity represents a major clinical problem and an impediment to new medicine development. Serum biomarkers hold the potential to provide information about pathways leading to cellular responses within inaccessible tissues, which can inform the medicinal chemist and the clinician with respect to safe drug design and use. Hepatocyte apoptosis, necrosis, and innate immune activation have been defined as features of the toxicological response associated with the hepatotoxin acetaminophen (APAP). Within this investigation, we have unambiguously identified and characterized by liquid chromatography-tandem mass spectrometry differing circulating molecular forms of high-mobility group box-1 protein (HMGB1) and keratin-18 (K18), which are linked to the mechanisms and pathological changes induced by APAP in the mouse. Hypoacetylated HMGB1 (necrosis indicator), caspase-cleaved K18 (apoptosis indicator), and full-length K18 (necrosis indicator) present in serum showed strong correlations with the histological time course of cell death and was more sensitive than alanine aminotransferase activity. We have further identified a hyperacetylated form of HMGB1 (inflammatory indicator) in serum, which indicated that hepatotoxicity was associated with an inflammatory response. The inhibition of APAP-induced apoptosis and K18 cleavage by the caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp(OMe) fluoromethyl ketone are associated with increased hepatic damage, by a shift to necrotic cell death only. These findings illustrate the initial verification of K18 and HMGB1 molecular forms as serum-based sensitive tools that provide insights into the cellular dynamics involved in APAP hepatotoxicity within an inaccessible tissue. Based on these findings, potential exists for the qualification and measurement of these proteins to further assist in vitro, in vivo, and clinical bridging in toxicological research. PMID:19783637

  7. Increased serum triglyceride clearance and elevated high-density lipoprotein 2 and 3 cholesterol during treatment of primary hypertriglyceridemia with bezafibrate☆

    PubMed Central

    Sakuma, Nagahiko; Ikeuchi, Reiko; Hibino, Takeshi; Yoshida, Takayuki; Mukai, Seiji; Akita, Sachie; Yajima, Kazuhiro; Miyabe, Hiromichi; Goto, Toshihiko; Takada, Norio; Ohte, Nobuyuki; Kunimatu, Mitoshi; Kimura, Genjiro

    2003-01-01

    Background Hypertriglyceridemia accompanied by low levels of high-density lipoprotein cholesterol (HDL-C) is a risk factor for coronary artery disease. High-density lipoprotein 2 (HDL2) and 3 (HDL3) are believed to suppress the progress of atherosclerosis through reverse cholesterol transport. As a result, peripheral tissues can be protected against excessive accumulation of cholesterol. Although bezafibrate is known to accelerate the increase of HDL-C, results are not standardized regarding increases of HDL3 and HDL2 subfractions. Objective This study assessed the effects of bezafibrate on serum triglyceride (TG) fractional clearance rate (K2) and HDL2 and HDL3 cholesterol (HDL2-C and HDL3-C, respectively) levels in patients with primary hypertriglyceridemia (serum TG ≥150 mg/dL). Methods Outpatients with primary hypertriglyceridemia were enrolled in this 8-week study conducted at the Third Department of Internal Medicine, Nagoya City University Hospital (Nagoya, Japan). Oral bezafibrate was administered at a dose of 400 mg/d (200-mg tablet BID, morning and evening) for 8 weeks. After 8 weeks, serum levels of total cholesterol (TC), TG, HDL-C, HDL2-C, and HDL3-C were measured. A fat emulsion tolerance test to assess K2 and measurements of plasma lipoprotein lipase (LPL) mass, LPL activity, and hepatic triglyceride lipase (HTGL) activity in postheparin plasma were performed before bezafibrate administration and after the course of treatment. Results Sixteen patients (10 men, 6 women; mean [SD] age, 54 [12] years [range, 30–69 years]; mean [SD] body mass index, 23 [2] kg/m2) entered the study. The following findings were observed in male and female patients after 8 weeks of treatment. A statistically significant reduction was observed in mean serum TG level (P<0.01). Significant increases were seen in HDL-C, HDL2-C, and HDL3-C (all P<0.01), K2 (P<0.01), and in plasma LPL mass (P<0.01) and LPL activity (P<0.05). TC level and HTGL activity did not change

  8. Characterization of the abnormal lipid profile in Chinese patients with psoriasis

    PubMed Central

    Pang, Xiaowen; Lin, Kai; Liu, Wen; Zhang, Ping; Zhu, Sainan

    2015-01-01

    Psoriasis is a chronic inflammatory skin disease that has been associated with abnormal lipid metabolism. To characterize the lipid profile in Chinese, 86 patients with psoriasis and 84 healthy control subjects were assessed. Compared with healthy controls, the fasting serum values of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (ApoA-I) were lower in the patient group. Compared with vulgaris psoriasis, special types of psoriasis had even lower levels of HDL-C and ApoA-I. Considering the severity of psoriasis, the level of ApoA-I and HDL-C were also the only two serum lipid parameters decreased in the mild group compared to those in controls. In the moderate and the severe group, the values of TC, LDL-C, HDL-C and ApoA-I were all decreased compared to healthy control group. Further analysis indicated that the values of HDL-C and ApoA-I were significantly lower in the severe group compared to the moderate group. Correlation analysis indicated that the levels of HDL-C but not ApoA-I was negatively associated with the severity of the disease. Interestingly, when psoriasis was improved by treatment, the serum levels of TG, TC, HDL-C and ApoA-I were increased from the pre-treatment values. We conclude that abnormalities in serum lipid metabolism may play an important role in the pathogenesis of Chinese patients with psoriasis. PMID:26823881

  9. Computer-assisted design and synthesis of a highly selective smart adsorbent for extraction of clonazepam from human serum.

    PubMed

    Aqababa, Heydar; Tabandeh, Mehrdad; Tabatabaei, Meisam; Hasheminejad, Meisam; Emadi, Masoomeh

    2013-01-01

    A computational approach was applied to screen functional monomers and polymerization solvents for rational design of molecular imprinted polymers (MIPs) as smart adsorbents for solid-phase extraction of clonazepam (CLO) form human serum. The comparison of the computed binding energies of the complexes formed between the template and functional monomers was conducted. The primary computational results were corrected by taking into calculation both the basis set superposition error (BSSE) and the effect of the polymerization solvent using the counterpoise (CP) correction and the polarizable continuum model, respectively. Based on the theoretical calculations, trifluoromethyl acrylic acid (TFMAA) and acrylonitrile (ACN) were found as the best and the worst functional monomers, correspondingly. To test the accuracy of the computational results, three MIPs were synthesized by different functional monomers and their Langmuir-Freundlich (LF) isotherms were studied. The experimental results obtained confirmed the computational results and indicated that the MIP synthesized using TFMAA had the highest affinity for CLO in human serum despite the presence of a vast spectrum of ions. PMID:25428061

  10. PERFORMANCE AND SERUM GLUCOSE, INSULIN, IGF-1, AND NEFA CONCENTRATIONS OF CALVES NURSING BEEF COWS CONSUMING HIGH-LINOLEATE OR HIGH-OLEATE SAFFLOWER SEED SUPPLEMENTS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Three-year-old Angus ' Gelbvieh beef cows nutritionally managed to achieve a BCS of 4 or 6 at parturition were used in a 2-yr experiment (n = 36/yr) to determine the effects of dietary lipid supplementation on suckling calf ADG and calf serum concentrations of glucose, insulin, IGF-1, and NEFA. Beg...

  11. Evaluation of aminotransferase abnormality in dengue patients: A meta analysis.

    PubMed

    Wang, Xiao-Jun; Wei, Hai-Xia; Jiang, Shi-Chen; He, Cheng; Xu, Xiu-Juan; Peng, Hong-Juan

    2016-04-01

    Dengue virus is a type of flavivirus transmitted by Aedes mosquitoes. The symptoms of infection by this virus range from asymptomatic or mild symptomatic dengue fever (DF) to dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS). Significant abnormality in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) has been shown in a large number of dengue infection cases and to be indicator for liver injury provided that there are no other combined infections or liver injury. This study aims to assess the abnormal levels of liver aminotransferase in dengue patients. The related literature was searched in multiple databases, including PubMed, Embase, Google Scholar and Cochrane Library. The literature was selected through strict inclusion and exclusion criteria, and the quantitative synthesis of the liver aminotransferase abnormality was performed with R software. The fixed or random effects model was employed based on the results of the statistical test for homogeneity. In total, 15 studies were included. The proportion of AST abnormality with 95% confidence interval (95% CI) was 0.80 (95% CI: 0.56-0.92) in DHF patients and 0.75 (95% CI: 0.63-0.84) in DF patients; the proportion of ALT abnormality was 0.54 (95% CI: 0.34-0.73) in DHF patients and 0.52 (95% CI: 0.41-0.63) in DF patients. Serum ALT and AST levels may be indicators for evaluating liver injury in dengue infection and for diagnosis and treatment effect. PMID:26739659

  12. Detection of an endocrine disrupter biomarker, vitellogenin, in largemouth bass serum using AlGaN/GaN high electron mobility transistors

    NASA Astrophysics Data System (ADS)

    Chu, Byung Hwan; Chang, C. Y.; Kroll, Kevin; Denslow, Nancy; Wang, Yu-Lin; Pearton, S. J.; Dabiran, A. M.; Wowchak, A. M.; Cui, B.; Chow, P. P.; Ren, Fan

    2010-01-01

    Endocrine disrupters are known to have negative effects on the environment and human health. Real time detection of vitellogenin, an endocrine disrupter biomarker, was demonstrated using AlGaN/GaN high electron mobility transistors (HEMTs). Anti-vitellogenin antibodies were chemically anchored to the gold-coated gate area of the HEMT and immobilized with thioglycolic acid. The potential difference that occurs from the vitellogenin antigen-antibody interaction-induced caused a drain current change in the HEMT. The HEMT sensor was tested for vitellogenin detection both in phosphate buffer saline and largemouth bass serum.

  13. Determination of sulfur in bovine serum albumin and L-cysteine using high-resolution continuum source molecular absorption spectrometry of the CS molecule

    NASA Astrophysics Data System (ADS)

    Andrade-Carpente, Eva; Peña-Vázquez, Elena; Bermejo-Barrera, Pilar

    2016-08-01

    In this study, the content of sulfur in bovine serum albumin and L-cysteine was determined using high-resolution continuum source molecular absorption spectrometry of the CS molecule, generated in a reducing air-acetylene flame. Flame conditions (height above the burner, measurement time) were optimized using a 3.0% (v/v) sulfuric acid solution. A microwave lab station (Ethos Plus MW) was used for the digestion of both compounds. During the digestion step, sulfur was converted to sulfate previous to the determination. Good repeatability (4-10%) and analytical recovery (91-106%) was obtained.

  14. Body mass index, serum total cholesterol, and risk of gastric high-grade dysplasia: A case-control study among Chinese adults.

    PubMed

    Huang, Ya-Kai; Kang, Wei-Ming; Ma, Zhi-Qiang; Liu, Yu-Qin; Zhou, Li; Yu, Jian-Chun

    2016-08-01

    Obesity is related to an increased risk of gastric cardia cancer. However, the influences of excess body weight and serum total cholesterol on the risk of gastric high-grade dysplasia have not been fully characterized.A case-control study was conducted to explore the relationships between body mass index (BMI), serum total cholesterol level, and the risk of gastric high-grade dysplasia in Chinese adults. A total of 893 consecutive patients with gastric high-grade dysplasia (537 men and 356 women) and 902 controls (543 men and 359 women) were enrolled from January 2000 to October 2015. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated, and a multivariate analysis was conducted.After adjusting for age, alcohol consumption, smoking status, family history of gastric cancer or esophageal cancer, and serum total cholesterol level, a BMI ranging from 27.5 to 29.9 was significantly related to an increased risk of gastric high-grade dysplasia in both men (adjusted OR = 1.87, 95% CI = 1.24-2.81) and women (adjusted OR = 2.72, 95% CI = 1.44-5.16). The 2 highest BMI categories (27.5-29.9 and ≥30.0) were identified as risk factors for gastric cardia high-grade dysplasia in both men (BMI = 27.5-29.9: adjusted OR = 1.78, 95% CI = 1.02-3.10; BMI ≥ 30.0: adjusted OR = 2.54, 95% CI = 1.27-5.08) and women (BMI = 27.5-29.9: adjusted OR = 2.88, 95% CI = 1.27-6.55; BMI ≥ 30.0: adjusted OR = 2.77, 95% CI = 1.36-5.64), whereas only a BMI ranging from 27.5 to 29.9 was a risk factor for gastric noncardia high-grade dysplasia in both men (adjusted OR = 1.98, 95% CI = 1.25-3.14) and women (adjusted OR = 2.88, 95% CI = 1.43-5.81). In addition, higher serum total cholesterol was associated with an increased risk of gastric noncardia high-grade dysplasia (adjusted OR = 1.83, 95% CI = 1.25-2.69) in women.Increased BMI was associated with an increased risk of gastric high-grade dysplasia in

  15. Cationic isotachophoresis separation of the biomarker cardiac troponin I from a high-abundance contaminant, serum albumin

    PubMed Central

    Jacroux, Thomas; Bottenus, Danny; Rieck, Bennett; Ivory, Cornelius F.; Dong, Wen-ji

    2014-01-01

    Cationic ITP was used to separate and concentrate fluorescently tagged cardiac troponin I (cTnI) from two proteins with similar isoelectric properties in a PMMA straight-channel microfluidic chip. In an initial set of experiments, cTnI was effectively separated from R-Phycoerythrin using cationic ITP in a pH 8 buffer system. Then, a second set of experiments was conducted in which cTnI was separated from a serum contaminant, albumin. Each experiment took ~ 10 min or less at low electric field strengths (34 V/cm) and demonstrated that cationic ITP could be used as an on-chip removal technique to isolate cTnI from albumin. In addition to the experimental work, a 1D numerical simulation of our cationic ITP experiments has been included to qualitatively validate experimental observations. PMID:24723384

  16. Cationic isotachophoresis separation of the biomarker cardiac troponin I from a high-abundance contaminant, serum albumin.

    PubMed

    Jacroux, Thomas; Bottenus, Danny; Rieck, Bennett; Ivory, Cornelius F; Dong, Wen-Ji

    2014-07-01

    Cationic ITP was used to separate and concentrate fluorescently tagged cardiac troponin I (cTnI) from two proteins with similar isoelectric properties in a PMMA straight-channel microfluidic chip. In an initial set of experiments, cTnI was effectively separated from R-Phycoerythrin using cationic ITP in a pH 8 buffer system. Then, a second set of experiments was conducted in which cTnI was separated from a serum contaminant, albumin. Each experiment took ∼10 min or less at low electric field strengths (34 V/cm) and demonstrated that cationic ITP could be used as an on-chip removal technique to isolate cTnI from albumin. In addition to the experimental work, a 1D numerical simulation of our cationic ITP experiments has been included to qualitatively validate experimental observations. PMID:24723384

  17. Ultra-high sensitivity analysis of estrogens for special populations in serum and plasma by liquid chromatography-mass spectrometry: Assay considerations and suggested practices.

    PubMed

    Wang, Qingqing; Mesaros, Clementina; Blair, Ian A

    2016-09-01

    Estrogen measurements play an important role in the clinical evaluation of many endocrine disorders as well as in research on the role of hormones in human biology and disease. It remains an analytical challenge to quantify estrogens and their metabolites in specimens from special populations including older men, children, postmenopausal women and women receiving aromatase inhibitors. Historically, immunoassays have been used for measuring estrogens and their metabolites in biological samples for risk assessment. However, the lack of specificity and accuracy of immunoassay-based methods has caused significant problems when interpreting data generated from epidemiological studies and across different laboratories. Stable isotope dilution (SID) methodology coupled with liquid chromatography-selected reaction monitoring-mass spectrometry (LC-SRM/MS) is now accepted as the 'gold-standard' to quantify estrogens and their metabolites in serum and plasma due to improved specificity, high accuracy, and the ability to monitor multiple estrogens when compared with immunoassays. Ultra-high sensitivity can be obtained with pre-ionized derivatives when using triple quadruple mass spectrometers in the selected reaction monitoring (SRM) mode coupled with nanoflow LC. In this review, we have examined the special issues related to utilizing ultra-high sensitivity SID LC-SRM/MS-based methodology to accurately quantify estrogens and their metabolites in the serum and plasma from populations with low estrogen levels. The major issues that are discussed include: sample preparation for both unconjugated and conjugated estrogens, derivatization, chromatographic separation, matrix effects, and assay validation. PMID:26767303

  18. The effect of different high-fat diets on erythrocyte osmotic fragility, growth performance and serum lipid concentrations in male, Japanese quail (Coturnix coturnix japonica).

    PubMed

    Donaldson, J; Pillay, K; Madziva, M T; Erlwanger, K H

    2015-04-01

    Poultry diets are formulated with additional animal fat or vegetable oils to improve growth rate and feed conversion efficiency. High-fat diet feeding in rats and fish has been shown to result in alterations in the phospholipid composition and cholesterol content of the erythrocyte membrane, in turn affecting erythrocyte osmotic fragility. In contrast, the few studies performed using high-fat diet feeding in avian species show no changes in erythrocyte osmotic fragility. This study made use of the Japanese quail as no data exists on investigation of this species with respect to high-fat diet feeding and erythrocyte osmotic fragility. Fifty-seven male quail were randomly divided into six groups and fed either a standard diet (commercial poultry feed) or one of five high-fat diets (commercial poultry feed with 22% of either coconut oil, lard, palm oil, soya bean oil or sunflower oil on a weight/weight basis) for 12 weeks. All birds on the high-fat diets were significantly heavier (p < 0.05) after the 12-week feeding period, than when commencing the dietary intervention. Serum triglyceride concentrations of birds in all high-fat diet groups were significantly lower (p < 0.05) than birds in the standard diet group, whereas only birds in the palm oil group had significantly lower (p < 0.05) serum cholesterol concentrations compared to the standard diet group. Fragiligrams of erythrocytes from birds in the various dietary groups were similar. High-fat diet feeding with different types of additional fat did not affect the osmotic fragility of the quail erythrocytes. Feeding quail high-energy diets of varying degrees of fatty acid saturation was well tolerated and did not seem to affect the overall health status of the birds. Resistance of avian erythrocytes to modification by excess dietary fat may be a general characteristic of avian erythrocytes. PMID:25244110

  19. High-serum carotenoids associated with lower risk for developing type 2 diabetes among Japanese subjects: Mikkabi cohort study

    PubMed Central

    Sugiura, Minoru; Nakamura, Mieko; Ogawa, Kazunori; Ikoma, Yoshinori; Yano, Masamichi

    2015-01-01

    Objective Recent epidemiological studies show the association of antioxidant carotenoids with type 2 diabetes, but thorough longitudinal cohort studies regarding this association have not been well conducted. The objective of this study was to investigate longitudinally whether serum carotenoids are associated with the risk for developing type 2 diabetes among Japanese subjects. Research design and methods We conducted a follow-up study on 1073 males and females aged 30–79 years at the baseline from the Mikkabi prospective cohort study. Those who participated in the baseline and completed follow-up surveys were examined longitudinally. Over the 10-year period, 910 subjects (295 males and 615 females) took part in the follow-up survey at least one time. A cohort of 264 males and 600 females free of diabetes at baseline was studied. Results Over a mean follow-up period of 7.8 years (SD=2.9), 22 males and 33 females developed new type 2 diabetes. After adjustments for confounders, the HRs for type 2 diabetes in the highest tertiles of serum α-carotene, β-cryptoxanthin, and total provitamin A carotenoids against the lowest tertiles were 0.35 (95% CI 0.15 to 0.82), 0.43 (CI 0.20 to 0.92) and 0.41 (CI 0.19 to 0.90), respectively. For β-carotene and zeaxanthin, borderline reduced risks were also observed, but these were not significant. Conclusions Our results further support the hypothesis that eating a diet rich in carotenoids, especially provitamin A carotenoids, might help prevent the development of type 2 diabetes in Japanese patients. Trial registration number NIFT-2013001. PMID:26688736

  20. Comparison of the Digene Hybrid Capture 2 Assay and Roche AMPLICOR and LINEAR ARRAY Human Papillomavirus (HPV) Tests in Detecting High-Risk HPV Genotypes in Specimens from Women with Previous Abnormal Pap Smear Results▿

    PubMed Central

    Stevens, Matthew P.; Garland, Suzanne M.; Rudland, Elice; Tan, Jeffrey; Quinn, Michael A.; Tabrizi, Sepehr N.

    2007-01-01

    The development of cervical cancer is strongly associated with the presence of persistent high-risk (HR) human papillomavirus (HPV) infection. Recently, the commercially manufactured PCR-based Roche AMPLICOR (AMP) and LINEAR ARRAY (LA) HPV tests have become available for HPV detection. However, knowledge of their clinical performance compared to the U.S. Food and Drug Administration-approved Hybrid Capture 2 (HC2) assay is limited. This study evaluated the concordance between the HC2, AMP, and LA tests in detecting HR-HPV among a cohort of 1,679 women with previous abnormal Pap smear results. Overall, 1,393 specimens (81.3%) generated concordant results for HR-HPV presence or absence by the three assays. The concordance levels were substantial between the HC2 and AMP tests (84.4%, κ = 0.6419) and between the HC2 and LA tests (84.0%, κ = 0.6341) and nearly perfect between the AMP and LA tests (97.8%, κ = 0.9441). HR-HPV prevalence, as detected by the AMP or LA tests, was significantly higher among women with cytological or histological high-grade disease (CIN2 or greater) than that detected by HC2 (P < 0.0001). The AMP and LA tests exhibited greater sensitivity, but lower specificity, than HC2 for detecting HR-HPV among this cohort of women with underlying cervical abnormalities, particularly among subjects with histologically proven high-grade disease. Both PCR-based HPV tests may be valuable in the management of care for women with underlying cervical abnormalities, in predicting treatment success, and in studying the clearance or acquisition of new infections. PMID:17494721

  1. Ictal Cardiac Ryhthym Abnormalities

    PubMed Central

    Ali, Rushna

    2016-01-01

    Cardiac rhythm abnormalities in the context of epilepsy are a well-known phenomenon. However, they are under-recognized and often missed. The pathophysiology of these events is unclear. Bradycardia and asystole are preceded by seizure onset suggesting ictal propagation into the cortex impacting cardiac autonomic function, and the insula and amygdala being possible culprits. Sudden unexpected death in epilepsy (SUDEP) refers to the unanticipated death of a patient with epilepsy not related to status epilepticus, trauma, drowning, or suicide. Frequent refractory generalized tonic-clonic seizures, anti-epileptic polytherapy, and prolonged duration of epilepsy are some of the commonly identified risk factors for SUDEP. However, the most consistent risk factor out of these is an increased frequency of generalized tonic–clonic seizures (GTC). Prevention of SUDEP is extremely important in patients with chronic, generalized epilepsy. Since increased frequency of GTCS is the most consistently reported risk factor for SUDEP, effective seizure control is the most important preventive strategy. PMID:27347227

  2. [A comparative study between low-dose and high-dose medroxyprogesterone acetate (MPA) in the treatment of advanced and recurrent breast cancer--in relation to dose, serum concentration and response. Osaka Breast Cancer Research Group].

    PubMed

    Furukawa, J; Yayoi, E; Takatsuka, Y; Aikawa, T; Maeura, Y; Kobayashi, T; Miyauchi, K; Kotsuma, Y

    1997-05-01

    A prospective randomized study was carried out to evaluate the effectiveness of MPA in the treatment of breast cancer by comparing low dose (600 mg/day) with high dose (1,200 mg/day) of MPA. In 35 evaluable cases, the response rate to treatment was 40.0% (8/20) with low dose MPA and 26.7% (4/15) with high dose MPA. There was no significant difference between the two groups. The serum MPA concentration measured by high-performance liquid chromatography (HPLC) assay was 23.2 +/- 17.6 ng/ml in the low-dose group and 89.5 +/- 56.7 ng/ml in the high-dose group. Intrapatient variability in serum MPA concentration was relatively stable, but interpatient variability was large. No correlation was found between the response rate and serum MPA concentration. The above results indicate that a low dose of MPA (600 mg/day) is a useful treatment with high effectiveness and safety in advanced and recurrent breast cancer patients. Though no exact data on the optimal serum concentration could not be obtained, it was obvious that a successful response cannot be expected from a serum MPA concentration of less than 17 ng/ml, which was the average serum concentration in NC and PD patients of the low-dose group. PMID:9170519

  3. High incidence of functional ion-channel abnormalities in a consecutive Long QT cohort with novel missense genetic variants of unknown significance

    PubMed Central

    Steffensen, Annette Buur; Refaat, Marwan M.; David, Jens-Peter; Mujezinovic, Amer; Calloe, Kirstine; Wojciak, Julianne; Nussbaum, Robert L.; Scheinman, Melvin M.; Schmitt, Nicole

    2015-01-01

    The Long QT syndrome (LQTS) is a disorder characterized by a prolongation of the QT interval and a propensity to ventricular tachyarrhythmias, which may lead to syncope, cardiac arrest, or sudden death. Our objective was to (1) determine the incidence of variants with unknown significance (VUS) in a cohort of consecutive LQTS patients and (2) to determine the percentage of those with novel missense VUS that have demonstrable functional channel abnormalities from a single referral center. We performed genetic screening of candidate genes in 39 probands with a diagnosis of LQTS to identify mutations and variants. Seven variants of unknown significance were identified, six were missense variants and one was a splice site variant. We investigated the six novel missense VUS in five patients; three missense variants in KCNQ1 (L236R, W379R, Y522S) and three missense variants in KCNH2 (R35W, S620G, V491I). We employed two-electrode voltage-clamp experiments in Xenopus laevis oocytes and confocal imaging to characterize the novel missense mutations functionally. We revealed electrophysiological and trafficking loss-of-function phenotypes. This report emphasizes the frequency of adverse channel function in patients with LQTS and the importance of heterologous studies to define channel function. PMID:26066609

  4. Abnormal grain growth in Ni-5at.%W

    NASA Astrophysics Data System (ADS)

    Witte, M.; Belde, M.; Barrales Mora, L.; de Boer, N.; Gilges, S.; Klöwer, J.; Gottstein, G.

    2012-12-01

    The growth of abnormally large grains in textured Ni-5at.%W substrates for high-temperature superconductors deteriorates the sharp texture of these materials and thus has to be avoided. Therefore the growth of abnormal grains is investigated and how it is influenced by the grain orientation and the annealing atmosphere. Texture measurements and grain growth simulations show that the grain orientation only matters so far that a high-angle grain boundary exists between an abnormally growing grain and the Cube-orientated matrix grains. The annealing atmosphere has a large influence on abnormal grain growth which is attributed to the differences in oxygen partial pressure.

  5. Effects of the Polysaccharide from the Sporophyll of Brown Alga Undaria Pinnatifida on Serum Lipid Profile and Fat Tissue Accumulation in Rats Fed a High-Fat Diet.

    PubMed

    Kim, Byoung-Mok; Park, Jae-Ho; Kim, Dong-Soo; Kim, Young-Myung; Jun, Joon-Young; Jeong, In-Hak; Chi, Young-Min

    2016-07-01

    We investigated the effects of the polysaccharide from the sporophyll of a selected brown alga Undaria pinnatifida on serum lipid profile, fat tissue accumulation, and gastrointestinal transit time in rats fed a high-fat diet. The algal polysaccharide (AP) was prepared by the treatment of multiple cellulase-producing fungi Trichoderma reesei and obtained from the sporophyll with a yield of 38.7% (dry basis). The AP was mostly composed of alginate and fucoidan (up to 89%) in a ratio of 3.75:1. The AP was added to the high-fat diet in concentrations of 0.6% and 1.7% and was given to male Sprague-Dawley rats (5-wk-old) for 5 wk. The 1.7% AP addition notably reduced body weight gain and fat tissue accumulation, and it improved the serum lipid profile, including triglycerides, total cholesterol, and very low-density lipoprotein-cholesterol. The effects were associated with increased feces weight and shortened gastrointestinal transit time. In addition, the lipid peroxidation of the liver was decreased in both groups. PMID:27384013

  6. Highly sensitive chemiluminescent analysis of residual bovine serum albumin (BSA) based on a pair of specific monoclonal antibodies and peroxyoxalate-glyoxaline-PHPPA dimer chemiluminescent system in vaccines.

    PubMed

    Xue, Pan; Zhang, Kui; Zhang, Zhujun; Li, Yun; Liu, Feng; Sun, Yuanjie; Zhang, Xiaoming; Song, Chaojun; Fu, Aihua; Jin, Boquan; Yang, Kun

    2012-03-01

    Enzyme-linked immunosorbent assay (ELISA), horseradish peroxidase (HRP)-catalyzed fluorescent reaction, and oxalate chemiluminescence analysis have been combined to develop a highly sensitive, simple, and rapid method for analysis of bovine serum albumin (BSA) based on a pair of specific monoclonal antibodies in vaccines. A typical "sandwich type" immunoassay was used. Reaction of 3-(4-hydroxyphenyl propionate) (PHPPA) with hydrogen peroxide-urea, catalyzed by HRP, produced fluorescence of 3-(4-hydroxyphenyl propionate) dimer, which was detected by chemiluminescence analysis with the bis(2,4,6-trichlorophenyl)oxalate (TCPO)-H(2)O(2)-glyoxaline-PHPPA dimer chemiluminescent system. This method exhibited high performance with a linear correlation between response and amount of bovine serum albumin (BSA) in the range 0.1 to 100.0 ng mL(-1) (r = 0.9988), and the detection limit was 0.03 ng mL(-1) (S/N = 3). Intra- and interassay coefficient variations were all lower than 9.0% at three concentrations (1.0, 20.0, and 80.0 ng mL(-1)). The proposed method has been used for successful analysis of the amount of residual BSA in vaccines. The results obtained compared well with those obtained by conventional colorimetric ELISA and luminol chemiluminescent ELISA. PMID:22328250

  7. Determination of bile acids in human serum by on-line restricted access material-ultra high-performance liquid chromatography-mass spectrometry.

    PubMed

    Bentayeb, K; Batlle, R; Sánchez, C; Nerín, C; Domeño, C

    2008-06-15

    This paper describes a new, fully automated on-line method combining restricted access material (RAM) extraction and ultra high-performance liquid chromatography (UHPLC) with mass spectrometric (MS) detection for determining congeners of bile acids (BAs) in human serum. In this method, low-pressure RAM and high-pressure UHPLC-MS are hyphenated by using a 2.5-mL loop-type interface. The compatibility problem between the large volume (1.2mL) of strong solvent (methanol) used for RAM elution and the need for a weak solvent in UHPLC injection has been addressed by using an auxiliary pre-column cross-flow of 0.1% aqueous formic acid. In this way, the complete 2.5mL loop volume can be injected into the UHPLC system, thereby maximizing sensitivity while maintaining good chromatographic performance. The optimised method allows the simultaneous analysis of 13 bile acids in a single run, including glycine- and taurine-conjugated bile acids, cholic acid (CA), deoxycholic acid (DCA), chenodeoxycholic acid (CDCA), ursodeoxycholic acid (UDCA), and litocholic acid. The complete analysis of a 100-microL single serum sample is performed in 30 min, providing detection limits in the pg range (corresponding with clinically relevant concentration levels) for all of the analytes except lithocholic acid, intra-day precision values (%R.S.D.) below 4% (except ursodeoxycholic acid) and inter-day precision lower than 15% (except ursodeoxycholic, glycoursodeoxycholic acid (GUDCA) and lithocholic acid). PMID:18514045

  8. Synthesis of molecular imprinted polymers for selective extraction of domperidone from human serum using high performance liquid chromatography with fluorescence detection.

    PubMed

    Salehi, Simin; Rasoul-Amini, Sara; Adib, Noushin; Shekarchi, Maryam

    2016-08-01

    In this study a novel method is described for selective quantization of domperidone in biological matrices applying molecular imprinted polymers (MIPs) as a sample clean up procedure using high performance liquid chromatography coupled with a fluorescence detector. MIPs were synthesized with chloroform as the porogen, ethylene glycol dimethacrylate as the crosslinker, methacrylic acid as the monomer, and domperidone as the template molecule. The new imprinted polymer was used as a molecular sorbent for separation of domperidone from serum. Molecular recognition properties, binding capacity and selectivity of MIPs were determined. The results demonstrated exceptional affinity for domperidone in biological fluids. The domperidone analytical method using MIPs was verified according to validation parameters, such as selectivity, linearity (5-80ng/mL, r(2)=0.9977), precision and accuracy (10-40ng/mL, intra-day=1.7-5.1%, inter-day=4.5-5.9%, and accuracy 89.07-98.9%).The limit of detection (LOD) and quantization (LOQ) of domperidone was 0.0279 and 0.092ng/mL, respectively. The simplicity and suitable validation parameters makes this a highly valuable selective bioequivalence method for domperidone analysis in human serum. PMID:27288934

  9. High-efficiency secretory expression of human neutrophil gelatinase-associated lipocalin from mammalian cell lines with human serum albumin signal peptide.

    PubMed

    Chen, Wei; Zhao, Xiaozhi; Zhang, Mingxin; Yuan, Yimin; Ge, Liyuan; Tang, Bo; Xu, Xiaoyu; Cao, Lin; Guo, Hongqian

    2016-02-01

    Human neutrophil gelatinase associated lipocalin (NGAL) is a secretory glycoprotein initially isolated from neutrophils. It is thought to be involved in the incidence and development of immunological diseases and cancers. Urinary and serum levels of NGAL have been investigated as a new biomarker of acute kidney injury (AKI), for an earlier and more accurate detection method than with creatinine level. However, expressing high-quality recombinant NGAL is difficult both in Escherichia coli and mammalian cells for the low yield. Here, we cloned and fused NGAL to the C-terminus of signal peptides of human NGAL, human interleukin-2 (IL2), gaussia luciferase (Gluc), human serum albumin preproprotein (HSA) or an hidden Markov model-generated signal sequence (HMM38) respectively for transient expression in Expi293F suspension cells to screen for their ability to improve the secretory expression of recombinant NGAL. The best results were obtained with signal peptide derived from HSA. The secretory recombinant protein could react specifically with NGAL antibody. For scaled production, we used HSA signal peptide to establish stable Chinese hamster ovary cell lines. Then we developed a convenient colony-selection system to select high-expression, stable cell lines. Moreover, we purified the NGAL with Ni-Sepharose column. The recombinant human NGAL displayed full biological activity. We provide a method to enhance the secretory expression of recombinant human NGAL by using the HSA signal peptide and produce the glycoprotein in mammalian cells. PMID:26518367

  10. Serum Hepcidin Predicts Uremic Accelerated Atherosclerosis in Chronic Hemodialysis Patients with Diabetic Nephropathy

    PubMed Central

    Li, Han; Feng, Su-Juan; Su, Lu-Lu; Wang, Wei; Zhang, Xiao-Dong; Wang, Shi-Xiang

    2015-01-01

    Background: Hepcidin, as a regulator of body iron stores, has been recently discovered to play a critical role in the pathogenesis of anemia of chronic disease. Atherosclerotic cardiovascular disease is the most common complication and the leading cause of death in chronic hemodialysis (CHD) patients. In the current study, we aimed to explore the relationship between serum hepcidin and uremic accelerated atherosclerosis (UAAS) in CHD patients with diabetic nephropathy (CHD/DN). Methods: A total of 78 CHD/DN and 86 chronic hemodialyzed nondiabetic patients with chronic glomerulonephritis (CHD/non-DN) were recruited in this study. The level of serum hepcidin-25 was specifically measured by liquid chromatography-tandem mass spectrometry. Serum levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were measured by enzyme-linked immunosorbent assay. Results: High serum level of hepcidin-25 was seen in CHD patients. Serum hepcidin-25 in CHD/DN was significantly higher than that in CHD/non-DN patients. Serum hepcidin-25 was positively correlated with ferritin, high-sensitivity C-reactive protein (hs-CRP), TNF-α, and IL-6 in CHD/DN patients. CHD/DN patients exhibited higher common carotid artery intima media thickness (CCA-IMT), hs-CRP, and hepcidin-25 levels than that in CHD/non-DN patients. Moreover, in CHD/DN patients, CCA-IMT was positively correlated with serum hepcidin, hs-CRP, and low-density lipoprotein-cholesterol. On multiple regression analysis, serum hepcidin and hs-CRP level exhibited independent association with IMT in CHD/DN patients. Conclusions: These findings suggest possible linkage between iron metabolism and hepcidin modulation abnormalities that may contribute to the development of UAAS in CHD/DN patients. PMID:25963357

  11. Abnormal Grain Growth Suppression in Aluminum Alloys

    NASA Technical Reports Server (NTRS)

    Hales, Stephen J. (Inventor); Claytor, Harold Dale (Inventor); Alexa, Joel A. (Inventor)

    2015-01-01

    The present invention provides a process for suppressing abnormal grain growth in friction stir welded aluminum alloys by inserting an intermediate annealing treatment ("IAT") after the welding step on the article. The IAT may be followed by a solution heat treatment (SHT) on the article under effectively high solution heat treatment conditions. In at least some embodiments, a deformation step is conducted on the article under effective spin-forming deformation conditions or under effective superplastic deformation conditions. The invention further provides a welded article having suppressed abnormal grain growth, prepared by the process above. Preferably the article is characterized with greater than about 90% reduction in area fraction abnormal grain growth in any friction-stir-welded nugget.

  12. Cone photopigment bleaching abnormalities in diabetes.

    PubMed

    Elsner, A E; Burns, S A; Lobes, L A; Doft, B H

    1987-04-01

    We have used a color-matching technique to obtain estimates of the optical density of cone photopigments as a function of retinal illuminance in patients with insulin-dependent diabetes mellitus (IDDM). We found that the half-bleach illuminance of some patients is abnormally high. That is, it takes more light to bleach an equivalent amount of photopigment in these patients. Since low illuminance color matches for these patients are normal, this implies that these patients have normal amounts of photopigment, but the photopigment is not bleaching normally. This result clearly points to abnormalities in the outer retina of these diabetic patients. The most likely causes of this abnormality are either decreases in the ability of the cones to absorb light, or an increased rate of regeneration of the cone photopigments. PMID:3557875

  13. Influence of high-normal serum TSH levels on major cardiovascular risk factors and Visceral Adiposity Index in euthyroid type 2 diabetic subjects.

    PubMed

    Giandalia, A; Russo, G T; Romeo, E L; Alibrandi, A; Villari, P; Mirto, A A; Armentano, G; Benvenga, S; Cucinotta, D

    2014-09-01

    Although several observations indicate that serum TSH levels in the high normal range are related to cardiovascular (CVD) risk factors in the general population, similar data are limited in diabetic subjects. The aim of this study was to investigate the potential associations between TSH serum levels within the normal range and major metabolic and non-metabolic CVD risk factors in a cohort of euthyroid type 2 diabetic subjects. Thyroid hormones, TSH levels, anthropometric parameters, lipid profile, glucose control, and blood pressure were measured in 490 euthyroid type 2 diabetic subjects, consecutively attending two outpatient diabetic units in Southern Italy. In all subjects, we also calculated the Visceral Adiposity Index (VAI), an obesity-related index associated with CVD risk. Diabetic women showed higher mean serum TSH levels and lower FT4 concentration than diabetic men, while FT3 levels were comparable in the two genders. Stratifying the study population according to quartiles of TSH levels, subjects in the highest TSH quartile were more likely to be female and younger, with higher values of BMI and waist circumference (P = 0.05 both), higher triglycerides (P = 0.002) and non-HDL cholesterol concentrations (P = 0.01), higher VAI values (P = 0.02), and lower FT4 levels (P = 0.05), when compared to those in the lowest quartile. At multivariate analysis, a younger age, female gender, triglycerides levels, and waist circumference were independently associated with higher TSH levels. In conclusion, in type 2 diabetic subjects with no evidence of thyroid disease, higher TSH concentrations within the normal range were more frequent in women and in younger subjects, and they were associated with visceral obesity and higher triglycerides concentrations, two well-known CVD risk factors. PMID:24385267

  14. A method for the simultaneous determination of creatinine and uric acid in serum by high-performance-liquid-chromatography evaluated versus reference methods.

    PubMed

    Kock, R; Seitz, S; Delvoux, B; Greiling, H

    1995-01-01

    A high performance liquid chromatography (HPLC) with isocratic ion-pair-reversed-phase separation and simultaneous UV-detection at 232 nm and 292 nm is proposed as a method for the simultaneous determination of uric acid and creatinine in serum. The only sample preparation required is an appropriate dilution with the eluent and membrane filtration on non-adsorbent 0.2 micron membrane-filtration-devices. The inaccuracy of the method has been determined for NIST-SRM-909 (n = 10) and was + 0.5% for creatinine as well as for uric acid. The imprecision in this case was 0.8% for both analytes. The within-run imprecision for creatinine/uric acid was 0.4-0.5%/0.2-0.4% in the case of standards and 0.6-0.8%/0.4-0.7% in the case of serum-pools. The between-run imprecision for creatinine/uric acid obtained from serum pools was 0.8-1.1%/0.7-1.0%. The results for creatinine have been compared to those from an isotope dilution-gas chromatography-mass spectrometry using [13C, 15N2]creatinine as internal standard and selected mass detection at m/e = 329 and m/e = 332. The results for uric acid have been compared to an HPLC-method published previously (Kock R et al. J Clin Chem Clin Biochem 1989; 27:157-62). The method comparisons (n = 55) for the new combined method presented versus the reference method for creatinine and the candidate reference method for uric acid resulted in coefficients of correlation of r = 1.000 for both analytes. The new combined method presented is useful for the analysis of patient samples where the classical photometric procedures do not give reliable results, as often observed in monitoring after transplantation surgery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7756438

  15. Adults with Chromosome 18 Abnormalities.

    PubMed

    Soileau, Bridgette; Hasi, Minire; Sebold, Courtney; Hill, Annice; O'Donnell, Louise; Hale, Daniel E; Cody, Jannine D

    2015-08-01

    The identification of an underlying chromosome abnormality frequently marks the endpoint of a diagnostic odyssey. However, families are frequently left with more questions than answers as they consider their child's future. In the case of rare chromosome conditions, a lack of longitudinal data often makes it difficult to provide anticipatory guidance to these families. The objective of this study is to describe the lifespan, educational attainment, living situation, and behavioral phenotype of adults with chromosome 18 abnormalities. The Chromosome 18 Clinical Research Center has enrolled 483 individuals with one of the following conditions: 18q-, 18p-, Tetrasomy 18p, and Ring 18. As a part of the ongoing longitudinal study, we collect data on living arrangements, educational level attained, and employment status as well as data on executive functioning and behavioral skills on an annual basis. Within our cohort, 28 of the 483 participants have died, the majority of whom have deletions encompassing the TCF4 gene or who have unbalanced rearrangement involving other chromosomes. Data regarding the cause of and age at death are presented. We also report on the living situation, educational attainment, and behavioral phenotype of the 151 participants over the age of 18. In general, educational level is higher for people with all these conditions than implied by the early literature, including some that received post-high school education. In addition, some individuals are able to live independently, though at this point they represent a minority of patients. Data on executive function and behavioral phenotype are also presented. Taken together, these data provide insight into the long-term outcome for individuals with a chromosome 18 condition. This information is critical in counseling families on the range of potential outcomes for their child. PMID:25403900

  16. Neural systems for social cognition: gray matter volume abnormalities in boys at high genetic risk of autism symptoms, and a comparison with idiopathic autism spectrum disorder.

    PubMed

    Goddard, Marcia N; Swaab, Hanna; Rombouts, Serge A R B; van Rijn, Sophie

    2016-09-01

    Klinefelter syndrome (47, XXY) is associated with several physical, cognitive, and behavioral consequences. In terms of social development, there is an increased risk of autism symptomatology. However, it remains unclear how social deficits are related to abnormal brain development and to what degree underlying mechanisms of social dysfunction in 47, XXY are similar to, or different from, those in idiopathic autism (ASD). This study was aimed at investigating the neural architecture of brain structures related to social information processing in boys with 47, XXY, also in comparison with boys with idiopathic ASD. MRI scans of 16 boys with 47, XXY, 16 with ASD, and 16 nonclinical, male controls were analyzed using voxel-based morphometry (VBM). A region of interest mask containing the superior temporal cortex, amygdala, orbitofrontal cortex (OFC), insular cortex, and medial frontal cortex was used. The Social Responsiveness Scale (SRS) was used to assess degree of autism spectrum symptoms. The 47, XXY group could not be distinguished from the ASD group on mean SRS scores, and their scores were significantly higher than in controls. VBM showed that boys with 47, XXY have significant gray matter volume reductions in the left and right insula, and the left OFC, compared with controls and boys with ASD. Additionally, boys with 47, XXY had significantly less gray matter in the right superior temporal gyrus than controls. These results imply social challenges associated with 47, XXY may be rooted in neural anatomy, and autism symptoms in boys with 47, XXY and boys with ASD might have, at least partially, different underlying etiologies. PMID:26233431

  17. Rapid and Highly Sensitive Detection of Variant Creutzfeldt - Jakob Disease Abnormal Prion Protein on Steel Surfaces by Protein Misfolding Cyclic Amplification: Application to Prion Decontamination Studies

    PubMed Central

    Belondrade, Maxime; Nicot, Simon; Béringue, Vincent; Coste, Joliette; Lehmann, Sylvain; Bougard, Daisy

    2016-01-01

    The prevalence of variant Creutzfeldt-Jakob disease (vCJD) in the population remains uncertain, although it has been estimated that 1 in 2000 people in the United Kingdom are positive for abnormal prion protein (PrPTSE) by a recent survey of archived appendix tissues. The prominent lymphotropism of vCJD prions raises the possibility that some surgical procedures may be at risk of iatrogenic vCJD transmission in healthcare facilities. It is therefore vital that decontamination procedures applied to medical devices before their reprocessing are thoroughly validated. A current limitation is the lack of a rapid model permissive to human prions. Here, we developed a prion detection assay based on protein misfolding cyclic amplification (PMCA) technology combined with stainless-steel wire surfaces as carriers of prions (Surf-PMCA). This assay allowed the specific detection of minute quantities (10−8 brain dilution) of either human vCJD or ovine scrapie PrPTSE adsorbed onto a single steel wire, within a two week timeframe. Using Surf-PMCA we evaluated the performance of several reference and commercially available prion-specific decontamination procedures. Surprisingly, we found the efficiency of several marketed reagents to remove human vCJD PrPTSE was lower than expected. Overall, our results demonstrate that Surf-PMCA can be used as a rapid and ultrasensitive assay for the detection of human vCJD PrPTSE adsorbed onto a metallic surface, therefore facilitating the development and validation of decontamination procedures against human prions. PMID:26800081

  18. Rapid and Highly Sensitive Detection of Variant Creutzfeldt-Jakob Disease Abnormal Prion Protein on Steel Surfaces by Protein Misfolding Cyclic Amplification: Application to Prion Decontamination Studies.

    PubMed

    Belondrade, Maxime; Nicot, Simon; Béringue, Vincent; Coste, Joliette; Lehmann, Sylvain; Bougard, Daisy

    2016-01-01

    The prevalence of variant Creutzfeldt-Jakob disease (vCJD) in the population remains uncertain, although it has been estimated that 1 in 2000 people in the United Kingdom are positive for abnormal prion protein (PrPTSE) by a recent survey of archived appendix tissues. The prominent lymphotropism of vCJD prions raises the possibility that some surgical procedures may be at risk of iatrogenic vCJD transmission in healthcare facilities. It is therefore vital that decontamination procedures applied to medical devices before their reprocessing are thoroughly validated. A current limitation is the lack of a rapid model permissive to human prions. Here, we developed a prion detection assay based on protein misfolding cyclic amplification (PMCA) technology combined with stainless-steel wire surfaces as carriers of prions (Surf-PMCA). This assay allowed the specific detection of minute quantities (10-8 brain dilution) of either human vCJD or ovine scrapie PrPTSE adsorbed onto a single steel wire, within a two week timeframe. Using Surf-PMCA we evaluated the performance of several reference and commercially available prion-specific decontamination procedures. Surprisingly, we found the efficiency of several marketed reagents to remove human vCJD PrPTSE was lower than expected. Overall, our results demonstrate that Surf-PMCA can be used as a rapid and ultrasensitive assay for the detection of human vCJD PrPTSE adsorbed onto a metallic surface, therefore facilitating the development and validation of decontamination procedures against human prions. PMID:26800081

  19. Electrocardiograph abnormalities revealed during laparoscopy

    PubMed Central

    Nijjer, Sukhjinder; Dubrey, Simon William

    2010-01-01

    This brief case presents a well patient in whom an electrocardiograph abnormality consistent with an accessory pathway was found during a routine procedure. We present the electrocardiographs, explain the underlying condition, and consider why the abnormality was revealed in this manner. PMID:22419949

  20. Haem degradation in abnormal haemoglobins.

    PubMed Central

    Brown, S B; Docherty, J C

    1978-01-01

    The coupled oxidation of certain abnormal haemoglobins leads to different bile-pigment isomer distributions from that of normal haemoglobin. The isomer pattern may be correlated with the structure of the abnormal haemoglobin in the neighbourhood of the haem pocket. This is support for haem degradation by an intramolecular reaction. PMID:708385

  1. Vitamin C may have similar beneficial effects to Gemfibrozil on serum high-density lipoprotein-cholesterol in type 2 diabetic patients

    PubMed Central

    Siavash, Mansour; Amini, Masoud

    2014-01-01

    Objective: Type 2 diabetes mellitus (DM-T2) is commonly associated with increased triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) and low high-density lipoprotein cholesterol (HDL-C) levels. Fibrates like gemfibrozil are frequently used in diabetic patients to decrease TG and increase HDL-C levels. We compared the efficacy of Vitamin C, an antioxidant vitamin, with gemfibrozil on serum HDL-C in diabetic patients. Methods: Type 2 diabetic patients, referred to our out-patient clinic were randomly divided into three groups. After 1 month of lifestyle and diet modifications, groups A, B, and C were prescribed 1000 mg Vitamin C, 600 mg gemfibrozil and combination of both, respectively. Before the study initiation and after 6th week of drug prescription, the blood samples were taken and analyzed for total cholesterol (Total-C), HDL-C, TG, fasting blood sugar (FBS), and hemoglobin A1c (HbA1c) levels. Findings: Sixty-seven patients entered, and 50 patients (18 male, 32 female) finished the study. Overall, serum HDL-C increased significantly from 39.8 to 45.2 mg/dL in the participants (P = 0.001). HDL-C increased 6.3, 4.4 and 5.0 mg/dL in groups A, B and C, respectively (related significances were 0.017, 0.022 and 0.033, respectively). Significant decrease of serum TG and Total-C occurred in gemfibrozil and combination groups, but not in Vitamin C group. Changes in serum HDL-C between three groups were not significant (P = 0.963). We found a significant decrease in TG and Total-C in the groups B and C (P < 0.05), but no significant changes of TG, Total-C, LDL-C, FBS and HbA1c in group A (P > 0.05). Conclusion: The results demonstrated that Vitamin C may have beneficial effects on HDL-C in diabetic patients without significant effects on plasma glucose or other lipid parameters; however, its role for the treatment of low HDL-C patients should be evaluated in larger studies. PMID:25328896

  2. Utility of the combination of serum highly-sensitive C-reactive protein level at discharge and a risk index in predicting readmission for acute exacerbation of COPD*,**

    PubMed Central

    Chang, Chun; Zhu, Hong; Shen, Ning; Han, Xiang; Chen, Yahong; He, Bei

    2014-01-01

    OBJECTIVE: Frequent readmissions for acute exacerbations of COPD (AECOPD) are an independent risk factor for increased mortality and use of health-care resources. Disease severity and C-reactive protein (CRP) level are validated predictors of long-term prognosis in such patients. This study investigated the utility of combining serum CRP level with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) exacerbation risk classification for predicting readmission for AECOPD. METHODS: This was a prospective observational study of consecutive patients hospitalized for AECOPD at Peking University Third Hospital, in Beijing, China. We assessed patient age; gender; smoking status and history (pack-years); lung function; AECOPD frequency during the last year; quality of life; GOLD risk category (A-D; D indicating the greatest risk); and serum level of high-sensitivity CRP at discharge (hsCRP-D). RESULTS: The final sample comprised 135 patients. Of those, 71 (52.6%) were readmitted at least once during the 12-month follow-up period. The median (interquartile) time to readmission was 78 days (42-178 days). Multivariate analysis revealed that serum hsCRP-D ≥ 3 mg/L and GOLD category D were independent predictors of readmission (hazard ratio = 3.486; 95% CI: 1.968-6.175; p < 0.001 and hazard ratio = 2.201; 95% CI: 1.342-3.610; p = 0.002, respectively). The ordering of the factor combinations by cumulative readmission risk, from highest to lowest, was as follows: hsCRP-D ≥ 3 mg/L and GOLD category D; hsCRP-D ≥ 3 mg/L and GOLD categories A-C; hsCRP-D < 3 mg/L and GOLD category D; hsCRP-D < 3 mg/L and GOLD categories A-C. CONCLUSIONS: Serum hsCRP-D and GOLD classification are independent predictors of readmission for AECOPD, and their predictive value increases when they are used in combination. PMID:25410837

  3. Triple Quadrupole Versus High Resolution Quadrupole-Time-of-Flight Mass Spectrometry for Quantitative LC-MS/MS Analysis of 25-Hydroxyvitamin D in Human Serum

    NASA Astrophysics Data System (ADS)

    Geib, Timon; Sleno, Lekha; Hall, Rabea A.; Stokes, Caroline S.; Volmer, Dietrich A.

    2016-08-01

    We describe a systematic comparison of high and low resolution LC-MS/MS assays for quantification of 25-hydroxyvitamin D3 in human serum. Identical sample preparation, chromatography separations, electrospray ionization sources, precursor ion selection, and ion activation were used; the two assays differed only in the implemented final mass analyzer stage; viz. high resolution quadrupole-quadrupole-time-of-flight (QqTOF) versus low resolution triple quadrupole instruments. The results were assessed against measured concentration levels from a routine clinical chemiluminescence immunoassay. Isobaric interferences prevented the simple use of TOF-MS spectra for extraction of accurate masses and necessitated the application of collision-induced dissociation on the QqTOF platform. The two mass spectrometry assays provided very similar analytical figures of merit, reflecting the lack of relevant isobaric interferences in the MS/MS domain, and were successfully applied to determine the levels of 25-hydroxyvitamin D for patients with chronic liver disease.

  4. Triple Quadrupole Versus High Resolution Quadrupole-Time-of-Flight Mass Spectrometry for Quantitative LC-MS/MS Analysis of 25-Hydroxyvitamin D in Human Serum

    NASA Astrophysics Data System (ADS)

    Geib, Timon; Sleno, Lekha; Hall, Rabea A.; Stokes, Caroline S.; Volmer, Dietrich A.

    2016-05-01

    We describe a systematic comparison of high and low resolution LC-MS/MS assays for quantification of 25-hydroxyvitamin D3 in human serum. Identical sample preparation, chromatography separations, electrospray ionization sources, precursor ion selection, and ion activation were used; the two assays differed only in the implemented final mass analyzer stage; viz. high resolution quadrupole-quadrupole-time-of-flight (QqTOF) versus low resolution triple quadrupole instruments. The results were assessed against measured concentration levels from a routine clinical chemiluminescence immunoassay. Isobaric interferences prevented the simple use of TOF-MS spectra for extraction of accurate masses and necessitated the application of collision-induced dissociation on the QqTOF platform. The two mass spectrometry assays provided very similar analytical figures of merit, reflecting the lack of relevant isobaric interferences in the MS/MS domain, and were successfully applied to determine the levels of 25-hydroxyvitamin D for patients with chronic liver disease.

  5. Carbohydrate-deficient glycoprotein syndrome: not an N-linked oligosaccharide processing defect, but an abnormality in lipid-linked oligosaccharide biosynthesis?

    PubMed Central

    Powell, L D; Paneerselvam, K; Vij, R; Diaz, S; Manzi, A; Buist, N; Freeze, H; Varki, A

    1994-01-01

    The carbohydrate-deficient glycoprotein syndrome (CDGS) is a developmental disease associated with an abnormally high isoelectric point of serum transferrin. Carbohydrate analyses of this glycoprotein initially suggested a defect in N-linked oligosaccharide processing, although more recent studies indicate a defect in the attachment of these sugar chains to the protein. We studied both serum glycoproteins and fibroblast-derived [2-3H]mannose-labeled oligosaccharides from CDGS patients and normal controls. While there was a decrease in the glycosylation of serum glycoproteins of affected individuals, differences were not seen in either monosaccharide composition or oligosaccharide structures. The lectin-binding profiles of glycopeptides from [2-3H]-mannose-labeled fibroblasts were likewise indistinguishable. However, the incorporation of [2-3H]mannose into both glycoproteins and the dolichol-linked oligosaccharide precursor was significantly reduced. Thus, at least in some patients, CDGS is not due to a defect in processing of N-linked oligosaccharides, but rather to defective synthesis and transfer of nascent dolichol-linked oligosaccharide precursors. This abnormality could result in both a failure to glycosylate some sites on some proteins, as well as secondary abnormalities in overall glycoprotein processing and/or function. PMID:7962535

  6. Wear of ultra-high molecular weight polyethylene acetabular cups in a physiological hip joint simulator in the anatomical position using bovine serum as a lubricant.

    PubMed

    Bigsby, R J; Hardaker, C S; Fisher, J

    1997-01-01

    The Leeds physiological anatomical (PA) hip joint simulator was developed to apply three axes of loading and a complex three-dimensional motion so that the forces and motions can reproduce exactly the walking cycles defined by Paul. This paper presents the results of a study using the Leeds PA hip joint simulator to determine the wear of 32 mm ultra-high molecular weight polyethylene (UHMWPE) acetabular cups against stainless steel and zirconia ceramic heads, using bovine serum as lubricant. These results have been compared with the results of a previous study that used water as the lubricant, which led to UHMWPE transfer film being formed on the stainless steel head. Comparisons are also made with clinical results and results from other simulators. The study indicates that it is preferable to use bovine serum in simulator studies. In addition, the results indicate that if the surface roughness of the metallic and femoral heads are similar, and they remain undamaged during the tests, the wear rates of the UHMWPE cups are likely to be similar. PMID:9256003

  7. Urine and serum metabolite profiling of rats fed a high-fat diet and the anti-obesity effects of caffeine consumption.

    PubMed

    Kim, Hyang Yeon; Lee, Mee Youn; Park, Hye Min; Park, Yoo Kyoung; Shon, Jong Cheol; Liu, Kwang-Hyeon; Lee, Choong Hwan

    2015-01-01

    In this study, we investigated the clinical changes induced by a high fat diet (HFD) and caffeine consumption in a rat model. The mean body weight of the HFD with caffeine (HFDC)-fed rat was decreased compared to that of the HFD-fed rat without caffeine. The levels of cholesterol, triglycerides (TGs), and free fatty acid, as well as the size of adipose tissue altered by HFD, were improved by caffeine consumption. To investigate the metabolites that affected the change of the clinical factors, the urine and serum of rats fed a normal diet (ND), HFD, and HFDC were analyzed using ultra performance liquid chromatography quadruple time-of-flight mass spectrometry (UPLC-Q-TOF-MS), gas chromatography (GC-TOF-MS), and linear trap quadruple mass spectrometry (LTQ-XL-MS) combined with multivariate analysis. A total of 68 and 52 metabolites were found to be different in urine and serum, respectively. After being fed caffeine, some glucuronide-conjugated compounds, lysoPCs, CEs, DGs, TGs, taurine, and hippuric acid were altered compared to the HFD group. In this study, caffeine might potentially inhibit HFD-induced obesity and we suggest possible biomarker candidates using MS-based metabolite profiling. PMID:25689639

  8. Ovarian acyclicity in zoo African elephants (Loxodonta africana) is associated with high body condition scores and elevated serum insulin and leptin.

    PubMed

    Morfeld, Kari A; Brown, Janine L

    2016-04-01

    The purpose of the present study was to determine whether excessive body fat and altered metabolic hormone concentrations in the circulation were associated with ovarian acyclicity in the world's largest land mammal, the African elephant. We compared body condition, glucose, insulin and leptin concentrations and the glucose-to-insulin ratio (G:I) between cycling (n=23; normal 14-16 week cycles based on serum progestagens for at least 2 years) and non-cycling (n=23; consistent baseline progestagen concentrations for at least 2 years) females. A validated body condition score (BCS) index (five-point scale; 1=thinnest, 5=fattest) was used to assess the degree of fatness of the study elephants. The mean BCS of non-cycling elephants was higher than that of their cycling counterparts. There were differences in concentrations of serum metabolic biomarkers, with non-cycling elephants in the BCS 5 category having higher leptin and insulin concentrations and a lower G:I ratio than cycling BCS 5 females. Using 'non-cycling' as the outcome variable in regression models, high BCS was a strong predictor of a non-cycling status. This study provides the first evidence that ovarian acyclicity in zoo African elephants is associated with body condition indicative of obesity, as well as elevated, perturbed biomarkers of metabolic status. PMID:25375263

  9. Extract of okra lowers blood glucose and serum lipids in high-fat diet-induced obese C57BL/6 mice.

    PubMed

    Fan, Shengjie; Zhang, Yu; Sun, Qinhu; Yu, Lijing; Li, Mingxia; Zheng, Bin; Wu, Ximin; Yang, Baican; Li, Yiming; Huang, Cheng

    2014-07-01

    Okra is an important tropical vegetable and source of dietary medicine. Here, we assayed the effects of an ethanol extract of okra (EO) and its major flavonoids isoquercitrin and quercetin 3-O-gentiobioside on metabolic disorders in high-fat diet-induced obese mouse. We found that treatment with EO, isoquercitrin and quercetin 3-O-gentiobioside reduced blood glucose and serum insulin levels and improved glucose tolerance in obese mice. Meanwhile, serum triglyceride levels and liver morphology in the mice were significantly ameliorated by EO and isoquercitrin treatment. Total cholesterol levels in isoquercitrin and quercetin 3-O-gentiobioside treated mice were also reduced. We also found that EO inhibited the expression of nuclear receptor transcription factor PPARγ, which is an important regulator of lipid and glucose homeostasis. Furthermore, we determined that EO and quercetin 3-O-gentiobioside have antioxidant activity in vitro. Our results indicate that okra may serve as a dietary therapy for hyperglycemia and hypertriglyceridemia. PMID:24746837

  10. Serum metabolic profiling study of lung cancer using ultra high performance liquid chromatography/quadrupole time-of-flight mass spectrometry.

    PubMed

    Li, Yanjie; Song, Xue; Zhao, Xinjie; Zou, Lijuan; Xu, Guowang

    2014-09-01

    Lung cancer is currently the leading cause of cancer-related mortality worldwide. It is, therefore, important to enhance understanding and add a new auxiliary detection tool of lung cancer. In this work, serum metabolic characteristics of lung cancer were investigated with a non-targeted metabolomics method. The metabolic profiling of 23 patients with lung cancer and 23 healthy controls were analyzed using ultra high performance liquid chromatography/quadrupole time of flight mass spectrometry (UPLC/Q-TOF MS). Partial least squares discriminant analysis (PLS-DA) model of the metabolic data allowed the clear separation of the lung cancer patients from the healthy controls. In total, 27 differential metabolites were identified, which were mostly related to the perturbation of lipid metabolism, including choline, free fatty acids, lysophosphatidylcholines, etc. Choline and linoleic acid were defined as one combinational biomarker using binary logistic regression, which was supported by the validation with a smaller sample-set (9 patients and 9 healthy controls). These findings show that LC/MS-based serum metabolic profiling has potential application in complementary identification of lung cancer patients, and could be a powerful tool for cancer research. PMID:24856296

  11. High serum n6 fatty acid proportion is associated with lowered LDL oxidation and inflammation: the Cardiovascular Risk in Young Finns Study.

    PubMed

    Kaikkonen, J E; Kresanov, P; Ahotupa, M; Jula, A; Mikkilä, V; Viikari, J S A; Kähönen, M; Lehtimäki, T; Raitakari, O T

    2014-04-01

    The intake of polyunsaturated fatty acids (PUFAs) is generally linked with a reduced cardiovascular disease (CVD) risk, but an elevated n6PUFA intake, without simultaneous n3PUFA supply, may elevate the risk. PUFAs are suspected as being easily oxidized and have a potential role in lipoprotein oxidation and inflammation. Saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs) are resistant to oxidation. However, in a Western diet, their most important source is red meat, a food stuff rich in heme iron which can catalyze oxidative reactions. Therefore, different serum fatty acid (FA) proportions (free + esterified) were correlated with the status of low-density lipoprotein (LDL) oxidation in vivo (conjugated dienes = oxLDLlipids and antibody-based oxidized proteins = oxLDLprot) and inflammation (serum CRP) in 2196 Finnish subjects (age: 24-39 years) using CVD risk factor-adjusted linear regression models. High n6PUFA, PUFA/SFA and n6/n3 ratios, and low SFA and MUFA were all associated with reduced levels of oxLDLlipids, oxLDLprot, and CRP. These findings at the population level suggest that PUFAs are negatively and SFAs and MUFAs positively related with LDL oxidation and inflammation; these conclusions are in line with previous observations linking PUFAs, particularly n6PUFAs, with lower CVD risk, and SFAs with increased risk. PMID:24437974

  12. Serum antibody response to respiratory syncytial virus F and N proteins in two populations at high risk of infection: children and elderly.

    PubMed

    Sastre, P; Cusi, M G; Manoha, C; Schildgen, O; Ruiz, T; Vela, C; Rueda, P

    2010-09-01

    Human respiratory syncytial virus (hRSV) is the main viral cause of severe respiratory infections in children and a common cause of morbidity in the elderly. The nucleocapsid (N) and fusion (F) proteins of hRSV were expressed in insect cells and used as antigens in two independent enzyme-linked immunosorbent assays (ELISAs) to measure the serum antibody response in two populations at high risk of hRSV infection, children and the elderly. Fifty-seven serum specimens from children aged from 1 to 10 years old and 91 sera from adults over 60 years old were tested. The ELISA results were compared with those obtained by an immunofluorescence assay (IFA) based on hRSV-infected cells, which was considered as the reference technique. Sensitivity and specificity were 94% and 85% for the N-ELISA and 86% and 81% for the F-ELISA, respectively. When the immune responses of the two groups of individuals were compared, it appeared that almost 100% of the elderly had antibodies against the N or F protein whereas only 50% of the sera from children had antibodies against either of the two viral proteins. In conclusion, the F and N ELISAs can be used successfully for detecting a specific antibody response to hRSV. PMID:20488207

  13. Impact of Serum High Mobility Group Box 1 and Soluble Receptor for Advanced Glycation End-Products on Subclinical Atherosclerosis in Patients with Granulomatosis with Polyangiitis

    PubMed Central

    de Souza, Alexandre W. S.; de Leeuw, Karina; van Timmeren, Mirjan M.; Limburg, Pieter C.; Stegeman, Coen A.; Bijl, Marc; Westra, Johanna; Kallenberg, Cees G. M.

    2014-01-01

    The objective of this study was to evaluate whether levels of high mobility group box 1 (HMGB1) in granulomatosis with polyangiitis (GPA) patients are associated with carotid atherosclerosis, related to levels of soluble receptor for advanced glycation end-products (sRAGE) and influenced by immunosuppressive or lipid-lowering therapy. Twenty-three GPA patients and 20 controls were evaluated for HMGB1- and sRAGE levels and for carotid atherosclerosis using ultrasound to determine intima-media thickness (IMT). In vitro the effect of atorvastatin on the production of HMGB1 by lipopolysaccharide (LPS)-stimulated human umbilical vein endothelial cells (HUVEC) was assessed. Serum HMGB1 and sRAGE levels did not differ between patients and controls. A negative correlation was found between sRAGE and maximum IMT but HMGB1 and carotid IMT were not related. HMGB1 levels were reduced in GPA patients on statins and prednisolone. In vitro, atorvastatin reduced HMGB1 levels in supernatants of activated HUVEC. In conclusion, carotid IMT is inversely correlated with sRAGE levels but not with HMGB1 levels. Statins and prednisolone are associated with reduced serum HMGB1 levels and atorvastatin decreases HMGB1 release by activated HUVEC in vitro, indicating an additional anti-inflammatory effect of statins. PMID:24776932

  14. Chromosome 13q deletion and IgH abnormalities may be both masked by near-tetraploidy in a high proportion of multiple myeloma patients: a combined morphology and I-FISH analysis.

    PubMed

    Koren-Michowitz, Maya; Hardan, Izhar; Berghoff, Janina; Yshoev, Galina; Amariglio, Ninette; Rechavi, Gideon; Nagler, Arnon; Trakhtenbrot, Luba

    2007-10-01

    Ploidy status and chromosomal aberrations involving chromosome 13q and the immunoglobulin heavy chain locus (IgH) are important prognostic features in multiple myeloma (MM). However, conventional cytogenetic studies are often not reveling and determination of plasma cells (PC) ploidy status in MM is technically difficult. We have used a combined cell morphology and interphase FISH (I-FISH) analysis in 184 consecutive BM samples from 136 MM patients for the diagnosis of chromosome 13q deletion [del (13q)] and IgH abnormalities. We have found a high prevalence (37%) of near-tetraploid (NT) PC in the BM samples studied. NT status of PC was verified with DNA index (DI) measurements. del (13q) was found in 69% and a total absence of one IgH copy (loss of IgH) in 20% of NT samples. We have shown that the presence of del (13q) and loss of IgH can be masked in NT cases: in 12 NT samples originally identified as normal for del (13q) the abnormality was obscured in the majority of plasma cells due to the presence of NT. Similarly, loss of IgH was masked in four samples with a large population of NT cells. Moreover, in one case the appearance of a 100% tetraploidy during disease progression masked the presence of del (13q), originally present, and could therefore falsely appear as disappearance of this prognostic marker. In conclusion, we have shown that a combination of three abnormalities, i.e., del (13q), loss of IgH and NT, all of potential prognostic significance, can be overlooked unless NT is specifically searched for and ruled out. Therefore, we suggest that a search for NT should be added to the routine BM assessment in MM patients. PMID:17590504

  15. High frequency of known copy number abnormalities and maternal duplication 15q11-q13 in patients with combined schizophrenia and epilepsy

    PubMed Central

    2011-01-01

    Background Many copy number variants (CNVs) are documented to be associated with neuropsychiatric disorders, including intellectual disability, autism, epilepsy, schizophrenia, and bipolar disorder. Chromosomal deletions of 1q21.1, 3q29, 15q13.3, 22q11.2, and NRXN1 and duplications of 15q11-q13 (maternal), 16p11, and 16p13.3 have the strongest association with schizophrenia. We hypothesized that cases with both schizophrenia and epilepsy would have a higher frequency of disease-associated CNVs and would represent an enriched sample for detection of other mutations associated with schizophrenia. Methods We used array comparative genomic hybridization (CGH) to analyze 235 individuals with both schizophrenia and epilepsy, 80 with bipolar disorder and epilepsy, and 191 controls. Results We detected 10 schizophrenia plus epilepsy cases in 235 (4.3%) with the above mentioned CNVs compared to 0 in 191 controls (p = 0.003). Other likely pathological findings in schizophrenia plus epilepsy cases included 1 deletion 16p13 and 1 duplication 7q11.23 for a total of 12/235 (5.1%) while a possibly pathogenic duplication of 22q11.2 was found in one control for a total of 1 in 191 (0.5%) controls (p = 0.008). The rate of abnormality in the schizophrenia plus epilepsy of 10/235 for the more definite CNVs compares to a rate of 75/7336 for these same CNVs in a series of unselected schizophrenia cases (p = 0.0004). Conclusion We found a statistically significant increase in the frequency of CNVs known or likely to be associated with schizophrenia in individuals with both schizophrenia and epilepsy compared to controls. We found an overall 5.1% detection rate of likely pathological findings which is the highest frequency of such findings in a series of schizophrenia patients to date. This evidence suggests that the frequency of disease-associated CNVs in patients with both schizophrenia and epilepsy is significantly higher than for unselected schizophrenia. PMID:22118685

  16. Measurement of acetol in serum.

    PubMed

    Casazza, J P; Fu, J L

    1985-08-01

    A method for the derivatization of acetol (1-hydroxyacetone) with 2,4-dinitrophenylhydrazine (DNPH) and for the measurement of the acetol dinitrophenylhydrazone derivative (acetol-DNPH) by high-performance liquid chromatography is presented. The chromatographic separation described here resulted in baseline resolution of the acetol-DNPH peak. Peak integration was proportional to serum acetol concentration over a 5- to 500-nmol/ml range. No other method for the determination of acetol in serum currently exists. Serum from rats in diabetic ketoacidosis was found to contain 11.2 +/- 1.1 nmol acetol/ml serum (N = 3). Serum from a 21-day-fasted human contained 16 nmol/ml acetol. Serum from rats maintained on drinking water containing 1% acetone (v:v) for 6 days contained 152 +/- 31 nmol/ml acetol (N = 5). The presence of acetol in serum under conditions where acetoacetate and acetone are chronically elevated suggests that acetoacetate may be converted to glucose through the conversion of acetone to acetol and L-1,2-propanediol. PMID:3933378

  17. High Vitamin C Intake with High Serum β-Cryptoxanthin Associated with Lower Risk for Osteoporosis in Post-Menopausal Japanese Female Subjects: Mikkabi Cohort Study.

    PubMed

    Sugiura, Minoru; Nakamura, Mieko; Ogawa, Kazunori; Ikoma, Yoshinori; Yano, Masamichi

    2016-01-01

    Recent epidemiological studies show that antioxidant vitamins and carotenoids might be beneficial to the maintenance of bone health. Recently, we found that serum carotenoids were inversely associated with the risk of developing osteoporosis in post-menopausal Japanese female subjects. However, little is known about the vitamin alone and/or the combination of the vitamin and carotenoid with the risk of osteoporosis. The objective of this study was to investigate longitudinally whether antioxidant vitamins and their combination with carotenoids are associated with the risk of developing of osteoporosis. We conducted a follow-up study on 187 post-menopausal female subjects from the Mikkabi prospective cohort study. Those who participated in previous bone mineral density (BMD) surveys and completed four years of follow-up were examined longitudinally. During a four-year follow-up, fifteen of the post-menopausal female subjects developed new-onset osteoporosis. After adjustment for confounders, the odds ratios (OR) for osteoporosis in the highest tertiles of vitamins C and E and retinol intakes against the lowest tertiles were 0.15 (95% confidence interval (CI): 0.02-0.99), 0.50 (CI: 0.08-3.23), and 1.49 (CI: 0.36-6.22), respectively. Furthermore, a significantly lower odds ratio was observed in the higher vitamin C intake group (169-625 mg/d) with higher serum β-cryptoxanthin (1.88-10.53 μM) against the lower vitamin C intake group (47-168 mg/d) with lower serum β-cryptoxanthin (0.24-1.84 μM) used for the reference group (p<0.05). The combination of β-cryptoxanthin and vitamin C is inversely associated with the risk of developing osteoporosis in post-menopausal Japanese female subjects. PMID:27465725

  18. Pharmacologic Approaches to Electrolyte Abnormalities in Heart Failure.

    PubMed

    Grodin, Justin L

    2016-08-01

    Electrolyte abnormalities are common in heart failure and can arise from a variety of etiologies. Neurohormonal activation from ventricular dysfunction, renal dysfunction, and heart failure medications can perturb electrolyte homeostasis which impact both heart failure-related morbidity and mortality. These include disturbances in serum sodium, chloride, acid-base, and potassium homeostasis. Pharmacological treatments differ for each electrolyte abnormality and vary from older, established treatments like the vaptans or acetazolamide, to experimental or theoretical treatments like hypertonic saline or urea, or to newer, novel agents like the potassium binders: patiromer and zirconium cyclosilicate. Pharmacologic approaches range from limiting electrolyte intake or directly repleting the electrolyte, to blocking or promoting their resorption, and to neurohormonal antagonism. Because of the prevalence and clinical impact of electrolyte abnormalities, understanding both the older and newer therapeutic options is and will continue to be necessity for the management of heart failure. PMID:27278221

  19. Thyroid abnormalities after therapeutic external radiation

    SciTech Connect

    Hancock, S.L.; McDougall, I.R.; Constine, L.S.

    1995-03-30

    The thyroid gland is the largest pure endocrine gland in the body and one of the organs most likely to produce clinically significant abnormalities after therapeutic external radiation. Radiation doses to the thyroid that exceed approximately 26 Gy frequently produce hypothyroidism, which may be clinically overt or subclinical, as manifested by increased serum thyrotropin and normal serum-free thyroxine concentrations. Pituitary or hypothalamic hypothyroidism may arise when the pituitary region receives doses exceeding 50 Gy with conventional, 1.8-2 Gy fractionation. Direct irradiation of the thyroid may increase the risk of Graves` disease or euthyroid Graves` ophthalmopathy. Silent thyroiditis, cystic degeneration, benign adenoma, and thyroid cancer have been observed after therapeutically relevant doses of external radiation. Direct or incidental thyroid irradiation increases the risk for well-differentiated, papillary, and follicular thyroid cancer from 15- to 53-fold. Thyroid cancer risk is highest following radiation at a young age, decreases with increasing age at treatment, and increases with follow-up duration. The potentially prolonged latent period between radiation exposure and the development of thyroid dysfunction, thyroid nodularity, and thyroid cancer means that individuals who have received neck or pituitary irradiation require careful, periodic clinical and laboratory evaluation to avoid excess morbidity. 39 refs.

  20. Prenatal imaging of distal limb abnormalities using OCT in mice

    NASA Astrophysics Data System (ADS)

    Larina, Irina V.; Syed, Saba H.; Dickinson, Mary E.; Overbeek, Paul; Larin, Kirill V.

    2012-01-01

    Congenital abnormalities of the limbs are common birth defects. These include missing or extra fingers or toes, abnormal limb length, and abnormalities in patterning of bones, cartilage or muscles. Optical Coherence Tomography (OCT) is a 3-D imaging modality, which can produce high-resolution (~8 μm) images of developing embryos with an imaging depth of a few millimeters. Here we demonstrate the capability of OCT to perform 3D imaging of limb development in normal embryos and a mouse model with congenital abnormalities. Our results suggest that OCT is a promising tool to analyze embryonic limb development in mammalian models of congenital defects.

  1. Chromosomal abnormalities in human sperm

    SciTech Connect

    Martin, R.H.

    1985-01-01

    The ability to analyze human sperm chromosome complements after penetration of zona pellucida-free hamster eggs provides the first opportunity to study the frequency and type of chromosomal abnormalities in human gametes. Two large-scale studies have provided information on normal men. We have studied 1,426 sperm complements from 45 normal men and found an abnormality rate of 8.9%. Brandriff et al. (5) found 8.1% abnormal complements in 909 sperm from 4 men. The distribution of numerical and structural abnormalities was markedly dissimilar in the 2 studies. The frequency of aneuploidy was 5% in our sample and only 1.6% in Brandriff's, perhaps reflecting individual variability among donors. The frequency of 24,YY sperm was low: 0/1,426 and 1/909. This suggests that the estimates of nondisjunction based on fluorescent Y body data (1% to 5%) are not accurate. We have also studied men at increased risk of sperm chromosomal abnormalities. The frequency of chromosomally unbalanced sperm in 6 men heterozygous for structural abnormalities varied dramatically: 77% for t11;22, 32% for t6;14, 19% for t5;18, 13% for t14;21, and 0% for inv 3 and 7. We have also studied 13 cancer patients before and after radiotherapy and demonstrated a significant dose-dependent increase of sperm chromosome abnormalities (numerical and structural) 36 months after radiation treatment.

  2. A Study on the Relationship between Serum Beta 2-Microglobulin Levels, Underlying Chronic Kidney Disease, and Peripheral Arterial Disease in High-Vascular-Risk Patients

    PubMed Central

    Real de Asúa, Diego; Puchades, Ramón; García-Polo, Iluminada; Suárez, Carmen

    2012-01-01

    Background Serum beta 2-microglobulin (B2M) levels have been found to be increased in patients with peripheral arterial disease (PAD), yet it is still unknown whether B2M correlates with PAD intensity. Objectives We aim to evaluate the correlation between B2M and the ankle-brachial index (ABI) values in high-vascular-risk patients. Methods This is a cross-sectional study of 63 high-vascular-risk patients admitted to the Cardiology Department or evaluated as outpatients in the Internal Medicine Department of our institution. Patients were classified into two groups according to their ABI: patients without PAD (n = 44, ABI values between 0.9 and 1.4) and patients with PAD (n = 19, ABI values lower than 0.9 or higher than 1.4). We performed univariate and multivariate analysis based on a multiple linear regression model. Results Serum B2M levels were higher in patients with pathological ABI values than in those without PAD (2.36 ± 1.13 vs. 1.80 ± 0.65 mg/L; P<0.05). We found no correlation between B2M and ABI in our total population (r = –0.12) or in patients with PAD (r = –0.09; NS for both comparisons). Age, gender, arterial hypertension, estimated glomerular filtration rate (eGFR), uric acid, total cholesterol, and LDL-cholesterol correlated with B2M in the univariate analysis. In the final linear regression model, eGFR, uric acid and total cholesterol correlated independently with B2M (P<0.01). Conclusion We found no correlation between B2M levels and ABI values in high-vascular-risk patients that could usefully help in the subsequent diagnosis of PAD. However, we observed a significant correlation between B2M and eGFR, even when renal function was only slightly impaired. PMID:24757603

  3. Optimal Vitamin D Supplementation Doses that Minimize the Risk for Both Low and High Serum 25-Hydroxyvitamin D Concentrations in the General Population

    PubMed Central

    Veugelers, Paul J.; Pham, Truong-Minh; Ekwaru, John Paul

    2015-01-01

    The Recommended Dietary Allowance (RDA) is the nutrient intake considered to be sufficient to meet the requirements of 97.5% of the population. Recent reports revealed a statistical error in the calculation of the RDA for vitamin D opening the question of what the recommendation should be. We took a dual approach to answer this question: (1) we aggregated 108 published estimates on vitamin D supplementation and vitamin D status; and (2) we analyzed 13,987 observations of program participants. The aggregation of published data revealed that 2909 IU of vitamin D per day is needed to achieve serum 25-hydroxyvitamin D (25(OH)D) concentrations of 50 nmol/L or more in 97.5% of healthy individuals. For normal weight, overweight and obese program participants this was 3094, 4450 and 7248 IU respectively. These supplementation doses would also result in 2.5% of normal weight, overweight and obese participants having 25(OH)D concentrations above 210, 200 and 214 nmol/L respectively. As these concentrations are high, an approach that minimizes the risk for both low and high concentrations seems desirable. With this approach we estimated, for example, that doses of 1885, 2802 and 6235 IU per day are required for normal weight, overweight and obese individuals respectively to achieve natural 25(OH)D concentrations (defined as 58 to 171 nmol/L). In conclusion, the large extent of variability in 25(OH)D concentrations makes a RDA for vitamin D neither desirable nor feasible. We therefore propose recommendations be articulated in the form of an optimal intake that minimizes the risk for both low and high serum 25(OH)D concentrations. This contribution includes body weight specific recommendations for optimal intakes for various combinations of lower and upper 25(OH)D concentration targets. PMID:26690210

  4. High serum level of C-reactive protein is associated with worse outcome of patients with advanced-stage NSCLC treated with erlotinib.

    PubMed

    Fiala, Ondrej; Pesek, Milos; Finek, Jindrich; Topolcan, Ondrej; Racek, Jaroslav; Minarik, Marek; Benesova, Lucie; Bortlicek, Zbynek; Poprach, Alexandr; Buchler, Tomas

    2015-12-01

    Erlotinib is a low molecular weight tyrosine kinase inhibitor (TKI) directed at epidermal growth factor receptor (EGFR), widely used in the treatment of locally advanced or metastatic-stage non-small cell lung cancer (NSCLC). Although introduction of EGFR-TKIs have significantly extended survival of advanced-stage NSCLC patients, their efficacy in the entire patient population is relatively low. Aside from activating EGFR mutations, no reliable biochemical or molecular predictors of response to erlotinib have been established. The aim of our retrospective study was to evaluate the association of baseline serum levels of C-reactive protein (CRP) with outcomes in patients with advanced-stage NSCLC treated with erlotinib. We retrospectively analyzed clinical data of 595 patients with advanced-stage NSCLC (IIIB or IV) treated with erlotinib. Serum CRP was measured using an immunoturbidimetric method. High baseline levels of CRP (≥10 mg/l) were measured in 387 (65 %) patients, and normal levels (<10 mg/l) were measured in 208 (35 %) patients. The median progression-free survival (PFS) and overall survival (OS) for patients with high CRP was 1.8 and 7.7 compared to 2.8 and 14.4 months for patients with low CRP (p < 0.001 and p < 0.001). The multivariable Cox proportional hazards model revealed that CRP was significantly associated with PFS and also with OS (hazard ratio (HR) = 1.57, p < 0.001, and HR = 1.63, p < 0.001, respectively). In conclusion, the results of the conducted retrospective study suggest that high baseline level of CRP was independently associated with worse outcome of patients with advanced-stage NSCLC treated with erlotinib. CRP is a commonly used biomarker which is simple and easy to detect, and thus, it is feasible for the use in the routine clinical practice. PMID:26088452

  5. Haematological abnormalities in mitochondrial disorders

    PubMed Central

    Finsterer, Josef; Frank, Marlies

    2015-01-01

    INTRODUCTION This study aimed to assess the kind of haematological abnormalities that are present in patients with mitochondrial disorders (MIDs) and the frequency of their occurrence. METHODS The blood cell counts of a cohort of patients with syndromic and non-syndromic MIDs were retrospectively reviewed. MIDs were classified as ‘definite’, ‘probable’ or ‘possible’ according to clinical presentation, instrumental findings, immunohistological findings on muscle biopsy, biochemical abnormalities of the respiratory chain and/or the results of genetic studies. Patients who had medical conditions other than MID that account for the haematological abnormalities were excluded. RESULTS A total of 46 patients (‘definite’ = 5; ‘probable’ = 9; ‘possible’ = 32) had haematological abnormalities attributable to MIDs. The most frequent haematological abnormality in patients with MIDs was anaemia. 27 patients had anaemia as their sole haematological problem. Anaemia was associated with thrombopenia (n = 4), thrombocytosis (n = 2), leucopenia (n = 2), and eosinophilia (n = 1). Anaemia was hypochromic and normocytic in 27 patients, hypochromic and microcytic in six patients, hyperchromic and macrocytic in two patients, and normochromic and microcytic in one patient. Among the 46 patients with a mitochondrial haematological abnormality, 78.3% had anaemia, 13.0% had thrombopenia, 8.7% had leucopenia and 8.7% had eosinophilia, alone or in combination with other haematological abnormalities. CONCLUSION MID should be considered if a patient’s abnormal blood cell counts (particularly those associated with anaemia, thrombopenia, leucopenia or eosinophilia) cannot be explained by established causes. Abnormal blood cell counts may be the sole manifestation of MID or a collateral feature of a multisystem problem. PMID:26243978

  6. Catechin averts experimental diabetes mellitus-induced vascular endothelial structural and functional abnormalities.

    PubMed

    Bhardwaj, Pooja; Khanna, Deepa; Balakumar, Pitchai

    2014-03-01

    Diabetes mellitus is associated with an induction of vascular endothelial dysfunction (VED), an initial event that could lead to the pathogenesis of atherosclerosis and hypertension. Previous studies showed that catechin, a key component of green tea, possesses vascular beneficial effects. We investigated the effect of catechin hydrate in diabetes mellitus-induced experimental vascular endothelial abnormalities (VEA). Streptozotocin (50 mg/kg, i.p., once) administration to rats produced diabetes mellitus, which subsequently induced VEA in 8 weeks by markedly attenuating acetylcholine-induced endothelium-dependent relaxation in the isolated aortic ring preparation, decreasing aortic and serum nitrite/nitrate concentrations and impairing aortic endothelial integrity. These abnormalities in diabetic rats were accompanied with elevated aortic superoxide anion generation and serum lipid peroxidation in addition to hyperglycemia. Catechin hydrate treatment (50 mg/kg/day p.o., 3 weeks) markedly prevented diabetes mellitus-induced VEA and vascular oxidative stress. Intriguingly, in vitro incubation of L-NAME (100 μM), an inhibitor of nitric oxide synthase, or Wortmannin (100 nM), a selective inhibitor of phosphatidylinositol 3-kinase (PI3K), markedly prevented catechin hydrate-induced improvement in acetylcholine-provoked endothelium-dependent relaxation in the diabetic rat aorta. Moreover, catechin hydrate treatment considerably reduced the elevated level of serum glucose in diabetic rats. In conclusion, catechin hydrate treatment prevents diabetes mellitus-induced VED through the activation of endothelial PI3K signal and subsequent activation of eNOS and generation of nitric oxide. In addition, reduction in high glucose, vascular oxidative stress, and lipid peroxidation might additionally contribute to catechin hydrate-associated prevention of diabetic VEA. PMID:24048981

  7. The Human Serum Metabolome

    PubMed Central

    Psychogios, Nikolaos; Hau, David D.; Peng, Jun; Guo, An Chi; Mandal, Rupasri; Bouatra, Souhaila; Sinelnikov, Igor; Krishnamurthy, Ramanarayan; Eisner, Roman; Gautam, Bijaya; Young, Nelson; Xia, Jianguo; Knox, Craig; Dong, Edison; Huang, Paul; Hollander, Zsuzsanna; Pedersen, Theresa L.; Smith, Steven R.; Bamforth, Fiona; Greiner, Russ; McManus, Bruce; Newman, John W.; Goodfriend, Theodore; Wishart, David S.

    2011-01-01

    Continuing improvements in analytical technology along with an increased interest in performing comprehensive, quantitative metabolic profiling, is leading to increased interest pressures within the metabolomics community to develop centralized metabolite reference resources for certain clinically important biofluids, such as cerebrospinal fluid, urine and blood. As part of an ongoing effort to systematically characterize the human metabolome through the Human Metabolome Project, we have undertaken the task of characterizing the human serum metabolome. In doing so, we have combined targeted and non-targeted NMR, GC-MS and LC-MS methods with computer-aided literature mining to identify and quantify a comprehensive, if not absolutely complete, set of metabolites commonly detected and quantified (with today's technology) in the human serum metabolome. Our use of multiple metabolomics platforms and technologies allowed us to substantially enhance the level of metabolome coverage while critically assessing the relative strengths and weaknesses of these platforms or technologies. Tables containing the complete set of 4229 confirmed and highly probable human serum compounds, their concentrations, related literature references and links to their known disease associations are freely available at http://www.serummetabolome.ca. PMID:21359215

  8. CCDC115 Deficiency Causes a Disorder of Golgi Homeostasis with Abnormal Protein Glycosylation.

    PubMed

    Jansen, Jos C; Cirak, Sebahattin; van Scherpenzeel, Monique; Timal, Sharita; Reunert, Janine; Rust, Stephan; Pérez, Belén; Vicogne, Dorothée; Krawitz, Peter; Wada, Yoshinao; Ashikov, Angel; Pérez-Cerdá, Celia; Medrano, Celia; Arnoldy, Andrea; H