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Sample records for serum tgf-beta1 se-cad

  1. Serum concentrations of sIL-2R, IL-6, TGF-beta1, neopterin, and zinc in chronic hepatitis C patients treated with interferon-alpha.

    PubMed

    Grüngreiff, K; Reinhold, D; Ansorge, S

    1999-12-01

    T lymphocytes and immunoregulatory cytokines play an important role in the host response to hepatitis C virus (HCV) infection. Zinc is required for a wide spectrum of immune functions, including T-cell activity. To determine the clinical significance of the cytokines sIL-2R, IL-6, TGF-beta1, neopterin, and of zinc in chronic heptatitis C virus (HCV) infection, we investigated their concentrations in the serum of 16 patients with chronic HCV infection before, during and at the end of therapy with interferon (IFN) alpha (Roferon A), and after 6 months follow-up. Elevated concentrations of sIL-2R, IL-6, TGF-beta1, and neopterin were found in the serum of all patients prior to therapy, as compared to healthy controls. sIL-2R patterns differed in responders and non-responders. While the mean concentration of sIL-2R (335.75 pg/ml) before therapy was about 40% higher in complete responders (n=4) than in controls (272.20 pg/ml), the mean concentration in non-responders (n=6) was 4-fold higher than in controls (1153.33 pg/ml). During therapy, sIL-2R levels in responders decreased by about 40%. Mean IL-6 concentrations in both complete and partial responders (n=6) decreased continuously during treatment, while mean concentrations in non-responders decreased for only a short time, and increased again after cessation of therapy. Mean levels of TGF-beta1 behaved similarly to those of IL-6. Only negligible differences in mean neopterin levels were found between responders and non-responders over the entire observation time. The mean serum zinc concentrations slightly decreased in all 3 patient groups, the greatest reduction occurring in 3 of the 4 responders. The present findings underscore the importance of the immune system in the pathogenesis of chronic HCV infection. Serum sIL-2R levels may be used as a serological marker of outcome following IFN-alpha treatment. PMID:10623433

  2. TGF-beta1 and IGF-1 expression are differently regulated by serum in metastatic and non-metastatic human breast cancer cells.

    PubMed

    Perlino, E; Tommasi, S; Moro, L; Bellizzi, A; Marra, E; Casavola, V; Reshkin, S J

    2000-01-01

    Transforming growth factor-beta (TGF-beta) exerts an inhibitory effect on epithelial cell proliferation while insulin-like growth factor-1 (IGF-1) is a positive regulator of proliferation and together they may participate in driving neoplastic progression. The regulation of TGF-beta1 and IGF-1 gene expression was analyzed in an in vitro model of an estrogen receptor positive (ER+), non-metastatic (MCF-7) and an (ER-), metastatic (MDA-MB-435) breast cancer cell line, respectively. Our results indicate a loss of the regulation of TGF-beta1 and the gain of the expression and upregulation of IGF-1 pathways during malignant progression. These data demonstrate that two factors, convergent on cell growth, can have divergent roles in the regulation of the expression of TGF-beta1. PMID:10601561

  3. TGF-beta1 release from biodegradable polymer microparticles: its effects on marrow stromal osteoblast function

    NASA Technical Reports Server (NTRS)

    Lu, L.; Yaszemski, M. J.; Mikos, A. G.; McIntire, L. V. (Principal Investigator)

    2001-01-01

    BACKGROUND: Controlled release of transforming growth factor-beta1 (TGF-beta1) to a bone defect may be beneficial for the induction of a bone regeneration cascade. The objectives of this work were to assess the feasibility of using biodegradable polymer microparticles as carriers for controlled TGF-beta1 delivery and the effects of released TGF-beta1 on the proliferation and differentiation of marrow stromal cells in vitro. METHODS: Recombinant human TGF-beta1 was incorporated into microparticles of blends of poly(DL-lactic-co-glycolic acid) (PLGA) and poly(ethylene glycol) (PEG). Fluorescein isothiocynate-labeled bovine serum albumin (FITC-BSA) was co-encapsulated as a porogen. The effects of PEG content (0, 1, or 5% by weight [wt%]) and buffer pH (3, 5, or 7.4) on the protein release kinetics and the degradation of PLGA were determined in vitro for as long as 28 days. Rat marrow stromal cells were seeded on a biodegradable poly(propylene fumarate) (PPF) substrate. The dose response and biological activity of released TGF-beta1 was determined after 3 days in culture. The effects of TGF-beta1 released from PLGA/PEG microparticles on marrow stromal cell proliferation and osteoblastic differentiation were assessed during a 21-day period. RESULTS: TGF-beta1 was encapsulated along with FITC-BSA into PLGA/PEG blend microparticles and released in a multiphasic fashion including an initial burst for as long as 28 days in vitro. Increasing the initial PEG content resulted in a decreased cumulative mass of released proteins. Aggregation of FITC-BSA occurred at lower buffer pH, which led to decreased release rates of both proteins. The degradation of PLGA was increased at higher PEG content and significantly accelerated at acidic pH conditions. Rat marrow stromal cells cultured on PPF substrates showed a dose response to TGF-beta1 released from the microparticles similar to that of added TGF-beta1, indicating that the activity of TGF-beta1 was retained during microparticle

  4. Association of transforming growth factor-beta1 (TGFbeta1) T29 --> C gene polymorphism with bone mineral density (BMD), changes in BMD, and serum concentrations of TGF-beta1 in a population-based sample of postmenopausal german women.

    PubMed

    Hinke, V; Seck, T; Clanget, C; Scheidt-Nave, C; Ziegler, R; Pfeilschifter, J

    2001-12-01

    TGF-beta1 is thought to play an important role in bone turnover. Thus, the gene encoding TGF-beta1 is a prime candidate for the genetic regulation of bone density. Recent studies have suggested that a T29 --> C polymorphism in the signal sequence region of the TGF-beta1 gene may be related to bone mineral density (BMD) and bone loss in postmenopausal Japanese women. In the present study, we examined the relationship between this polymorphism and BMD in a population-based sample of 102 estrogen-deficient postmenopausal women from the Heidelberg cohort of the European Vertebral Osteoporosis Study (EVOS). Average BMD in women with the TT genotype was approximately 10% higher at both the lumbar spine and the femoral neck compared with women with the CC genotype (spine: 980 vs. 887 mg/cm2, P = 0.05; femoral neck: 755 vs. 674 mg/cm2; P = 0.02). Women with the TT genotype also experienced less overall bone loss at the total hip, compared with women with the CC genotype. Serum levels of TGF-beta1 were higher in women with the TT genotype than in those with the CC genotype (46.5 ng/ml vs. 32.3 ng/ml, P = 0.001). These data are clearly in contrast to findings in postmenopausal Japanese women where the CC genotype was associated with higher BMD and decreased bone loss. Further studies are therefore necessary to clarify the relationship between this polymorphism and BMD. PMID:11800227

  5. Angiotensin type 1 (AT1) and type 2 (AT2) receptors mediate the increase in TGF-beta1 in thyroid hormone-induced cardiac hypertrophy.

    PubMed

    Diniz, G P; Carneiro-Ramos, M S; Barreto-Chaves, M L M

    2007-04-01

    Increased thyroid hormone (TH) levels are known to induce cardiac hypertrophy. Some studies have provided evidence for a functional link between angiotensin II (ANG II) and transforming growth factor beta1 (TGF-beta1) in the heart, both being able to also induce cardiac hypertrophy. However, the contribution of this growth factor activated directly by TH or indirectly by ANG II in cardiac hypertrophy development remains unknown. To analyze the possible role of TGF-beta1 in cardiac hypertrophy induced by TH and also to evaluate if the TGF-beta1 effect is mediated by ANG II receptors, we employed Wistar rats separated into control, hypothyroid (hypo) and hyperthyroid (T4 - 10) groups combined or not with ANG II receptor blockers (losartan or PD123319). Serum levels of T3 and T4, systolic pressure and heart rate confirmed the thyroid state of the groups. The T4 - 10 group presented a significant increase in cardiac TGF-beta1 levels; however, TGF-beta1 levels in the hypo group did not change in relation to the control. Inhibition of the increase in cardiac TGF-beta1 levels was observed in the groups treated with T4 in association with losartan or PD123319 when compared to the T4 - 10 group. These results demonstrate for the first time the TH-modulated induction of cardiac TGF-beta1 in cardiac hypertrophy, and that this effect is mediated by ANG II receptors. PMID:17206447

  6. Elevated D-glucose concentrations modulate TGF-beta 1 synthesis by human cultured renal proximal tubular cells. The permissive role of platelet-derived growth factor.

    PubMed Central

    Phillips, A. O.; Steadman, R.; Topley, N.; Williams, J. D.

    1995-01-01

    Interstitial fibrosis is a marker of progression of renal impairment in diabetic nephropathy. Transforming growth factor (TGF)-beta 1 is one of a group of pro-fibrotic cytokines and growth factors that have been associated with the development of interstitial fibrosis. We have examined the modulating influence of glucose on the production of TGF-beta 1 by cultured human proximal tubular cells. Incubation of growth-arrested human proximal tubular cells (HPTC) (72 hours in serum free medium) in 25 mmol/L D-glucose resulted in increased expression of TGF-beta 1 mRNA (as assessed by reverse transcription polymerase chain reaction). This was apparent after 6 hours and increased up to 120 hours exposure. TGF-beta 1 secretion, however, as measured by specific enzyme-linked immunoassay, was unaffected by exposure to 25 mmol/L D-glucose. Sequential stimulation of HPTC, first with 25 mmol/L D-glucose for 48 hours and then with platelet-derived growth factor (PDGF) isoforms, resulted in a dose-dependent secretion of TGF-beta 1. Pre-exposure to 5 mmol/L D-glucose or 25 mmol/L L-glucose did not prime for TGF-beta 1 release. At 50 ng/ml PDGF this effect was greatest for the AA isoform (AA 31.4 +/- 7.1, AB 20.98 +/- 8.9, BB 7.8 +/- 2.2, P < 0.05 for all versus control, n = 3, mean +/- SEM ng/10(6) cells/24 hours). These effects were blocked by the addition of antibody to the PDGF alpha-receptor. TGF-beta 1 secretion was inhibited in a dose-dependent manner by pretreatment with cyclohexamide, but was not affected by pretreatment with actinomycin D. Stimulation of HPTC with a single dose of PDGF induced TGF-beta 1 mRNA; however, only after application of a second dose of PDGF (after TGF-beta 1 mRNA induction) did TGF-beta 1 protein secretion occur. We also demonstrated that PDGF stimulation of HPTC induced an inherently more stable TGF-beta 1 mRNA transcript. These findings demonstrate that elevated D-glucose concentration alone is insufficient to lead to increased TGF-beta 1

  7. The antifibrotic effects of TGF-{beta}1 siRNA on hepatic fibrosis in rats

    SciTech Connect

    Lang, Qing; Liu, Qi; Xu, Ning; Qian, Ke-Li; Qi, Jing-Hu; Sun, Yin-Chun; Xiao, Lang; Shi, Xiao-Feng

    2011-06-10

    Highlights: {yields} We constructed CCL4 induced liver fibrosis model successfully. {yields} We proofed that the TGF-{beta}1 siRNA had a definite therapy effect to CCL4 induced liver fibrosis. {yields} The therapy effect of TGF-{beta}1 siRNA had dose-dependent. -- Abstract: Background/aims: Hepatic fibrosis results from the excessive secretion of matrix proteins by hepatic stellate cells (HSCs), which proliferate during fibrotic liver injury. Transforming growth factor (TGF)-{beta}1 is the dominant stimulus for extracellular matrix (ECM) production by stellate cells. Our study was designed to investigate the antifibrotic effects of using short interference RNA (siRNA) to target TGF-{beta}1 in hepatic fibrosis and its mechanism in rats exposed to a high-fat diet and carbon tetrachloride (CCL4). Methods: A total of 40 healthy, male SD (Sprague-Dawley) rats were randomly divided into five even groups containing of eight rats each: normal group, model group, TGF-{beta}1 siRNA 0.125 mg/kg treatment group, TGF-{beta}1 siRNA 0.25 mg/kg treatment group and TGF-{beta}1 siRNA negative control group (0.25 mg/kg). CCL4 and a high-fat diet were used for 8 weeks to induce hepatic fibrosis. All the rats were then sacrificed to collect liver tissue samples. A portion of the liver samples were soaked in formalin for Hematoxylin-Eosin staining, classifying the degree of liver fibrosis, and detecting the expression of type I and III collagen and TGF-{beta}1; the remaining liver samples were stored in liquid nitrogen to be used for detecting TGF-{beta}1 by Western blotting and for measuring the mRNA expression of type I and III collagen and TGF-{beta}1 by quantitative real-time polymerase chain reaction. Results: Comparing the TGF-{beta}1 siRNA 0.25 mg/kg treatment group to the model group, the TGF-{beta}1 siRNA negative control group and the TGF-{beta}1 siRNA 0.125 mg/kg treatment group showed significantly reduced levels of pathological changes, protein expression and the m

  8. Transforming growth factor beta1 (TGF-beta1) is a preoperative prognostic indicator in advanced gastric carcinoma.

    PubMed Central

    Nakamura, M.; Katano, M.; Kuwahara, A.; Fujimoto, K.; Miyazaki, K.; Morisaki, T.; Mori, M.

    1998-01-01

    It has been generally accepted that transforming growth factor beta1 (TGF-beta1) has both negative and positive effects on tumour growth and progression. This study analysed the prognostic value of TGF-beta1 mRNA in advanced gastric carcinoma. A reverse transcriptase-polymerase chain reaction analysis (RT-PCR) was used for TGF-beta1 in endoscopic biopsy specimens from 42 advanced gastric carcinomas. Thirty specimens expressed TGF-beta1 mRNA while 12 specimens did not. The follow-up duration ranged from 4 to 37 months (mean 22.8 months). TGF-beta1-positive group demonstrated a shorter overall survival compared with the TGF-beta1 -negative group (P=0.0014). A significant correlation was also found in the 32 patients who underwent curative resection (P=0.0048). Significant correlations were found between TGF-beta1 mRNA expression and both stage (P=0.0015) and nodal involvement (P=0.0060). Multivariate analysis demonstrated that only TGF-beta1 mRNA expression (P=0.0306) was an independent prognostic factor. All of ten patients who underwent non-curative resection expressed TGF-beta1 mRNA. Expression of TGF-beta1 mRNA in gastric biopsy specimens may be an important preoperative prognostic variable for advanced gastric carcinoma. Images Figure 1 PMID:9823982

  9. IL-4 and TGF-beta 1 counterbalance one another while regulating mast cell homeostasis.

    PubMed

    Macey, Matthew R; Sturgill, Jamie L; Morales, Johanna K; Falanga, Yves T; Morales, Joshua; Norton, Sarah K; Yerram, Nitin; Shim, Hoon; Fernando, Josephine; Gifillan, Alasdair M; Gomez, Gregorio; Schwartz, Lawrence; Oskeritzian, Carole; Spiegel, Sarah; Conrad, Daniel; Ryan, John J

    2010-05-01

    Mast cell responses can be altered by cytokines, including those secreted by Th2 and regulatory T cells (Treg). Given the important role of mast cells in Th2-mediated inflammation and recent demonstrations of Treg-mast cell interactions, we examined the ability of IL-4 and TGF-beta1 to regulate mast cell homeostasis. Using in vitro and in vivo studies of mouse and human mast cells, we demonstrate that IL-4 suppresses TGF-beta1 receptor expression and signaling, and vice versa. In vitro studies demonstrated that IL-4 and TGF-beta1 had balancing effects on mast cell survival, migration, and FcepsilonRI expression, with each cytokine cancelling the effects of the other. However, in vivo analysis of peritoneal inflammation during Nippostrongylus brasiliensis infection in mice revealed a dominant suppressive function for TGF-beta1. These data support the existence of a cytokine network involving the Th2 cytokine IL-4 and the Treg cytokine TGF-beta1 that can regulate mast cell homeostasis. Dysregulation of this balance may impact allergic disease and be amenable to targeted therapy. PMID:20304823

  10. IGF-I and TGF-beta1 have distinct effects on phenotype and proliferation of intestinal fibroblasts.

    PubMed

    Simmons, James G; Pucilowska, Jolanta B; Keku, Temitope O; Lund, P Kay

    2002-09-01

    Insulin-like growth factor I (IGF-I) and transforming growth factor-beta1 (TGF-beta1) are upregulated in myofibroblasts at sites of fibrosis in experimental enterocolitis and in Crohn's disease (CD). We compared the sites of expression of IGF-I and TGF-beta1 in a rat peptidoglycan-polysaccharide (PG-PS) model of chronic granulomatous enterocolitis and fibrosis. We used the human colonic CCD-18Co fibroblast/myofibroblast cell line to test the hypothesis that TGF-beta1 and IGF-I interact to regulate proliferation, collagen synthesis, and activated phenotype typified by expression of alpha-smooth muscle actin and organization into stress fibers. IGF-I potently stimulated while TGF-beta1 inhibited basal DNA synthesis. TGF-beta1 and IGF-I each had similar but not additive effects to induce type I collagen. TGF-beta1 but not IGF-I potently stimulated expression of alpha-smooth muscle actin and stress fiber formation. IGF-I in combination with TGF-beta1 attenuated stress fiber formation without reducing alpha-smooth muscle actin expression. Stress fibers were not a prerequisite for increased collagen synthesis. TGF-beta1 upregulated IGF-I mRNA, which led us to examine the effects of IGF-I in cells previously activated by TGF-beta1 pretreatment. IGF-I potently stimulated proliferation of TGF-beta1-activated myofibroblasts without reversing activated fibrogenic phenotype. We conclude that TGF-beta1 and IGF-I both stimulate type I collagen synthesis but have differential effects on activated phenotype and proliferation. We propose that during intestinal inflammation, regulation of activated phenotype and proliferation may require sequential actions of TGF-beta1 and IGF-I, but they may act in concert to increase collagen deposition. PMID:12181198

  11. The immunomodulatory activity of human amniotic fluid can be correlated with transforming growth factor-beta 1 (TGF-beta 1) and beta 2 activity.

    PubMed Central

    Lang, A K; Searle, R F

    1994-01-01

    The role of alphafetoprotein (AFP) in the immunomodulatory activity of amniotic fluids (AF) from normally progressing human pregnancy (weeks 14-16) was investigated. A panel of 42 AF (25% v/v) reduced significantly phytohaemagglutinin (PHA)-induced peripheral blood mononuclear cell (PBMC) proliferation in serum-free cultures with a mean per cent inhibition of 68.4 +/- 5.5%. In contrast, AFP preparations, with one exception (U.AFP), failed to display inhibitory activity. Pretreatment of AF with anti-TGF-beta 1 and beta 2 antibodies used alone resulted in the mean per cent loss of inhibition of 33.1 +/- 3.9% and 52.3 +/- 7.5%, respectively. A summative loss of AF-mediated inhibition was detected when anti-TGF-beta 1 and beta 2 antibodies were used in combination, but immunomodulation was rarely abolished 100% by this treatment. Anti-TGF-beta 2 antibody treatment, unlike anti-TGF-beta 1 antibody treatment, reversed the inhibitory activity of U.AFP. The amount of TGF-beta 1 and beta 2 contained in human AF was studied by growth inhibition of Mv1 Lu cells. The mean levels of TGF-beta 1 and beta 2 in AF were 11 +/- 0.9 U/ml and 2.3 +/- 0.4 U/ml, respectively, which corresponds with a mean per cent inhibition of 49 +/- 4.7%. U.AFP also significantly inhibited Mv1 Lu cell growth. To investigate the mechanism of AF-mediated inhibition, the effect of AF and AFP on IL-2 production by concanavalin A (Con A)-stimulated PBMC blasts was determined by the CTLL-2 cell bioassay. IL-2 production was reduced 55.5% in AF-treated blasts and 61% in U.AFP-treated blasts compared with controls. Our findings indicate that the immunomodulatory activity of human AF can be correlated with TGF-beta 1 and beta 2 and not with AFP, the inhibitory activity of U.AFP preparation reflecting copurifying TGF-beta 2 activity. PMID:7518368

  12. TGF-beta1 and C-erb-B2 neu oncoprotein in Egyptian HCV related chronic liver disease and hepatocellular carcinoma patients.

    PubMed

    El Bassuoni, Maha A; Talaat, Randa M; Ibrahim, Amany A; Shaker, Olfat T

    2008-01-01

    Transforming growth factor beta (TGF-beta), a pro-fibrogenic cytokine, has several polymorphism in humans with difference in activity levels. Hepato-carcinogenesis involves alterations in the action of protooncogenes such as the; neu (C-erb-B2) oncogene. Overexpression of the neu-oncogene has been implicated in experimental cellular transformation and tumorigenesis in a wide range of human cancer. We examined TGF-beta1 and C-erb-B2 mRNA expression and their protein levels in hepatitis C virus (HCV) patients and those developing Hepatocellular carcinoma (HCC). Sixty patients (30 HCV and 30 HCC) and 30 controls were enrolled. HCV patients were classified into mild, moderate, marked and no fibrosis. HCC patients were categorized into grade I, II, Ill. TGP-beta1 and C-erb-B2 expression were studied. Messenger RNA was extracted using the guanidinum thiocyanate phenol chloroform method, and used of RT-PCR. Protein serum levels were estimated by (EIA). Significant difference were obtained when comparing TGF-bet1 and C-erb-B2 mRNA in HCV and HCC P = 0.0076, and controls. The HCV group revealed significant difference with C-erb-B2 but not TGF-B1 mRNA as compared to controls P < 0.005 and P > 0.05 respectively. Serum protein levels demonstrated difference increase significance shown when comparing their levels in both studied groups P < 0.001, P < 0.05 respectively and when compared to controls (P < 0.001). TGF-beta1 serum levels in HCV patients showed increase with degree of fibrosis (P = 0.003) while, C-erbB-2 serum levels showed no significance (P = 0.089). In different grades of HCC patients, TGF-beta1 levels showed no significant difference (P = 0.769). However, C-erb-B2 levels revealed significant difference (P = 0.002) between grade I & III and grade II &. Ill (P < 0.001). Positive correlations to protein serum level were obtained with TGF beta1mRNA in HCV group, while, C-erb-B2 mRNA in HCC patients. In conclusion, TGF-beta1 upregulation in HCC suggests its role in

  13. Epidermal growth factor (EGF) antagonizes transforming growth factor (TGF)-beta1-induced collagen lattice contraction by human skin fibroblasts.

    PubMed

    Park, J S; Kim, J Y; Cho, J Y; Kang, J S; Yu, Y H

    2000-12-01

    Wound contraction plays an important role in healing, but in extreme conditions, it may lead to excessive scar formation and pathological wound contracture. To date, the key regulator of excessive contracture is known to be transforming growth factor-beta (TGF-beta1). In this study, we have evaluated epidermal growth factor (EGF) antagonism in fibroblast-populated collagen lattice (FPCL) gel contraction, which has been generally used as an in vitro model thought to mimic wound contraction in vivo. As expected, TGF-beta1 treatment enhanced normal fibroblast-induced collagen gel contraction in a dose-dependent manner. In contrast, EGF did not affect normal gel formation, but significantly antagonized TGF-beta1-induced gel formation (p<0.05 at 100 ng/ml), whereas the other growth factor, platelet-derived growth factor (PDGF), did not altered either normal or TGF-beta1-induced gel contractions. Similarly, EGF treatment, but not PDGF, also significantly suppressed TGF-beta1 release that was autologously elicited by TGF-beta1 treatment (p<0.01 at 100 ng/ml). Therefore, the results suggest that EGF may negatively regulate the role of TGF-beta1 through attenuating autologous release of TGF-beta1. PMID:11145189

  14. Role of alpha 5 beta 1 integrin in TGF-beta 1-costimulated CD8+ T cell growth and apoptosis.

    PubMed

    Rich, S; Van Nood, N; Lee, H M

    1996-10-01

    TGF-beta 1 regulates cell growth, differentiation, and adhesion and is a potent immunosuppressant, in part through its well-recognized growth-inhibitory effects. However, certain T cell subsets, particularly of naive phenotype, can instead be costimulated to proliferate by TGF-beta 1. We have previously demonstrated that naive murine CD8+ T cells, TCR activated by platebound anti-CD3 Ab or SEB superantigen, are growth stimulated by TGF-beta 1, acquire a memory phenotype, express elevated IL-10 and TGF-beta 1, and cause T cell growth inhibition as effector CD8+ T cells. TGF-beta 1 causes growth among certain nonlymphoid cells in part by inducing or mimicking integrin activation. The present studies thus addressed mediation of TGF-beta 1-dependent growth and survival of anti-CD3-triggered CD8+ T cells via beta 1 integrins. TGF-beta 1 reduced anti-CD3-activated alpha 4 beta 1 integrin expression and constitutive adhesion to fibronectin, while initial alpha 5 beta 1 expression was heightened and adhesive function sustained. Fibronectin-based RGD peptides that bind alpha 5 beta 1 integrins and alpha 5 or beta 1 integrin chain-specific Abs blocked TGF-beta 1-dependent proliferation, while connecting segment-1 peptide that binds alpha 4 beta 1 integrin and alpha 4 chain-specific Abs had no effect. Cross-linked alpha 5- but not alpha 4-specific Ab mimicked TGF-beta 1 function by costimulating CD8+ T cell growth. TGF-beta 1 also caused RGD peptide-sensitive CD8+ T cell aggregation. Additionally, TGF-beta 1-costimulated proliferation correlated with TGF-beta 1 protection of CD8+ T cells from anti-CD3-induced apoptosis. RGD peptides and alpha 5 integrin-specific Ab abolished TGF-beta 1 prevention of activation-induced apoptosis. Therefore, TGF-beta 1 costimulates CD8+ T cell growth via activation of the alpha 5 beta 1 integrin and/or its ligand and supports sustained growth at least in part by alpha 5 beta 1-mediated protection from activation-induced apoptosis. PMID:8816397

  15. Lysyl oxidase like 4, a novel target gene of TGF-{beta}1 signaling, can negatively regulate TGF-{beta}1-induced cell motility in PLC/PRF/5 hepatoma cells

    SciTech Connect

    Kim, Dong Joon; Lee, Dong Chul; Yang, Suk-Jin; Lee, Jung Ju; Bae, Eun Mi; Kim, Dong Min; Min, Sang Hyun; Kim, Soo Jung; Kang, Dong Chul; Sang, Byung Chan; Myung, Pyung Keun; Park, Kyung Chan Yeom, Young Il

    2008-09-05

    Transforming growth factor-{beta}1 (TGF-{beta}1) is a multi-functional cytokine involved in the regulation of cell proliferation, differentiation and extracellular matrix formation. In search for novel genes mediating the TGF-{beta}1 function at downstream signaling, we performed a cDNA microarray analysis and identified 60 genes whose expression is regulated by TGF-{beta}1 in the liver cancer cell line PLC/PRF/5. Among them, we report here lysyl oxidase like 4 (LOXL4) as a novel target of TGF-{beta}1 signaling, and provide experimental evidence for its expression regulation and function. LOXL4 was found to be the only member of LOX family whose expression is induced by TGF-{beta}1 in hepatoma cells. Deletion mapping of the LOXL4 promoter indicated that the TGF-{beta}1 regulation of LOXL4 expression is mediated through the binding of AP1 transcription factor to a conserved region of the promoter. This was confirmed by the chromatin immunoprecipitation assay that captured c-Fos-bound chromatin from TGF-{beta}1-treated cells. Forced expression of LOXL4 in PLC/PRF/5 cells resulted in inhibition of cell motility through Matrigel in the presence of TGF-{beta}1 treatment. In parallel, LOXL4 suppressed the expression of laminins and {alpha}3 integrin and the activity of MMP2. These results suggest that LOXL4 may function as a negative feedback regulator of TGF-{beta}1 in cell invasion by inhibiting the metabolism of extracellular matrix (ECM) components.

  16. FGF-1 reverts epithelial-mesenchymal transition induced by TGF-{beta}1 through MAPK/ERK kinase pathway.

    PubMed

    Ramos, Carlos; Becerril, Carina; Montaño, Martha; García-De-Alba, Carolina; Ramírez, Remedios; Checa, Marco; Pardo, Annie; Selman, Moisés

    2010-08-01

    Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease characterized by the expansion of the fibroblast/myofibroblast population and aberrant remodeling. However, the origin of mesenchymal cells in this disorder is still under debate. Recent evidence indicates that epithelial-mesenchymal transition (EMT) induced primarily by TGF-beta1 plays an important role; however, studies regarding the opposite process, mesenchymal-epithelial transition, are scanty. We have previously shown that fibroblast growth factor-1 (FGF-1) inhibits several profibrogenic effects of TGF-beta1. In this study, we examined the effects of FGF-1 on TGF-beta1-induced EMT. A549 and RLE-6TN (human and rat) alveolar epithelial-like cell lines were stimulated with TGF-beta1 for 72 h, and then, in the presence of TGF-beta1, were cultured with FGF-1 plus heparin for an additional 48 h. After TGF-beta1 treatment, epithelial cells acquired a spindle-like mesenchymal phenotype with a substantial reduction of E-cadherin and cytokeratins and concurrent induction of alpha-smooth muscle actin measured by real-time PCR, Western blotting, and immunocytochemistry. FGF-1 plus heparin reversed these morphological changes and returned the epithelial and mesenchymal markers to control levels. Signaling pathways analyzed by selective pharmacological inhibitors showed that TGF-beta1 induces EMT through Smad pathway, while reversion by FGF-1 occurs through MAPK/ERK kinase pathway, resulting in ERK-1 phosphorylation and Smad2 dephosphorylation. These findings indicate that TGF-beta1-induced EMT is reversed by FGF-1 and suggest therapeutic approaches to target this process in IPF. PMID:20495078

  17. RhoC is essential for TGF-{beta}1-induced invasive capacity of rat ascites hepatoma cells

    SciTech Connect

    Mukai, M.; Endo, H.; Iwasaki, T.; Tatsuta, M.; Togawa, A.; Nakamura, H.; Inoue, M. . E-mail: inoue-ma2@mc.pref.osaka.jp

    2006-07-21

    Transforming growth factor-{beta}1 (TGF-{beta}1) is a multifunctional growth factor that plays a role in cell proliferation, differentiation, extracellular matrix production, apoptosis, and cell motility. We show here that TGF-{beta}1 increased the invasiveness of MM1 cells, which are a highly invasive clone of rat ascites hepatoma cells. Both mRNA and protein levels of RhoC but not RhoA in TGF-{beta}1-treated MM1 cells increased. In parallel with this increase in expression, RhoC activity was induced by TGF-{beta}1 treatment. When RhoC was overexpressed in MM1 cells, the invasive capacity increased. The RhoC-overexpressing cells formed more nodules than did mock cells when injected into rat peritoneum. Furthermore, when RhoC expression was reduced by transfection with shRNA/RhoC, the invasiveness of MM1 cells decreased with concomitant suppression of RhoC expression. Thus, the induced expression of RhoC by TGF-{beta}1 in MM1 cells plays a critical role in TGF-{beta}1-induced cell migration.

  18. Inhibiting and stimulating effects of TGF-. beta. 1 on osteoclastic bone resorption in fetal mouse bone organ cultures

    SciTech Connect

    Dieudonne, S.C.; Foo, P.; van Zoelen, E.J.; Burger, E.H. )

    1991-05-01

    The effects of TGF-{beta} 1 on osteoclastic resorption of fetal mouse calvaria and long bones at various stages of development was studied in organ culture. In resorbing calvariae and long bones with an established marrow cavity TGF-beta 1 (4-10 ng/ml) had a stimulating effect on 45Ca release that was partially inhibited by indomethacin. In primitive long bones, however, which were explanted before osteoclast invasion and excavation of a marrow cavity had started, TGF-beta 1 (1-4 ng/ml) inhibited 45Ca release by an indomethacin-insensitive mechanism. Histomorphometry of long bones after staining for tartrate-resistant acid phosphatase (TRAP) revealed that TGF-beta 1 treatment inhibited the migration of TRAP-positive cells from periosteum to developing marrow cavity and inhibited cell fusion. However, the formation of (mononuclear) TRAP-positive cells in the periosteum-perichondrium was strongly enhanced. These data suggest that TGF-beta 1 modulates various steps in the cascade of osteoclast development, recruitment, and activation in different ways, involving both prostaglandin-mediated and prostaglandin-independent pathways. Therefore the net effect of exogenous TGF-beta 1 on osteoclastic resorption in bone organ cultures depends on the relative prevalence of osteoclast progenitors, precursors, and mature osteoclasts in the tissue under study.

  19. TGF{beta}1 polymorphisms and late clinical radiosensitivity in patients treated for gynecologic tumors

    SciTech Connect

    Ruyck, Kim de . E-mail: kim.deruyck@UGent.be; Van Eijkeren, Marc; Claes, Kathleen; Bacher, Klaus; Vral, Anne; Neve, Wilfried de; Thierens, Hubert

    2006-07-15

    Purpose: To investigate the association between six transforming growth factor {beta}1 gene (TGF{beta}1) polymorphisms (-1.552delAGG, -800G>A, -509C>T, Leu10Pro, Arg25Pro, Thr263Ile) and the occurrence of late normal tissue reactions after gynecologic radiotherapy (RT). Methods and Materials: Seventy-eight women with cervical or endometrial cancer and 140 control individuals were included in the study. According to the Common Terminology Criteria for Adverse Events version 3.0 (CTCAEv3.0) scale, 25 patients showed late adverse RT reactions (CTC2+), of whom 11 had severe complications (CTC3+). Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), single base extension and genotyping assays were performed to examine the polymorphic sites in TGF{beta}1. Results: Homozygous variant -1.552delAGG, -509TT, and 10Pro genotypes were associated with the risk of developing late severe RT reactions. Triple (variant) homozygous patients had a 3.6 times increased risk to develop severe RT reactions (p = 0.26). Neither the -800A allele, nor the 25Pro allele or the 263Ile allele were associated with clinical radiosensitivity. There was perfect linkage disequilibrium (LD) between the -1.552delAGG and the -509C>T polymorphisms, and tight LD between the -1.552/-509 and the Leu10Pro polymorphisms. Haplotype analysis revealed two major haplotypes but could not distinguish radiosensitive from nonradiosensitive patients. Conclusions: The present study shows that homozygous variant TGF{beta}1 -1.552delAGG, -509TT, and 10Pro genotypes may be associated with severe clinical radiosensitivity after gynecologic RT.

  20. Angiotensin II increases CTGF expression via MAPKs/TGF-{beta}1/TRAF6 pathway in atrial fibroblasts

    SciTech Connect

    Gu, Jun; Liu, Xu; Wang, Quan-xing; Tan, Hong-wei; Guo, Meng; Jiang, Wei-feng; Zhou, Li

    2012-10-01

    The activation of transforming growth factor-{beta}1(TGF-{beta}1)/Smad signaling pathway and increased expression of connective tissue growth factor (CTGF) induced by angiotensin II (AngII) have been proposed as a mechanism for atrial fibrosis. However, whether TGF{beta}1/non-Smad signaling pathways involved in AngII-induced fibrogenetic factor expression remained unknown. Recently tumor necrosis factor receptor associated factor 6 (TRAF6)/TGF{beta}-associated kinase 1 (TAK1) has been shown to be crucial for the activation of TGF-{beta}1/non-Smad signaling pathways. In the present study, we explored the role of TGF-{beta}1/TRAF6 pathway in AngII-induced CTGF expression in cultured adult atrial fibroblasts. AngII (1 {mu}M) provoked the activation of P38 mitogen activated protein kinase (P38 MAPK), extracellular signal-regulated kinase 1/2(ERK1/2) and c-Jun NH(2)-terminal kinase (JNK). AngII (1 {mu}M) also promoted TGF{beta}1, TRAF6, CTGF expression and TAK1 phosphorylation, which were suppressed by angiotensin type I receptor antagonist (Losartan) as well as p38 MAPK inhibitor (SB202190), ERK1/2 inhibitor (PD98059) and JNK inhibitor (SP600125). Meanwhile, both TGF{beta}1 antibody and TRAF6 siRNA decreased the stimulatory effect of AngII on TRAF6, CTGF expression and TAK1 phosphorylation, which also attenuated AngII-induced atrial fibroblasts proliferation. In summary, the MAPKs/TGF{beta}1/TRAF6 pathway is an important signaling pathway in AngII-induced CTGF expression, and inhibition of TRAF6 may therefore represent a new target for reversing Ang II-induced atrial fibrosis. -- Highlights: Black-Right-Pointing-Pointer MAPKs/TGF{beta}1/TRAF6 participates in AngII-induced CTGF expression in atrial fibroblasts. Black-Right-Pointing-Pointer TGF{beta}1/TRAF6 participates in AngII-induced atrial fibroblasts proliferation. Black-Right-Pointing-Pointer TRAF6 may represent a new target for reversing Ang II-induced atrial fibrosis.

  1. Inhibitory effect of genistein on mouse colon cancer MC-26 cells involved TGF-{beta}1/Smad pathway

    SciTech Connect

    Yu Zengli . E-mail: zengliy@yahoo.com.cn; Tang Yunan; Hu Dongsheng; Li Juan

    2005-08-05

    TGF-{beta}1/signaling has been shown to be associated with proapoptotic and antimitotic activities in epithelial tissues. Genistein, a major component of soybean isoflavone, has multiple functions resulting in anticancer proliferation. We herein showed that genistein dose-dependently increased TGF-{beta}1 mRNA expression in mouse colon cancer MC-26 cells. A mouse monoclonal anti-TGF-{beta}1 neutralizing antibody partially, but not completely, blocked the growth inhibition by genistein. By using adenoviral vector, we demonstrated that Smad7 overexpression attenuated genistein-induced growth inhibition and apoptosis as determined by MTT and apoptosis ELISA. Smad7 overexpression also inhibited upregulation of p21 and caspase-3 activity by geinistein. To further confirm inhibitory effect of genistein in MC-26 cells require TGF-{beta}1/Smad signaling, we employed Western blot and electrophoretic mobility shift assay to detect formation of Smad-DNA complexes and phosphorylation of Smad2 and Smad3, respectively. Data revealed that genistein induced an evident formation of Smad-DNA complexes and phosphorylation of Smad2 and Smad3, indicating increased TGF-{beta}1 signaling. Taken together, these findings first provided insights into possible molecular mechanisms of growth inhibition by genistein that required Smad signaling, which could aid in its evaluation for colon tumor prevention.

  2. Comparative functional analysis of rat TGF-beta1 and Xenopus laevis TGF-beta5 promoters suggest differential regulations.

    PubMed

    Goswami, Moloy T; Desai, Kartiki V; Kondaiah, Paturu

    2003-07-01

    We have carried out a comparative functional analysis of the rat TGF-beta1 and Xenopus laevis TGF-beta5 promoters across several mammalian and amphibian cell lines. Progressive deletion constructs of both the promoters have been made using a PCR based approach and the basal promoter activities studied in Xenopus tadpole cell line (XTC), Xenopus adult kidney fibroblast cell line (A6), human hepatoma cell line (HepG2), normal rat kidney cell line (NRK), and Chinese hamster ovary cell line (CHO). Data suggests that the basal promoter activity of TGF-beta1 is low as compared to TGF-beta5 promoter in XTC cells but comparable in A6 cells, while TGF-beta5 promoter shows nearly negligible activity as compared to TGF-beta5 promoter in all the tested mammalian cell lines. Moreover, TGF-beta5 promoter is found to be repressed in XTC cells on treatment with TGF-beta5 protein. Thus, the regulation of TGF-beta1 and TGF-beta5 promoters is distinct in amphibian and mammalian species. We therefore suggest that contrary to the suggested functional equivalence of TGF-beta1 and TGF-beta5 proteins, TGF-beta1 and TGF-beta5 genes have distinct functions in their respective species. PMID:12962305

  3. Antisense targeting of TGF-{beta}1 augments BMP-induced upregulation of osteopontin, type I collagen and Cbfa1 in human Saos-2 cells

    SciTech Connect

    Shen, Zhong-Jian . E-mail: zshen2@wisc.edu; Kook Kim, Sang; Youn Jun, Do; Park, Wan; Ho Kim, Young; Malter, James S.; Jo Moon, Byung . E-mail: bjmoon@mail.knu.ac.kr

    2007-04-15

    Despite commonalities in signal transduction in osteoblasts from different species, the role of TGF-{beta}1 on bone formation remains elusive. In particular, the role of autocrine TGF-{beta}1 on human osteoblasts is largely unknown. Here we show the effect of TGF-{beta}1 knock-down on the proliferation and differentiation of osteoblasts induced by BMP2. Treatment with antisense TGF-{beta}1 moderately increased the rate of cell proliferation, which was completely reversed by the exogenous addition of TGF-{beta}1. Notably, TGF-{beta}1 blockade significantly enhanced BMP2-induced upregulation of mRNAs encoding osteopontin, type I collagen and Cbfa1, which was suppressed by exogenous TGF-{beta}1. Moreover, TGF-{beta}1 knock-down increased BMP2-induced phosphorylation of Smad1/5 as well as their nuclear import, which paralleled a reduction of inhibitory Smad6. These data suggest autocrine TGF-{beta}1 antagonizes BMP signaling through modulation of inducible Smad6 and the activity of BMP specific Smad1/5.

  4. The role played by endocytosis in albumin-induced secretion of TGF-beta1 by proximal tubular epithelial cells.

    PubMed

    Diwakar, Ramaswamy; Pearson, Alex L; Colville-Nash, Paul; Brunskill, Nigel J; Dockrell, Mark E C

    2007-05-01

    Proteinuria predicts the decline of renal function in chronic kidney disease. Reducing albuminuria has been shown to be associated with a reduction in this rate of decline. Proximal tubular epithelial cells (PTECs), when exposed to albumin produce matrix proteins, proinflammatory and profibrotic cytokines like TGF-beta(1). Some of these effects are dependent on endocytosis of albumin by PTECs. However, conditions like diabetic nephropathy, believed to be associated with reduced albumin endocytosis, are associated with interstitial fibrosis. Moreover, megalin, the putative albumin binding receptor in PTECs, has potential signaling motifs in its cytoplasmic domain, suggesting its ability to signal in response to ligand binding from the apical surface of PTECs. Hence, we looked to see whether albumin-induced secretion of TGF-beta(1) by PTECs is dependent on albumin endocytosis or whether it could occur in the absence of albumin endocytosis. We studied the production of TGF-beta(1) in two accepted models of PTECs, opossum kidney cells and human kidney cell clone-8 cells, with widely varying degrees of endocytosis. We then studied the effect of inhibiting albumin endocytosis with various inhibitors on albumin-induced TGF-beta(1) secretion. Our results indicate that albumin-induced TGF-beta(1) secretion by PTECs does not require albumin endocytosis and therefore the mechanism for the induction of some profibrotic responses by albumin may differ from those required for some of the inflammatory responses. Moreover, we found that albumin-induced TGF-beta(1) secretion by PTECs is not dependent on its interaction with megalin. PMID:17213467

  5. TGF-beta 1 attenuates myocardial ischemia-reperfusion injury via inhibition of upregulation of MMP-1.

    PubMed

    Chen, Hongjiang; Li, Dayuan; Saldeen, Tom; Mehta, Jawahar L

    2003-05-01

    Ischemia-reperfusion (I/R) is thought to upregulate the expression and activity of matrix metalloproteinases (MMPs), which regulate myocardial and vascular remodeling. Previous studies have shown that transforming growth factor-beta(1) (TGF-beta(1)) can attenuate myocardial injury induced by I/R. TGF-beta(1) is also reported to suppress the release of MMPs. To study the modulation of MMP-1 by TGF-beta(1) in I/R myocardium, Sprague-Dawley rats were given saline and subjected to 1 h of myocardial ischemia [total left coronary artery (LCA) ligation] followed by 1 h of reperfusion (n = 9). Parallel groups of rats were pretreated with recombinant TGF-beta(1) (rTGF-beta(1), 1 mg/rat, n = 9) before reperfusion or exposure to sham I/R (control group). I/R caused myocardial necrosis and dysfunction, indicated by decreased first derivative of left ventricular pressure, mean arterial blood pressure, and heart rate (all P < 0.01 vs. sham-operated control group). Simultaneously, I/R upregulated MMP-1 (P < 0.01). Treatment of rats with rTGF-beta(1) reduced the extent of myocardial necrosis and dysfunction despite I/R (all P < 0.01). rTGF-beta(1) treatment also inhibited the upregulation of MMP-1 in the I/R myocardium (P < 0.05). To determine the direct effect of MMP-1 on the myocardium, isolated adult rat myocytes were treated with active MMP-1, which caused injury and death of cultured myocytes, measured as lactate dehydrogenase release and trypan blue staining, in a dose- and time-dependent manner (P < 0.05). Pretreatment with PD-166793, a specific MMP inhibitor, attenuated myocardial injury and death induced by active MMP-1. The present study for the first time shows that MMP-1 can directly cause myocyte injury or death and that attenuation of myocardial I/R injury by TGF-beta(1) may, at least partly, be mediated by the inhibition of upregulation of MMP-1. PMID:12679326

  6. Identification of novel inhibitors of the transforming growth factor beta1 (TGF-beta1) type 1 receptor (ALK5).

    PubMed

    Callahan, James F; Burgess, Joelle L; Fornwald, James A; Gaster, Laramie M; Harling, John D; Harrington, Frank P; Heer, Jag; Kwon, Chet; Lehr, Ruth; Mathur, A; Olson, Barbara A; Weinstock, Joseph; Laping, Nicholas J

    2002-02-28

    Screening of our internal compound collection for inhibitors of the transforming growth factor beta1 (TGF-beta1) type I receptor (ALK5) identified several hits. Optimization of the dihydropyrroloimidazole hit 2 by introduction of a 2-pyridine and 3,4-methylenedioxyphenyl group gave 7, a selective ALK5 inhibitor. With this information, optimization of the triarylimidazole hit 8 gave the selective inhibitor 14, which inhibits TGF-beta1-induced fibronectin mRNA formation while displaying no measurable cytotoxicity in the 48 h XTT assay. PMID:11855979

  7. IGF-binding proteins mediate TGF-beta 1-induced apoptosis in bovine mammary epithelial BME-UV1 cells.

    PubMed

    Gajewska, Małgorzata; Motyl, Tomasz

    2004-10-01

    TGF-beta 1 is an antiproliferative and apoptogenic factor for mammary epithelial cells (MEC) acting in an auto/paracrine manner and thus considered an important local regulator of mammary tissue involution. However, the apoptogenic signaling pathway induced by this cytokine in bovine MEC remains obscure. The present study was focused on identification of molecules involved in apoptogenic signaling of transforming growth factor-beta 1 (TGF-beta 1) in the model of bovine mammary epithelial cell line (BME-UV1). Laser scanning cytometry (LSC), Western blot and electrophoretic mobility shift assay (EMSA) were used for analysis of expression and activity of TGF-beta 1-related signaling molecules. The earliest response occurring within 1-2 h after TGF-beta 1 administration was an induction and activation of R-Smads (Smad2 and Smad3) and Co-Smad (Smad4). An evident formation of Smad-DNA complexes began from 2nd hour after MEC exposure to TGF-beta 1. Similarly to Smads, proteins of AP1 complex: phosphorylated c-Jun and JunD appeared to be early reactive molecules; however, an increase in their expression was detected only in cytosolic fraction. In the next step, an increase of IGF binding protein-3 (IGFBP-3) and IGFBP-4 expression was observed from 6th hour followed by a decrease in the activity of protein kinase B (PKB/Akt), which occurred after 24 h of MEC exposure to TGF-beta 1. The decrease in PKB/Akt activity coincided in time with the decline of phosphorylated Bad expression (inactive form). Present study supported additional evidence that stimulation of insulin-like growth factor I (IGF-I) was associated with complete abrogation of TGF-beta 1-induced activation of Bad and Bax and in the consequence protection against apoptosis. In conclusion, apoptotic effect of TGF-beta 1 in bovine MEC is mediated by IGFBPs and occurs through IGF-I sequestration, resulting in inhibition of PKB/Akt-dependent survival pathway. PMID:15556067

  8. PPAR{gamma} agonists prevent TGF{beta}1/Smad3-signaling in human hepatic stellate cells

    SciTech Connect

    Zhao Caiyan; Chen, Wei; Yang Liu; Chen Lihong; Stimpson, Stephen A.; Diehl, Anna Mae . E-mail: annamae.diehl@duke.edu

    2006-11-17

    PPAR{gamma} agonists inhibit liver fibrosis, but the mechanisms involved are uncertain. We hypothesized that PPAR{gamma} agonists inhibit transforming growth factor (TGF){beta}1-activation of TGF{beta} receptor (TGF{beta}R)-1 signaling in quiescent stellate cells, thereby abrogating Smad3-dependent induction of extracellular matrix (ECM) genes, such as PAI-1 and collagen-1{alpha}I. To test this, human HSC were cultured to induce a quiescent phenotype, characterized by lipid accumulation and PPAR{gamma} expression and transcriptional activity. These adipocytic HSC were then treated with TGF{beta}1 {+-} a TGF{beta}R-1 kinase inhibitor (SB431542) or a PPAR{gamma} agonist (GW7845). TGF{beta}1 caused dose- and time-dependent increases in Smad3 phosphorylation, followed by induction of collagen and PAI-1 expression. Like the TGF{beta}R-1 kinase inhibitor, the PPAR{gamma} agonist caused dose-dependent inhibition of all of these responses without effecting HSC proliferation or viability. Thus, the anti-fibrotic actions of PPAR{gamma} agonists reflect their ability to inhibit TGF{beta}1-TGF{beta}R1 signaling that initiates ECM gene expression in quiescent HSC.

  9. TGF-{beta}1 increases invasiveness of SW1990 cells through Rac1/ROS/NF-{kappa}B/IL-6/MMP-2

    SciTech Connect

    Binker, Marcelo G.; Binker-Cosen, Andres A.; Gaisano, Herbert Y.; Cosen, Rodica H. de; Cosen-Binker, Laura I.

    2011-02-04

    Research highlights: {yields} Rac1 mediates TGF-{beta}1-induced SW1990 invasion through MMP-2 secretion and activation. {yields} NADPH-generated ROS act downstream of Rac1 in TGF-{beta}1-challenged SW1990 cells. {yields} TGF-{beta}1-stimulated ROS activate NF-{kappa}B in SW1990 cells. {yields} NF{kappa}B-induced IL-6 release is required for secretion and activation of MMP-2 in SW1990 cells. -- Abstract: Human pancreatic cancer invasion and metastasis have been found to correlate with increased levels of active matrix metalloproteinase 2 (MMP-2). The multifunctional cytokine transforming growth factor beta 1 (TGF-{beta}1) has been shown to increase both secretion of MMP-2 and invasion by several pancreatic cancer cell types. In the present study, we investigated the signaling pathway involved in TGF-{beta}1-promoted MMP-2 secretion and invasion by human pancreatic cancer cells SW1990. Using specific inhibitors, we found that stimulation of these tumor cells with TGF-{beta}1 induced secretion and activation of the collagenase MMP-2, which was required for TGF-{beta}1-stimulated invasion. Our results also indicate that signaling events involved in TGF-{beta}1-enhanced SW1990 invasiveness comprehend activation of Rac1 followed by generation of reactive oxygen species through nicotinamide adenine dinucleotide phosphate-oxidase, activation of nuclear factor-kappa beta, release of interleukin-6, and secretion and activation of MMP-2.

  10. GSK3 inactivation is involved in mitochondrial complex IV defect in transforming growth factor (TGF) {beta}1-induced senescence

    SciTech Connect

    Byun, Hae-Ok; Jung, Hyun-Jung; Seo, Yong-Hak; Lee, Young-Kyoung; Hwang, Sung-Chul; Seong Hwang, Eun; Yoon, Gyesoon

    2012-09-10

    Transforming growth factor {beta}1 (TGF {beta}1) induces Mv1Lu cell senescence by persistently producing mitochondrial reactive oxygen species (ROS) through decreased complex IV activity. Here, we investigated the molecular mechanism underlying the effect of TGF {beta}1 on mitochondrial complex IV activity. TGF {beta}1 progressively phosphorylated the negative regulatory sites of both glycogen synthase kinase 3 (GSK3) {alpha} and {beta}, corresponding well to the intracellular ROS generation profile. Pre-treatment of N-acetyl cysteine, an antioxidant, did not alter this GSK3 phosphorylation (inactivation), whereas pharmacological inhibition of GSK3 by SB415286 significantly increased mitochondrial ROS, implying that GSK3 phosphorylation is an upstream event of the ROS generation. GSK3 inhibition by SB415286 decreased complex IV activity and cellular O{sub 2} consumption rate and eventually induced senescence of Mv1Lu cell. Similar results were obtained with siRNA-mediated knockdown of GSK3. Moreover, we found that GSK3 not only exists in cytosol but also in mitochondria of Mv1Lu cell and the mitochondrial GSK3 binds complex IV subunit 6b which has no electron carrier and is topologically located in the mitochondrial intermembrane space. Involvement of subunit 6b in controlling complex IV activity and overall respiration rate was proved with siRNA-mediated knockdown of subunit 6b. Finally, TGF {beta}1 treatment decreased the binding of the subunit 6b to GSK3 and subunit 6b phosphorylation. Taken together, our results suggest that GSK3 inactivation is importantly involved in TGF {beta}1-induced complex IV defects through decreasing phosphorylation of the subunit 6b, thereby contributing to senescence-associated mitochondrial ROS generation.

  11. Specific signals involved in the long-term maintenance of radiation-induced fibrogenic differentiation: a role for CCN2 and low concentration of TGF-beta1.

    PubMed

    Haydont, Valérie; Riser, Bruce L; Aigueperse, Jocelyne; Vozenin-Brotons, Marie-Catherine

    2008-06-01

    The fibrogenic differentiation of resident mesenchymal cells is a key parameter in the pathogenesis of radiation fibrosis and is triggered by the profibrotic growth factors transforming growth factor (TGF)-beta1 and CCN2. TGF-beta1 is considered the primary inducer of fibrogenic differentiation and is thought to control its long-term maintenance, whereas CCN2 is considered secondary effector of TGF-beta1. Yet, in long-term established fibrosis like that associated with delayed radiation enteropathy, in situ TGF-beta1 deposition is low, whereas CCN2 expression is high. To explore this apparent paradox, cell response to increasing doses of TGF-beta1 was investigated in cells modeling initiation and maintenance of fibrosis, i.e., normal and fibrosis-derived smooth muscle cells, respectively. Activation of cell-specific signaling pathways by low TGF-beta1 doses was demonstrated with a main activation of the Rho/ROCK pathway in fibrosis-derived cells, whereas the Smad pathway was mainly activated in normal cells. This leads to subsequent and cell-specific regulation of the CCN2 gene. These results suggested a specific profibrotic role of CCN2 in fibrosis-initiated cells. Furthermore, the modulation of CCN2 expression by itself and the combination of TGF-beta1 and CCN2 was investigated in fibrosis-derived cells. In fibrosis-initiated cells CCN2 triggered its autoinduction; furthermore, low concentration of TGF-beta1-potentiated CCN2 autoinduction. Our findings showed a differential requirement and action of TGF-beta1 in the fibrogenic response of normal vs. fibrosis-derived cells. This study defines a novel Rho/ROCK but Smad3-independent mode of TGF-beta signaling that may operate during the chronic stages of fibrosis and provides evidence of both specific and combinatorial roles of low TGF-beta1 dose and CCN2. PMID:18400984

  12. Id-1 promotes TGF-{beta}1-induced cell motility through HSP27 activation and disassembly of adherens junction in prostate epithelial cells

    SciTech Connect

    Di Kaijun; Wong, Y.C. Wang Xianghong

    2007-11-15

    Id-1 (inhibitor of differentiation or DNA binding-1) has been positively associated with cell proliferation, cell cycle progression, and invasiveness during tumorigenesis. In addition, Id-1 has been shown to modulate cellular sensitivity to TGF-{beta}1 (transforming growth factor {beta}1). Here we demonstrate a novel role of Id-1 in promoting TGF-{beta}1-induced cell motility in a non-malignant prostate epithelial cell line, NPTX. We found that Id-1 promoted F-actin stress fiber formation in response to TGF-{beta}1, which was associated with increased cell-substrate adhesion and cell migration in NPTX cells. In addition, this positive effect of Id-1 on TGF-{beta}1-induced cell motility was mediated through activation of MEK-ERK signaling pathway and subsequent phosphorylation of HSP27 (heat shock protein 27). Furthermore, Id-1 disrupted the adherens junction complex in TGF-{beta}1-treated cells through down-regulation of E-cadherin, redistribution of {beta}-catenin, along with up-regulation of N-cadherin. These lines of evidence reveal a novel tumorigenic role of Id-1 through reorganization of actin cytoskeleton and disassembly of cell-cell adhesion in response to TGF-{beta}1 in human prostate epithelial cells, and suggest that intracellular Id-1 levels might be a determining factor for switching TGF-{beta}1 from a growth inhibitor to a tumor promoter during prostate carcinogenesis.

  13. C-peptide reverses TGF-beta1-induced changes in renal proximal tubular cells: implications for treatment of diabetic nephropathy.

    PubMed

    Hills, Claire E; Al-Rasheed, Nawal; Al-Rasheed, Nouf; Willars, Gary B; Brunskill, Nigel J

    2009-03-01

    The crucial pathology underlying progressive chronic kidney disease in diabetes is tubulointerstitial fibrosis. Central to this process is epithelial-mesenchymal transformation (EMT) of proximal tubular epithelial cells driven by maladaptive transforming growth factor-beta1 (TGF-beta1) signaling. Novel signaling roles for C-peptide have recently been discovered with evidence emerging that C-peptide may mitigate microvascular complications of diabetes. We studied the potential for C-peptide to interrupt injurious TGF-beta1 signaling pathways and thus block development of EMT in HK2 human kidney proximal tubular cells. Cells were incubated with TGF-beta1 either alone or with C-peptide in low or high glucose. Changes in cell morphology, TGF-beta1 receptor expression, vimentin, E-cadherin, and phosphorylated Smads were assessed. Luciferase reporters were used to assess Smad activity. The cytoskeleton was visualized by TRITC-phalloidin staining. The typical TGF-beta1-stimulated, EMT-associated morphological alterations of proximal tubular cells, including increased vimentin expression, decreased E-cadherin expression, and cytoskeletal rearrangements, were prevented by C-peptide treatment. C-peptide also blocked TGF-beta1-induced upregulation of expression of both type I and type II TGF-beta1 receptors and attenuated TGF-beta1-mediated Smad phosphorylation and Smad transcriptional activity. These effects of C-peptide were inhibited by pertussis toxin. The results demonstrate that C-peptide almost completely reversed the morphological changes in PT cells induced by TGF-beta1 and suggest a role or C-peptide as a renoprotective agent in diabetic nephropathy. PMID:19091788

  14. Lactate adversely affects the in vitro formation of endothelial cell tubular structures through the action of TGF-{beta}1

    SciTech Connect

    Schmid, Stephan A. . E-mail: leoni.kunz-schughart@oncoray.de; Gaumann, Andreas; Wondrak, Marit; Eckermann, Christoph; Schulte, Stephanie; Mueller-Klieser, Wolfgang; Wheatley, Denys N.; Kunz-Schughart, Leoni A.

    2007-07-15

    When lactate accumulation in a tumor microenvironment reaches an average concentration of 10-20 mM, it tends to reflect a high degree of malignancy. However, the hypothesis that tumor-derived lactate has a number of partially adverse biological effects on malignant and tumor-associated host cells requires further evidence. The present study attempted to evaluate the impact of lactate on the process of angiogenesis, in particular on the formation of tubular structures. The endothelial cell (EC) network in desmoplastic breast tumors is primarily located in areas of reactive fibroblastic stroma. We employed a fibroblast-endothelial cell co-culture model as in vitro angiogenesis system normally producing florid in vitro tubule formation to analyze this situation. In contrast to previous studies, we found that lactate significantly reduces EC network formation in a dose-dependent manner as quantified by semi-automated morphometric analyses following immunohistochemical staining. The decrease in CD31-positive tubular structures and the number of intersections was independent of VEGF supplementation and became more pronounced in the presence of protons. The number of cells, primarily of the fibroblast population, was reduced but cell loss could not be attributed to a decrease in proliferative activity or pronounced apoptotic cell death. Treatment with 10 mM lactate was accompanied by enhanced mRNA expression and release of TGF-{beta}1, which also shows anti-angiogenic activity in the model. Both TGF-{beta}1 and lactate induced myofibroblastic differentiation adjacent to the EC tubular structures. The lactate response on the EC network was diminished by TGF-{beta}1 neutralization, indicating a causal relationship between lactate and TGF-{beta}1 in the finely tuned processes of vessel formation and maturation which may also occur in vivo within tumor tissue.

  15. Reduction of isoprenaline-induced myocardial TGF-{beta}1 expression and fibrosis in osthole-treated mice

    SciTech Connect

    Chen Rong; Xue Jie; Xie Meilin

    2011-10-15

    Peroxisome proliferator-activated receptor (PPAR) {alpha} and PPAR{gamma} ligands can attenuate myocardial fibrosis. Osthole, an active constituent isolated from the fruit of Cnidium monnieri (L.) Cusson, may be a dual PPAR{alpha}/{gamma} agonist, but there has been no report on its effect on myocardial fibrosis. In the present study, we investigated the inhibitory effect of osthole on myocardial fibrotic formation in mice and its possible mechanisms. A mouse model with myocardial fibrosis was induced by hypodermic injection of isoprenaline while the mice were simultaneously treated with 40 and 80 mg/kg osthole for 40 days. After the addition of osthole, the cardiac weight index and hydroxyproline content in the myocardial tissues were decreased, the degree of collagen accumulation in the heart was improved, and the downregulation of myocardial PPAR{alpha}/{gamma} mRNA expression induced by isoprenaline was reversed. Moreover, the mRNA expression of transforming growth factor (TGF)-{beta}1 and the protein levels of nuclear factor (NF)-{kappa}B and TGF-{beta}1 in the myocardial tissues were decreased. These findings suggest that osthole can prevent isoprenaline-induced myocardial fibrosis in mice, and its mechanisms may be related to the reduction of TGF-{beta}1 expression via the activation of PPAR{alpha}/{gamma} and subsequent inhibition of NF-{kappa}B in myocardial tissues. - Highlights: > Osthole could inhibit the myocardial fibrosis induced by isoprenaline in mice. > The mechanism was related to reduction of TGF-{beta}1 expression in myocardial tissue. > The result of osthole was from the activation of PPAR{alpha}/{gamma} and inhibition of NF-{kappa}B.

  16. The effect of transforming growth factor beta1 (TGF-beta1) on the regenerate bone in distraction osteogenesis.

    PubMed

    Ozkan, Korhan; Eralp, Levent; Kocaoglu, Mehmet; Ahishali, Bulent; Bilgic, Bilge; Mutlu, Zihni; Turker, Mehmet; Ozkan, Feyza Unlu; Sahin, Kemal; Guven, Melih

    2007-04-01

    Distraction osteogenesis is a well established clinical treatment for limb length discrepancy and skeletal deformities. Transforming growth factor beta 1 (TGF-beta1) is a multifunctional peptide which controls proliferation and expression of cells specific to bone like chondrocytes, osteoblasts, osteoclasts including mesenchymal precursor cells. To decrease the external fixation time with increasing the strength of regenerate (newly formed bone after distraction) we tested the effect of locally applied transforming growth factor beta 1 on distraction osteogenesis. A total of 28 mature female white New zealand rabbits weighing 3,5 kg-4,5 kg were studied. 10 animals were belonging to biomechanical testing group (5 for the study and 5 for the control subgroups), and the others were to histology group. In biomechanical group after tibial osteotomy TGF-beta1 was applied subperiosteally for 5 days just proximal to osteotomy site. Control group received only the solvent. Seven days after tibial osteotomy distraction was started at a rate of 0.25 mm/12 hours for 3 weeks with a unilateral fixator. Rabbits were sacrificed at the end of a consolidation period 8 week after tibial osteotomy. We assessed density of the elongation zone of rabbit tibial bones with the computed tomography. Then biomechanical parametres were assessed using the torsional testing using the material testing machine. In histology group rabbits were classified as control and study (rabbits that were given TGF-beta1). Rabbits were sacrificed at the end of first week, second week and fourth week also at the end of consolidation period 8 week after tibial osteotomy. Immunohistochemical and histologic parameters were examined. Biomechanical testing was applied as torsional testing. These values are used in determination of maximal loading, stiffness and energy absorbed during testing (brittleness). The histomorphometric examination looked for the differences between the study and control groups in terms of

  17. A Polymorphism Within the Promoter of the TGF{beta}1 Gene Is Associated With Radiation Sensitivity Using an Objective Radiologic Endpoint

    SciTech Connect

    Kelsey, Chris R.; Jackson, Lauren; Langdon, Scott; Owzar, Kouros; Hubbs, Jessica; Vujaskovic, Zeljko; Das, Shiva; Marks, Lawrence B.

    2012-02-01

    Purpose: To evaluate whether single nucleotide polymorphisms (SNPs) in the transforming growth factor-{beta}1 (TGF{beta}1) gene are associated with radiation sensitivity using an objective radiologic endpoint. Methods and Materials: Preradiation therapy and serial postradiation therapy single photon emission computed tomography (SPECT) lung perfusion scans were obtained in patients undergoing treatment for lung cancer. Serial blood samples were obtained to measure circulating levels of TGF{beta}1. Changes in regional perfusion were related to regional radiation dose yielding a patient-specific dose-response curve, reflecting the patient's inherent sensitivity to radiation therapy. Six TGF{beta}1 SNPs (-988, -800, -509, 869, 941, and 1655) were assessed using high-resolution melting assays and DNA sequencing. The association between genotype and slope of the dose-response curve, and genotype and TGF{beta}1 ratio (4-week/preradiation therapy), was analyzed using the Kruskal-Wallis test. Results: 39 white patients with preradiation therapy and {>=}6-month postradiation therapy SPECT scans and blood samples were identified. Increasing slope of the dose-response curve was associated with the C(-509)T SNP (p = 0.035), but not the other analyzed SNPs. This SNP was also associated with higher TGF{beta}1 ratios. Conclusions: This study suggests that a polymorphism within the promoter of the TGF{beta}1 gene is associated with increased radiation sensitivity (defined objectively by dose-dependent changes in SPECT lung perfusion).

  18. PI-3 kinase pathway can mediate the effect of TGF-beta1 in inducing the expression of SHARP-2 in LLC-PK1 cells.

    PubMed

    Shou, Zhang-fei; Zhou, Qin; Cai, Jie-ru; Chen, Jiang-hua; Yamada, Kazuya; Miyamoto, Kaoru

    2009-09-01

    We aim to investigate the effect of transforming growth factor (TGF)-beta1 on the expression of enhancer of split- and hairy-related protein-2 (SHARP-2) messenger RNA (mRNA) and its signaling pathway. In this study, several cell lines including LLC-PK1 (a porcine kidney tubular epithelial cell line), MDCK (Madin-Darby canine kidney) and CTLL-2 (cytotoxic T-lymphocyte line) were treated with recombinant human TGF-beta1, and a series of experiments were carried out, involving Northern blot analysis of total RNA from these cells. Further, several specific chemical inhibitors were applied before TGF-beta1 treatment to probe the signaling pathway. The results showed that TGF-beta1 can significantly up-regulate SHARP-2 mRNA expression in the LLC-PK1 cell line. The peak level of induction was found 2 h after TGF-beta1 stimulation. While one phosphoinositide 3-kinases (PI-3) kinase inhibitor, LY294002, completely blocked the effect of TGF-beta1 on SHARP-2 mRNA expression in LLC-PK1 cells at a low concentration, other inhibitors, including PD98059, staurosporine, AG490, wortmannin, okadaic acid and rapamycin, had no effect. The effect of LY294002 was dose-dependent. We conclude that, in LLC-PK1 cells at least, TGF-beta1 can effectively induce the SHARP-2 mRNA expression and that the PI-3 kinase pathway can mediate this effect. PMID:19735104

  19. [Relationship between artesunate influence on the process of TGF-beta1 induced alveolar epithelial cells transform into mesenchymal cells and on idiopathic pulmonary fibrosis].

    PubMed

    Wang, Chang-Ming; Chen, Juan; Jiang, Ming; Xuan, Xiu-Ping; Li, Hong-Xiu

    2014-01-01

    This study is to investigate the effect of artesunate on transforming growth factor-beta1 (TGF-beta1) induced epithelial-mesenchymal transition (EMT) and its possible mechanism. After the in vitro cultured RLE-6TN cells were treated with TGF-beta1 then artesunate intervened on it, after 24 h, expression of the markers of mesenchymal cell was assayed using Western blotting and real-time PCR analysis. Western blotting was also used to detect the effect of TGF-beta1 on the Smad3 and Smad7 expressions of RLE-6TN cells. Morphological alterations were examined by phase-contrast microscope, and ultrastructure changes by electron microscope. Incubation of RLE-6TN cells with TGF-beta1 resulted in the up-regulation of the expression of the mesenchymal cell markers, after artesunate intervened on it, resulted in the down-regulation of the expression. Meanwhile, incubation with artesunate intervened on RLE-6TN cells could lead to the apparent down-regulation of the expression of Smad3 and up-regulation of Samd7 and the transition of RLE-6TN cells to mesenchymal-like by TGF-beta1 induction, after artesunate intervened on it, RLE-6TN cells to epithelial-like. TGF-beta1 induced epithelial-mesenchymal transition process; artesunate can inhibit TGF-beta1-induced epithelial-mesenchymal transition process, the possible mechanism is up-regulation of the expression of Smad7 and down-regulation of the expression of Smad3, meanwhile inhibits phosphorylation of Smad3. PMID:24783520

  20. SNP analyses of growth factor genes EGF, TGF{beta}-1, and HGF reveal haplotypic association of EGF with autism

    SciTech Connect

    Toyoda, Takao; Thanseem, Ismail; Kawai, Masayoshi; Sekine, Yoshimoto; Nakamura, Kazuhiko; Anitha, Ayyappan; Suda, Shiro . E-mail: nakamura@hama-med.ac.jp; Yamada, Kazuo; Tsujii, Masatsugu |; Iwayama, Yoshimi; Hattori, Eiji; Toyota, Tomoko; Yoshikawa, Takeo; Miyachi, Taishi; Tsuchiya, Kenji; Sugihara, Gen-ichi; Matsuzaki, Hideo; Iwata, Yasuhide; Suzuki, Katsuaki; Mori, Norio |; Ouchi, Yasuomi |; Sugiyama, Toshiro; Takei, Nori

    2007-09-07

    Autism is a pervasive neurodevelopmental disorder diagnosed in early childhood. Growth factors have been found to play a key role in the cellular differentiation and proliferation of the central and peripheral nervous systems. Epidermal growth factor (EGF) is detected in several regions of the developing and adult brain, where, it enhances the differentiation, maturation, and survival of a variety of neurons. Transforming growth factor-{beta} (TGF{beta}) isoforms play an important role in neuronal survival, and the hepatocyte growth factor (HGF) has been shown to exhibit neurotrophic activity. We examined the association of EGF, TGF{beta}1, and HGF genes with autism, in a trio association study, using DNA samples from families recruited to the Autism Genetic Resource Exchange; 252 trios with a male offspring scored for autism were selected for the study. Transmission disequilibrium test revealed significant haplotypic association of EGF with autism. No significant SNP or haplotypic associations were observed for TGF{beta}1 or HGF. Given the role of EGF in brain and neuronal development, we suggest a possible role of EGF in the pathogenesis of autism.

  1. Regulation of extracellular matrix synthesis by TNF-alpha and TGF-beta1 in type II cells exposed to coal dust.

    PubMed

    Lee, Y C; Rannels, D E

    1998-10-01

    Type II pulmonary epithelial cells respond to anthracite coal dust PSOC 867 with increased synthesis of extracellular matrix (ECM) components. Alveolar macrophages modulate this response by pathways that may involve soluble mediators, including tumor necrosis factor-alpha (TNF-alpha) or transforming growth factor-beta1 (TGF-beta1). The effects of TNF-alpha (10 ng/ml) and/or TGF-beta1 (2 ng/ml) were thus investigated in dust-exposed primary type II cell cultures. In control day 1 or day 3 cultures, TNF-alpha and/or TGF-beta1 had little or no effect on the synthesis of type II cellular proteins, independent of whether the cells were exposed to dust. With PSOC 867 exposure, where ECM protein synthesis is elevated, TNF-alpha and TGF-beta1 further increased both the absolute and relative rates of ECM synthesis on day 3 but had little effect on day 1. Each mediator increased expression of fibronectin mRNA, as well as of ECM fibronectin content, in a manner qualitatively similar to their effects on synthesis. Thus TNF-alpha and TGF-beta1 modulate both ECM synthesis and fibronectin content in coal dust-exposed type II cell cultures. PMID:9755095

  2. Decreased type II/type I TGF-beta receptor ratio in cells derived from human atherosclerotic lesions. Conversion from an antiproliferative to profibrotic response to TGF-beta1.

    PubMed Central

    McCaffrey, T A; Consigli, S; Du, B; Falcone, D J; Sanborn, T A; Spokojny, A M; Bush, H L

    1995-01-01

    Atherosclerosis and postangioplasty restenosis may result from abnormal wound healing. The present studies report that normal human smooth muscle cells are growth inhibited by TGF-beta1, a potent wound healing agent, and show little induction of collagen synthesis to TGF-beta1, yet cells grown from human vascular lesions are growth stimulated by TGF-beta1 and markedly increase collagen synthesis. Both cell types increase plasminogen activator inhibitor-1 production, switch actin phenotypes in response to TGF-beta1, and produce similar levels of TGF-beta activity. Membrane cross-linking of 125I-TGF-beta1 indicates that normal human smooth muscle cells express type I, II, and III receptors. The type II receptor is strikingly decreased in lesion cells, with little change in the type I or III receptors. RT-PCR confirmed that the type II TGF-beta1 receptor mRNA is reduced in lesion cells. Transfection of the type II receptor into lesion cells restores the growth inhibitory response to TGF-beta1, implying that signaling remains responsive. Because TGF-beta1 is overexpressed in fibroproliferative vascular lesions, receptor-variant cells would be allowed to grow in a slow, but uncontrolled fashion, while overproducing extracellular matrix components. This TGF-beta1 receptor dysfunction may be relevant for atherosclerosis, restenosis and related fibroproliferative diseases. Images PMID:8675633

  3. Localization of insulin-like growth factor (IGFBP)-3 in cultured porcine embryonic myogenic cells before and after TGF-beta1 treatment.

    PubMed

    Xi, G; Hathaway, M R; White, M E; Dayton, W R

    2007-11-01

    Insulin-like growth factor binding protein (IGFBP)-3 binds IGFs with high affinity and affects their biological activity. IGFBP-3 that is not bound to IGF also affects cells via mechanisms involving binding to specific cell surface receptors and/or transport into the cell. IGFBP-3 is produced by porcine embryonic myogenic cell (PEMC) cultures. Additionally, IGFBP-3 facilitates the proliferation-suppressing actions of TGF-beta(1) and myostatin in PEMC cultures via mechanisms that do not involve IGF binding. Moreover, these mechanisms do not involve preventing myostatin or TGF-beta(1)-induced increases in phosphosmad2 or phosphosmad3 level. Consequently, the mechanism(s) by which IGFBP-3 facilitates the proliferation-suppressing actions of TGF-beta(1) and myostatin in PEMC is unclear. Since IGFBP-3 reportedly interacts with nuclear proteins that regulate transcription, TGF-beta(1) or myostatin-induced translocation of IGFBP-3 into the nucleus may facilitate the proliferation-suppressing actions of these cytokines. Here, we show that IGFBP-3 is localized in cells containing the muscle specific protein desmin, thus establishing the presence of this IGFBP in myogenic cells. IGFBP-3 is present in the cytoplasm of all myogenic cells and approximately 50% of the nuclei of proliferating PEMC. IGFBP-3 is also detectable in fused myotubes. IGFBP-3 suppresses IGF-I-stimulated differentiation of PEMC but has no affect on Long-R3-IGF-I-stimulated differentiation of PEMC. Treatment of PEMC for 24h with TGF-beta(1) (20 ng/ml) results in a 78% (p<0.01) increase in the number of nuclei that contain detectable IGFBP-3. These results suggest that translocation of IGFBP-3 into the nucleus of PEMC could play a role in mediating the proliferation-suppressing action of TGF-beta(1). PMID:17049199

  4. Differential regulation of immature articular cartilage compressive moduli and Poisson's ratios by in vitro stimulation with IGF-1 and TGF-beta1.

    PubMed

    Williams, Gregory M; Dills, Kristin J; Flores, Christian R; Stender, Michael E; Stewart, Kevin M; Nelson, Lauren M; Chen, Albert C; Masuda, Koichi; Hazelwood, Scott J; Klisch, Stephen M; Sah, Robert L

    2010-09-17

    Mechanisms of articular cartilage growth and maturation have been elucidated by studying composition-function dynamics during in vivo development and in vitro culture with stimuli such as insulin-like growth factor-1 (IGF-1) and transforming growth factor-beta 1 (TGF-beta1). This study tested the hypothesis that IGF-1 and TGF-beta1 regulate immature cartilage compressive moduli and Poisson's ratios in a manner consistent with known effects on tensile properties. Bovine calf articular cartilage from superficial-articular (S) and middle-growth (M) regions were analyzed fresh or following culture in medium with IGF-1 or TGF-beta1. Mechanical properties in confined (CC) and unconfined (UCC) compression, cartilage matrix composition, and explant size were assessed. Culture with IGF-1 resulted in softening in CC and UCC, increased Poisson's ratios, substantially increased tissue volume, and accumulation of glycosaminoglycan (GAG) and collagen (COL). Culture with TGF-beta1 promoted maturational changes in the S layer, including stiffening in CC and UCC and increased concentrations of GAG, COL, and pyridinoline crosslinks (PYR), but little growth. Culture of M layer explants with TGF-beta1 was nearly homeostatic. Across treatment groups, compressive moduli in CC and UCC were positively related to GAG, COL, and PYR concentrations, while Poisson's ratios were negatively related to concentrations of these matrix components. Thus, IGF-1 and TGF-beta1 differentially regulate the compressive mechanical properties and size of immature articular cartilage in vitro. Prescribing tissue growth, maturation, or homeostasis by controlling the in vitro biochemical environment with such growth factors may have applications in cartilage repair and tissue engineering. PMID:20570267

  5. Generational Analysis Reveals that TGF-Beta1 Inhibits the Rate of Angiogenesis in Vivo by Selective Decrease in the Number of New Vessels

    NASA Technical Reports Server (NTRS)

    Parsons-Wingerter, Patricia; Elliott, Katherine E.; Farr, Andrew G.; Radhakrishnan, Krishnan; Clark, John I.; Sage, E. Helene

    2000-01-01

    Quantitative analysis of vascular generational branching demonstrated that transforming growth factor-beta1 (TGF-beta1), a multifunctional cytokine and angiogenic regulator, strongly inhibited angiogenesis in the arterial tree of the developing quail chorioallantoic membrane (CAM) by inhibition of the normal increase in the number of new, small vessels. The cytokine was applied uniformly in solution at embryonic day 7 (E7) to the CAMs of quail embryos cultured in petri dishes. After 24 h the rate of arterial growth was inhibited by as much as 105% as a function of increasing TGF-beta1 concentration. Inhibition of the rate of angiogenesis in the arterial tree by TGF-beta1 relative to controls was measured in digital images by three well-correlated, computerized methods. The first computerized method, direct measurement by the computer code VESGEN of vascular morphological parameters according to branching generations G(sub 1) through G(sub greater than or equal to 5), revealed that TGF-beta1 selectively inhibited the increase in the number density of small vessels, N(sub v greater than or equal to 5), (382 plus or minus 85 per square centimeter) for specimens treated with 1 microgram TGF-beta1/CAM for 24 h, compared to 583 plus or minus 99 per square centimeter for controls), but did not significantly affect other parameters such as average vessel length or vessel diameter. The second and third methods, the fractal dimension (D(sub f)) and grid intersection (rho (sub v)), are statistical descriptors of spatial pattern and density. According to D(sub f) and rho(sub v), arterial density increased in control specimens from 1.382 plus or minus 0.007 and 662 plus or minus 52 per square centimeters at E7 (0 h) to 1.439 plus or minus 0.013 and 884 plus or minus 55 per square centimeters at E8 (24 h), compared to 1.379 plus or minus 0.039 and 650 plus or minus 111 per square centimeter for specimens treated with 1 microgram TGF-beta1/CAM for 24 h. TGF-beta1 therefore

  6. Requirement of a novel splicing variant of human histone deacetylase 6 for TGF-{beta}1-mediated gene activation

    SciTech Connect

    Zhuang, Yan; Nguyen, Hong T.; Lasky, Joseph A.; Cao, Subing; Li, Cui; Hu, Jiyao; Guo, Xinyue; Burow, Matthew E.; Shan, Bin

    2010-02-19

    Histone deacetylase 6 (HDAC6) belongs to the family of class IIb HDACs and predominantly deacetylates non-histone proteins in the cytoplasm via the C-terminal deacetylase domain of its two tandem deacetylase domains. HDAC6 modulates fundamental cellular processes via deacetylation of {alpha}-tubulin, cortactin, molecular chaperones, and other peptides. Our previous study indicates that HDAC6 mediates TGF-{beta}1-induced epithelial-mesenchymal transition (EMT) in A549 cells. In the current study, we identify a novel splicing variant of human HDAC6, hHDAC6p114. The hHDAC6p114 mRNA arises from incomplete splicing and encodes a truncated isoform of the hHDAC6p114 protein of 114 kDa when compared to the major isoform hHDAC6p131. The hHDAC6p114 protein lacks the first 152 amino acids from N-terminus in the hHDAC6p131 protein, which harbors a nuclear export signal peptide and 76 amino acids of the N-terminal deacetylase domain. hHDAC6p114 is intact in its deacetylase activity against {alpha}-tubulin. The expression hHDAC6p114 is elevated in a MCF-7 derivative that exhibits an EMT-like phenotype. Moreover, hHDAC6p114 is required for TGF-{beta}1-activated gene expression associated with EMT in A549 cells. Taken together, our results implicate that expression and function of hHDAC6p114 is differentially regulated when compared to hHDAC6p131.

  7. Role of plasminogen activator inhibitor in the reciprocal regulation of bovine aortic endothelial and smooth muscle cell migration by TGF-beta 1.

    PubMed Central

    Petzelbauer, E.; Springhorn, J. P.; Tucker, A. M.; Madri, J. A.

    1996-01-01

    Vascular endothelial and smooth muscle cells exhibit reciprocal migratory responses after transforming growth factor (TGF)-beta 1 treatment. Endothelial cells exhibit a decreased migratory rate and smooth muscle cells exhibit an increased migratory rate. Previous studies have demonstrated increases in extracellular matrix and integrin synthesis and expression in response to TGF-beta 1. In this report, we illustrate the roles of plasminogen activator inhibitor in modulating the migratory rates in these two cell types. Endothelial cells appear to require a proteolytic phenotype for rapid migration, whereas vascular smooth muscle cells appear to require an anti-proteolytic phenotype. Modulation of proteinase/anti-proteinase activity ratios was accomplished via TGF-beta 1 induction, addition of exogenous plasminogen activator inhibitor, addition of anti-catalytic antibodies directed against urokinase plasminogen activator, overexpression of plasminogen activator inhibitor utilizing stable transfectants, and the use of vitronectin as a substratum. The reciprocal migratory behaviors exhibited by these two vascular cell types in response to TGF-beta 1 is discussed in the context that these two vascular cell types utilize distinct adhesive and signaling pathways in their interactions with extracellular matrix components and responsiveness to proteolytic activity. Images Figure 1 Figure 2 Figure 3 PMID:8780396

  8. Extracellular heat shock protein HSP90{beta} secreted by MG63 osteosarcoma cells inhibits activation of latent TGF-{beta}1

    SciTech Connect

    Suzuki, Shigeki; Kulkarni, Ashok B.

    2010-07-30

    Transforming growth factor-beta 1 (TGF-{beta}1) is secreted as a latent complex, which consists of latency-associated peptide (LAP) and the mature ligand. The release of the mature ligand from LAP usually occurs through conformational change of the latent complex and is therefore considered to be the first step in the activation of the TGF-{beta} signaling pathway. So far, factors such as heat, pH changes, and proteolytic cleavage are reportedly involved in this activation process, but the precise molecular mechanism is still far from clear. Identification and characterization of the cell surface proteins that bind to LAP are important to our understanding of the latent TGF-{beta} activation process. In this study, we have identified heat shock protein 90 {beta} (HSP90{beta}) from the cell surface of the MG63 osteosarcoma cell line as a LAP binding protein. We have also found that MG63 cells secrete HSP90{beta} into extracellular space which inhibits the activation of latent TGF-{beta}1, and that there is a subsequent decrease in cell proliferation. TGF-{beta}1-mediated stimulation of MG63 cells resulted in the increased cell surface expression of HSP90{beta}. Thus, extracellular HSP90{beta} is a negative regulator for the activation of latent TGF-{beta}1 modulating TGF-{beta} signaling in the extracellular domain. -- Research highlights: {yields} Transforming growth factor-beta 1 (TGF-{beta}1) is secreted as a latent complex. {yields} This complex consists of latency-associated peptide (LAP) and the mature ligand. {yields} The release of the mature ligand from LAP is the first step in TGF-{beta} activation. {yields} We identified for the first time a novel mechanism for this activation process. {yields} Heat shock protein 90 {beta} is discovered as a negative regulator for this process.

  9. Diabetes-induced upregulation of urotensin II and its receptor plays an important role in TGF-beta1-mediated renal fibrosis and dysfunction.

    PubMed

    Tian, Lin; Li, Cai; Qi, Jiping; Fu, Peng; Yu, Xiaoyan; Li, Xiaokun; Cai, Lu

    2008-11-01

    Urotensin II (UII) was identified as the ligand for a novel G protein-coupled receptor, GPR14. UII was found not only to have a potent vasoconstrictive action but also to have profibrotic effects in the heart. The present study was to define whether UII and GPR14 also play important roles in diabetes-induced renal fibrosis and dysfunction. Diabetic rats were induced using streptozotocin, and the rat proximal tubular epithelial cells (NRK-52E) were used for the in vitro mechanism study. Results showed that expression of UII and GPR14 was significantly upregulated at both mRNA and protein levels in the diabetic kidneys compared with controls. The upregulated expressions of UII and GPR14 in the kidney were accompanied by significant increases in the renal profibrotic factor transforming growth factor (TGF)-beta1 expression, the renal extracellular matrix (fibronectin and collagen IV) accumulation, and the renal dysfunction (increases in urinal N-acetyl-beta-d-glucosaminidase content, 24-h urinary retinol-binding protein excretion rate, and decrease in creatinine clearance rate). Exposure of NRK-52E cells to 10(-8) mol/l UII for 48 h caused a significant increase of TGF-beta1, but not ANG II, production that was GPR14- and calcium-dependent, since GPR14 small-interfering RNA and calcium channel blocker nimodipine or calcium chelator EDTA all could abolish the induction of TGF- beta1 by UII. Furthermore, exposure of NRK-52E cells to TGF-beta1 or ANG II also increased UII and GPR14 mRNA expressions. These results suggested that diabetes-induced upregulation of UII and GPR14, most likely through autocrine and/or paracrine mechanisms, plays an important role in TGF-beta1-mediated renal fibrosis and dysfunction. PMID:18796544

  10. Ganoderma lucidum suppresses angiogenesis through the inhibition of secretion of VEGF and TGF-{beta}1 from prostate cancer cells

    SciTech Connect

    Stanley, Gwenaelle; Harvey, Kevin; Slivova, Veronika; Jiang Jiahua; Sliva, Daniel . E-mail: dsliva@clarian.org

    2005-04-29

    Ganoderma lucidum (G. lucidum) is a popular medicinal mushroom that has been used as a home remedy for the general promotion of health and longevity in East Asia. The dried powder of G. lucidum, which was recommended as a cancer chemotherapy agent in traditional Chinese medicine, is currently popularly used worldwide in the form of dietary supplements. We have previously demonstrated that G. lucidum induces apoptosis, inhibits cell proliferation, and suppresses cell migration of highly invasive human prostate cancer cells PC-3. However, the molecular mechanism(s) responsible for the inhibitory effects of G. lucidum on the prostate cancer cells has not been fully elucidated. In the present study, we examined the effect of G. lucidum on angiogenesis related to prostate cancer. We found that G. lucidum inhibits the early event in angiogenesis, capillary morphogenesis of the human aortic endothelial cells. These effects are caused by the inhibition of constitutively active AP-1 in prostate cancer cells, resulting in the down-regulation of secretion of VEGF and TGF-{beta}1 from PC-3 cells. Thus, G. lucidum modulates the phosphorylation of Erk1/2 and Akt kinases in PC-3 cells, which in turn inhibits the activity of AP-1. In summary, our results suggest that G. lucidum inhibits prostate cancer-dependent angiogenesis by modulating MAPK and Akt signaling and could have potential therapeutic use for the treatment of prostate cancer.

  11. Elevation of Plasma TGF-{beta}1 During Radiation Therapy Predicts Radiation-Induced Lung Toxicity in Patients With Non-Small-Cell Lung Cancer: A Combined Analysis From Beijing and Michigan

    SciTech Connect

    Zhao Lujun; Wang Luhua Ji Wei; Wang Xiaozhen; Zhu Xiangzhi; Hayman, James A.; Kalemkerian, Gregory P.; Yang Weizhi; Brenner, Dean; Lawrence, Theodore S.; Kong, F.-M.

    2009-08-01

    Purpose: To test whether radiation-induced elevations of transforming growth factor-{beta}1 (TGF-{beta}1) during radiation therapy (RT) correlate with radiation-induced lung toxicity (RILT) in patients with non-small-cell lung cancer (NSCLC) and to evaluate the ability of mean lung dose (MLD) to improve the predictive power. Methods and Materials: Eligible patients included those with Stage I-III NSCLC treated with RT with or without chemotherapy. Platelet-poor plasma was obtained pre-RT and at 4-5 weeks (40-50 Gy) during RT. TGF-{beta}1 was measured using an enzyme-linked immunosorbent assay. The primary endpoint was {>=} Grade 2 RILT. Mann-Whitney U test, logistic regression, and chi-square were used for statistical analysis. Results: A total of 165 patients were enrolled in this study. The median radiation dose was 60 Gy, and the median MLD was 15.3 Gy. Twenty-nine patients (17.6%) experienced RILT. The incidence of RILT was 46.2% in patients with a TGF-{beta}1 ratio > 1 vs. 7.9% in patients with a TGF-{beta}1 ratio {<=} 1 (p < 0.001), and it was 42.9% if MLD > 20 Gy vs. 17.4% if MLD {<=} 20 Gy (p = 0.024). The incidence was 4.3% in patients with a TGF-{beta}1 ratio {<=} 1 and MLD {<=} 20 Gy, 47.4% in those with a TGF-{beta}1 ratio >1 or MLD > 20 Gy, and 66.7% in those with a TGF-{beta}1 ratio >1 and MLD > 20 Gy (p < 0.001). Conclusions: Radiation-induced elevation of plasma TGF-{beta}1 level during RT is predictive of RILT. The combination of TGF- {beta}1 and MLD may help stratify the patients for their risk of RILT.

  12. Elevated plasma levels of transforming growth factor (TGF)-beta1 and TGF-beta2 in patients with disseminated malignant melanoma.

    PubMed Central

    Krasagakis, K.; Thölke, D.; Farthmann, B.; Eberle, J.; Mansmann, U.; Orfanos, C. E.

    1998-01-01

    Overexpression of transforming growth factor-beta isoforms (TGF-beta1, -beta2, -beta3) has been previously reported in human melanoma cell lines and tumours. The aim of the present study was to evaluate the plasma levels of TGF-beta isoforms in melanoma patients. Significantly elevated levels of TGF-beta1 (4.2 x the controls, P = 0.0094) and of TGF-beta2 (1.5 x the controls, P = 0.012) but not of TGF-beta3 were measured in patients with disseminated but not locoregional melanoma. These results indicate systemic circulation of potentially immunosuppressive peptides of the TGF-beta family in end-stage melanoma patients. PMID:9652767

  13. Proinsulin C-peptide antagonizes the profibrotic effects of TGF-beta1 via up-regulation of retinoic acid and HGF-related signaling pathways.

    PubMed

    Hills, Claire E; Willars, Gary B; Brunskill, Nigel J

    2010-04-01

    Novel signaling roles for C-peptide have recently been discovered with evidence that it can ameliorate complications of type 1 diabetes. Here we sought to identify new pathways regulated by C-peptide of relevance to the pathophysiology of diabetic nephropathy. Microarray analysis was performed to identify genes regulated by either C-peptide and/or TGF-beta1 in a human proximal tubular cell line, HK-2. Expression of retinoic acid receptor beta (RARbeta), hepatocyte growth factor (HGF), cellular retinoic acid-binding protein II (CRABPII), vimentin, E-cadherin, Snail, and beta-catenin was assessed by immunoblotting. The cellular localization of vimentin and beta-catenin was determined by immunocytochemistry. Changes in cell morphology were assessed by phase contrast microscopy. Gene expression profiling demonstrated differential expression of 953 and 1458 genes after C-peptide exposure for 18 h or 48 h, respectively. From these, members of the antifibrotic retinoic acid (RA)- and HGF-signaling pathways were selected. Immunoblotting demonstrated that C-peptide increased RARbeta, CRABPII, and HGF. We confirmed a role for RA in reversal of TGF-beta1-induced changes associated with epithelial-mesenchymal transition, including expression changes in Snail, E-cadherin, vimetin, and redistribution of beta-catenin. Importantly, these TGF-beta1-induced changes were inhibited by C-peptide. Further, effects of TGF-beta1 on Snail and E-cadherin expression were blocked by HGF, and inhibitory effects of C-peptide were removed by blockade of HGF activity. This study identifies a novel role for HGF as an effector of C-peptide, possibly via an RA-signaling pathway, highlighting C-peptide as a potential therapy for diabetic nephropathy. PMID:20197308

  14. Determination of cell proliferation using Mcm2 antigen and evaluation of apoptosis and TGF-beta1 expression in GH-secreting or clinically nonfunctioning pituitary adenomas.

    PubMed

    Dallago, Cristina Micheletto; Barbosa-Coutinho, Ligia Maria; Ferreira, Nelson Pires; Meurer, Rosalva; Pereira-Lima, Julia Fernanda Semmelmann; Oliveira, Miriam da Costa

    2010-03-01

    Pituitary adenomas (PA) occasionally show aggressive behavior, with invasion of the surrounding tissues. The identification of markers able to recognize aggressive PA in early stages remains a challenge. We aimed to determine the expression of a new cell proliferation marker, Mcm2, and the presence of apoptosis in PA, and to evaluate the association of clinicopathological features with the apoptotic and proliferative indices. Additionally, the TGF-beta1 expression, an inducer of apoptosis, was determined. The proliferative index was determined in GH-secreting or clinically nonfunctioning PA using immunohistochemical (IH) methods for Mcm2 and Ki-67 antigens. The apoptosis was assessed by the TUNEL method and the TGF-beta1 expression by IH. A significant positive correlation was found between log Mcm2 index and log Ki-67 index (p < 0.001). Mcm2 and Ki-67 detected a similar number of proliferating cells. Mcm2 index showed a significant association with tumor extension (p = 0.02), but not with tumor invasion. Apoptosis was detected in 17% of the adenomas, with a maximum apoptotic index of 0.77%. Immunoreactivity to TGF-beta1 was observed in 77% of the adenomas, showing an association with tumor extension. We concluded that, in this sample, Mcm2 was similar to Ki-67 in the identification of the proliferating cells and that apoptosis was rare. PMID:20174894

  15. Acute Radiation-Induced Nocturia in Prostate Cancer Patients Is Associated With Pretreatment Symptoms, Radical Prostatectomy, and Genetic Markers in the TGF{beta}1 Gene

    SciTech Connect

    De Langhe, Sofie; De Ruyck, Kim; Ost, Piet; Fonteyne, Valerie; Werbrouck, Joke; De Meerleer, Gert; De Neve, Wilfried; Thierens, Hubert

    2013-02-01

    Purpose: After radiation therapy for prostate cancer, approximately 50% of the patients experience acute genitourinary symptoms, mostly nocturia. This may be highly bothersome with a major impact on the patient's quality of life. In the past, nocturia is seldom reported as a single, physiologically distinct endpoint, and little is known about its etiology. It is assumed that in addition to dose-volume parameters and patient- and therapy-related factors, a genetic component contributes to the development of radiation-induced damage. In this study, we investigated the association among dosimetric, clinical, and TGF{beta}1 polymorphisms and the development of acute radiation-induced nocturia in prostate cancer patients. Methods and Materials: Data were available for 322 prostate cancer patients treated with primary or postoperative intensity modulated radiation therapy (IMRT). Five genetic markers in the TGF{beta}1 gene (-800 G>A, -509 C>T, codon 10 T>C, codon 25 G>C, g.10780 T>G), and a high number of clinical and dosimetric parameters were considered. Toxicity was scored using an symptom scale developed in-house. Results: Radical prostatectomy (P<.001) and the presence of pretreatment nocturia (P<.001) are significantly associated with the occurrence of radiation-induced acute toxicity. The -509 CT/TT (P=.010) and codon 10 TC/CC (P=.005) genotypes are significantly associated with an increased risk for radiation-induced acute nocturia. Conclusions: Radical prostatectomy, the presence of pretreatment nocturia symptoms, and the variant alleles of TGF{beta}1 -509 C>T and codon 10 T>C are identified as factors involved in the development of acute radiation-induced nocturia. These findings may contribute to the research on prediction of late nocturia after IMRT for prostate cancer.

  16. Transforming growth factor-beta 1 (TGF-beta 1)- and beta 2-like activities in malignant pleural effusions caused by malignant mesothelioma or primary lung cancer.

    PubMed Central

    Maeda, J; Ueki, N; Ohkawa, T; Iwahashi, N; Nakano, T; Hada, T; Higashino, K

    1994-01-01

    We investigated the levels of TGF-beta in malignant pleural effusions (MPE) caused by malignant mesothelioma (MESO) or primary lung cancer. TGF-beta levels in MPE caused by MESO were 283.9 +/- 219.2 pm (mean +/- s.d.) and were three to six times higher than those due to primary lung cancers (P < 0.01 or P < 0.05). We also evaluated TGF-beta 1- and beta 2-like activities in MPE using specific polyclonal antibodies. Although TGF-beta 1-like activity could be detected in all cases, TGF-beta 2-like activities were detected in five of seven in MESO and in a few cases with primary lung cancer. These results demonstrate that the levels of total TGF-beta and TGF-beta 2-like activity may be clinically useful to differentiate MESO from primary lung cancer. Our data also suggest that TGF-beta may help further characterize the clinical features of MESO. PMID:7955539

  17. Nuclear-factor-{kappa}B (NF-{kappa}B) and radical oxygen species play contrary roles in transforming growth factor-{beta}1 (TGF-{beta}1)-induced apoptosis in hepatocellular carcinoma (HCC) cells

    SciTech Connect

    Wang Fang Kaur, Swayamjot; Cavin, Lakita G.; Arsura, Marcello

    2008-12-26

    Nuclear-Factor-{kappa}B (NF-{kappa}{beta} can counteract transforming growth factor-{beta}1 (TGF-{beta}1)-induced apoptosis in malignant hepatocytes through up-regulation of its downstream genes, such as X-linked inhibitor of apoptosis protein (XIAP). Reports have demonstrated that TGF-{beta}1 can induce oxidative stress, and c-Jun N-terminal Kinase1 (JNK1) is indispensable for TGF-{beta}1-induced apoptosis pathway, but the relationship between radical oxygen species (ROS) and the activation of JNKs is still unclear. In the present study, we found that ROS can induce JNK activation in TGF-{beta}1 mediated apoptosis in hepatocytes. The inhibitors of hydrogen peroxide and superoxide, which were produced by mitochondria under stress, could inhibit the phosphorylation of c-Jun in XIAP knockdown cells. In conclusion, it is the first time to show that both NF-{kappa}B and antioxidants can counteract TGF-{beta}1-induced apoptosis in hepatic cell death through JNK1 pathway.

  18. Common Variants of GSTP1, GSTA1, and TGF{beta}1 are Associated With the Risk of Radiation-Induced Fibrosis in Breast Cancer Patients

    SciTech Connect

    Terrazzino, Salvatore; La Mattina, Pierdaniele; Gambaro, Giuseppina; Masini, Laura; Franco, Pierfrancesco; Canonico, Pier Luigi; Genazzani, Armando A.; Krengli, Marco

    2012-06-01

    Purpose: To provide new insights into the genetic basis of normal tissue radiosensitivity, we evaluated the association between eight polymorphic variants located in six genes related to DNA repair mechanisms, oxidative stress, and fibroblast proliferation (XRCC1 Arg399Gln, XRCC1 Arg194Trp, TP53 Arg72Pro, GSTP1 Ile105Val, GSTA1 C-69T, eNOS G894T, TGF{beta}1 C-509T, and TGF{beta}1 T869C) and the risk of subcutaneous fibrosis in a retrospective series of patients who received radiotherapy after breast-conserving surgery. Methods and Materials: Subcutaneous fibrosis was scored according to the Late Effects of Normal Tissue-Subjective Objective Management Analytical scale in 257 breast cancer patients who underwent surgery plus adjuvant radiotherapy. Genotyping was conducted by polymerase chain reaction-restriction fragment length polymorphism analysis on genomic DNA extracted from peripheral blood. The association between genetic variants and the risk of moderate to severe fibrosis was evaluated by binary logistic regression analysis. Results: Two hundred thirty-seven patients were available for the analysis. Among them, 41 patients (17.3%) developed moderate to severe fibrosis (Grade 2-3), and 196 (82.7%) patients displayed no or minimal fibrotic reactions (Grade 0-1). After adjustment of confounding factors, GSTP1 Ile105Val (odds ratio [OR] 2.756; 95% CI, 1.188-6.393; p = 0.018), GSTA1 C-69T (OR 3.223; 95% CI, 1.176-8.826; p = 0.022), and TGF{beta}1 T869C (OR 0.295; 95% CI, 0.090-0.964; p = 0.043) polymorphisms were found to be significantly associated with the risk of Grade 2-3 radiation-induced fibrosis. In the combined analysis, carriers of three risk genotypes were found to be at higher odds for the development of Grade 2-3 fibrosis than were patients with two risk genotypes (OR 4.415; 95% CI, 1.553-12.551, p = 0.005) or with no or one risk genotype (OR 8.563; 95% CI, 2.671-27.447; p = 0.0003). Conclusions: These results suggest that functional variations in

  19. Identification of cellular target genes of the Epstein-Barr virus transactivator Zta: activation of transforming growth factor beta igh3 (TGF-beta igh3) and TGF-beta 1.

    PubMed Central

    Cayrol, C; Flemington, E K

    1995-01-01

    The lytic switch transactivator Zta initiates the ordered cascade of Epstein-Barr virus gene expression that culminates in virus production. Zta is a sequence-specific DNA-binding protein that transactivates early viral promotes via cis-acting sequences. Activation of some of these genes is mediated through binding to consensus AP-1 promoter elements. This observation suggests that Zta may also regulate the expression of cellular genes. While many targets of Zta have been identified in the Epstein-Barr virus genome, putative host cell targets remain largely unknown. To address this issue, a tetracycline-regulated Zta expression system was generated, and differential hybridization screening was used to isolate Zta-responsive cellular genes. The major target identified by this analysis is a gene encoding a fasciclin-like secreted factor, transforming growth factor beta igh3 (TGF-beta igh3), that was originally identified as a gene that is responsive to the potent immunosuppressor TGF-beta 1. Northern (RNA) blot analysis demonstrated that induction of Zta expression results in a 10-fold increase in TGF-beta igh3 mRNA levels. Zta was also found to increase TGF-beta 1 mRNA levels as well as the amount of active TGF-beta 1 secreted into the medium. Interestingly, alpha 1-collagen IV, which has been shown to potentiate the effects of TGF-beta 1, is also a cellular target of Zta. These results suggest that Zta could play a role in modulating the host cell environment through activating the expression of secreted factors. PMID:7769680

  20. TGF{beta}1 induces apoptosis in invasive prostate cancer and bladder cancer cells via Akt-independent, p38 MAPK and JNK/SAPK-mediated activation of caspases

    SciTech Connect

    Al-Azayzih, Ahmad; Gao, Fei; Goc, Anna; Somanath, Payaningal R.

    2012-10-12

    Highlights: Black-Right-Pointing-Pointer TGF{beta} induced apoptosis in invasive prostate cancer and bladder cancer cells. Black-Right-Pointing-Pointer TGF{beta} inhibited prostate/bladder cancer cell proliferation and colony/foci formation. Black-Right-Pointing-Pointer TGF{beta} induced prostate/bladder cancer cell apoptosis independent of Akt inhibition. Black-Right-Pointing-Pointer TGF{beta} inhibited ERK1/2 phosphorylation in prostate/bladder cancer cells. Black-Right-Pointing-Pointer TGF{beta} induced p38 MAPK and JNK-mediated activation of caspases-9, -8 and -3. -- Abstract: Recent findings indicate that advanced stage cancers shun the tumor suppressive actions of TGF{beta} and inexplicably utilize the cytokine as a tumor promoter. We investigated the effect of TGF{beta}1 on the survival and proliferation of invasive prostate (PC3) and bladder (T24) cancer cells. Our study indicated that TGF{beta}1 decreased cell viability and induced apoptosis in invasive human PC3 and T24 cells via activation of p38 MAPK-JNK-Caspase9/8/3 pathway. Surprisingly, no change in the phosphorylation of pro-survival Akt kinase was observed. We postulate that TGF{beta}1 pathway may be utilized for specifically targeting urological cancers without inflicting side effects on normal tissues.

  1. A novel method for detecting apoptosis shows that hepatocytes undergo a time dependent increase in DNA cleavage and chromatin condensation which is augmented after TGF-beta 1 treatment.

    PubMed

    Cain, K; Inayat-Hussain, S H; Couet, C; Qin, H M; Oberhammer, F A

    1996-04-01

    This study describes a new method for quantitating apoptosis in hepatocyte monolayers in which nuclei were isolated from the cells and DNA strand breaks detected by in situ end-labeling and flow cytometry. Most (97%) nuclei from untreated hepatocytes had low end-labelling and were derived from non-apoptotic cells. Approximately 2-3% of the nuclei had high end-labelling and originated from apoptotic hepatocytes. The numbers of these nuclei increased linearly from 3 to 85% between 0 and 48 h after treatment with transforming growth factor-beta 1 (TGF-beta 1). However, a morphological assessment of apoptosis with Hoechst H33258 showed that the proportion of apoptotic nuclei plateaued at 18-19% between 24 and 48 h after TGF-beta 1 treatment. Thus, the in situ end-labeling technique also detected DNA cleavage in nuclei which did not have an obvious apoptotic morphology. Confocal microscopy of low and high end-labelled nuclei which had been separated by fluorescent cell sorting showed that nuclei with high levels of end-labeling exhibited a wide diversity of morphologies. These included nuclei with little or no chromatin condensation and nuclei with characteristic apoptotic morphology. In addition, nuclei from untreated hepatocytes contained low levels of DNA cleavage, which were localized in areas of condensed chromatin and increased according to the time in culture. Thus, hepatocytes undergo a progressive and cumulative process of DNA cleavage/chromatin condensation which is markedly enhanced by TGF-beta 1. PMID:8900474

  2. Heterotopic endochondrial ossification with mixed tumor formation in C3(1)/Tag transgenic mice is associated with elevated TGF-beta1 and BMP-2 expression.

    PubMed

    Maroulakou, I G; Shibata, M A; Anver, M; Jorcyk, C L; Liu, M l; Roche, N; Roberts, A B; Tsarfaty, I; Reseau, J; Ward, J; Green, J E

    1999-09-23

    Transgenic mice which express the simian virus 40 large T-antigen (Tag) under the regulatory control of the hormone responsive rat C3(1) gene develop unusual lesions of heterotopic bone growth associated with mixed tumor formation arising from eccrine sweat glands found only in the foot pads of mice, ischiocavernosus muscle adjacent to bulbourethral glands and occasionally the salivary and mammary glands. These lesions are very similar to mixed tumors arising in several types of human cancers. Based upon electron microscopic examination and immunocytochemical analyses of cellular differentiation markers, the mixed proliferative lesions in this transgenic mouse model begin with the Tag-induced proliferation of epithelial and myoepithelial cells. The proliferation of these two types of cells results in hyperplasia and adenomatous transformation of the epithelial component, whereas the proliferating myoepithelial cells undergo metaplasia to form chondrocytes which deposit extracellular matrix, including collagen fibers. Cartilage develops focally between areas of epithelial proliferation and subsequently ossifies through a process of endochondrial bone formation. The metaplasia of myoepithelial cells to chondrocytes appears to require the inductive interaction of factors produced by the closely associated proliferating epithelial cells, including members of the TGF-beta superfamily. We demonstrate that TGF-beta1 protein accumulates in the extracellular matrix of the lesions, whereas RNA in situ hybridization reveals that BMP-2, another strong inducer of heterotopic bone formation, is overexpressed by the proliferating epithelial cells during the development of ectopic bone. The formation of sarcomatous tumors within the mixed tumors appears to be androgen-dependent and more frequent in mice lacking a normal allele of p53. This process of cartilage and bone induction may mimic epithelial-mesenchymal interactions which occur during embryonic bone formation. These

  3. The protective effects of omega-6 fatty acids in experimental autoimmune encephalomyelitis (EAE) in relation to transforming growth factor-beta 1 (TGF-beta1) up-regulation and increased prostaglandin E2 (PGE2) production.

    PubMed

    Harbige, L S; Layward, L; Morris-Downes, M M; Dumonde, D C; Amor, S

    2000-12-01

    Polyunsaturated fatty acids are known to affect the immune response and administration of the omega-6 fatty acid linoleic acid has been reported to be beneficial in multiple sclerosis (MS) and EAE. In this study we have investigated the effects of oral feeding of plant lipid rich in the omega-6 fatty acid gamma-linolenic acid from Borago officinalis on acute and relapse disease and the immune response in EAE using SJL mice. EAE was induced by an encephalitogenic peptide (92-106) of myelin oligodendrocyte glycoprotein (MOG), and mice were fed the plant lipid daily from 7 days after EAE induction to assess the effects on acute disease and from day 25 to assess the effects on disease relapse. The clinical incidence and histological manifestations of acute EAE, and the clinical relapse phase of chronic relapsing EAE (CREAE) were markedly inhibited by omega-6 fatty acid feeding. A significant increase in the production of TGF-beta1 in response to concanavalin A (Con A) at day 13 and a significant increase in TGF-beta1 and PGE2 to Con A, PPD and MOG peptide (92-106) at day 21 were detected in spleen mononuclear cells from fatty acid-fed mice. There was no difference in interferon-gamma, IL-4 and IL-2 production between the fatty acid-fed and control groups. Significantly higher TGF-beta mRNA expression was found in the spleens of omega-6 fatty acid-fed mice at day 21. There were no differences in spleen cell proliferative response to Con A, PPD and MOG peptide (92-106). Biochemical analysis of spleen cell membrane fatty acids revealed significant increases in the eicosanoid precursor fatty acids dihomo-gamma-linolenic acid and arachidonic acid in response to gamma-linolenic acid feeding, indicating rapid metabolism to longer chain omega-6 fatty acids. These results show that oral feeding of gamma-linolenic acid-rich plant lipid markedly affects the disease course of acute EAE and CREAE and is associated with an increase in cell membrane long chain omega-6 fatty acids

  4. Apoptosis in vascular endothelial cells caused by serum deprivation, oxidative stress and transforming growth factor-beta.

    PubMed

    Hogg, N; Browning, J; Howard, T; Winterford, C; Fitzpatrick, D; Gobé, G

    1999-01-01

    Vascular endothelial cell apoptosis has previously been shown to play a role in the pathogenesis of hypertension-induced vessel deletion and damage. In the present in vitro study we analyse several possible relevant causative factors of vascular endothelial cell apoptosis, namely, serum deprivation and nutrient depletion, oxidative stress in the forms of hypoxia, hyperoxia or free radical damage, and altered levels of transforming growth factor-beta1 (TGF-beta1) protein. An established cell line, bovine aortic endothelial cells (BAEC), was maintained in complete growth medium (RPMI-1640 plus 15% fetal calf serum and antibiotics, abbreviated as RPMI) in 25cm2 flasks or in 12-well plates on glass coverslips. Confluent but actively-growing cultures were treated with either hypoxia (PO2 of RPMI = 50mmHg), serum-free media (SFM), SFM plus hypoxia, hyperoxia (PO2 of RPMI = 450mmHg), hydrogen peroxide (H2O2, 1mM) in SFM, or TGF-beta1 protein (10ng/mL) in SFM. Appropriate control cultures were used. BAEC were collected 48h or 72h after all treatments except for TGF-beta1 and H2O2 treatments that were collected at 16-18h. Cell death was assessed using morphological characteristics or in situ end labeling (ISEL), cell proliferation assessed using proliferating cell nuclear antigen (PCNA), and TGF-beta1 expression assessed using transcript levels or immunohistochemistry. All treatments significantly increased levels of apoptosis over control cultures (P<0.05), and decreased levels of cell proliferation. Treatment with TGF-beta1 protein or SFM plus hypoxia induced greatest levels of apoptosis. TGF-beta1 protein and transcript levels were decreased in treated cultures, results suggesting that a paracrine source of TGF-beta1 protein would be needed as a cause of endothelial cell apoptosis in viva. Future therapies against inappropriate vessel deletion in disease states may use the known gene-driven nature of apoptosis to modify this sort of cell death in endothelial cells. PMID

  5. Two Faces of TGF-Beta1 in Breast Cancer

    PubMed Central

    Zarzynska, Joanna Magdalena

    2014-01-01

    Breast cancer (BC) is potentially life-threatening malignancy that still causes high mortality among women. Scientific research in this field is focused on deeper understanding of pathogenesis and progressing of BC, in order to develop relevant diagnosis and improve therapeutic treatment. Multifunctional cytokine TGF-β1 is one of many factors that have a direct influence on BC pathophysiology. Expression of TGF-β1, induction of canonical and noncanonical signaling pathways, and mutations in genes encoding TGF-β1 and its receptors are correlated with oncogenic activity of this cytokine. In early stages of BC this cytokine inhibits epithelial cell cycle progression and promotes apoptosis, showing tumor suppressive effects. However, in late stages, TGF-β1 is linked with increased tumor progression, higher cell motility, cancer invasiveness, and metastasis. It is also involved in cancer microenvironment modification and promotion of epithelial to mesenchymal transition (EMT). This review summarizes the current knowledge on the phenomenon called “TGF-β1 paradox”, showing that better understanding of TGF-β1 functions can be a step towards development of new therapeutic approaches. According to current knowledge several drugs against TGF-β1 have been developed and are either in nonclinical or in early stages of clinical investigation. PMID:24891760

  6. miR-181b Promotes hepatic stellate cells proliferation by targeting p27 and is elevated in the serum of cirrhosis patients

    SciTech Connect

    Wang, Baocan; Li, Wenxi; Guo, Kun; Xiao, Yongtao; Wang, Yuqin; Fan, Jiangao

    2012-04-27

    Highlights: Black-Right-Pointing-Pointer miR-181a and miR-181b, especially, miR-181b could be induced by transforming growth factor-beta 1 (TGF-{beta}1) in hepatic stellate cells. Black-Right-Pointing-Pointer miR-181b could promote HSC-T6 cell proliferation by directly targeting the negative cell regulator-p27 in HSC-T6 cell. Black-Right-Pointing-Pointer miR-181b was identified as potential serum diagnostic marker for liver cirrhosis patients. -- Abstract: MicroRNAs, as a kind of negative gene regulators, were demonstrated to be involved in many types of diseases. In this study, we found that transforming growth factor-beta 1 could induce the expression of miR-181a and miR-181b, and miR-181b increased in the much higher folds than miR-181a. Because of the important role of transforming growth factor-beta 1 in HSC activation and liver cirrhosis, we investigate the effect of miR-181a and miR-181b on HSC proliferation. The results showed that miR-181b could promote HSC-T6 cell proliferation by regulating cell cycle. Further study showed p27, the cell cycle regulator, was the direct target of miR-181b in HSC-T6 cell. But miR-181a had no effects on HSC-T6 cell proliferation and cell cycle, and did not target p27. Interestingly, miR-181b is elevated significantly in serum of liver cirrhosis cases comparing to that of normal persons, whereas miR-181a expression was in the similar level with that of normal persons. These results suggested that miR-181b could be induced by TGF-{beta}1 and promote the growth of HSCs by directly targeting p27. The elevation of miR-181b in serum suggested that it may be potential diagnostic biomarkers for cirrhosis. As for miR-181a, it may work in TGF-{beta}1 pathway by a currently unknown mechanism.

  7. TGF-beta 1 and 25-hydroxycholesterol stimulate osteoblast-like vascular cells to calcify.

    PubMed Central

    Watson, K E; Boström, K; Ravindranath, R; Lam, T; Norton, B; Demer, L L

    1994-01-01

    Previous studies in our laboratory demonstrated messenger RNA for bone morphogenetic protein-2a in human calcified plaque, suggesting that arterial calcification is a regulated process, similar to osteogenesis. To further test this hypothesis, we have isolated and cloned a subpopulation of cells from bovine aortic media that show osteoblastic potential. These novel cells are primarily distinguished from smooth muscle cells by expression of a surface marker preliminarily identified as a modified form of the ganglioside sialyl-lactosylceramide (GM3). Osteoblastic potential was indicated by high levels of alkaline phosphatase and collagen I, expression of osteopontin and osteonectin (SPARC), and production of bone-specific osteocalcin and hydroxyapatite. Cultures of these cells were stimulated to form increased numbers of calcium-mineral-producing nodules by the oxysterol 25-hydroxycholesterol as well as by transforming growth factor-beta 1, both known to be present in atherosclerotic lesions. The stimulation of calcifying vascular cells in the artery wall by these two factors suggests a possible mechanism for the colocalization of calcification with atherosclerosis in vivo. Images PMID:8182141

  8. SNF5 is Involved in Suppression of Hepatocellular Carcinoma Progression via TGF-Beta 1 Signaling.

    PubMed

    Sun, Hongmiao; Zhong, Xinping; Wang, Chunyu; Wang, Shengli; Lin, Lin; Zou, Renlong; Wu, Yi; Sun, Ning; Sun, Ge; Wen, Tao; Chi, Zhi-Hong; Zhao, Yue

    2016-07-01

    SNF5 (SMARCB1/INI1/BAF47), a core subunit of SWI/SNF complex, has been reported to modulate cell proliferation and apoptosis. Genetic evidence has suggested that SNF5 participates in tumor suppression. However, the detailed biological function and underlying mechanisms of SNF5 in hepatocellular carcinoma (HCC) progression remain unclear. Here, SNF5 expression reduction in HCC tissues compared with the adjacent non-cancerous tissues has been demonstrated. Importantly, the results showed that reduced SNF5 expression has a strong correlation with worse overall survival of HCC patients. The data demonstrated that knockdown of SNF5 significantly promoted cell growth and migration in Hep3B and HCCLM3 cell lines. Interestingly, it was found that SNF5 suppressed transforming growth factor-β1 (TGF-β1) expression, and SNF5 mRNA expression was negatively correlated with TGF-β1 in HCC tissues. Furthermore, depletion of SNF5 attenuated the sensitivity of HCC cells to sorafenib. Thus, the data suggested that SNF5 may participate in HCC suppression, and reduced expression of SNF5 correlates with the poor differentiation and prognosis of HCC, indicating that SNF5 might be an important prognostic biomarker and promising therapeutic target for HCC. Anat Rec, 299:869-877, 2016. © 2016 Wiley Periodicals, Inc. PMID:27111394

  9. Treatment of muscle injuries by local administration of autologous conditioned serum: a pilot study on sportsmen with muscle strains.

    PubMed

    Wright-Carpenter, T; Klein, P; Schäferhoff, P; Appell, H J; Mir, L M; Wehling, P

    2004-11-01

    Muscle injuries represent a major part of sports injuries and are a challenging problem in traumatology. Strain injuries are the most common muscle injuries after contusions. These injuries can lead to significant pain and disability causing time to be lost to training and competition. Despite the frequency of strain injuries the treatment available is limited and is generally not sufficient to enhance muscle regeneration efficiently when fast resumption of sport activity is a primary target. A number of growth factors play a specific role in regeneration and it has been proven that a previously described method of physically and chemically stimulating whole blood (to produce autologous conditioned serum) induces concentration increases in FGF-2, HGF, and TGF-beta1. A preliminary study was conducted on muscle strain injuries in professional sportsmen receiving either: 1. autologous conditioned serum (ACS) or 2. Actovegin/Traumeel treatment as control. Assessment of recovery from injury was done by: 1. sport professional's ability to participate to 100 % under competition conditions in their respective sport and 2. MRI analysis. A significant difference in the recovery time from injury was demonstrated: 16.6 +/- 0.9 in the ACS treated instead of 22.3 +/- 1.2 (mean +/- SEM) days in the Actovegin/Traumeel control group (p = 0.001). MRI analysis supported the observed acceleration of the lesion recovery time. We conclude that ACS injection is a promising approach to reduce the time to recovery from muscle injury. PMID:15532001

  10. The expression of the TGF beta 1 gene in the first trimester human eye and other embryonic organs.

    PubMed

    Hyldahl, L; Engström, W; Schofield, P

    1990-09-01

    We have examined the expression of the transforming growth factor beta 1 gene in a variety of tissues in the developing human embryo. Northern blot analysis revealed the presence of TGF B1 mRNA in the 10-12 week old eye as well as in most first trimester organs with the notable exception of the yolk sack. In an attempt to determine the topographical distribution of TGF B1 transcripts within the eye, we found that messenger RNA levels were higher in the posterior regions of the eye globe. PMID:2279276

  11. Statin medication in patients with epiretinal membrane is associated with low intravitreal EPO, TGF-beta-1, and VEGF levels

    PubMed Central

    Tuuminen, Raimo; Loukovaara, Sirpa

    2016-01-01

    Background In eyes with idiopathic epiretinal membrane (iERM), the intravitreal growth factor and cytokine levels may associate with postvitrectomy outcomes. Here, we have analyzed the perioperative intravitreal protein levels of potent vasoactive, proinflammatory, and extracellular matrix-remodeling factors in iERM eyes and evaluated the postvitrectomy outcomes. Methods This was an institutional, observational study. Eyes operated on for iERM (n=26) were analyzed according to the use of statin medication. Vitreous samples were subjected to protein measurements of angiopoietin-1 and -2, erythropoietin, transforming growth factor-β1, and vascular endothelial growth factor by enzyme-linked immunosorbent assay, and of matrix metalloproteinase-2 and -9 by gelatin zymography. One-month visual outcomes and 1-year revitrectomy rates were recorded. Results In iERM eyes of patients taking statins, intravitreal levels of erythropoietin (mean ± standard deviation, 10.8±4.9 vs 82.9±119.5 mIU/mg, P=0.003), transforming growth factor-β1 (2.3±4.7 vs 15.8±16.3 pg/mg, P=0.035), and vascular endothelial growth factor (5.5±9.9 vs 236.6±491.6 pg/mg, P=0.006) were lower than in nonstatin-treated patients. At 1-month, visual gain did not significantly differ between iERM eyes of patients with statins and those without (improvement 0.27±0.20 vs 0.16±0.38 logarithm of the minimum angle of resolution units, P=0.118). Conclusion Systemic statin therapy might have a favorable effect on intravitreal factors involved in vascular permeability, inflammation, and fibroproliferation in aging human iERM eyes. PMID:27284236

  12. Involvement of KLF14 and egr-1 in the TGF-beta1 action on Leydig cell proliferation.

    PubMed

    Gonzalez, C R; Vallcaneras, S S; Calandra, R S; Gonzalez Calvar, S I

    2013-02-01

    Transforming growth factor β1 (TGF-β1) is a pleiotropic cytokine that modulates cell homeostasis. In Leydig cells, TGF-β1 exerts stimulatory and inhibitory effect depending on the type I receptor involved in the signaling pathway. The aim of the present work was to study the signaling mechanisms and the intermediates involved in the action of TGF-β1 on TM3 Leydig cell proliferation in the presence or absence of progesterone. The MTT assay showed that the presence of progesterone in the culture media lead to a proliferative effect that was blocked by Ru 486, an inhibitor of progesterone receptor; and ALK-5 did not participate in this effect. TGF-β1 (1 ng/ml) increased the expression of p15 (an inhibitor of cell cycle) in TM3 Leydig cells, and this effect was blocked by progesterone (1μM). The expression of PCNA presented a higher increase in the cell cultured with TGF-β1 plus progesterone than in cells cultured only with TGF-β1. Progesterone induced the gene expression of endoglin, a cofactor of TGF-β1 receptor that leads to a stimulatory signaling pathway, despite of the absence of progesterone response element in endoglin gene. In addition, the presence of progesterone induced the gene expression of egr-1 and also KLF14, indicating that this steroid channels the signaling pathway into a non-canonical mechanism. In conclusion, these findings suggest that the proliferative action of TGF-β1 involves endoglin. This co-receptor might be induced by KLF14 which is probably activated by progesterone. PMID:23317878

  13. Association between Plasma Levels of Transforming Growth Factor-beta1, IL-23 and IL-17 and the Severity of Autism in Egyptian Children

    ERIC Educational Resources Information Center

    Hashim, Haitham; Abdelrahman, Hadeel; Mohammed, Doaa; Karam, Rehab

    2013-01-01

    It has been recently shown that dysregulation of transforming growth factor-beta1 (TGF-beta1), IL-23 and IL-17 has been identified as a major factor involved in autoimmune disorders. Based on the increasing evidence of immune dysfunction in autism the aim of this study was to measure serum levels of TGF-beta1, IL-23 and IL-17 in relation to the…

  14. Angiotensin II stimulated expression of transforming growth factor-beta1 in cardiac fibroblasts and myofibroblasts.

    PubMed

    Campbell, S E; Katwa, L C

    1997-07-01

    Angiotensin II (Ang II) stimulates pathologic myocardial fibrosis. Cardiac fibroblasts (CFb) and myofibroblasts mediate this response, perhaps in part by indirect production of specific cytokines. We sought to determine if Ang II could stimulate transforming growth factor-beta1 (TGF-beta1) gene expression and protein production in adult rat CFb and two cardiac myofibroblast cell types, scar myofibroblasts (MyoFb) and valvular interstitial cells (VIC). Confluent CFb, MyoFb, and VIC in serum-deprived (0.4% FCS) media were treated with Ang II (10(-7) m for CFb; 10(-9) m for MyoFb, VIC) for 24 h. Untreated cells served as controls. Culture media was collected and TGF-beta1 levels determined in triplicate using a sandwich ELISA. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis was performed to determine TGF-beta1 mRNA expression. Ang II increased CFb (P<0.02) and VIC (P<0.04) TGF-beta1 mRNA expression, while the increase in MyoFb was not statistically significant. MyoFb produced the highest TGF-beta1 levels under control conditions compared to VIC and CFb. Ang II stimulated further TGF-beta1 secretion in VIC and CFb, but not MyoFb. The AT1 receptor antagonist Losartan (10(-7) m) greatly attenuated Ang II-stimulated TGF-B1 secretion and decreased TGF-beta1 immunostaining in VIC. The AT2 receptor antagonist PD123177 (10(-7) m) also decreased secretion and immunostaining of TGF-beta1 in VIC, but to a lesser extent than Losartan. TGF-beta1 secretion by MyoFb was unaffected by Losartan and PD123177, although TGF-B1 immunostaining was absent or greatly decreased, respectively, compared to Ang II-treated MyoFb. Ang II stimulates TGF-beta1 gene expression and/or protein production in cardiac fibroblast-like cells which may act as an autocrine/paracrine stimulus to collagen formation. Furthermore, TGF-beta1 production and secretion in these cells can be modulated by specific Ang II receptor antagonists, suggesting a potential benefit in preventing

  15. Diabetes mellitus affects the biomechanical function of the callus and the expression of TGF-beta1 and BMP2 in an early stage of fracture healing

    PubMed Central

    Xu, M.T.; Sun, S.; Zhang, L.; Xu, F.; Du, S.L.; Zhang, X.D.; Wang, D.W.

    2015-01-01

    Transforming growth factor beta 1 (TGF-β1) and bone morphogenetic protein-2 (BMP-2) are important regulators of bone repair and regeneration. In this study, we examined whether TGF-β1 and BMP-2 expressions were delayed during bone healing in type 1 diabetes mellitus. Tibial fractures were created in 95 diabetic and 95 control adult male Wistar rats of 10 weeks of age. At 1, 2, 3, 4, and 5 weeks after fracture induction, five rats were sacrificed from each group. The expressions of TGF-β1 and BMP2 in the fractured tibias were measured by immunohistochemistry and quantitative reverse-transcription polymerase chain reaction, weekly for the first 5 weeks post-fracture. Mechanical parameters (bending rigidity, torsional rigidity, destruction torque) of the healing bones were also assessed at 3, 4, and 5 weeks post-fracture, after the rats were sacrificed. The bending rigidity, torsional rigidity and destruction torque of the two groups increased continuously during the healing process. The diabetes group had lower mean values for bending rigidity, torsional rigidity and destruction torque compared with the control group (P<0.05). TGF-β1 and BMP-2 expression were significantly lower (P<0.05) in the control group than in the diabetes group at postoperative weeks 1, 2, and 3. Peak levels of TGF-β1 and BMP-2 expression were delayed by 1 week in the diabetes group compared with the control group. Our results demonstrate that there was a delayed recovery in the biomechanical function of the fractured bones in diabetic rats. This delay may be associated with a delayed expression of the growth factors TGF-β1 and BMP-2. PMID:26628397

  16. Treatment of colitis with a commensal gut bacterium engineered to secrete human TGF-beta1 under the control of dietary xylan

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Growth factors have shown promise in treating inflammatory bowel disease. They are unstable when administered orally and required in higher doses with systemic administration. In consideration of these problems, we have engineered the commensal bacterium Bacteroides ovatus for the con...

  17. Loss of beta1-integrin enhances TGF-beta1-induced collagen expression in epithelial cells via increased alphavbeta3-integrin and Rac1 activity.

    PubMed

    Hayashida, Tomoko; Jones, Jonathan C R; Lee, Carrie K; Schnaper, H William

    2010-10-01

    Transforming growth factor β (TGF-β) promotes tissue fibrosis via the receptor-specific Smad pathway and non-canonical pathways. We recently reported that TGF-β1-stimulated collagen expression by cultured kidney cells requires integrin-dependent activation of focal adhesion kinase (FAK) and consequent ERK MAP kinase activity leading to Smad3 linker region phosphorylation. Here, we defined a role for αvβ3-integrin in this non-canonical pathway. A human kidney tubular cell line in which β1-integrin was knocked down (β1-k/d) demonstrated enhanced type I collagen mRNA expression and promoter activity. A second shRNA to either αv-integrin or β3-integrin, but not to another αv-binding partner, β6-integrin, abrogated the enhanced COL1A2 promoter activity in β1-k/d cells. Although αvβ3-integrin surface expression levels were not different, αvβ3-integrins colocalized with sites of focal adhesion significantly more in β1-k/d cells, and activated αvβ3-integrin was detected only in β1-k/d cells. Further, the collagen response was decreased by a function-blocking antibody or a peptide inhibitor of αvβ3-integrin. In cells lacking αvβ3-integrin, the responses were attenuated, whereas the response was enhanced in αvβ3-overexpressing cells. Rac1 and ERK, previously defined mediators for this non-canonical pathway, showed increased activities in β1-k/d cells. Finally, inhibition of αvβ3-integrin decreased Rac1 activity and COL1A2 promoter activity in β1-k/d cells. Together, our results indicate that decreasing β1 chain causes αvβ3-integrin to become functionally dominant and promotes renal cell fibrogenesis via Rac1-mediated ERK activity. PMID:20650890

  18. 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 ...

  19. Molecular mechanism of teratogenic effects induced by the fungicide triadimefon: Study of the expression of TGF-{beta} mRNA and TGF-{beta} and CRABPI proteins during rat in vitro development

    SciTech Connect

    Di Renzo, F.; Corsini, E.; Broccia, M.L.; Marinovich, M.; Galli, C.L.; Giavini, E.; Menegola, E.

    2009-01-01

    Azole derivatives are teratogenic in rats and mice in vitro and in vivo. The postulated mechanism for the dysmorphogenetic effects is the inhibition of retinoic acid (RA)-degrading enzyme CYP26. Azole-related abnormalities are confined to structures controlled by RA, especially the neural crest cells, hindbrain, cranial nerves, and craniofacial structures, through a complex signal cascade. The aim of this work is to study the expression of signal molecules activated by RA (TGF-{beta}s) or involved in the modulation of cellular RA concentrations (CRABPI). E9.5 (9.5 day post coitum old embryos) rat embryos, exposed in vitro to triadimefon (FON) for 24 h, were examined or cultured in normal serum for extra 4, 16, and 24 h. RT-PCR was performed to quantify TGF-{beta}1, TGF-{beta}2, TGF-{beta}3, TGF-{beta}RI, TGF-{beta}RII, and TGF-{beta}RIII mRNA in the hindbrain after 24 h of culture. TGF-{beta}1, TGF-{beta}2, and TGF-{beta}RI were found significantly decreased by FON exposure, and consequently their protein expression was analyzed by Western blot and immunohistochemistry. In both controls and FON-exposed embryos, TGF-{beta}1 and TGF-{beta}RI were detected at 24 and 24 + 4 h; TGF-{beta}2 was present only at 24 h. Only TGF-{beta}1 was expressed at the level of hindbrain and branchial tissues. After quantization, TGF-{beta}1 was reduced in the FON group. The expression of CRABPI was observed at all developmental stages. However, in FON-exposed embryos, it was increased at 24 and 24 + 4 h. The hindbrain distribution of CRABPI-positive cells was abnormal in FON-exposed embryos. The results show that the two RA-related molecules (TGF-{beta}1 and CRABPI) are altered by FON exposure in vitro.

  20. Expression of transforming growth factors beta-1, beta 2 and beta 3 in human bladder carcinomas.

    PubMed Central

    Eder, I. E.; Stenzl, A.; Hobisch, A.; Cronauer, M. V.; Bartsch, G.; Klocker, H.

    1997-01-01

    We previously detected elevated transforming growth factor beta-1 (TGF-beta1) serum levels in patients with invasive bladder carcinomas. In this study, we therefore investigated whether elevated serum levels correlate with enhanced TGF-beta expression in human bladder tumours. mRNA levels of TGF-beta1, -beta2 and -beta3 were reduced in bladder tumour tissue to 86%, 68% and 56%, respectively, of the levels in normal urothelium. On the other hand, TGF-beta1 protein levels were found to be higher in superficial tumours (Ta-T1) (mean level of 0.153 ng mg(-1)) and in invasive T2/T3 tumours (mean level of 0.104 ng mg(-1)) compared with normal urothelium (mean level of 0.065 ng mg(-1)). Invasive T4 tumours, however, contained only low amounts of TGF-beta1 (mean level of 0.02 ng mg(-1)). Neither in mean nor in individual patients were serum and tissue TGF-beta levels correlated with each other. Cell culture experiments on primary bladder cells revealed a 57% decrease in TGF-beta1 mRNA levels in tumour compared with normal epithelial cells. Tumour epithelial cells contained about two times higher levels of TGF-beta2 and TGF-beta3 mRNA than normal epithelial cells. Fibroblasts expressed about the same amount of TGF-beta1 or TGF-beta2 as epithelial cells. Yet, fibroblasts released only 19% and 13% of the amount secreted by tumour epithelial cells into the supernatant. TGF-beta3, on the other hand, was expressed by fibroblasts with higher levels than by epithelial cells. TGF-beta1 was the predominent isoform in bladder tissue and cells at protein as well as on mRNA levels indicating that TGFs-beta2 and -beta3 are of minor importance in bladder cancer. In summary, there is a lack of correlation between TGF-beta serum levels and TGF-beta expression in tumour tissue in bladder cancer. Images Figure 1 PMID:9192977

  1. Expression of Caveolin-1 reduces cellular responses to TGF-{beta}1 through down-regulating the expression of TGF-{beta} type II receptor gene in NIH3T3 fibroblast cells

    SciTech Connect

    Lee, Eun Kyung; Lee, Youn Sook; Han, In-Oc; Park, Seok Hee . E-mail: parks@skku.edu

    2007-07-27

    Transcriptional repression of Transforming Growth Factor-{beta} type II receptor (T{beta}RII) gene has been proposed to be one of the major mechanisms leading to TGF-{beta} resistance. In this study, we demonstrate that expression of Caveolin-1 (Cav-1) gene in NIH3T3 fibroblast cells down-regulates the expression of T{beta}RII gene in the transcriptional level, eventually resulting in the decreased responses to TGF-{beta}. The reduced expression of T{beta}RII gene by Cav-1 appeared to be due to the changes of the sequence-specific DNA binding proteins to either Positive Regulatory Element 1 (PRE1) or PRE2 of the T{beta}RII promoter. In addition, Cav-1 expression inhibited TGF-{beta}-mediated cellular proliferation and Plasminogen Activator Inhibitor (PAI)-1 gene expression as well as TGF-{beta}-induced luciferase activity. Furthermore, the inhibition of endogeneous Cav-1 by small interfering RNA increased the expression of T{beta}RII gene. These findings strongly suggest that expression of Cav-1 leads to the decreased cellular responsiveness to TGF-{beta} through down-regulating T{beta}RII gene expression.

  2. The Src family kinase inhibitors PP2 and PP1 block TGF-beta1-mediated cellular responses by direct and differential inhibition of type I and type II TGF-beta receptors.

    PubMed

    Ungefroren, Hendrik; Sebens, Susanne; Groth, Stephanie; Gieseler, Frank; Fändrich, Fred

    2011-05-01

    Both the nonreceptor tyrosine kinase Src and the receptors for transforming growth factor (TGF)-β (TβRI, TβRII) play major roles during tumorigenesis by regulating cell growth, migration/invasion and metastasis. The common Src family kinase inhibitors PP2 and PP1 effectively block Src activity in vitro and in vivo, however, they may exert non-specific effects on other kinases. In this study, we have evaluated PP2 and PP1 for their ability to inhibit TGFβ1-mediated responses in the TGF-β-responsive pancreatic adenocarcinoma cell line Panc1. We show that PP2 and PP1 but not the more specific Src inhibitor SU6656 effectively relieved TGF-b1-induced growth arrest and p21(WAF1) induction, while basal growth was enhanced by PP2 and PP1, and suppressed by SU6656. PP2 and PP1 but not SU6656 also suppressed TGF-β1-induced epithelial-to-mesenchymal transition (EMT) as evidenced by their ability to inhibit downregulation of the epithelial marker E-cadherin, and upregulation of the EMT-associated transcription factor Slug. Likewise, PP2 and PP1 but not SU6656 effectively blocked TGF-β1-induced activation of Smad2 and p38 MAPK and partially suppressed Smad activation and transcriptional activity on TGF-β/Smad-responsive reporters of a kinase-active TβRI mutant ectopically expressed in Panc1 cells. Interestingly, PP2 and PP1 strongly inhibited recombinant TβRI in an in vitro kinase assay, with PP1 being more potent and PP2 being nearly as potent as the established TβRI inhibitor SB431542. PP2 but not PP1 also weakly inhibited the TβRII kinase. Together, these data provide evidence that PP2 and PP1 are powerful inhibitors of TβR function that can block TGF-β/Smad signaling in a Src-unrelated fashion. Both agents may be useful as dual TGF-β/Src inhibitors in experimental therapeutics of late stage metastatic disease. PMID:21395548

  3. Serum herpes simplex antibodies

    MedlinePlus

    ... gov/ency/article/003352.htm Serum herpes simplex antibodies To use the sharing features on this page, please enable JavaScript. Serum herpes simplex antibodies is a blood test that looks for antibodies ...

  4. Serum free hemoglobin test

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/003677.htm Serum free hemoglobin test To use the sharing features on this page, please enable JavaScript. Serum free hemoglobin is a blood test that measures the ...

  5. Serum bactericidal test.

    PubMed Central

    Stratton, C W

    1988-01-01

    The serum bactericidal test represents one of the few in vitro tests performed in the clinical microbiology laboratory that combines the interaction of the pathogen, the antimicrobial agent, and the patient. Although the use of such a test antedates the antimicrobial era, its performance, results, and interpretation have been subject to question and controversy. Much of the confusion concerning the serum bactericidal test can be avoided by an understanding of the various factors which influence bactericidal testing. In addition, the methodologic aspects of the serum bactericidal test have recently been addressed and should place this test on firmer ground. New information on the clinical utility of this test is becoming available; additional data are needed to establish more clearly the usefulness of the serum bactericidal test in specific infections. Such clinical trials from multiple centers will enable firmer recommendations for the future use of the serum bactericidal test. PMID:3060242

  6. Serum free hemoglobin test

    MedlinePlus

    Blood hemoglobin; Serum hemoglobin ... Hemoglobin (Hb) is the main component of red blood cells. It is a protein that carries oxygen. ... people may contain up to 5 mg/dL hemoglobin. Normal value ranges may vary slightly among different ...

  7. Serum globulin electrophoresis

    MedlinePlus

    ... may indicate: Acute infection Bone marrow cancer called multiple myeloma Chronic inflammatory disease (for example, rheumatoid arthritis and ... test Hemoglobin Hyperimmunization Immunoelectrophoresis - ... electrophoresis - serum Rheumatoid arthritis Systemic lupus erythematosus ...

  8. Pregnancy outcome in dairy and beef cattle after artificial insemination and treatment with seminal plasma or transforming growth factor beta-1.

    PubMed

    Odhiambo, J F; Poole, D H; Hughes, L; Dejarnette, J M; Inskeep, E K; Dailey, R A

    2009-09-01

    Reduced capability of the uterus to support pregnancy in the absence of its interaction with secretions from male accessory glands has been demonstrated in rodents and to some extent in pigs. However, in cattle, the role of postmating inflammatory response on pregnancy success has not been studied. The current study examined the influence of uterine presensitization with seminal antigens at breeding on pregnancy outcome in cows. Lactating beef (n=1090) and dairy (n=800) cows received 0.5 mL seminal plasma (SP), 40 ng recombinant human transforming growth factor-beta1 (rhTGF-beta1), or 0.5 mL bovine serum albumin (BSA), or were left untreated before or at insemination. Semen was deposited into the anterior cervix using a second insemination gun. Pregnancy was diagnosed at 35 to 40 d postinsemination by transrectal ultrasonography or from records of calves born the subsequent calving season. Pregnancy rates in beef cows did not differ among treatments but differed among trials (69.8%, 52.5% vs. 40.3%; P<0.05). In trials where average pregnancy rates were below 50%, treatments with TGF-beta1 but not SP tended (P<0.07) to increase pregnancy rates in beef cows. In dairy cows, SP and TGF-beta1 improved pregnancy outcome by 10 percentage points, but these increments did not achieve statistical significance. In conclusion, this study did not find any conclusive evidence for the effect of TGF-beta1 or seminal plasma on pregnancy outcome in lactating dairy or beef cows but realized marginal improvements when pregnancy rates were below 50% (compromised fertility). PMID:19501392

  9. Recombinant soluble betaglycan is a potent and isoform-selective transforming growth factor-beta neutralizing agent.

    PubMed Central

    Vilchis-Landeros, M M; Montiel, J L; Mendoza, V; Mendoza-Hernández, G; López-Casillas, F

    2001-01-01

    Betaglycan is an accessory receptor of members of the transforming growth factor-beta (TGF-beta) superfamily, which regulates their actions through ligand-dependent interactions with type II receptors. A natural soluble form of betaglycan is found in serum and extracellular matrices. Soluble betaglycan, prepared as a recombinant protein using the baculoviral expression system, inhibits the actions of TGF-beta. Because of its potential use as an anti-TGF-beta therapeutic agent, we have purified and characterized baculoviral recombinant soluble betaglycan. Baculoviral soluble betaglycan is a homodimer formed by two 110 kDa monomers associated by non-covalent interactions. This protein is devoid of glycosaminoglycan chains, although it contains the serine residues, which, in vertebrate cells, are modified by these carbohydrates. On the other hand, mannose-rich carbohydrates account for approximately 20 kDa of the mass of the monomer. End-terminal sequence analysis of the soluble betaglycan showed that Gly(24) is the first residue of the mature protein. Similarly to the natural soluble betaglycan, baculoviral soluble betaglycan has an equilibrium dissociation constant (K(d)) of 3.5 nM for TGF-beta1. Ligand competition assays indicate that the relative affinities of recombinant soluble betaglycan for the TGF-beta isoforms are TGF-beta2>TGF-beta3>TGF-beta1. The anti-TGF-beta potency of recombinant soluble betaglycan in vitro is 10-fold higher for TGF-beta2 than for TGF-beta1. Compared with a commercial pan-specific anti-TGF-beta neutralizing antibody, recombinant soluble betaglycan is more potent against TGF-beta2 and similar against TGF-beta1. These results indicate that baculoviral soluble betaglycan has the biochemical and functional properties that would make it a suitable agent for the treatment of the diseases in which excess TGF-beta plays a central physiopathological role. PMID:11256966

  10. Serum susceptibility of bovine pasteurellas.

    PubMed Central

    Blau, K A; Ward, A C; Prieur, D J; Corbeil, L B

    1987-01-01

    In this study, the serum sensitivity of 23 P. haemolytica isolates and 18 P. multocida isolates was determined by incubating dilutions of bacteria with equal volumes of fresh or heat-inactivated bovine serum for one, two, or three hours. Clinical isolates of both Pasteurella species were resistant to serum, whereas isolates from asymptomatic cattle varied in serum susceptibility. The classical pathway of complement appeared to be the principal means of complement mediated killing as detected by incubation in the presence or absence of EGTA-MgCl2. Lyzozyme and iron saturation of serum did not greatly affect serum susceptibility with either of the Pasteurella species. PMID:3300919

  11. 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

  12. Structure of Serum Albumin

    NASA Technical Reports Server (NTRS)

    Carter, Daniel C.; Ho, Joseph X.

    1994-01-01

    Because of its availability, low cost, stability, and unusual ligand-binding properties, serum albumin has been one of the mst extensively studied and applied proteins in biochemistry. However, as a protein, albumin is far from typical, and the widespread interest in and application of albumin have not been balanced by an understanding of its molecular structure. Indeed, for more than 30 years structural information was surmised based solely on techniques such as hydrodynamics, low-angle X-ray scattering, and predictive methods.

  13. Restoring Blood Flow Beats Exercise for Poor Leg Circulation

    MedlinePlus

    ... the researchers analyzed levels of a protein, called TGF-Beta1, that triggers scarring in patients with severe ... The study also found that collagen fibers and TGF-Beta1 levels increased in the exercise and control ...

  14. Expression of Cyclooxygenase-2 and Transforming Growth Factor-beta1 in HCV-Induced Chronic Liver Disease and Hepatocellular Carcinoma

    PubMed Central

    El-Bassiouny, Azza E.I.; Zoheiry, Mona M.K.; Nosseir, Mona M.F.; El-Ahwany, Eman G.; Ibrahim, Raafat A.; El-Bassiouni, Nora E.I.

    2007-01-01

    Cyclooxygenase-2 (COX-2) and transforming growth factor-beta1 (TGF-beta1) were modulated in a variety of viral infections, but there is a paucity of data about their role in the pathologic process of cirrhosis and/or hepatocellular carcinoma (HCC) following chronic hepatitis C virus (HCV) infection. The material of the current study included 50 cases of chronic hepatitis C (CHC) without cirrhosis, 30 cases of CHC with cirrhosis, and 30 cases of HCC with HCV admitted to the Gastroenterology and Hepatology Department of Theodor Bilharz Research Institute, Giza, Egypt. Fifteen wedge liver biopsies, taken during laparoscopic cholecystectomy, were included in the study as normal controls. Laboratory investigations, serologic markers for viral hepatitis, and serum alpha fetoprotein levels (alpha-FP) were done for all cases of the study. Immunohistochemistry using primary antibodies against both factors revealed weak to faint immunoreactivity to COX-2 and TGF-beta1 in normal hepatic tissue (< 30% and < 50% of the cells, respectively). COX-2 expression was upregulated in patients with CHC with and without cirrhosis, yet 80% of positively stained cirrhotic cases showed marked staining intensity. Higher COX-2 expression was observed in well-differentiated HCC cases (80%) with marked staining intensity (75%) compared with advanced HCC tumors (P < .001). TGF-beta1 was expressed in the hepatocytes of all cases of CHC with and without cirrhosis as well as in 67% of HCC cases. Extensive cytoplasmic expression was detected in 52%, 93.3%, and 46.6% of CHC patients without cirrhosis, patients with cirrhosis, and patients with HCC, respectively. A positive correlation was observed between hepatic expression of COX-2 and TGF-beta1 (r = 0.67, P < .05); however, no correlation was detected between the latter and grade of HCC differentiation (r = 0.33, P > .05). Conclusion These findings may suggest that TGF-beta1 plays a role in hepatic cell damage following HCV infection thus stressing

  15. 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

  16. Serum albumin: touchstone or totem?

    PubMed

    Margarson, M P; Soni, N

    1998-08-01

    A decrease in serum albumin concentrations is an almost inevitable finding in disease states, and is primarily mediated in the acute phase by alterations in vascular permeability and redistribution. This change is not disease specific but marked changes that persist are generally associated with a poorer prognosis. Critical appraisal of long-standing practices and the availability of alternative colloid solutions have led to a reduction in albumin replacement therapy, and a widespread tolerance of lower albumin concentrations in patients. The factors determining serum albumin concentrations, their measurement and the implications of hypoalbuminaemia are reviewed. The clinical value of serum albumin measurement is discussed. PMID:9797524

  17. Brain injury-associated biomarkers of TGF-beta1, S100B, GFAP, NF-L, tTG, AbetaPP, and tau were concomitantly enhanced and the UPS was impaired during acute brain injury caused by Toxocara canis in mice

    PubMed Central

    Liao, Chien-Wei; Fan, Chia-Kwung; Kao, Ting-Chang; Ji, Dar-Der; Su, Kua-Eyre; Lin, Yun-Ho; Cho, Wen-Long

    2008-01-01

    Background Because the outcomes and sequelae after different types of brain injury (BI) are variable and difficult to predict, investigations on whether enhanced expressions of BI-associated biomarkers (BIABs), including transforming growth factor β1 (TGF-β1), S100B, glial fibrillary acidic protein (GFAP), neurofilament light chain (NF-L), tissue transglutaminases (tTGs), β-amyloid precursor proteins (AβPP), and tau are present as well as whether impairment of the ubiquitin-proteasome system (UPS) is present have been widely used to help delineate pathophysiological mechanisms in various BIs. Larvae of Toxocara canis can invade the brain and cause BI in humans and mice, leading to cerebral toxocariasis (CT). Because the parasitic burden is light in CT, it may be too cryptic to be detected in humans, making it difficult to clearly understand the pathogenesis of subtle BI in CT. Since the pathogenesis of murine toxocariasis is very similar to that in humans, it appears appropriate to use a murine model to investigate the pathogenesis of CT. Methods BIAB expressions and UPS function in the brains of mice inoculated with a single dose of 250 T. canis embryonated eggs was investigated from 3 days (dpi) to 8 weeks post-infection (wpi) by Western blotting and RT-PCR. Results Results revealed that at 4 and 8 wpi, T. canis larvae were found to have invaded areas around the choroid plexus but without eliciting leukocyte infiltration in brains of infected mice; nevertheless, astrogliosis, an indicator of BI, with 78.9~142.0-fold increases in GFAP expression was present. Meanwhile, markedly increased levels of other BIAB proteins including TGF-β1, S100B, NF-L, tTG, AβPP, and tau, with increases ranging 2.0~12.0-fold were found, although their corresponding mRNA expressions were not found to be present at 8 wpi. Concomitantly, UPS impairment was evidenced by the overexpression of conjugated ubiquitin and ubiquitin in the brain. Conclusion Further studies are needed to determine whether there is an increased risk of CT progression into neurodegenerative disease because neurodegeneration-associated AβPP and phosphorylated tau emerged in the brain. PMID:18573219

  18. Serum Uric Acid in Smokers

    PubMed Central

    Hanna, Bassam E.; Hamed, Jamal M.; Touhala, Luma M.

    2008-01-01

    Objectives To demonstrate the possible effect of smoking on serum uric acid. Methods Subjects enrolled in study were divided into two groups; nonsmokers and smokers, each with 60 male volunteers of the same social class and dietary habit without history of alcohol consumption, diabetes mellitus, hyperuricemia and gout, renal, joint, lung or heart diseases. Fasting blood and random urine samples were obtained from both groups for measurement of uric acid and creatinine. Calculation of both urine uric acid/urine creatinine ratio and fraction excretion of uric acid were done. The results were statistically evaluated by standard statistical methods. Results No significant differences in the age, serum creatinine, spot urine uric acid/urine creatinine ratio and fraction excretion of uric acid between the two groups, serum uric acid was significantly lower in smokers. In smokers there was significant negative correlation of smoking status (average number of cigarette smoked/day, duration of smoking and cumulative amount of smoking) with serum uric acid. Conclusion After exclusion of other factors affecting uric acid level, the significant low serum uric acid level in smokers was attributed to reduce endogenous production as a result of chronic exposure to cigarette smoke that is a significant source of oxidative stress. As this reduction is proportionate with smoking status and predisposes to cardiovascular disease, it is, therefore, recommended for smokers to stop or reduce smoking and introduce serum uric acid estimation as routine test since its cheap and simple to reflect their antioxidant level. Keywords Smokers; Uric acid; CVD. PMID:22334840

  19. Role of ROS-mediated TGF beta activation in laser photobiomodulation

    NASA Astrophysics Data System (ADS)

    Arany, Praveen R.; Chen, Aaron Chih-Hao; Hunt, Tristan; Mooney, David J.; Hamblin, Michael

    2009-02-01

    The ability of laser light to modulate specific biological processes has been well documented but the precise mechanism mediating these photobiological interactions remains an area of intense investigation. We recently published the results of our clinical trial with 30 patients in an oral tooth-extraction wound healing model using a 904nm GaAs laser (Oralaser 1010, Oralia, Konstnaz, Germany), assessing healing parameters using routine histopathology and immunostaining (Arany et al Wound Rep Regen 2007, 15, 866). We observed a better organized healing response in laser irradiated oral tissues that correlated with an increased expression of TGF-beta1 immediately post laser irradiation. Our data suggested the source of latent TGF-beta1 might be from the degranulating platelets in the serum, an abundant source of in vivo latent TGF-beta, in the freshly wounded tissues. Further, we also demonstrated the ability of the low power near-infrared laser irradiation to activate the latent TGF-beta complexes in vitro at varying fluences from 10sec (0.1 J/cm2) to 600secs (6 J/cm2). Using serum we observed two isoforms, namely TGF-beta1 and TGF-beta3, were capable of being activated by laser irradiation using an isoform-specific ELISA and a reporter based (p3TP) assay system. We are presently pursuing the precise photomolecular mechanisms focusing on potential chromophores, wavelength and fluence parameters affecting the Latent TGF-beta activation process in serum. As ROS mediated TGF-beta activation has been previously demonstrated and we are also exploring the role of Laser generated-ROS in this activation process. In summary, we present evidence of a potential molecular mechanism for laser photobiomodulation in its ability to activate latent TGF-beta complexes.

  20. [Serum resistance of Escherichia coli in chronic pyelonephritis. 1. Serum resistance in the human serum pool].

    PubMed

    Falkenhagen, U; Handschuck, I; Ulisko, I N; Ratiner YuA; Nimmich, W; Zingler, G; Naumann, G

    1984-07-01

    123 patients of the kidney department of the Clinic for Inner Medicine of Rostock University suffering from chronic pyelonephritis were taken into microbiological observation for between one and four years. 170 E. coli strains were bred from 59 patients with significant bacteriuria in the course of the disease and their serum resistence was determined with pooled human serum using Taylor's method. 78.24% of the strains examined were serum-sensitive, 11.18% intermediate and 10.59% serum-resistent. All strains were O-, K- and H-typed. 57.06% were successfully O-typed and were distributed over 40 O-serogroups. 24.12% were not typable and 18.82% were rough colonies. 86.50% of the resistent and intermediate strains strains were O-typable, 13.50% could not be typed. The significance of E. coli antigens (O, K, H) and serum resistence for the maintenance of a chronic infection is discussed. PMID:6385542

  1. Liver regeneration after partial hepatectomy in rat is more impaired in a steatotic liver induced by dietary fructose compared to dietary fat

    SciTech Connect

    Tanoue, Shirou; Uto, Hirofumi; Kumamoto, Ryo; Arima, Shiho; Hashimoto, Shinichi; Nasu, Yuichiro; Takami, Yoichiro; Moriuchi, Akihiro; Sakiyama, Toshio; Oketani, Makoto; Ido, Akio; Tsubouchi, Hirohito

    2011-04-01

    Highlights: {yields} Hepatic steatosis in rats fed a high fructose diet was less severe than that in rats fed a high fat diet. {yields} Liver regeneration was more impaired in rats fed a high fructose diet than in rats fed a high fat diet. {yields} Dysregulation of genes associated with metabolism may contribute to impairment of liver regeneration. {yields} Regulation of the TGF-{beta}1 level after partial hepatectomy may be impaired in rats fed a high fructose diet. -- Abstract: Hepatic steatosis (HS) has a negative effect on liver regeneration, but different pathophysiologies of HS may lead to different outcomes. Male Sprague-Dawley rats were fed a high fructose (66% fructose; H-fruc), high fat (54% fat; H-fat), or control chow diet for 4 weeks. Based on hepatic triglyceride content and oil red O staining, HS developed in the H-fruc group, but was less severe compared to the H-fat group. Hepatic mRNA expression levels of fatty acid synthase and fructokinase were increased and those of carnitine palmitoyltransferase-1 and peroxisome proliferator-activated receptor-{alpha} were decreased in the H-fruc group compared to the H-fat group. Liver regeneration after 70% partial hepatectomy (PHx) was evaluated by measuring the increase in postoperative liver mass and PCNA-positive hepatocytes, and was impaired in the H-fruc group compared to the H-fat and control groups on days 3 and 7. Serum levels of tumor necrosis factor-{alpha}, interleukin-6 and hepatocyte growth factor did not change significantly after PHx. In contrast, serum TGF-{beta}1 levels were slightly but significantly lower in the control group on day 1 and in the H-fat group on day 3 compared to the level in each group on day 0, and then gradually increased. However, the serum TGF-{beta}1 level did not change after PHx in the H-fruc group. These results indicate that impairment of liver regeneration after PHx in HS is related to the cause, rather than the degree, of steatosis. This difference may result

  2. Piezoelectric microcantilever serum protein detector

    NASA Astrophysics Data System (ADS)

    Capobianco, Joseph A.

    The development of a serum protein detector will provide opportunities for better screening of at-risk cancer patients, tighter surveillance of disease recurrence and better monitoring of treatment. An integrated system that can process clinical samples for a number of different types of biomarkers would be a useful tool in the early detection of cancer. Also, screening biomarkers such as antibodies in serum would provide clinicians with information regarding the patient's response to treatment. Therefore, the goal of this study is to develop a sensor which can be used for rapid, all-electrical, real-time, label-fee, in-situ, specific quantification of cancer markers, e.g., human epidermal receptor 2 (Her2) or antibodies, in serum. To achieve this end, piezoelectric microcantilever sensors (PEMS) were constructed using an 8 mum thick lead magnesium niobate-lead titanate (PMN-PT) freestanding film as the piezoelectric layer. The desired limit of detection is on the order of pg/mL. In order to achieve this goal the higher frequency lateral extension modes were used. Also, as the driving and sensing of the PEMS is electrical, the PEMS must be insulated in a manner that allows it to function in aqueous solutions. The insulation layer must also be compatible with standardized bioconjugation techniques. Finally, detection of both cancer antigens and antibodies in serum was carried out, and the results were compared to a standard commercialized protocol. PEMS have demonstrated the capability of detecting Her2 at a concentration of 5 pg/mL in diluted human serum (1:40) in less than 1 hour. The approach can be easily translated into the clinical setting because the sensitivity is more than sufficient for monitoring prognosis of breast cancer patients. In addition to Her2 detection, antibodies in serum were assayed in order to demonstrate the feasibility of monitoring the immune response for antibody-dependent cellular cytotoxicity (ADCC) in patients on antibody therapies

  3. The making of "truth serum".

    PubMed

    Winter, Alison

    2005-01-01

    This essay reconstructs a social and cultural history of "truth serum" in America during the 1920s and 1930s, identifying the intellectual ingredients of the idea of a physiological "truth technique," and examining why it seemed to meet an urgent need. It argues that truth serum had the patina of modern science but produced a phenomenon that could be understood and evaluated by every man. It therefore offered the public a technique with the benefits of expertise but without its attendant costs to lay authority. The paper also argues that truth serum helped develop an account of memory as a permanent record of experience, accessible through altered states of mind. This view contributed to the production of a public understanding of memory that both diverged from previous claims about memory and recall, and ran counter to the direction of current psychological research. It thus helped lay the groundwork for claims about memory permanence and scientific recall techniques later in the twentieth century. PMID:16184018

  4. Serum cholesterol concentrations in parasuicide.

    PubMed Central

    Gallerani, M.; Manfredini, R.; Caracciolo, S.; Scapoli, C.; Molinari, S.; Fersini, C.

    1995-01-01

    OBJECTIVE--To evaluate whether people who have committed parasuicide have low serum cholesterol concentrations. DESIGN--Results of blood tests in subjects admitted to hospital for parasuicide compared with those of a control group of non-suicidal subjects; comparison in subgroup of parasuicide subjects of two sets of blood test results (one set from admission for parasuicide and the other from admission for some other illness). SETTING--General hospital, Ferrara, Italy. SUBJECTS--331 parasuicide subjects aged 44 (SD 21) years (109 with two sets of blood test results) and 331 controls. MAIN OUTCOME MEASURES--Serum cholesterol concentrations and possible association with parasuicide, considering sex, violence of method of parasuicide, and underlying psychiatric disorder. RESULTS--Lower serum cholesterol concentrations (4.96 (SD 1.16) mmol/l) were found in the parasuicide subjects than in the controls (5.43 (1.30); P < 0.001), regardless of sex and degree of violence of parasuicide method. Both men and women with two sets of blood test results had lower cholesterol concentrations after parasuicide. Linear regression analysis showed that the difference in cholesterol concentrations was significantly related to the length of time between the taking of the two sets of blood samples. CONCLUSION--The study showed low cholesterol concentrations after parasuicide. This finding agrees with previous studies, which suggest an association between low cholesterol concentration and suicide. PMID:7795448

  5. Serum Survivin Increases in Prolactinoma

    PubMed Central

    Dellal, Fatma Dilek; Niyazoglu, Mutlu; Gorar, Suheyla; Ademoglu, Esranur; Candan, Zehra; Bekdemir, Handan; Hacioglu, Yalcin; Kaya, Fatih Oner

    2015-01-01

    Background Prolactinoma is the most common adult pituitary adenoma. Survivin is a member of the family of inhibitors of apoptosis proteins. Its expression is observed in many tumors. Survivin expression has shown in prolactinoma tissue before but no study exists showing serum survivin level. The aim of the present study was to investigate serum survivin levels in patients with prolactinoma and demonstrate its value in diagnosis of the disease. Methods The group of patients consisted of 25 women, aged from 17 to 51 years. As a control group, 21 healthy women, aged from 22 to 45 years were included. Twenty patients had microprolactinoma, while five patients had macroprolactinoma. All patients had received dopamine agonist treatment. Serum survivin levels were measured in all of the groups. Results Survivin levels were significantly higher in prolactinoma patients compared to controls (19.04 (10 - 38) pg/mL; 15.05 (8 - 22) pg/mL; P = 0.042). There was no difference between microadenoma and macroadenoma patients in survivin levels (19.22 (10 - 38) pg/mL; 18.40 (16 - 22) pg/mL; P = 0.914). In correlation analysis, survivin was not correlated with other parameters. Conclusions We consider that higher survivin levels might be a molecular marker predicting the presence of prolactinoma and may be useful for the diagnosis. But large-scale research is needed to clarify its role in diagnosis of prolactinoma patients. PMID:25699121

  6. Cytokines modulate the sensitivity of human fibroblasts to stimulation with insulin-like growth factor-I (IGF-I) by altering endogenous IGF-binding protein production.

    PubMed

    Yateman, M E; Claffey, D C; Cwyfan Hughes, S C; Frost, V J; Wass, J A; Holly, J M

    1993-04-01

    Human dermal fibroblasts produce a number of insulin-like growth factor-binding proteins (IGFBPs) including the main circulating form, IGFBP-3. It has been suggested that the regulation of IGFBP secretion may play a major role in modulating insulin-like growth factor (IGF) bioactivity. We have quantified the effects of two cytokines, transforming growth factor-beta 1 (TGF-beta 1) and tumour necrosis factor-alpha (TNF-alpha) which have opposing actions on fibroblast IGFBP-3 production, and examined their subsequent role in IGF-I mitogenesis. TGF-beta 1 caused a dose-dependent increase in IGFBP-3 in serum-free fibroblast-conditioned media. TGF-beta 1 (1 microgram/l) resulted in immunoreactive IGFBP-3 levels reaching 286.5 +/- 22.4% of control after 20 h, the increase being confirmed by Western ligand blot. TNF-alpha caused a dose-dependent decrease in fibroblast IGFBP-3 secretion, 1 microgram TNF-alpha/l reducing IGFBP-3 levels to 32.1 +/- 11.% of control. This effect was not due to cytotoxicity and was not cell-density-dependent. Fibroblast proliferation was examined using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric cytochemical bioassay. The addition of IGF-I resulted in dose-dependent growth stimulation after 48 h, the effective range being 20-100 micrograms/l. The IGF-I analogue Long-R3-IGF-I which has little affinity for the IGFBPs was approximately 20-fold more potent in this assay, and was unaffected by exogenous IGFBP-3.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7684061

  7. Serum neopterin levels in alcoholic liver disease.

    PubMed

    González-Reimers, E; Santolaria-Fernández, F; Rodríguez-Rodríguez, E; Rodríguez-Moreno, F; Martínez-Riera, A; Milena-Abril, A; González-García, C

    1993-09-01

    Serum neopterin levels have been determined by RIA in 105 patients affected by chronic alcoholic liver disease, 68 of them cirrhotics, and in 12 controls. Serum Neopterin was significantly higher in patients than in controls, correlated with Pughs' score and Child's classification, and also with serum laminin and type III collagen N-terminal propeptide, and with histomorphometrically determined liver fibrosis. Serum neopterin levels were higher in patients who died than in survivors, serum neopterin levels over 19.15 nmol/l being associated with higher mortality rates. PMID:8261879

  8. Reduction of blood serum cholesterol

    NASA Technical Reports Server (NTRS)

    Winitz, M. (Inventor)

    1974-01-01

    By feeding a human subject as the sole source of sustenance a defined diet wherein the carbohydrate consists substantially entirely of glucose, maltose or a polysaccharide of glucose, the blood serum cholesterol level of the human subject is substantially reduced. If 25 percent of the carbohydrate is subsequently supplied in the form of sucrose, an immediate increase from the reduced level is observed. The remainder of the defined diet normally includes a source of amino acids, such as protein or a protein hydrolysate, vitamins, minerals and a source of essential fatty acid.

  9. Cultivation of Plasmodium falciparum using animal serum (horse, calf and bovine) as human serum substitute.

    PubMed

    Ramos, M I; Hermosura, M E; Nakabayashi, T

    1986-11-01

    Horse, calf and bovine serum were successfully used as human serum substitutes in the in vitro cultivation of Plasmodium falciparum. Positive results were obtained only after gradually adapting the parasites to the substitute serum. Adapted lines were established within 4-5 weeks. 10% horse serum was observed to be the best substitute with growth rates comparable or even surprising that obtained in human serum. Pure calf or bovine serum supported stable growths of 20-30% less which was enhanced to comparable levels after addition of 1% glucose-peptone to the medium. Direct transfers of adapted cultures to human serum showed enhanced growth rates. Lower growth rates of adapted cultures (i.e. horse serum-adapted cultures) in other substitute sera (i.e. calf or bovine sera) were improved in subsequent subcultures. Similarly, there were no adverse effects when they were returned back to the substitute serum they were originally adapted to. PMID:3541461

  10. Serum markers of intrahepatic cholangiocarcinoma.

    PubMed

    Malaguarnera, Giulia; Paladina, Isabella; Giordano, Maria; Malaguarnera, Michele; Bertino, Gaetano; Berretta, Massimiliano

    2013-01-01

    Cholangiocarcinoma (CCA) is a relatively rare type of primary liver cancer that originates in the bile duct epithelium. It is an aggressive malignancy typified by unresponsiveness to chemotherapy and radiotherapy. Despite advances in radiologic techniques and laboratory diagnostic test, the diagnosis of CCA remains highly challenging. Development in molecular techniques has led to go into the possible use of serum markers in diagnosing of cholangiocarcinoma. This review summarizes the principal characteristics of serum markers of cholangiocarcinoma. The tumour markers used frequently such as Carbohydrate antigen 19-9 (CA 19-9), Carcinogenic Embryonic antigen (CEA), and Cancer Antigen 125 have shown sufficient sensitivity and specificity to detect and monitor CCA. In particular, the combination of these tumour markers seems to increase their efficiency in diagnosing of cholangiocarcinoma. New markers such as Soluble fragment of cytokeratin 19 (CYFRA 21-1) Mucins, Tumour Markers_{2} pyruvate-Kinase (TuM_{2-} PK) and metalloproteinase-7 (MMP-7) have been recently shown to help in the diagnosis of CCA, with in some cases a prognostic value. PMID:23396291

  11. Control of growth and squamous differentiation in normal human bronchial epithelial cells by chemical and biological modifiers and transferred genes

    SciTech Connect

    Pfeifer, A.M.; Lechner, J.F.; Masui, T.; Reddel, R.R.; Mark, G.E.; Harris, C.C.

    1989-03-01

    The majority of human lung cancers arise from bronchial epithelial cells. The normal pseudostratified bronchial epithelium is composed of basal, mucous, and ciliated cells. This multi-differentiated epithelium usually responds to xenobiotics and physical injury by undergoing basal cell hyperplasia, mucous cell hyperplasia, and squamous metaplasia. One step of the multistage process of carcinogenesis is thought to involve aberrations in control of the squamous metaplastic processes. Decreased responsiveness to regulators of terminal squamous differentiation may confer a selective clonal expansion advantage to an initiated cell. We studied the effects of endogenous (e.g., transforming growth factor beta 1 (TGF-beta 1) and serum) and exogenous (e.g., 12-O-tetradecanoyl-13-phorbol-acetate (TPA), tobacco smoke condensate, and aldehydes) modifiers of normal human bronchial epithelial (NHBE) cell in a serum-free culture system. NHBE cells are growth inhibited by all of these compounds and induced to undergo squamous differentiation by TGF-beta 1 or TPA. In contrast, lung carcinoma cell lines are relatively resistant to inducers of terminal squamous differentiation which may provide them with a selective growth advantage. Chemical agents and activated protooncogenes (ras,raf,myc) altered the response to endogenous and exogenous inducers of squamous differentiation and caused extended cellular lifespan, aneuploidy, and/or tumorigenicity. The data suggest a close relationship between dysregulation of terminal differentiation pathways and neoplastic transformation of human bronchial epithelial cells.

  12. A SPECIFIC ANTI-PROINSULIN SERUM AND THE PRESENCE OF PROINSULIN IN CALF SERUM*

    PubMed Central

    Yip, C. C.; Logothetopoulos, J.

    1969-01-01

    A specific antibody against proinsulin has been obtained by adsorbing the original anti-proinsulin guinea pig serum with a solid immunosorbent of Sephadex-insulin. The specificity of the antibody against antigenic determinants of proinsulin was established by radioimmunoassay and by passive cutaneous anaphylaxis (PCA) tests. The presence of proinsulin in calf serum has been demonstrated by (a) gel filtration of an acid alcohol extract of the serum followed by immunoassays of the fractions using anti-insulin or the specific anti-proinsulin serum, and (b) direct assay of calf serum with the specific anti-proinsulin serum. PMID:5256220

  13. SERUM LIPID PROFILE IN SUICIDE ATTEMPTERS

    PubMed Central

    Verma, Sandeep; Trivedi, J.K.; Singh, H.; Dalal, P.K.; Asthana, O.P.; Srivastava, J.S.; Mishra, Rakesh; Ramakant; Sinha, P.K.

    1999-01-01

    Practical difficulties associated with assessment of central parameters necessitates the development of peripheral markers of suicidal risk. Recent research suggest that serum lipid profile may be a useful indicator of suicidal behaviour. Serum lipid profiles of forty suicide attempters were compared with forty age, sex and BMI matched controls. Total serum cholesterol, serum Triglyceride, LDL levels and HDL levels were found to be lower in suicide attempters but were not statistically significant. Statistically significant negative con-elation was seen between risk-rescue score and above mentioned parameters. No statitically significant difference was observed when various diagnostic break-up groups of patients were compared. PMID:21430801

  14. Serum Protein Profile Alterations in Hemodialysis Patients

    SciTech Connect

    Murphy, G A; Davies, R W; Choi, M W; Perkins, J; Turteltaub, K W; McCutchen-Maloney, S L; Langlois, R G; Curzi, M P; Trebes, J E; Fitch, J P; Dalmasso, E A; Colston, B W; Ying, Y; Chromy, B A

    2003-11-18

    Background: Serum protein profiling patterns can reflect the pathological state of a patient and therefore may be useful for clinical diagnostics. Here, we present results from a pilot study of proteomic expression patterns in hemodialysis patients designed to evaluate the range of serum proteomic alterations in this population. Methods: Surface-Enhanced Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (SELDI-TOFMS) was used to analyze serum obtained from patients on periodic hemodialysis treatment and healthy controls. Serum samples from patients and controls were first fractionated into six eluants on a strong anion exchange column, followed by application to four array chemistries representing cation exchange, anion exchange, metal affinity and hydrophobic surfaces. A total of 144 SELDI-TOF-MS spectra were obtained from each serum sample. Results: The overall profiles of the patient and control samples were consistent and reproducible. However, 30 well-defined protein differences were observed; 15 proteins were elevated and 15 were decreased in patients compared to controls. Serum from one patient exhibited novel protein peaks suggesting possible additional changes due to a secondary disease process. Conclusion: SELDI-TOF-MS demonstrated dramatic serum protein profile differences between patients and controls. Similarity in protein profiles among dialysis patients suggests that patient physiological responses to end-stage renal disease and/or dialysis therapy have a major effect on serum protein profiles.

  15. Blood serum atherogenicity and coronary artery calcification.

    PubMed

    Sobenin, Igor A; Myasoedova, Veronica A; Anisimova, Elena V; Pavlova, Xenia N; Möhlenkamp, Stefan; Schmermund, Axel; Seibel, Rainer; Berenbein, Sina; Lehmann, Nils; Moebus, Susanne; Jöckel, KarlHeinz; Orekhov, Alexander N; Erbel, Raimund

    2014-01-01

    The phenomenon of blood serum atherogenicity was described as the ability of human serum to induce lipid accumulation in cultured cells. The results of recent two-year prospective study in asymptomatic men provided the evidence for association between the changes in serum atherogenicity and dynamics of carotid intima-media thickness progression. The present study was undertaken to test the hypothesis that blood serum atherogenicity and its changes in dynamics may be associated with accumulation of coronary calcium in subclinical atherosclerosis. It was performed in 782 CHD-free participants of The Heinz Nixdorf RECALL (Risk Factors, Evaluation of Coronary Calcium and Lifestyle) Study, in whom blood samples have been taken at the baseline and at the end of 5-year follow-up. Opposite to the previous findings, the changes in serum atherogenicity did not correlate neither with the extent of coronary artery calcification, nor with the changes in Agatston CAC score. There was a moderate but significant rise in serum atherogenicity after 5-year followup period, and the same dynamics was observed for Agatston CAC score, but not for convenient lipid-related risk factors. The absence of association of the changes in serum atherogenicity with the changes in Agatston CAC score, along with previous findings, provides a point of view that serum-induced intracellular cholesterol accumulation is not related to the processes of calcium deposition in arterial wall, since the last one reflects the progression of already existing subclinical atherosclerotic lesions. PMID:24533940

  16. Serum Trace Element Concentrations in Rheumatoid Arthritis.

    PubMed

    Sahebari, Maryam; Ayati, Razie; Mirzaei, Hamed; Sahebkar, Amirhossein; Hejazi, Sepideh; Saghafi, Massoud; Saadati, Nayyereh; Ferns, Gordon A; Ghayour-Mobarhan, Majid

    2016-06-01

    Rheumatoid arthritis (RA) is a condition that is associated with oxidative stress. Serum trace elements and their related transport proteins, e.g., albumin and ceruloplasmin, play an important role in the antioxidant defense. Trace element status may therefore be involved in the pathogenesis of RA or be affected by the disease activity of this chronic inflammatory condition. The study participants were 110 patients with RA and 100 sex- and age-matched healthy volunteers. Serum concentrations of albumin, ceruloplasmin, selenium, zinc, copper, and zinc/copper ratio were measured in all subjects. The relationship between these parameters and disease activity score was also assessed. Lower concentrations of serum Alb, Zn, and Se were independently related to disease activity index. High concentrations of serum copper were associated with the presence of RA. Serum Cu concentrations were positively related to disease activity as assessed by the disease activity score. Low serum concentrations of Zn and Se, and high serum Cu concentrations may be associated with the presence of RA or be a consequence of this condition. Of the trace elements that were investigated in the present study, only serum Cu was positively correlated with disease activity. PMID:26450515

  17. Identification of a murine high-proliferative-potential colony-forming cell (HPP-CFC) capable of producing a number of megakaryocytes and replating for secondary HPP-CFCs in culture.

    PubMed

    Han, Z C

    1994-04-01

    The high-proliferative-potential colony-forming cell (HPP-CFC) has been shown to be clearly heterogeneous. Hierarchical subpopulations can be identified by analyzing the kinetics of cell regeneration and the specific cellular requirement for cytokines. In this study, a new type of HPP-CFC, termed high-proliferative potential mixed colony-forming unit-megakaryocyte (HPP-mCFU-MK), was detected in murine bone marrow cell cultures. The HPP-mCFU-MK was able to form macroscopic colonies that fit the criteria of the HPP-CFC colony but contained a number of megakaryocytes. Its growth was stimulated by either aplastic anemia serum (AAS) or a combination of three or more recombinant hematopoietic growth factors but was not inhibited by transforming growth factor-beta 1 (TGF-beta 1) and platelet factor 4 (PF4) in vitro. The recloning of the 12-day-old HPP-mCFU-MK colonies picked up from AAS-stimulated primary cultures caused secondary formation of HPP-CFC colonies. These data suggest that HPP-mCFC-MK is a new subset of stem cell characterized by its ability to produce directly a number of megakaryocytes in response to multifactor stimulation, to generate a secondary set of HPP-CFC in replating culture, and to be unaffected by TGF-beta 1 and PF4 treatment. PMID:8145010

  18. Transforming growth factor-beta and transforming growth factor beta-receptor expression in human meningioma cells.

    PubMed Central

    Johnson, M. D.; Federspiel, C. F.; Gold, L. I.; Moses, H. L.

    1992-01-01

    The transforming growth factor-beta (TGF beta) family in mammals includes three closely related peptides that influence proliferation and numerous physiologic processes in most mesenchymal cells. In this study, Northern blots, immunohistochemistry, TGF beta radioreceptor assays, TGF beta receptor affinity labeling and [3H] thymidine incorporation were used to evaluate whether primary cell cultures of human meningiomas synthesize the three TGF beta isoforms, bear TGF beta receptors, and respond to TGF beta. Transcripts for TGF beta 1 and 2 were detected in the three cases analyzed. Transforming growth factor-beta 1 immunoreactivity was detected in three of six cases, and TGF beta 2 and 3 immunoreactivity were detected in each case analyzed. Media conditioned by cells cultured from six meningiomas also contained latent TGF beta-like activity. Transforming growth factor-beta receptor cross-linking studies identified TGF beta binding sites corresponding to the type 1, type 2, and type 3 receptors on meningioma cells. Treatment with active TGF beta 1 produced a statistically significant reduction in [3H] thymidine incorporation after stimulation with 10% fetal calf serum and epidermal growth factor in all six cases studied. Images Figure 1 Figure 2 Figure 4 PMID:1325741

  19. Serum antimuscarinic activity during clozapine treatment.

    PubMed

    de Leon, Jose; Odom-White, Aruby; Josiassen, Richard C; Diaz, Francisco J; Cooper, Thomas B; Simpson, George M

    2003-08-01

    This study attempts: (1) to verify that serum antimuscarinic activity is related to clozapine dose, and more importantly to clozapine plasma concentrations; (2) to explore whether norclozapine has serum antimuscarinic activity; (3) to explore whether antimuscarinic activity is related to clozapine side effects; and (4) to compare the serum antimuscarinic activities of clozapine with those of antiparkinsonian drugs and other antipsychotics. In 39 patients participating in a double-blind clozapine study, the [3H]QNB assay was used to measure serum antimuscarinic activity: (1) on baseline medications; (2) after a 4-week haloperidol trial; (3) after a 16-week clozapine trial of either 100, 300, or 600 mg/d; and (4) after 1 or 2 consecutive 16-week clozapine trials with remaining doses in nonresponders. Clozapine levels predicted serum antimuscarinic activity better than clozapine dose. At the end of the 1st clozapine trial, the correlation with the levels explained 69% of the variance of serum antimuscarinic activity (r = 0.83, P < 0.001, N = 34). Clozapine levels were good predictors of serum antimuscarinic activity only in patients taking 300 or 600 mg/d. After correcting for clozapine levels, the within-subject correlation between norclozapine levels and serum antimuscarinic activity was relatively high and significant (r = 0.54, F = 26.7, df = 1.65, P < 0.001). Constipation was significantly associated with higher serum antimuscarinic activity during the 1st clozapine trial. Clozapine was associated with clearly higher antimuscarinic activity than other antipsychotics or low doses of antiparkinsonians. In vitro studies and new clinical studies are needed to verify whether norclozapine may significantly contribute to antimuscarinic activity during clozapine treatment. PMID:12920408

  20. Killing of Brucella abortus by bovine serum.

    PubMed Central

    Corbeil, L B; Blau, K; Inzana, T J; Nielsen, K H; Jacobson, R H; Corbeil, R R; Winter, A J

    1988-01-01

    Studies of the serum bactericidal system in bovine brucellosis were undertaken to investigate the role of the humoral immune response in protection of cattle against the facultative intracellular parasite Brucella abortus. Fresh sera from normal control cattle, infected cattle, and cattle immunized with B. abortus cell envelopes were collected before treatment and during the course of immunization or infection. Normal fresh bovine serum or fresh agammaglobulinemic serum from colostrum-deprived calves was effective in killing smooth virulent B. abortus 2308, but rough strains RB51 (a rough mutant of strain 2308) and 45/20 were much more sensitive to serum. The difference in susceptibility to serum was shown to be correlated with differences in lipopolysaccharide chemotype, with the more resistant strain 2308 having O polysaccharide and the more susceptible strains 45/20 and RB51 lacking O side chains. By treatment of fresh serum with MgCl2 and EGTA [ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid] killing was shown to occur via the classical pathway of complement activation. When antibody to B. abortus was present, killing of strain RB51 increased but killing of smooth strain 2308 decreased. The earliest antibody response in serum from infected animals did not interfere with killing. When affinity-purified bovine immunoglobulins specific for B. abortus smooth lipopolysaccharide were added to fresh normal bovine serum, immunoglobulin G1 (IgG1) and IgG2 isotypes blocked killing but IgM and IgA isotypes did not. Thus, it appears that serum from previously unexposed animals or animals early during infection can kill smooth B. abortus, an appropriate defense mechanism before the organism becomes intracellular. At later stages of infection, blocking antibodies predominate. Images PMID:3141287

  1. Photothermal Measurements on Human Serum and Plasma

    NASA Astrophysics Data System (ADS)

    Bernal-Alvarado, J.; Sosa, M.; Hernández, L. C.; Hernández-Cabrera, F.; Mayén-Mondragón, R.; Yánez-Limón, J. M.; Flores-Farías, R.; Palomares, P.; Juárez, P.; Ramírez, R.

    2003-09-01

    Using a thermal lens experimental set up, the thermal diffusivity of serum and plasma was measured. Several samples were studied and the results are reported as the average with the standard deviation. The serum and plasma were obtained by aleatory sampling of healthy adult donors at the Guanajuato State Transfusion Center, Mexico; the donors were free of hepatitis and other diseases, clinically tested. The parameters reported were obtained using the thermal lens aberrant model with the lasers operating in the mismatched mode.

  2. [Pu(IV) behavior in the serum].

    PubMed

    Surova, Z I

    1984-01-01

    This paper presents the results of studies of the hydrolysis and polymerization of Pu(IV) in blood serum. With nitrite Pu(IV) solutions incubated with blood serum 20-34% of the nuclide were precipitated as hydroxide and 11-36% converted into polymeric forms bound by high molecular weight proteins. For citrate solutions, these values were 3.8 and 3.0%, respectively. PMID:6505160

  3. (PCG) Protein Crystal Growth Horse Serum Albumin

    NASA Technical Reports Server (NTRS)

    1995-01-01

    Horse Serum Albumin crystals grown during the USML-1 (STS-50) mission's Protein Crystal Growth Glovebox Experiment. These crystals were grown using a vapor diffusion technique at 22 degrees C. The crystals were allowed to grow for nine days while in orbit. Crystals of 1.0 mm in length were produced. The most abundant blood serum protein, regulates blood pressure and transports ions, metabolites, and therapeutic drugs. Principal Investigator was Edward Meehan.

  4. Refractory intraoperative hypotension with elevated serum tryptase

    PubMed Central

    Larson, Kelly J.; Divekar, Rohit D.; Butterfield, Joseph H.; Schwartz, Lawrence B.; Weingarten, Toby N.

    2015-01-01

    Severe intraoperative hypotension has been reported in patients on angiotensin-converting enzyme inhibitors and angiotensin II receptor subtype 1 antagonists. We describe a patient on lisinopril who developed refractory intraoperative hypotension associated with increased serum tryptase level suggesting mast cell activation (allergic reaction). However, allergology workup ruled out an allergic etiology as well as mastocytosis, and hypotension recalcitrant to treatment was attributed to uninterrupted lisinopril therapy. Elevated serum tryptase was attributed to our patient's chronic renal insufficiency. PMID:25653920

  5. Serum Biochemical Phenotypes in the Domestic Dog

    PubMed Central

    Chang, Yu-Mei; Hadox, Erin; Szladovits, Balazs; Garden, Oliver A.

    2016-01-01

    The serum or plasma biochemical profile is essential in the diagnosis and monitoring of systemic disease in veterinary medicine, but current reference intervals typically take no account of breed-specific differences. Breed-specific hematological phenotypes have been documented in the domestic dog, but little has been published on serum biochemical phenotypes in this species. Serum biochemical profiles of dogs in which all measurements fell within the existing reference intervals were retrieved from a large veterinary database. Serum biochemical profiles from 3045 dogs were retrieved, of which 1495 had an accompanying normal glucose concentration. Sixty pure breeds plus a mixed breed control group were represented by at least 10 individuals. All analytes, except for sodium, chloride and glucose, showed variation with age. Total protein, globulin, potassium, chloride, creatinine, cholesterol, total bilirubin, ALT, CK, amylase, and lipase varied between sexes. Neutering status significantly impacted all analytes except albumin, sodium, calcium, urea, and glucose. Principal component analysis of serum biochemical data revealed 36 pure breeds with distinctive phenotypes. Furthermore, comparative analysis identified 23 breeds with significant differences from the mixed breed group in all biochemical analytes except urea and glucose. Eighteen breeds were identified by both principal component and comparative analysis. Tentative reference intervals were generated for breeds with a distinctive phenotype identified by comparative analysis and represented by at least 120 individuals. This is the first large-scale analysis of breed-specific serum biochemical phenotypes in the domestic dog and highlights potential genetic components of biochemical traits in this species. PMID:26919479

  6. Serum Biochemical Phenotypes in the Domestic Dog.

    PubMed

    Chang, Yu-Mei; Hadox, Erin; Szladovits, Balazs; Garden, Oliver A

    2016-01-01

    The serum or plasma biochemical profile is essential in the diagnosis and monitoring of systemic disease in veterinary medicine, but current reference intervals typically take no account of breed-specific differences. Breed-specific hematological phenotypes have been documented in the domestic dog, but little has been published on serum biochemical phenotypes in this species. Serum biochemical profiles of dogs in which all measurements fell within the existing reference intervals were retrieved from a large veterinary database. Serum biochemical profiles from 3045 dogs were retrieved, of which 1495 had an accompanying normal glucose concentration. Sixty pure breeds plus a mixed breed control group were represented by at least 10 individuals. All analytes, except for sodium, chloride and glucose, showed variation with age. Total protein, globulin, potassium, chloride, creatinine, cholesterol, total bilirubin, ALT, CK, amylase, and lipase varied between sexes. Neutering status significantly impacted all analytes except albumin, sodium, calcium, urea, and glucose. Principal component analysis of serum biochemical data revealed 36 pure breeds with distinctive phenotypes. Furthermore, comparative analysis identified 23 breeds with significant differences from the mixed breed group in all biochemical analytes except urea and glucose. Eighteen breeds were identified by both principal component and comparative analysis. Tentative reference intervals were generated for breeds with a distinctive phenotype identified by comparative analysis and represented by at least 120 individuals. This is the first large-scale analysis of breed-specific serum biochemical phenotypes in the domestic dog and highlights potential genetic components of biochemical traits in this species. PMID:26919479

  7. Serum fatty acids and breast cancer incidence.

    PubMed

    Rissanen, Harri; Knekt, Paul; Järvinen, Ritva; Salminen, Irma; Hakulinen, Timo

    2003-01-01

    Fatty acid composition of the diet may be essential to the development of breast cancer. We studied the ability of several fatty acids of serum total lipids to predict breast cancer incidence in a case-control study nested within a longitudinal population study. The proportions of fatty acids in serum total lipids were determined from stored serum samples collected at baseline for 127 incident breast cancer cases and 242 matched controls. Women with a higher proportion of total polyunsaturated fatty acids (PUFAs) in serum had a reduced risk of breast cancer. The odds ratio (OR) between the highest and lowest tertiles of serum PUFA was 0.31 (95% confidence interval, CI = 0.12-0.77). This association was mainly due to n-6 PUFAs and especially to linoleic acid. The ORs were 0.35 (CI = 0.14-0.84) and 0.29 (CI = 0.12-0.73), respectively. Of the monounsaturated fatty acids (MUFAs), higher trans-11-18:1 levels were related to an increased breast cancer risk (OR = 3.69, CI = 1.35-10.06). The association was stronger in postmenopausal than in premenopausal women. The present study suggests that higher serum proportions of the n-6 PUFA linoleic acid and lower proportions of the MUFA trans-11-18:1 fatty acid predict a reduced incidence of breast cancer. PMID:12881010

  8. Neuroticism, depressive symptoms, and serum BDNF

    PubMed Central

    Terracciano, Antonio; Lobina, Monia; Piras, Maria Grazia; Mulas, Antonella; Cannas, Alessandra; Meirelles, Osorio; Sutin, Angelina R.; Zonderman, Alan B; Uda, Manuela; Crisponi, Laura; Schlessinger, David

    2011-01-01

    Objective Animal models and clinical studies suggest that brain-derived neurotrophic factor (BDNF) is involved in the pathophysiology of depression. We test whether serum and plasma levels of BDNF are associated with trait Neuroticism and its facets, and with state measure of depressive symptoms. Method In a community-based cohort (N = 2099) we measured serum and plasma BDNF concentration, administered the Revised NEO Personality Inventory (NEO-PI-R) and the Center for Epidemiologic Studies Depression Scale (CES-D). Covariates included age, sex, cigarette smoking, obesity, and antidepressant use. Results Serum BDNF concentrations were inversely related to Neuroticism (r = −0.074, P < 0.001), in particular the Depression facet (r = −0.08, P < 0.001). Lower BDNF concentrations were also associated with severe depressive symptoms (CES-D ≥ 28; OR = 0.906; 95%CI = 0.851–0.965). The association of serum BDNF with Neuroticism was independent of depressive symptoms, indicating that serum BDNF might represent a biological correlate of Neuroticism and not just of transient depressive states. Plasma BDNF was not associated with measures of depression. Conclusions Our study suggests that lower serum BDNF is associated with both a dispositional vulnerability to depression and acute depressive states in the general population. PMID:21949427

  9. Specific binding of endocrine transforming growth factor-beta 1 to vascular endothelium.

    PubMed Central

    Dickson, K; Philip, A; Warshawsky, H; O'Connor-McCourt, M; Bergeron, J J

    1995-01-01

    The presentation of recombinant biologically active 125I-TGF-beta 1 via the bloodstream to potential target cells in mice and rats was evaluated by quantitative light and electron microscope radioautography. Specificity was evaluated by in vivo competition with excess unlabeled TGF-beta 1, and integrity of the ligand at the binding site was demonstrated by trichloroacetic acid precipitation after extraction from tissues. The distribution of radiolabel at 2.5, 15, 30, 45, and 60 min after 125I-TGF-beta 1 injection revealed radiolabel principally over microvasculature endothelium but at times > 2.5 min over endothelial endocytic components indicative of internalization. Nonspecific binding of 125I-TGF-beta 1 to the apex of the proximal convoluted tubule of the kidney indicated it as the likely site of rapid clearance of TGF-beta 1 from the circulation, while a comparison of the binding of 125I-TGF-beta 1 (endothelial) to that of 125I-TGF-beta 1 complexed with alpha 2-macroglobulin-methylamine (liver parenchyma) indicated that clearance of TGF-beta 1 complexed alpha 2-macroglobulin was likely via the hepatic alpha 2-macroglobulin receptor. The endothelial TGF-beta receptors uncovered here are likely involved in the local regulatory mechanism of leukocyte and monocyte adhesion and tissue infiltration regulated by endocrine TGF-beta 1. Images PMID:7539454

  10. Tissue localization of transforming growth factor-beta1 in pulmonary eosinophilic granuloma.

    PubMed

    Asakura, S; Colby, T V; Limper, A H

    1996-11-01

    Pulmonary eosinophilic granuloma is characterized by infiltration of the lungs with fibronodular lesions containing specialized Langerhans' cells. In some patients, progressive pulmonary fibrosis leads to significant respiratory impairment. Transforming growth factor-beta1 (TGF-beta1) promotes fibrosis by enhancing the synthesis of extracellular matrix components. The role of TGF-beta1 in promoting fibrosis in the setting of pulmonary eosinophilic granuloma is currently unknown. We used immunohistochemistry to evaluate the extent and distribution of TGF-beta1 and the extracellular matrix components type I collagen and decorin, a TGF-beta1-binding proteoglycan. Lung biopsies from 11 patients with pulmonary eosinophilic granuloma were evaluated. In biopsies with active inflammatory lesions containing Langerhans' cells, hyperplastic type 2 pneumocytes and alveolar macrophages within and surrounding the fibronodular lesions contained abundant TGF-beta1. Langerhans' cells were consistently devoid of immunoreactive TGF-beta1. Active inflammatory lesions also exhibited staining for decorin, in a loosely organized distribution. Advanced fibrotic lesions of eosinophilic granuloma, containing minimal inflammatory cells and few or no Langerhans' cells, exhibited weak or absent staining for TGF-beta1 within either hyperplastic type 2 pneumocytes or alveolar macrophages. The fibroconnective tissues of these advanced fibrotic lesions consistently revealed dense staining for decorin. Through their actions on extracellular matrix protein accumulation, TGF-beta1 and the TGF-beta1-binding proteoglycan decorin may modulate fibrotic repair accompanying pulmonary eosinophilic granuloma. PMID:8912775

  11. 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

  12. Aqueous garlic extract alleviates liver fibrosis and renal dysfunction in bile-duct-ligated rats.

    PubMed

    Mahmoud, Mona F; Zakaria, Sara; Fahmy, Ahmed

    2014-01-01

    There is accumulating evidence that the renin-angiotensin system (RAS) is involved in hepatic inflammation and fibrogenesis. Garlic was found to lower the activity of the angiotensin converting enzyme (ACE) in the serum of rats in a diabetic model. We examined the effect of an aqueous garlic extract (AGE) on the ACE activity, cholestasis-induced liver fibrosis, and associated renal dysfunction in comparison with the effect of the standard drug enalapril. Both AGE and enalapril were administered orally for six weeks starting from the third day after bile duct ligation (BDL). BDL significantly increased the serum activities of liver enzymes, serum lactate dehydrogenase (LDH) activity, an indicator of liver cell death, serum total bilirubin (TB) level, liver myeloperoxidase (MPO) activity, and liver malondialdehyde (MDA) content. BDL was associated with elevation of serum urea and creatinine levels indicating renal dysfunction. BDL also caused an increase in the transcript levels of the genes coding for tumour necrosis factor alpha (TNF-alpha), transforming growth factor beta-1 (TGF-beta1), and matrix metalloproteinase-13 (MMP-13), a collagenase, in liver tissues. A significant decrease in hepatic reduced glutathione (GSH) was observed in BDL rats, while serum ACE activity was increased. Both AGE and enalapril counteracted all these deleterious changes, with the exception that only AGE reduced the MPO activity. These findings suggest that AGE possesses hepato- and renoprotective properties, similar to enalapril, probably by modulating the levels of proteins such as TNF-alpha, TGF-beta1 and MMP-13, and involving a reduction of ACE and of oxidative stress. PMID:24873034

  13. Serum Prolactin Level of Subfertile Women.

    PubMed

    Anwary, S A; Fatima, P; Alfazzaman, M; Mahzabin, Z; Rahman, M M; Bari, N

    2016-01-01

    Subfertility is a major reproductive health problem all over the world as well as Bangladesh, and the problem is increasing day by day. This study was done to estimate the serum prolactin concentration in primary and secondary subfertile women. Laboratory investigation included serum prolactin level, as well as LH, FSH, TSH blood glucose (2 hours after 75 gm glucose load) of 50 women who attended infertility unit, Department of Obstetrics and Gynaecology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from March 2009 and February 2010. In most cases, common age group 26-30 years (52%), primary subfertility (74%), duration of marriage >5 years (60%), trying to conceive duration ≤5 years (54%), BMI >25 kg/m² (60%), menstrual cycle regular (58%), history of abortion absent (90%), and history of menstrual regulation absent (94%). Common investigation findings was normal serum follicle stimulating hormone (FSH) 1.0-10.0 mIU/ml in 82%, normal serum luteinizing hormone (LH) 1.0-10.0 mIU/ml in 50%, normal serum prolactin 1.9-25.0 ng/ml in 36%, normal serum thyroid stimulating hormone (TSH) 0.4-4.0 μIU/ml in 56%, and normal blood glucose level (2 hours after breakfast) (<7.8 mmol/) in 66% women. Ultrasonographic finding of lower abdomen was normal in 14% women. Common finding of semen analysis husbands of the study women was normozoospermia in 88% cases. Serum prolactin concentration may have role to play in subfertility of women. PMID:26931256

  14. Fluorimetric determination of cholesterol in hypercholesterolemia serum

    NASA Astrophysics Data System (ADS)

    Lan, Xiufeng; Liu, Jiangang; Liu, Ying; Luo, Xiaosen; Lu, Jian; Ni, Xiaowu

    2005-01-01

    With the increase of people"s living standard and the changes of living form, the number of people who suffer from hypercholesterolemia is increasing. It is not only harmful to heart and blood vessel, but also leading to obstruction of cognition. The conventional blood detection technology has weakness such as complex operation, long detecting period, and bad visibility. In order to develop a new detection method that can checkout hypercholesterolemia conveniently, spectroscopy of cholesterol in hypercholesterolemia serum is obtained by the multifunctional grating spectrograph. The experiment results indicate that, under the excitation of light-emitting diode (LED) with the wavelength at 407 nm, the serum from normal human and the hypercholesterolemia serum emit different fluorescence spectra. The former can emit one fluorescence region with the peak locating at 516 nm while the latter can emit two more regions with peaks locating at 560 nm and 588 nm. Moreover, the fluorescence intensity of serum is non-linear increasing with the concentration of cholesterol increases when the concentration of cholesterol is lower than 13.8 mmol/L, and then, with the concentration of cholesterol increase, the fluorescence intensity decreases. However, the fluorescence intensity is still much higher than that of serum from normal human. Conclusions can be educed from the experiments: the intensity and the shape of fluorescence spectra of hypercholesterolemia serum are different of those of normal serum, from which the cholesterol abnormal in blood can be judged. The consequences in this paper may offer an experimental reference for the diagnosis of the hypercholesterolemia.

  15. Antifungal serum concentration monitoring: an update.

    PubMed

    Goodwin, Megan L; Drew, Richard H

    2008-01-01

    Invasive fungal infections (IFIs) are occurring with increasing incidence and are associated with significant morbidity and mortality. Understanding the relationship between the pharmacokinetic and pharmacodynamic properties of antifungals is essential to optimize the potential for favourable clinical and microbiological outcomes while minimizing risks of treatment-related toxicity. Antifungal serum concentrations may aid in the determination of appropriate dosing in select circumstances. The polyene and echinocandin classes of antifungals lack sufficient data to justify serum concentration monitoring in routine clinical practice. In contrast, serum concentration monitoring of flucytosine may help to reduce the risk of treatment-related haematological toxicity. Determination of itraconazole serum concentrations is advised in situations where the drug is used for prolonged periods to treat serious IFIs (such as invasive aspergillosis or histoplasmosis) because of variability in absorption following oral administration (most notable for the capsule formulation). The use of serum concentration monitoring during therapy with the extended-spectrum triazoles (i.e. voriconazole and posaconazole) is still evolving, due primarily to inter-patient variability in drug exposure combined with sparse data regarding relationships with efficacy (posaconazole) and both safety and efficacy (voriconazole). PMID:17999982

  16. Radioimmunoassy for phencyclidine (PCP) in serum. [Dogs

    SciTech Connect

    Owens, S.M.; Woodworth, J.; Mayersohn, M.

    1982-07-01

    This accurate, sensitive radioimmunoassay for determining phencyclidine concentrations in serum specimens involves the use of anti-phencyclidine sera, 0.1 mL of serum specimen, an iodinated tracer, and a solid-phase separation. Phencyclidine metabolities do not show significant cross reactivity, but several phencyclidine analogs do cross react. Within-run coefficients of variation for human and dog serum ranged from 2.5 to 13% for concentrations from 2.0 to 500 ..mu..g/L. Day-to-day coefficients of variation for human and dog serum ranged from 4.3 to 16.7% for concentrations ranging from 2.0 to 09.0 ..mu..g/L. The sensitivity of the radioimmunoassay is <0.5 ..mu..g/L. Thirty serum specimens from two dogs given 1 mg of phencyclidine per kilogram body weight were analyzed by radioimmunoassay and a gas-chromatographic method. Nonparametris statistical comparison and linear regression showed that results from the two procedures correlate well (r/sup 2/ = 0.952). Concentration-time data from the two dogs are presented to illustrate the utility of the radioimmunoassay for examining phencyclidine disposition.

  17. Proteomic evaluation of sheep serum proteins

    PubMed Central

    2012-01-01

    Background The applications of proteomic strategies to ovine medicine remain limited. The definition of serum proteome may be a good tool to identify useful protein biomarkers for recognising sub-clinical conditions and overt disease in sheep. Findings from bovine species are often directly translated for use in ovine medicine. In order to characterize normal protein patterns and improve knowledge of molecular species-specific characteristics, we generated a two-dimensional reference map of sheep serum. The possible application of this approach was tested by analysing serum protein patterns in ewes with mild broncho-pulmonary disease, which is very common in sheep and in the peripartum period which is a stressful time, with a high incidence of infectious and parasitic diseases. Results This study generated the first reference 2-DE maps of sheep serum. Overall, 250 protein spots were analyzed, and 138 identified. Compared with healthy sheep, serum protein profiles of animals with rhino-tracheo-bronchitis showed a significant decrease in protein spots identified as transthyretin, apolipoprotein A1 and a significant increase in spots identified as haptoglobin, endopin 1b and alpha1B glycoprotein. In the peripartum period, haptoglobin, alpha-1-acid glycoprotein, apolipoprotein A1 levels rose, while transthyretin content dropped. Conclusions This study describes applications of proteomics in putative biomarker discovery for early diagnosis as well as for monitoring the physiological and metabolic situations critical for ovine welfare. PMID:22630135

  18. Serum estradiol levels in male cigarette smokers.

    PubMed

    Klaiber, E L; Broverman, D M; Dalen, J E

    1984-11-01

    Serum estradiol levels were compared in smoking and nonsmoking men in two separate samples. Sample I consisted of 41 young adult male volunteers ranging in age from 18 to 24 years. Twenty-three men smoked an average of 24.5 +/- 6.9 cigarettes daily. The duration of smoking averaged 5.2 +/- 2.2 years. Sample II consisted of 35 husbands who had been evaluated for infertility; they ranged in age from 19 to 49 years. Eighteen men smoked an average of 21.6 +/- 7.9 cigarettes daily. The duration of smoking averaged 11.5 +/- 4.5 years. Age, height, and weight did not differ significantly between smokers and nonsmokers within either group. Serum estradiol levels were significantly elevated in smokers compared with nonsmokers in both groups (p less than 0.001 and p less than 0.0001 in Samples I and II, respectively). No significant correlations were found between serum estradiol levels and the number of cigarettes smoked daily, or with the duration of smoking in either sample. The differences in serum estradiol levels between smokers and nonsmokers could not be attributed to the differences in marijuana and alcohol use that existed between the smokers and nonsmokers in each sample. The recent reports of elevated serum estradiol levels as a possible risk factor in coronary heart disease are discussed in view of the known relationship of cigarette smoking to coronary heart disease. PMID:6496540

  19. Crocodylus siamensis serum and macrophage phagocytic activity.

    PubMed

    Aree, Kalaya; Siruntawineti, Jindawan; Chaeychomsri, Win

    2011-12-01

    Antimicrobial activity of sera from many crocodilian species has been recognized. This activity was proposed to be mediated, at least in part, by complement. Due to the fact that complement proteins have different functions in the immune system, they may be involved in phagocytic process of phagocytes. In the present study, the effects of Siamese crocodile serum on phagocytic activity of macrophages as well as the possible involvement of complement in this process were examined. The results showed increases in the phagocytosis of both Escherichia coli and to a lesser extent, Staphylococcus aureus upon incubation of murine macrophage cell line with fresh crocodile serum (FS). Similar to FS, other crocodile blood products, including freeze dried serum (DS) and freeze dried whole blood (DWB) exhibited phagocytosis-enhancing property. However the ability of DWB to enhance phagocytosis was less efficient than that of FS and DS, suggesting that serum factors were involved in this process. Treatment of FS with heat at 56 degrees C for 30 min deteriorated the effect of FS on bacterial uptake of macrophages, suggesting that complement proteins play a role in the modulation of the phagocytic process. Collectively, the results of the present study suggested that crocodile serum enhances the macrophage phagocytic activity through complement activity and, therefore, may be taken as an alternative medicine for supporting the human immune responses. PMID:22619919

  20. A radioimmunoassay for serum medroxyprogesterone acetate.

    PubMed

    Shrimanker, K; Saxena, B N; Fotherby, K

    1978-04-01

    When injected intramuscularly in a dose of 150 mg, Depo Provera, a microcrystalline suspension of medroxyprogesterone acetate (MPA), will provide a contraceptive effect for at least 3 months. This paper describes a sensitive radioimmunoassay for MPA which has been used in the author's laboratory for the past 2 years. MPA was converted to MPA-3-CMO and the oxime was conjugated with bovine serum albumin (BSA) by the mixed anahydride method. 4 rabbits were immunized with the antiserum. A high titre of MPA antibodies was detected 6 months after immunization. Serum from the rabbit with the highest titre of antibodies to MPA was subjected to radioimmunoassay. 7 days after the intramuscular injection of 150 mg Depo-Provera, serum levels of MPA were found in the range of 1750 to 9000 pg/ml. By 75 days, the levels had decreased to 680-2600 pg/ml. The method was found to have adequate accuracy, precision and sensitivity. PMID:661315

  1. Serum fucose level in malignant diseases.

    PubMed

    Sawke, N G; Sawke, G K

    2010-01-01

    We review the present knowledge of serum fucose with special attention to its relation with various malignant diseases. We summarize the role of serum fucose as a useful diagnostic and prognostic marker when used singly or in combination. The purpose of this review is to provide an expert opinion on the practical and applied aspect of serum fucose level in clinical practice and research settings. Our review is based on information from published research studies, library books, and electronic searches through Medline and PubMed. The available published data were used as the basis for recommendations. Each of the subsections concludes to provide information to assist the clinicians and the research scientists make informed decisions. PMID:21131761

  2. Isolation of human serum spreading factor.

    PubMed

    Barnes, D W; Silnutzer, J

    1983-10-25

    Serum spreading factor (SF) was isolated from human serum by a four-step procedure employing affinity chromatography on glass beads, concanavalin A-Sepharose, DEAE-agarose, and heparin-agarose. The final product was purified approximately 260-fold from the starting material and was maximally active in assays of cell spreading-promoting activity at 300 ng/ml. The isolated human SF preparation consisted of two proteins of apparent molecular weights approximately 65,000 (SF65) and 75,000 (SF75). Both SF65 and SF75 have been shown previously to exhibit cell spreading-promoting activity and to bind monoclonal antibody to human serum SF. PMID:6630199

  3. Thermal diffusivity of human serum and plasma

    NASA Astrophysics Data System (ADS)

    Mayén-Mondragón, R.; Yánez-Limón, J. M.; Palomares, P.; Sosa, M.; Bernal-Alvarado, J.

    2005-06-01

    Using a thermal lens experimental set up, the thermal diffusivity of human serum and plasma were measured. Several samples were studied and the results are reported as the average, including the standard deviation. The samples of serum and plasma were obtained in healthy adult donors from the Guanajuato State Blood Transfusion Center, Mexico; the donors were clinically tested and they were free of hepatitis, AIDS and other infectious diseases. The parameters reported were obtained using the thermal lens aberrant model with the lasers arranged in the mismatched mode.

  4. Erythropoietin suppresses epithelial to mesenchymal transition and intercepts Smad signal transduction through a MEK-dependent mechanism in pig kidney (LLC-PK1) cell lines

    SciTech Connect

    Chen, Chien-Liang; Chou, Kang-Ju; Lee, Po-Tsang; Chen, Ying-Shou; Chang, Tsu-Yuan; Hsu, Chih-Yang; Huang, Wei-Chieh; Chung, Hsiao-Min; Fang, Hua-Chang

    2010-04-15

    Purpose: Tumor growth factor-{beta}1 (TGF-{beta}1) plays a pivotal role in processes like kidney epithelial-mesenchymal transition (EMT) and interstitial fibrosis, which correlate well with progression of renal disease. Little is known about underlying mechanisms that regulate EMT. Based on the anatomical relationship between erythropoietin (EPO)-producing interstitial fibroblasts and adjacent tubular cells, we investigated the role of EPO in TGF-{beta}1-mediated EMT and fibrosis in kidney injury. Methods: We examined apoptosis and EMT in TGF-{beta}1-treated LLC-PK1 cells in the presence or absence of EPO. We examined the effect of EPO on TGF-{beta}1-mediated Smad signaling. Apoptosis and cell proliferation were assessed with flow cytometry and hemocytometry. We used Western blotting and indirect immunofluorescence to evaluate expression levels of TGF-{beta}1 signal pathway proteins and EMT markers. Results: We demonstrated that ZVAD-FMK (a caspase inhibitor) inhibited TGF-{beta}1-induced apoptosis but did not inhibit EMT. In contrast, EPO reversed TGF-{beta}1-mediated apoptosis and also partially inhibited TGF-{beta}1-mediated EMT. We showed that EPO treatment suppressed TGF-{beta}1-mediated signaling by inhibiting the phosphorylation and nuclear translocation of Smad 3. Inhibition of mitogen-activated protein kinase kinase 1 (MEK 1) either directly with PD98059 or with MEK 1 siRNA resulted in inhibition of EPO-mediated suppression of EMT and Smad signal transduction in TGF-{beta}1-treated cells. Conclusions: EPO inhibited apoptosis and EMT in TGF-{beta}1-treated LLC-PK1 cells. This effect of EPO was partially mediated by a mitogen-activated protein kinase-dependent inhibition of Smad signal transduction.

  5. Hypertrophic stimuli induce transforming growth factor-beta 1 expression in rat ventricular myocytes.

    PubMed Central

    Takahashi, N; Calderone, A; Izzo, N J; Mäki, T M; Marsh, J D; Colucci, W S

    1994-01-01

    Transforming growth factor-beta 1 (TGF-beta 1) is a peptide growth factor that may play a role in the myocardial response to hypertrophic stimuli. However, the cellular distribution, mechanism of induction, and source of increased TGF-beta 1 in response to hypertrophic stimuli are not known. We tested the hypothesis that the cardiac myocyte responds to hypertrophic stimuli with the increased expression of TGF-beta 1. In adult rat ventricular myocardium freshly dissociated into myocyte and nonmyocyte cellular fractions, the preponderance of TGF-beta 1 mRNA visualized by Northern hybridization was in the nonmyocyte fraction. Abdominal aortic constriction (7 d) and subcutaneous norepinephrine infusion (36 h) each caused ventricular hypertrophy associated with 3.1-fold and 3.8-fold increases, respectively, in TGF-beta 1 mRNA in the myocyte fraction, but had no effect on the level of TGF-beta 1 mRNA in the nonmyocyte fraction. In ventricular myocytes, norepinephrine likewise caused a 4.1-fold increase in TGF-beta 1 mRNA associated with an increase in TGF-beta bioactivity. This induction of TGF-beta 1 mRNA occurred at norepinephrine concentrations as low as 1 nM and was blocked by prazosin, but not propranolol. NE did not increase the TGF-beta 1 mRNA level in nonmyocytes, primarily fibroblasts, cultured from neonatal rat ventricle. Thus, the cardiac myocyte responds to two hypertrophic stimuli, pressure overload and norepinephrine, with the induction of TGF-beta 1. These data support the view that TGF-beta 1, released by myocytes and acting in an autocrine and/or paracrine manner, is involved in myocardial remodeling by hypertrophic stimuli. Images PMID:7929822

  6. Ampicillin levels in sputum, serum, and saliva

    PubMed Central

    Stewart, Sheila M.; Fisher, Mary; Young, Joy E.; Lutz, W.

    1970-01-01

    The ampicillin levels in sputum, serum, and saliva from 40 patients receiving a dose of 250 mg., 26 patients receiving a dose of 500 mg., and 11 patients receiving a dose of 1 g. were estimated. The ampicillin was given orally four times daily. The 1-2 hour and 2-3 hour sputum levels were similar in individual patients. There was no difference in the range or mean sputum or saliva levels between specimens from patients receiving 250 mg. and 500 mg., but the levels were significantly higher after the 1 g. dose. The mean serum level showed a small increase after 500 mg. ampicillin as compared with the 250 mg. dose and a big increase after the 1 g. dose: only the latter difference was significant. The sputum levels were approximately 30 to 40 times lower than the corresponding serum levels. There was considerable scatter in the sputum level for any level of ampicillin in the serum: in only two of the 1-2 hour sputum specimens was there no detectable ampicillin. There was no correlation between the sputum levels and either the body weight or the dose in milligrams per kilogram. There was no evidence that corticosteroids or diuretics affected the sputum level. It was not possible to demonstrate any relationship between the purulence of the sputum and the level of ampicillin after doses of 250 mg. or 500 mg., but higher levels were found in the more purulent specimens after 1 g. doses. PMID:4318047

  7. 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.

  8. 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

  9. Serum amyloid P inhibits dermal wound healing

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The repair of open wounds depends on granulation tissue formation and contraction, which is primarily mediated by myofibroblasts. A subset of myofibroblasts originates from bone-marrow-derived monocytes which differentiate into fibroblast-like cells called fibrocytes. Serum amyloid P (SAP) inhibits ...

  10. Menaquinones content of human serum and feces

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bacterially-synthesized menaquinones (MKn) may contribute to vitamin K (VK) nutriture. There are limited data on interindividual variability in endogenous MK synthesis and its relation to circulating forms of VK. Serum and fecal VK concentrations were assessed in 13 healthy adults (45-65 yr) consumi...

  11. 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...

  12. Rapid weight loss decreases serum testosterone.

    PubMed

    Karila, T A M; Sarkkinen, P; Marttinen, M; Seppälä, T; Mero, A; Tallroth, K

    2008-11-01

    To investigate the effects of a rapid weight reduction program under authentic pre-competition conditions, eighteen elite wrestlers were studied with dual-energy X-ray absorptiometry (DXA) before and after two to three weeks' weight reduction regimens. In order to establish the degree of dehydration and hormonal status, blood samples were collected to obtain blood chemistry, electrolytes and endocrinological parameters after both DXA measurements. The mean weight loss was 8.2 +/- 2.3 % and it was constituted by the mean reductions of fat mass of 16 +/- 6.9 % (p < or = 0.001) and lean body mass of 7.9 +/- 2.5 %. The rapid weight reduction caused significant dehydration which was noticed as increased blood hemoglobin (7.8 +/- 5.9 %, p < or = 0.001), hematocrit (11.3 +/- 6.8 %, p < or = 0.001), and serum creatinine (35 +/- 23 %, p < or = 0.001). There was a significant decrease in serum testosterone (63 +/- 33 %, p < or = 0.001) and luteinizing hormone (54 +/- 47 %, p < or = 0.001) concentrations. A reduced body weight correlated with decreased serum testosterone concentration (r = 0.53, p < or = 0.024). Serum sex hormone binding globulin concentration increased significantly (40 +/- 21 %, p < or = 0.001). The results suggest that even short-term weight reduction may have marked effects on body composition, blood chemistry and hormonal parameters. It may constitute a possible health risk at least in a growing adolescent athlete. PMID:18516767

  13. Exercise and Serum Androgens in Women.

    ERIC Educational Resources Information Center

    Westerlind, Kim C.; And Others

    1987-01-01

    This study examining the effect of a 10-week hydraulic resistance exercise program on serum androgen levels, strength, and lean body weight in 18 college women revealed that training did not result in significant increases in androgen hormones, although there were significant gains in strength. (Author/CB)

  14. Serum estradiol and coronary artery disease.

    PubMed

    Goldberg, R J; Gore, J M; Zive, M; Brady, P; Klaiber, E; Broverman, D; Ockene, I S; Dalen, J E

    1987-01-01

    Serum estradiol levels were measured in 300 men undergoing coronary angiography. Among these men, there were no significant differences in the serum estradiol levels between patients with (mean, 26.4 pg/ml) and those without (mean, 30.9 pg/ml) angiographically confirmed coronary artery disease. There were no significant differences in any of the established coronary risk factors when patients were subdivided according to the presence or absence of coronary artery disease or according to the extent of disease. In addition, no significant correlation was noted between mean serum estradiol levels and the extent of coronary artery disease as classified by the number of obstructed coronary vessels. A matched-pairs analysis was carried out in which patients who had normal coronary arteries were matched with those who had coronary artery disease on the basis of age, cigarette smoking, prior history of myocardial infarction, and body mass index. The mean serum estradiol level in the patients with coronary artery disease was 28.7 pg/ml, and the mean estradiol level was 31.4 pg/ml for the matched patients with normal coronary arteries. In addition, when serial (three) estradiol determinations were carried out in 100 patients, no association was observed between degree of estradiol variability and the occurrence and/or extent of coronary artery disease. The results of this observational study fail to support an association between serum estradiol levels and the presence or degree of coronary artery disease in men as documented by coronary angiography. PMID:3799667

  15. Serum periostin in obstructive airways disease.

    PubMed

    Fingleton, James; Braithwaite, Irene; Travers, Justin; Bowles, Darren; Strik, Rianne; Siebers, Rob; Holweg, Cecile; Matthews, John; Weatherall, Mark; Beasley, Richard

    2016-05-01

    Serum periostin is a potential biomarker of response to therapies that target type 2 inflammation in asthma. The objectives of this study were to describe: 1) the distribution of serum periostin levels in adults with symptomatic airflow obstruction; 2) its relationship with other variables, including type 2 biomarkers; and 3) the effect of inhaled corticosteroids on periostin levels.Serum periostin levels were measured in a cross-sectional study exploring phenotypes and biomarkers in 386 patients aged 18-75 years who reported wheeze and breathlessness in the past 12 months. In 49 ICS-naïve patients, periostin levels were measured again after 12 weeks of budesonide (800 μg·day(-1)).The distribution of serum periostin levels was right skewed (mean±sd 57.3±18.6 ng·mL(-1), median (interquartile range) 54.0 (45.1-65.6) ng·mL(-1), range 15.0-164.7 ng·mL(-1)). Periostin was positively associated with exhaled nitric oxide (Spearman's rho=0.22, p<0.001), blood eosinophil count (Spearman's rho=0.21, p<0.001), and total IgE (Spearman's rho=0.14, p=0.007). The Hodges-Lehmann estimator (95% CI) of change in periostin level after ICS therapy was -4.8 (-6.7- -3.2) ng·mL(-1) (p<0.001).These findings provide data on the distribution of serum periostin in adults with symptomatic airflow obstruction, the weak associations between periostin and other type 2 markers, and the reduction in periostin with inhaled corticosteroid therapy. PMID:26917610

  16. Serum periostin in obstructive airways disease

    PubMed Central

    Braithwaite, Irene; Travers, Justin; Bowles, Darren; Strik, Rianne; Siebers, Rob; Holweg, Cecile; Matthews, John; Weatherall, Mark; Beasley, Richard

    2016-01-01

    Serum periostin is a potential biomarker of response to therapies that target type 2 inflammation in asthma. The objectives of this study were to describe: 1) the distribution of serum periostin levels in adults with symptomatic airflow obstruction; 2) its relationship with other variables, including type 2 biomarkers; and 3) the effect of inhaled corticosteroids on periostin levels. Serum periostin levels were measured in a cross-sectional study exploring phenotypes and biomarkers in 386 patients aged 18–75 years who reported wheeze and breathlessness in the past 12 months. In 49 ICS-naïve patients, periostin levels were measured again after 12 weeks of budesonide (800 μg·day−1). The distribution of serum periostin levels was right skewed (mean±sd 57.3±18.6 ng·mL−1, median (interquartile range) 54.0 (45.1–65.6) ng·mL−1, range 15.0–164.7 ng·mL−1). Periostin was positively associated with exhaled nitric oxide (Spearman's rho=0.22, p<0.001), blood eosinophil count (Spearman's rho=0.21, p<0.001), and total IgE (Spearman's rho=0.14, p=0.007). The Hodges–Lehmann estimator (95% CI) of change in periostin level after ICS therapy was −4.8 (−6.7– −3.2) ng·mL−1 (p<0.001). These findings provide data on the distribution of serum periostin in adults with symptomatic airflow obstruction, the weak associations between periostin and other type 2 markers, and the reduction in periostin with inhaled corticosteroid therapy. PMID:26917610

  17. Serum lipoperoxides in induced and spontaneous abortions.

    PubMed

    Sane, A S; Chokshi, S A; Mishra, V V; Barad, D P; Shah, V C; Nagpal, S

    1991-01-01

    Abortion, primarily as a measure of population control, certainly continues to be an emotional, frustrating and stressful event. In continuation of our work on stressful situations in the female life span and biochemical parameters, serum lipid peroxide levels in terms of malondialdehyde (nmol/ml) have been determined in females undergoing abortion [suction curettage (n = 30), Emcredil-induced abortion (n = 30) and spontaneous abortion (n = 40)] and were compared with appropriate gestational controls. Irrespective of the type of abortion, the serum lipid peroxide levels before abortion [mean malondialdehyde concentrations (nmol/ml): suction curettage 2.67, Emcredil-induced abortion 3.22, and spontaneous abortion 3.49] were found to be significantly elevated in comparison with those after abortion (suction curettage 1.91, Emcredil 1.97 and spontaneous abortion 1.95), indicating a maximum at peak time of stress and a minimum at the end of stress. The levels of serum lipid peroxide encountered before abortion were found to be significantly elevated in case of Emcredil-induced abortion and spontaneous abortion when compared with controls (second trimester mean levels 1.82 and first trimester 2.4) whereas the levels before suction curettage were found to be nonsignificant in comparison with controls, indicating a lesser degree of stress. It is felt that monitoring of serum lipid peroxide levels in serum and tissues (placenta), backed by scavenging enzyme superoxide dismutase, can be more helpful for corroborating safety and the risk of free radical toxicity in pregnancy and abortion. PMID:2071057

  18. Organochlorine pesticide gradient levels among maternal adipose tissue, maternal blood serum and umbilical blood serum.

    PubMed

    Herrero-Mercado, Margarita; Waliszewski, S M; Caba, M; Martínez-Valenzuela, C; Gómez Arroyo, S; Villalobos Pietrini, R; Cantú Martínez, P C; Hernández-Chalate, F

    2011-03-01

    The objective of the present study was to determine levels and calculate ratios of copartition coefficients among organochlorine pesticides β-HCH, pp'DDE, op'DDT and pp'DDT in maternal adipose tissue, maternal blood serum and umbilical blood serum of mother-infant pairs from Veracruz, Mexico. Organochlorine pesticides were analyzed in 70 binomials: maternal adipose tissue, maternal serum and umbilical cord serum samples, using gas chromatography with electron capture detection (GC-ECD). The results were expressed as mg/kg on fat basis. p,p'-DDE was the major organochlorine component, detected in every maternal adipose tissue (0.770 mg/kg), maternal serum sample (5.8 mg/kg on fat basis) and umbilical cord blood sample (6.9 mg/kg on fat basis). p,p'-DDT was detected at 0.101 mg/kg, 2.2 mg/kg and 5.9 mg/kg respectively, according to the order given above. β-HCH was detected at 0.027 mg/kg, 4.2 mg/kg and 28.0 mg/kg respectively. op'DDT was detected only in maternal adipose tissue at 0.011 mg/kg. The copartition coefficients among samples identify significant increases in concentrations from adipose tissue to maternal blood serum and to umbilical blood serum. The increase indicated that maternal adipose tissue released organochlorine pesticides to blood serum and that they are carried over to umbilical cord blood. PMID:21290101

  19. Interaction between smoking and functional polymorphism in the TGFB1 gene is associated with ischaemic heart disease and myocardial infarction in patients with rheumatoid arthritis: a cross-sectional study

    PubMed Central

    2012-01-01

    Introduction Transforming growth factor-beta1 (TGF-beta1) is a pleiotropic cytokine that plays important roles in immunity and inflammation. Some studies have suggested that polymorphism in the TGFB1 gene is associated with heart disease in the general population. The purpose of the present study was to determine whether common single-nucleotide polymorphisms (SNP) in the TGFB1 gene are associated with ischaemic heart disease (IHD) and/or myocardial infarction (MI) in patients with rheumatoid arthritis (RA), and to investigate the influence of smoking on any association. Methods PCR-based assays were used to determine the genotypes of TGFB1 SNPs including TGFB1-509 C/T (rs1800469, in the promoter region), +868 T/C (rs1800470, in exon 1) and +913 G/C (rs1800471, in exon 1) in 414 subjects with established RA. Genotyping for the +868 SNP was also carried out on a second study population of RA patients (n = 259) with early disease. Serum levels of TGF-beta1 were measured using a commercial ELISA kit. Smoking history and IHD/MI status were obtained on each patient. Associations with IHD/MI were assessed using contingency tables and logistic regression analyses. Results The heterozygous genotype of TGFB+868 was associated with an increased risk of IHD (OR 2.14, 95% CI 1.30 - 3.55) and MI (OR 2.42, 95% CI 1.30-4.50), compared to the homozygous genotypes combined. Smoking was an independent risk for IHD and MI, and evidence of interaction between smoking and TGFB+868 was found. Multivariate analyses indicated that the strongest associations with IHD and MI were due to the combined effect of the TGFB1+868 TC genotype and smoking (OR 2.75, 95% CI 1.59-4.75; and OR 2.58 95% CI 1.33-4.99, respectively), independent of other cardiovascular risk factors. The association of the +868 TC genotype and evidence of +868 TC-smoking interaction with IHD were replicated in a second population of RA patients with early disease. Serum TGF-beta1 levels were not associated with TGFB1

  20. Serum selenium concentrations in rheumatoid arthritis.

    PubMed Central

    O'Dell, J R; Lemley-Gillespie, S; Palmer, W R; Weaver, A L; Moore, G F; Klassen, L W

    1991-01-01

    Selenium is a trace element and an essential part of the enzyme glutathione peroxidase, which protects cells from oxidative damage. Selenium has been shown to have antiproliferative, anti-inflammatory, antiviral, and immune altering effects. Serum selenium concentrations in 101 patients with seropositive rheumatoid arthritis were found to be significantly lower than those in 29 normal, healthy controls (mean (SD) 148 (42) v 160 (25) micrograms/l) and also lower than those in eight patients with fibrositis (148 (42) v 166 (25) micrograms/l). It is speculated that serum selenium concentrations may modulate the effect of viral or other infections in subjects with the appropriate genetic background and in this way enhance the development or progression of rheumatoid arthritis. PMID:2059080

  1. Spectral characteristic analysis of lung cancer serum

    NASA Astrophysics Data System (ADS)

    Li, Xiao Zhou; Jin, Huiqiang; Liu, Huasheng; Ding, Jianhua; Lin, Junxiu

    2001-10-01

    Spectral changes of lung cancer serum in the process of tumor evolution were investigated in this study. We kept close watch on the tumor progression of a group of patients, and measured their serum spectra using 488.0nm and 514.5nm excitation of an Ar-ion laser once a week. There was no apparent change observed in fluorescence spectrum in different period. However, the relative intensity of three Raman peaks (mode A, B and C) decreased every week later. For quantitative analysis of such changes, a parameter Ir (relative intensity of C Raman peak) was introduced and Ir-value was calculated. Calculation showed that Ir-value was degressive with tumor evolution, but (beta) (Ir5145 /Ir4880) varied irregularly. To the end, no Raman peak was observed. We assumed that three Raman peaks were derived from beta carotene. It indicated that the content of beta carotene decreased with the aggravation of lung cancer.

  2. BILIARY LIPIDS SUPPORT SERUM-FREE GROWTH OF 'GIARDIA LAMBLIA'

    EPA Science Inventory

    Giardia lamblia has only been grown in vitro in media containing serum or serum fractions. How this pathogen can grow in the human small intestinal lumen without serum is not known. The authors found that samples of human hepatic or gall bladder bile maintained G. lamblia surviva...

  3. Iron and ADHD: Time to Move beyond Serum Ferritin Levels

    ERIC Educational Resources Information Center

    Donfrancesco, Renato; Parisi, Pasquale; Vanacore, Nicola; Martines, Francesca; Sargentini, Vittorio; Cortese, Samuele

    2013-01-01

    Objective: (a) To compare serum ferritin levels in a sample of stimulant-naive children with ADHD and matched controls and (b) to assess the association of serum ferritin to ADHD symptoms severity, ADHD subtypes, and IQ. Method: The ADHD and the control groups included 101 and 93 children, respectively. Serum ferritin levels were determined with…

  4. Seasonal folate serum concentrations at different nutrition.

    PubMed

    Krajcovicová-Kudlácková, Marica; Valachovicová, Martina; Blazícek, Pavel

    2013-03-01

    Folic acid (vitamin B9) rich sources are leafy green vegetables, legumes, whole grains, egg yolk, liver, and citrus fruit. In winter and early spring, there could be insufficient supply of vegetables and fruit and thus lower intake of folic acid and possible deficient folic acid blood concentrations. The aim of the study was to assess serum vitamin B9 concentrations depending on the season (the last third of winter - March, the last third of spring - May/June and the beginning of autumn - September) and different nutritional habits (apparently healthy adults non-smoking, non-obese 366 subjects; 204 persons of general population on traditional mixed diet; and 162 long-term lacto-ovo vegetarians). In general population group, the mean concentration of folate in March was low (narrowly above lower reference limit) with high incidence of deficient values - 31.5%. In May/ June vs. March was folate concentration significantly higher with deficient values in 13.2% of individuals. The highest serum values were observed in September with 11.1% of deficient values. In vegetarian vs. non-vegetarian group, significantly higher folate concentrations were found in each season with no deficient values. Folate and vitamin B12 are the regulators of homocysteinemia; plant food lacks of vitamin B12. The deficient folate serum values in March caused the mild hyperhomocysteinemia in 12.3% of individuals vs. only 5.9% and 4.8% of subjects in groups investigated in May/June and September. In spite of high folate concentrations in all investigations and no deficient value, 19.6-22.8% of vegetarians suffer from mild hyperhomocysteinemia as a consequence of deficient vitamin B12 concentrations in one quarter of subjects. As far as the general population is concerned, our findings suggest that winter and early spring are critical seasons in regards to optimal serum folate concentrations. PMID:23741898

  5. (PCG) Protein Crystal Growth Human Serum Albumin

    NASA Technical Reports Server (NTRS)

    1989-01-01

    (PCG) Protein Crystal Growth Human Serum Albumin. Contributes to many transport and regulatory processes and has multifunctional binding properties which range from various metals, to fatty acids, hormones, and a wide spectrum of therapeutic drugs. The most abundant protein of the circulatory system. It binds and transports an incredible variety of biological and pharmaceutical ligands throughout the blood stream. Principal Investigator on STS-26 was Larry DeLucas.

  6. Indices of serum tonicity in clinical practice.

    PubMed

    Rohrscheib, Mark; Rondon-Berrios, Helbert; Argyropoulos, Christos; Glew, Robert H; Murata, Glen H; Tzamaloukas, Antonios H

    2015-06-01

    Although disturbances of serum tonicity (effective osmolality) may have dire consequences, only surrogate indices of tonicity are available in practice. This report identifies the appropriate index for expressing clinical states of dystonicity. Serum sodium concentration ([Na]S) and osmolality ([Osm]S) may be incongruent. When the tonicity state shown by [Osm]S is higher than [Na]S and the difference between the 2 indices is caused by an excess of solute that distributes in total body water, tonicity is described by [Na]S. When this difference results from a gain of solute with extracellular distribution like mannitol or a decrease in serum water content, causing a falsely low measurement of [Na]S, [Osm]S accurately reflects tonicity. Two indices of tonicity are applicable during hyperglycemia: the tonicity formula (2 ·[Na]S + [Glucose]S/18) and the corrected [Na]S ([Na]S corrected to a normal [Glucose]S using an empirically derived coefficient). Clinicians should understand the uses and limitations of the tonicity indices. PMID:26002851

  7. Serum sickness secondary to ciprofloxacin use.

    PubMed

    Guharoy, S R

    1994-12-01

    Although serum sickness-like reactions are uncommon, various drugs have recently been implicated to manifest the reaction. The following case report is of a possible serum sickness-like reaction secondary to ciprofloxacin use, a commonly prescribed antibiotic in the US. A 62-y-old female developed polyarthralgias, myalgia and a generalized urticarial rash following 5 d use of ciprofloxacin. On admission to the hospital, patient was placed on cefazolin and gentamicin for suspected bacteremia. However, the regimen was discontinued after 72 h because of worsening clinical condition. Patient was placed on iv methylprednisolone therapy, and within 18 h a significant improvement was noted in her myalgias and rash. Over the next 72 h the steroid therapy was changed to a po regimen and the patient became asymptomatic 5 d after the initiation of steroid therapy. Patient was discharged on day 9 of hospital admission. Though serum sickness-like reactions have been reported with various drugs, only 1 case has been reported implicating ciprofloxacin. Clinicians should be aware of this potential adverse event secondary to ciprofloxacin use. PMID:7900274

  8. Mammographic breast density and serum phytoestrogen levels.

    PubMed

    Lowry, Sarah J; Sprague, Brian L; Aiello Bowles, Erin J; Hedman, Curtis J; Hemming, Jocelyn; Hampton, John M; Burnside, Elizabeth S; Sisney, Gale A; Buist, Diana S M; Trentham-Dietz, Amy

    2012-08-01

    Some forms of estrogen are associated with breast cancer risk as well as with mammographic density (MD), a strong marker of breast cancer risk. Whether phytoestrogen intake affects breast density, however, remains unclear. We evaluated the association between serum levels of phytoestrogens and MD in postmenopausal women. We enrolled 269 women, ages 55-70 yr, who received a screening mammogram and had no history of postmenopausal hormone use. Subjects completed a survey on diet and factors related to MD and provided a blood sample for analysis of 3 phytoestrogens: genistein, daidzein, and coumestrol. We examined whether mean percent MD was related to serum level of phytoestrogens, adjusting for age and body mass index. Genistein and daidzein levels correlated with self-reported soy consumption. Mean percent MD did not differ across women with different phytoestrogen levels. For example, women with nondetectable genistein levels had mean density of 11.0% [95% confidence intervals (CI) = 9.9-12.4], compared to 10.5% (95% CI = 8.0-13.7) and 11.2% (95% CI = 8.7-14.6) for < and ≥ median detectable levels, respectively. In a population with relatively low soy intake, serum phytoestrogens were not associated with mammographic density. Additional studies are needed to determine effects of higher levels, particularly given patterns of increasing phytoestrogen intake. PMID:22860715

  9. Serum copeptin and pregnancy outcome in preeclampsia

    PubMed Central

    Akinlade, Kehinde Sola; Adediji, Isaac Oluwole; Rahamon, Sheu Kadiri; Fawole, Adeniran Olubukola; Tongo, Olukemi Oluwatoyin

    2015-01-01

    Background: A number of biochemical predictors of preeclampsia have been reported, but little is known about their possible relationship with maternal and fetal outcomes. This study determined serum copeptin in pregnant women with preeclampsia and assessed its relationship with pregnancy outcomes. Materials and Methods: Thirty women with severe preeclampsia (SP), 30 with mild preeclampsia (MP), and 30 with uncomplicated pregnancy were enrolled into this study. Serum copeptin, creatinine, and liver function were determined using enzyme-linked immunosorbent assay and colorimetry as appropriate. Pregnancy outcomes, both maternal and fetal, were taken using standard methods. Results: Copeptin was significantly elevated in preeclampsia subjects compared with controls and in SP compared with MP. Assessing the diagnostic property of copeptin for preeclampsia, the area under the curve for copeptin was 0.99. Nine (30%) and 3 (10%) of SP and MP, respectively had abruptio placenta while 6 (20%), 2 (6.7%), and 1 (3.3%) still births were recorded in SP, MP, and controls, respectively. Neonates of mothers with preeclampsia had significantly lower birth weight, infant length, ponderal index, and head circumference compared with neonates of the controls. Copeptin had a significant inverse relationship with birth weight, ponderal index, head circumference, Apgar score, and infant length in neonates of mothers with preeclampsia. Conclusion: Serum copeptin level in the third trimester could predict preeclampsia and its elevation is associated with adverse perinatal outcome. PMID:26778890

  10. Reductions in Serum Lipids with a 4-year Decline in Serum Perfluorooctanoic Acid and Perfluorooctanesulfonic Acid

    PubMed Central

    Fitz-Simon, Nicola; Fletcher, Tony; Luster, Michael I.; Steenland, Kyle; Calafat, Antonia M.; Kato, Kayoko; Armstrong, Ben

    2016-01-01

    Background Several epidemiological cross-sectional studies have found positive associations between serum concentrations of lipids and perfluorooctanoic acid (PFOA, or C8). A longitudinal study should be less susceptible to biases from uncontrolled confounding or reverse causality. Methods We investigated the association between within-individual changes in serum PFOA and perfluorooctanesulfonic acid (PFOS) and changes in serum lipid levels (low-density lipoprotein [LDL] cholesterol, high-density lipoprotein cholesterol, total cholesterol, and triglycerides) over a 4.4-year period. The study population consisted of 560 adults living in parts of Ohio and West Virginia where public drinking water had been contaminated with PFOA. They had participated in a cross-sectional study in 2005–2006, and were followed up in 2010, by which time exposure to PFOA had been substantially reduced. Results Overall serum concentrations of PFOA and PFOS fell by half from initial geometric means of 74.8 and 18.5 ng/mL, respectively, with little corresponding change in LDL cholesterol (mean increase 1.8%, standard deviation 26.6%). However, there was a tendency for people with greater declines in serum PFOA or PFOS to have greater LDL decrease. For a person whose serum PFOA fell by half, the predicted fall in LDL cholesterol was 3.6% (95% confidence interval = 1.5–5.7%). The association with a decline in PFOS was even stronger, with a 5% decrease in LDL (2.5–7.4%). Conclusions Our findings from this longitudinal study support previous evidence from cross-sectional studies of positive associations between PFOA and PFOS in serum and LDL cholesterol. PMID:23685825

  11. Inhibiting albumin glycation attenuates dysregulation of VEGFR-1 and collagen IV subchain production and the development of renal insufficiency.

    PubMed

    Cohen, Margo P; Lautenslager, Gregory T; Hud, Elizabeth; Shea, Elizabeth; Wang, Amy; Chen, Sheldon; Shearman, Clyde W

    2007-02-01

    Glomerular cells in culture respond to albumin containing Amadori glucose adducts (the principal serum glycated protein), with activation of protein kinase C-beta(1), increased expression of transforming growth factor (TGF)-beta1, the TGF-beta type II signaling receptor, and the extracellular matrix proteins alpha(1)(IV) collagen and fibronectin and with decreased production of the podocyte protein nephrin. Decreasing the burden of glycated albumin in diabetic db/db mice significantly reduces glomerular overexpression of TGF-beta1 mRNA, restores glomerular nephrin immunofluorescence, and lessens proteinuria, mesangial expansion, renal extracellular matrix protein production, and increased glomerular vascular endothelial growth factor (VEGF) immunostaining. In the present study, db/db mice were treated with a small molecule, designated 23CPPA, that inhibits the nonenzymatic condensation of glucose with the albumin protein to evaluate whether increased glycated albumin influences the production of VEGF receptors (VEGFRs) and type IV collagen subchains and ameliorates the development of renal insufficiency. Renal levels of VEGF and VEGFR-1 proteins and serum creatinine concentrations were significantly higher and renal levels of alpha(3)(IV) collagen and nephrin proteins and endogenous creatinine clearance values were significantly lower in control diabetic than in age-matched nondiabetic (db/m) mice. These changes were significantly attenuated in db/db littermate mice treated from 9 to 18 wk of age with 23CPPA. The findings indicate that inhibiting excess nonenzymatic glycation of serum albumin improves renal molecular biology abnormalities and protects against the development of renal insufficiency in the db/db mouse. PMID:17018845

  12. Proliferation of Estrogen Receptor alpha Positive Mammary Epithelial Cells is Restrained by TGFbeta1 in Adult Mice

    SciTech Connect

    Ewan, Kenneth B.R.; Oketch-Rabah, Hellen A.; Ravani, Shraddha A.; Shyamala, G.; Moses, Harold L.; Barcellos-Hoff, Mary Helen

    2005-03-03

    Transforming growth factor {beta}1 (TGF{beta}1) is a potent inhibitor of mammary epithelial proliferation. In human breast, estrogen receptor {alpha} (ER{alpha}) cells rarely co-localize with markers of proliferation, but their increased frequency correlates with breast cancer risk. To determine whether TGF{beta}1 is necessary for the quiescence of ER{alpha}-positive population, we examined mouse mammary epithelial gland at estrus. Approximately 35% of cells showed TGF{beta}1 activation, which co-localized with nuclear receptor-phosphorylated Smad 2/3, indicating that TGF{beta} signaling is autocrine. Furthermore, nuclear Smad co-localized with nuclear ER{alpha}. To test whether TGF{beta} was functional, we examined genetically engineered mice with different levels of TGF{beta}1. ER{alpha} co-localization with markers of proliferation (i.e. Ki-67 or BrdU) at estrus was significantly increased in the mammary glands of Tgf{beta}1 C57/bl/129SV heterozygote mice. This relationship was maintained following pregnancy, but was absent at puberty. Conversely, mammary epithelial expression of constitutively active TGF{beta}1 via the MMTV promoter suppressed proliferation of ER{alpha} positive cells. Thus, TGF{beta}1 activation functionally restrains ER{alpha} positive cells from proliferating in adult mammary gland. Accordingly, we propose that TGF{beta}1 dysregulation may promote proliferation of ER{alpha} positive cells associated with breast cancer risk in humans.

  13. Direct transfer of transforming growth factor beta 1 gene into arteries stimulates fibrocellular hyperplasia.

    PubMed Central

    Nabel, E G; Shum, L; Pompili, V J; Yang, Z Y; San, H; Shu, H B; Liptay, S; Gold, L; Gordon, D; Derynck, R

    1993-01-01

    The arterial wall responds to thrombosis or mechanical injury through the induction of specific gene products that increase cellular proliferation and connective tissue formation. These changes result in intimal hyperplasia that is observed in restenosis and the early phases of atherosclerosis. Transforming growth factor beta 1 (TGF-beta 1) is a secreted multi-functional protein that plays an important role in embryonal development and in repair following tissue injury. However, the function of TGF-beta 1 in vascular cell growth in vivo has not been defined. In this report, we have evaluated the role of TGF-beta 1 in the pathophysiology of intimal and medial hyperplasia by gene transfer of an expression plasmid encoding active TGF-beta 1 into porcine arteries. Expression of TGF-beta 1 in normal arteries resulted in substantial extracellular matrix production accompanied by intimal and medial hyperplasia. Increased procollagen, collagen, and proteoglycan synthesis in the neointima was demonstrated by immunohistochemistry relative to control transfected arteries. Expression of TGF-beta 1 induced a distinctly different program of gene expression and biologic response from the platelet-derived growth factor B (PDGF B) gene: procollagen synthesis induced by TGF-beta 1 was greater, and cellular proliferation was less prominent. These findings show that TGF-beta 1 differentially modulates extracellular matrix production and cellular proliferation in the arterial wall in vivo and could play a reparative role in the response to arterial injury. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:8248168

  14. Transforming growth factor-beta1-induced activation of the Raf-MEK-MAPK signaling pathway in rat lung fibroblasts via a PKC-dependent mechanism.

    PubMed

    Axmann, A; Seidel, D; Reimann, T; Hempel, U; Wenzel, K W

    1998-08-19

    In fibroblasts transforming growth factor-beta1 (TGF-beta1) regulates cell proliferation and turnover of macromolecular components of the extracellular matrix. Here, intracellular signaling events in growth-inhibited embryonic rat lung fibroblasts (RFL-6) upon stimulation with TGF-beta1 were investigated. TGF-beta1 rapidly induced the activation of c-Raf-1, MEK-1, and MAPK p42 and p44. The activation of this pathway by TGF-beta1 did not depend on autocrine platelet-derived growth factor (PDGF) or basic fibroblast growth factor (bFGF). Inhibition of the binding of growth factors to their tyrosine kinase receptors did not affect MAPK activation by TGF-beta1. Ras activation by TGF-beta1 was significantly lower compared to the activation by PDGF or bFGF. The intracellular transduction of the TGF-beta1 signal was completely suppressed by depletion or inhibition of protein kinase C (PKC). It is shown that calcium-dependent isoforms of PKC are required for MAPK activation by TGF-beta1. PMID:9712718

  15. In vivo protection against interleukin-1-induced articular cartilage damage by transforming growth factor-beta 1: age-related differences.

    PubMed Central

    van Beuningen, H M; van der Kraan, P M; Arntz, O J; van den Berg, W B

    1994-01-01

    OBJECTIVES--Transforming growth factor-beta (TGF-beta) has been shown to antagonise interleukin-1 (IL-1) effects in different systems. Investigations were carried out to study whether TGF-beta 1 modulates IL-1 induced inflammation and IL-1 effects on articular cartilage in the murine knee joint. METHODS--IL-1, TGF-beta 1 or both factors together were injected into the knee joint. Inflammation was studied in whole knee histological sections. Patellar cartilage proteoglycan synthesis was measured using 35S-sulphate incorporation while patellar cartilage glycosaminoglycan content was determined with automated image analysis on joint sections. RESULTS--Co-injection of TGF-beta 1 and IL-1 resulted in synergistic attraction of inflammatory cells. In contrast, TGF-beta 1 counteracted IL-1 induced suppression of articular cartilage proteoglycan synthesis. Proteoglycan depletion was similar shortly after the last injection of IL-1 or IL-1/TGF-beta 1, but accelerated recovery was found with the combination at later days. This protective effect of TGF-beta 1 could not be demonstrated in older mice. CONCLUSIONS--TGF-beta 1 aggravates IL-1 induced knee joint inflammation, but counteracts the deleterious effects of IL-1 on articular cartilage proteoglycan synthesis and content. The data indicate that TGF-beta 1 could play an important part in articular cartilage restoration after IL-1 induced proteoglycan depletion. Images PMID:7979598

  16. Increased central nervous system production of extracellular matrix components and development of hydrocephalus in transgenic mice overexpressing transforming growth factor-beta 1.

    PubMed Central

    Wyss-Coray, T.; Feng, L.; Masliah, E.; Ruppe, M. D.; Lee, H. S.; Toggas, S. M.; Rockenstein, E. M.; Mucke, L.

    1995-01-01

    A number of important neurological diseases, including HIV-1 encephalitis, Alzheimer's disease, and brain trauma, are associated with increased cerebral expression of the multifunctional cytokine transforming growth factor-beta 1 (TGF-beta 1). To determine whether overexpression of TGF-beta 1 within the central nervous system (CNS) can contribute to the development of neuropathological alterations, a bioactive form of TGF-beta 1 was expressed in astrocytes of transgenic mice. Transgenic mice with high levels of cerebral TGF-beta 1 expression developed a severe communicating hydrocephalus, seizures, motor incoordination, and early runting. While unmanipulated heterozygous transgenic mice from a low expressor line showed no such alterations, increasing TGF-beta 1 expression in this line by injury-induced astroglial activation or generation of homozygous offspring did result in the abnormal phenotype. Notably, astroglial overexpression of TGF-beta 1 consistently induced a strong upmodulation of the extracellular matrix proteins laminin and fibronectin in the CNS, particularly in the vicinity of TGF-beta 1-expressing perivascular astrocytes, but was not associated with obvious CNS infiltration by hematogenous cells. While low levels of extracellular matrix protein expression may assist in CNS wound repair and regeneration, excessive extracellular matrix deposition could result in the development of hydrocephalus. As an effective inducer of extracellular matrix components, TGF-beta 1 may also contribute to the development of other neuropathological alterations, eg, the formation of amyloid plaques in Alzheimer's disease. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:7604885

  17. Exogenous transforming growth factor-beta amplifies its own expression and induces scar formation in a model of human fetal skin repair.

    PubMed Central

    Lin, R Y; Sullivan, K M; Argenta, P A; Meuli, M; Lorenz, H P; Adzick, N S

    1995-01-01

    OBJECTIVE: Fetal skin wounds heal without scarring. To determine the role of TGF-beta 1 in fetal wound healing, mRNA expression of TGF-beta 1 was analyzed in human fetal and adult skin wounds. METHODS: Human fetal skin transplanted to a subcutaneous location on an adult athymic mouse that was subsequently wounded heals without scar, whereas human adult skin heals with scar formation in that location. In situ hybridization for TGF-beta 1 mRNA expression and species-specific immunohistochemistry for fibroblasts, macrophages, and neutrophils were performed in human adult wounds, fetal wounds, and fetal wounds treated with a TGF-beta 1 slow release disk. RESULTS: Transforming growth factor-beta 1 mRNA expression was induced by wounding adult skin. No TGF-beta 1 mRNA upregulation was detected in human fetal skin after wounding. However, when exogenous TGF-beta 1 was added to human fetal skin, induction of TGF-beta 1 mRNA expression in human fetal fibroblasts occurred, an adult-like inflammatory response was detected, and the skin healed with scar formation. CONCLUSIONS: Transforming growth factor-beta 1 is an important modulator in scar formation. Anti-TGF-beta 1 strategies may promote scarless healing in adult wounds. Images Figure 1. Figure 2. Figure 3. Figure 5. Figure 6. PMID:7639582

  18. Serum- and substratum-dependent modulation of neuritic growth.

    PubMed

    Skaper, S D; Selak, I; Varon, S

    1983-01-01

    Explants of embryonic day 8 (E8) chicken dorsal root ganglia (DRG) have been cultured with medium containing serum or the serum-free supplement N1 on one of three substrata: collagen, polyornithine (PORN), or PORN exposed to a polyornithine-binding neurite-promoting factor (PNPF-PORN). Replicate cultures were maintained with or without nerve growth factor (NGF). NGF elicited its classical neuritic outgrowth on all three substrata in serum-containing or serum-free medium. In the absence of NGF, however, a gradation of increasing neurite growth was seen with: PNPF-PORN greater than PORN greater than collagen. This response occurred in both media. In addition, the neuritic halo in each instance was markedly more developed in the absence of serum, especially on PNPF-PORN. Nonneuronal behaviors reflected both serum and substratum influences: thus, nonneuronal outgrowth consisted mainly of flat cells with serum and collagen, was nonexistent with serum and PORN or PNPF-PORN, and involved mostly Schwann-like scattered cells in the absence of serum on any one substratum. The serum-dependent behaviors of ganglionic neurites were examined further with explants from chicken E11 sympathetic ganglia. A single substratum was used (PORN), without exogenous trophic factor. Neurite outgrowth was depressed by the presence of fetal calf serum, thus supporting the generality of this phenomenon. Lastly, PC12 cells, a clonal line of rat pheochromocytoma, will grow neurites in the presence of NGF after 48 hr in serum-free, but not serum-containing media. Addition of serum to serum-free cultures at this time results in the rapid and complete retraction of neurites. PMID:6876195

  19. Serum and tissue biomarkers in aortic stenosis

    PubMed Central

    Kapelouzou, Alkistis; Tsourelis, Loukas; Kaklamanis, Loukas; Degiannis, Dimitrios; Kogerakis, Nektarios; Cokkinos, Dennis V.

    2015-01-01

    Background: Calcific aortic valve stenosis (CAVS) is seen in a large proportion of individuals over 60 years. It is an active process, influenced by lipid accumulation, mechanical stress, inflammation, and abnormal extracellular matrix turnover. Various biomarkers (BMs) are studied, as regards mechanisms, diagnosis and prognosis. Methods: In the calcified valves calcium deposition, elastin fragmentation and disorganization of cellular matrix were assessed, together with expression of OPN, OPG, osteocalcin (OCN) and RL2. We prospectively studied the following serum BMs in 60 patients with CAVS and compared them to 20 healthy controls, free from any cardiac disease: Matrix metalloproteinases (MMP) 2 and 9 and tissue inhibitor of metalloproteinase 1 (TIMP1), which regulate collagen turnover, inflammatory factors, i.e. tumor necrosis factor a (TNFa), interleukin 2 (IL2), transforming growth factor β1 (TGF-β1) which regulates fibrosis, fetuin-A (fet-A), osteopontin (OPN), osteoprotegerin (OPG), sclerostin (SOST), and relaxin-2 (RL2) which positively or negatively regulate calcification. Monocyte chemoattractant protein 1 (MCP-1) which regulates migration and infiltration of monocytes/macrophages was also studied as well as malondialdehyde (MDA) an oxidative marker. Results: Extent of tissue valve calcification (Alizarin Red stain) was negatively correlated with tissue elastin, and RL2, and positively correlated with tissue OCN and serum TIMP1 and MCP-1 and negatively with MMP9. Tissue OCN was positively correlated with OPN and negatively with the elastin. Tissue OPN was negatively correlated with elastin and OPG. Tissue OPN OPG and RL2 were not correlated with serum levels In the serum we found in patients statistically lower TIMP1, fet-A and RL2 levels, while all other BMs were higher compared to the healthy group. Positive correlations between SOST and IL2, OPG and MDA but negative with TNFa and OPN were found; also MMP9 was negatively correlated with TNFa and MCP-1

  20. Preliminary crystallographic studies of four crystal forms of serum albumin

    NASA Technical Reports Server (NTRS)

    Carter, D. C.; Chang, B.; Ho, J. X.; Keeling, K.; Krishnasami, Z.

    1994-01-01

    Several crystal forms of serum albumin suitable for three-dimensional structure determination have been grown. These forms include crystals of recombinant and wild-type human serum albumin, baboon serum albumin, and canine serum albumin. The intrinsic limits of X-ray diffraction for these crystals are in the range 0.28-0.22 nm. Two of the crystal forms produced from human and canine albumin include incorporated long-chain fatty acids. Molecular replacement experiments have been successfully conducted on each crystal form using the previously determined atomic coordinates of human serum albumin illustrating the conserved tertiary structure.

  1. Preliminary crystallographic studies of four crystal forms of serum albumin.

    PubMed

    Carter, D C; Chang, B; Ho, J X; Keeling, K; Krishnasami, Z

    1994-12-15

    Several crystal forms of serum albumin suitable for three-dimensional structure determination have been grown. These forms include crystals of recombinant and wild-type human serum albumin, baboon serum albumin, and canine serum albumin. The intrinsic limits of X-ray diffraction for these crystals are in the range 0.28-0.22 nm. Two of the crystal forms produced from human and canine albumin include incorporated long-chain fatty acids. Molecular replacement experiments have been successfully conducted on each crystal form using the previously determined atomic coordinates of human serum albumin illustrating the conserved tertiary structure. PMID:7813459

  2. IL-8 and cathepsin B as melanoma serum biomarkers.

    PubMed

    Zhang, Hongtao; Fu, Ting; McGettigan, Suzanne; Kumar, Suresh; Liu, Shujing; Speicher, David; Schuchter, Lynn; Xu, Xiaowei

    2011-01-01

    Melanoma accounts for only a small portion of skin cancer but it is associated with high mortality. Melanoma serum biomarkers that may aid early diagnosis or guide therapy are needed clinically. However, studies of serum biomarkers have often been hampered by the serum interference that causes false readouts in immunological tests. Here we show that, after using a special buffer to eliminate the serum interference, IL-8 and cathepsin B levels were significantly elevated in melanoma patients (p < 0.05). More importantly, the combination of IL-8 and cathepsin B were also studied as a prognosis marker for melanoma mortality. Our study provides a novel approach to examine serum biomarkers. PMID:21673904

  3. IL8 and Cathepsin B as Melanoma Serum Biomarkers

    PubMed Central

    Zhang, Hongtao; Fu, Ting; McGettigan, Suzanne; Kumar, Suresh; Liu, Shujing; Speicher, David; Schuchter, Lynn; Xu, Xiaowei

    2011-01-01

    Melanoma accounts for only a small portion of skin cancer but it is associated with high mortality. Melanoma serum biomarkers that may aid early diagnosis or guide therapy are needed clinically. However, studies of serum biomarkers have often been hampered by the serum interference that causes false readouts in immunological tests. Here we show that, after using a special buffer to eliminate the serum interference, IL-8 and cathepsin B levels were significantly elevated in melanoma patients (p < 0.05). More importantly, the combination of IL-8 and cathepsin B were also studied as a prognosis marker for melanoma mortality. Our study provides a novel approach to examine serum biomarkers. PMID:21673904

  4. Effect of oral glucose on serum zinc in the elderly

    SciTech Connect

    Lopez, A.L.; Kohrs, M.B.; Horwitz, D.L.; Cyborski, C.K.; Czajka-Narins, D.M.; Kamath, S.

    1986-03-05

    To determine the effect of glucose loading on serum zinc concentrations, 34 elderly subjects aged 60-86 y were studied. Anthropometric data, medical and dietary histories were obtained. Serum zinc and glucose concentrations were obtained fasting and 1/2, 1, 1 1/2, 2 and 3 h after 75 g oral glucose load; glycohemoglobin and fasting serum lipids were also determined. For comparison, the subjects were categorized as: normal or low serum zinc concentrations; normal or high body mass index BMI; normal or high sum of skinfolds and normal or high serum cholesterol. Results showed that low serum zinc concentrations increased significantly over baseline values after the glucose load and did not return to fasting levels. On the other hand, mean serum zinc concentrations significantly declined without recovery for those with normal zinc values. For the total group, no significant differences were noted between fasting values and subsequent time periods. No correlations were noted between fasting serum zinc and area under the curve for zinc except in the high BMI group (positive correlation observed). For the high BMI group, fasting serum zinc differed significantly from the succeeding measurements except for 30 min. For the group as a whole, mean serum zinc concentration was within normal limits (76.9 +/- 2.8 mcg/ml): mean zinc intake was less than 2/3rds the RDA. They conclude that glucose ingestion may alter serum zinc and should be considered in interpreting these levels.

  5. Plasmid Carriage and the Serum Sensitivity of Enterobacteria

    PubMed Central

    Taylor, Peter W.; Hughes, Colin

    1978-01-01

    The carriage of a range of plasmids by rough, serum-sensitive laboratory strains of Escherichia coli made no difference to their reactivity in human serum as determined by two methods. Plasmid-carrying enterobacteria isolated from polluted river water gave a variety of responses to serum. Smooth E. coli river isolate C8 was killed by serum but only after a delay of 1 h, and curing of antibiotic resistance and colicin determinants from this strain led to a small but significant increase in serum sensitivity. Plasmids from eight strains were transferred by conjugation to a cured derivative of C8 (C8−NalR), and in six cases a significant increase in the serum resistance of the progeny was observed. Plasmid-mediated enhancement of resistance was particularly marked with plasmids R1 and NR1, and a round of replication mutant of NR1 conferred greater resistance than did the normal R factor. However, R1 and NR1 were unable to modify the serum response of a cured strain (P21−NalR) derived from promptly serum-sensitive isolate P21. These findings suggest that lipopolysaccharide O-side chains, the cell surface components responsible for the delay in serum killing, are essential for the expression of plasmid factors that modify sensitivity to serum. Examination of K(A)− variants of two isolates indicated that the K(A) antigen has only a marginal effect on the serum response. PMID:365738

  6. Biliary lipids support serum-free growth of Giardia lamblia.

    PubMed Central

    Gillin, F D; Gault, M J; Hofmann, A F; Gurantz, D; Sauch, J F

    1986-01-01

    Giardia lamblia has been grown in vitro only in media containing serum or serum fractions. How this pathogen can grow in the human small intestinal lumen without serum is not known. We found that samples of human hepatic or gall bladder bile maintained G. lamblia survival for 24 to 48 h in medium without serum but did not support growth. By contrast, an artificial biliary lipid dispersion containing six bile salts, phosphatidylcholine (PC), and cholesterol, in the ratios characteristic of human bile, supported parasite growth in medium without serum or serum fractions. To define the requirements, we showed that 1-palmitoyl-2-linoleoyl-PC or 1-palmitoyl-2-oleoyl-PC (which predominate in human bile) satisfied the requirement for PC. Moreover, either glycocholate or glycodeoxycholate could be substituted for the bile salt mixture. The finding that biliary lipids can support serum-free growth of G. lamblia may help explain why this parasite colonizes the upper small intestine. PMID:3744557

  7. Pro: Higher serum bicarbonate in dialysis patients is protective.

    PubMed

    Misra, Madhukar

    2016-08-01

    Chronic metabolic acidosis is common in dialysis patients. Bicarbonate administration via the dialysate helps maintain the acid-base balance in these patients. Serum bicarbonate level in dialysis patients is determined by several factors that include dietary protein intake, nutritional status and dialysis prescription, etc. Additionally, a meaningful interpretation of serum bicarbonate in dialysis patients requires an understanding of complexities involving its measurement. Both very low as well very high levels of serum bicarbonate have been associated with adverse outcomes in observational studies. However, recent observational data, when adjusted for the confounding effects of nutritional status, do not associate higher predialysis serum bicarbonate with adverse consequences. At this time, there are no prospective studies available that have examined the association of serum bicarbonate with hard outcomes in dialysis patients. The ideal level of serum bicarbonate in dialysis patients is therefore unknown. This article examines the available data with regard to the benefits of higher predialysis serum bicarbonate. PMID:27411723

  8. Transforming growth factor-beta1 mediates cellular response to DNA damage in situ

    NASA Technical Reports Server (NTRS)

    Ewan, Kenneth B.; Henshall-Powell, Rhonda L.; Ravani, Shraddha A.; Pajares, Maria Jose; Arteaga, Carlos; Warters, Ray; Akhurst, Rosemary J.; Barcellos-Hoff, Mary Helen

    2002-01-01

    Transforming growth factor (TGF)-beta1 is rapidly activated after ionizing radiation, but its specific role in cellular responses to DNA damage is not known. Here we use Tgfbeta1 knockout mice to show that radiation-induced apoptotic response is TGF-beta1 dependent in the mammary epithelium, and that both apoptosis and inhibition of proliferation in response to DNA damage decrease as a function of TGF-beta1 gene dose in embryonic epithelial tissues. Because apoptosis in these tissues has been shown previously to be p53 dependent, we then examined p53 protein activation. TGF-beta1 depletion, by either gene knockout or by using TGF-beta neutralizing antibodies, resulted in decreased p53 Ser-18 phosphorylation in irradiated mammary gland. These data indicate that TGF-beta1 is essential for rapid p53-mediated cellular responses that mediate cell fate decisions in situ.

  9. Serum Albumin Domain Structures in Human Blood Serum by Mass Spectrometry and Computational Biology*

    PubMed Central

    Belsom, Adam; Schneider, Michael; Fischer, Lutz; Brock, Oliver; Rappsilber, Juri

    2016-01-01

    Chemical cross-linking combined with mass spectrometry has proven useful for studying protein-protein interactions and protein structure, however the low density of cross-link data has so far precluded its use in determining structures de novo. Cross-linking density has been typically limited by the chemical selectivity of the standard cross-linking reagents that are commonly used for protein cross-linking. We have implemented the use of a heterobifunctional cross-linking reagent, sulfosuccinimidyl 4,4′-azipentanoate (sulfo-SDA), combining a traditional sulfo-N-hydroxysuccinimide (sulfo-NHS) ester and a UV photoactivatable diazirine group. This diazirine yields a highly reactive and promiscuous carbene species, the net result being a greatly increased number of cross-links compared with homobifunctional, NHS-based cross-linkers. We present a novel methodology that combines the use of this high density photo-cross-linking data with conformational space search to investigate the structure of human serum albumin domains, from purified samples, and in its native environment, human blood serum. Our approach is able to determine human serum albumin domain structures with good accuracy: root-mean-square deviation to crystal structure are 2.8/5.6/2.9 Å (purified samples) and 4.5/5.9/4.8Å (serum samples) for domains A/B/C for the first selected structure; 2.5/4.9/2.9 Å (purified samples) and 3.5/5.2/3.8 Å (serum samples) for the best out of top five selected structures. Our proof-of-concept study on human serum albumin demonstrates initial potential of our approach for determining the structures of more proteins in the complex biological contexts in which they function and which they may require for correct folding. Data are available via ProteomeXchange with identifier PXD001692. PMID:26385339

  10. The human serum paraoxonase/arylesterase polymorphism.

    PubMed Central

    Eckerson, H W; Wyte, C M; La Du, B N

    1983-01-01

    The heterozygous human serum paraoxonase phenotype can be clearly distinguished from both homozygous phenotypes on the basis of its distinctive ratio of paraoxonase to arylesterase activities. A trimodal distribution of the ratio values was found with 348 individual serum samples, measuring the ratio of paraoxonase activity (with 1 M NaCl in the assay) to arylesterase activity, using phenylacetate. The three modes corresponded to the three paraoxonase phenotypes, A, AB, and B (individual genotypes), and the expected Mendelian segregation of the trait was observed within families. The paraoxonase/arylesterase activity ratio showed codominant inheritance. We have defined the genetic locus determining the aromatic esterase (arylesterase) responsible for the polymorphic paraoxonase activity as esterase-A (ESA) and have designated the two common alleles at this locus by the symbols ESA*A and ESA*B. The frequency of the ESA*A allele was estimated to be .685, and that of the ESA*B allele, 0.315, in a sample population of unrelated Caucasians from the United States. We postulate that a single serum enzyme, with both paraoxonase and arylesterase activity, exists in two different isozymic forms with qualitatively different properties, and that paraoxon is a "discriminating" substrate (having a polymorphic distribution of activity) and phenylacetate is a "nondiscriminating" substrate for the two isozymes. Biochemical evidence for this interpretation includes the cosegregation of the degree of stimulation of paraoxonase activity by salt and paraoxonase/arylesterase activity ratio characteristics; the very high correlation between both the basal (non-salt stimulated) and salt-stimulated paraoxonase activities with arylesterase activity; and the finding that phenylacetate is an inhibitor for paraoxonase activities in both A and B types of enzyme. PMID:6316781

  11. Serum Neurotrophin Profile in Systemic Sclerosis

    PubMed Central

    Lise, Marie-Claude; Sparsa, Agnès; Marie, Isabelle; Lalloué, Fabrice; Ly, Kim; Martel, Clothilde; Bezanahary, Holy; Gondran, Guillaume; Loustaud-Ratti, Véronique; Bonnetblanc, Jean-Marie; Vidal, Elisabeth; Jauberteau, Marie-Odile; Fauchais, Anne-Laure

    2010-01-01

    Background Neurotrophins (NTs) are able to activate lymphocytes and fibroblasts; they can modulate angiogenesis and sympathic vascular function. Thus, they can be implicated in the three pathogenic processes of systemic sclerosis (SSc). The aims of this study are to determine blood levels of Nerve Growth Factor (NGF), Brain-Derived Neurotrophic Factor (BDNF) and Neurotrophin-3 (NT-3) in SSc and to correlate them with clinical and biological data. Methods Serum samples were obtained from 55 SSc patients and 32 control subjects to measure NTs levels by ELISA and to determine their relationships with SSc profiles. Findings Serum NGF levels were higher in SSc patients (288.26±170.34 pg/mL) than in control subjects (170.34±50.8 pg/mL, p<0.001) and correlated with gammaglobulins levels and the presence of both anti-cardiolipin and anti-Scl-70 antibodies (p<0.05). In contrast, BDNF levels were lower in SSc patients than in controls (1121.9±158.1 vs 1372.9±190.9 pg/mL, p<0.0001), especially in pulmonary arterial hypertension and diffuse SSc as compared to limited forms (all p<0.05). NT-3 levels were similar in SSc and in the control group (2657.2±2296 vs 2959.3±2555 pg/mL, NS). BDNF levels correlated negatively with increased NGF levels in the SSc group (and not in controls). Conclusion Low BDNF serum levels were not previously documented in SSc, particularly in the diffuse SSc subset and in patients with pulmonary hypertension or anti-Scl-70 antibodies. The negative correlation between NGF and BDNF levels observed in SSc and not in healthy controls could be implicated in sympathic vascular dysfunction in SSc. PMID:21085492

  12. Familial resemblance for serum metabolite concentrations.

    PubMed

    Draisma, Harmen H M; Beekman, Marian; Pool, René; van Ommen, Gert-Jan B; Adamski, Jerzy; Prehn, Cornelia; Vaarhorst, Anika A M; de Craen, Anton J M; Willemsen, Gonneke; Slagboom, P Eline; Boomsma, Dorret I

    2013-10-01

    Metabolomics is the comprehensive study of metabolites, which are the substrates, intermediate, and end products of cellular metabolism. The heritability of the concentrations of circulating metabolites bears relevance for evaluating their suitability as biomarkers for disease. We report aspects of familial resemblance for the concentrations in human serum of more than 100 metabolites, measured using a targeted metabolomics platform. Age- and sex-corrected monozygotic twin correlations, midparent-offspring regression coefficients, and spouse correlations in subjects from two independent cohorts (Netherlands Twin Register and Leiden Longevity Study) were estimated for each metabolite. In the Netherlands Twin Register subjects, who were largely fasting, we found significant monozygotic twin correlations for 121 out of 123 metabolites. Heritability was confirmed by midparent-offspring regression. For most detected metabolites, the correlations between spouses were considerably lower than those between twins, indicating a contribution of genetic effects to familial resemblance. Remarkably high heritability was observed for free carnitine (monozygotic twin correlation 0.66), for the amino acids serine (monozygotic twin correlation 0.77) and threonine (monozygotic twin correlation 0.64), and for phosphatidylcholine acyl-alkyl C40:3 (monozygotic twin correlation 0.77). For octenoylcarnitine, a consistent point estimate of approximately 0.50 was found for the spouse correlations in the two cohorts as well as for the monozygotic twin correlation, suggesting that familiality for this metabolite is explained by shared environment. We conclude that for the majority of metabolites targeted by the used metabolomics platform, the familial resemblance of serum concentrations is largely genetic. Our results contribute to the knowledge of the heritability of fasting serum metabolite concentrations, which is relevant for biomarker research. PMID:23985338

  13. Exploring the Glycosylation of Serum CA125

    PubMed Central

    Saldova, Radka; Struwe, Weston B.; Wynne, Kieran; Elia, Giuliano; Duffy, Michael J.; Rudd, Pauline M.

    2013-01-01

    Ovarian cancer is the most lethal gynaecologic cancer affecting women. The most widely used biomarker for ovarian cancer, CA125, lacks sensitivity and specificity. Here, we explored differences in glycosylation of CA125 between serum from patients with ovarian cancer and healthy controls. We found differences between CA125 N-glycans from patient sera compared to controls. These include increases in core-fucosylated bi-antennary monosialylated glycans, as well as decreases in mostly bisecting bi-antennary and non-fucosylated glycans in patients compared to controls. Measurement of the glycosylated state of CA125 may therefore provide a more specific biomarker for patients with ovarian cancer. PMID:23896595

  14. Serum protein electrophoresis in spontaneous canine hyperadrenocorticalism.

    PubMed

    van den Broek, A H; Lida, J

    1989-01-01

    The serum protein concentrations of dogs with confirmed spontaneous hyperadrenocorticalism were determined by agarose gel electrophoresis before and during treatment with mitotane. In untreated animals a significant increase was detected in the mean concentration of total protein and the mean concentration and percentage of alpha-2 globulin. The mean concentration and percentage of albumin and gamma-globulin were significantly decreased. In animals on treatment the mean concentration of total proteins and the mean concentration and percentage of beta-2 globulin were significantly reduced. PMID:2466309

  15. Administration of antisomatotropin serum in diabetes mellitus.

    PubMed

    Góth, M; Szabolcs, I

    1981-03-01

    The effect of antisomatotropin serum (ASS), raised in horse against human growth hormone, on the carbohydrate metabolism of diabetics has been investigated. Among the eight diabetic patients treated so far two had GH secreting pituitary adenoma, two insulin-dependent, and four others adult onset diabetes mellitus. The glucose tolerance curve improved in all but one patient. The effect lasted for two--four weeks. Because of this short time of efficiency, the place of ASS in the definite treatment of diabetes mellitus cannot been judged so far, however, its administration in diabetic retinopathy seems to be advantageous. PMID:7227326

  16. The expression of transforming growth factor-beta by cultured chick growth plate chondrocytes: differential regulation by 1,25-dihydroxyvitamin D3.

    PubMed

    Farquharson, C; Law, A S; Seawright, E; Burt, D W; Whitehead, C C

    1996-05-01

    1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) and transforming growth factor-beta (TGF-beta) are both important regulators of chondrocyte growth and differentiation. We report here that 1,25(OH)2D3 differentially regulates the expression of the genes for TGF-beta 1 to -beta 3 and the secretion of the corresponding proteins in cultured chick chondrocytes. Confluent growth plate chondrocytes were serum-deprived and cultured in varying concentrations of 1,25(OH)2D3. Cells were assayed for TGF-beta mRNA and conditioned medium was assayed for TGF-beta activity and isoform composition. Active TGF-beta was only detected in 10(-8) M 1,25(OH)2D3-treated cultures (8.37 ng active TGF-beta/mg protein). There was a significant decrease in total (latent-active) TGF-beta activity in conditioned medium of 10(-12) M (23.4%; P < 0.05) and 10(-10) M (20.7%; P < 0.05) 1,25(OH)2D3-treated cultures but 10(-8) M 1,25(OH)2D3 significantly increased (30.9%; P < 0.01) TGF-beta activity. The amounts of TGF-beta 1, -beta 2 and -beta 3 isoforms produced were similar in control, 10(-10) or 10(-12) M 1,25(OH)2D3-treated cultures but the conditioned medium of 10(-8) M 1,25(OH)2D3-treated cultures contained significantly higher amounts of all three isoforms. Quantification of TGF-beta mRNA demonstrated differential control of TGF-beta gene expression with TGF-beta 1 and -beta 3 mRNA levels reduced by all concentrations of 1,25(OH)2D3 examined (10(-8), 10(-10) and 10(-12) M) whilst TGF-beta 2 mRNA concentrations were elevated. Our results indicated that 1,25(OH)2D3 regulates chick growth plate chondrocyte TGF-beta secretion and mRNA expression in a concentration-dependent and isoform-specific manner. This interaction may be important in the regulation of chondrocyte metabolism and endochondral bone growth. PMID:8708539

  17. Peritoneal solute transport rate as an independent risk factor for total and cardiovascular mortality in a population of peritoneal dialysis patients.

    PubMed

    Janda, Katarzyna; Krzanowski, Marcin; Dumnicka, Paulina; Kuśnierz-Cabala, Beata; Miarka, Przemysław; Sułowicz, Władysław

    2014-01-01

    The aim of the present study was to assess the influence of peritoneal permeability expressed as the dialysate-to-plasma ratio of creatinine (D/P Cr) on total and cardiovascular (CV) mortality in a population of peritoneal dialysis (PD) patients during a 6-year observation period. The study recruited 55 patients (mean age: 53 years) treated with PD for a median of 24 months. Hematology parameters and serum albumin were determined using routine methods. Tumor necrosis factor alpha (TNF-alpha) and transforming growth factor beta (TGF-beta1) were determined by high-sensitivity ELISA. Peritoneal transport characteristics were identified using D/P Cr reference values after a peritoneal equilibration test. During the 6-year observation period, 22 patients (40%) died, mostly from CV complications (77% of deaths). In multiple Cox regression, D/P Cr and dialysate volume at PD initiation predicted total [hazard ratio (HR): 1.57; p = 0.02; and HR: 1.20; p = 0.04 respectively] and CV mortality (HR: 1.65; p = 0.02; and HR: 1.23; p = 0.05 respectively) independent of age, dialysis therapy duration, serum albumin concentration, dialysis adequacy measures, TGF-beta1, and TNF-alpha. Additionally, TNF-alpha was independently associated with all-cause and CV mortality, and albumin, with all-cause mortality. Baseline D/P Cr was a strong independent marker of survival in PD patients. Baseline D/P Cr and dialysate volume were independent risk factors for total and CV mortality in the PD population and could be significant for assessing CV risk in this population. PMID:25338416

  18. Protective effects of melittin on transforming growth factor-{beta}1 injury to hepatocytes via anti-apoptotic mechanism

    SciTech Connect

    Lee, Woo-Ram; Park, Ji-Hyun; Kim, Kyung-Hyun; Park, Yoon-Yub; Han, Sang-Mi; Park, Kwan-kyu

    2011-10-15

    Melittin is a cationic, hemolytic peptide that is the main toxic component in the venom of the honey bee (Apis mellifera). Melittin has multiple effects, including anti-bacterial, anti-viral and anti-inflammatory, in various cell types. However, the anti-apoptotic mechanisms of melittin have not been fully elucidated in hepatocytes. Apoptosis contributes to liver inflammation and fibrosis. Knowledge of the apoptotic mechanisms is important to develop new and effective therapies for treatment of cirrhosis, portal hypertension, liver cancer, and other liver diseases. In the present study, we investigated the anti-apoptotic effect of melittin on transforming growth factor (TGF)-{beta}1-induced apoptosis in hepatocytes. TGF-{beta}1-treated hepatocytes were exposed to low doses (0.5 and 1 {mu}g/mL) and high dose (2 {mu}g/mL) of melittin. The low doses significantly protected these cells from DNA damage in TGF-{beta}1-induced apoptosis compared to the high dose. Also, melittin suppressed TGF-{beta}1-induced apoptotic activation of the Bcl-2 family and caspase family of proteins, which resulted in the inhibition of poly-ADP-ribose polymerase (PARP) cleavage. These results demonstrate that TGF-{beta}1 induces hepatocyte apoptosis and that an optimal dose of melittin exerts anti-apoptotic effects against TGF-{beta}1-induced injury to hepatocytes via the mitochondrial pathway. These results suggest that an optimal dose of melittin can serve to protect cells against TGF-{beta}1-mediated injury. - Highlights: > We investigated the anti-apoptotic effect of melittin on TGF-{beta}1-induced hepatocyte. > TGF-{beta}1 induces hepatocyte apoptosis. > TGF-{beta}1-treated hepatocytes were exposed to low doses and high dose of melittin. > Optimal dose of melittin exerts anti-apoptotic effects to hepatocytes.

  19. A Putatively Functional Haplotype in the Gene Encoding Transforming Growth Factor Beta-1 as a Potential Biomarker for Radiosensitivity

    SciTech Connect

    Schirmer, Markus A.; Brockmoeller, Juergen; Rave-Fraenk, Margret; Virsik, Patricia; Wilken, Barbara; Kuehnle, Elna; Campean, Radu; Hoffmann, Arne O.; Mueller, Katarina; Goetze, Robert G.; Neumann, Michael; Janke, Joerg H.; Nasser, Fatima; Wolff, Hendrik A.; Ghadimi, B. Michael; Schmidberger, Heinz; Hess, Clemens F.; Christiansen, Hans; Hille, Andrea

    2011-03-01

    Purpose: To determine whether genetic variability in TGFB1 is related to circulating transforming growth factor-{beta}1 (TGF-{beta}1) plasma concentrations after radiotherapy and to radiosensitivity of lymphoid cells. Patients and Methods: Transforming growth factor-{beta}1 plasma concentrations (n = 79) were measured in patients 1 year after radiotherapy and chromosomal aberrations (n = 71) ex vivo before therapy start. Furthermore, TGF-{beta}1 secretion and apoptosis were measured in isolated peripheral blood mononuclear cells of 55 healthy volunteers. These phenotypes were analyzed in relation to five germline polymorphisms in the 5' region of the TGFB1 gene. Because of high linkage disequilibrium, these five polymorphisms reflect frequent genetic variation in this region. A presumed impact of TGF-{beta}1 on DNA damage or repair was measured as micronucleus formation in 30 lymphoblastoid cell lines. Results: We identified a hypofunctional genetic haplotype termed H3 tagging the 5' region of the TGFB1 gene encoding TGF-{beta}1. H3 was associated with lower TGF-{beta}1 plasma concentrations in patients (p = 0.01) and reduced TGF-{beta}1 secretion in irradiated peripheral blood mononuclear cells (p = 0.003). Furthermore, cells with H3 were less prone to induction of chromosomal aberrations (p = 0.001) and apoptosis (p = 0.003) by irradiation. The hypothesis that high TGF-{beta}1 could sensitize cells to DNA damage was further supported by increased micronuclei formation in 30 lymphoblastoid cell lines when preincubated with TGF-{beta}1 before irradiation (p = 0.04). Conclusions: On the basis of TGF-{beta}1 plasma levels and radiation sensitivity of lymphoid cells, this study revealed a putatively hypofunctional TGFB1 haplotype. The significance of this haplotype and the suggested link between TGF-{beta}1 function and DNA integrity should be further explored in other cell types, as well as other experimental and clinical conditions.

  20. Modulation of tumor induction and progression of oncogenic K-ras-positive tumors in the presence of TGF- b1 haploinsufficiency.

    PubMed

    Pandey, Jyotsna; Umphress, Sarah M; Kang, Yang; Angdisen, Jerry; Naumova, Alena; Mercer, Kim L; Jacks, Tyler; Jakowlew, Sonia B

    2007-12-01

    Oncogenic K-ras is one of the most common genetic alterations in human lung adenocarcinomas. In addition, inactivation of clusters of tumor suppressor genes is required to bring about classical characteristics of cancer including angiogenesis as a prelude to invasion and metastasis. Transforming growth factor-beta (TGF-beta) 1 is a tumor suppressor gene that is implicated in lung cancer progression. Although in vitro studies have shown that TGF-beta1 and Ras pathways cooperate during tumorigenesis, the biology of interaction of TGF-beta1 and Ras has not been studied in in vivo tumorigenesis. We hypothesized that inactivation of TGF-beta1 in addition to oncogeneic activation of K-ras would lead to early initiation and faster progression to lung adenocarcinoma and invasion and metastasis. Heterozygous (HT) TGF-beta1 mice were mated with latent activatable (LA) mutated K-ras mice to generate TGF-beta1(+/+), K-ras LA (wild-type (WT)/LA) and TGF-beta1(+/-), K-ras LA (HT/LA) mice. Both HT/LA and WT/LA mice developed spontaneous lung tumors, but HT/LA mice progressed to adenocarcinomas significantly earlier compared with WT/LA mice. In addition, WT/LA adenocarcinomas had significantly higher angiogenic activity compared with HT/LA adenocarcinomas. Thus, while oncogenic K-ras mutation and insensitivity to the growth regulatory effects of TGF-beta1 is essential for initiation and progression of mouse lung tumors to adenocarcinoma, a full gene dosage of TGF-beta1 is required for tumor-induced angiogenesis and invasive potential. This study identifies a number of genes not previously associated with lung cancer that are involved in tumor induction and progression. In addition, we provide evidence that progression to invasive angiogenic lesions requires TGF-beta1 responsiveness in addition to Ras mutation. PMID:17690114

  1. N-acetylcysteine inhibits alveolar epithelial-mesenchymal transition.

    PubMed

    Felton, V M; Borok, Z; Willis, B C

    2009-11-01

    The ability of transforming growth factor-beta1 (TGF-beta1) to induce epithelial-mesenchymal transition (EMT) in alveolar epithelial cells (AEC) in vitro and in vivo, together with the demonstration of EMT in biopsies of idiopathic pulmonary fibrosis (IPF) patients, suggests a role for TGF-beta1-induced EMT in disease pathogenesis. We investigated the effects of N-acetylcysteine (NAC) on TGF-beta1-induced EMT in a rat epithelial cell line (RLE-6TN) and in primary rat alveolar epithelial cells (AEC). RLE-6TN cells exposed to TGF-beta1 for 5 days underwent EMT as evidenced by acquisition of a fibroblast-like morphology, downregulation of the epithelial-specific protein zonula occludens-1, and induction of the mesenchymal-specific proteins alpha-smooth muscle actin (alpha-SMA) and vimentin. These changes were inhibited by NAC, which also prevented Smad3 phosphorylation. Similarly, primary alveolar epithelial type II cells exposed to TGF-beta1 also underwent EMT that was prevented by NAC. TGF-beta1 decreased cellular GSH levels by 50-80%, whereas NAC restored them to approximately 150% of those found in TGF-beta1-treated cells. Treatment with glutathione monoethyl ester similarly prevented an increase in mesenchymal marker expression. Consistent with its role as an antioxidant and cellular redox stabilizer, NAC dramatically reduced intracellular reactive oxygen species production in the presence of TGF-beta1. Finally, inhibition of intracellular ROS generation during TGF-beta1 treatment prevented alveolar EMT, but treatment with H2O2 alone did not induce EMT. We conclude that NAC prevents EMT in AEC in vitro, at least in part through replenishment of intracellular GSH stores and limitation of TGF-beta1-induced intracellular ROS generation. We speculate that beneficial effects of NAC on pulmonary function in IPF may be mediated by inhibitory effects on alveolar EMT. PMID:19648289

  2. Transforming growth factor-beta2 induces bronchial epithelial mucin expression in asthma.

    PubMed

    Chu, Hong Wei; Balzar, Silvana; Seedorf, Gregory J; Westcott, Jay Y; Trudeau, John B; Silkoff, Phil; Wenzel, Sally E

    2004-10-01

    The transforming growth factor (TGF)-beta family is important for tissue repair in pathological conditions including asthma. However, little is known about the impact of either TGF-beta1 or TGF-beta2 on asthmatic airway epithelial mucin expression. We evaluated bronchial epithelial TGF-beta1 and TGF-beta2 expression and their effects on mucin expression, and the role of TGF-beta1 or TGF-beta2 in interleukin (IL)-13-induced mucin expression. Epithelial TGF-beta1, TGF-beta2, and mucin expression were evaluated in endobronchial biopsies from asthmatics and normal subjects. The effects of TGF-beta1 or TGF-beta2 on mucin MUC5AC protein and mRNA expression, and the impact of IL-13 on epithelial TGF-beta1, TGF-beta2, and MUC5AC were determined in cultured bronchial epithelial cells from endobronchial brushings of both subject groups. In biopsy tissue, epithelial TGF-beta2 expression levels were higher than TGF-beta1 in both asthmatics and normals. TGF-beta2, but not TGF-beta1, was increased in asthmatics compared with normals, and significantly correlated with mucin expression. TGF-beta2, but not TGF-beta1, increased mucin expression in cultured epithelial cells from both subject groups. IL-13 increased the release of TGF-beta2, but not TGF-beta1, from epithelial cells. A neutralizing TGF-beta2 antibody partially inhibited IL-13-induced mucin expression. These data suggest that TGF-beta2 production by asthmatic bronchial epithelial cells may increase airway mucin expression. IL-13-induced mucin expression may occur in part through TGF-beta2 up-regulation. PMID:15466377

  3. Differential Gene Expression in Adipose Stem Cells Cultured in Allogeneic Human Serum Versus Fetal Bovine Serum

    PubMed Central

    Aho, Kaisa-Leena; Kuokkanen, Hannu; Räty, Sari; Huhtala, Heini; Lemponen, Riina; Yli-Harja, Olli; Suuronen, Riitta; Miettinen, Susanna

    2010-01-01

    In preclinical studies, human adipose stem cells (ASCs) have been shown to have therapeutic applicability, but standard expansion methods for clinical applications remain yet to be established. ASCs are typically expanded in the medium containing fetal bovine serum (FBS). However, sera and other animal-derived culture reagents stage safety issues in clinical therapy, including possible infections and severe immune reactions. By expanding ASCs in the medium containing human serum (HS), the problem can be eliminated. To define how allogeneic HS (alloHS) performs in ASC expansion compared to FBS, a comparative in vitro study in both serum supplements was performed. The choice of serum had a significant effect on ASCs. First, to reach cell proliferation levels comparable with 10% FBS, at least 15% alloHS was required. Second, while genes of the cell cycle pathway were overexpressed in alloHS, genes of the bone morphogenetic protein receptor–mediated signaling on the transforming growth factor beta signaling pathway regulating, for example, osteoblast differentiation, were overexpressed in FBS. The result was further supported by differentiation analysis, where early osteogenic differentiation was significantly enhanced in FBS. The data presented here underscore the importance of thorough investigation of ASCs for utilization in cell therapies. This study is a step forward in the understanding of these potential cells. PMID:20184435

  4. [Serum procalcitonin and respiratory tract infections].

    PubMed

    Zarka, V; Valat, C; Lemarié, E; Boissinot, E; Carré, P; Besnard, J C; Diot, P

    1999-12-01

    The aim of our study was to evaluate the prognostic value of serum procalcitonine (PCT) assay in adult respiratory infections. Forty-nine patients admitted with pleurisy, community-acquired pneumonia, tuberculosis, infection were included in this prospective study. PCT was assayed on admission and discharge. Biological and clinical parameters of gravity were also evaluated. Twenty patients had elevated PCT of more than 0.50 ng/ml. In 29 patients, PCT was undetectable. The serum PCT level was normal in the patients with tuberculosis, infection, pneumocytosis. PCT did not correlate with the biological and clinical markers of the disease severity but the evolution of PCT correlated with the evolution of C-reactive-protein (r = 0.58, p < 0.05). PCT seems to be an early marker of the evolution of respiratory infections, but it does not help to establish prognosis. Further studies are necessary to assess the potential value of PCT in more severe respiratory infections requiring assisted ventilation. PMID:10685471

  5. An Initial Characterization of the Serum Phosphoproteome

    PubMed Central

    Zhou, Weidong; Ross, Mark M.; Tessitore, Alessandra; Ornstein, David; VanMeter, Amy; Liotta, Lance A.; Petricoin, Emanuel F.

    2009-01-01

    Phosphorylation is a dynamic post-translational protein modification that is the basis of a general mechanism for maintaining and regulating protein structure and function, and of course underpins key cellular processes through signal transduction. In the last several years, many studies of large-scale profiling of phosphoproteins and mapping phosphorylation sites from cultured human cells or tissues by mass spectrometry technique have been published; however, there is little information on general (or global) phosphoproteomic characterization and description of the content of phosphoprotein analytes within the circulation. Circulating phosphoproteins and phosphopeptides could represent important disease biomarkers because of their well-known importance in cellular function, and these analytes frequently are mutated and activated in human diseases such as cancer. Here we report an initial attempt to characterize the phosphoprotein content of serum. To accomplish this, we developed a method in which phosphopeptides are enriched from digested serum proteins and analyzed by LC-MS/MS using LTQ-Orbitrap (CID) and LTQ-ETD mass spectrometers. Using this approach we identified ~100 unique phosphopeptides with stringent filtering criteria and a lower than 1% false discovery rate. PMID:19824718

  6. Evaluation of three gentamicin serum assay techniques

    SciTech Connect

    Matzke, G.R.; Gwizdala, C.; Wery, J.; Ferry, D.; Starnes, R.

    1982-01-01

    This investigation was designed to compare the enzyme-modified immunoassay (Syva--EMIT) with a radioimmunoassay (New England Nuclear--RIA) and the radiometric assay (Johnston--BACTEC) to determine the optimal assay for use in our aminoglycoside dosing service. The serum concentration determinations obtained via the three assay methods were analyzed by linear regression analysis. Significant positive correlations were noted between the three assay techniques (p less than 0.005) during both sample collection phases. The coefficients of determination for EMIT vs BACTEC and RIA vs BACTEC were 0.73 and 0.83 during phase 1, respectively, and 0.65 and 0.68 during phase 2, respectively. The slope of the regression lines also varied markedly during the two phases; 0.49 and 0.42 for EMIT and for RIA vs BACTEC, respectively, during phase 1 compound with 1.12 and 0.77, respectively, during phase 2. The differences noted in these relationships during phase 1 and 2 may be related to the alteration of the pH of the control sera utilized in the BACTEC assay. In contrast, RIA vs EMIT regression analysis indicated that existence of a highly significant relationship (p less than 0.0005 and r2 . 0.90). The EMIT technique was the easiest and most accurate for determination of serum gentamicin concentrations, whereas the BACTEC method was judged unacceptable for clinical use.

  7. Interaction of Citrinin with Human Serum Albumin

    PubMed Central

    Poór, Miklós; Lemli, Beáta; Bálint, Mónika; Hetényi, Csaba; Sali, Nikolett; Kőszegi, Tamás; Kunsági-Máté, Sándor

    2015-01-01

    Citrinin (CIT) is a mycotoxin produced by several Aspergillus, Penicillium, and Monascus species. CIT occurs worldwide in different foods and drinks and causes health problems for humans and animals. Human serum albumin (HSA) is the most abundant plasma protein in human circulation. Albumin forms stable complexes with many drugs and xenobiotics; therefore, HSA commonly plays important role in the pharmacokinetics or toxicokinetics of numerous compounds. However, the interaction of CIT with HSA is poorly characterized yet. In this study, the complex formation of CIT with HSA was investigated using fluorescence spectroscopy and ultrafiltration techniques. For the deeper understanding of the interaction, thermodynamic, and molecular modeling studies were performed as well. Our results suggest that CIT forms stable complex with HSA (logK ~ 5.3) and its primary binding site is located in subdomain IIA (Sudlow’s Site I). In vitro cell experiments also recommend that CIT-HSA interaction may have biological relevance. Finally, the complex formations of CIT with bovine, porcine, and rat serum albumin were investigated, in order to test the potential species differences of CIT-albumin interactions. PMID:26633504

  8. Serum fibroblast growth factor 23, serum iron and bone mineral density in premenopausal women.

    PubMed

    Imel, Erik A; Liu, Ziyue; McQueen, Amie K; Acton, Dena; Acton, Anthony; Padgett, Leah R; Peacock, Munro; Econs, Michael J

    2016-05-01

    Fibroblast growth factor 23 (FGF23) circulates as active protein and inactive fragments. Low iron status increases FGF23 gene expression, and iron deficiency is common. We hypothesized that in healthy premenopausal women, serum iron influences C-terminal and intact FGF23 concentrations, and that iron and FGF23 associate with bone mineral density (BMD). Serum iron, iron binding capacity, percent iron saturation, phosphorus, and other biochemistries were measured in stored fasting samples from healthy premenopausal white (n=1898) and black women (n=994), age 20-55years. Serum C-terminal and intact FGF23 were measured in a subset (1631 white and 296 black women). BMD was measured at the lumbar spine and femur neck. Serum phosphorus, calcium, alkaline phosphatase and creatinine were lower in white women than black women (p<0.001). Serum iron (p<0.0001) and intact FGF23 (p<0.01) were higher in white women. C-terminal FGF23 did not differ between races. Phosphorus correlated with intact FGF23 (white women, r=0.120, p<0.0001; black women r=0.163, p<0.01). However, phosphorus correlated with C-terminal FGF23 only in black women (r=0.157, p<0.01). Intact FGF23 did not correlate with iron. C-terminal FGF23 correlated inversely with iron (white women r=-0.134, p<0.0001; black women r=-0.188, p<0.01), having a steeper slope at iron <50mcg/dl than ≥50mcg/dl. Longitudinal changes in iron predicted changes in C-terminal FGF23. Spine BMD correlated with iron negatively (r=-0.076, p<0.01) in white women; femur neck BMD correlated with iron negatively (r=-0.119, p<0.0001) in black women. Both relationships were eliminated in weight-adjusted models. BMD did not correlate with FGF23. Serum iron did not relate to intact FGF23, but was inversely related to C-terminal FGF23. Intact FGF23 correlated with serum phosphorus. In weight-adjusted models, BMD was not related to intact FGF23, C-terminal FGF23 or iron. The influence of iron on FGF23 gene expression is not important in

  9. Relationship of serum uric acid, serum creatinine and serum cystatin C with maternal and fetal outcomes in rural Indian pregnant women

    PubMed Central

    Yalamati, Padma; Bhongir, Aparna Varma; Betha, Kalpana; Verma, Ritika; Dandge, Shailendra

    2015-01-01

    Background Hypertensive disorders are the most common in pregnancy. Several studies showed a positive correlation between elevated maternal serum uric acid (UA), serum creatinine and adverse maternal and fetal outcomes, but only a few studies are available on serum cystatin C and maternal and fetal outcomes. The present study was undertaken to study the association of serum UA, creatinine and cystatin C with maternal and fetal outcomes. Methods Out of 116 pregnant women 69 women had no hypertension and 47 had hypertension with or without proteinuria. Serum UA, creatinine and cystatin C was measured by modified Uricase method, modified kinetic Jaffe’s reaction and particle-enhanced immunonephelometric assay respectively. Multivariate logistic regression was performed to determine the independent effects of serum UA, creatinine and cystatin C on maternal and fetal outcomes using stata 13.1. Results The adjusted odds ratio (OR) was 3.73 (95% CI: 1.18-11.75; P=0.024) for UA; 15.79 (95% CI: 3.04-81.94; P=0.001) for creatinine and 2.03 (95% CI: 0.70-5.87; P=0.192) for cystatin C in hypertensive disorders of pregnancy. All the three renal parameters were not significantly associated with birth weight, gestational age of delivery and mode of delivery after adjusting for the confounding factors. Conclusions Serum creatinine and uric acid are independent risk factors for hypertensive disorders of pregnancy. High serum uric acid is associated with low birth weight and delivery by caesarian section whereas high serum creatinine with preterm delivery only before adjustment for confounding factors and not after adjustment. Serum cystatin C was not significantly associated with the maternal and fetal outcomes. PMID:26583159

  10. Studies on serum requirements for the cultivation of Plasmodium falciparum

    PubMed Central

    Divo, A. A.; Jensen, J. B.

    1982-01-01

    Previous experiments using RPMI 1640 medium have indicated that the dialysis of human serum removes components of low relative molecular mass (6000-8000 RMM) that are essential for continuous cultivation of Plasmodium falciparum. To determine which low-RMM components are important for parasite development, we compared growth in normal serum to that in dialysed serum using a number of other commercially available media, which we considered to be richer than RPMI 1640. Through these comparisons, we determined that hypoxanthine was the major dialysable nutrient required for parasite development. High quality bovine serum requires 3 - 12 × 10-5 mol/litre of hypoxanthine as a supplement to support continuous cultures of P. falciparum. Thus far we have been unable to attain parasite growth in medium containing supplemented bovine serum that is as good as growth in medium containing human serum. PMID:6754122

  11. Cartilage extracellular matrix metabolism differs in serum and synovial fluid.

    PubMed

    Martin, James A; Wilkey, Andrew L; Brand, Richard A

    2002-01-01

    Most cartilage explant culture studies assume conventional serum-supplemented growth media are biologically equivalent to the natural synovial fluid which baths cartilage in vivo. Few studies have systematically compared the effects of serum versus synovial fluid in culture. To address this assumption we conducted a series of studies to determine if cartilage matrix synthesis is significantly different in serum-based versus synovial fluid-based media. Normal bovine cartilage explants were cultured in DMEM either alone or supplemented with bovine serum or bovine synovial fluid. Matrix synthesis was measured with radiolabeling techniques. We then compared responses to insulin-like growth factor I (IGF-I, a stimulator of matrix synthesis), and interleukin-1beta (IL-1beta, an inhibitor of matrix synthesis). We observed significantly lower matrix synthesis activity in synovial fluid versus serum. Caution shoud be used in extrapolating studies of cartilage grown in media supplemented with serum rather than synovial fluid. PMID:12843702

  12. Serum eye drop preparation in Australia: Current manufacturing practice.

    PubMed

    Marks, Denese C; Fisher, Jenny; Mondy, Phillip; Segatchian, Jerard; Dennington, Peta M

    2015-08-01

    Serum eye drops are used to treat diseases such as dry eye syndrome (keratoconjunctivitis sicca), a disease of the surface of the eye that results in an unstable tear film. Patients are referred to the Australian Red Cross Blood Service by ophthalmologists for autologous serum eye drops when other therapies such as artificial tears or topical immunosuppressive agents have failed. In order to manufacture autologous serum eye drops, whole blood is collected from the patients using standard blood collection procedures. The blood is then allowed to clot to produce serum and processed into 20% serum eye drops, which are then returned to the patient for their own use. The eye drops are packaged into a long length of tubing, which is then heat-sealed to produce single-use segments. The demand for serum eye drops in Australia is increasing every year, with a 30% increase in the past 12 months. PMID:26123029

  13. Relation of serum uric acid to cardiovascular disease.

    PubMed

    Wu, Audrey H; Gladden, James D; Ahmed, Mustafa; Ahmed, Ali; Filippatos, Gerasimos

    2016-06-15

    This review summarizes recent published literature on the association between serum uric acid and cardiovascular disease, a relationship which is complex and not fully elucidated. Uric acid may be a marker for risk, a causative agent in cardiovascular disease, or both. Various biologic factors can influence serum uric acid levels, and serum uric acid level itself is closely related to conditions such as hypertension, dyslipidemia, obesity, and impaired glucose metabolism, that contribute to cardiovascular disease pathophysiology. Serum uric acid levels have been found to be associated with adverse outcomes, including mortality, in the general population. In addition, serum uric acid is associated with increased risk for incident coronary heart disease, heart failure, and atrial fibrillation. In the setting of established systolic heart failure, serum uric acid is positively associated with disease severity and mortality risk. Whether targeting treatment based on uric acid levels might affect clinical outcomes is still being studied. PMID:26341316

  14. Superovulation in the cow with pregnant mare serum gonadotrophin: effects of dose and antipregnant mare serum gonadotrophin serum.

    PubMed Central

    Gonzalez, A; Wang, H; Carruthers, T D; Murphy, B D; Mapletoft, R J

    1994-01-01

    The effects of pregnant mare serum gonadotrophin (PMSG) dose and PMSG antiserum on superovulation in crossbred beef cows were studied. In experiment I, three groups were treated with 1200, 2400 or 3600 IU of PMSG and 48 h later with prostaglandin (PGF). The mean numbers of corpora lutea (CL), unovulated follicles, and total ova/embryos collected increased as the PMSG dose increased. The percent of fertilized ova and transferable embryos was lowest in the highest dose group (p < 0.05). In experiment II, all cows received 2500 IU of PMSG; groups 1 and 2 were treated with sheep anti-PMSG serum at 48 h or 60 h after PGF; group 3 cows were PMSG-only controls. The number of CL was lowest and the number of unovulated follicles highest in the PMSG-only group (p < 0.05). The number of CL was higher in group 2 (anti-PMSG at 60 h) than in the control group, with the anti-PMSG at 48 h not different from the other groups. Numbers of total ova/embryos, fertilized ova, and transferable embryos were higher (p < 0.05) in both antiserum-treated groups relative to the PMSG-only group. We conclude that superovulation of beef cows with PMSG and treatment with PMSG antiserum will induce a higher superovulatory response and will result in higher CL numbers and fewer unovulated follicles. Further, the variability in the superovulatory response to PMSG treatment was still evident when PMSG antiserum was administered. PMID:8055430

  15. Farm Animal Serum Proteomics and Impact on Human Health

    PubMed Central

    Girolamo, Francesco Di; D’Amato, Alfonsina; Lante, Isabella; Signore, Fabrizio; Muraca, Marta; Putignani, Lorenza

    2014-01-01

    Due to the incompleteness of animal genome sequencing, the analysis and characterization of serum proteomes of most farm animals are still in their infancy, compared to the already well-documented human serum proteome. This review focuses on the implications of the farm animal serum proteomics in order to identify novel biomarkers for animal welfare, early diagnosis, prognosis and monitoring of infectious disease treatment, and develop new vaccines, aiming at determining the reciprocal benefits for humans and animals. PMID:25257521

  16. Resistance of Gardnerella vaginalis to bactericidal activity of human serum.

    PubMed Central

    Boustouller, Y L; Johnson, A P

    1986-01-01

    To assess the sensitivity of Gardnerella vaginalis to the complement mediated bactericidal activity of serum, six laboratory strains were incubated with normal human serum and two strains freshly isolated from women with non-specific vaginitis (NSV) were each incubated with homologous patient serum. There was no significant difference between the number of organisms recovered from unheated or heat inactivated serum after incubation at 37 degrees C for one hour with any of the strains tested. A suspension of G vaginalis incubated at 37 degrees C for one hour in heat inactivated homologous mouse antiserum with unheated normal human serum as a source of complement did not show any less viability than the control mixture using heat inactivated human serum. In contrast, a serum resistant strain of Neisseria gonorrhoeae incubated in heat inactivated homologous mouse antiserum with unheated normal human serum showed noticeably less viability than the control. G vaginalis therefore seems to be resistant to the bactericidal activity of both normal and immune serum. PMID:3493201

  17. Specific Antigen in Serum of Patients with Colon Carcinoma

    NASA Astrophysics Data System (ADS)

    Koprowski, Hilary; Herlyn, Meenhard; Steplewski, Zenon; Sears, Henry F.

    1981-04-01

    The binding of monoclonal antibody specific for colon carcinoma was inhibited by serum from patients with adenocarcinoma of the colon but not by serum from patients with other bowel diseases or from healthy volunteers. Of other malignancies studied, serum from two patients with gastric carcinoma and two patients with pancreatic carcinoma also inhibited the specific binding of monoclonal antibody. The levels of carcinoembryonic antigen in these serum samples were not correlated with their levels of binding inhibition. Such monoclonal antibodies may prove useful for the detection of colorectal carcinoma.

  18. Serum Endocan Levels in Children with Febrile Neutropenia

    PubMed Central

    Kiral, Eylem; Bozkurt-Turhan, Ayse; Bor, Ozcan; Akgun, Yurdanur; Akgun, Necat Akdeniz

    2016-01-01

    Endocan is an endotelial cell specific molecule; previous studies have shown that serum endocan levels increased in cancer and sepsis and are also related to the severity of sepsis. There are no clinical study about serum endocan levels in children with febrile neutropenia. The aim of this study was to evaluate serum endocan levels in pediatric leukemia patients with febrile neutropenia (n=33) and compare them with children with leukemia without fever (n=33) and also with healthy children (n=24). The median serum endocan level in the first group (children with febrile neutropenia) was statistically significantly higher compared to the leukemic children without febrile neutropenia and also control group (P<0.01 for both). No difference was determined between the serum endocan levels of the leukaemia patients without febrile neutropenia and the healthy control group (P>0.05). Serum endocan levels were also similar with febrile neutropenia due to bacterial causes comparing with the idiopathic febril neutropenia. The results of this study showed increased serum endocan in children with leukemia during the febrile neutropenia episode, and no changes of serum endocan levels in children without leukemia without infection/fever. The monitoring of a series of serum endocan levels would be helpful for the course of febrile neutropenia. PMID:27103976

  19. Schistosoma mansoni: modulation of schistosomular lipid composition by serum.

    PubMed

    Rumjanek, F D; McLaren, D J

    1981-08-01

    Human serum and foetal calf serum have been compared in terms of their ability to modify the biochemical and immunological properties of the schistosomular surface. Artificially transformed schistosomula were incubated in the presence of serum for 24 h and then radioiodinated using the chloramine T method. With this method only lipids are labelled. Foetal calf serum produces a net loss of lipids from the schistosomula, particularly of mono- and diglycerides. Human serum however, promotes not only a loss of mono- and diglycerides, but also a substantial uptake of cholesterol and triglycerides. Schistosomula recovered from the lungs of mice could also be labelled and contained besides triglycerides, an increased amount of cholesterol esters. The modulation of surface lipids in worms cultured with human serum correlates with the observation that such schistosomula develop significantly greater protection against eosinophil-mediated cytotoxicity in vitro than do individuals incubated with foetal calf serum. On the other hand, schistosomula cultured in the presence of either human serum or foetal calf serum develop the same degree of protection against complement-dependent lethal antibody; this result indicates that resistance against complement-mediated damage may be independent of the uptake of cholesterol and/or triglycerides, and might involve only limited alterations in the surface configuration of the schistosomulum. PMID:7278882

  20. Polymerized soluble venom--human serum albumin

    SciTech Connect

    Patterson, R.; Suszko, I.M.; Grammer, L.C.

    1985-03-01

    Extensive previous studies have demonstrated that attempts to produce polymers of Hymenoptera venoms for human immunotherapy resulted in insoluble precipitates that could be injected with safety but with very limited immunogenicity in allergic patients. We now report soluble polymers prepared by conjugating bee venom with human serum albumin with glutaraldehyde. The bee venom-albumin polymer (BVAP) preparation was fractionated on Sephacryl S-300 to have a molecular weight range higher than catalase. /sup 125/I-labeled bee venom phospholipase A was almost completely incorporated into BVAP. Rabbit antibody responses to bee venom and bee venom phospholipase A were induced by BVAP. Human antisera against bee venom were absorbed by BVAP. No new antigenic determinants on BVAP were present as evidenced by absorption of antisera against BVAP by bee venom and albumin. BVAP has potential immunotherapeutic value in patients with anaphylactic sensitivity to bee venom.

  1. Total Antioxidant Capacity of Serum Determined Using the Potassium Permanganate Agar Method Based on Serum Diffusion in Agar.

    PubMed

    Zhou, Ying; Zhang, Meijuan; Liu, Hui

    2015-01-01

    Objectives. To develop a new method for determining total antioxidants in serum and to evaluate the total antioxidant capacity of organisms. Design and Methods. Sodium hyposulfite (Na2S2O3) and serum were used to evaluate the linearity and precision of the potassium permanganate agar method. The area of serum diffusion in samples from 30 intensive care unit (ICU) patients compared with 44 healthy subjects was determined by the potassium permanganate agar method. Results. The linearity (R (2) in the linear experiment of Na2S2O3 was 0.994; R (2) in the linear experiment of serum was 0.987) and precision (coefficient of variation of area of high level serum diffusion within-run, between-run, and between-day and coefficient of variation of area of low serum diffusion within-run, between-run, and between-day were all less than 10%) were acceptable using the potassium permanganate agar method. Total antioxidants of serum between the ICU group and the healthy group were different (p = 0.002, two tailed). Conclusions. Total antioxidants in serum can be determined by the potassium permanganate agar method. The total antioxidant capacity of an organism can be evaluated by the amount of total antioxidants in serum. PMID:26347595

  2. Total Antioxidant Capacity of Serum Determined Using the Potassium Permanganate Agar Method Based on Serum Diffusion in Agar

    PubMed Central

    Zhou, Ying; Zhang, Meijuan; Liu, Hui

    2015-01-01

    Objectives. To develop a new method for determining total antioxidants in serum and to evaluate the total antioxidant capacity of organisms. Design and Methods. Sodium hyposulfite (Na2S2O3) and serum were used to evaluate the linearity and precision of the potassium permanganate agar method. The area of serum diffusion in samples from 30 intensive care unit (ICU) patients compared with 44 healthy subjects was determined by the potassium permanganate agar method. Results. The linearity (R2 in the linear experiment of Na2S2O3 was 0.994; R2 in the linear experiment of serum was 0.987) and precision (coefficient of variation of area of high level serum diffusion within-run, between-run, and between-day and coefficient of variation of area of low serum diffusion within-run, between-run, and between-day were all less than 10%) were acceptable using the potassium permanganate agar method. Total antioxidants of serum between the ICU group and the healthy group were different (p = 0.002, two tailed). Conclusions. Total antioxidants in serum can be determined by the potassium permanganate agar method. The total antioxidant capacity of an organism can be evaluated by the amount of total antioxidants in serum. PMID:26347595

  3. Value of serum marker HE4 in pulmonary carcinoma diagnosis.

    PubMed

    Tang, Qin-Fang; Zhou, Zhong-Wei; Ji, Hong-Bing; Pan, Wu-Hua; Sun, Ming-Zhong

    2015-01-01

    An effective blood test is valuable to aid clinicians in making case management decisions. The present study was to analyze the value of four serum tumor markers for the diagnosis of pulmonary carcinoma. The case group consisted of 80 pulmonary carcinoma patients, which were compared to a control group of 30 patients with benign pulmonary disease and a control group of 30 healthy individuals. Serum levels of carcinoma embryonic antigen (CEA), cytokeratin protein fragment 21-1 (CYFRA21-1), neuron-specific enolase (NSE), and human epididymis protein 4 (HE4) were detected using electrochemiluminescence. Serum CEA, NSE, CYFRA21-1, and HE4 levels were significantly higher in pulmonary carcinoma patients than those in both control groups (P < 0.05). Serum CEA and HE4 levels were significantly higher in adenocarcinoma patients, while serum CYFRA21-1 levels were significantly higher in squamous cell carcinoma patients and serum NSE levels were significantly higher in small cell lung cancer (SCLC) patients (P < 0.05). Analysis of area-under-the-receiver operating characteristic (ROC) curves (AUC) revealed that serum CYFRA21-1, CEA, and HE4 levels were valuable for squamous cell carcinoma, serum CEA and HE4 levels were valuable for adenocarcinoma, and serum NSE level was valuable for SCLC (P < 0.05). Serum CEA and HE4 levels of pulmonary carcinoma patients with metastasis were higher than those with TNM stage I-II or III-IV disease without metastasis. In brief, detection of serum HE4 levels may be useful in auxiliary diagnosis and evaluation of the progression of pulmonary carcinoma. PMID:26770527

  4. Value of serum marker HE4 in pulmonary carcinoma diagnosis

    PubMed Central

    Tang, Qin-Fang; Zhou, Zhong-Wei; Ji, Hong-Bing; Pan, Wu-Hua; Sun, Ming-Zhong

    2015-01-01

    An effective blood test is valuable to aid clinicians in making case management decisions. The present study was to analyze the value of four serum tumor markers for the diagnosis of pulmonary carcinoma. The case group consisted of 80 pulmonary carcinoma patients, which were compared to a control group of 30 patients with benign pulmonary disease and a control group of 30 healthy individuals. Serum levels of carcinoma embryonic antigen (CEA), cytokeratin protein fragment 21-1 (CYFRA21-1), neuron-specific enolase (NSE), and human epididymis protein 4 (HE4) were detected using electrochemiluminescence. Serum CEA, NSE, CYFRA21-1, and HE4 levels were significantly higher in pulmonary carcinoma patients than those in both control groups (P < 0.05). Serum CEA and HE4 levels were significantly higher in adenocarcinoma patients, while serum CYFRA21-1 levels were significantly higher in squamous cell carcinoma patients and serum NSE levels were significantly higher in small cell lung cancer (SCLC) patients (P < 0.05). Analysis of area-under-the-receiver operating characteristic (ROC) curves (AUC) revealed that serum CYFRA21-1, CEA, and HE4 levels were valuable for squamous cell carcinoma, serum CEA and HE4 levels were valuable for adenocarcinoma, and serum NSE level was valuable for SCLC (P < 0.05). Serum CEA and HE4 levels of pulmonary carcinoma patients with metastasis were higher than those with TNM stage I-II or III-IV disease without metastasis. In brief, detection of serum HE4 levels may be useful in auxiliary diagnosis and evaluation of the progression of pulmonary carcinoma. PMID:26770527

  5. [Inhibitory effect of Panax notoginseng saponins on alveolar epithelial to mesenchymal transition].

    PubMed

    Ren, Zhou-xin; Yu, Hai-bin; Li, Jian-sheng; Shen, Jun-ling; Li, Jun-kai; Luo, Shan

    2015-12-01

    In the study, the effects of Panax notoginseng saponins (PNS) on alveolar epithelial to mesenchymal transition (EMT) and extracellular matrix degradation were observed in a type of human alveolar epithelial cell, A549 cells, stimulated by TGF-beta1. Firstly, MTT method was applied to evaluation of cellular proliferation and found that PNS from 12.5 mg x L(-1) to 200 mg x L(-1) dosage could not inhibit significantly cellular proliferation. Then, cells were divided into five groups, normal group, TGF-beta1 group, TGF-beta1 + 50 mg x L(-1) PNS group, TGF-beta1 + 100 mg x L(-1) PNS group and TGF-beta1 + 200 mg x L(-1) PNS group. Normal cells were not stimulatec by TGF-beta1; TGF-beta1 cells were only stimulated by TGF-beta1 and the other cells were stimulated by TGF-beta1 with different doses of PNS, respectively. After stimulation, cells and supernatants were collected for assays. Cellular roundness was applied to quantitative evaluation of morphological change. Immunocytochemistry was applied to examine E-cadherion, a-SMA and FN proteins expression in the cells. Enzyme linked-immunosorbent assay was applied to MMP-9 and TIMP-1 levels. The results showed that EMT of A549 cells was induced by TGF-beta1, showing significant change of roundness, E-cadherion, alpha-SMA and FN (P < 0.05, P < 0.01). Compared to TGF-beta1, PNS significantly inhibited the changes of roundness (P < 0.05), FN and alpha-SMA (P < 0.05, P < 0.01) and not significantly inhibited the change of E-cadherion. Furthermore, MMP-9 levels were significantly increased by TGFbeta1 stimulation (P < 0.05), without significant change of TIMP-1. Compared with TGF-beta1, PNS could significantly increase MMP-9 level (P < 0.05) and decrease TIMP-1 levels (P < 0.05, P < 0.01). In conclusion, PNS could inhibit alveolar epithelial cell EMT induced by TGF-beta1, with increase of extracellular matrix degradation ability, which showed anti-fibrosis of lung ability. PMID:27141681

  6. Serum cytokeratin 19 fragment in advanced lung cancer: could we eventually have a serum tumor marker?

    PubMed Central

    Bastawisy, Ahmed El; azzouny, Mahmoud El; Mohammed, Gamal; allah, Ahmad Awad; Behiry, Eman

    2014-01-01

    Introduction: Lung cancer is one of the most lethal malignancies; however, no serum marker has been routinely recommended until now. Methods: This is a prospective case control study including two groups of patients: Group I—patients with advanced lung cancer and Group II—patients with benign lung disease as control. Serum cytokeratin 19 (CK19) fragment levels were measured at baseline by real-time polymerase chain reaction before first-line chemotherapy. The CK19 cut-off taken was 15-cycle threshold. The primary end point was the comparison of high CK19 in cases and controls. The secondary end point was the correlation between high CK19 and progressive disease (PD), progression-free survival, and overall survival (OS) in advanced lung cancer patients. Results: A total of 30 patients with advanced lung cancer (16 non-small and 14 small cell lung cancer) and 15 patients with benign lung disease were included and followed up during the period from October 2008 to October 2011 with median follow-up of one and half years. High CK19 was found in 90% of lung cancer cases as compared with 7% in controls (p < 0.001). High CK19 was found in all cases showing PD (p = 0.04). One-year OS in high CK was 61% as compared with 33% in normal CK (p = 0.1). Conclusion: Serum CK19 fragment is a potential diagnostic and prognostic marker for advanced lung cancer. PMID:24567753

  7. Cotinine levels in serum and bronchoalveolar lavage fluid.

    PubMed

    Diken, Ozlem Erçen; Unculu, Serap; Karnak, Demet; Cağlayan, Osman; Göçmen, Julide Sedef; Kayacan, Oya

    2010-09-01

    Cotinine is a major metabolite of nicotine. This study was planned to investigate the relationship between bronchoalveolar lavage (BAL) fluid cotinine levels and serum cotinine levels in smokers and nonsmokers with various pulmonary diseases and to investigate whether these levels are affected by passive smoking. Serum and BAL fluid cotinine levels were measured in 27 patients. BAL cotinine levels were measured using a sensitive ELISA kit produced to measure cotinine in saliva. Plates were read by microuant (BioTek, USA) micro plate reader. All patient serum cotinine levels were detectable except for one nonsmoker patient. However, BAL fluid cotinine levels were measurable in only 6 patients (two of them were nonsmokers). A significant positive correlation was seen between serum and BAL fluid cotinine levels (r = 0.726; p = 0.000). Serum cotinine levels were significantly higher in present smokers than non-smokers (21.0 +/- 16.01; 5.35 +/- 7.65; p = 0.004). However, there were no significant differences in BAL fluid cotinine levels between smokers and nonsmokers. Passive smoking can increase nicotine metabolites in serum and other body fluids, including BAL fluid. Since BAL fluid and serum cotinine levels were well correlated, there is no need to use invasive procedures, such as bronchoscopy and expensive, time consuming BAL fluid analyses. Serum cotinine levels can give a rough idea of smoking status. BAL fluid cotinine meaurements should be done for only scientific reasons. PMID:21073047

  8. Protein extracts from cultured cells contain nonspecific serum albumin.

    PubMed

    Miyara, Masatsugu; Umeda, Kanae; Ishida, Keishi; Sanoh, Seigo; Kotake, Yaichiro; Ohta, Shigeru

    2016-06-01

    Serum is an important component of cell culture media. The present study demonstrates contamination of intracellular protein extract by bovine serum albumin from the culture media and illustrates how this contamination can cause the misinterpretation of western blot results. Preliminary experiments can prevent the misinterpretation of some experimental results, and optimization of the washing process may enable specific protein detection. PMID:26967711

  9. Serum zinc and pneumonia in nursing home elderly

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Zinc plays an important role in immune function. The association between serum zinc and pneumonia in the elderly has not been studied. The study aim is to determine if serum zinc concentrations in nursing home elderly are associated with incidence and duration of pneumonia, total and duration of ant...

  10. Association of Serum Adropin Concentrations with Diabetic Nephropathy

    PubMed Central

    2016-01-01

    Objective. Adropin is a newly identified regulatory protein encoded by the Enho gene and is critically involved in energy homeostasis and insulin sensitivity. This study aims to determine the correlation of serum adropin concentrations with diabetic nephropathy (DN). Methods. This study consisted of 245 patients with type 2 diabetes mellitus (T2DM) and 81 healthy subjects. Then T2DM patients were divided into normoalbuminuria, microalbuminuria, and macroalbuminuria subgroups based on urine albumin to creatinine ratio (ACR). Results. T2DM patients showed significantly lower serum adropin concentrations than those in the controls. T2DM patients with macroalbuminuria had significantly decreased serum adropin concentrations compared with the other three groups. In addition, T2DM patients with microalbuminuria showed lower serum adropin concentrations than those in patients with normoalbuminuria. Logistic regression analysis showed that serum adropin was correlated with decreased risk of developing T2DM and DN. Pearson correlation analysis indicated that serum adropin was negatively correlated with body mass index (BMI), blood urea nitrogen, creatinine, and ACR and positively correlated with glomerular filtration rate. Furthermore, multiple linear regression analysis showed that BMI and ACR were negatively correlated with serum adropin levels. Conclusion. Serum adropin concentrations are negatively associated with renal function. Adropin may be implicated in the pathogenesis of DN development. PMID:27546995

  11. 21 CFR 610.16 - Total solids in serums.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 7 2013-04-01 2013-04-01 false Total solids in serums. 610.16 Section 610.16 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS GENERAL BIOLOGICAL PRODUCTS STANDARDS General Provisions § 610.16 Total solids in serums. Except...

  12. 21 CFR 610.16 - Total solids in serums.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 7 2011-04-01 2010-04-01 true Total solids in serums. 610.16 Section 610.16 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS GENERAL BIOLOGICAL PRODUCTS STANDARDS General Provisions § 610.16 Total solids in serums. Except...

  13. 21 CFR 610.16 - Total solids in serums.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 7 2012-04-01 2012-04-01 false Total solids in serums. 610.16 Section 610.16 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS GENERAL BIOLOGICAL PRODUCTS STANDARDS General Provisions § 610.16 Total solids in serums. Except...

  14. 21 CFR 610.16 - Total solids in serums.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Total solids in serums. 610.16 Section 610.16 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS GENERAL BIOLOGICAL PRODUCTS STANDARDS General Provisions § 610.16 Total solids in serums. Except...

  15. 21 CFR 610.16 - Total solids in serums.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 7 2014-04-01 2014-04-01 false Total solids in serums. 610.16 Section 610.16 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS GENERAL BIOLOGICAL PRODUCTS STANDARDS General Provisions § 610.16 Total solids in serums. Except...

  16. Association between serum folic acid level and erectile dysfunction.

    PubMed

    Karabakan, M; Erkmen, A E; Guzel, O; Aktas, B K; Bozkurt, A; Akdemir, S

    2016-06-01

    This study measured the serum folic acid (FA) level in patients with erectile dysfunction (ED) and evaluated the possible association between the serum FA level and erectile function. The study divided 120 patients with ED into 3 groups of 40 patients each: those with severe, moderate and mild ED. Forty healthy men served as controls. Fasting serum samples were obtained, and the total testosterone, cholesterol and FA levels were measured using chemiluminescent immunoassays. There were no significant differences in the mean age, mean body mass index or mean serum total testosterone and cholesterol levels among the three ED groups and controls (P > 0.05). The mean serum FA concentrations were 7.2 ± 3.7, 7.1 ± 3.2, 10.2 ± 4.6 and 10.7 ± 4.6 ng ml(-1) in the severe, moderate and mild ED and control groups respectively. The mean serum FA concentration was significantly higher in the control group than in the severe and moderate ED groups (both P < 0.001), but not the mild ED group (P = 0.95). Considering the significant differences in the serum FA levels between the control and ED groups, serum FA deficiency might reflect the severity of ED. PMID:26302884

  17. SERUM BIOMARKERS OF AGING IN THE BROWN NORWAY RAT

    EPA Science Inventory

    Serum biomarkers to identify susceptibility to disease in aged humans are well researched. On the other hand, our understanding of biomarkers in animal models of aging is limited. Hence, we applied a commercially available panel of 58 serum analytes to screen for possible biomark...

  18. Rapid and precise analysis for calcium in blood serum

    NASA Technical Reports Server (NTRS)

    Holtzman, R. B.; Ilcewicz, F. H.

    1969-01-01

    Differential absorption spectrophotometric technique, using murexide, gives a highly precise analysis of calcium in volumes of blood serum as small as 0.01 ml. The method of additions and proper timing allows compensation to be made for fading, variation in type of serum or plasma, and aging of the specimen.

  19. 9 CFR 147.2 - The rapid serum test. 2

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false The rapid serum test. 2 147.2 Section 147.2 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE LIVESTOCK IMPROVEMENT AUXILIARY PROVISIONS ON NATIONAL POULTRY IMPROVEMENT PLAN Blood Testing Procedures § 147.2 The rapid serum test. 2 2...

  20. 9 CFR 147.2 - The rapid serum test. 2

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false The rapid serum test. 2 147.2 Section 147.2 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE LIVESTOCK IMPROVEMENT AUXILIARY PROVISIONS ON NATIONAL POULTRY IMPROVEMENT PLAN Blood Testing Procedures § 147.2 The rapid serum test. 2 2...

  1. SIMPLIFIED METHOD FOR EXTRACTING BOUND PESTICIDES FROM AVIAN SERUM

    EPA Science Inventory

    A simple solid-phase extraction (SPE) method was developed to extract organochlorine pesticides (OCs) and persistent organic pollutants (POPs) from avian serum. In this method, a 1-mL serum sample fortified with two levels of OCs or POPs was treated with 8M urea or 4M urea and 4...

  2. Microneutralization assay for swine influenza virus in swine serum

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The microneutralization (MN) assay is a modification of the serum virus neutralization assay and is a serological test to detect the presence of functional systemic antibodies that prevent infectivity of virus. When infectious virus is mixed with serum antibody, the virus infectivity can be "neutral...

  3. Association of Serum Adropin Concentrations with Diabetic Nephropathy.

    PubMed

    Hu, Wenchao; Chen, Li

    2016-01-01

    Objective. Adropin is a newly identified regulatory protein encoded by the Enho gene and is critically involved in energy homeostasis and insulin sensitivity. This study aims to determine the correlation of serum adropin concentrations with diabetic nephropathy (DN). Methods. This study consisted of 245 patients with type 2 diabetes mellitus (T2DM) and 81 healthy subjects. Then T2DM patients were divided into normoalbuminuria, microalbuminuria, and macroalbuminuria subgroups based on urine albumin to creatinine ratio (ACR). Results. T2DM patients showed significantly lower serum adropin concentrations than those in the controls. T2DM patients with macroalbuminuria had significantly decreased serum adropin concentrations compared with the other three groups. In addition, T2DM patients with microalbuminuria showed lower serum adropin concentrations than those in patients with normoalbuminuria. Logistic regression analysis showed that serum adropin was correlated with decreased risk of developing T2DM and DN. Pearson correlation analysis indicated that serum adropin was negatively correlated with body mass index (BMI), blood urea nitrogen, creatinine, and ACR and positively correlated with glomerular filtration rate. Furthermore, multiple linear regression analysis showed that BMI and ACR were negatively correlated with serum adropin levels. Conclusion. Serum adropin concentrations are negatively associated with renal function. Adropin may be implicated in the pathogenesis of DN development. PMID:27546995

  4. Central injection of CDP-choline suppresses serum ghrelin levels while increasing serum leptin levels in rats.

    PubMed

    Kiyici, Sinem; Basaran, Nesrin Filiz; Cavun, Sinan; Savci, Vahide

    2015-10-01

    In this study we aimed to test central administration of CDP-choline on serum ghrelin, leptin, glucose and corticosterone levels in rats. Intracerebroventricular (i.c.v.) 0.5, 1.0 and 2.0 µmol CDP-choline and saline were administered to male Wistar-Albino rats. For the measurement of serum leptin and ghrelin levels, blood samples were obtained baseline and at 5, 15, 30, 60 and 120 min following i.c.v. CDP-choline injection. Equimolar doses of i.c.v. choline (1.0 µmol) and cytidine (1.0 µmol) were administered and measurements were repeated throughout the second round of the experiment. Atropine (10 µg) and mecamylamine (50 µg) were injected intracerebroventricularly prior to CDP-choline and measurements repeated in the third round of the experiment. After 1 µmol CDP-choline injection, serum ghrelin levels were suppressed significantly at 60 min (P=0.025), whereas serum leptin levels were increased at 60 and 120 min (P=0.012 and P=0.017 respectively). CDP-choline injections also induced a dose- and time-dependent increase in serum glucose and corticosterone levels. The effect of choline on serum leptin and ghrelin levels was similar with CDP-choline while no effect was seen with cytidine. Suppression of serum ghrelin levels was eliminated through mecamylamine pretreatment while a rise in leptin was prevented by both atropine and mecamylamine pretreatments. In conclusion; centrally injected CDP-choline suppressed serum ghrelin levels while increasing serum leptin levels. The observed effects following receptor antagonist treatment suggest that nicotinic receptors play a role in suppression of serum ghrelin levels,whereas nicotinic and muscarinic receptors both play a part in the increase of serum leptin levels. PMID:26162700

  5. Serum Hepcidin Levels in Childhood-Onset Ischemic Stroke

    PubMed Central

    Azab, Seham F.; Akeel, Nagwa E.; Abdalhady, Mohamed A.; Elhewala, Ahmed A.; Ali, Al Shymaa A.; Amin, Ezzat K.; Sarhan, Dina T.; Almalky, Mohamed A.A.; Elhindawy, Eman M.; Salam, Mohamed M.A.; Soliman, Attia A.; Abdellatif, Sawsan H.; Ismail, Sanaa M.; Elsamad, Nahla A.; Hashem, Mustafa I.A.; Aziz, Khalid A.; Elazouni, Osama M.A.; Arafat, Manal S.

    2016-01-01

    Abstract Recently, hepcidin, an antimicrobial-like peptide hormone, has evolved as the master regulator of iron homeostasis. Despite the growing evidence of iron imbalance in childhood-onset ischemic stroke, serum hepcidin level in those patients has not yet been researched. In this study, we aimed to estimate serum (hepcidin) level in acute ischemic stroke (AIS) patients and to investigate whether subcutaneous enoxaparin sodium, which is a low-molecular-weight heparin (LMWH) derivative, could modulate serum hepcidin level in those patients. This was a case–control study included 60 (AIS) cases, and 100 healthy children with comparable age and gender as control group. For all subjects’ serum hepcidin, interleukin-6 (IL-6), and soluble transferrin receptor [sTfR]) levels were assessed by (enzyme-linked immunosorbent assay [ELISA] method). Iron parameters including (serum iron, ferritin, transferrin, and total iron binding capacity [TIBC]) were also measured. The patients were subdivided according to treatment with an LMWH derivative into 2 groups and serum hepcidin levels were assessed initially and 1 week after stroke onset for all cases. We found that AIS cases had higher serum iron, ferritin, and IL6 levels compared to the control group (all P < 0.01). Serum hepcidin was significantly higher in AIS cases (median, 36[15–73]ng/mL) compared to the control group (median, 24[10–41]ng/mL; P < 0.01). On the 1st day of AIS diagnosis, serum hepcidin levels were similar in both stroke subgroups (P > 0.05). However, on the 7th day of diagnosis serum hepcidin level decreased significantly in AIS cases treated with LMWH (group 1) (median, 36 vs 21 ng/mL; P < 0.01, respectively). Meanwhile, no significant change was observed in serum hepcidin level in AIS cases not treated with LMWH (group 2) (P > 0.05). Serum hepcidin showed significant positive correlations with serum iron, transferrin saturation, ferritin, and IL6 (r = 0.375, P < 0

  6. Early effects of erythropoietin on serum hepcidin and serum iron bioavailability in healthy volunteers.

    PubMed

    Lainé, Fabrice; Laviolle, Bruno; Ropert, Martine; Bouguen, Guillaume; Morcet, Jeff; Hamon, Catherine; Massart, Catherine; Westermann, Mark; Deugnier, Yves; Loréal, Olivier

    2012-04-01

    Hepcidin regulates plasma iron bioavailability and subsequently iron availability for erythropoiesis. rHuEPO has been reported to decrease hepcidin expression in case of repeated subcutaneous injections. Thus, hepcidin level measurement could be a candidate marker for detection of rHuEPO abuse. However, when used for doping, rHuEPO can be injected intravenously and the scheme of injection is unknown. Our aim was to evaluate the early effects of a single intravenous rHuEPO injection on serum hepcidin levels. Fourteen male healthy volunteers received one intravenous injection of 50 U/Kg of rHuEPO during a placebo-controlled, randomized, double-blind, cross-over study. Serum hepcidin, quantified by a competitive ELISA method and iron parameters was then evaluated for 24 h. Serum levels of hepcidin were significantly increased 4 h after rHuEPO injection when compared with placebo injection (78.3 ± 55.5 vs. 57.5 ± 34.6 ng/ml, respectively; +36%, p < 0.05), whereas iron and transferrin saturation dramatically decreased 12 h after rHuEPO injection when compared with placebo injection (9.2 ± 3.5 vs. 15.8 ± 4.2 μg/l, respectively; -42%, p < 0.05 and 14.8 ± 5.0 vs. 26.3 ± 6.4%, respectively; -44%, p < 0.05). In addition, 12 and 24 h after rHuEPO injection serum hepcidin levels were lower compared with placebo injection (41.6 ± 27.4 vs. 56.6 ± 28.1 ng/ml after 12 h; -27%, p < 0.05 and 26.0 ± 29.6 vs. 81.2 ± 29.4 ng/ml after 24 h; -68%, p < 0.05). Intravenous injection of recombinant EPO induces a precocious and transient increase of serum hepcidin leading to a transient decrease of iron bioavailability. The transitory increase and dynamics of its concentration make difficult the practical use of hepcidin to detect rHuEPO doping. PMID:21818622

  7. Serum insulin concentration in horses: Effect of storage and handling.

    PubMed

    Carslake, Harry; Karikoski, Ninja; Pinchbeck, Gina; McGowan, Catherine

    2016-05-01

    Serum insulin concentration is commonly measured during investigation of suspected endocrinopathic disease in horses, but immediate analysis is frequently unavailable. The aim of this study was to examine the effect of storing samples at room temperature for 72 h as serum and as whole blood, compared to immediate separation and freezing. Samples from 14 horses were evaluated. Correlation was excellent for all comparisons (≥0.992). Bland-Altman plots revealed a negative bias (mean difference 2.16 µIU/mL) in samples stored as whole blood compared to serum, but this difference was not considered clinically significant. At two commonly used diagnostic cut-offs, there was no effect of storage on result. This study indicates that storage at room temperature for 72 h, either as serum or whole blood, has minimal effect on measured serum insulin concentration in horses. PMID:27033594

  8. Preoperative Serum Levels of Mesothelin in Patients with Colon Cancer

    PubMed Central

    Bostancı, Özgür; Kemik, Özgür; Kemik, Ahu; Battal, Muharrem; Demir, Uygar; Purisa, Sevim; Mihmanlı, Mehmet

    2014-01-01

    Background. Screening for biochemical markers is important for diagnosing colon cancer. In this study, the reliability of serum mesothelin levels as a potential diagnostic and screening instrument was evaluated concerning colon cancer. Methods. Ninety-five patients who had undergone colonoscopic examination and who were diagnosed with colon cancer were included in the study. The serum mesothelin levels were measured with the ELISA kits and were evaluated in terms of significant difference when compared between colon cancer and control group. Results. Patients with colon cancer had significantly higher mesothelin serum levels (P < 0.001) than the control groups. We found significant associations between serum levels and tumor grade, perineural invasion, and vascular invasion (resp., P < 0.001). Conclusion. Evaluating the serum levels of mesothelin has a potential to detect and screen the colon cancer in affected patients. Our data suggest that mesothelin exhibits effects towards colon cancer and serves as a biomarker for this deadly disease. PMID:25477701

  9. A Survey of Membrane Proteins in Human Serum

    PubMed Central

    Dung, Nguyen Tien; Van Chi, Phan

    2012-01-01

    Serum and membrane proteins are two of the most attractive targets for proteomic analysis. Previous membrane protein studies tend to focus on tissue sample, while membrane protein studies in serum are still limited. In this study, an analysis of membrane proteins in normal human serum was carried out. Nano-liquid chromatography-electrospray ionization mass spectrometry (NanoLC-ESI-MS/MS) and bioinformatics tools were used to identify membrane proteins. Two hundred and seventeen membrane proteins were detected in the human serum, of which 129 membrane proteins have at least one transmembrane domain (TMD). Further characterizations of identified membrane proteins including their subcellular distributions, molecular weights, post translational modifications, transmembrane domains and average of hydrophobicity, were also implemented. Our results showed the potential of membrane proteins in serum for diagnosis and treatment of diseases. PMID:25288886

  10. Induction of tenascin-C by cyclic tensile strain versus growth factors: distinct contributions by Rho/ROCK and MAPK signaling pathways.

    PubMed

    Chiquet, Matthias; Sarasa-Renedo, Ana; Tunç-Civelek, Vildan

    2004-09-17

    Expression of the extracellular matrix (ECM) protein tenascin-C is induced in fibroblasts by growth factors as well as by tensile strain. Mechanical stress can act on gene regulation directly, or indirectly via the paracrine release of soluble factors by the stimulated cells. To distinguish between these possibilities for tenascin-C, we asked whether cyclic tensile strain and soluble factors, respectively, induced its mRNA via related or separate mechanisms. When cyclic strain was applied to chick embryo fibroblasts cultured on silicone membranes, tenascin-C mRNA and protein levels were increased twofold within 6 h compared to the resting control. Medium conditioned by strained cells did not stimulate tenascin-C mRNA in resting cells. Tenascin-C mRNA in resting cells was increased by serum; however, cyclic strain still caused an additional induction. Likewise, the effect of TGF-beta1 or PDGF-BB was additive to that of cyclic strain, whereas IL-4 or H2O2 (a reactive oxygen species, ROS) did not change tenascin-C mRNA levels. Antagonists for distinct mitogen-activated protein kinases (MAPK) inhibited tenascin-C induction by TGF-beta1 and PDGF-BB, but not by cyclic strain. Conversely, a specific inhibitor of Rho-dependent kinase strongly attenuated the response of tenascin-C mRNA to cyclic strain, but had limited effect on induction by growth factors. The data suggest that regulation of tenascin-C in fibroblasts by cyclic strain occurs independently from soluble mediators and MAPK pathways; however, it requires Rho/ROCK signaling. PMID:15363633

  11. Angiotensin II-induced hypertrophy of cultured murine proximal tubular cells is mediated by endogenous transforming growth factor-beta.

    PubMed Central

    Wolf, G; Mueller, E; Stahl, R A; Ziyadeh, F N

    1993-01-01

    Previous studies by our group have demonstrated that angiotensin II (ANG II), as a single factor in serum-free medium, induces cellular hypertrophy of a cultured murine proximal tubular cell line (MCT). The present study was performed to test the hypothesis that this growth effect was mediated by activation of endogenous transforming growth factor-beta (TGF-beta). Exogenous TGF-beta 1 (1 ng/ml) mimicked the growth effects observed with 10(-8) M ANG II (inhibition of DNA synthesis and induction of cellular hypertrophy). A neutralizing anti-TGF-beta antibody attenuated the ANG II-induced increase in de novo protein and total RNA synthesis as well as total protein content. This antibody also abolished the ANG II-mediated inhibition of [3H]thymidine incorporation into quiescent MCT cells. Control IgG or an unrelated antibody had no effect. A bioassay for TGF-beta using mink lung epithelial cells revealed that MCT cells treated with ANG II released active TGF-beta into the cell culture supernatant. Northern blot analysis and semi-quantitative cDNA amplification demonstrated increases in steady-state levels for TGF-beta 1 mRNA after ANG II stimulation of MCT cells, but not in a syngeneic murine mesangial cell line. Our data indicate that the ANG II-induced hypertrophy in MCT cells is mediated by synthesis and activation of endogenous TGF-beta. It is intriguing to speculate that TGF-beta may play a role in the early tubular cell hypertrophy and the subsequent interstitial scarring observed in several models of chronic renal injury that are characterized by increased activity of intrarenal ANG II. Images PMID:7690779

  12. Effects of transforming growth factor type beta on expression of cytoskeletal proteins in endosteal mouse osteoblastic cells

    SciTech Connect

    Lomri, A.; Marie, P.J. )

    1990-01-01

    Transforming growth factor beta (TGF beta) has been shown to influence the growth and differentiation of many cell types in vitro. We have examined the effects of TGF beta on cell morphology and cytoskeletal organization in relation to parameters of cell proliferation and differentiation in endosteal osteoblastic cells isolated from mouse caudal vertebrae. Treatment of mouse osteoblastic cells cultured in serum free medium for 24 hours with TGF beta (1.5-30 ng/mL) slightly (-23%) inhibited alkaline phosphatase activity. In parallel, TGF beta (0.5-30 ng/mL, 24 hours) greatly increased cell replication as evaluated by (3H)-thymidine incorporation into DNA (157% to 325% of controls). At a median dose (1.5 ng/mL) that affected both alkaline phosphatase and DNA synthesis (235% of controls) TGF beta induced rapid (six hours) cell respreading of quiescent mouse osteoblastic cells. This effect was associated with increased polymerization of actin, alpha actinin, and tubulins, as evaluated by both biochemical and immunofluorescence methods. In addition, TGF beta (1.5 ng/mL) increased the de novo biosynthesis of actin, alpha actinin, vimentin, and tubulins, as determined by {sup 35}S methionine labeling and fractionation of cytoskeletal proteins using two-dimensional gel electrophoresis. These effects were rapid and transient, as they occurred at six hours and were reversed after 24 hours of TGF beta exposure. The results indicate that the stimulatory effect of TGF beta on DNA synthesis in endosteal mouse osteoblastic cells is associated with a transient increase in cell spreading associated with enhanced polymerization and synthesis of cytoskeletal proteins.

  13. Transforming growth factor-beta as a differentiating factor for cultured smooth muscle cells.

    PubMed

    Gawaziuk, J P; X; Sheikh, F; Cheng, Z-Q; Cattini, P A; Stephens, N L

    2007-10-01

    The aim of the present study was to determine whether the development of supercontractile smooth muscle cells, contributing to the nonspecific hyperreactivity of airways in asthmatic patients, is due to transforming growth factor (TGF)-beta. In cultured smooth muscle cells starved by removal of 10% foetal bovine serum for 7 days, growth arrest was seen; 30% became elongated and demonstrated super contractility. Study of conditioned medium suggested that the differentiating factor was TGF-beta. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) was carried out on conditioned medium from the arrested cells. Two protein bands were identified as matrix metalloproteinase (MMP)-2 and TGF-beta1. To determine second messenger signalling by SMAD2, Western blotting and confocal microscopy were employed. Conditioned medium from arrested cultures showed the presence of MMP-2 and TGF-beta1, as revealed by SDS-PAGE; 68- and 25-kDa bands were seen. Differentiation was confirmed by upregulation of marker proteins, smooth muscle type myosin heavy chain and myosin light chain kinase. Confirmation was obtained by downregulating these proteins with decorin treatment, which reduces the levels of active TGF-beta and an adenoviral dominant-negative vector coding for a mutated type II TGF-beta-receptor. Activation of second messenger signalling was demonstrated immunocytochemically by the presence of phosphorylated SMAD2 and SMAD4. Transforming growth factor-beta is likely to be the differentiating factor responsible for the development of these supercontractile smooth muscle cells. The development of such cells in vivo after cessation of an asthmatic attack could contribute to the nonspecific hyperreactivity of airways seen in patients. PMID:17596270

  14. Cigarette smoke extract inhibits chemotaxis and collagen gel contraction mediated by human bone marrow osteoprogenitor cells and osteoblast-like cells.

    PubMed

    Liu, Xiangde; Kohyama, Tadashi; Kobayashi, Tetsu; Abe, Shinji; Kim, Hui Jung; Reed, Elizabeth C; Rennard, Stephen I

    2003-05-01

    Cell migration and matrix remodeling are key events in tissue repair and restructuring. Osteoblasts are responsible for the production of new bone matrix during bone remodeling. The activity of these cells can be modulated by a number of factors. The current study evaluated the hypothesis that cigarette smoke extract can alter repair and remodeling responses of human osteoprogenitor cells and osteoblast-like cells and, therefore, could explain one mechanism by which cigarette smoking leads to osteoporosis. Human osteoprogenitor cells were isolated from normal human bone marrow and maintained in culture under either control conditions or conditions that induced differentiation into osteoblast-like cells. Both cell types migrated toward fibronectin and PDGF-BB as chemoattractants. Neither responded to TGF-beta1. The osteoprogenitor cells were more active in their chemotactic response. The chemotactic response of both cell types was inhibited by cigarette smoke extract in a concentration-dependent manner. Both cell types, when cultured in three-dimensional native collagen gels maintained in floating culture, induced contraction of their surrounding matrices. Contraction was augmented by serum, PDGF-BB, and TGF-beta1. Osteoprogenitor cells were less active in inducing contraction than were osteoblast-like cells. Contraction of both cell types was inhibited by cigarette smoke extract. Cigarette smoke extract also inhibited the production of fibronectin by both cell types maintained in three-dimensional culture. Addition of exogenous fibronectin partially restored the ability of the cells to contract three-dimensional collagen gels. The current study demonstrates that cigarette smoke can interfere with the ability of bone cells to participate in repair and remodeling events. Such an effect may be one mechanism leading to the development of osteoporosis. PMID:12730796

  15. Inhibitor of DNA synthesis is present in normal chicken serum

    SciTech Connect

    Franklin, R.A.; Davila, D.R.; Westly, H.J.; Kelley, K.W.

    1986-03-05

    The authors have found that heat-inactivated serum (57/sup 0/C for 1 hour) from normal chickens reduces the proliferation of mitogen-stimulated chicken and murine splenocytes as well as some transformed mammalian lymphoblastoid cell lines. Greater than a 50% reduction in /sup 3/H-thymidine incorporation was observed when concanavalin A (Con A)-activated chicken splenocytes that were cultured in the presence of 10% autologous or heterologous serum were compared to mitogen-stimulated cells cultured in the absence of serum. Normal chicken serum (10%) also caused greater than 95% suppression of /sup 3/H-thymidine incorporation by bovine (EBL-1 and BL-3) and gibbon ape (MLA 144) transformed lymphoblastoid cell lines. The only cell line tested that was not inhibited by chicken serum was an IL-2-dependent, murine cell line. Chicken serum also inhibited both /sup 3/H-thymidine incorporation and IL-2 synthesis by Con A-activated murine splenocytes. Suppression was caused by actions other than cytotoxicity because viability of chicken splenocytes was unaffected by increasing levels of chicken serum. Furthermore, dialyzed serum retained its activity, which suggested that thymidine in the serum was not inhibiting uptake of radiolabeled thymidine. Suppressive activity was not due to adrenal glucocorticoids circulating in plasma because neither physiologic nor pharmacologic doses of corticosterone had inhibitory effects on mitogen-stimulated chicken splenocytes. These data demonstrate that an endogenous factor that is found in normal chicken serum inhibits proliferation of T-cells from chickens and mice as well as some transformed mammalian lymphoblastoid cell lines.

  16. Serum copper concentration as an index of clinical lung injury

    SciTech Connect

    Molteni, A.; Ward, W.F.; Kim, Y.T.; Shetty, R.; Brizio-Molteni, L.; Giura, R.; Ribner, H.; Lomont, M. )

    1989-01-01

    The purpose of this ongoing study is to determine whether thoracic radiotherapy for lung cancer produces an early increase in serum copper (Cu) concentration, an increase which might predict clinical outcome. Copper and iron concentrations were measured in serum obtained from nonsmall cell lung cancer patients at 0, 1, 2, 4, and 6 weeks after the start of radiotherapy. Control groups included patients irradiated for breast cancer (low dose of radiation to the lung), for endometrial, cervical or prostatic cancer, and patients with congestive heart failure, pulmonary hypertension, chronic obstructive pulmonary disease (COPD), and cutaneous burns with or without smoke inhalation. Serum Cu concentration increased at least 10 micrograms/dl from the pretreatment level in approximately 75% of the adenocarcinoma and squamous cell lung cancer patients, but in only 1 of 4 undifferentiated lung cancer cases. In virtually all of these responders, serum Cu increased to a maximum at 2 weeks after the start of therapy, then plateaued or decreased slightly despite continuing irradiation. Within the subset of squamous cell lung cancers, there was a direct correlation between the degree of histologic differentiation and both baseline serum Cu concentration and the probability of an early increase therein. In contrast, only 33% of breast cancer patients and 15% of endometrial, cervical and prostate cancer patients exhibited an increase in serum Cu concentration at 2 weeks after the start of radiotherapy. Serum Cu concentration was within normal limits in virtually all patients with congestive heart failure, pulmonary hypertension, and COPD. Burn patients exhibited a significant reduction in serum Cu, although concomitant smoke inhalation increased serum Cu back to low-normal levels. Serum iron concentration did not change significantly in any category of patients.

  17. Dietary fat modulates serum paraoxonase 1 activity in rats.

    PubMed

    Kudchodkar, B J; Lacko, A G; Dory, L; Fungwe, T V

    2000-10-01

    We examined the effects of dietary fats with specific fatty acid compositions, on serum paraoxonase (PON1) activity in rats. Male adult Sprague-Dawley rats were divided randomly into four dietary groups. One group received the control diet [AIN 93M with soybean oil (5 g/100 g diet)], whereas the remaining three groups received the modified control diet supplemented with (15 g/100 g diet) triolein, tripalmitin or fish oil, respectively. After 20 d, blood was obtained after overnight food deprivation and PON1 activity was determined. Serum lipids and lipid components of lipoproteins were also determined. Serum PON1 activity [micromol/(L.min)] was significantly (P: < 0.05) higher in triolein (98 +/- 6) and lower in fish oil (41 +/- 4), compared with tripalmitin-fed rats (63 +/- 11). Serum PON1 activity in tripalmitin-fed rats was comparable to that of controls (67 +/- 9). Serum PON1 activity correlated significantly with serum lecithin:cholesterol acyltransferase (LCAT) activity (r = 0.77, P: < 0.001) and was transported in blood principally in association with the denser subfraction of HDL, very high density lipoprotein (VHDL; d > 1.15 kg/L). Serum PON1 activity correlated strongly with serum lipids as well as lipids of VLDL, HDL and its subfractions. Multiple linear regression analysis, however, showed a significant relationship of serum PON1 activity, principally with the phospholipids of VHDL (r = 0.47, P: < 0.002). These data suggest that the modulation of serum PON1 activity by dietary fat may be mediated via the effect of the specific fatty acids on the synthesis and secretion of VHDL, the subfraction of HDL that transports the majority of PON1 in the blood. PMID:11015468

  18. The purification of cholinesterase from horse serum.

    PubMed

    Main, A R; Soucie, W G; Buxton, I L; Arinc, E

    1974-12-01

    A relatively simple method is described by which cholinesterase was purified about 19000-fold starting from horse serum. Typically 20 litres of serum were processed to yield 15-18mg of electrophoretically pure cholinesterase in the form of an active salt-free dry powder. The method included two stages: fractionation with (NH(4))(2)SO(4) and ion-exchange chromatography. The (NH(4))(2)SO(4) stage included, in principle, the acid (pH3) step of the Strelitz (1944) procedure. The step took advantage of the stabilizing effect that 33%-satd. (NH(4))(2)SO(4) has on cholinesterase activity at pH3 and it is recognized that in the absence of (NH(4))(2)SO(4) the enzyme is rapidly destroyed at pH3. Cholinesterase was significantly more stable to pH3.0 at 2 degrees C than at 24 degrees C, and the acid step was done at both temperatures. The specific activities of the final products obtained by way of acid steps were the same at either temperature, thus indicating that the step has not harmed the enzyme active sites. The product from the first two stages was purified over 18000-fold and was 85-90% cholinesterase. The remaining impurities were removed by preparative gel electrophoresis. The product was about 40% more active and contained 40% more active sites per unit weight than electrophoretically pure cholinesterase prepared from partially purified commercial starting material. Although the number of active sites per molecule was not determined with certainty, a value of at least 3 and possibly 4 was indicated. The partial specific volumes were determined with a precision density meter, on the ultracentrifuge and from the amino acid and carbohydrate composition. The values by these independent methods were 0.688, 0.71 and 0.712ml/g, respectively. The amino acid and carbohydrate composition was determined. The cholinesterase contained 17.4% carbohydrate including 3.2% N-acetylneuraminic acid. PMID:4462752

  19. Serum thrombopoietin level in various hematological diseases.

    PubMed

    Usuki, K; Tahara, T; Iki, S; Endo, M; Osawa, M; Kitazume, K; Kato, T; Miyazaki, H; Urabe, A

    1996-09-01

    To investigate the pathophysiological role of thrombopoietin (TPO) in thrombopoiesis, we measured its serum levels in 15 healthy individuals, 84 patients with various hematological diseases and 2 patients with liver cirrhosis using an enzyme immunoassay procedure. The TPO level was 0.84 +/- 0.40 f mol/ml in normal individuals. TPO levels were considerably elevated in patients with myelosuppression after intensification chemotherapy of acute leukemia in complete remission (postchemotherapy group; n = 18; 18.46 +/- 9.70 f mol/ml). When the data of normal individuals and the postchemotherapy group were combined, TPO levels were inversely correlated with the platelet count in this combined group. We compared these data of normal individuals and the postchemotherapy group with various hematological disease states. In aplastic anemia (n = 13; 16.03 +/- 9.44 f mol/ml), acute lymphoblastic leukemia (n = 5; 10.36 +/- 5.57 f mol/ml), malignant lymphoma (n = 6; 2.79 +/- 2.27 f mol/ml), multiple myeloma (n = 3; 3.34 +/- 0.20 f mol/ml) and chronic lymphocytic leukemia (n = 2; 1.71 +/- 3.91 f mol/ml), the relationship of serum TPO levels and platelet counts was almost the same as in the combined group with normal individuals and the postchemotherapy group. However, the TPO levels were slightly higher in myeloproliferative disorders (n = 12; 1.99 +/- 1.47 f mol/ml) and lower in acute myelogenous leukemia (n = 8; 2.27 +/- 1.25 f mol/ml), hypoplastic leukemia (n = 3; 2.76 +/- 2.23 f mol/ml), myelodysplastic syndrome (n = 2; 0.42 +/- 0.60 f mol/ml), liver cirrhosis (n = 2; 1.50 +/- 0.92 f mol/ml) and idiopathic thrombocytopenic purpura (n = 12; 2.08 +/- 1.41 f mol/ml), when compared to the regression line for the combined group with normal individuals and postchemotherapy group. These findings suggest that TPO might play an important role in regulation of the platelet count in normal and pathological conditions. PMID:8888496

  20. Smoking and Serum Lipid Profiles in Schizophrenia.

    PubMed

    An, Hui-Mei; Tan, Yun-Long; Tan, Shu-Ping; Shi, Jing; Wang, Zhi-Ren; Yang, Fu-De; Huang, Xu-Feng; Soars, Jair C; Kosten, Thomas R; Zhang, Xiang-Yang

    2016-08-01

    Schizophrenia is associated with a high prevalence of cigarette-smoking and abnormal lipid profiles. The purpose of this study was to determine whether the profiles differ between schizophrenic smokers and non-smokers and whether the lipid profiles are related to psychopathological symptoms. Serum lipid profiles were measured in 130 male inpatients with DSM-IV-defined schizophrenia: 104 smokers and 26 non-smokers. Symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). Our results showed that positive PANSS symptoms were fewer in smokers than in non-smokers, while the negative symptoms were fewer in those who smoked more cigarettes. Total protein and globulin levels were significantly lower in the smokers than in the non-smokers. However, there was no significant difference in total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol, apolipoprotein A1, or apolipoprotein B between the smokers and non-smokers. However, the PANSS positive subscale had a significant negative correlation with the HDL-c levels (a protective factor) in the smokers but not in the non-smokers. Our findings suggest that schizophrenic patients who smoke have fewer psychotic symptoms, but contrary to expectation, smoking does not alter lipid profile levels. PMID:27017941

  1. Alteration of serum bilirubin level in schizophrenia.

    PubMed

    Semnani, Yousef; Nazemi, Farzad; Azariyam, Aileen; Ardakani, Mohammad Javad Ehsani

    2010-11-01

    Abstract Objective. Alteration of serum bilirubin level in acute episodes of psychosis in patients with schizophrenia has been reported but the pattern of this alteration is controversial. Methods. Patients diagnosed as schizophrenia (162, group S) or bipolar disorder (155, group B) entered the study. The control group consisted of 95 patients admitted to cardiac care unit who had no personal or family history of major psychiatric disorders. Pre- and post-admission levels of bilirubin were measured and compared within and between the groups. Patients were examined to exclude all other causes of hyperbilirubinemia. Group S and B participants were also evaluated using positive and negative syndrome subscale (PANSS) both at admission and discharge. Results. The mean admission bilirubin levels of all the groups were in the normal range (significantly higher in group S than groups B and C) and were affected by the score of general psychopathology subscale rather than the scores of positive symptoms subscale. Conclusions. Although bilirubin decreased in all three groups at discharge, the rate of decrease was significantly higher in group S. The reason for this is not clear and needs further study. PMID:24917437

  2. Serum protein polymorphism in Bali (Indonesia).

    PubMed

    Constans, J; Gouaillard, C; Breguet, G

    1986-01-01

    Serum samples from Bali, obtained in three different ethnic groups and in one isolated village were tested by isoelectric focusing electrophoresis for Gc, Pi, Tf and Hp subtyping. In addition to the three common alleles Gc1F, Gc1S and Gc2, two variants Gc1A1 and Gc1A8 were observed. In the Pi system, five alleles were present: PiM1, PiM2, PiM3, PiM4 and PiX. The Tf variability was exceptional with the presence of eight alleles: TfB1, TfC1, TfC2, TfC3, TfC4, TfC8, TfD1 and TfDchi. For Hp, there were two common alleles Hp1S and Hp1FS and two rare ones: Hp1F and Hp2SS. As expected, the genetic polymorphism is reduced in the isolated community. The anthropological significance of these genetic data is discussed. PMID:3493727

  3. Serum trace element levels in febrile convulsion.

    PubMed

    Amiri, Mojtaba; Farzin, Leila; Moassesi, Mohammad Esmail; Sajadi, Fattaneh

    2010-06-01

    Febrile convulsion is the most common disorder in childhood with good prognosis. There are different hypotheses about neurotransmitters and trace element changes in biological fluids which can have a role in pathogenesis of febrile convulsion. In this study, serum selenium, zinc, and copper were measured by atomic absorption spectrometry in the children with febrile convulsion (n = 30) and in the control group (n = 30). The age and sex of the subjects were registered. Selenium and zinc were found to be significantly lower in febrile convulsion cases than in the control group (p < 0.0001 and p < 0.0001, respectively). There was no significant difference in the value of copper between the two groups (p = 0.16). While selenium and zinc levels were 44.92 +/- 10.93 microg/l and 66.13 +/- 18.97 microg/dl in febrile convulsion, they were found to be 62.98 +/- 9.80 microg/l and 107.87 +/- 28.79 microg/dl in healthy children. Meanwhile, copper levels were 146.40 +/- 23.51 microg/dl in the patients and 137.63 +/- 24.19 microg/dl in the control group, respectively. This study shows that selenium and zinc play an important role in the pathogenesis of febrile convulsion. PMID:19669113

  4. Multiplexed microfluidic quantification of proteins in serum

    NASA Astrophysics Data System (ADS)

    Rajan, Nitin; Rajauria, Sukumar; Cleland, Andrew

    2015-03-01

    Rapid and low cost immunoassays targeting proteins in blood or other bodily fluids are highly sought after for point-of-care devices and early screening of patients. Immunoturbidimetric assays utilize latex particles functionalized with antibodies, with particle aggregation in the presence of the analyte detected by a change in absorbance. Using a high throughput micro-fluidic particle analyzer based solely on electrical signals (resistive pulse sensing), we are able to accurately quantify the degree of aggregation by analyzing the changes in the particle size distribution. Thus we study the aggregation of streptavidin (SAv) coated beads in the presence of biotinylated bovine serum albumin as a proof-of-principle assay and extract the binding capacity of the SAv beads from the dose-response curve. We also use our aggregation measurement platform to characterize a commercial C-reactive protein (CRP) immunoturbidimetric assay (hsCRP, Diazyme Inc.). We obtain a linear calibration curve as well as a better limit of detection of CRP than that obtained by absorbance measurements. By using different bead sizes functionalized with different antibodies, multiplexed analyte detection is also possible. We demonstrate this by combining the commercial anti-CRP functionalized beads (0.4 microns) with biotin coated beads (1.0 microns), and carry out the simultaneous detection of SAv and CRP in a single sample.

  5. Serum albumin complexation of acetylsalicylic acid metabolites.

    PubMed

    Jurkowski, Wiktor; Porebski, Grzegorz; Obtułowicz, Krystyna; Roterman, Irena

    2009-06-01

    One possible origin of the type I hypersensitivity reaction is reaction of drugs such as acetylsalicylic acid and its metabolites being complexed with human serum albumin. Albumin, being transporting molecule abundant in blood plasma is able to bind large array of ligands varying from small single carbon particles to long hydrophobic tailed lipidic acids (e.g. myristic acid). This non specificity is possible because of multi domain scaffold and large flexibility of inter-domain loops, which results in serious reorientation of domains. Hypothesis that acetylsalicylic acid metabolites may play indirect role in activation of allergic reaction has been tested. Binding of acetylsalicylic acid metabolites in intra-domain space causes significant increase of liability of domains IIIA and IIIB. One of metabolites, salicyluric acid, once is bound causes distortion and partial unfolding of helices in domains IA, IIB and IIIB. Changed are both directions and amplitude of relative motions as well as intra-domain distances. In result albumin is able to cross-link of adjacent IgE receptors which subsequently starts allergic reaction. PMID:19689242

  6. Complexes of dendrimers with bovine serum albumin.

    PubMed

    Mandeville, J S; Tajmir-Riahi, H A

    2010-02-01

    We report the complexation of bovine serum albumin (BSA) with several dendrimers of different compositions mPEG-PAMAM (G3), mPEG-PAMAM (G4), and PAMAM (G4) at physiological conditions using constant protein concentration and various dendrimer contents. FTIR, CD, and fluorescence spectroscopic methods were used to analyze polymer binding mode, the binding constant, and the effects of dendrimer complexation on BSA stability and conformation. Structural analysis showed that dendrimers bind BSA via hydrophilic and hydrophobic interactions with a number of bound polymers (n): 1.30 for mPEG-PAMAM-G3, 1.30 for mPEG-PAMAM-G4, and 1.0 for PAMAM-G4. The polymer-BSA binding constants were K(mPEG-G3) = 5.0 (+/-0.8) x 10(3) M(-1), K(mPEG-G4) = 1.0 (+/-0.3) x 10(4) M(-1), and K(PAMAM-G4) = 1.1 (+/-0.4) x 10(4) M(-1). Dendrimer binding altered BSA conformation with a major reduction of alpha-helix and an increase in random coil and turn structures, indicating a partial protein unfolding. PMID:20085247

  7. Serum-free primary human fibroblast and keratinocyte coculture.

    PubMed

    Mujaj, Sally; Manton, Kerry; Upton, Zee; Richards, Sean

    2010-04-01

    Research has shown that the inclusion of a fibroblast cell support layer is required for the isolation and expansion of primary keratinocytes. Recent advances have provided keratinocyte culture with fibroblast-free alternatives. However, these technologies are often undefined and rely on the incorporation of purified proteins/components. To address this problem we developed a medium that used recombinant proteins to support the serum-free isolation and expansion of human dermal fibroblasts and keratinocytes. The human dermal fibroblasts were able to be isolated serum free by adding recombinant human albumin to a collagenase solution. These fibroblasts were then expanded using a serum-free medium containing recombinant proteins: epidermal growth factor, basic fibroblast growth factor, chimeric vitronectin:insulin-like growth factor-I protein, and recombinant human albumin. These fibroblasts maintained a typical morphology and expressed fibroblast markers during their serum-free isolation, expansion, and freezing. Moreover, these fibroblasts were able to support the serum-free isolation and expansion of primary keratinocytes using these recombinant proteins. Real-time polymerase chain reaction and immunofluorescence analysis confirmed that there were no differences in expression levels of p63 or keratins 1, 6, and 10 when keratinocytes were grown in either serum-supplemented or serum-free medium. Using a three-dimensional human skin equivalent model we demonstrated that these keratinocytes also maintained their ability to reform an epidermal layer. In summary, the techniques described provide a valuable alternative for culturing fibroblasts and keratinocytes using recombinant proteins. PMID:19929322

  8. Zuclopenthixol decanoate in schizophrenia: serum levels and clinical state.

    PubMed

    Jørgensen, A; Aaes-Jørgensen, T; Gravem, A; Amthor, K F; Dencker, S J; Rosell, I; Baastrup, P C; Buckhave, J; Gram, L F

    1985-01-01

    Serum concentrations of zuclopenthixol were determined in a group of 20 patients treated with a depot preparation, zuclopenthixol decanoate in Viscoleo. Clinical assessments according to a Clinical Global Impression (CGI) scale, Comprehensive Psychological Rating Scale (CPRS), 16-item subscale for schizophrenia, and the UKU side effect scale were performed on 3 consecutive days of injection. The serum concentrations showed a limited individual variation and a high and significant correlation between dose and serum concentration. One patient had a particularly high serum concentration of zuclopenthixol. This patient also had an elevated concentration of the N-dealkyl metabolite, but a low concentration of the sulphoxide. For serum concentrations versus clinical state and side effects some significant correlations were found. All correlations were positive, which means that the higher the serum concentration the poorer the clinical state of the patient. We think that this probably reflects a common clinical pattern of increasing the dose, when the antipsychotic response is unsatisfactory. The study also showed that for moderately ill patients, who were given the optimum dose of drug, the subgroup of patients not experiencing side effects had significantly lower serum concentrations than the subgroup with side effects. PMID:2867572

  9. EFFECT OF THE ANTIBACTERIAL SERUM FACTOR ON STAPHYLOCOCCAL INFECTIONS

    PubMed Central

    Yotis, William W.

    1962-01-01

    Yotis, W. W. (Loyola University Medical School, Chicago, Ill.). Effect of the antibacterial serum factor on staphylococcal infections. J. Bacteriol. 83:137–143. 1962—Intracerebral injections of mice with 1 to 5 × 106 washed viable cells previously exposed for 1 hr at 4 C to 2 mg/ml of the serum factor resulted in 0 to 30% mortality when three recent isolates of yellow, hemolytic, coagulase-positive strains of Staphylococcus aureus were used. Mice inoculated in the same manner with the above strains, but exposed to an inactive preparation of the serum factor, showed a 60 to 90% mortality. Addition of partially purified coagulase to the serum factor neutralized the protective action of the serum factor. The serum factor was found primarily in the supernatant obtained following 62% (NH4)2SO4 saturation of the water-soluble globulin portion and precipitated by one-half volume of undiluted 95% ethanol. Plate counts, manometric techniques, and animal protection studies were employed to follow purification of the serum factor. If dry weight is taken as the criterion of purification, the active substance showed a 40-fold purification over a previous preparation of this substance. PMID:14009315

  10. Sertoli cells secrete both testis-specific and serum proteins.

    PubMed Central

    Wright, W W; Musto, N A; Mather, J P; Bardin, C W

    1981-01-01

    The secretions of the Sertoli cell were examined with two polyvalent antisera--one prepared against proteins in rat serum and the other against testis-specific proteins in rete testis fluid. These antisera detected 12 serum and 9 testis-specific proteins in rete testis fluid. To determine the origin of these proteins, primary cultures enriched in Sertoli cells were incubated with [35S]methionine, and the radiolabeled proteins in the medium were immunoprecipitated. Gel electrophoresis of the two immunoprecipitates resolved eight serum and nine testis-specific proteins. These two sets of proteins were specifically bound to their respective antiserum and were immunologically distinct. Medium from Sertoli cell cultures contained 10 times more of the testis-specific proteins than did cultures enriched for testicular myoid or interstitial cells. The concentration of the serum proteins in Sertoli cell medium was 5 and 10 times greater, respectively, than in myoid or interstitial cell preparations. The proteins from Sertoli cells were next characterized on two-dimensional gels. Seven of the proteins recognized by antiserum against serum proteins had identical molecular weights and isoelectric points as serum proteins. Three of these proteins were ceruloplasmin, transferrin, and glycoprotein 2. In addition to the proteins immunoprecipitated by the two antisera, more than 60 other proteins were detected on two-dimensional gels of the total secretory proteins. We conclude that the Sertoli cell secretes many proteins, some of which are specific to the testis and others of which are similar to serum proteins. Images PMID:6950398

  11. Radioimmunoassay of beta lipoprotein—protein of rat serum

    PubMed Central

    Eaton, R. Philip; Kipnis, David M.

    1969-01-01

    A double antibody radioimmunoassay for rat serum beta lipoprotein-protein (beta Lp-protein) is described. The protein was purified by ultracentrifugation, selective heparin-manganous precipitation, and gel filtration on Sephadex G-200. Antiserum was prepared in rabbits by biweekly immunization and absorbed with nonbeta lipoprotein containing rat serum. Iodination with 125I and purification by gel filtration provided a radiolabeled protein which was > 98% displaced by purified beta lipoprotein in the immunoassay. The radioimmunoassay was sensitive to beta Lp-protein concentrations from 0.1 to 1.5 μg. Specificity of the immunoassay for beta Lp-protein was established by comparison of the displacement curves obtained with serum very low density lipoprotein (VLDL), low density lipoprotein (LDL), high density lipoprotein (HDL), and density (d) > 1.21 fractions and with the beta and alpha migrating lipoproteins eluted from paper electrophoretograms. Suitability of the assay for measuring beta Lp-protein in serum was established by demonstrating 100% recovery of beta lipoprotein added to whole serum and by the absence of immunoreactive beta Lp-protein in serum of orotic acid-treated rats. Examination of sera from six other vertebrates species revealed partial cross-reactivity. Normal rat serum was found to contain 0.25±0.01 mg/ml of beta Lp-protein and hepatic production by an isolated perfused rat liver system was determined as 0.145 mg/hr. Images PMID:4978731

  12. Control of declared origin of bovine serum, a pilot study

    NASA Astrophysics Data System (ADS)

    Horacek, M.; Papesch, W.

    2009-04-01

    Bovine serum is the essential culture medium for cell cultures. Therefore it is highly demanded and the quality of the serum, e.g.: absence of bacteria, viruses certain antibodies, etc.., are important criteria. as some cattle diseases are endemic in certain regions, the origin of bovine serum is an important quality measure for its value. Thus the need to control the declared origins is present. Bovine serum was measured for d2H, d13C, d15N and d34S of proteine (dry residue) and d2H and d18O of the serum water. The hydrogen and oxygen are mainly depending by the isotopic composition of the water ingested by the cattle, and thus usually influenced by the isotopic signal of the precipitation. The carbon isotope signal is reflecting the diet of the cattle, whether it mainly feed on C3- or C4-plants. The nitrogen and sulphur isotope ratio is transferred from the ground/soil into the plant material and into the animal tissue, with some offset for nitrogen and without any significant offset for sulphur. Bovine serum samples from Canada, USA, Mexico, Brazil, Australia and New Zealand have been analysed. Due to the variations in the environmental conditions in different countries and regions which influence the isotope signatures of the serum samples it is possible to discriminate samples of different origin. Main discriminating parameters are d2H and d18O, d13C and d34S.

  13. Serum screening for oncogene proteins in workers exposed to PCBs.

    PubMed Central

    Brandt-Rauf, P W; Niman, H L

    1988-01-01

    A cohort of 16 municipal workers engaged in cleaning oil from old transformers was examined for possible health effects from exposure to polychlorinated biphenyls (PCBs). In addition to the evaluation of routine clinical parameters (history, physical examination, liver function tests, serum triglycerides, serum PCB values), a new screening technique for the presence of oncogene proteins in serum using monoclonal antibodies was used to ascertain the potential carcinogenic risk from exposure in these workers. Except for one individual, serum PCB concentrations were found to be relatively low in this cohort, probably due to the observance of appropriate protective precautions. The results of liver function test were within normal limits and serum triglyceride concentrations showed no consistent relation to PCB concentrations. Six individuals, all of whom were smokers, showed abnormal banding patterns for fes oncogene related proteins. The individual with the highest serum PCB concentration also exhibited significantly raised levels of the H-ras oncogene related P21 protein in his serum. These oncogene protein findings may be indicative of an increased risk for the development of malignant disease in these individuals. Images PMID:3143397

  14. Malnutrition Markers and Serum Ghrelin Levels in Hemodialysis Patients

    PubMed Central

    Montazerifar, Farzaneh; Karajibani, Mansour; Gorgij, Farnia; Akbari, Ommolbanin

    2014-01-01

    Objective. The aim of study was to investigate the changes levels of serum ghrelin in HD patients and its relationship to some malnutrition markers compared with healthy controls. Methods. Forty-five patients on hemodialysis and forty healthy controls were studied. Biochemical parameters and serum ghrelin levels were measured. Both daily dietary intakes and body mass index (BMI) assessments were performed for evaluation of nutritional status. Results. Ghrelin concentrations were significantly reduced in patients undergoing hemodialysis when compared to healthy controls (5 ± 0.68 (1.1–18.5) pg/mL versus 7.8 ± 0.84 (2.4–18.3) pg/mL; P = 0.004). BMI and serum albumin in HD patients were markedly reduced compared to controls. The patients with an insufficient intake of energy and protein demonstrated slightly lower levels of serum ghrelin. A negative correlation between serum ghrelin concentration with age (r = −0.34, P = 0.02), BUN (r = −0.26, P < 0.01), and serum creatinine (r = −0.27, P < 0.01) was observed in HD patients. Conclusions. The findings suggest that decreased ghrelin levels in HD patients might be associated with anorexia. Further studies are needed to determine changes in serum ghrelin levels during dialysis and to clarify whether the decrease in ghrelin levels contributes to the malnutrition that is common in these patients.

  15. Fatty acyltranferases in serum in cystic fibrosis (CF) patients

    SciTech Connect

    Zielenski, J.; Newman, L.J.; Slomiany, B.L.; Slomiany, A.

    1987-05-01

    Studies on serum and gastrointestinal secretion from CF patient is suggest that defective accumulation of mucus in gastrointestinal tract and excessive amount of a protease resistant peptides in serum are related to the abnormal activity of enzymes responsible for fatty acylation of proteins. Here, the authors investigated the fatty acyltransferase activities in serum of normal and CF patients. A 15 l of serum was mixed with 0.85 nmol ( UC)palmitoyl CoA, 200 g of serine and threonine and incubated at 37C for 30 min. The incubates were immediately frozen, dried extracted with C/M and chromatographed in chloroform/methanol/water. The incorporation of ( UC)palmitate was determined using linear radioscanner and authoradiography. The results of HPTLC revealed that CF serum in addition of ACAT and LCAT contained enzymes responsible for the transfer of ( UC)palmitate to monoacylphosphoglycerides, and serine and threonine. In normal serum the formation of a small amount of palmitoyl serine and palmitoyl threonine was also observed but the acylation of monoacylphosphoglycerides was not detectable. The authors conclude that in cystic fibrosis the abnormal fatty acyltransferases are responsible for the occurrence of protease resistant glycoprotein, unusual peptides in serum and possibly for the modification of membrane proteins and lipids.

  16. Levels of Serum Brain-Derived Neurotrophic Factor in Schizophrenia.

    PubMed

    Lee, Jimmy; Nurjono, Milawaty; Lee, Tih-Shih

    2016-08-01

    Recent meta-analyses of serum brain-derived neurotrophic factor (BDNF) have reported lower levels in patients with schizophrenia. However, most studies did not consider the potential confounding effects of time of collection, age, sex, smoking, and obesity. Here, we sought to examine differences in serum BDNF between medicated patients with schizophrenia compared with control subjects, taking into consideration the potential confounders of serum BDNF. Serum was obtained from a sample of fasted blood collected from all participants, and BDNF was assayed on a commercially available kit. After adjusting for potential confounders, there was no statistically significant difference between cases and control subjects (p = 0.261). In the model, body mass index emerged as the most significant predictor of serum BDNF (β = 0.22, p = 0.009). The present study did not support a role for serum BDNF as a biomarker in schizophrenia. This could be due to the nonspecific nature of serum BDNF and its association with both mental and physical conditions. PMID:27479612

  17. E6 and E7 oncoproteins from human papillomavirus type 16 induce activation of human transforming growth factor beta1 promoter throughout Sp1 recognition sequence.

    PubMed

    Peralta-Zaragoza, Oscar; Bermúdez-Morales, Víctor; Gutiérrez-Xicotencatl, Lourdes; Alcocer-González, Juan; Recillas-Targa, Félix; Madrid-Marina, Vicente

    2006-01-01

    Human Papillomavirus (HPV) infection is the main etiologic agent of cervical cancer and HPV E6 and E7 oncogenes trans-regulate many cellular genes. An association between TGF-beta1 gene expression and cervical cancer development has been suggested; however, the mechanisms by which HPV influences TGF-beta1 expression remain unclear. In the present study we analyzed the mechanism through which HPV-16 E6 and E7 oncoproteins regulate the TGF-beta1 promoter in cervical tumor cells. Our results showed that E6 and E7 increased TGF-beta1 promoter activity. Furthermore, we identified a specific DNA sequence motif in the TGF-beta1 core promoter that is responsible for trans-activation and that corresponds to the Sp1e-binding site associated with HPV-16 E6 and E7 oncoproteins. Mutational analysis showed that the Sp1e recognition site abolished the trans-activation caused by E6 and E7. These results suggest a physical interaction and functional cooperation between viral oncoproteins and cellular regulatory elements of the TGF-beta1 promoter, and may explain the contribution of HPV-16 to TGF-beta1 gene expression in cervical cancer. PMID:16987065

  18. Transforming growth factor-beta 1 in experimental autoimmune neuritis. Cellular localization and time course.

    PubMed Central

    Kiefer, R.; Funa, K.; Schweitzer, T.; Jung, S.; Bourde, O.; Toyka, K. V.; Hartung, H. P.

    1996-01-01

    Experimental autoimmune neuritis (EAN) is a monophasic inflammatory disorder of the peripheral nervous system that resolves spontaneously by molecular mechanisms as yet unknown. We have investigated whether the immunosuppressive cytokine transforming growth factor-beta 1 (TGF-beta 1) might be endogenously expressed in the peripheral nervous system of Lewis rats with actively induced and adoptive transfer EAN. TGF-beta 1 mRNA was upregulated to high levels in sensory and motor roots, spinal ganglia, and sciatic nerve as revealed by quantitative Northern blot analysis and in situ hybridization histochemistry, with peak levels just preceding the first signs of clinical recovery. TGF-beta 1 mRNA was localized to scattered round cells and dense cellular infiltrates, but only rarely to Schwann cell profiles. Double labeling studies revealed macrophages and subpopulations of T cells as the major cellular source of TGF-beta 1 mRNA. TGF-beta 1 protein was visualized immunocytochemically and localized to infiltrating mononuclear cells with peak expression around the same time as mRNA, in addition to some constitutive expression in axons and Schwann cells. Our studies suggest that the spontaneous recovery observed in Lewis rat EAN might be mediated by the endogenous elaboration of TGF-beta 1 within the peripheral nerve, and that macrophages might control their own cytotoxicity by expressing TGF-beta 1. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 PMID:8546208

  19. Hepatic expression of mature transforming growth factor beta 1 in transgenic mice results in multiple tissue lesions.

    PubMed

    Sanderson, N; Factor, V; Nagy, P; Kopp, J; Kondaiah, P; Wakefield, L; Roberts, A B; Sporn, M B; Thorgeirsson, S S

    1995-03-28

    Aberrant expression of transforming growth factor beta 1 (TGF-beta 1) has been implicated in a number of disease processes, particularly those involving fibrotic and inflammatory lesions. To determine the in vivo effects of overexpression of TGF-beta 1 on the function and structure of hepatic as well as extrahepatic tissues, transgenic mice were generated containing a fusion gene (Alb/TGF-beta 1) consisting of modified porcine TGF-beta 1 cDNA under the control of the regulatory elements of the mouse albumin gene. Five transgenic lines were developed, all of which expressed the Alb/TGF-beta 1 transgene selectively in hepatocytes. The transgenic line 25 expressing the highest level of the transgene in the liver also had high (> 10-fold over control) plasma levels of TGF-beta 1. Hepatic fibrosis and apoptotic death of hepatocytes developed in all the transgenic lines but was more pronounced in line 25. The fibrotic process was characterized by deposition of collagen around individual hepatocytes and within the space of Disse in a radiating linear pattern. Several extrahepatic lesions developed in line 25, including glomerulonephritis and renal failure, arteritis and myocarditis, as well as atrophic changes in pancreas and testis. The results from this transgenic model strongly support the proposed etiological role for TGF-beta 1 in a variety of fibrotic and inflammatory disorders. The transgenic model may also provide an appropriate paradigm for testing therapeutic interventions aimed at neutralizing the detrimental effects of this important cytokine. PMID:7708687

  20. Serum estrogen levels in men with acute myocardial infarction.

    PubMed

    Klaiber, E L; Broverman, D M; Haffajee, C I; Hochman, J S; Sacks, G M; Dalen, J E

    1982-12-01

    Serum estradiol and serum estrone levels were assessed in 29 men in 14 men in whom myocardial infarction was ruled out; in 12 men without apparent coronary heart disease but hospitalized in an intensive care unit; and in 28 men who were not hospitalized and who acted as control subjects. (The 12 men who were hospitalized but who did not have coronary heart disease were included to control for physical and emotional stress of a severe medical illness.) Ages ranged from 21 to 56 years. Age, height, and weight did not differ significantly among groups. Blood samples were obtained in the patient groups on each of the first three days of hospitalization. The serum estrone level was significantly elevated in all four patient groups when compared with that in the control group. Estrone level, then, did not differentiate patients with and without coronary heart disease. Serum estradiol levels were significantly elevated in the groups with myocardial infarction, unstable angina, and in the group in whom myocardial infarction was ruled out. However, estradiol levels were not significantly elevated in the group in the intensive care unit without coronary heart disease when compared to the level in the normal control group. Serum estradiol levels, then, were elevated in men with confirmed or suspected coronary heart disease but were not elevated in men without coronary heart disease even under the stressful conditions found in an intensive care unit. Serum estradiol levels were significantly and positively correlated (p less than 0.03) with serum total creatine phosphokinase levels in the patients with myocardial infarction. The five patients with myocardial infarction who died within 10 days of admission had markedly elevated serum estradiol levels. The potential significance of these serum estradiol elevations is discussed in terms of estradiol's ability to enhance adrenergic neural activity and the resultant increase in myocardial oxygen demand. PMID:7148879

  1. Rapamycin selectively alters serum chemistry in diabetic mice

    PubMed Central

    Tabatabai-Mir, Hooman; Sataranatarajan, Kavithalakshmi; Lee, Hak Joo; Bokov, Alex F.; Fernandez, Elizabeth; Diaz, Vivian; Choudhury, Goutam Ghosh; Richardson, Arlan; Kasinath, Balakuntalam S.

    2012-01-01

    The study was undertaken to explore the effect of rapamycin, an anti-inflammatory agent, on the metabolic profile of type 2 diabetic mice. Seven-month-old diabetic db/db mice and their lean littermate non-diabetic controls (db/m) were randomized to receive control chow or chow mixed with rapamycin (2.24 mg/kg/day) (each group n =20, males and females) for 4 months and sacrificed. Serum samples were analyzed for the measurement of glucose, creatinine, blood urea nitrogen (BUN), alkaline phosphatase (ALP), alanine aminotransferase (ALT), total cholesterol, total triglyceride, and total protein, using the automated dry chemistry analysis. Rapamycin elevated serum glucose in female diabetic mice. Serum creatinine tended to be higher in diabetic mice but was not affected by rapamycin; there was no difference in BUN levels among the groups. Serum ALP was elevated in diabetic mice and rapamycin lowered it only in female diabetic mice; serum ALT levels were increased in female diabetic mice, unaffected by rapamycin. Serum total protein was elevated in diabetic mice of both genders but was not affected by rapamycin. Diabetic mice from both genders had elevated serum cholesterol and triglycerides; rapamycin did not affect serum cholesterol but decreased serum total triglycerides in male diabetic mice. We conclude that rapamycin elicits complex metabolic responses in aging diabetic mice, worsening hyperglycemia in females but improving ALP in female diabetic and total triglycerides in male diabetic mice, respectively. The metabolic effects of rapamycin should be considered while performing studies with rapamycin in mice. PMID:22953036

  2. Low Serum Hepcidin in Patients with Autoimmune Liver Diseases

    PubMed Central

    Saitis, Asterios; Gabeta, Stella; Eliades, Petros; Paraskeva, Efrosini; Zachou, Kalliopi; Koukoulis, George K.; Mamalaki, Avgi; Dalekos, George N.; Simos, George

    2015-01-01

    Hepcidin, a liver hormone, is important for both innate immunity and iron metabolism regulation. As dysfunction of the hepcidin pathway may contribute to liver pathology, we analysed liver hepcidin mRNA and serum hepcidin in patients with chronic liver diseases. Hepcidin mRNA levels were determined in liver biopsies obtained from 126 patients with HCV (n = 21), HBV (n = 23), autoimmune cholestatic disease (primary biliary cirrhosis and primary sclerosing cholangitis; PBC/PSC; n = 34), autoimmune hepatitis (AIH; n = 16) and non-alcoholic fatty liver disease (NAFLD; n = 32). Sera sampled on the biopsy day from the same patients were investigated for serum hepcidin levels. Hepatic hepcidin mRNA levels correlated positively with ferritin and negatively with serum γ-GT levels. However, no correlation was found between serum hepcidin and either ferritin or liver hepcidin mRNA. Both serum hepcidin and the serum hepcidin/ferritin ratio were significantly lower in AIH and PBC/PSC patients’ sera compared to HBV, HCV or NAFLD (P<0.001 for each comparison) and correlated negatively with serum ALP levels. PBC/PSC and AIH patients maintained low serum hepcidin during the course of their two-year long treatment. In summary, parallel determination of liver hepcidin mRNA and serum hepcidin in patients with chronic liver diseases shows that circulating hepcidin and its respective ratio to ferritin are significantly diminished in patients with autoimmune liver diseases. These novel findings, once confirmed by follow-up studies involving bigger size and better-matched disease subgroups, should be taken into consideration during diagnosis and treatment of autoimmune liver diseases. PMID:26270641

  3. 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

  4. Atomic structure and chemistry of human serum albumin

    NASA Technical Reports Server (NTRS)

    He, Xiao M.; Carter, Daniel C.

    1992-01-01

    The three-dimensional structure of human serum albumin has been determined crystallographically to a resolution of 2.8 A. It comprises three homologous domains that assemble to form a heart-shaped molecule. Each domain is a product of two subdomains that possess common structural motifs. The principal regions of ligand binding to human serum albumin are located in hydrophobic cavities in subdomains IIA and ILIA, which exhibit similar chemistry. The structure explains numerous physical phenomena and should provide insight into future pharmacokinetic and genetically engineered therapeutic applications of serum albumin.

  5. Determinants that increase the serum resistance of Escherichia coli.

    PubMed Central

    Taylor, P W; Robinson, M K

    1980-01-01

    The rfb locus, determining biosynthesis of O8-specific lipopolysaccharide side chains, was transferred to a rough mutant of Escherichia coli; recombinants producing a complete lipopolysaccharide were more resistant to the complement-mediated bactericidal action of human serum than the rough recipient. Inheritance of the his-linked genes for K27 antigen production did not alter the response to serum. The serum resistance of strains carrying O8 side chains, but not of strains with incomplete lipopolysaccharides, was further increased by inheritance of plasmids R1 and NR1.20 PMID:6995340

  6. Polychlorinated biphenyl (PCB) partitioning between adipose tissue and serum

    SciTech Connect

    Brown, J.F. Jr.; Lawton, R.W.

    1984-09-01

    It has been recently suggested that variabilities in the partitioning of chronically retained lipophilic xenobiotics between adipose tissue and serum may be relatable to variations in the lipid content of the serum. Here, the authors present theoretical considerations and experimental data showing that this is indeed the case for polychlorinated biphenyls (PCBs) in humans. At equilibrium, in the absence of active transport, any lipophilic substance must distribute itself among body tissues in such a way that its chemical activity and also its chemical potential are the same at all points. In order to verify the theoretical relationships, three sorts of data relating to serum PCB levels in a human population were examined.

  7. New serum biomarkers for prostate cancer diagnosis

    PubMed Central

    Chadha, Kailash C.; Miller, Austin; Nair, Bindukumar B.; Schwartz, Stanley A.; Trump, Donald L.; Underwood, Willie

    2014-01-01

    Background Prostate-specific antigen (PSA) is currently used as a biomarker for diagnosis and management of prostate cancer (CaP). However, PSA typically lacks the sensitivity and specificity desired of a diagnostic marker. Objective The goal of this study was to identify an additional biomarker or a panel of biomarkers that is more sensitive and specific than PSA in differentiating benign versus malignant prostate disease and/or localized CaP versus metastatic CaP. Methods Concurrent measurements of circulating interleukin-8 (IL-8), Tumor necrosis factor-α (TNF-α) and soluble tumor necrosis factor-α receptors 1 (sTNFR1) were obtained from four groups of men: (1) Controls (2) with elevated prostate-specific antigen with a negative prostate biopsy (elPSA_negBx) (3) with clinically localized CaP and (4) with castration resistant prostate cancer. Results TNF-α Area under the receiver operating characteristic curve (AUC = 0.93) and sTNFR1 (AUC = 0.97) were strong predictors of elPSA_negBx (vs. CaP). The best predictor of elPSA_negBx vs CaP was sTNFR1 and IL-8 combined (AUC = 0.997). The strongest single predictors of localized versus metastatic CaP were TNF-α (AUC = 0.992) and PSA (AUC = 0.963) levels. Conclusions The specificity and sensitivity of a PSA-based CaP diagnosis can be significantly enhanced by concurrent serum measurements of IL-8, TNF-α and sTNFR1. In view of the concerns about the ability of PSA to distinguish clinically relevant CaP from indolent disease, assessment of these biomarkers in the larger cohort is warranted. PMID:25593898

  8. Human serum metabolic profiles are age dependent.

    PubMed

    Yu, Zhonghao; Zhai, Guangju; Singmann, Paula; He, Ying; Xu, Tao; Prehn, Cornelia; Römisch-Margl, Werner; Lattka, Eva; Gieger, Christian; Soranzo, Nicole; Heinrich, Joachim; Standl, Marie; Thiering, Elisabeth; Mittelstraß, Kirstin; Wichmann, Heinz-Erich; Peters, Annette; Suhre, Karsten; Li, Yixue; Adamski, Jerzy; Spector, Tim D; Illig, Thomas; Wang-Sattler, Rui

    2012-12-01

    Understanding the complexity of aging is of utmost importance. This can now be addressed by the novel and powerful approach of metabolomics. However, to date, only a few metabolic studies based on large samples are available. Here, we provide novel and specific information on age-related metabolite concentration changes in human homeostasis. We report results from two population-based studies: the KORA F4 study from Germany as a discovery cohort, with 1038 female and 1124 male participants (32-81 years), and the TwinsUK study as replication, with 724 female participants. Targeted metabolomics of fasting serum samples quantified 131 metabolites by FIA-MS/MS. Among these, 71/34 metabolites were significantly associated with age in women/men (BMI adjusted). We further identified a set of 13 independent metabolites in women (with P values ranging from 4.6 × 10(-04) to 7.8 × 10(-42) , α(corr) = 0.004). Eleven of these 13 metabolites were replicated in the TwinsUK study, including seven metabolite concentrations that increased with age (C0, C10:1, C12:1, C18:1, SM C16:1, SM C18:1, and PC aa C28:1), while histidine decreased. These results indicate that metabolic profiles are age dependent and might reflect different aging processes, such as incomplete mitochondrial fatty acid oxidation. The use of metabolomics will increase our understanding of aging networks and may lead to discoveries that help enhance healthy aging. PMID:22834969

  9. Challenges of measuring monoclonal proteins in serum.

    PubMed

    Keren, David F; Schroeder, Lee

    2016-06-01

    The measurement of monoclonal protein (M-protein) is vital for stratifying risk and following individuals with a variety of monoclonal gammopathies. Direct measurement of the M-protein spike by electrophoresis and immunochemical measurements of specific isotypes or free light chains pairs has provided useful information about the quantity of M-protein. Nonetheless, both traditional electrophoresis and immunochemical methods give poor quantification with M-proteins smaller than 10 g/L (1 g/dL) when in the presence of polyclonal immunoglobulins that co-migrate with the M-protein. In addition, measurements by electrophoresis of M-proteins migrating in the β- and α-regions are contaminated by normal serum proteins in those regions. The most precise electrophoretic method to date for quantification involves exclusion of the polyclonal immunoglobulins by using the tangent skimming method on electropherograms, which provides a 10-fold improvement in precision. So far, however, tangent measurements are limited to γ migrating M-proteins. Another way to improve M-protein measurements is the use of capillary electrophoresis (CE). With CE, one can employ immunosubtraction to select a region of interest in the β region thereby excluding much of the normal proteins from the M-protein measurement. Recent development of an immunochemical method distinguishing heavy/light chain pairs (separately measuring IgGK and IgGL, IgAK and IgAL, and IgMK and IgML) provides measurements that could exclude polyclonal contaminants of the same heavy chain with the uninvolved light chain type. Yet, even heavy/light results contain an immeasurable quantity of polyclonal heavy/light chains of the involved isotype. Finally, use of liquid chromatography-tandem mass spectrometry (LC-MS/MS) looms on the horizon as a means to provide more consistent and sensitive measurements of M-proteins. PMID:26910744

  10. Protection of transforming growth factor-beta 1 activity by heparin and fucoidan.

    PubMed

    McCaffrey, T A; Falcone, D J; Vicente, D; Du, B; Consigli, S; Borth, W

    1994-04-01

    The transforming growth factor-beta (TGF-beta) family of proteins exert diverse and potent effects on proliferation, differentiation, and extracellular matrix synthesis. However, relatively little is known about the stability or processing of endogenous TGF-beta activity in vitro or in vivo. Our previous work indicated that 1) TGF-beta 1 has strong heparin-binding properties that were not previously recognized because of neutralization by iodination, and 2) heparin, and certain other polyanions, could block the binding of TGF-beta 1 to alpha 2-macroglobulin (alpha 2-M). The present studies investigated the influence of heparin-like molecules on the stability of the TGF-beta 1 signal in the pericellular environment. The results indicate that heparin and fucoidan, a naturally occurring sulfated L-fucose polymer, suppress the formation of an initial non-covalent interaction between 125I-TGF-beta 1 and activated alpha 2-M. Electrophoresis of 125I-TGF-beta 1 showed that fucoidan protects TGF-beta 1 from proteolytic degradation by plasmin and trypsin. While plasmin caused little, if any, activation of latent TGF-beta derived from vascular smooth muscle cells (SMC), plasmin degraded acid-activated TGF-beta, and purified TGF-beta 1, and this degradation was inhibited by fucoidan. In vitro, heparin and fucoidan tripled the half-life of 125I-TGF-beta 1 and doubled the amount of cell-associated 125I-TGF-beta 1. Consistent with this protective effect, heparin- and fucoidan-treated SMC demonstrated elevated levels of active, but not latent, TGF-beta activity. PMID:7511146

  11. Long-term exposure of proximal tubular epithelial cells to glucose induces transforming growth factor-beta 1 synthesis via an autocrine PDGF loop.

    PubMed

    Fraser, Donald; Brunskill, Nigel; Ito, Takafumi; Phillips, Aled

    2003-12-01

    We have recently reported increased transforming growth factor (TGF)-beta1 gene transcription in proximal tubular cells within 12 hours of exposure to 25 mmol/L D-glucose, with a requirement for a second stimulus such as platelet-derived growth factor (PDGF) to increase its translation in short-term experiments. In the current study we investigated the effect on TGF-beta 1 production of prolonged exposure of proximal tubular cells to high glucose concentrations. Enzyme-linked immunosorbent assay of cell culture supernatant showed significant increase in latent TGF-beta 1 only after 7 days exposure to high glucose. Radiolabeling of glucose-stimulated cells with (3)H amino acids and subsequent immunoprecipitation of TGF-beta 1 demonstrated de novo synthesis from day 5 of high glucose exposure onwards. Similarly, polysome analysis showed enhanced translation of TGF-beta mRNA after 4 or more days of high glucose exposure. TGF-beta 1 synthesis, following addition of glucose, was inhibited by blockade of the PDGF-alpha receptor subunit. Glucose did not alter PDGF expression, nor expression of PDGF alpha-receptors. Activation of the receptor following addition of 25 mm D-glucose could be demonstrated suggesting increased sensitivity to endogenous PDGF. Exposure to glucose activated p38MAP kinase, and inhibition of this activation abrogated both glucose induced TGF-beta 1 transcriptional activation and TGF-beta 1 synthesis. Inhibition of p38MAP kinase did not influence the effect of exogenous PDGF when cells were stimulated sequentially by glucose and PDGF. We postulate that glucose induces an early increase in TGF-beta 1 transcription via activation of p38MAP kinase. In addition, glucose causes a late increase in PDGF-dependent TGF-beta 1 translation by enhancing cellular sensitivity to PDGF. This provides a potential explanation for the clinical observation that prolonged poor glycemic control may contribute to progression of diabetic nephropathy. PMID:14633628

  12. Posaconazole in Human Serum: a Greater Pharmacodynamic Effect than Predicted by the Non-Protein-Bound Serum Concentration ▿

    PubMed Central

    Lignell, Anders; Löwdin, Elisabeth; Cars, Otto; Chryssanthou, Erja; Sjölin, Jan

    2011-01-01

    It is generally accepted that only the unbound fraction of a drug is pharmacologically active. Posaconazole is an antifungal agent with a protein binding of 98 to 99%. Taking into account the degree of protein binding, plasma levels in patients, and MIC levels of susceptible strains, it can be assumed that the free concentration of posaconazole sometimes will be too low to exert the expected antifungal effect. The aim was therefore to test the activity of posaconazole in serum in comparison with that of the calculated unbound concentrations in protein-free media. Significant differences (P < 0.05) from the serum control were found at serum concentrations of posaconazole of 1.0 and 0.10 mg/liter, with calculated free concentrations corresponding to 1× MIC and 0.1× MIC, respectively, against one Candida lusitaniae strain selected for proof of principle. In RPMI 1640, the corresponding calculated unbound concentration of 0.015 mg/liter resulted in a significant effect, whereas that of 0.0015 mg/liter did not. Also, against seven additional Candida strains tested, there was an effect of the low posaconazole concentration in serum, in contrast to the results in RPMI 1640. Fluconazole, a low-grade-protein-bound antifungal, was used for comparison at corresponding concentrations in serum and RPMI 1640. No effect was observed at the serum concentration, resulting in a calculated unbound concentration of 0.1× MIC. In summary, there was a substantially greater pharmacodynamic effect of posaconazole in human serum than could be predicted by the non-protein-bound serum concentration. A flux from serum protein-bound to fungal lanosterol 14α-demethylase-bound posaconazole is suggested. PMID:21502622

  13. Fluorescence lifetime measurements of native and glycated human serum albumin and bovine serum albumin

    NASA Astrophysics Data System (ADS)

    Joshi, Narahari V.; Joshi, Virgina O. d.; Contreras, Silvia; Gil, Herminia; Medina, Honorio; Siemiarczuk, Aleksander

    1999-05-01

    Nonenzymatic glycation, also known as Maillard reaction, plays an important role in the secondary complications of the diabetic pathology and aging, therefore, human serum albumin (HSA) and bovine serum albumin (BSA) were glycated by a conventional method in our laboratory using glucose as the glycating agent. Fluorescence lifetime measurements were carried out with a laser strobe fluorometer equipped with a nitrogen/dye laser and a frequency doubler as a pulsed excitation source. The samples were excited at 295 nm and the emission spectra were recorded at 345 nm. The obtained decay curves were tried for double and triple exponential functions. It has been found that the shorter lifetime increases for glycated proteins as compared with that of the native ones. For example, in the case of glycated BSA the lifetime increased from 1.36 ns to 2.30 ns. Similarly, for HSA, the lifetime increases from 1.58 ns to 2.26 ns. Meanwhile, the longer lifetime changed very slightly for both proteins (from 6.52 ns to 6.72 ns). The increase in the lifetime can be associated with the environmental effect; originated from the attachment of glucose to some lysine residues. A good example is Trp 214 which is in the cage of Lys 225, Lys 212, Lys 233, Lys 205, Lys 500, Lys 199 and Lys 195. If fluorescence lifetime technique is calibrated and properly used it could be employed for assessing glycation of proteins.

  14. Detection of decreased glomerular filtration rate in intensive care units: serum cystatin C versus serum creatinine

    PubMed Central

    2014-01-01

    Background Detecting impaired glomerular filtration rate (GFR) is important in intensive care units (ICU) in order to diagnose acute kidney injuries and adjust the dose of renally excreted drugs. Whether serum Cystatin C (SCysC) may better reflect glomerular filtration rate than serum creatinine (SCr) in the context of intensive care medicine is uncertain. Methods We compared the performance of SCysC and SCr as biomarkers of GFR in 47 critically ill patients (median SOFA (Sepsis-related Organ Failure Assessment) score of 5) for whom GFR was measured by a reference method (urinary clearance of iohexol). Results Mean Iohexol clearance averaged 96 ± 54 mL/min and was under 60 mL/min in 28% of patients. Mean SCr and SCysC concentrations were 0.70 ± 0.33 mg/dL and 1.26 ± 0.61 mg/L, respectively. Area under the ROC curve for a GFR threshold of 60 mL/min was 0.799 and 0.942 for SCr and SCysC, respectively (p = 0.014). Conclusions We conclude that ScysC significantly outperfoms SCr for the detection of an impaired GFR in critically ill patients. Trial registration ClinicalTrials.gov: B7072006347 PMID:24410757

  15. Interaction of ergosterol with bovine serum albumin and human serum albumin by spectroscopic analysis.

    PubMed

    Cheng, Zhengjun

    2012-10-01

    This study was designed to examine the interactions of ergosterol with bovine serum albumin (BSA) and human serum albumin (HSA) under physiological conditions with the drug concentrations in the range of 2.99-105.88 μM and the concentration of proteins was fixed at 5.0 μM. The analysis of emission spectra quenching at different temperatures revealed that the quenching mechanism of HSA/BSA by ergosterol was the static quenching. The number of binding sites n and the binding constants K were obtained at various temperatures. The distance r between ergosterol and HSA/BSA was evaluated according to Föster non-radioactive energy transfer theory. The results of synchronous fluorescence, 3D fluorescence, FT-IR, CD and UV-Vis absorption spectra showed that the conformations of HSA/BSA altered in the presence of ergosterol. The thermodynamic parameters, free energy change (ΔG), enthalpy change (ΔH) and entropy change (ΔS) for BSA-ergosterol and HSA-ergosterol systems were calculated by the van't Hoff equation and discussed. Besides, with the aid of three site markers (for example, phenylbutazone, ibuprofen and digitoxin), we have reported that ergosterol primarily binds to the tryptophan residues of BSA/HSA within site I (subdomain II A). PMID:22733490

  16. Prevalence of antileptospiral serum antibodies in dogs in Ireland

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A total of 474 serum samples from client owned Irish dogs were tested for the presence of antibodies against serovars Canicola, Icterohaemorrhagiae, Bratislava, Autumnalis, Pomona, Altodouro, Grippotyphosa, Mozdok, Hardjobovis and Ballum. Six percent of dogs presented to veterinary practitioners for...

  17. 99M-technetium labeled macroaggregated human serum albumin pharmaceutical

    DOEpatents

    Winchell, Harry S.; Barak, Morton; Van Fleet, III, Parmer

    1977-05-17

    A reagent comprising macroaggregated human serum albumin having dispersed therein particles of stannous tin and a method for instantly making a labeled pharmaceutical therefrom, are disclosed. The labeled pharmaceutical is utilized in organ imaging.

  18. Preterm delivery and low maternal serum cholesterol level: Any correlation?

    PubMed Central

    Oluwole, Ayodeji A.; Adegbesan-Omilabu, Maymunah A.; Okunade, Kehinde S.

    2014-01-01

    Background: The study assessed whether low maternal serum cholesterol during early pregnancy is associated with preterm delivery. Patients and Methods: It was a prospective observational cohort study involving pregnant women at gestational age of 14-20 weeks over a period of 12 months. Blood samples were obtained to measure total serum cholesterol concentrations and the sera were then analysed enzymatically by the cholesterol oxidase: p-aminophenazone (CHOD PAP) method. Results: The study showed an incidence of 5.0% for preterm delivery in the low risk study patients. Preterm birth was 4.83-times more common with low total maternal cholesterol than with midrange total cholesterol (11.8% versus 2.2%, P = 0.024). Conclusion: Low maternal serum cholesterol (hypocholesterolaemia) is associated with preterm delivery. Optimal maternal serum cholesterol during pregnancy may have merit, therefore pregnant women should be encouraged to follow a healthy, balanced diet. PMID:25298606

  19. Interaction of Serum Proteins with Surface of Hemodialysis Fiber Membranes

    NASA Astrophysics Data System (ADS)

    Afrin, Rehana; Shirako, Yuji; Kishimoto, Kikuo; Ikai, Atsushi

    2012-08-01

    The poly(vinyl pyrrolidone)-covered hydrophilic surface of hollow-fiber membranes (fiber membrane, hereafter) for hemodialysis was mechanically probed using modified tips on an atomic force microscope (AFM) with covalent crosslinkers and several types of serum protein. The retraction part of many of the force extension (F-E) curves obtained with AFM tips coated with serum albumin had a long and smooth extension up to 200-300 nm indicating forced elongation of poly(vinyl pyrrolidone) chains. When fibrinogen-coated tips were used, long extension F-E curves up to 500 nm with multiple peaks were obtained in addition to smooth curves most likely reflecting the unfolding of fibrinogen molecules. The results indicated that individual polymer chains had a significant affinity toward serum proteins. The adhesion frequency of tips coated with serum proteins was lower on the poly(vinyl pyrrolidone) surface than on the uncoated hydrophobic polysulfone surface.

  20. Depressed serum erythropoietin in pregnant women with elevated blood lead.

    PubMed

    Graziano, J H; Slavkovic, V; Factor-Litvak, P; Popovac, D; Ahmedi, X; Mehmeti, A

    1991-01-01

    During the course of a prospective study of lead exposure and pregnancy outcome in 1,502 women, we tested the hypothesis that environmental lead exposure is associated with depressed serum erythropoietin concentration. At mid-pregnancy and at delivery, blood samples were stratified by hemoglobin concentration; within each hemoglobin stratum, sera of women with the lowest and highest whole blood lead concentrations were selected for serum erythropoietin analysis. Analysis of variance revealed that women with higher blood lead levels had inappropriately low serum erythropoietin at both mid-pregnancy and at delivery. Thus, depressed serum erythropoietin appears to indicate lead nephrotoxicity, and it may also be responsible for the anemia associated with lead poisoning. PMID:1772259

  1. The replacement of serum by hormones in cell culture media.

    PubMed

    Sato, G; Hayashi, I

    1976-12-01

    The replacement of serum by hormones in cell culture media. (Reemplazo del suero por hormonas en el medio de cultivo de células). Arch. Biol. Med. Exper. 10: 120-121, 1976. The serum used in cell culture media can be replaced by a mixture of hormones and some accesory blood factors. The pituitary cell line GH3 can be grown in a medium in which serum is replaced by triiodothyronine, transferrin, parathormone, tyrotrophin releasing hormone and somatomedins. Hela and BHK cell strains can also be grown in serum free medium supplemented with hormones. Each cell type appears to have different hormonal requirements yet it may found that some hormones are required for most cell types. PMID:1026199

  2. Immunoblot technique to visualise serum pepsinogen A isozymogen patterns.

    PubMed Central

    Zwiers, A; Toonstra, C; Pals, G; Donker, A J; Meuwissen, S G; ten Kate, R W

    1990-01-01

    Pepsinogen A (PGA) isozymogen patterns in urine and gastric mucosa can be visualised in non-denatured polyacrylamide gel electrophoresis by showing proteolytic activity after the conversion of pepsinogen into pepsin by acid. This method is not suitable for visualising PGA patterns in serum due to low PGA concentrations. To obtain a more sensitive visualisation method an immunoblotting technique was developed. PGA isozymogen patterns from urine and sonified gastric mucosa specimens obtained by immunoblotting were identical with those obtained by activity staining. The immunostaining method was at least 50 times more sensitive. PGA isozymogen patterns could be visualised in serum. Preliminary results suggest that the PGA patterns in serum and gastric mucosa are identical. As an association has been found between the genetically determined PGA isozymogen patterns in gastric mucosa and gastric malignancies in man, immunoblotting of PGA isozymogens in serum may provide a screening tool for subjects at risk of malignant gastric disease. Images PMID:2229438

  3. Goat serums for fluorescent antibody conjugates to chlamydial antigens.

    PubMed Central

    Tessler, J

    1984-01-01

    Serums from goats hyperimmunized with Chlamydia psittaci consistently produce antichlamydial fluorescent antibody conjugate of high titer. The titer of the fluorescent antibody conjugate prepared from a given serum correlated well with the titer obtained by agar gel precipitin, but not with the complement fixation. The agar gel precipitin test can be used to predict whether a given serum is satisfactory for use in production of a conjugate for direct fluorescent antibody tests. Serums with an agar gel precipitin titer of 1/8 or higher generally produce a usable fluorescent antibody conjugate. Labeling gamma globulins with fluorescein isothiocyanate at a ratio of 1/150 resulted in satisfactory fluorescent antibody conjugates. Cultures of Vero cells infected with chlamydiae were found to be suitable for titration of the fluorescent antibody conjugates. PMID:6372973

  4. Reductions in serum IGF-1 during aging impair health span

    PubMed Central

    Gong, Zhenwei; Kennedy, Oran; Sun, Hui; Wu, YingJie; Williams, Garry A; Klein, Laura; Cardoso, Luis; Matheny, Ronald W; Hubbard, Gene B; Ikeno, Yuji; Farrar, Roger P; Schaffler, Mitchell B; Adamo, Martin L; Muzumdar, Radhika H; Yakar, Shoshana

    2014-01-01

    In lower or simple species, such as worms and flies, disruption of the insulin-like growth factor (IGF)-1 and the insulin signaling pathways has been shown to increase lifespan. In rodents, however, growth hormone (GH) regulates IGF-1 levels in serum and tissues and can modulate lifespan via/or independent of IGF-1. Rodent models, where the GH/IGF-1 axis was ablated congenitally, show increased lifespan. However, in contrast to rodents where serum IGF-1 levels are high throughout life, in humans, serum IGF-1 peaks during puberty and declines thereafter during aging. Thus, animal models with congenital disruption of the GH/IGF-1 axis are unable to clearly distinguish between developmental and age-related effects of GH/IGF-1 on health. To overcome this caveat, we developed an inducible liver IGF-1-deficient (iLID) mouse that allows temporal control of serum IGF-1. Deletion of liver Igf -1 gene at one year of age reduced serum IGF-1 by 70% and dramatically impaired health span of the iLID mice. Reductions in serum IGF-1 were coupled with increased GH levels and increased basal STAT5B phosphorylation in livers of iLID mice. These changes were associated with increased liver weight, increased liver inflammation, increased oxidative stress in liver and muscle, and increased incidence of hepatic tumors. Lastly, despite elevations in serum GH, low levels of serum IGF-1 from 1 year of age compromised skeletal integrity and accelerated bone loss. We conclude that an intact GH/IGF-1 axis is essential to maintain health span and that elevated GH, even late in life, associates with increased pathology. PMID:24341939

  5. Reductions in serum IGF-1 during aging impair health span.

    PubMed

    Gong, Zhenwei; Kennedy, Oran; Sun, Hui; Wu, YingJie; Williams, Garry A; Klein, Laura; Cardoso, Luis; Matheny, Ronald W; Hubbard, Gene B; Ikeno, Yuji; Farrar, Roger P; Schaffler, Mitchell B; Adamo, Martin L; Muzumdar, Radhika H; Yakar, Shoshana

    2014-06-01

    In lower or simple species, such as worms and flies, disruption of the insulin-like growth factor (IGF)-1 and the insulin signaling pathways has been shown to increase lifespan. In rodents, however, growth hormone (GH) regulates IGF-1 levels in serum and tissues and can modulate lifespan via/or independent of IGF-1. Rodent models, where the GH/IGF-1 axis was ablated congenitally, show increased lifespan. However, in contrast to rodents where serum IGF-1 levels are high throughout life, in humans, serum IGF-1 peaks during puberty and declines thereafter during aging. Thus, animal models with congenital disruption of the GH/IGF-1 axis are unable to clearly distinguish between developmental and age-related effects of GH/IGF-1 on health. To overcome this caveat, we developed an inducible liver IGF-1-deficient (iLID) mouse that allows temporal control of serum IGF-1. Deletion of liver Igf-1 gene at one year of age reduced serum IGF-1 by 70% and dramatically impaired health span of the iLID mice. Reductions in serum IGF-1 were coupled with increased GH levels and increased basal STAT5B phosphorylation in livers of iLID mice. These changes were associated with increased liver weight, increased liver inflammation, increased oxidative stress in liver and muscle, and increased incidence of hepatic tumors. Lastly, despite elevations in serum GH, low levels of serum IGF-1 from 1 year of age compromised skeletal integrity and accelerated bone loss. We conclude that an intact GH/IGF-1 axis is essential to maintain health span and that elevated GH, even late in life, associates with increased pathology. PMID:24341939

  6. Serum metabolic profiles of pregnant women with burdened obstetrical history.

    PubMed

    Khaustova, S A; Senyavina, N V; Tonevitsky, A G; Eremina, O V; Pavlovich, S V

    2013-11-01

    The content of low-molecular-weight components in blood serum was studied by tandem mass-spectrometry in pregnant women. Serum metabolic profiles of patients with a grave obstetrical history were detected. The most significant changes were observed for the concentrations of low-molecular-weight substances involved in glucogenesis and β-oxidation processes and in metabolic chains involving carbohydrates, carnitines, amino acids, and lipids. PMID:24319740

  7. Relationship between urinary and serum growth hormone and pubertal status.

    PubMed Central

    Crowne, E C; Wallace, W H; Shalet, S M; Addison, G M; Price, D A

    1992-01-01

    Urinary growth hormone (uGH) excretion and serum growth hormone concentrations have been compared in three groups of children. Group 1 consisted of 21 children who had had cranial irradiation as part of their treatment for acute lymphoblastic leukaemia; group 2, 18 normal children; and group 3, 12 boys with constitutional delay in growth and puberty who were in early puberty. Children in groups 1 and 2 each had a 24 hour serum growth hormone profile (sampling every 20 minutes) and concurrent urine collection. The 12 boys in group 3 had a total of 21 profiles (sampling every 15 minutes for 12 hours) and concurrent urine collections. In the prepubertal children (n = 17), in both groups 1 and 2, there was a significant correlation between mean serum growth hormone and total uGHng/g creatinine. There were also significant correlations between total uGHng/g creatinine and both peak serum growth hormone and mean amplitude of the pulses in the growth hormone profile. In the pubertal children (n = 22), in groups 1 and 2, whether combined or in separate groups, there was no significant correlation between total uGHng/g creatinine and mean serum growth hormone, peak serum growth hormone, or mean amplitude of the pulses in the growth hormone profile. In group 3 there were significant correlations between total uGHng/g creatinine and both the mean serum growth hormone and mean amplitude of the pulses in the profile. Therefore uGH estimations appear to correlate well with serum growth hormone profiles in children who are prepubertal or in early puberty, but not in those further advanced in pubertal development. These results may reflect a variation in the renal handling of growth hormone during pubertal development. uGH estimation may be an unreliable screening investigation for growth hormone sufficiency in mid to late puberty. PMID:1739346

  8. [Serum beta 2 microglobulin (beta 2M) following renal transplantation].

    PubMed

    Pacheco-Silva, A; Nishida, S K; Silva, M S; Ramos, O L; Azjen, H; Pereira, A B

    1994-01-01

    Although there was an important improvement in graft and patient survival the last 10 years, graft rejection continues to be a major barrier to the success of renal transplantation. Identification of a laboratory test that could help to diagnose graft rejection would facilitate the management of renal transplanted patients. PURPOSE--To evaluate the utility of monitoring serum beta 2M in recently transplanted patients. METHODS--We daily determined serum beta 2M levels in 20 receptors of renal grafts (10 from living related and 10 from cadaveric donors) and compared them to their clinical and laboratory evolution. RESULTS--Eight patients who presented immediate good renal function following grafting and did not have rejection had a mean serum beta 2M of 3.7 mg/L on the 4th day post transplant. The sensitivity of the test for the diagnosis of acute rejection was 87.5%, but the specificity was only 46%. Patients who presented acute tubular necrosis (ATN) without rejection had a progressive decrease in their serum levels of beta 2M, while their serum creatinine changed as they were dialyzed. In contrast, patients with ATN and concomitance of acute rejection or CSA nephrotoxicity presented elevated beta 2M and creatinine serum levels. CONCLUSION--Daily monitoring of serum beta 2M does not improve the ability to diagnose acute rejection in patients with good renal function. However, serum beta 2M levels seemed to be useful in diagnosing acute rejection or CSA nephrotoxicity in patients with ATN. PMID:7787867

  9. A serum component mediates food restriction-induced growth attenuation.

    PubMed

    Pando, Rakefet; Shtaif, Biana; Phillip, Moshe; Gat-Yablonski, Galia

    2014-03-01

    Proper nutrition in terms of calories and essential food components is required to maximize longitudinal growth in children. Our previous study showed that prepubertal male rats subjected to 10 days of 40% food restriction (RES) exhibited a dramatic reduction in weight and epiphyseal growth plate height, as well as changes in gene expression and microRNAs (miRNAs) in the epiphyseal growth plate. These findings reversed rapidly after renewal of the regular food supply (catch-up [CU]). To further elucidate the mechanisms underlying the nutrition-growth association, serum collected from the RES and CU rats and control rats fed ad libitum (AL) was added to the culture medium of the chondrocyte cell line ATDC5 (instead of fetal calf serum). Serum from the RES group induced a reduction in cell viability (25%, P < .05) concomitant with an increase in cell differentiation compared with that for the AL group serum. The most interesting observation, in our opinion, was the significant reduction in the expression of specific miRNAs, including the chondro-specific miR-140. These effects were not observed for serum from refed (CU) rats. Serum levels of IGF-I, leptin, and fibroblast growth factor 21 were reduced by food restriction. The addition of IGF-I and leptin to the culture increased cell viability, whereas fibroblast growth factor 21 reduced it, suggesting the involvement of IGF-I, leptin, and possibly other still unidentified serum factors in chondrocyte cell growth. In conclusion, specific miRNAs respond to nutritional cues, and these effects are mediated by serum-borne factors. These results may promote the development of superior interventions for children with malnutrition and growth abnormalities. PMID:24456162

  10. TRANSFERRIN: VARIATIONS IN BLOOD SERUM OF RED HOWLER MONKEYS.

    PubMed

    SCHOEN, M A; ARENDS, T

    1964-11-01

    Blood serum samples from 33 red howler monkeys (Alouatta seniculus) were examined. Three different phenotypes were found and denominated A, B, and C. Four serums could not be classified because their transferrin apparently did not bind iron-59, possibly owing to saturation. A difference was observed in the electrophoretic migration and pattern of the transferrins in these monkeys compared with those of other primates. PMID:14197564

  11. Serum vitamin c and iron levels in oral submucous fibrosis

    PubMed Central

    Guruprasad, R; Nair, Preeti P; Singh, Manika; Singh, Manishi; Singh, MP; Jain, Arpit

    2014-01-01

    Background: In this study Serum Vitamin C and Iron levels in Oral submucous fibrosis (OSMF) were estimated. The objective was to evaluate the correlation between Serum Vitamin C and Iron levels in OSMF individuals. Serum Iron content can be a predictor for the progression of this condition. OSMF is basically a disorder of collagen metabolism where Vitamin C gets utilized in conversion of proline into hydroxyproline, this hydroxylation reaction requires ferrous Iron and Vitamin C. Many studies regarding micronutrients and other antioxidants levels have been emphasized, but very few studies are done on the Serum levels of Vitamin C and its correlation with Iron in OSMF patients. Methods: Thirty five OSMF patients and 50 deleterious habit free healthy individuals (controls) were selected. Two ml of venous blood was collected from each individual. Vitamin C level in serum was estimated by 2-4 dinitrophenylhydrazine method and Iron estimated by Tripyridyl method. Results: The level of Serum Vitamin-C and Iron was significantly decreased in OSMF patients when compared to controls which were statistically significant. Conclusion: On the basis of these observations, it seems possible that the chemical, thermal and/or mechanical factors associated with the use of areca nut may act in conjunction with the Vitamin C and Iron deficiency leading to the development of OSMF. Therapeutic substitution of vitamin C and Iron may be recommended in the management of OSMF PMID:25565730

  12. Neutrophil functions and serum IgG in growing foals.

    PubMed

    Demmers, S; Johannisson, A; Gröndahl, G; Jensen-Waern, M

    2001-11-01

    The aim of this study was to investigate the phagocytic and killing capacities as well as expression of CD18 of neutrophils obtained from healthy foals from birth to age 8 months. Blood was taken from 6 Standardbred foals at 7 time-points between ages 2-56 days and thereafter once a month. For comparison, cells from 16 mature horses were evaluated. Neutrophil phagocytosis of yeast cells was assessed by flow cytometry after opsonisation with mature pooled serum, autologous serum or anti-yeast IgG. The killing capacity of the neutrophils, as indicated by the oxidative burst, was monitored by chemiluminescence. Serum IgG concentration was measured by radial immunodiffusion. In addition to clinical examination, the amount of serum amyloid A and the total leucocyte count were used as markers for infection. The phagocytic ability was impaired until age 3 weeks, when autologous serum was used as opsonin. Killing capacity was also low initially but, from 3 months onwards, chemiluminescence values were equal to or higher than in mature horses. Serum IgG decreased from 10 g/l at 2 days to 5 g/l at 2 months and then increased gradually to 10 g/l at the end of the study. These findings may in part explain the increased susceptibility to bacterial infections in young horses. PMID:11770989

  13. Prognostic Utility of Serum Potassium in Chronic Digoxin Toxicity

    PubMed Central

    Manini, Alex F.; Nelson, Lewis S.; Hoffman, Robert S.

    2016-01-01

    Objective In contrast to patients with acute digoxin overdose, the prognostic utility of the serum potassium concentration for patients with chronic digoxin toxicity is unclear. In such patients, we aimed to evaluate the relationship between pre-treatment serum potassium and survival. Methods This was a case-control study at an urban Poison Control Center affiliated with a large urban medical center. We compared the serum potassium concentration between patients with chronic digoxin toxicity resulting in fatality (cases) over a 7-year period (2000–2006) versus survivors (controls) over a 1-year period (2007–2008). Results During the study period, there were 13 fatalities (cases) and 13 survivors (controls), of whom seven cases and five controls received appropriately dosed digoxin-specific antibody Fab fragments (Fab). There were no statistically significant differences between cases and controls with respect to serum digoxin concentration, creatinine, age, or sex. Serum potassium elevation pre-Fab was significantly associated with fatality both in mean difference (p < 0.03) and using a dichotomous cutoff of 5.0 mEq/L (p < 0.001), which performed with 92% sensitivity (95% CI 67, 99). In 86% of deaths despite appropriate Fab administration, the clinical presentation included the combination of bradycardia plus hyperkalemia. Conclusion In these patients with chronic digoxin toxicity, elevated serum potassium was associated with fatality. The combination of bradycardia and hyperkalemia strongly predicted fatality even in cases with appropriate Fab administration. PMID:21619380

  14. Effect of antacid and ascorbic acid on serum salicylate concentration.

    PubMed

    Hansten, P D; Hayton, W L

    1980-01-01

    To determine the effect of antacid or ascorbic acid administration on plateau serum salicylate concentrations, nine healthy subjects were given each of the following treatments by balanced block design: choline salicylate (equivalent to 3.76 or 5.62 Gm/day of aspirin); choline salicylate plus magnesium-aluminum hydroxide (120 ml/day); or choline salicylate plus ascorbic acid (3 Gm/day). In subjects developing a control serum salicylate level above 10 mg/dl, antacid administration produced a decrease in serum salicylate level (mean 19.8 mg/dl vs. 15.8 mg/dl) (P less than 0.01). Ascorbic acid administration was not associated with a significant change in serum salicylate. The reduction in serum salicylate following antacid appears to be due to antacid-induced alkalinization of the urine with resultant increase in renal salicylate clearance. Antacid administration should be considered a potential cause of altered serum salicylate concentration in patients receiving large doses of salicylate. PMID:7400368

  15. Elevated Serum Aminotransferases Secondary to Rippling Muscle Disease

    PubMed Central

    Nalankilli, Kumanan; Lubel, John

    2013-01-01

    A 43-year-old man was referred by his general practitioner to the hepatology clinic with deranged serum aminotransferases, discovered as part of routine blood tests. The objective was to identify the cause of elevated serum aminotransferases in this patient in a systematic manner. Thorough history and physical examination revealed a background history of rippling muscle disease secondary to caveolin-3 protein deficiency, with typical clinical signs. There was a positive family history of musculoskeletal disease in the patient's father and brother. Previous diagnostic tests performed to investigate the patient's musculoskeletal symptoms, including muscle biopsies, were revisited. Subsequent systematic investigations such as blood tests, liver ultrasound scan and Fibroscan® were performed to exclude potential causes of the deranged serum aminotransferases. Liver biopsy was not performed. A consistent pattern of chronic low-grade elevations of serum aminotransferases, less than three times the upper limit of the normal range, was found. This was associated with a consistently elevated serum creatine kinase and normal renal function tests. Previous muscle biopsies had revealed chronic degenerative and regenerative changes suggestive of a focal necrotizing myopathy. Liver ultrasound scan and Fibroscan® were normal. With exclusion of other liver diseases and identification of profoundly elevated serum creatine kinase concentration, the deranged aminotransferases were attributed to rippling muscle disease. PMID:23798914

  16. Grizzly bear corticosteroid binding globulin: Cloning and serum protein expression.

    PubMed

    Chow, Brian A; Hamilton, Jason; Alsop, Derek; Cattet, Marc R L; Stenhouse, Gordon; Vijayan, Mathilakath M

    2010-06-01

    Serum corticosteroid levels are routinely measured as markers of stress in wild animals. However, corticosteroid levels rise rapidly in response to the acute stress of capture and restraint for sampling, limiting its use as an indicator of chronic stress. We hypothesized that serum corticosteroid binding globulin (CBG), the primary transport protein for corticosteroids in circulation, may be a better marker of the stress status prior to capture in grizzly bears (Ursus arctos). To test this, a full-length CBG cDNA was cloned and sequenced from grizzly bear testis and polyclonal antibodies were generated for detection of this protein in bear sera. The deduced nucleotide and protein sequences were 1218 bp and 405 amino acids, respectively. Multiple sequence alignments showed that grizzly bear CBG (gbCBG) was 90% and 83% identical to the dog CBG nucleotide and amino acid sequences, respectively. The affinity purified rabbit gbCBG antiserum detected grizzly bear but not human CBG. There were no sex differences in serum total cortisol concentration, while CBG expression was significantly higher in adult females compared to males. Serum cortisol levels were significantly higher in bears captured by leg-hold snare compared to those captured by remote drug delivery from helicopter. However, serum CBG expression between these two groups did not differ significantly. Overall, serum CBG levels may be a better marker of chronic stress, especially because this protein is not modulated by the stress of capture and restraint in grizzly bears. PMID:20347821

  17. Serum antioxidant capacity in neurological, psychiatric, renal diseases and cardiomyopathy.

    PubMed

    Sofic, E; Rustembegovic, A; Kroyer, G; Cao, G

    2002-05-01

    The role of free radicals (FR) in the pathogenesis and in the progression of many diseases has been often discussed, but not widely investigated. However, the total antioxidant capacity in the serum seems to be of great evidence. Total antioxidant capacity was determined using oxygen absorbance capacity assay (ORAC) in serum of patients suffering from depression, schizophrenia, Alzheimer's disease (AD), anorexia nervosa, Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Aids-encephalopathy, diabetic polyneuropathy (PNP), cardiomyopathy (CM), renal disease, and healthy individuals as controls (C). The results showed that the total antioxidant capacity in serum decreased significantly (p < 0.01) by 24, 20, 13, and 17% for anorexia nervosa, Aids-encephalopathy, PNP and CM respectively. In serum of patients with renal disease significantly elevated antioxidant capacity was found. The data indicated that increased oxidative stress can be involved in the pathogenesis or in the progression of PNP and CM. Decrease of serum antioxidant capacity in patients with anorexia nervosa and Aids-encephalopathy are probably due primarily to malnutrition and secondly to insufficient antioxidant and immune system. In renal disease, the accumulation of urea in serum seems to be responsible for high antioxidant capacity. In contrast, there were no changes in PD, AD, depression syndrome and schizophrenia. PMID:12111462

  18. Superior serum half life of albumin tagged TNF ligands

    SciTech Connect

    Mueller, Nicole; Schneider, Britta; Pfizenmaier, Klaus; Wajant, Harald

    2010-06-11

    Due to their immune stimulating and apoptosis inducing properties, ligands of the TNF family attract increasing interest as therapeutic proteins. A general limitation of in vivo applications of recombinant soluble TNF ligands is their notoriously rapid clearance from circulation. To improve the serum half life of the TNF family members TNF, TWEAK and TRAIL, we genetically fused soluble variants of these molecules to human serum albumin (HSA). The serum albumin-TNF ligand fusion proteins were found to be of similar bioactivity as the corresponding HSA-less counterparts. Upon intravenous injection (i.v.), serum half life of HSA-TNF ligand fusion proteins, as determined by ELISA, was around 15 h as compared to approximately 1 h for all of the recombinant control TNF ligands without HSA domain. Moreover, serum samples collected 6 or 24 h after i.v. injection still contained high TNF ligand bioactivity, demonstrating that there is only limited degradation/inactivation of circulating HSA-TNF ligand fusion proteins in vivo. In a xenotransplantation model, significantly less of the HSA-TRAIL fusion protein compared to the respective control TRAIL protein was required to achieve inhibition of tumor growth indicating that the increased half life of HSA-TNF ligand fusion proteins translates into better therapeutic action in vivo. In conclusion, our data suggest that genetic fusion to serum albumin is a powerful and generally applicable mean to improve bioavailability and in vivo activity of TNF ligands.

  19. The association between serum ferritin with colorectal cancer

    PubMed Central

    Feng, Zhe; Chen, Ji-Wei; Feng, Jian-Hua; Shen, Fei; Cai, Wen-Song; Cao, Jie; Xu, Bo

    2015-01-01

    There are conflicting reports on the correlation between serum levels of ferritin with colorectal cancer. The purpose of the present study is to clarify the association between serum ferritin with colorectal cancer using a meta-analysis approach. We searched articles indexed in Pubmed published as of July 2015 that met our predefined criteria. Six eligible articles involving 927 subjects were identified. Overall, pooled analysis indicated that subjects with colorectal cancer had lower serum level of ferritin than the healthy controls (SMD=-1.569, 95% CI=[-2.718, -0.420], P= 0.007). Further subgroup analysis found lower serum level of ferritin among patients with colorectal cancer in eastern country (SMD=-1.956, 95% CI=[-3.750, -0.162], P=0.033), but not in western country (SMD=-1.285, 95% CI=[-2.778, 0.207], P=0.091). In conclusion, this meta-analysis supports a significant association between serum ferritin with colorectal cancer. However, the subgroup analysis found that there was significant effect modification of ferritin level by ethnic. Thus this finding needs further confirmation by trans-regional multicenter, long-term observation in a cohort design to obtain better understanding of causal relationships between serum ferrintin levels and colorectal cancer, through measuring ferritin at baseline to investigate whether the highest ferritin category versus lowest is associated with colorectal cancer risk. PMID:26885206

  20. The epidemiology of serum sex hormones in postmenopausal women

    SciTech Connect

    Cauley, J.A.; Kuller, L.H.; LeDonne, D. ); Gutai, J.P. ); Powell, J.G. )

    1989-06-01

    Serum sex hormones may be related to the risk of several diseases including osteoporosis, heart disease, and breast and endometrial cancer in postmenopausal women. In the current report, the authors examined the epidemiology of serum sex hormones in 176 healthy, white postmenopausal women (mean age 58 years) recruited from the metropolitan Pittsburgh, Pennsylvania, area. The data were collected during 1982-1983; none of the women were on estrogen replacement therapy. Serum concentrations of estrone, estradiol, testosterone, and androstenedione were measured by a combination of extraction, column chromatography, and radioimmunoassay. Neither age nor time since menopause was a significant predictor of sex hormones. The degree of obesity was a major determinant of estrone and estradiol. The estrone levels of obese women were about 40% higher than the levels of nonobese women. There was a weak relation between obesity and the androgens. Cigarette smokers had significantly higher levels of androstenedione than nonsmokers, with little difference in serum estrogens between smokers and nonsmokers. Both estrone and estradiol levels tended to decline with increasing alcohol consumption. Physical activity was an independent predictor of serum estrone. More active women had lower levels of estrone. There was a positive relation of muscle strength with estrogen levels. The data suggest interesting relations between environmental and lifestyle factors and serum sex hormones. These environmental and lifestyle factors are potentially modifiable and, hence, if associations between sex hormones and disease exist, modification of these factors could affect disease risks.

  1. Is accuracy of serum free light chain measurement achievable?

    PubMed

    Jacobs, Joannes F M; Tate, Jillian R; Merlini, Giampaolo

    2016-06-01

    The serum free light chain (FLC) assay has proven to be an important complementary test in the management of patients with monoclonal gammopathies. The serum FLC assay has value for patients with plasma cell disorders in the context of screening and diagnosis, prognostic stratification, and quantitative monitoring. Nonetheless, serum FLC measurements have analytical limitations which give rise to differences in FLC reporting depending on which FLC assay and analytical platform is used. As the FLC measurements are incorporated in the International Myeloma Working Group guidelines for the evaluation and management of plasma cell dyscrasias, this may directly affect clinical decisions. As new certified methods for serum FLC assays emerge, the need to harmonise patient FLC results becomes increasingly important. In this opinion paper we provide an overview of the current lack of accuracy and harmonisation in serum FLC measurements. The clinical consequence of non-harmonized FLC measurements is that an individual patient may or may not meet certain diagnostic, prognostic, or response criteria, depending on which FLC assay and platform is used. We further discuss whether standardisation of serum FLC measurements is feasible and provide an overview of the steps needed to be taken towards harmonisation of FLC measurements. PMID:26641970

  2. Serum Osteoprotegerin Is Associated With Calcified Carotid Plaque

    PubMed Central

    Kwon, Ami; Choi, Yun-Seok; Choi, Yong-Won; Chung, Woo-Baek; Park, Chul-Soo; Chung, Wook-Sung; Lee, Man-Young; Youn, Ho-Joong

    2016-01-01

    Abstract Osteoprotegerin (OPG) is a kind of tumor necrosis factor, which is related to bone metabolism and vascular calcification. The increase of Osteoprotegerin concentration in serum is related to cardiovascular diseases in humans. The purpose of this study was to figure out the relevance between osteoprotegerin in serum and carotid calcification. Serum OPG concentrations were compared in 145 patients who underwent carotid sonography (average age: 68 ± 9 years old, male: female = 81:64). A calcified plaque (CP) (37 people [27%]), a noncalcified plaque (NCP) (54 people [37%]), and a nonplaque (NP) (54 people [37%]) were classified for this study. No significant differences among 3 groups were demonstrated in the distribution of age, diabetes, high blood pressure, and hyperlipidemia. Serum osteoprotegerin concentrations were significantly increased in CP group rather than NCP group or NP group; (median [interquartile range], 4016 [1410] vs 3210 [1802] pg/mL, P < 0.05 and 4016 [1410] vs 3204 [1754] pg/mL, P < 0.05). Serum osteoprotegerin concentrations did not indicate a significant difference between NCP Group or NP Group. This study had proved that patient group accompanied with carotid calcification in carotid artery disease had an increased serum OPG concentration, so it could consider that OPG plays an important function on calcification related to arteriosclerosis. PMID:27082605

  3. Preparation of Rat Serum Suitable for Mammalian Whole Embryo Culture

    PubMed Central

    Takahashi, Masanori; Makino, Sayaka; Kikkawa, Takako; Osumi, Noriko

    2014-01-01

    Mammalian whole embryo culture (WEC) is a widely used technique for examining pharmacological toxicity in developing mouse and rat embryos and for investigating the mechanisms of developmental processes. Immediately centrifuged (IC) rat serum is commonly used for WEC and is essential for the growth and development of cultured mouse and rat embryos ex vivo. For the culture of midgestation embryos (i.e., E8.0-12.5 for the mouse, and E10.0-14.5 for the rat), 100% rat serum is the best media for supporting the growth of the embryo ex vivo. To prepare rat serum suitable for WEC, the collected blood should be centrifuged immediately to separate the blood cells from the plasma fraction. After centrifugation, the fibrin clot forms in the upper layer; this clot should be squeezed gently using a pair of sterile forceps and subsequently centrifuged to completely separate the blood cells from the serum. In this video article, we demonstrate our standard protocol for the preparation of optimal IC rat serum, including blood collection from the abdominal aorta of male rats and extraction of the serum by centrifugation. PMID:25145996

  4. Serum Biopterin and Neopterin Levels as Predictors of Empty Follicles

    PubMed Central

    Hamuro, Akihiro; Tachibana, Daisuke; Misugi, Takuya; Katayama, Hiroko; Ozaki, Koji; Fujino, Yuji; Yoshihiro, Nakamura; Shintaku, Haruo; Koyama, Masayasu

    2015-01-01

    OBJECTIVE This study measured serum and follicular fluid (FF) levels of biopterin, neopterin, vascular endothelial growth factor (VEGF), and macrophage colony-stimulating factor (M-CSF) in patients receiving mild ovarian stimulation for oocyte retrieval. PATIENTS AND METHODS Infertile patients who underwent ovarian stimulation were divided into the following: Group 1, no oocyte retrieval (n = 12), and Group 2, retrieval of more than four oocytes (n = 13). Median total gonadotropin dose in both groups was 150 IU. Biopterin and neopterin levels were measured using high-performance liquid chromatography. VEGF and M-CSF levels were measured by enzyme-linked immunosorbent assay. RESULTS Compared to Group 2, serum and FF levels of neopterin and VEGF and serum levels of M-CSF were significantly increased, and serum and FF levels of biopterin were significantly decreased in Group 1 (P < 0.05 each). CONCLUSION Biopterin and neopterin levels showed similar differences in FF and serum of patients with empty follicles. Decreased biopterin and increased neopterin in serum could predict poor oocyte retrieval. PMID:26568687

  5. A structural comparison of human serum transferrin and human lactoferrin.

    PubMed

    Wally, Jeremy; Buchanan, Susan K

    2007-06-01

    The transferrins are a family of proteins that bind free iron in the blood and bodily fluids. Serum transferrins function to deliver iron to cells via a receptor-mediated endocytotic process as well as to remove toxic free iron from the blood and to provide an anti-bacterial, low-iron environment. Lactoferrins (found in bodily secretions such as milk) are only known to have an anti-bacterial function, via their ability to tightly bind free iron even at low pH, and have no known transport function. Though these proteins keep the level of free iron low, pathogenic bacteria are able to thrive by obtaining iron from their host via expression of outer membrane proteins that can bind to and remove iron from host proteins, including both serum transferrin and lactoferrin. Furthermore, even though human serum transferrin and lactoferrin are quite similar in sequence and structure, and coordinate iron in the same manner, they differ in their affinities for iron as well as their receptor binding properties: the human transferrin receptor only binds serum transferrin, and two distinct bacterial transport systems are used to capture iron from serum transferrin and lactoferrin. Comparison of the recently solved crystal structure of iron-free human serum transferrin to that of human lactoferrin provides insight into these differences. PMID:17216400

  6. Inactivation of Staphylococcal Phenol Soluble Modulins by Serum Lipoprotein Particles

    PubMed Central

    Surewaard, Bas G. J.; Nijland, Reindert; Spaan, András N.; Kruijtzer, John A. W.; de Haas, Carla J. C.; van Strijp, Jos A. G.

    2012-01-01

    Staphylococcus aureus virulence has been associated with the production of phenol soluble modulins (PSM). PSM are known to activate, attract and lyse neutrophils. However, the functional characterizations were generally performed in the absence of human serum. Here, we demonstrate that human serum can inhibit all the previously-described activities of PSM. We observed that serum can fully block both the cell lysis and FPR2 activation of neutrophils. We show a direct interaction between PSM and serum lipoproteins in human serum and whole blood. Subsequent analysis using purified high, low, and very low density lipoproteins (HDL, LDL, and VLDL) revealed that they indeed neutralize PSM. The lipoprotein HDL showed highest binding and antagonizing capacity for PSM. Furthermore, we show potential intracellular production of PSM by S. aureus upon phagocytosis by neutrophils, which opens a new area for exploration of the intracellular lytic capacity of PSM. Collectively, our data show that in a serum environment the function of PSM as important extracellular toxins should be reconsidered. PMID:22457627

  7. Serum Biochemistry of Lumpy Skin Disease Virus-Infected Cattle

    PubMed Central

    Avci, Oğuzhan; Doğan, Müge; İnce, Ömer Barış

    2016-01-01

    Lumpy skin disease is an economically important poxvirus disease of cattle. Vaccination is the main method of control but sporadic outbreaks have been reported in Turkey. This study was carried out to determine the changes in serum biochemical values of cattle naturally infected with lumpy skin disease virus (LSDV). For this study, blood samples in EDTA, serum samples, and nodular skin lesions were obtained from clinically infected animals (n = 15) whereas blood samples in EDTA and serum samples were collected from healthy animals (n = 15). A quantitative real-time PCR method was used to detect Capripoxvirus (CaPV) DNA in clinical samples. A real-time PCR high-resolution melt assay was performed to genotype CaPVs. Serum cardiac, hepatic, and renal damage markers and lipid metabolism products were measured by autoanalyzer. LSDV nucleic acid was detected in all samples which were obtained from clinically infected cattle. The results of serum biochemical analysis showed that aspartate aminotransferase, alkaline phosphatase, total protein, and creatinine concentrations were markedly increased in serum from infected animals. However, there were no significant differences in the other biochemical parameters evaluated. The results of the current study suggest that liver and kidney failures occur during LSDV infection. These findings may help in developing effective treatment strategies in LSDV infection. PMID:27294125

  8. Transforming growth factor-beta1 incorporated during setting in calcium phosphate cement stimulates bone cell differentiation in vitro.

    PubMed

    Blom, E J; Klein-Nulend, J; Klein, C P; Kurashina, K; van Waas, M A; Burger, E H

    2000-04-01

    Growth stimulation of periimplant tissues by growth factors like transforming growth factor-beta1 (TGF-beta1) may increase the indication for and success of implant use. Calcium phosphate as a material for implants or for coating of implants is known for its good biologic interaction with bone. Therefore, calcium phosphate implants combined with TGF-beta1 might improve osseointegration. In this study we hypothesise that the addition of recombinant human TGF-beta1 (rhTGF-beta1) to calcium phosphate cement (CPC) affects the differentiation of bone cells growing on the cement layer. rhTGF-beta1 incorporated during setting in a CPC layer at 20 ng rhTGF-beta1/60 mg cement was found to be gradually released into tissue culturing medium leading to a 20% release after 24 h. Two cell populations were obtained from collagenase-treated fragments of adult rat long bones: preosteoblastic cells, which were released by the collagenase treatment, and osteoblastic cells, which grew from the collagenase-stripped bone fragments. Both cell populations were tested for their osteoblastic characteristic phenotype by measuring their alkaline phosphatase (ALP) activity after vitamin D treatment and cyclic AMP after parathyroid hormone stimulation. After preculture the cells were plated on a layer of CPC containing 0 (control), 10, or 20 ng rhTGF-beta1/60 mg CPC. Bone cell differentiation was analyzed after 10 days by measuring the ALP activity, as well as the protein content of the cell layer. Incorporation of rhTGF-beta1 in the CPC did not change the ALP activity in osteoblastic cells, but a significant (analyzed by multivariate analysis of variance) increase was observed in preosteoblastic cells. Incorporation of 10 ng of rhTGF-beta1 in 60 mg of CPC increased the ALP activity in preosteoblastic cells by threefold and 20 ng rhTGF-beta1/60 mg CPC increased it by fivefold. The total protein content was not affected by rhTGF-beta1 in either of the cell populations. We conclude that rhTGF-beta

  9. Autologous serum eye drops for dry eye

    PubMed Central

    Pan, Qing; Angelina, Adla; Zambrano, Andrea; Marrone, Michael; Stark, Walter J; Heflin, Thomas; Tang, Li; Akpek, Esen K

    2014-01-01

    Background Theoretically, autologous serum eye drops (AS) have a potential advantage over traditional therapies based on the assumption that AS serve not only as a lacrimal substitute to provide lubrication, but also contain other biochemical components mimicking natural tears more closely. The application of AS in dry eye treatment has gained popularity as a second-line therapy in the treatment of dry eye. Published studies on the subject indicate that autologous serum could be an effective treatment for dry eye. Objectives To evaluate the efficacy and safety of AS compared to artificial tears for treating dry eye. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2013, Issue 3), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLD MEDLINE, (January 1950 to April 2013), EMBASE (January 1980 to April 2013), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to April 2013), the meta Register of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We also searched the Science Citation Index Expanded database (September 2013) and reference lists of included studies. We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 15 April 2013. Selection criteria We included randomized controlled trials (RCTs) in which AS was compared to artificial tears in the treatment of dry eye in adults. Data collection and analysis Two review authors independently screened all titles and abstracts and assessed full-text articles of potentially eligible trials. Two review authors extracted data and assessed the methodological quality and characteristics of the included trials.We contacted investigators for missing data

  10. Mycovirus-like DNA virus sequences from cattle serum and human brain and serum samples from multiple sclerosis patients.

    PubMed

    Lamberto, Iranzu; Gunst, Karin; Müller, Hermann; Zur Hausen, Harald; de Villiers, Ethel-Michele

    2014-01-01

    Myco-like viruses have been isolated from fungi, feces of various animals, and plant leaves. We report here the isolation of 3 complete genome sequences of gemycircularvirus-related viruses from healthy bovine serum and human brain and serum samples from patients with multiple sclerosis (MS). Their putative capsid proteins share similarity to Torque teno virus (TTV) open reading frame 1 (ORF1) proteins. PMID:25169858

  11. Mycovirus-Like DNA Virus Sequences from Cattle Serum and Human Brain and Serum Samples from Multiple Sclerosis Patients

    PubMed Central

    Lamberto, Iranzu; Gunst, Karin; Müller, Hermann; zur Hausen, Harald

    2014-01-01

    Myco-like viruses have been isolated from fungi, feces of various animals, and plant leaves. We report here the isolation of 3 complete genome sequences of gemycircularvirus-related viruses from healthy bovine serum and human brain and serum samples from patients with multiple sclerosis (MS). Their putative capsid proteins share similarity to Torque teno virus (TTV) open reading frame 1 (ORF1) proteins. PMID:25169858

  12. Serum Bicarbonate and Bone Mineral Density in US Adults

    PubMed Central

    Chen, Wei; Melamed, Michal L.; Abramowitz, Matthew K.

    2014-01-01

    Background Chronic metabolic acidosis leads to bone mineral loss and results in lower bone mineral density (BMD), which is a risk factor for osteoporosis-related fractures. The effect of low-level metabolic acidosis on bone density in the general population is unknown. Study Design Cross-sectional study. Setting & Participants 9,724 nationally representative adults aged 20 years or older in the National Health and Nutrition Examination Survey 1999-2004. Factor Serum bicarbonate level. Outcomes Lumbar and total BMD as well as low lumbar and total bone mass defined as 1.0 SD below sex-specific mean of young adults. Measurements BMD was measured by dual-energy X-ray absorptiometry and serum bicarbonate levels were measured in all participants. Results Both men and women with lower serum bicarbonate levels were more likely to be current smokers and had higher body mass index and estimated net endogenous acid production. There was a significant linear trend across quartiles of serum bicarbonate with lumbar BMD among the total population as well as in sex-specific models (p=0.02 for all three models, p=0.1 for interaction). For total BMD, a significant association was seen with serum bicarbonate levels among women but not men (p=0.02 and p=0.1, respectively; p=0.8 for interaction); and a significant association was seen among post-menopausal women but not pre-menopausal women (p=0.02 and p=0.2, respectively; p=0.5 for interaction). Compared to women with serum bicarbonate level <24 mEq/L, those with serum bicarbonate ≥27 mEq/L had 0.018 g/cm2 higher total BMD (95% CI, 0.004-0.032; p=0.01) and had 31% lower odds of having low total bone mass (OR, 0.68; 95% CI, 0.46-0.99; p=0.05). Limitations Cross-sectional study using a single measurement of serum bicarbonate level. The subgroup differences are not definitive. Conclusions Lower serum bicarbonate levels are associated with lower BMD in US adults. Further studies should examine whether serum bicarbonate levels should be

  13. Serum Magnesium and Sudden Death in European Hemodialysis Patients

    PubMed Central

    de Roij van Zuijdewijn, Camiel L. M.; Grooteman, Muriel P. C.; Bots, Michiel L.; Blankestijn, Peter J.; Steppan, Sonja; Büchel, Janine; Groenwold, Rolf H. H.; Brandenburg, Vincent; van den Dorpel, Marinus A.; ter Wee, Piet M.; Nubé, Menso J.; Vervloet, Marc G.

    2015-01-01

    Despite suggestions that higher serum magnesium (Mg) levels are associated with improved outcome, the association with mortality in European hemodialysis (HD) patients has only scarcely been investigated. Furthermore, data on the association between serum Mg and sudden death in this patient group is limited. Therefore, we evaluated Mg in a post-hoc analysis using pooled data from the CONvective TRAnsport STudy (CONTRAST, NCT00205556), a randomized controlled trial (RCT) evaluating the survival risk in dialysis patients on hemodiafiltration (HDF) compared to HD with a mean follow-up of 3.1 years. Serum Mg was measured at baseline and 6, 12, 24 and 36 months thereafter. Cox proportional hazards models, adjusted for confounders using inverse probability weighting, were used to estimate hazard ratios (HRs) of baseline serum Mg on all-cause mortality, cardiovascular mortality, non-cardiovascular mortality and sudden death. A generalized linear mixed model was used to investigate Mg levels over time. Out of 714 randomized patients, a representative subset of 365 (51%) were analyzed in the present study. For every increase in baseline serum Mg of 0.1 mmol/L, the HR for all-cause mortality was 0.85 (95% CI 0.77–94), the HR for cardiovascular mortality 0.73 (95% CI 0.62–0.85) and for sudden death 0.76 (95% CI 0.62–0.93). These findings did not alter after extensive correction for potential confounders, including treatment modality. Importantly, no interaction was found between serum phosphate and serum Mg. Baseline serum Mg was not related to non-cardiovascular mortality. Mg decreased slightly but statistically significant over time (Δ -0.011 mmol/L/year, 95% CI -0.017 to -0.009, p = 0.03). In short, serum Mg has a strong, independent association with all-cause mortality, cardiovascular mortality and sudden death in European HD patients. Serum Mg levels decrease slightly over time. PMID:26600017

  14. Two major ruminant acute phase proteins, haptoglobin and serum amyloid A, as serum biomarkers during active sheep scab infestation

    PubMed Central

    2013-01-01

    Two ruminant acute phase proteins (APPs), haptoglobin (Hp) and serum amyloid A (SAA), were evaluated as serum biomarkers (BMs) for sheep scab–a highly contagious ectoparasitic disease caused by the mite Psoroptes ovis, which is a major welfare and production threat worldwide. The levels of both APPs increased in serum following experimental infestation of sheep with P. ovis, becoming statistically significantly elevated from pre-infestation levels at 4 weeks post-infestation. Following successful treatment of infested sheep with an endectocide, Hp and SAA serum levels declined rapidly, with half lives of less than 3 days. In contrast, serum IgG levels which specifically bound the P. ovis-derived diagnostic antigen Pso o 2 had a half-life of 56 days. Taking into account pre-infestation serum levels, rapidity of response to infestation and test sensitivity at the estimated optimum cut-off values, SAA was the more discriminatory marker. These studies illustrated the potential of SAA and Hp to indicate current sheep scab infestation status and to augment the existing Pso o 2 serological assay to give disease-specific indications of both infestation and successful treatment. PMID:24176040

  15. Direct /sup 125/I-radioligand assays for serum progesterone compared with assays involving extraction of serum

    SciTech Connect

    Ratcliffe, W.A.; Corrie, J.E.; Dalziel, A.H.; Macpherson, J.S.

    1982-06-01

    Researchers compared two direct radioimmunoassays for progesterone in 50 microL of unextracted serum or plasma with assays involving extraction of serum. The direct assays include the use of either danazol at pH 7.4 or 8-anilino-1-naphthalenesulfonic acid at pH 4.0 to displace progesterone from serum binding-proteins. Progesterone is then assayed by using an antiserum to a progesterone 11 alpha hemisuccinyl conjugate and the radioligand /sup 125/I-labeled progesterone 11 alpha-glucuronyl tyramine, with separation by double-antibody techniques. Direct assays with either displacing agent gave good analytical recovery of progesterone added to human serum, and progesterone values for patients' specimens correlated well (r greater than 0.96) with results of assays involving extraction of serum. Precision was similar with each displacing agent over the working range 2.5-100 nmol/L and superior to that of extraction assays. Researchers conclude that these direct assays of progesterone are analytically valid and more robust, precise, and technically convenient than many conventional methods involving extraction of serum.

  16. Association Between Serum B12 and Serum Homocysteine Levels in Diabetic Patients on Metformin

    PubMed Central

    Kothari, Nitin; Shah, Hitesh

    2016-01-01

    Introduction Type-2 Diabetes Mellitus (T2DM) and metformin both can lower serum B12 (s.B12). Raised serum Homocysteine (s.Hcy) is considered as an early marker of B12 deficiency. Aim The study aimed to check whether homocysteine levels are more sensitive indicator of s. B12 deficiency or not among diabetics using metformin. Materials and Methods Mean s.B12 and s.Hcy levels of 30 cases (diabetics on metformin <5years) were compared with 30 diabetic controls not on metformin and 31 nondiabetic controls and statistically analysed by ANOVA and post-hoc tests. Results No significant differences in either s.B12 mean or s.Hcy mean were found between cases and diabetic controls. s.B12 mean did not differ significantly but s.Hcy mean was significantly higher among nondiabetics as compared to diabetic control. s. B12 level of Nondiabetic group was in borderline category while mean s. B12 levels of cases and diabetic control groups was in normal category but nearer to the lower cut off. Mean s.Hcy values in all the groups were high. Pearson correlation showed strong association between s.B12 and s.Hcy in all the groups. Additionally equation based on linear regression was derived to calculate either of the s.B12 or s.Hcy. On Receiver Operative Characteristic (ROC) curve, area under curve value was 0.842 for the value of s.Hcy. Conclusion In this study neither metformin nor T2DM could be identified as a cause for s.B12 lowering and raised s.Hcy in the scenario of low normal levels of s.B12 (<300pmol/L). If B12 deficiency recognized early using s. Hcy, consequences due to B12 deficiency can be prevented or delayed among nondiabetics as well as among diabetics and metformin users. PMID:27190787

  17. Serum prostacyclin binding defects in thrombotic thrombocytopenic purpura.

    PubMed Central

    Wu, K K; Hall, E R; Rossi, E C; Papp, A C

    1985-01-01

    To understand the pathophysiologic significance of abnormal serum prostacyclin (PGI2) binding activities in thrombotic thrombocytopenic purpura (TTP), we evaluated the PGI2 binding characteristics in three chronic TTP sera and 19 normal sera. PGI2 binding by serum was rapid and reversible. The binding activity in TTP sera (22.1 +/- SD, 4.4%) was significantly lower than that of normal sera (42.2 +/- 6.2%). Moreover, the antiaggregating activity and 6-keto-prostaglandin F1 alpha (6KPGF1 alpha) content in the gel filtrates representing the binding peak was proportionally lower in a TTP serum than normal serum. Although normal and TTP sera bound [14C]arachidonate with similar activity, and neither bound [3H]6KPGF1 alpha, there was a difference in prostaglandin E1 (PGE1) binding. Binding of [3H]PGE1 was subnormal in two TTP sera (W.J. and T.G.) and normal in the third (H.S.). Normal serum corrected the binding defects of TTP serum. Interestingly, the mixture of two TTP sera (W.J. and H.S.) mutually corrected their PGI2 binding defects. In addition, although in vivo plasma transfusions improved the PGI2 binding activity of W.J. and H.S., there existed a striking difference in the nature of their response. These observations indicate that there is at least two types of PGI2 binding defects in TTP. Our data indicate that TTP is associated with diminished serum binding of PGI2. This defect may reduce the availability of PGI2 to damaged vascular sites and decrease an important modulator of platelet thrombus formation at times of severe vascular insult. Images PMID:3880771

  18. Total serum immunoglobulin E in patients with alopecia areata

    PubMed Central

    Bakry, Ola Ahmed; El Shazly, Rania Mohamed Azmy; Basha, Mohamed Ahmed; Mostafa, Hanan

    2014-01-01

    Context: Alopecia areata (AA) is a common form of localized, non-scarring hair loss. The pathogenesis of the disease is unknown. Previous evidence suggested the involvement of Th2 cytokines in disease pathogenesis. Aim: To determine serum level of total IgE, this is mainly influenced by Th2 cytokines, in Egyptian patients with AA. Materials and Methods: Fifty subjects with AA (28 males and 22 females) were selected from Dermatology Outpatient Clinic, Menoufiya University Hospital from February 2012 to December 2012. Subjects with other conditions that might elevate serum IgE were excluded from the study. Fifty age- and sex-matched healthy subjects were selected as a control group. Venous blood samples were taken from cases and controls for measurement of total serum IgE by enzyme-linked immunosorbent assay. Skin biopsy was taken from every case from an active area of hair loss. Results: Total serum IgE was elevated in 27 (54%) cases. Its values among patients ranged from 13.5 IU/ml to 780 IU/ml. There was a statistically significant difference between cases and controls with regard to mean value of serum IgE (P < 0.05). Mean value of IgE did not vary significantly with disease severity, patients’ age, patients’ gender, disease duration, site of lesions, and positive family history of AA. No correlation was found between serum IgE levels and histopathological changes detected in examined cases. Conclusions: Total serum IgE is elevated in AA. This elevation is not related to age, gender, disease duration, disease severity, site of affection or family history of AA. PMID:24860742

  19. Manifold significance of serum eosinophil cationic protein in asthmatic children.

    PubMed

    Zubović, Ivan; Rozmanić, Vojko; Ahel, Vladimir; Banac, Srdan

    2002-01-01

    Asthma is the result of complex interaction between different cells, mediators and nervous system that leads to an inflammatory response accompanied by increased bronchial hyperactivity. Its clinical manifestations include recurrent cough, wheezing and difficult breathing. The purpose of this study was to establish the possibility of diagnosing inflammation in asthmatic patients based on the assessment of serum eosinophil cationic protein (ECP), and of following the efficacy of asthmatic treatment by the levels of inflammation mediators. In a prospective study, 134 children aged 1 to 18 (mean 8) years underwent serum ECP assessment. Experimental group included 87 patients with asthma, 56 boys and 31 girls, mean age 9.1 (range 2-17) years. Control group included patients with recurrent non-allergic disorders, 27 boys and 20 girls aged 1-16 (mean 6.1) years. Serum ECP was assessed using the Pharmacia CAP system ECP-FEIA method, i.e. fluoroimmunoassay test for quantitative assessment of serum ECP levels. Serum values of ECP were significantly higher in asthmatics than in controls (p = 0.001). Our results showed that increased levels of serum ECP to significantly correlate with increased eosinophil (p = 0.018) and immunoglobulin E (p = 0.003) levels. Increased ECP levels reflect the degree of inflammation and correlate with the clinical picture severity in asthmatic patients. Assessment of serum ECP levels can reveal eosinophilic activity, and indirectly detect immunologic inflammation in asthmatics. It is possible to follow the dynamics of immunologic inflammation during the course of treatment as well as treatment efficacy. PMID:12596625

  20. Clinical significance of serum claudin-1 levels in melanoma patients.

    PubMed

    Tas, Faruk; Bilgin, Elif; Erturk, Kayhan; Duranyildiz, Derya

    2016-08-01

    Claudins are the most important structural and functional components of tight-junction integral membrane proteins. They play roles in major cellular functions including growth and adhesion and are responsible for regulating the paracellular transport of molecules. The objective of this study was to determine the clinical significance of the serum levels of claudin-1, an oldest and important member of the claudin family, in melanoma patients. A total of 98 patients with a pathologically confirmed melanoma were enrolled into this study. Serum claudin-1 concentrations were determined by the solid-phase sandwich enzyme-linked immunosorbent assay method. Age-matched and sex-matched 43 healthy controls were included in the analysis. The median age at diagnosis was 51 years, ranging from 16 to 85 years. The majority of the patients were male (61%) and had axial localized (54%) and metastatic disease (61%). Moreover, most of the patients with metastatic disease had M1c (73%). The baseline serum claudin-1 levels of the melanoma patients were significantly lower than those of control subjects (median values 9.17 vs. 13.82 ng/ml, respectively, P<0.001). However, known clinical variables including age of the patient, sex, site of lesion, histology, lymph node involvement, stage of disease, serum lactate dehydrogenase levels, and response to chemotherapy were not found to be correlated with serum claudin-1 concentrations (P>0.05). Similarly, serum claudin-1 concentration was found to have no prognostic role in survival (P=0.524). In conclusion, serum levels of claudin-1 may have a diagnostic value in melanoma patients. However, its predictive and prognostic value has not been determined. PMID:26886788

  1. Determinants of serum 25-hydroxyvitamin D in Hong Kong.

    PubMed

    Xu, Cuiling; Perera, Ranawaka A P M; Chan, Yap-Hang; Fang, Vicky J; Ng, Sophia; Ip, Dennis K M; Kam, Andrea May-Sin; Leung, Gabriel M; Peiris, J S Malik; Cowling, Benjamin J

    2015-07-14

    Vitamin D plays an important role in skeletal health throughout life. Some studies have hypothesised that vitamin D may reduce the risk of other diseases. Our study aimed to estimate age-specific and sex-specific serum 25-hydroxyvitamin D (25(OH)D) status and to identify the determinants of serum 25(OH)D status in Hong Kong, a subtropical city in southern China. In 2009-2010, households in Hong Kong were followed up to identify acute respiratory illnesses, and sera from 2694 subjects were collected in three to four different study phases to permit measurement of 25(OH)D levels at different times of the year. A questionnaire survey on diet and lifestyle was conducted among children, with simultaneous serum collection in April and May 2010. The mean of serum 25(OH)D levels in age groups ranged from 39 to 63 nmol/l throughout the year with the mean values in all age groups in spring below 50 nmol/l. Children aged 6-17 years, and girls and women had significantly lower serum 25(OH)D levels than adults, and boys and men, respectively (all P< 0.001). We estimated that serum 25(OH)D levels in Hong Kong followed a lagged pattern relative to climatic season by 5 weeks with lowest observed levels in early spring (March). For children aged 6-17 years, reporting a suntan, having at least 1 servings of fish/week and having at least 1 serving of eggs/week were independently associated with higher serum 25(OH)D levels. Adequate sunlight exposure and increased intake of dietary vitamin D could improve vitamin D status, especially for children and females in the winter and spring. PMID:26051634

  2. Timing of Levothyroxine Administration Affects Serum Thyrotropin Concentration

    PubMed Central

    Bach-Huynh, Thien-Giang; Nayak, Bindu; Loh, Jennifer; Soldin, Steven; Jonklaas, Jacqueline

    2009-01-01

    Context: Patients treated with levothyroxine typically ingest it in a fasting state to prevent food impairing its absorption. The serum thyrotropin concentration is the therapeutic index of levothyroxine action. Objective: The study objective was to determine the effect of the timing of levothyroxine administration in relationship to food on serum thyrotropin levels. Design: Participants were randomized to one of six sequences, each consisting of three 8-wk regimens in a three-period crossover design. These regimens were in a fasting state, at bedtime, and with breakfast. The concentrations of TSH, free T4, and total T3 during each of the three timing regimens were documented. The primary outcome was the difference between serum TSH concentrations under fasting conditions compared with concentrations during the other 8-wk regimens. Setting: The study was conducted in an academic medical center. Participants: Study participants were receiving levothyroxine for treatment of hypothyroidism or thyroid cancer. Results: Sixty-five patients completed the study. The mean thyrotropin concentration was 1.06 ± 1.23 mIU/liter when levothyroxine was administered in the fasting state. When levothyroxine was taken with breakfast, the serum thyrotropin concentration was significantly higher (2.93 ± 3.29 mIU/liter). When levothyroxine was taken at bedtime, the serum TSH concentration was also significantly higher (2.19 ± 2.66 mIU/liter). Conclusion: Nonfasting regimens of levothyroxine administration are associated with higher and more variable serum TSH concentrations. If a specific serum TSH goal is desired, thereby avoiding iatrogenic subclinical thyroid disease, then fasting ingestion of levothyroxine ensures that TSH concentrations remain within the narrowest target range. PMID:19584184

  3. Factors influencing serum concentration of zonisamide in epileptic patients.

    PubMed

    Kimura, M; Tanaka, N; Kimura, Y; Miyake, K; Kitaura, T; Fukuchi, H; Harada, Y

    1992-01-01

    The relationship between daily dose and serum concentration of zonisamide (ZNS) and the effects of patient age on the serum level/dose (L/D) ratio for ZNS were studied in epileptic patients (mean age +/- S.D. = 10.6 +/- 6.2 years) who chronically received ZNS. The influence of phenytoin (PHT), phenobarbital (PB), carbamazepine (CBZ) and valproic acid (VPA) on the serum protein binding of ZNS in vitro and the correlation between total and unbound serum levels of ZNS in patients were also examined. Significant correlations were obtained between daily dose per body weight or per body surface area and serum level of ZNS. The correlation coefficient of the latter was higher than that of the former. There was no effect of age on the L/D ratio on the basis of body surface area, whereas that on the basis of body weight increased significantly with age. No significant increase in the free fraction of ZNS was observed in the presence of PHT, PB and CBZ except VPA in vitro. There were significant correlations between total and unbound serum levels of ZNS in the two patient groups coadministered with and without VPA. Although the free fraction of ZNS in the former was significantly higher than that of the latter, the increase was small. These results suggest that dosage regimens on the basis of body surface area would be more accurate than those on a body weight basis and that there is little effect of other antiepileptics on the serum protein binding of ZNS. PMID:1576673

  4. Serum biomarker panels for diagnosis of gastric cancer

    PubMed Central

    Tong, Weihua; Ye, Fei; He, Liang; Cui, Lifeng; Cui, Miao; Hu, Yuan; Li, Wei; Jiang, Jing; Zhang, David Y; Suo, Jian

    2016-01-01

    Purpose Currently, serum biomarkers that are sufficiently sensitive and specific for early detection and risk classification of gastric adenocarcinomas are not known. In this study, ten serum markers were assessed using the Luminex system and enzyme-linked immunosorbent assay for the diagnosis of gastric cancer and analysis of the relation between prognosis and metastases. Patients and methods A training set consisting of 228 gastric adenocarcinoma and 190 control samples was examined. A Luminex multiplex panel with nine biomarkers, consisting of three proteins discovered through our previous studies and six proteins previously reported to be cancer-associated, was constructed. One additional biomarker was detected using a commercial kit containing EDTA. Logistic regression, random forest (RF), and support vector machine (SVM) were used to identify the panel of discriminatory biomarkers in the training set. After selecting five proteins as candidate biomarkers, multivariate classification analyses were used to identify algorithms for diagnostic biomarker combinations. These algorithms were independently validated using a set of 57 gastric adenocarcinoma and 48 control samples. Results Serum pepsinogen I, serum pepsinogen II, A Disintegrin And Metalloproteinase domain-containing protein 8 (ADAM8), vascular endothelial growth factor (VEGF), and serum IgG to Helicobacter pylori were selected as classifiers in the three algorithms. These algorithms differentiated between the majority of gastric adenocarcinoma and control serum samples in the training/test set with high accuracy (RF 79.0%, SVM 83.8%, logistic regression 76.2%). These algorithms also differentiated the samples in the validation set (accuracy: RF 82.5%, SVM 86.1%, logistic regression 78.7%). Conclusion A panel of combinatorial biomarkers comprising VEGF, ADAM8, IgG to H. pylori, serum pepsinogen I, and pepsinogen II were developed. The use of biomarkers is a less invasive method for the diagnosis of

  5. Serum PCB levels and congener profiles among US construction workers

    PubMed Central

    Herrick, Robert F; Meeker, John D; Hauser, Russ; Altshul, Larisa; Weymouth, George A

    2007-01-01

    Background The presence of PCB in caulking (sealant) material found in masonry buildings has been well-documented in several countries. A recent investigation of 24 buildings in the greater Boston area found that 8 buildings had high PCB levels in caulking materials used around window frames and in joints between masonry blocks. Workers removing caulking material have been shown to have elevated serum PCB levels. Methods This project compared serum PCB levels among male workers who installed and/or removed PCB-containing caulking material from buildings in the greater Boston area with reference serum PCB levels from 358 men from the same area. Serum PCB levels were measured in the same laboratory by liquid-liquid extraction, column chromatography clean-up and dual capillary column GC/microECD analysis. Results When the congener profiles were compared between the reference population and the construction workers, the serum levels of the more volatile, lighter PCBs (di-, tri-and tetrachloro, sum of IUPAC# 6–74) were substantially higher among the construction workers. One of the youngest workers had the lowest total serum PCB levels (sum of 57 congeners) of all 6 workers, but the contribution of more volatile (less chlorinated) PCB congeners (#16, 26,28,33,74,66, and 60) was markedly higher than in other 5 workers and reference men. Only this worker was working on a job that involved removing PCB caulking at the time of the blood sampling. Conclusion While the results of this pilot study are based upon small numbers (6 construction workers who handled PCB caulking), the serum PCB levels among the construction workers exceed the referents. Comparison of the congener profiles suggests that there are substantial differences between the construction workers and the general population samples. These differences, and the similarities of profiles among the construction workers strongly suggest that occupational contact with caulking material can be a major source of PCB

  6. Isolation of Small Noncoding RNAs from Human Serum

    PubMed Central

    Khoury, Samantha; Ajuyah, Pamela; Tran, Nham

    2014-01-01

    The analysis of RNA and its expression is a common feature in many laboratories. Of significance is the emergence of small RNAs like microRNAs, which are found in mammalian cells. These small RNAs are potent gene regulators controlling vital pathways such as growth, development and death and much interest has been directed at their expression in bodily fluids. This is due to their dysregulation in human diseases such as cancer and their potential application as serum biomarkers. However, the analysis of miRNA expression in serum may be problematic. In most cases the amount of serum is limiting and serum contains low amounts of total RNA, of which small RNAs only constitute 0.4-0.5%1. Thus the isolation of sufficient amounts of quality RNA from serum is a major challenge to researchers today. In this technical paper, we demonstrate a method which uses only 400 µl of human serum to obtain sufficient RNA for either DNA arrays or qPCR analysis. The advantages of this method are its simplicity and ability to yield high quality RNA. It requires no specialized columns for purification of small RNAs and utilizes general reagents and hardware found in common laboratories. Our method utilizes a Phase Lock Gel to eliminate phenol contamination while at the same time yielding high quality RNA. We also introduce an additional step to further remove all contaminants during the isolation step. This protocol is very effective in isolating yields of total RNA of up to 100 ng/µl from serum but can also be adapted for other biological tissues. PMID:24998448

  7. Serum Levels of Follistatin Are Positively Associated With Serum-Free Thyroxine Levels in Patients With Hyperthyroidism or Euthyroidism.

    PubMed

    Tseng, Fen-Yu; Chen, Yen-Ting; Chi, Yu-Chao; Chen, Pei-Lung; Yang, Wei-Shiung

    2016-02-01

    Follistatin is a glycoprotein with various biologic functions that plays a role in adipocyte differentiation, muscle stimulation, anti-inflammation, and energy homeostasis. Thyroid hormones influence energy expenditure, glucose, and lipid metabolism. The association between serum follistatin level and thyroid function statuses has seldom been evaluated.The objectives of this study were to compare serum follistatin concentrations in different thyroid function statuses and to evaluate the associations between serum follistatin and free thyroxine (fT4) levels.In this study, 30 patients with hyperthyroidism (HY group) and 30 euthyroid individuals (EU group) were recruited. The patients of HY group were treated with antithyroid regimens as clinically indicated, whereas no medication was given to EU group. The demographic and anthropometric characteristics, biochemical data, serum levels of follistatin, and thyroid function of both groups at baseline and at the 6th month were compared. Data of all patients were pooled for the analysis of the associations between the levels of follistatin and fT4.At baseline, the HY group had significantly higher serum follistatin levels than the EU group (median [Q1, Q3]: 1.81 [1.33, 2.78] vs 1.13 [0.39, 1.45] ng/mL, P < 0.001). When treated with antithyroid regimens, the follistatin serum levels in HY group decreased to 1.54 [1.00, 1.88] ng/mL at the 6th month. In all patients, the serum levels of follistatin were positively associated with fT4 levels at baseline (β = 0.54, P = 0.005) and at the 6th month (β = 0.59, P < 0.001). The association between follistatin and fT4 levels remained significant in the stepwise multivariate regression analysis, both initially and at the 6th month.In comparison to the EU group, patients with hyperthyroidism had higher serum follistatin levels, which decreased after receiving antithyroid treatment. In addition, the serum follistatin concentrations were positively associated with

  8. Serum Levels of Follistatin Are Positively Associated With Serum-Free Thyroxine Levels in Patients With Hyperthyroidism or Euthyroidism

    PubMed Central

    Tseng, Fen-Yu; Chen, Yen-Ting; Chi, Yu-Chao; Chen, Pei-Lung; Yang, Wei-Shiung

    2016-01-01

    Abstract Follistatin is a glycoprotein with various biologic functions that plays a role in adipocyte differentiation, muscle stimulation, anti-inflammation, and energy homeostasis. Thyroid hormones influence energy expenditure, glucose, and lipid metabolism. The association between serum follistatin level and thyroid function statuses has seldom been evaluated. The objectives of this study were to compare serum follistatin concentrations in different thyroid function statuses and to evaluate the associations between serum follistatin and free thyroxine (fT4) levels. In this study, 30 patients with hyperthyroidism (HY group) and 30 euthyroid individuals (EU group) were recruited. The patients of HY group were treated with antithyroid regimens as clinically indicated, whereas no medication was given to EU group. The demographic and anthropometric characteristics, biochemical data, serum levels of follistatin, and thyroid function of both groups at baseline and at the 6th month were compared. Data of all patients were pooled for the analysis of the associations between the levels of follistatin and fT4. At baseline, the HY group had significantly higher serum follistatin levels than the EU group (median [Q1, Q3]: 1.81 [1.33, 2.78] vs 1.13 [0.39, 1.45] ng/mL, P < 0.001). When treated with antithyroid regimens, the follistatin serum levels in HY group decreased to 1.54 [1.00, 1.88] ng/mL at the 6th month. In all patients, the serum levels of follistatin were positively associated with fT4 levels at baseline (β = 0.54, P = 0.005) and at the 6th month (β = 0.59, P < 0.001). The association between follistatin and fT4 levels remained significant in the stepwise multivariate regression analysis, both initially and at the 6th month. In comparison to the EU group, patients with hyperthyroidism had higher serum follistatin levels, which decreased after receiving antithyroid treatment. In addition, the serum follistatin concentrations were positively

  9. Retrospective Study of Serum Sclerostin Measurements in Bed Rest Subjects

    NASA Technical Reports Server (NTRS)

    Spatz, J. M.; Fields, E. E.; Yu, E. W.; Divieti, Pajevic P.; Bouxsein, M. L.; Sibonga, M. L.; Zwart, S. R.; Smith, S. M.

    2011-01-01

    Animal models and human studies suggest that osteocytes regulate the skeleton s response to mechanical unloading at the cellular level in part by an increase in sclerostin, an inhibitor of the anabolic Wnt pathway. However, few studies have reported changes in serum sclerostin in humans exposed to reduced mechanical loading. Thus, we determined changes in serum sclerostin and bone turnover markers in healthy adult men who participated in a controlled bed rest study. Seven healthy adult men (31 +/- 3 yrs old) underwent 90-day six-degree head down tilt bed rest at the University of Texas Medical Branch in Galveston's Institute for Translational Sciences - Clinical Research Center (ITS-CRC). Serum sclerostin, PTH, serum markers of bone turnover (bone specific alkaline phosphatase, RANKL/OPG, and osteocalcin), urinary calcium and phosphorus excretion, and 24 hour pooled urinary markers of bone resorption (NTX, DPD, PYD) were evaluated pre-bed rest (BL), bed rest day 28 (BR-28), bed rest day 60 (BR-60), and bed rest day 90 (BR-90). In addition, bone mineral density (BMD) was assessed by dual-energy X-ray absorptiometry (DXA) at BL, BR-60, and post bed rest day 5 (BR+5). Data are reported as mean +/- standard deviation. We used repeated measures ANOVA to compare baseline values to BR-28, BR-60, and BR-90. RESULTS Consistent with prior reports, BMD declined significantly (1-2% per month) at weight-bearing skeletal sites (spine, hip, femur neck, and calcaneus). Serum sclerostin levels were elevated above BL at BR-28 (+29% +/- 20%, p = 0.003), BR-60 (+42% +/- 31%, p < 0.001), and BR-90 (22% +/- 21%, p = 0.07). Serum PTH levels were reduced at BR-28 (-17% +/- 16%, p = 0.02), BR-60 (-24% +/- 14%, p = 0.03), and returned to baseline at BR-90 (-21% +/- 21%, p = 0.14). Serum bone turnover markers did not change, however urinary bone resorption markers and calcium were significantly elevated following bed rest (p < 0.01). CONCLUSION We observed an increase of serum sclerostin

  10. Association Between Serum Relaxin and Subsequent Shoulder Instability.

    PubMed

    Owens, Brett D; Cameron, Kenneth L; Clifton, Kari B; Svoboda, Steven J; Wolf, Jennifer Moriatis

    2016-07-01

    Ligamentous laxity correlates with shoulder instability. Relaxin is a hormone that has been linked to laxity in the knee and has been shown to be a risk factor for anterior cruciate ligament (ACL) injury. This study prospectively evaluated the association between relaxin and acute shoulder instability. A prospective cohort study of 1050 young athletes was performed between 2006 and 2010. The authors conducted a nested case-control analysis within this cohort to evaluate the association between preinjury serum relaxin concentration and the likelihood of subsequent shoulder instability. The study compared 53 patients who had shoulder instability and 53 control subjects who were matched for sex, age, height, and weight. The serum relaxin concentration in preinjury baseline samples was tested with enzyme-linked immunosorbent assay analysis in duplicate. Independent t tests were performed to identify differences in mean serum relaxin concentration between patients with shoulder instability and uninjured control subjects. Logistic regression was used to evaluate whether preinjury baseline serum relaxin concentration was associated with the subsequent likelihood of shoulder instability. Of the 53 patients with instability, 13 (25%) had a detectable serum relaxin concentration compared with 9 (17%) of uninjured control subjects (P=.34). Mean serum relaxin concentration in the injury group was 3.69±1.78 pg/mL and 2.20±0.97 pg/mL in uninjured control subjects (P=.02). Increased serum relaxin concentration was associated with the subsequent likelihood of acute shoulder instability. Subjects were 2.18 times (odds ratio, 2.18; 95% confidence interval, 1.01-4.76) more likely to have acute shoulder instability during the follow-up period for every 1-pg/mL increase in serum relaxin concentration at baseline. The findings suggest that serum relaxin concentration is associated with a risk of subsequent shoulder instability in young athletes. Further research on the role of relaxin

  11. Prolactin Serum Concentrations During Aripiprazole Treatment in Youth

    PubMed Central

    Calarge, Chadi A.; Safer, Alan M.

    2013-01-01

    Abstract Objective This study aimed to: document the extent of the reduction of serum prolactin (PRL) levels induced by aripiprazole (ARI) treatment in children and adolescents, compare this effect by age group, and shed light on this phenomenon. Methods PRL serum levels in unmedicated subjects were compared to those in subjects treated with aripiprazole to calculate the rate of subnormal PRL levels during aripiprazole treatment. Next, a literature search was performed to better understand the effects of dopaminergic drugs on PRL levels by age group. Results Sixty percent of those treated with aripiprazole exhibited subnormal PRL serum levels versus 8% of unmedicated subjects. The rate of PRL subnormality in response to aripiprazole was half as frequent in adolescents and was minimal in adults. The drug-induced reduction of PRL serum levels became more prominent with increasing doses of aripiprazole and with an increased treatment duration. Conclusions With the increasing use of aripiprazole in the United States population, it is important that future research be conducted to explore the potential sequelae of subnormal PRL serum levels in children and adolescents. PMID:23647135

  12. The relationship between maternal serum magnesium level and preterm birth.

    PubMed

    Khani, S; Shokrzadeh, M; Karamoddini, P K; Shahmohammadi, S

    2010-04-01

    The aim of this study was to evaluate the relationship between maternal serum magnesium levels and preterm birth. This Nested case-control study carried out on 20 with preterm birth and 20 women at term birth at Imam Khomeini Hospital in Sari/Iran in 2008. The women with singleton gestation and intact fetal membrane suspected to preterm labor (case group), 10 cc blood samples were drawn into syringes and sent to laboratory of the hospital immediately. Sampling for control group was same as the case group. These samples recognized as control group just as birth occurring after week 37. Finally, serum magnesium level measured. Data analyzed using chi2, t-test and OR (Odd's Ratio). There was a relationship between the number of prenatal visits (p = 0.008) and stressful events associated with preterm birth (p < 0.02). Serum magnesium level was associated with preterm birth OR = 4.75, CI 95% = (0.48-46.91), Sensitivity, specificity, positive and negative predictive value of serum magnesium for preterm birth was 95, 50, 66.5 and 83.33%, respectively. Although, there was a correlation between serum magnesium levels and preterm birth, due to methodology of the study, a cohort study with the same cut off point and supplementation of magnesium in RTC studies is recommended. PMID:20836289

  13. 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

  14. THE SECRETORY PATHWAYS OF RAT SERUM GLYCOPROTEINS AND ALBUMIN

    PubMed Central

    Redman, Colvin M.; Cherian, M. George

    1972-01-01

    These studies compare the secretory pathways of newly formed rat serum glycoproteins and albumin by studying their submicrosomal localization at early times after the beginning of their synthesis and also by determining the submicrosomal site of incorporation of N-acetylglucosamine, mannose, galactose, and leucine into protein. N-acetylglucosamine, mannose, and galactose were only incorporated in vitro into proteins from membrane-attached polysomes and not into proteins from free polysomes. Mannose incorporation occurred in the rough endoplasmic reticulum, was stimulated by puromycin but not by cycloheximide, and 90% of the mannose-labeled protein was bound to the membranes. Galactose incorporation, by contrast, occurred in the smooth microsome fraction and 89% of the radioactive protein was in the cisternae. Albumin was mostly recovered (98%) in the cisternae, with negligible amounts in the membranes. To determine whether the radio-active sugars were being incorporated into serum proteins or into membrane protein, the solubilized in vivo-labeled proteins were treated with specific antisera to rat serum proteins or to albumin. Immunoelectrophoresis of the 14C-labeled leucine membrane and cisternal proteins showed that the membranes contained radioactive serum glycoprotein but no albumin, while the cisternal fraction contained all of the radioactive albumin and some glycoproteins. The results indicate that newly formed serum glycoproteins remain attached to the membranes of the rough endoplasmic reticulum after they are released from the membrane-attached polysomes, while albumin passes directly into the cisternae. PMID:5057975

  15. Increased serum cortisol binding in chronic active hepatitis

    SciTech Connect

    Orbach, O.; Schussler, G.C.

    1989-01-01

    A high serum cortisol concentration, apparently due to increased cortisol-binding globulin (CBG), was found in a patient (index case) with chronic active hepatitis (CAH). We therefore performed further studies to determine whether increased cortisol binding is generally associated with CAH. Serum samples were obtained from 15 hospitalized patients with long-term liver function test elevations but no evidence of cirrhosis, 15 normal subjects without a history of hepatitis, four healthy pregnant women, and 10 alcoholic patients with stigmata of cirrhosis. Serum cortisol binding was measured by an adaptation of a previously described charcoal uptake method. Thyroxine-binding globulin (TBG) and sex hormone-binding globulin were determined by radioimmunoassays. Charcoal uptake of 125I cortisol from sera of normal subjects and additional patients with CAH revealed that increased serum cortisol binding by a saturable site, presumably CBG, was associated with CAH. Cortisol binding was significantly correlated with immunoassayable TBG, suggesting that in CAH, similar mechanisms may be responsible for increasing the serum concentrations of CBG and TBG.

  16. 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.

  17. Impaired opsonization by serum from patients with chronic liver disease.

    PubMed Central

    Wyke, R J; Rajkovic, I A; Williams, R

    1983-01-01

    Serum opsonization of two organisms, E. coli and yeasts (S. cerivisiae), was examined in 68 patients with chronic liver disease (CLD). Impaired opsonization for yeasts was found in seven (29%) of 24 patients with chronic active hepatitis, six (27%) of 22 with alcoholic cirrhosis and five (23%) of 22 with primary biliary cirrhosis. Opsonization for E. coli was normal in patients with primary biliary cirrhosis but impaired in seven (29%) patients with chronic active hepatitis and three (14%) of those with alcoholic cirrhosis. The defect of opsonization in chronic active hepatitis was found mainly in patients with histological evidence of active disease. A deficiency, rather than antagonism or inhibition, of normal opsonization factors was responsible, but could not be related to reduced levels of serum complement factors of either the classical or the alternative pathway present in 45% of the patients with chronic active hepatitis, 71% with alcoholic cirrhosis and 18% of those with primary biliary cirrhosis. Serum from two of 11 patients with impaired opsonization antagonised the function of normal polymorphonuclear leucocytes, and polymorphonuclear leucocytes from six of seven patients had slightly reduced phagocytosis/killing of E. coli opsonized in normal serum. Defects of serum opsonization, complement activity and polymorphonuclear leucocyte function may be causes of the increased susceptibility to bacterial infection in patients with CLD. PMID:6339126

  18. Low serum levels of ghrelin are associated with gallstone disease

    PubMed Central

    Méndez-Sánchez, Nahum; Ponciano-Rodríguez, Guadalupe; Bermejo-Martínez, Luisa; Villa, Antonio R; Chávez-Tapia, Norberto C; Zamora-Valdés, Daniel; Pichardo-Bahena, Raúl; Barredo-Prieto, Blanca; Uribe-Ramos, Martha H; Ramos, Martha H; Baptista-González, Héctor A; Uribe, Misael

    2006-01-01

    AIM: To explore the role of ghrelin in gallstone disease. METHODS: We carried out a cross-sectional study in 150 subjects, 38 with gallstones (cases) and 112 controls. We also did a real-time PCR-RT study in twenty gallbladder samples each. Body mass index (BMI), serum insulin, ghrelin, and serum lipids were measured. Logistic regression analyses (univariate and multivariate) were conducted to estimate the probability of gallstone disease associated with serum ghrelin concentrations. RESULTS: Cases were statistically different from controls in gender distribution (P = 0.01), age (53 vs 44 yr, P = 0.002), BMI (28 vs 25; P = 0.004), and glucose (5.26 vs 4.98 mmol/L; P = 0.05). The prevalence of ghrelin serum levels above the third tercile was lower in subjects without metabolic syndrome (P < 0.05). In a multivariate model, we found a protective effect, when ghrelin values were higher than the median value (OR = 0.27, 95%CI 0.09-0.82, P = 0.02). Twenty (20%) gallbladder specimens expressed ghrelin mRNA. CONCLUSION: Serum ghrelin concentrations are associated with a protective effect of GD. PMID:16718795

  19. Whole blood versus serum ionized calcium concentrations in dialysis patients

    PubMed Central

    Kang, Seok Hui; Cho, Kyu Hyang; Park, Jong Won; Yoon, Kyung Woo

    2014-01-01

    Background/Aims The aim of this study is to measure the difference of ionized calcium between heparinized whole blood and serum. Methods We recruited 107 maintenance hemodialysis (HD) patients from our hospital HD unit. The clinical and laboratory data included ionized calcium in serum and in whole blood (reference, 4.07 to 5.17 mg/dL). Results The level of ionized calcium in serum was higher than that in whole blood (p < 0.001). Bland-Altman analysis showed that difference for ionized calcium was 0.5027. For the difference, the nonstandardized β was -0.4389 (p < 0.001) and the intercept was 2.2418 (p < 0.001). There was a significant difference in the distribution of categories of ionized calcium level between two methods (κ, 0.279; p < 0.001). Conclusions This study demonstrates that whole blood ionized calcium is underestimated compared with serum ionized calcium. Positive difference increases as whole blood ionized calcium decreases. Therefore, significant hypocalcemia in whole blood ionized calcium should be verified by serum ionized calcium. PMID:24648806

  20. Serum-Induced Differentiation of Human Meibomian Gland Epithelial Cells

    PubMed Central

    Sullivan, David A.; Liu, Yang; Kam, Wendy R.; Ding, Juan; Green, Karin M.; Shaffer, Scott A.; Hatton, Mark P.; Liu, Shaohui

    2014-01-01

    Purpose. We hypothesize that culturing immortalized human meibomian gland epithelial cells in serum-containing medium will induce their differentiation. The purpose of this investigation was to begin to test our hypothesis, and explore the impact of serum on gene expression and lipid accumulation in human meibomian gland epithelial cells. Methods. Immortalized and primary human meibomian gland epithelial cells were cultured in the presence or absence of serum. Cells were evaluated for lysosome and lipid accumulation, polar and neutral lipid profiles, and gene expression. Results. Our results support our hypothesis that serum stimulates the differentiation of human meibomian gland epithelial cells. This serum-induced effect is associated with a significant increase in the expression of genes linked to cell differentiation, epithelium development, the endoplasmic reticulum, Golgi apparatus, vesicles, and lysosomes, and a significant decrease in gene activity related to the cell cycle, mitochondria, ribosomes, and translation. These cellular responses are accompanied by an accumulation of lipids within lysosomes, as well as alterations in the fatty acid content of polar and nonpolar lipids. Of particular importance, our results show that the molecular and biochemical changes of immortalized human meibomian gland epithelial cells during differentiation are analogous to those of primary cells. Conclusions. Overall, our findings indicate that immortalized human meibomian gland epithelial cells may serve as an ideal preclinical model to identify factors that control cellular differentiation in the meibomian gland. PMID:24867579

  1. Serum MicroRNAs as Potential Biomarkers of AMD

    PubMed Central

    Szemraj, Maciej; Bielecka-Kowalska, Anna; Oszajca, Katarzyna; Krajewska, Marta; Goś, Roman; Jurowski, Piotr; Kowalski, Michał; Szemraj, Janusz

    2015-01-01

    Background Age-related macular degeneration (AMD) is a major cause of blindness worldwide. Circulating microRNAs (miRNAs) in serum have emerged as novel candidate biomarkers for many diseases. The aim of the present study was to identify a serum microRNA (miRNA) expression profile specific for dry and wet forms of AMD. Material/Methods Serum miRNA expression was first screened using TaqMan® Human MicroRNA Array A (Applied Biosystems). An extensive, self-validated, individual, quantitative RT-PCR (qRT-PCR) study was then performed on a cohort of 300 AMD patients (150 wet form and 150 dry form) and 200 controls. The Mann-Whitney U test and nonparametric Spearman’s rank correlation coefficient were used for statistical analysis. Results miRNA expression analysis revealed increased expression of miR661 and miR3121 in serum of patients with dry AMD and miR4258, miR889, and Let7 in patients with wet form. Expression of analyzed miRNA was not observed or remained at low level in controls. Conclusions Differences in miRNA serum profile exist between patients with wet and dry form of AMD, which indicates miRNAs as potential biomarkers of AMD. Further studies should be performed to confirm its significance in clinical practice. PMID:26366973

  2. The Serum Lead level in Patients With Retained Lead Pellets

    PubMed Central

    Moazeni, Mohammad; Mohammad Alibeigi, Faramarz; Sayadi, Masoud; Poorya Mofrad, Ebrahim; Kheiri, Soleiman; Darvishi, Malihe

    2014-01-01

    Background: Patients, who survived from shotgun injuries, often have some retained lead pellets in their bodies. Several cases of lead toxicity have been reported regarding these patients. Objectives: This study seeks to compare the serum lead level in patients who have retained lead pellets in their bodies with the control group. Patients and Methods: In this case-control study, we gathered the serum lead levels of 25 patients with some retained lead pellets in their bodies due to shotgun and 25 volunteers without similar lead exposure and compared them in view of the age, gender, and living place. Results: While the mean serum lead level in both groups was lower than the standard level (i.e. 40 µg/dL) , the mean ± SD of serum lead level were 29 ± 12.8 µg/dL and 25.3 ± 6.4 µg/dL in the case and control groups, respectively without any significant difference (P = 0. 30) . However, a positive relationship was seen between serum lead level, and the number of retained lead pellets (r = 0.447, P = 0. 025) . Conclusions: Although extensive surgery to remove the lead pellets is not recommended in patients injured with shotguns, those with many retained lead pellets in their bodies should be considered at risk for lead poisoning and monitored carefully. PMID:25147780

  3. Serum Enzyme Profiles Differentiate Five Types of Muscular Dystrophy

    PubMed Central

    Zhu, Yuling; Zhang, Huili; Sun, Yiming; Li, Yaqin; Deng, Langhui; Wen, Xingxuan; Wang, Huaqiao; Zhang, Cheng

    2015-01-01

    Background. Differentiation among types of muscular dystrophy (MD) has remained challenging. In this retrospective study, we sought to develop a methodology for differentiation of MD types using analysis of serum enzyme profiles. Methods. The serum levels of enzymes from 232 patients, including 120 with DMD, 36 with BMD, 36 with FSHD, 46 with LGMD, and 11 with EDMD, were evaluated. Results. The characteristic profiles of serum enzymes facilitated differentiation of these five types of MD. DMD was characterized by simultaneous elevation of ALT, AST, LDH, and ALP; BMD and LGMD were characterized by elevation of ALT, AST, and LDH; and FSHD and EDMD were characterized by a lack of abnormal serum enzyme levels. We further developed discriminant functions to distinguish BMD and LGMD. For LGMD, LGMD2B patients had significantly higher ALP levels than non-LGMD2B patients (98 ± 59 U/L versus 45 ± 9 U/L, resp., p < 0.05). Conclusions. Our approach enabled the determination of MD subtypes using serum enzyme profiles prior to genetic testing, which will increase the chance a mutation will be found in the first gene analyzed. PMID:26063958

  4. Serum lipid pattern unifies following renal transplantation in children.

    PubMed

    Müller, Thomas; Koeppe, Silvie; Arbeiter, Klaus; Luckner, Doris; Salzer, Urike; Balzar, Egon; Aufricht, Christoph

    2003-09-01

    Hyperlipidemia is a common problem in solid organ transplant recipients. In this study we evaluated the role of pre-transplant renal replacement therapy on early and late changes of serum lipid levels in children following renal transplantation. In 46 children with chronic renal failure (median age 10.3 years) and 12 children with heart failure (median age 5.0 years), cholesterol and triglycerides were measured before and during follow-up after transplantation. Children with renal failure had significantly higher serum lipids than controls ( n=34, median age 9.2 years) and patients with heart failure. Pre transplantation, cholesterol and triglycerides were significantly lower in the hemodialysis than in the peritoneal dialysis population, whereas conservatively treated children had intermediate levels. After transplantation, serum cholesterol converged towards a mean level of 208 mg/dl and triglyceride levels converged towards a uniform level of 195 mg/dl at 9 months post transplant. The ratio of cholesterol/high-density lipoprotein significantly decreased from 4.7 to 3.8. The pattern of "post-transplant hyperlipidemia" was similar in both renal and cardiac allograft recipients. Hence, the early post-transplant changes of serum lipid pattern are markedly dependent on the mode of pre-transplant renal replacement therapy. Later, serum lipid levels were no longer influenced by prior renal replacement therapy and showed a new pattern of "post-transplant hyperlipidemia" in all children. PMID:12883978

  5. Serum homocysteine level in vegetarians in District Tharparker, Sindh

    PubMed Central

    Kapoor, Aneel; Zuberi, Nudrat Anwar; Rathore, M. Imran; Baig, Mukhtiar

    2015-01-01

    Objectives: The aim of present study was to investigate serum homocysteine levels in apparently healthy vegetarians and ominvores in Mithi, district Tharparker, Sindh, Pakistan. Methods: This study was conducted in the Department of Biochemistry, Basic Medical Sciences Institute (BMSI), Jinnah Postgraduate Medical Center (JPMC), Karachi and blood samples were collected from Mithi, district Tharparker, Sindh, Pakistan, in 2012. One hundred vegetarian and one hundred omnivores (age ranging from 20-40 years) were enrolled for this study. Serum homocysteine levels were measured by the chemiluminescence enzyme immunoassay method. Results: Serum homocysteine (Hcy) level was considerably higher (p<0.001) in vegetarian group compared to omnivores. We further grouped and analyzed our study subjects according to their gender and according to Hcy level (greater than or lower than 15µmol/L). A considerable number of vegetarian subjects 30% were having Hcy >15µmol/L compared to omnivores 6%, (p<0.001). Gender-wise comparison showed that 27.02% male and 38.46% females had >15µmol/L serum Hcy level in vegetarian group and 6.9% male and 3.5% females had >15µmol/L serum Hcy level in omnivores group, but the difference was not significant in any group. Conclusion: Vegetarians are more prone to develop hyperhomocysteinemia, so they are at high risk to develop cardiovascular disease. PMID:25878628

  6. Clinical significance of serum adipokines levels in lung cancer.

    PubMed

    Kerenidi, Theodora; Lada, Martha; Tsaroucha, Agori; Georgoulias, Panagiotis; Mystridou, Parthena; Gourgoulianis, Konstantinos I

    2013-06-01

    Adipokines have a significant effect on metabolism, immunoinflammatory responses as well as on carcinogenesis; therefore, we aimed at evaluating their potential predictive and prognostic significance in lung cancer. Eighty patients--mean age 62.9 ± 9.2 years--with previously untreated lung cancer (61 NSCLC and 19 SCLC) of all stages and 40 healthy individuals were enrolled in this study. Serum levels of leptin, adiponectin and ghrelin were measured using human Radioimmunoassay kits. Serum leptin levels in lung cancer patients were lower compared to control (p < 0.0001), while adiponectin and ghrelin levels were significantly increased in patients (p = 0.0003 and p = 0.0043, respectively). Additionally, the leptin/adiponectin ratio was significantly lower in the patients group compared to controls (p < 0.0001]. There was no association between serum levels of adipokines and any of the patient clinicopathological characteristics or response to therapy. Nevertheless, patients with lower values of serum leptin had shorter overall survival (p = 0.014), whereas multivariate analysis revealed leptin levels as an independent prognostic factor for survival (p = 0.024, HR 0.452, CI 95 % 0.232-0.899). These results suggest that adipokines may play a role in the pathogenesis of lung cancer, while leptin serum levels might provide useful prognostic information. PMID:23430445

  7. Serum vitamin A concentrations in captive sea otters (Enhydra lutris).

    PubMed

    Righton, Alison L; St Leger, Judy A; Schmitt, Todd; Murray, Michael J; Adams, Lance; Fascetti, Andrea J

    2011-03-01

    Individual dietary preferences and difficulty with animal training create challenges and nutritional concerns when evaluating a captive sea otter (Enhydra lutris) diet. The importance of vitamin A within the body reflects the necessity that it be ingested in adequate amounts to ensure optimal health. To compare levels of serum vitamin A concentrations from captive sea otters on daily oral vitamin A supplementation, serum samples from eight adult sea otters from three institutions were evaluated for serum vitamin A concentrations. The eight animals were fed a total of four different diets and received oral supplementation via three different methods. Multiple diet items were analyzed for vitamin A content and were found to have low to nondetectable levels of vitamin A. Oral vitamin A supplementation, as a slurry with dietary items, was shown to be effective and a mean serum concentration of approximately 170 +/- 51 microg/L was obtained for serum vitamin A concentrations in captive sea otters. Captive diets can be modified to increase vitamin A concentration and supplementation and, if accepted, can be used as a means to ensure adequate vitamin A intake. PMID:22946382

  8. Relationship between exposure to industrial noise and serum lipid profile.

    PubMed

    Mehrdad, Ramin; Bahabad, Afshin Malek; Moghaddam, Azadeh Nahan

    2011-01-01

    Aim of our study was to investigate the effects of exposure to industrial noise on serum lipid profile among workers who are exposed to noise at work. In a historical cohort study, we recruited 154 and 146 male workers as high and low level noise exposure groups respectively. We defined workers with at least one year exposure to noise level more than 90 dB as high exposure group, and those with exposure to less than 80 dB as low exposure group. Afterwards, in the fasting blood specimens of participants we measured serum Triglyceride (TG), total Cholesterol (TC), high and low density lipoprotein (HDL and LDL). Mean of TG, TC, HDL and LDL for low exposure group were 148, 189, 38 and 103 mg/dl and for high exposure group were 237, 189, 37 and 104 mg/dl respectively. Mean serum TG between two groups was different. Even after adjustment for age, BMI, smoking and work hours per week, serum TG among high exposure group was 89 mg/dl higher than low exposure group and this difference was statistically significant (P = 0.00). There was no significant difference between two groups in TC, LDL and HDL levels. This study did not find a statistically significant relationship between exposure to noise and serum TC, LDL and HDL, but TG in two groups was different and this difference was statistically significant. PMID:22131242

  9. Selective activity of butyrylcholinesterase in serum by a chemiluminescent assay.

    PubMed

    Yavo, B; Brunetti, I L; da Fonseca, L M; Catalani, L H; Campa, A

    2001-01-01

    In a previous study, we showed that purified commercial esterase activity can be detected in a chemiluminescent assay based on the hydrolysis of 2-methyl-1-propenylbenzoate (MPB) to 2-methyl-1-propenol, which is subsequently oxidized by the horseradish peroxidase (HRP)-H(2)O(2) system. The purpose of this study was to verify the applicability of this assay to human serum. The existence of an esterase activity capable of hydrolysing MPB is indicated by the fact that the MPB-serum-HRP-H(2)O(2) system consumes oxygen and emits light. Both signals were abolished by prior serum heat inactivation and were preserved when serum was stored at < or =4 degrees C. Addition of aliesterase inhibitors, such as fluoride ion and trichlorfon or the cholinesterase inhibitor eserine, totally prevents light emission. The butyrylcholinesterase-specific substrate benzoylcholine causes a delay in both O(2) uptake and light emission, while the specific acetylcholinesterase substrate, acetyl-beta-methylcholine, had practically no effect. Purified butyrylcholinesterase, but not acetylcholinesterase, triggered light emission. The finding that butyrylcholinesterase is responsible for the hydrolysis of MPB in serum should serve as the basis for the development of a specific chemiluminescent assay for this enzyme. PMID:11590700

  10. Serum YKL-40 and gestational diabetes - an observational cohort study.

    PubMed

    Gybel-Brask, Dorte; Johansen, Julia S; Christiansen, Ib J; Skibsted, Lillian; Høgdall, Estrid V S

    2016-09-01

    To examine serum YKL-40 in women developing gestational diabetes mellitus (GDM). In the present large observational cohort study of 1179 pregnant women, we determined serum YKL-40 four times during pregnancy (at gestational age 12, 20, 25, and 32 weeks). Pregnancy outcome was obtained from medical records. Sixty-eight women (5.8%) developed GDM. Serum YKL-40 increased from gestational age (GA) 12 weeks and the following weeks in the women who developed GDM and was independent of BMI, parity, and maternal age (OR = 2.69, 95% CI: 1.45-5.00, p = 0.002). No association was found between serum YKL-40 and the oral glucose tolerance test results. In conclusion, YKL-40 significantly increased in pregnant women with GDM compared with women without GDM, probably reflecting the low-grade inflammation of GDM. However, we did not find an association between serum concentrations of YKL-40 in early pregnancy and the development of GDM and thus we conclude that YKL-40 alone is not usable as a biomarker for early prediction of GDM. PMID:27457220

  11. Serum nickel concentrations in hemodialysis patients with environmental exposure

    SciTech Connect

    Hopfer, S.M.; Fay, W.P.; Sunderman, F.W. Jr.

    1989-05-01

    Nickel was analyzed by electrothermal atomic absorption spectrophotometry in serum specimens from 22 healthy hospital workers and 30 patients with end-stage renal disease treated by extracorporeal hemodialysis, who resided in Sudbury, Ontario, Canada, a city with extensive nickel mines and smelters. Samples of tap water from Sudbury contained 109 +/- 46 micrograms Ni per L (P less than 0.01 vs 0.4 +/- 0.2 micrograms Ni per L in corresponding water samples from Hartford, Connecticut). Serum nickel concentrations averaged 0.6 +/- 0.3 micrograms Ni per L in Sudbury hospital workers (P less than 0.05 vs 0.2 +/- 0.2 micrograms Ni per L in corresponding serums from 43 healthy hospital workers in Hartford). In serums collected post-treatment from Sudbury hemodialysis patients, nickel concentrations averaged 8.5 +/- 2.8 micrograms Ni per L, (i.e., 14-times the corresponding mean in Sudbury hospital workers, P less than 0.01), but were not significantly higher than the nickel concentrations in serums from 42 Hartford hemodialysis patients (7.2 +/- 2.2 micrograms Ni per L). This study confirms the presence of hypernickelemia in hemodialysis patients, but does not suggest that hemodialysis patients have significantly increased risk of nickel toxicity in Sudbury, compared to Hartford, despite the high nickel concentrations in Sudbury tap water. This favorable outcome attests to the efficient deionization of water used to prepare hemodialysis solutions in Sudbury.

  12. Serum phosphorus adds to value of serum parathyroid hormone for assessment of bone turnover in renal osteodystrophy.

    PubMed

    Gentry, Jimmy; Webb, Jonathan; Davenport, Daniel; Malluche, Hartmut H

    2016-07-01

    It is well-established that parathyroid hormone (PTH) correlates with the level of bone turnover in patients with chronic kidney disease stage 5D (CKD-5D). Hyperphosphatemia is a well-established complication of end-stage renal disease and is usually attributed to dietary intake. This study evaluates the relationship between serum phosphorus levels and bone turnover in patients with CKD-5D. 93 patients with CKD-5D from the Kentucky Bone Registry who had sequentially undergone anterior iliac bone biopsies were reviewed. Undecalcified bone sections were qualitatively assessed for turnover and placed into a group with low turnover and a group with non-low (normal/high) turnover. Results of PTH and phosphorus concentrations in blood drawn at the time of biopsies were compared between the groups. PTH and phosphorus levels were significantly higher in the non-low turnover group compared to the low turnover group. Cutoff levels for PTH and phosphorus were tested for predictive power of bone turnover. Both PTH and phosphorus correlated with turnover. Adding serum phosphorus to serum PTH enhanced predictive power of PTH for low turnover. The vast majority of patients with serum phosphorus levels ≥ 6.0 mg/dL had non-low turnover, while the majority of those with low turnover had phosphorus values < 6.0 mg/dL. Classification and regression-tree analysis showed that elevated serum phosphorus (> 6.2 mg/dL) in patients with PTH < 440 pg/mL was helpful in diagnosing nonlow turnover in this range of PTH. In patients with PTH ranges of 440 - 814 pg/mL, serum phosphorus levels > 4.55 mg/dL ruled out low turnover bone disease. This suggests that not only dietary intake but also bone affects serum phosphorus levels. PMID:27191663

  13. Enhanced Soluble Serum CD40L and Serum P-Selectin Levels in Primary Aldosteronism.

    PubMed

    Petramala, L; Iacobellis, G; Carnevale, R; Marinelli, C; Zinnamosca, L; Concistrè, A; Galassi, M; Iannucci, G; Lucia, P; Pignatelli, P; Ciardi, A; Violi, F; De Toma, G; Letizia, C

    2016-07-01

    Primary aldosteronism (PA) is one of the most frequent forms of secondary hypertension, associated with atherosclerosis and higher risk of cardiovascular events. Platelets play a key role in the atherosclerotic process. The aim of the study was to evaluate the platelet activation by measuring serum levels of soluble CD40L (sCD40L) and P-selectin (sP-selectin) in consecutive PA patients [subgroup: aldosterone-secreting adrenal adenoma (APA) and bilateral adrenal hyperplasia (IHA)], matched with essential hypertensive (EH) patients. The subgroup of APA patients was revaluated 6-months after unilateral adrenalectomy. In all PA group, we measured higher serum levels of both sP-selectin (14.29±9.33 pg/ml) and sCD40L (9.53±4.2 ng/ml) compared to EH patients (9.39±5.3 pg/ml and 3.54±0.94 ng/ml, respectively; p<0.001). After removal of APA, PA patients showed significant reduction of blood pressure (BP) values, plasma aldosterone (PAC) levels and ARR-ratio, associated with a significant reduction of sP-selectin (16.74±8.9 pg/ml vs. 8.1±3.8 pg/ml; p<0.01) and sCD40L (8.6±1 ng/ml vs. 5.24±0.94 ng/ml; p<0.001). In PA patients, we found a significant correlation between sP-selectin and sCD40L with PAC (r=0.52, p<0.01; r=0.50, p<0.01, respectively); this correlation was stronger in APA patients (r=0.54; p<0.01 r=0.63; p<0.01, respectively). Our results showed that PA is related to platelet activation, expressed as higher plasma values of sCD40L and sP-selectin values. Surgical treatment and consequent normalization of aldosterone secretion was associated with significant reduction of sCD40L and sP-selectin values in APA patients. PMID:27101095

  14. Elevated serum melatonin levels during human late pregnancy and labour.

    PubMed

    Wierrani, F; Grin, W; Hlawka, B; Kroiss, A; Grünberger, W

    1997-09-01

    Melatonin (MLT) shows an influence on gonadal steroid genesis, and has soporific effects. Serum MLT levels were examined during late pregnancy and 4 days after delivery in 25 women. Circulating levels of melatonin were analysed as integrated values (areas under the curve [AUC]) over 24 hours, 5 to 2 days before and 4 days after delivery. Antepartum AUCs were significantly increased compared with postpartum AUCs. Additionally, MLT levels were measured every 2 hours in a subgroup of 11 women during spontaneous labour between 08.00 and 12.00 h at a time when physiological serum MLT levels were low. Increased MLT levels were determined and compared to MLT levels measured in a previous evaluation of the antepartum AUCs. Elevated serum MLT levels during late-pregnancy and labour may influence the concentration of receptors of gonadal steroids in the gravid uterus at term and the psychic perception of painful uterine contractions during labour. PMID:15511919

  15. Serum inflammatory markers in obese mice: Effect of ghrelin

    PubMed Central

    Khazaei, Majid; Tahergorabi, Zoya

    2015-01-01

    Background: Ghrelin is involved in modulation of food intake and energy homeostasis; however, it may play a role in cardiovascular system and atherosclerosis process. This study aimed to investigate the effect of ghrelin on serum inflammatory markers in control and obese mice. Materials and Methods: Ghrelin (100 mg/kg/day, twice daily) was administered interaperitoneally to control and diet-induced obese mice. After 10 days, blood samples were taken. Results: Results showed that administration of ghrelin did not change serum hsCRP level; however, it reduced serum IL-6 concentration in obese mice (P < 0.05). Conclusion: It seems that the exact role and mechanism of ghrelin in prevention or treatment of atherosclerosis needs more studies. PMID:26322293

  16. Shrinkage of pegylated and non-pegylated liposomes in serum

    PubMed Central

    Wolfram, Joy; Suri, Krishna; Yang, Yong; Shen, Jianliang; Celia, Christian; Fresta, Massimo; Zhao, Yuliang; Shen, Haifa; Ferrari, Mauro

    2013-01-01

    An essential requisite for the design of nanodelivery systems is the ability to characterize the size, homogeneity and zeta potential of nanoparticles. Such properties can be tailored in order to create the most efficient drug delivery platforms. An important question is whether these characteristics change upon systemic injection. Here, we have studied the behavior of phosphatidylcholine/cholesterol liposomes exposed to serum proteins. The results reveal a serum-induced reduction in the size and homogeneity of both pegylated and non-pegylated liposomes, implicating the possible role of osmotic forces. In addition, changes to zeta-potential were observed upon exposing liposomes to serum. The liposomes with polyethylene glycol expressed different characteristics than their non-polymeric counterparts, suggesting the potential formation of a denser protein corona around the non-pegylated liposomes. PMID:24216620

  17. Binding of temoporfin to the lipoprotein fractions of human serum.

    PubMed Central

    Michael-Titus, A T; Whelpton, R; Yaqub, Z

    1995-01-01

    The binding of a new photosensitizer, temoporfin, to human serum lipoproteins was investigated. [14C]-Temoporfin (0.1-10 micrograms ml-1) was incubated with human serum for 30 min at room temperature or for 20 h at 4 degrees C, prior to stepwise density flotation to separate the lipoprotein fractions. The distribution of the drug was independent of the initial concentration or time and temperature of the incubation. The proportion of temoporfin in each fraction was: very low density lipoprotein 6%, low density lipoprotein 22%, lipoprotein(a) 17%, high density lipoprotein 39% and lipoprotein deficient serum 16%. Autoradiography of agarose gels showed that the drug was associated with the lipoprotein in the fractions. Fractionation of plasma samples collected from a patient after an intravenous infusion of temoporfin revealed a binding profile similar to that obtained in the in vitro study. Images Figure 1 PMID:8703668

  18. Selenium concentration in serum of healthy Greek adults.

    PubMed

    Van Cauwenbergh, R; Robberecht, H; Deelstra, H; Picramenos, D; Kostakopoulos, A

    1994-06-01

    Serum selenium levels of 160 healthy Greeks were determined by Zeeman-effect background-corrected atomic absorption spectrometry. Mean value for 101 men (70.7 +/- 16.2 micrograms/L) tended to be higher, but not statistically significant, compared to the mean value for 59 women (64.9 +/- 14.7 micrograms/L). When the subjects were divided into various age groups there appeared to be some increase as a function of age. Compared to the extensive literature data on serum Se levels for various countries healthy Greeks proved to be at the lower concentration range. The scarce, but conflicting literature data on serum Se values for Greeks is discussed. PMID:7881284

  19. Software-assisted serum metabolite quantification using NMR.

    PubMed

    Jung, Young-Sang; Hyeon, Jin-Seong; Hwang, Geum-Sook

    2016-08-31

    The goal of metabolomics is to analyze a whole metabolome under a given set of conditions, and accurate and reliable quantitation of metabolites is crucial. Absolute concentration is more valuable than relative concentration; however, the most commonly used method in NMR-based serum metabolic profiling, bin-based and full data point peak quantification, provides relative concentration levels of metabolites and are not reliable when metabolite peaks overlap in a spectrum. In this study, we present the software-assisted serum metabolite quantification (SASMeQ) method, which allows us to identify and quantify metabolites in NMR spectra using Chenomx software. This software uses the ERETIC2 utility from TopSpin to add a digitally synthesized peak to a spectrum. The SASMeQ method will advance NMR-based serum metabolic profiling by providing an accurate and reliable method for absolute quantification that is superior to bin-based quantification. PMID:27506360

  20. Formulas for fixing serum sodium: curb your enthusiasm

    PubMed Central

    Sterns, Richard H.

    2016-01-01

    A variety of formulas have been proposed to predict changes in serum sodium concentration. All are based on an experiment done over 50 years ago by Edelman, who derived a formula relating the plasma sodium concentration to isotopically measured body sodium, potassium, and water. Some of these formulas fail because they do not include urinary losses of electrolytes and water. Even those that include these essential variables are not accurate enough for clinical use because it is impractical to adjust calculations to rapid changes in urinary composition, and because the formulas do not account for changes in serum sodium caused by internal exchanges between soluble and bound sodium stores or shifts of water into or out of cells resulting from changes in intracellular organic osmolytes. Nephrologists should curb their enthusiasm for predictive formulas and rely instead on frequent measurements of the serum sodium when correcting hyponatremia and hypernatremia. PMID:27478590

  1. Formulas for fixing serum sodium: curb your enthusiasm.

    PubMed

    Sterns, Richard H

    2016-08-01

    A variety of formulas have been proposed to predict changes in serum sodium concentration. All are based on an experiment done over 50 years ago by Edelman, who derived a formula relating the plasma sodium concentration to isotopically measured body sodium, potassium, and water. Some of these formulas fail because they do not include urinary losses of electrolytes and water. Even those that include these essential variables are not accurate enough for clinical use because it is impractical to adjust calculations to rapid changes in urinary composition, and because the formulas do not account for changes in serum sodium caused by internal exchanges between soluble and bound sodium stores or shifts of water into or out of cells resulting from changes in intracellular organic osmolytes. Nephrologists should curb their enthusiasm for predictive formulas and rely instead on frequent measurements of the serum sodium when correcting hyponatremia and hypernatremia. PMID:27478590

  2. PRODUCTION OF UNIFORMLY SIZED SERUM ALBUMIN AND DEXTROSE MICROBUBBLES

    PubMed Central

    Borrelli, Michael J.; O’Brien, William D.; Bernock, Laura J.; Williams, Heather R.; Hamilton, Eric; Wu, Jonah; Oelze, Michael L.; Culp, William C.

    2011-01-01

    Uniformly-sized preparations with average microbubble (MB) diameters from 1 µm to 7 µm were produced reliably by sonicating decafluorobutane-saturated solutions of serum albumin and dextrose. Detailed protocols for producing and size-separating the MBs are presented, along with the effects that changing each production parameter (serum albumin concentration, sonication power, sonication time, etc.) had on MB size distribution and acoustic stability. These protocols can be used to produce MBs for experimental applications or serve as templates for developing new protocols that yield MBs with physical and acoustic properties better suited to specific applications. Size stability and ultrasonic performance quality control tests were developed to assure that successive MB preparations perform identically and to distinguish the physical and acoustic properties of identically sized MBs produced with different serum albumin-dextrose formulations and sonication parameters. MBs can be stored at 5°C for protracted periods (2 weeks to one year depending on formulation). PMID:21689961

  3. 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

  4. Serum calcium fractions in sheep treated with Solanum malacoxylon.

    PubMed

    Bingley, J B; Ruksan, B E; Carrillo, B J

    1976-07-01

    Sheep treated with a single dose of an extract of the dried leaves of Solanum malacoxylon (SM) at the rate of 0-2 g of leaves per kg liveweight produced a pronounced hypercalcaemia (49 per cent, P less than 0-005) after 24 h, which persisted for at least six days. The ultra-filtrable fraction of the serum calcium rose to approximately the same extent as the protein-bound calcium. This finding is consistent with osteosclerosis and parathyroid atrophy found to occur in cases of experimental SM intoxication. At the dose level given serum inorganic phosphorus was not significantly increased and packed cell volume, serum proteins and ceruloplasmin concentrations remained constant. PMID:951523

  5. Serum thyroglobulin as a risk factor for thyroid carcinoma.

    PubMed

    Hrafnkelsson, J; Tulinius, H; Kjeld, M; Sigvaldason, H; Jónasson, J G

    2000-01-01

    Samples from a biological serum bank taken up to 23 years prior to diagnosis of thyroid carcinoma were analysed for human thyroglobulin, thyroid-stimulating hormone and thyroxin. After exclusions, the final study material consisted of 59 cases of papillary and follicular carcinomas. These cases were compared with 164 controls, matched for sex, age and time of sample taking. The most interesting finding was that concentrations of thyroglobulin in serum were abnormally elevated in cases compared with controls, equal to or above 30 microg/L, with odds ratio 7.0 (CI 3.1-15.7). This elevation of serum thyroglobulin occurred in 44% of the carcinoma cases. Sensitivity was around 50 for measurements taken up to 15 years prior to diagnosis, but 21 when the interval was over 15 years. Specificity was 89. No differences were found between cases and controls in values for thyroid-stimulating hormone and thyroxin. PMID:11207005

  6. Analysis of pralidoxime in serum, brain and CSF of rats.

    PubMed

    Kalász, Huba; Szöko, Eva; Tábi, Tamás; Petroianu, Georg A; Lorke, Dietrich E; Omar, Abdulrab; Alafifi, Salem; Jasem, Almerri; Tekes, Kornélia

    2009-05-01

    After administration of various amounts of pralidoxime to rats, the levels in serum, brain and cerebrospinal fluid (CSF) were measured using capillary zone electrophoresis (CZE). The calibration curves were established using spiked samples. The calibration covers the ranges from 0.3 - 200 microg/mL, 0.3 - 7 microg/mL and 0.1 - 7 microg/mL for serum, brain and CSF, respectively. The CZE measurement opens the way to the fast and reliable determination of pyridinium aldoxime concentrations in serum, cerebrospinal fluid and brain, thereby monitoring blood-brain and blood-CSF penetration of pyridinium aldoxime-type antidotes clinically used in organophosphate poisoning. PMID:19442213

  7. Serum polysialylated neural cell adhesion molecule in childhood neuroblastoma.

    PubMed Central

    Glüer, S.; Schelp, C.; Madry, N.; von Schweinitz, D.; Eckhardt, M.; Gerardy-Schahn, R.

    1998-01-01

    Neuroblastoma cells express the polysialylated form of the neural cell adhesion molecule (NCAM), which normally becomes restricted to a few neural tissues after embryogenesis. In this study, we investigated serum levels of polysialylated NCAM in 14 children with different grades and stages of neuroblastoma using an immunoluminescence assay, and compared the results to 269 healthy control subjects. Simultaneously, the polysialylated NCAM content of the tumours was determined by immunohistochemistry. Serum levels were dramatically elevated (more than sixfold) in children with advanced stages and fatal courses of disease, whereas children with differentiated tumour types and limited disease had low or normal levels. Serum concentrations correlated with the polysialylated NCAM content of the tumours, and they decreased during successful therapy. We therefore suggest polysialylated NCAM to be a useful marker monitoring childhood neuroblastoma. Images Figure 2 Figure 3 PMID:9662259

  8. Interaction of coffee compounds with serum albumins. Part II: Diterpenes.

    PubMed

    Guercia, Elena; Forzato, Cristina; Navarini, Luciano; Berti, Federico

    2016-05-15

    Cafestol and 16-O-methylcafestol are diterpenes present in coffee, but whilst cafestol is found in both Coffea canephora and Coffea arabica, 16-O-methylcafestol (16-OMC) was reported to be specific of only C. canephora. The interactions of such compounds, with serum albumins, have been studied. Three albumins have been considered, namely human serum albumin (HSA), fatty acid free HSA (ffHSA) and bovine serum albumin (BSA). The proteins interact with the diterpenes at the interface between Sudlow site I and the fatty acid binding site 6 in a very peculiar way, leading to a significant change in the secondary structure. The diterpenes do not displace reference binding drugs of site 2, but rather they enhance the affinity of the site for the drugs. They, therefore, may alter the pharmacokinetic profile of albumin - bound drugs. PMID:26776001

  9. Inhibition of myeloperoxidase by synovial fluid and serum.

    PubMed Central

    Dularay, B; Yea, C M; Elson, C J

    1991-01-01

    An inhibitor of myeloperoxidase has been identified in the synovial fluids and sera from patients with rheumatoid arthritis and sera from normal subjects. Initially, these fluids were found to inhibit stimulus induced degranulation of polymorphonuclear leucocytes independently of the stimulating agent. Subsequently, the fluids were shown to inhibit the released enzyme rather than the degranulation response of polymorphonuclear leucocytes. Both rheumatoid and normal serum samples contained high concentrations of the inhibitor but the concentrations were lower in rheumatoid synovial fluids. The inhibitory activity seemed to be specific for peroxidase as the fluids did not inhibit beta-glucuronidase activity. A protein of relative molecular mass (Mr) 150 kd was purified from synovial fluid by affinity chromatography on myeloperoxidase-Sepharose. It is concluded that serum and synovial fluid contain a novel myeloperoxidase inhibitor, which acts by binding to myeloperoxidase and thereby prevents myeloperoxidase releasing oxidative products in serum. Images PMID:1647755

  10. Shrinkage of pegylated and non-pegylated liposomes in serum.

    PubMed

    Wolfram, Joy; Suri, Krishna; Yang, Yong; Shen, Jianliang; Celia, Christian; Fresta, Massimo; Zhao, Yuliang; Shen, Haifa; Ferrari, Mauro

    2014-02-01

    An essential requisite for the design of nanodelivery systems is the ability to characterize the size, homogeneity and zeta potential of nanoparticles. Such properties can be tailored in order to create the most efficient drug delivery platforms. An important question is whether these characteristics change upon systemic injection. Here, we have studied the behavior of phosphatidylcholine/cholesterol liposomes exposed to serum proteins. The results reveal a serum-induced reduction in the size and homogeneity of both pegylated and non-pegylated liposomes, implicating the possible role of osmotic forces. In addition, changes to zeta-potential were observed upon exposing liposomes to serum. The liposomes with polyethylene glycol expressed different characteristics than their non-polymeric counterparts, suggesting the potential formation of a denser protein corona around the non-pegylated liposomes. PMID:24216620

  11. Immunoproteomic Analysis of Potential Serum Biomarker Candidates in Human Glaucoma

    PubMed Central

    Tezel, Gülgün; Thornton, Ivey L.; Tong, Melissa G.; Luo, Cheng; Yang, Xiangjun; Cai, Jian; Powell, David W.; Soltau, Joern B.; Liebmann, Jeffrey M.; Ritch, Robert

    2012-01-01

    Purpose. Evidence supporting the immune system involvement in glaucoma includes increased titers of serum antibodies to retina and optic nerve proteins, although their pathogenic importance remains unclear. This study using an antibody-based proteomics approach aimed to identify disease-related antigens as candidate biomarkers of glaucoma. Methods. Serum samples were collected from 111 patients with primary open-angle glaucoma and an age-matched control group of 49 healthy subjects without glaucoma. For high-throughput characterization of antigens, serum IgG was eluted from five randomly selected glaucomatous samples and analyzed by linear ion trap mass spectrometry (LC-MS/MS). Serum titers of selected biomarker candidates were then measured by specific ELISAs in the whole sample pool (including an additional control group of diabetic retinopathy). Results. LC-MS/MS analysis of IgG elutes revealed a complex panel of proteins, including those detectable only in glaucomatous samples. Interestingly, many of these antigens corresponded to upregulated retinal proteins previously identified in glaucomatous donors (or that exhibited increased methionine oxidation). Moreover, additional analysis detected a greater immunoreactivity of the patient sera to glaucomatous retinal proteins (or to oxidatively stressed cell culture proteins), thereby suggesting the importance of disease-related protein modifications in autoantibody production/reactivity. As a narrowing-down strategy for selection of initial biomarker candidates, we determined the serum proteins overlapping with the retinal proteins known to be up-regulated in glaucoma. Four of the selected 10 candidates (AIF, cyclic AMP-responsive element binding protein, ephrin type-A receptor, and huntingtin) exhibited higher ELISA titers in the glaucomatous sera. Conclusions. A number of serum proteins identified by this immunoproteomic study of human glaucoma may represent diseased tissue-related antigens and serve as candidate

  12. Associations between Serum Perfluoroalkyl Acids and LINE-1 DNA Methylation

    PubMed Central

    Watkins, Deborah J.; Wellenius, Gregory A.; Butler, Rondi A.; Bartell, Scott M.; Fletcher, Tony; Kelsey, Karl T.

    2014-01-01

    Perfluoroalkyl acids (PFAAs) are persistent, synthetic compounds that are used in a number of consumer products. Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) have been associated with cardiovascular risk factors, and changes in gene expression and DNA methylation in animals and cellular systems. However, whether PFAA exposure is associated with LINE-1 DNA methylation, a potential marker of cardiovascular risk, in humans remains unknown. We sought to evaluate the cross-sectional associations between serum PFAAs and LINE-1 DNA methylation in a population highly exposed to PFOA. We measured serum PFAAs twice four to five years apart in 685 adult participants (47% male, mean age ± SD=42 ± 11 years). We measured percent LINE-1 DNA methylation in peripheral blood leukocytes at the second time point (follow-up), and estimated absolute differences in LINE-1 methylation associated with an interquartile (IQR) shift in mean PFAA serum levels. IQR increases in mean serum PFOA, PFOS, perfluorononanoic acid (PFNA), and perfluorohexane sulfonate (PFHxS) were associated with differences of −0.04 (p=0.16), 0.20 (p=0.001), 0.06 (p=0.19), and 0.02 (p=0.57), respectively, in % LINE-1 methylation at follow-up after adjustment for potential confounders. We observed a monotonic increase in LINE-1 DNA methylation across tertiles of PFOS and PFNA (ptrend=0.02 for both associations), but not across tertiles of PFOA or PFHxS (ptrend=0.71 and 0.44, respectively). In summary, serum PFOS was associated with LINE-1 methylation, while serum PFOA, PFHxS, and PFNA were not. Additional research is needed to more precisely determine whether these compounds are epigenetically active. PMID:24263140

  13. Serum adropin level and ENHO gene expression in systemic sclerosis.

    PubMed

    Yolbas, Servet; Kara, Murat; Yilmaz, Musa; Aydin, Suleyman; Koca, Suleyman Serdar

    2016-06-01

    Adropin, a secreted protein, is encoded by the energy homeostasis associated (ENHO) gene. It has been implicated in the several physiological and pathological processes such as angiogenesis and apoptosis. Therefore, the aim of present study was to investigate serum adropin levels and ENHO gene expressions in systemic sclerosis (SSc) characterized by vasculopathy, inflammation, and progressive fibrosis of the skin and internal organs. The study includes 27 patients with SSc, 39 patients with Behçet's disease (BD), and 20 healthy controls (HC). Serum adropin levels and ENHO gene expressions by peripheral blood mononuclear cells were analyzed by ELISA method and by real-time PCR, respectively. The serum adropin levels were higher in the SSc and BD groups than in the HC group (p = 0.023 and p < 0.001, respectively). However, there were no significant differences among the groups in terms of ENHO gene expressions (p ANOVA = 0.149). There was no significant difference between the limited and diffuse cutaneous subtypes of SSc in terms of serum adropin level and ENHO gene expression. Moreover, serum adropin level and ENHO gene expression were not associated with the disease activity and severity indexes. ENHO gene expression was correlated with the triglyceride levels in the BD group (r = -0.426, p = 0.027). The augmented serum adropin levels may be expected in the chronic inflammatory disease and seem not to be characteristic of only SSc. However, further studies are needed to explain the precise role of adropin in SSc. PMID:27079850

  14. Pathologies Associated with Serum IgG4 Elevation

    PubMed Central

    Ebbo, Mikael; Grados, Aurélie; Bernit, Emmanuelle; Vély, Frederic; Boucraut, José; Harlé, Jean-Robert; Daniel, Laurent; Schleinitz, Nicolas

    2012-01-01

    Statement of Purpose. IgG4-related disease (IgG4-RD) is usually associated to an increase of serum IgG4 levels. However other conditions have also been associated to high serum IgG4 levels. Methods. All IgG subclasses analyses performed in our hospital over a one-year period were analyzed. When IgG4 level were over 1.35 g/L, the patient's clinical observation was analyzed and both final diagnosis and reason leading to IgG subclasses analysis were recorded. Only polyclonal increases of IgG4 were considered. Summary of the Results. On 646 IgG subclass analysis performed, 59 patients had serum IgG4 over 1.35 g/L. The final diagnosis associated to serum IgG4 increase was very variable. Most patients (25%) presented with repeated infections, 13.5% with autoimmune diseases, and 10% with IgG4-RD. Other patients presented with cancer, primary immune deficiencies, idiopathic interstitial lung disease, cystic fibrosis, histiocytosis, or systemic vasculitis and 13.5% presented with various pathologies or no diagnosis. Mean IgG4 levels and IgG4/IgG ratio were higher in IgG4-RD than in other pathologies associated to elevated IgG4 levels. Conclusions. Our study confirms that elevation of serum IgG4 is not specific to IgG4-RD. Before retaining IgG4-RD diagnosis in cases of serum IgG4 above 1.35 g/L, several other pathological conditions should be excluded. PMID:22966232

  15. Serum 25-Hydroxyvitamin D in Patients with Major Depressive Disorder

    PubMed Central

    DANA-ALAMDARI, Leila; KHEIROURI, Sorayya; NOORAZAR, Seyed Gholamreza

    2015-01-01

    Background: We investigated the association between serum 25(OH) D levels and depressive symptoms in patients with major depressive disorder (MDD). Methods: Eighty-five adults, 44 drug free patients with MDD and 41 apparently healthy controls, participated in the study. The Hamilton Depression Rating Scale was used to assess severity of major depression. Mental health of the controls was assessed according to DSM-IV criteria. Stress level of the participants was assessed by the Holmes and Rahe stress scale. Serum 25(OH) D levels was measured by immunochemiluminescence assay. Vitamin D deficiency was defined as a serum 25(OH) D concentration of lower than 20 ng/ml. Results: Depressed patients had the higher levels of stress. There was a positive correlation between stress level and disease severity (r= 0.32, P= 0.03). In total participants, mean percentage of vitamin D deficiency was 77.6% with 75% in patients and 80.5% in the healthy subjects. There were no differences between the two groups in serum 25(OH) D levels and percentage of subjects with the vitamin deficiency. A negative correlation was observed between disease severity and serum 25(OH) D level of patients with depression episodes < 2 y (r= −0.38, P = 0.08) and winter samples (samples collected and measured from December to march, r= −0.62, P = 0.004). Conclusion: Serum 25(OH) D levels were not associated with depression. However, the inverse relationship between levels of vitamin D and depressive symptoms in current depression episodes and in sun-deprived season warrants further investigation. PMID:26284211

  16. Effects of electromagnetic pulse on serum element levels in rat.

    PubMed

    Li, Kangchu; Ma, Shirong; Ren, Dongqing; Li, Yurong; Ding, Guirong; Liu, Junye; Guo, Yao; Guo, Guozhen

    2014-04-01

    Electromagnetic pulse (EMP) was a potentially harmful factor to the human body, and a biological dosimetry to evaluate effects of EMP is necessary. Little is known about effects of EMP on concentration of macro and trace elements in serum so far. In this study, Sprague-Dawley rats were randomly divided into 50-kV/m EMP-exposed group (n = 10), 100-kV/m EMP-exposed group (n = 10), 200-kV/m EMP-exposed group (n = 40), and the sham-exposed group (n = 20). The macro and trace element concentrations in serum were examined at 6, 12, 24, and 48 h after EMP exposure at different electric field intensities. Compared with the sham-exposed groups, the concentration of sodium (Na), potassium (K), magnesium (Mg), calcium (Ca), zinc (Zn), copper (Cu), iron (Fe), selenium (Se), and manganese (Mn) in rat serum was not changed significantly within 48 h after 200 pulses of EMP exposure at electric field intensity of 50, 100, and 200 kV/m although the K level was decreased and the Ca level was increased with the electric field intensity of EMP increasing. In addition, there was a tendency that the Zn level was decreased with the time going on within 48 h after EMP exposure. Under our experimental conditions, EMP exposure cannot affect the concentration of macro and trace elements in rat serum. There was no time-effect or dose-effect relationship between EMP exposure and serum element levels. The macro and trace elements in serum are not suitable endpoints of biological dosimetry of EMP. PMID:24497087

  17. Predictors of serum polychlorinated biphenyl concentrations in Anniston residents.

    PubMed

    Pavuk, M; Olson, J R; Wattigney, W A; Dutton, N D; Sjödin, A; Shelton, C; Turner, W E; Bartell, S M; Bartell, S; Carpenter, D O; Cash, J; Foushee, R; Percy, A; Frumkin, H; Lavender, M; Moysich, K; Olson, J; Pavuk, M; Rosenbaum, P; Silverstone, A; Weinstock, R; Shelton, C

    2014-10-15

    The Anniston Community Health Survey was a community-based cross-sectional study of Anniston, Alabama, residents who live in close proximity to a former PCB production facility to identify factors associated with serum PCB levels. The survey comprises 765 Anniston residents who completed a questionnaire interview and provided a blood sample for analysis in 2005-2007. Several reports based on data from the Anniston survey have been previously published, including associations between PCB exposure and diabetes and blood pressure. In this study we examine demographic, behavioral, dietary, and occupational characteristics of Anniston survey participants as predictors of serum PCB concentrations. Of the 765 participants, 54% were White and 45% were African-American; the sample was predominantly female (70%), with a mean age of 55 years. Serum PCB concentrations varied widely between participants (range for sum of 35 PCBs: 0.11-170.4 ng/g wet weight). Linear regression models with stepwise selection were employed to examine factors associated with serum PCBs. Statistically significant positive associations were observed between serum PCB concentrations and age, race, residential variables, current smoking, and local fish consumption, as was a negative association with education level. Age and race were the most influential predictors of serum PCB levels. A small age by sex interaction was noted, indicating that the increase in PCB levels with age was steeper for women than for men. Significant interaction terms indicated that the associations between PCB levels and having ever eaten locally raised livestock and local clay were much stronger among African-Americans than among White participants. In summary, demographic variables and past consumption of locally produced foods were found to be the most important predictors of PCB concentrations in residents living in the vicinity of a former PCB manufacturing facility. PMID:25115605

  18. Assessing candidate serum biomarkers for Alzheimer's disease: a longitudinal study.

    PubMed

    Zabel, Matthew; Schrag, Matthew; Mueller, Claudius; Zhou, Weidong; Crofton, Andrew; Petersen, Floyd; Dickson, April; Kirsch, Wolff M

    2012-01-01

    Because of the growing impact of late onset cognitive loss, considerable effort has been directed toward the development of improved diagnostic techniques for Alzheimer's disease (AD) that may pave the way for earlier (and more effective) therapeutic efforts. Serum-based biomarkers are the least expensive and invasive modality for screening and routine monitoring. We systematically reviewed the literature to assemble a list of serum biomarkers relevant to AD. In parallel, we conducted a proteomic LC-MS/MS analysis of serum collected from neurologically normal subjects and subjects with mild cognitive impairment (MCI) and early AD (n = 6 in all). Complement C3 and alpha-2-macroglobulin were identified from both the literature review and our proteomic screen for further validation. For these two candidates, ELISA was performed on serum collected from a small independent cohort of subjects for longitudinal analysis. Serum was serially collected from neurologically normal subjects (n = 5) and subjects with MCI who were subsequently followed for a period of two years (n = 5) and regrouped into stable MCI and progressive MCI or AD (n = 6). The ability of each marker to predict which subjects with MCI would progress to dementia and which would remain cognitively stable was assessed. Patients with probable cerebral amyloid angiopathy were also identified (n = 3). This preliminary analysis tested the most-promising serum protein biomarkers for AD and we concluded that none are yet ready for use in the clinical diagnosis and management of dementia. However, a more thorough assessment in longitudinal studies with higher statistical power is warranted. PMID:22426016

  19. Serum Albumin Levels and Economic Status in Japanese Older Adults

    PubMed Central

    Ota, Asami; Kondo, Naoki; Murayama, Nobuko; Tanabe, Naohito; Shobugawa, Yugo; Kondo, Katsunori

    2016-01-01

    Background Low serum albumin levels are associated with aging and medical conditions such as cancer, liver dysfunction, inflammation, and malnutrition and might be an independent predictor of long-term mortality in healthy older populations. We tested the hypothesis that economic status is associated with serum albumin levels and explained by nutritional and health status in Japanese older adults. Design We performed a cross-sectional analysis using data from the Japan Gerontological Evaluation study (JAGES). The study participants were 6528 functionally independent residents (3189 men and 3339 women) aged ≥65 years living in four municipalities in Aichi prefecture. We used household income as an indicator of economic status. Multiple linear regression was used to compare serum albumin levels in relation to household income, which was classified as low, middle, and high. Additionally, mediation by nutritional and health-related factors was analyzed in multivariable models. Results With the middle-income group as reference, participants with low incomes had a significantly lower serum albumin level, even after adjustment for sex, age, residential area, education, marital status, and household structure. The estimated mean difference was −0.17 g/L (95% confidence interval, −0.33 to −0.01 g/L). The relation between serum albumin level and low income became statistically insignificant when “body mass index”, “consumption of meat or fish”, “self-rated health”, “presence of medical conditions”, “hyperlipidemia”, or “respiratory disease “was included in the model. Conclusion Serum albumin levels were lower in Japanese older adults with low economic status. The decrease in albumin levels appears to be mediated by nutrition and health-related factors with low household incomes. Future studies are needed to reveal the existence of other pathways. PMID:27276092

  20. Elevation of Serum Acid Sphingomyelinase Activity in Acute Kawasaki Disease.

    PubMed

    Konno, Yuuki; Takahashi, Ikuko; Narita, Ayuko; Takeda, Osamu; Koizumi, Hiromi; Tamura, Masamichi; Kikuchi, Wataru; Komatsu, Akira; Tamura, Hiroaki; Tsuchida, Satoko; Noguchi, Atsuko; Takahashi, Tsutomu

    2015-01-01

    Kawasaki disease (KD) is an acute systemic vasculitis that affects both small and medium-sized vessels including the coronary arteries in infants and children. Acid sphingomyelinase (ASM) is a lysosomal glycoprotein that hydrolyzes sphingomyelin to ceramide, a lipid, that functions as a second messenger in the regulation of cell functions. ASM activation has been implicated in numerous cellular stress responses and is associated with cellular ASM secretion, either through alternative trafficking of the ASM precursor protein or by means of an unidentified mechanism. Elevation of serum ASM activity has been described in several human diseases, suggesting that patients with diseases involving vascular endothelial cells may exhibit a preferential elevation of serum ASM activity. As acute KD is characterized by systemic vasculitis that could affect vascular endothelial cells, the elevation of serum ASM activity should be considered in these patients. In the present study, serum ASM activity in the sera of 15 patients with acute KD was determined both before and after treatment with infusion of high-dose intravenous immunoglobulin (IVIG), a first-line treatment for acute KD. Serum ASM activity before IVIG was significantly elevated in KD patients when compared to the control group (3.85 ± 1.46 nmol/0.1 ml/6 h vs. 1.15 ± 0.10 nmol/0.1 ml/6 h, p < 0.001), suggesting that ASM activation may be involved in the pathophysiology of this condition. Serum ASM activity before IVIG was significantly correlated with levels of C-reactive protein (p < 0.05). These results suggest the involvement of sphingolipid metabolism in the pathophysiology of KD. PMID:26447086

  1. Quantitating Metabolites in Protein Precipitated Serum Using NMR Spectroscopy

    PubMed Central

    2015-01-01

    Quantitative NMR-based metabolite profiling is challenged by the deleterious effects of abundant proteins in the intact blood plasma/serum, which underscores the need for alternative approaches. Protein removal by ultrafiltration using low molecular weight cutoff filters thus represents an important step. However, protein precipitation, an alternative and simple approach for protein removal, lacks detailed quantitative assessment for use in NMR based metabolomics. In this study, we have comprehensively evaluated the performance of protein precipitation using methanol, acetonitrile, perchloric acid, and trichloroacetic acid and ultrafiltration approaches using 1D and 2D NMR, based on the identification and absolute quantitation of 44 human blood metabolites, including a few identified for the first time in the NMR spectra of human serum. We also investigated the use of a “smart isotope tag,” 15N-cholamine for further resolution enhancement, which resulted in the detection of a number of additional metabolites. 1H NMR of both protein precipitated and ultrafiltered serum detected all 44 metabolites with comparable reproducibility (average CV, 3.7% for precipitation; 3.6% for filtration). However, nearly half of the quantified metabolites in ultrafiltered serum exhibited 10–74% lower concentrations; specifically, tryptophan, benzoate, and 2-oxoisocaproate showed much lower concentrations compared to protein precipitated serum. These results indicate that protein precipitation using methanol offers a reliable approach for routine NMR-based metabolomics of human blood serum/plasma and should be considered as an alternative to ultrafiltration. Importantly, protein precipitation, which is commonly used by mass spectrometry (MS), promises avenues for direct comparison and correlation of metabolite data obtained from the two analytical platforms to exploit their combined strength in the metabolomics of blood. PMID:24796490

  2. Predictors of serum polychlorinated biphenyl concentrations in Anniston residents

    PubMed Central

    Pavuk, M.; Olson, J.R.; Wattigney, W.A.; Dutton, N.D.; Sjödin, A.; Shelton, C.; Turner, W.E.; Bartell, S.M.; Bartell, S.; Carpenter, D.O.; Cash, J.; Foushee, R.; Percy, A.; Frumkin, H.; Lavender, M.; Moysich, K.; Olson, J.; Pavuk, M.; Rosenbaum, P.; Silverstone, A.; Weinstock, R.; Shelton, C.

    2015-01-01

    The Anniston Community Health Survey was a community-based cross-sectional study of Anniston, Alabama, residents who live in close proximity to a former PCB production facility to identify factors associated with serum PCB levels. The survey comprises 765 Anniston residents who completed a questionnaire interview and provided a blood sample for analysis in 2005–2007. Several reports based on data from the Anniston survey have been previously published, including associations between PCB exposure and diabetes and blood pressure. In this study we examine demographic, behavioral, dietary, and occupational characteristics of Anniston survey participants as predictors of serum PCB concentrations. Of the 765 participants, 54% were White and 45% were African-American; the sample was predominantly female (70%), with a mean age of 55 years. Serum PCB concentrations varied widely between participants (range for sum of 35 PCBs: 0.11–170.4 ng/g wet weight). Linear regression models with stepwise selection were employed to examine factors associated with serum PCBs. Statistically significant positive associations were observed between serum PCB concentrations and age, race, residential variables, current smoking, and local fish consumption, as was a negative association with education level. Age and race were the most influential predictors of serum PCB levels. A small age by sex interaction was noted, indicating that the increase in PCB levels with age was steeper for women than for men. Significant interaction terms indicated that the associations between PCB levels and having ever eaten locally raised livestock and local clay were much stronger among African-Americans than among White participants. In summary, demographic variables and past consumption of locally produced foods were found to be the most important predictors of PCB concentrations in residents living in the vicinity of a former PCB manufacturing facility. PMID:25115605

  3. Serum homocysteine level in patients with ankylosing spondylitis.

    PubMed

    Başkan, Bedriye Mermerci; Sivas, Filiz; Aktekin, Lale Akbulut; Doğan, Yasemin Pekin; Ozoran, Kürşat; Bodur, Hatice

    2009-10-01

    In this study serum homocystein (Hcy) level was measured and its relationship with disease activity criteria and treatment protocols was investigated in ankylosing spondylitis (AS) patients. Ninety-two AS patients and 58 healthy individuals were recruited. Erythrocyte sedimentation rate and serum C-reactive protein were determined. Bath AS disease activity index and Bath AS functional index were calculated. Serum Hcy levels >15 micromol/l were considered as hyperhomocysteinemia. The mean serum homocysteine levels were 14.40 and 12.60 micromol/l in patients with AS and the control group, respectively, and the difference between two groups was significant. While there was no significant difference between the sulfasalazine (SSZ) group with 14.25 micromol/l mean Hcy level and the methotrexate (MTX)/SSZ group with 16.05 micromol/l, there was a statistically significant difference between the Hcy levels of these two groups and Hcy level of 12.15 micromol/l of the non-steroidal anti-inflammatory drugs group, and 12.60 micromol/l Hcy level of the control group. Mean serum Hcy level was 13.65 micromol/l in patients with active AS and 14.60 micromol/l in patients with inactive AS, and there was no significant difference between the groups. In our study serum Hcy level was found to be significantly higher in patients with AS than in healthy control subjects. Especially for the AS patients receiving MTX and SSZ treatment without folic acid supplementation, addition of folic acid to their therapy may decrease the risk of cardiovascular disease which in turn decreases the mortality in these patients, but further prospective studies are needed for supporting these results. PMID:19288264

  4. The conversion of 16β hydroxyldehydroepiandrosterone in human serum.

    PubMed

    Ke, Yuyong; Gonthier, Renaud; Labrie, Fernand

    2016-05-01

    The circulating levels of 16β hydroxydehydroepiandrosterone (16β OH-DHEA) are at the limit of detection (less than 10pg/mL), unlike the serum concentrations of 16α-hydroxydehydroepiandrosterone (16α OH-DHEA, 10-300pg/mL) in premenopausal, postmenopausal and male serum. A major reason could be the rapid conversion of 16β OH-DHEA to 5-androstene-3beta, 17beta-diol 16 one (3β, 17β-diol 16-oxo) in serum due to the stereospecific structure of 16β OH-DHEA. In ultrapure H2O, there is no apparent conversion observed while 16β OH-DHEA (10ng/mL) spiked in stripped or unstripped serum is quickly converted to 3β, 17β-diol 16-oxo at room temperature. During this conversion, a further converted product was observed with a difference in molecular weight of 16Da from that of 16β OH-DHEA and 3β, 17β-diol 16-oxo, which could be their hydroxylation product, i.e. triol-ketone. Under basic conditions, further conversion occurs. The present data can explain the practically undetectable concentration of serum 16β OH-DHEA while 3β, 17β-diol 16-oxo is at the level of less than 50pg/mL. Serum concentrations of (0.0-9.9pg/mL for 16β OH-DHEA, 8.9-50.7pg/mL for 3β, 17β-diol 16-oxo and 10.0-285.0pg/mL for 16α OH-DHEA are measured in sera of premenopausal, postmenopausal women and men over 50years of age. PMID:26896786

  5. Serum Cotinine and Chronic Pain: NHANES 2003–2004

    PubMed Central

    Wiener, R Constance

    2016-01-01

    Purpose Tobacco smoke exposure continues to be the leading preventable risk factor for many diseases and has the potential to be a risk factor for chronic pain. The purpose of this study is to determine the relationship of chronic pain with smoking, secondhand smoke exposure and non-smoking using serum cotinine (and self-report of living with someone who smokes in the home) to identify the tobacco exposure groups. Methods The National Health and Nutrition Examination Survey (NHANES) 2003–2004 was used for this study. Participants were queried about pain duration and had serum cotinine levels determined during the course of the NHANES examination/survey. Participants, ages 20 years and above, with complete data on chronic pain, cotinine level, sex, race/ethnicity, and responses concerning living with someone who smoked in the home were included in the study (n=4429). Results The adjusted odds ratio of tobacco smoke exposure on chronic pain was 1.67 (95% CI: 1.08, 2.59; p=0.0220) for participants with a serum cotinine level >10 ng/mg (smokers) as compared with individuals who had a non-detectable serum cotinine level. For individuals with a serum cotinine level >0.011 ng/mg to 10 ng/mg who identified as living with someone who smoked in the home, the adjusted odds ratio was 0.88 (95% CI: 0.47, 1.65; p=0.6785) as compared with individuals who had a non-detectable serum cotinine level. Conclusion Chronic pain is a complex situation with many factors affecting it. Similarly, smoking is a complex addiction. The interplay of chronic pain and cotinine levels in this study were significant. PMID:26835515

  6. Serum copper and zinc levels in melanoma patients

    SciTech Connect

    Fisher, G.L.; Spitler, L.E.; McNeill, K.L.; Rosenblatt, L.S.

    1981-04-01

    Serum copper levels (SCL) and serum zinc levels (SZL) were evaluated in malignant melanoma patients at various clinical stages. Copper levels were generally found to be elevated, reflecting the degree and extent of tumor activity. Zinc levels and, hence, SCL:SZL ratios did not reflect tumor activity. SCL appeared to prognosticate disease progression in that all patients whose values never declined below 150 ..mu..g/100 ml died during the course of the study. However, not all patients who died from tumor metastases displayed persistent elevations of SCL. Patients receiving BCG immunotherapy appeared to have higher SCL than untreated patients.

  7. Serum Immunoglobulins in Newborn Calves Before and After Colostrum Feeding

    PubMed Central

    Merriman, Mohendra J. G. S.

    1971-01-01

    Pre-colostral and post-colostral sera of seven Holstein calves and colostral whey were analyzed immunoelectrophoretically. IgM, IgG1 (fast), and IgG2 (slow) were demonstrated while IgA was not detected in serum of new-born calves before colostrum feeding. In post-colostral serum IgG, IgM, in relatively higher levels, and IgA were present which corresponded with the classes of immunoglobulins found in whey. These observations suggest that the developing bovine fetus may be capable of independent immune response. ImagesFig. 1.Fig. 2.Fig. 3.Fig. 4. PMID:4260939

  8. Potassium toxicity at low serum potassium levels with refeeding syndrome.

    PubMed

    Vemula, Praveen; Abela, Oliver G; Narisetty, Keerthy; Rhine, David; Abela, George S

    2015-01-01

    Refeeding syndrome is a life-threatening condition occurring in severely malnourished patients after initiating feeding. Severe hypophosphatemia with reduced adenosine triphosphate production has been implicated, but little data are available regarding electrolyte abnormalities. In this case, we report electrocardiographic changes consistent with hyperkalemia during potassium replacement after a serum level increase from 1.9 to 2.9 mEq/L. This was reversed by lowering serum potassium back to 2.0 mEq/L. In conclusion, the patient with prolonged malnutrition became adapted to low potassium levels and developed potassium toxicity with replacement. PMID:25456880

  9. Recent advances in maternal serum screening for Down syndrome.

    PubMed

    Messerlian, Geralyn M; Canick, Jacob A

    2002-12-01

    For the past 15 years, addition of serum markers to screening for Down syndrome has enhanced the ability to identify affected pregnancies. During the 1990s, incremental improvements in screening have been tested and implemented, first with the addition of a fourth biochemical marker, inhibin A, to second trimester screening protocols, and second with the development of combined first trimester serum and ultrasound screening. With the new century, we are on the verge of a major breakthrough in the performance of prenatal screening for Down syndrome, with the opportunity to spare almost all pregnant women the risk of amniocentesis and CVS, yet attain levels of detection approaching 90%. PMID:12593353

  10. Serum Sclerostin Increases in Healthy Adult Men during Bed Rest

    PubMed Central

    Fields, E. E.; Yu, E. W.; Pajevic, P. Divieti; Bouxsein, M. L.; Sibonga, J. D.; Zwart, S. R.; Smith, S. M.

    2012-01-01

    Context: Animal models and human studies suggest that osteocytes regulate the skeleton's response to mechanical unloading in part by an increase in sclerostin. However, few studies have reported changes in serum sclerostin in humans exposed to reduced mechanical loading. Objective: We determined changes in serum sclerostin and bone turnover markers in healthy adult men undergoing controlled bed rest. Design, Setting, and Participants: Seven healthy adult men (31 ± 3 yr old) underwent 90 d of 6° head down tilt bed rest at the University of Texas Medical Branch Institute for Translational Sciences-Clinical Research Center. Outcomes: Serum sclerostin, PTH, vitamin D, bone resorption and formation markers, urinary calcium and phosphorus excretion, and 24-h pooled urinary markers of bone resorption were evaluated before bed rest [baseline (BL)] and at bed rest d 28 (BR-28), d 60 (BR-60), and d 90 (BR-90). Bone mineral density was measured at BL, BR-60, and 5 d after the end of the study (BR+5). Data are reported as mean ± sd. Results: Consistent with prior reports, bone mineral density declined significantly (1–2% per month) at weight-bearing skeletal sites. Serum sclerostin was elevated above BL at BR-28 (+29 ± 20%; P = 0.003) and BR-60 (+42 ± 31%; P < 0.001), with a lesser increase at BR-90 (+22 ± 21%; P = 0.07). Serum PTH levels were reduced at BR-28 (−17 ± 16%; P = 0.02) and BR-60 (−24 ± 14%; P = 0.03) and remained lower than BL at BR-90 (−21 ± 21%; P = 0.14), but did not reach statistical significance. Serum bone turnover markers were unchanged; however, urinary bone resorption markers and calcium were significantly elevated at all time points after bed rest (P < 0.01). Conclusions: In healthy men subjected to controlled bed rest for 90 d, serum sclerostin increased, with a peak at 60, whereas serum PTH declined, and urinary calcium and bone resorption markers increased. PMID:22767636

  11. Plasma betathromboglobulin and serum fragment E in acute partial stroke.

    PubMed

    de Boer, A C; Turpie, A G; Butt, R W; Duke, R J; Bloch, R F; Genton, E

    1982-02-01

    Plasma betathromboglobulin (BTG) and serum fragment E (FgE) were measured serially by radioimmunoassay for 7 d in 67 patients admitted with acute partial stroke. Twelve patients progressed within 7 d of admission. Plasma BTG was not different from normal in patients with acute partial stroke and did not increase significantly with stroke progression. Serum FgE was elevated in patients with acute partial stroke compared with normal values, and was significantly higher in patients who progressed compared with those who remained stable. The results indicate that fibrin formation may be more important in the process of stroke progression than activation of platelets. PMID:6174141

  12. Hematology and serum chemistry of cottontail rabbits of southern Illinois.

    PubMed

    Lepitzki, D A; Woolf, A

    1991-10-01

    In 1983 and 1984 blood was collected from 79 cottontail rabbits (Sylvilagus floridanus) confined to an outdoor enclosure in southern Illinois to establish reference values for hematology and serum chemistry. Packed cell volume, sodium, potassium, chloride, glucose, calcium, carbon dioxide, blood urea nitrogen, creatinine, uric acid, cholesterol, albumin, bilirubin, alkaline phosphatase, aspartate transaminase, alanine aminotransaminase, total protein, albumin/globulin ratio, and osmolality were measured. Sex and age (adult versus juvenile) of rabbit as well as season (June to September versus October to May) and method of capture (trap versus shot) variously affected most hematology and serum chemistry variables. PMID:1758030

  13. Operation of a DNA-Based Autocatalytic Network in Serum

    NASA Astrophysics Data System (ADS)

    Graugnard, Elton; Cox, Amber; Lee, Jeunghoon; Jorcyk, Cheryl; Yurke, Bernard; Hughes, William L.

    The potential for inferring the presence of cancer by the detection of miRNA in human blood has motivated research into the design and operation of DNA-based chemical amplifiers that can operate in bodily fluids. As a first step toward this goal, we have tested the operation of a DNA-based autocatalytic network in human serum and mouse serum. With the addition of sodium dodecyl sulfate to prevent degradation by nuclease activity, the network was found to operate successfully with both DNA and RNA catalysts.

  14. Specific serum binding of morphine, levorphanol and heroin

    PubMed Central

    Herndon, B. L.; Baeder, D. H.; Ringle, D. A.

    1976-01-01

    Effects of repeated subcutaneous pellet implantation of a series of narcotic drugs on the serum binding of [14C]morphine was studied in rabbits. Three of the compounds, morphine, heroin and levorphanol, elicited production of a morphine-binding globulin in the implanted rabbits. This serum response did not occur with several other compounds tested, including the potent analgesic methadone, and the narcotic antagonist naloxone. The time course of production of this globulin response, as well as the specificity of the binding for the drug that induced the response are both characteristic of an immunological reaction.

  15. Ixodes ticks: serum species sensitivity of anticomplement activity.

    PubMed

    Lawrie, C H; Randolph, S E; Nuttall, P A

    1999-12-01

    Ixodid ticks feed for extended periods of up to 2 weeks or more. To complete engorgement, they must overcome their host's innate immune mechanisms of which the complement system is a major component. Using in vitro assays, salivary gland extracts of the ixodid ticks, Ixodes ricinus, I. hexagonus, and I. uriae, were shown to inhibit activity of the alternative pathway of complement. The ability of the different Ixodes species to inhibit complement activity varied with the animal species used as a complement serum source. Serum species sensitivity correlates to the reported host range of the tick species tested. PMID:10600446

  16. Sequences Of Amino Acids For Human Serum Albumin

    NASA Technical Reports Server (NTRS)

    Carter, Daniel C.

    1992-01-01

    Sequences of amino acids defined for use in making polypeptides one-third to one-sixth as large as parent human serum albumin molecule. Smaller, chemically stable peptides have diverse applications including service as artificial human serum and as active components of biosensors and chromatographic matrices. In applications involving production of artificial sera from new sequences, little or no concern about viral contaminants. Smaller genetically engineered polypeptides more easily expressed and produced in large quantities, making commercial isolation and production more feasible and profitable.

  17. Detection and quantification of ATP in human blood serum.

    PubMed

    Akdeniz, Ali; Caglayan, Mehmet Gokhan; Polivina, Irina; Anzenbacher, Pavel

    2016-08-21

    Two fluorometric sensors based on the tri-serine tri-lactone scaffold and thiourea or sulfonamide moieties serving as hydrogen bond donors allowing for anion binding are described. The sensor utilizing thiourea as a recognition moiety shows fluorescence enhancement while the sensor with sulfonamide shows quenching upon addition of phosphates. Sensor arrays composed of two sensors are able to discriminate structurally similar organic phosphates in the presence of interferents in human blood serum. The quantitative analysis of ATP in human blood serum shows high accuracy (the root mean square error of prediction, 1.65%) without requiring any sample pretreatment. PMID:27454442

  18. [THE CHOLINESTERASE OF BLOOD SERUM IN WORKERS OF INDUSTRIAL ENTERPRISE].

    PubMed

    Radamishina, G G; Bakirov, A B; Gimranova, G G; Valeeva, O V

    2015-08-01

    The biochemical study of activity of serum cholinesterase in workers of industrial enterprise was carried out on the example of petrochemical industry. The indicators of average activity of enzyme and prevalence of indicators going beyond limits of reference values were analyzed depending on manufacturing-labor experience, profession and diseases established in workers. The main diseases, professional and labor experience groups were identified where activity of cholinesterase significantly changes. The impact of labor experience and profession on level of activity ofenzyme in blood serum is demonstrated. PMID:26596043

  19. The quantitative effect of serum albumin, serum urea, and valproic acid on unbound phenytoin concentrations in children.

    PubMed

    ter Heine, Rob; van Maarseveen, Erik M; van der Westerlaken, Monique M L; Braun, Kees P J; Koudijs, Suzanne M; Berg, Maarten J Ten; Malingré, Mirte M

    2014-06-01

    Dosing of phenytoin is difficult in children because of its variable pharmacokinetics and protein binding. Possible covariates for this protein binding have mostly been univariately investigated in small, and often adult, adult populations. We conducted a study to identify and quantify these covariates in children. We extracted data on serum phenytoin concentrations, albumin, triglycerides, urea, total bilirubin and creatinine concentrations and data on coadministration of valproic acid or carbamazepine in 186 children. Using nonlinear mixed effects modeling the effects of covariates on the unbound phenytoin fraction were investigated. Serum albumin, serum urea concentrations, and concomitant valproic acid use significantly influenced the unbound phenytoin fraction. For clinical practice, we recommend that unbound phenytoin concentrations are measured routinely. However, if this is impossible, we suggest to use our model to calculate the unbound concentration. In selected children, close treatment monitoring and dose reductions should be considered to prevent toxicity. PMID:23670246

  20. Serum Collagen Type II Cleavage Epitope and Serum Hyaluronic Acid as Biomarkers for Treatment Monitoring of Dogs with Hip Osteoarthritis

    PubMed Central

    Vilar, José M.; Rubio, Mónica; Spinella, Giuseppe; Cuervo, Belén; Sopena, Joaquín; Cugat, Ramón; Garcia-Balletbó, Montserrat; Dominguez, Juan M.; Granados, Maria; Tvarijonaviciute, Asta; Ceron, José J.; Carrillo, José M.

    2016-01-01

    The aim of this study was to evaluate the use of serum type II collagen cleavage epitope and serum hyaluronic acid as biomarkers for treatment monitoring in osteoarthritic dogs. For this purpose, a treatment model based on mesenchymal stem cells derived from adipose tissue combined with plasma rich in growth factors was used. This clinical study included 10 dogs with hip osteoarthritis. Both analytes were measured in serum at baseline, just before applying the treatment, and 1, 3, and 6 months after treatment. These results were compared with those obtained from force plate analysis using the same animals during the same study period. Levels of type II collagen cleavage epitope decreased and those of hyaluronic acid increased with clinical improvement objectively verified via force plate analysis, suggesting these two biomarkers could be effective as indicators of clinical development of joint disease in dogs. PMID:26886592

  1. Genome-Wide Association Studies of Serum Magnesium, Potassium, and Sodium Concentrations Identify Six Loci Influencing Serum Magnesium Levels

    PubMed Central

    van Rooij, Frank J. A.; Ehret, Georg B.; Boerwinkle, Eric; Felix, Janine F.; Leak, Tennille S.; Harris, Tamara B.; Yang, Qiong; Dehghan, Abbas; Aspelund, Thor; Katz, Ronit; Homuth, Georg; Kocher, Thomas; Rettig, Rainer; Ried, Janina S.; Gieger, Christian; Prucha, Hanna; Pfeufer, Arne; Meitinger, Thomas; Coresh, Josef; Hofman, Albert; Sarnak, Mark J.; Chen, Yii-Der Ida; Uitterlinden, André G.; Chakravarti, Aravinda; Psaty, Bruce M.; van Duijn, Cornelia M.; Kao, W. H. Linda; Witteman, Jacqueline C. M.; Gudnason, Vilmundur; Siscovick, David S.; Fox, Caroline S.; Köttgen, Anna

    2010-01-01

    Magnesium, potassium, and sodium, cations commonly measured in serum, are involved in many physiological processes including energy metabolism, nerve and muscle function, signal transduction, and fluid and blood pressure regulation. To evaluate the contribution of common genetic variation to normal physiologic variation in serum concentrations of these cations, we conducted genome-wide association studies of serum magnesium, potassium, and sodium concentrations using ∼2.5 million genotyped and imputed common single nucleotide polymorphisms (SNPs) in 15,366 participants of European descent from the international CHARGE Consortium. Study-specific results were combined using fixed-effects inverse-variance weighted meta-analysis. SNPs demonstrating genome-wide significant (p<5×10−8) or suggestive associations (p<4×10−7) were evaluated for replication in an additional 8,463 subjects of European descent. The association of common variants at six genomic regions (in or near MUC1, ATP2B1, DCDC5, TRPM6, SHROOM3, and MDS1) with serum magnesium levels was genome-wide significant when meta-analyzed with the replication dataset. All initially significant SNPs from the CHARGE Consortium showed nominal association with clinically defined hypomagnesemia, two showed association with kidney function, two with bone mineral density, and one of these also associated with fasting glucose levels. Common variants in CNNM2, a magnesium transporter studied only in model systems to date, as well as in CNNM3 and CNNM4, were also associated with magnesium concentrations in this study. We observed no associations with serum sodium or potassium levels exceeding p<4×10−7. Follow-up studies of newly implicated genomic loci may provide additional insights into the regulation and homeostasis of human serum magnesium levels. PMID:20700443

  2. Factors Influencing Measurement of Serum Iron Concentration in Dogs: Diurnal Variation and Hyperferritinemia

    PubMed Central

    CHIKAZAWA, Seishiro; HORI, Yasutomo; KANAI, Kazutaka; ITO, Naoyuki; HOSHI, Fumio; ORINO, Koichi; WATANABE, Kiyotaka; HIGUCHI, Seiichi

    2013-01-01

    ABSTRACT We evaluated diurnal variation and hyperferritinemia as factors that influence the values of serum iron concentration in dogs, using the International Committee for Standardization in Hematology (ICSH) colorimetric method. Serum iron levels were significantly higher in the morning than in the evening in 6 clinically healthy beagle dogs, and the maximum decrease in serum iron concentration was 47.3%. Moreover, the change in serum iron concentrations in 22 clinical canine cases with various serum ferritin levels was evaluated by immunoprecipitation of ferritin. The rate of decline in the serum iron concentrations positively correlated with serum ferritin levels (r=0.48, P=0.024). These results show that it is necessary to consider the sampling time and serum ferritin level for accurate interpretation of serum iron concentrations in dogs. PMID:23877842

  3. [Transforming growth factor beta-1: structure, function, and regulation mechanisms in cancer].

    PubMed

    Peralta-Zaragoza, O; Lagunas-Martínez, A; Madrid-Marina, V

    2001-01-01

    Transforming growth factor beta-1 (TGF-beta 1) is produced by several cell lineages such as lymphocytes, macrophages, and dendritic cells, and its expression serves in both autocrine and paracrine modes to control the differentiation, proliferation, and state of activation of these and other cells. In general, TGF-beta 1 has pleiotropic properties on the immune response during the development of infection diseases and cancer; however, the mechanisms of action and regulation of gene expression of this cytokine are poorly understood, in this review, the biological properties and the molecular mechanisms that regulate TGF-beta 1 gene expression are described, to understand the role of this cytokine in growth and cell differentiation. The knowledge of molecular mechanisms of gene expression of TGF-beta 1 may serve to develop new cancer therapies. The English version of this paper is available at: http://www.insp.mx/salud/index.html PMID:11547595

  4. Agglutinating serum for distinguishing Staphylococcus aureus of human biotype.

    PubMed

    Live, I

    1975-08-01

    Antiserum to Staphylococcus aureus strain 17 was treated with S. aureus strain 61218 until the antibodies against thermostable agglutinogen were removed. The absorbed serum agglutinated phage-typable as well as phageuntypable staphylococci of human biotype, whether recovered from people or from dogs. PMID:125241

  5. How Effective is Autologous Serum Therapy in Chronic Autoimmune Urticaria

    PubMed Central

    Majid, Imran; Shah, Shazia; Hassan, Altaf; Aleem, Saima; Aziz, Khalid

    2015-01-01

    Background: Chronic autoimmune urticaria (CAU) is one of the most challenging therapeutic problems faced by a dermatologist. Recently, weekly autologous serum injections have been shown to induce a prolonged remission in this disease. Aim: To evaluate the efficacy of repeated autologous serum injections in patients with CAU. Materials and Methods: Seventy patients of CAU were prospectively analyzed for the efficacy of nine consecutive weekly autologous serum injections with a post-intervention follow-up of 12 weeks. Total urticaria severity score (TSS) was monitored at the baseline, at the end of treatment and lastly at the end of 12 weeks of follow up. Response to treatment was judged by the percentage reduction in baseline TSS at the end of treatment and again at the end of 12 weeks-follow-up. Results: Out of the 70 patients enrolled, 11 dropped out of the injection treatment after one or the first few doses only. Among the rest of 59 patients, only 7 patients (12%) went into a partial or complete remission and remained so over the follow-up period of 12 weeks. Forty patients (68%) did not demonstrate any significant reduction in TSS at the end of the treatment period. Rest of the 12 patients showed either a good or excellent response while on weekly injection treatment, but all of them relapsed over the follow-up period of 12 weeks. Conclusion: Autologous serum therapy does not seem to lead to any prolonged remission in patients of CAU. PMID:25657418

  6. Fall in nocturnal serum melatonin during prepuberty and pubescence.

    PubMed

    Waldhauser, F; Weiszenbacher, G; Frisch, H; Zeitlhuber, U; Waldhauser, M; Wurtman, R J

    1984-02-18

    Morning (7:30 AM to 10:00 AM) and nighttime (11:00 PM to 1:00 AM) serum melatonin concentrations were measured in 89 children, adolescents, and young adults. Morning levels (generally 0-20 pg/ml) did not change with sexual maturation or with age. Nighttime levels decreased significantly both with sexual maturation and with age. Nighttime serum melatonin fell from 195 +/- 24 pg/ml (mean +/- SEM) in prepubertal children younger than 7 years of age, to 119 +/- 23 pg/ml in prepubertal children aged 7 years or older, to 49 +/- 4 pg/ml in young adults (puberty stage V). Similarly, nocturnal serum melatonin levels fell from 210 +/- 35 pg/ml in the youngest age group (ages 1-5) to 133 +/- 17 in children aged 5-11 years and to 46 +/- 4 in young adults. Nocturnal plasma concentrations of luteinising hormone measured at various stages of puberty tended to vary inversely with those of melatonin (r = -0.35). Past difficulties in demonstrating a relation between gonadal maturation and human pineal function may have reflected the use of insufficiently sensitive or specific melatonin assays, or serum sampling only during daytime, or the initiation of sample collection when subjects were already too old. PMID:6141425

  7. [Determination of human serum galactosyltransferase using a kinetic spectrophotometric technic].

    PubMed

    Gauduchon, P; Baumann, J J; Bar, E; Le Talaër, J Y

    1985-01-01

    A kinetic spectrophotometric method in which galactose transfer is coupled to the production of NADH, has been adapted to the assay of galactosyltransferase activity in human serum. Under the described conditions, the rate of NADH production is linear with regard to enzyme concentration, and directly depends upon the various biochemical factors which control galactosyltransferase activity. PMID:3924359

  8. Changes in serum protein profiles of chickens with tibial dyschondroplasia

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Differences in serum protein profiles were analyzed to identify biomarkers associated with a poultry leg problem named tibial dyschondroplasia (TD) that can cause lameness. We used a bead-based affinity matrix containing a combinatorial library of hexapeptides (ProteoMinerTM) to deplete high abundan...

  9. Indirect electrochemical detection for total bile acids in human serum.

    PubMed

    Zhang, Xiaoqing; Zhu, Mingsong; Xu, Biao; Cui, Yue; Tian, Gang; Shi, Zhenghu; Ding, Min

    2016-11-15

    Bile acids level in serum is a useful index for screening and diagnosis of hepatobiliary diseases. As bile acids concentration is closely related to the degree of hepatobiliary diseases, detecting it is a vital factor to understand the stage of the diseases. The prevalent determination for bile acids is the enzymatic cycling method which has low sensitivity while reagent-consuming. It is desirable to develop a new method with lower cost and higher sensitivity. An indirect electrochemical detection (IED) for bile acids in human serum was established using the screen printed carbon electrode (SPCE). Since bile acids do not show electrochemical signals, they were converted to 3-ketosteroids by 3-α-hydroxysteroid dehydrogenase (3α-HSD) in the presence of nicotinamide adenine dinucleotide (NAD(+)), which was reduced to NADH. NADH could then be oxidized on the surface of SPCE, generating a signal that was used to calculate the total bile acids (TBA) concentration. A good linear calibration for TBA was obtained at the concentration range from 5.00μM to 400μM in human serum. Both the precisions and recoveries were sufficient to be used in a clinical setting. The TBA concentrations in 35 human serum samples by our IED method didn't show significant difference with the result by enzymatic cycling method, using the paired t-test. Moreover, our IED method is reagent-saving, sensitive and cost-effective. PMID:27236139

  10. Maternal Serum Screening Markers and Adverse Outcome: A New Perspective

    PubMed Central

    Krantz, David; Hallahan, Terrence; Janik, David; Carmichael, Jonathan

    2014-01-01

    There have been a number of studies evaluating the association of aneuploidy serum markers with adverse pregnancy outcome. More recently, the development of potential treatments for these adverse outcomes as well as the introduction of cell-free fetal DNA (cffDNA) screening for aneuploidy necessitates a re-evaluation of the benefit of serum markers in the identification of adverse outcomes. Analysis of the literature indicates that the serum markers tend to perform better in identifying pregnancies at risk for the more severe but less frequent form of individual pregnancy complications rather than the more frequent but milder forms of the condition. As a result, studies which evaluate the association of biomarkers with a broad definition of a given condition may underestimate the ability of such markers to identify pregnancies that are destined to develop the more severe form of the condition. Consideration of general population screening using cffDNA solely must be weighed against the fact that traditional screening using serum markers enables detection of severe pregnancy complications, not detectable with cffDNA, of which many may be amenable to treatment options. PMID:26237472

  11. [Pulsed radiolysis of aqueous solutions of serum albumin containing naphthoquinones].

    PubMed

    Pribush, A G; Savich, A V

    1987-01-01

    As was shown by the pulse radiolysis method the simultaneous presence of naphthoquinone and human serum albumin molecules in an aqueous solution leads to the adsorption of the former on the surface of the latter. It is suggested that in these conditions the protein tertiary structure changes. New conformation reduces the reactivity of albumin toward the hydrated electron. PMID:3628723

  12. An improved ultrafiltration method for determining free testosterone in serum

    SciTech Connect

    Vlahos, I.; MacMahon, W.; Sgoutas, D.; Bowers, W.; Thompson, J.; Trawick, W.

    1982-11-01

    In this method, we use the Amicon MPS-1 centrifugal ultrafiltration device and the YMB membrane in measuring free testosterone in serum. Two independent assays are combined: total testosterone and the ultrafiltrable fraction of added (/sup 3/H)testosterone. The unbound fraction is determined in 0.15-0.5 mL ultrafiltrates of 0.6 to 1 mL of variably diluted serum that has been equilibrated with (/sup 3/H)testosterone at 37 degrees C. The assay is rapid (less than 1 h), practicable (requires 0.6 mL of serum), and reproducible (CV 3.2% within assay, 3.9% between assays). Accuracy was evaluated as the fraction of free testosterone in the ultrafiltrate of dialyzed serum vs that in a prior dialysate; they were the same confirming the validity of the free testosterone measurement. Samples from ostensibly healthy men and women and from hirsute and pregnant women gave results that agreed with those obtained by equilibrium dialysis. Total testosterone concentrations for normal and hirsute women showed considerable overlap, but data on free testosterone concentrations in these populations were better resolved.

  13. Etofenamate levels in human serum and synovial fluid following iontophoresis.

    PubMed

    Bender, T; Bariska, J; Rojkovich, B; Bálint, G

    2001-01-01

    The absorption of etofenamate (CAS 30544-47-9, Rheumon gel) by iontophoresis in 11 patients with low back pain and in 13 patients with synovitis of the knee was evaluated. During the 5-day treatment period, the test gel in a quantity corresponding to 100 mg etofenamate was applied to affected body regions every day by 20-min iontophoresis sessions. Two hours after the fifth application, the concentration of etofenamate in serum and synovial fluid (in patients who had knee joint iontophoresis) were measured by HPLC. Iontophoresis of etofenamate into the lumbar region as well as to the knee joint resulted in consistent serum levels: 219 +/- 136.3 micrograms/l and 191 +/- 84.6 micrograms/l, respectively. In patients with synovitis of the knee, the synovial level of etofenamate (368 +/- 109.2 micrograms/l) was almost twice as high than the serum concentration. The authors conclude that with topical application of etofenamate by iontophoresis the drug appears not only in the serum but also--with higher levels--in the synovial fluid. PMID:11455681

  14. 21 CFR 522.1079 - Serum gonadotropin and chorionic gonadotropin.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Serum gonadotropin and chorionic gonadotropin. 522.1079 Section 522.1079 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN.... (i) Gilts. For induction of fertile estrus (heat) in healthy prepuberal (noncycling) gilts. (ii)...

  15. 21 CFR 522.1079 - Serum gonadotropin and chorionic gonadotropin.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Serum gonadotropin and chorionic gonadotropin. 522.1079 Section 522.1079 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN.... (i) Gilts. For induction of fertile estrus (heat) in healthy prepuberal (noncycling) gilts. (ii)...

  16. 21 CFR 522.1079 - Serum gonadotropin and chorionic gonadotropin.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Serum gonadotropin and chorionic gonadotropin. 522.1079 Section 522.1079 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN.... (i) Gilts. For induction of fertile estrus (heat) in healthy prepuberal (noncycling) gilts. (ii)...

  17. Maternal Serum Meteorin Levels and the Risk of Preeclampsia

    PubMed Central

    Garcés, María F.; Sanchez, Elizabeth; Cardona, Luisa F.; Simanca, Elkin L.; González, Iván; Leal, Luis G.; Mora, José A.; Bedoya, Andrés; Alzate, Juan P.; Sánchez, Ángel Y.; Eslava-Schmalbach, Javier H.; Franco-Vega, Roberto; Parra, Mario O.; Ruíz—Parra, Ariel I.; Diéguez, Carlos; Nogueiras, Rubén; Caminos, Jorge E.

    2015-01-01

    Background Meteorin (METRN) is a recently described neutrophic factor with angiogenic properties. This is a nested case-control study in a longitudinal cohort study that describes the serum profile of METRN during different periods of gestation in healthy and preeclamptic pregnant women. Moreover, we explore the possible application of METRN as a biomarker. Methods and Findings Serum METRN was measured by ELISA in a longitudinal prospective cohort study in 37 healthy pregnant women, 16 mild preeclamptic women, and 20 healthy non-pregnant women during the menstrual cycle with the aim of assessing serum METRN levels and its correlations with other metabolic parameters. Immunostaining for METRN protein was performed in placenta. A multivariate logistic regression model was proposed and a classifier model was formulated for predicting preeclampsia in early and middle pregnancy. The performance in classification was evaluated using measures such as sensitivity, specificity, and the receiver operating characteristic (ROC) curve. In healthy pregnant women, serum METRN levels were significantly elevated in early pregnancy compared to middle and late pregnancy. METRN levels are significantly lower only in early pregnancy in preeclamptic women when compared to healthy pregnant women. Decision trees that did not include METRN levels in the first trimester had a reduced sensitivity of 56% in the detection of preeclamptic women, compared to a sensitivity of 69% when METRN was included. Conclusions The joint measurements of circulating METRN levels in the first trimester and systolic blood pressure and weight in the second trimester significantly increase the probabilities of predicting preeclampsia. PMID:26121675

  18. Radioenzymatic assay for trimethoprim in very small serum samples

    SciTech Connect

    Yogev, R.; Melick, C.; Tan-Pong, L.

    1985-02-01

    A modification of the methotrexate radioassay kit (supplied by New England Enzyme Center) enabled determination of trimethoprim levels in 5-microliter serum samples. An excellent correlation between this assay and high-pressure liquid chromatography assay was found. These preliminary results suggest that with this method rapid determination of trimethoprim levels in very small samples (5 to 10 microliters) can be achieved.

  19. Mechanism of serum cholesterol reduction by oat bran.

    PubMed

    Marlett, J A; Hosig, K B; Vollendorf, N W; Shinnick, F L; Haack, V S; Story, J A

    1994-12-01

    Nine normolipidemic young men consumed a constant diet for 2 mo into which oat bran was incorporated during the second month so that we might test the hypotheses that oats lower serum cholesterol concentrations by decreasing bile acid and fat absorption and increasing bile acid synthesis. Bile acid kinetics were determined by measuring the 13C enrichment of serum cholic and chenodeoxycholic acids. Oat bran consumption decreased serum cholesterol levels (p < 0.01) and cholic acid pool size (p < 0.05). Deoxycholic acid pool size (p < 0.01) and the synthesis and fractional turnover rates of both primary bile acids (p < 0.05) increased. Total bile acid pool size did not change. Fecal excretion of total bile acids, the two secondary bile acids and fat increased significantly. The results demonstrate that oat bran lowers serum cholesterol levels in part by altering bile acid metabolism. In addition, the substantial increase in the proportion of the total bile acid pool that was deoxycholic acid is consistent with the hypothesis that oat bran also decreases cholesterol synthesis. PMID:7982644

  20. Quantifying terpenes in rumen fluid, serum, and plasma from sheep

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Determining the fate of terpenes consumed by browsing ruminants require methods to quantify their presence in blood and rumen fluid. Our objective was to modify an existing procedure for plasma terpenes to quantify 25 structurally diverse mono- and sesquiterpenes in serum, plasma, and rumen fluid fr...

  1. Serum fractions inhibitory to the growth of Leptospires.

    PubMed

    Ryu, E

    1965-11-01

    It is known that the growth inhibitory substance of animal sera on Leptospires exists in the albumin fraction. Since the globulin fraction obtained from animal sera having growth inhibitory property may support, though variable individually, some degree of leptospiral growth, it may be added, with 5% of pooled rabbit serum, to the medium to be used for the propagation of Leptospires. PMID:4220645

  2. Serum MicroRNAs as Diagnostic Biomarkers for Macrosomia

    PubMed Central

    Wen, Yang; Hu, Lingmin; Miao, Tingting; Zhang, Ming; Dong, Jing

    2015-01-01

    Background: Macrosomia is defined as an infant’s birth weight of more than 4000 g. Although microRNAs (miRNAs) have been implicated in the pathogenesis of various diseases, the associations between serum miRNAs and macrosomia have been rarely reported. Methodology: We used the Taqman Low Density Array followed by quantitative reverse transcriptase polymerase chain reaction assays to screen for miRNAs associated with macrosomia using serum samples collected 1 week before delivery. Results: Profiling results showed that 1 miRNA was significantly upregulated and 10 miRNAs were significantly downregulated in serum samples of macrosomia (ΔΔCt > 3-fold). The expression levels of miR-21 were significantly decreased in macrosomia as compared to the controls in the third trimester. Receiver operating characteristic (ROC) curve analyses showed that the area under the ROC curve for miR-21 was 67.7% (sensitivity = 66.7% and specificity = 70.0%). Conclusions: miR-21 in maternal serum is differentially expressed between macrosomia and controls, and miR-21 could be used as a candidate biomarker to predict macrosomia. PMID:25519717

  3. OYSTER SERUM AGGLUTININS AND RESISTANCE TO PROTOZOAN PARASITES

    EPA Science Inventory

    Serum agglutinins or lectins are reported to be induced in marine molluscs by exposure to bacteria and may enhance bacterial clearance from the host; however, there is a little information on possible relationships between lectins and protozoan parasites of molluscs. wo protozoan...

  4. Hair: A Diagnostic Tool to Complement Blood Serum and Urine.

    ERIC Educational Resources Information Center

    Maugh, Thomas H., II

    1978-01-01

    Trace elements and some drugs can be identified in hair and it seems likely that other organic chemicals will be identifiable in the future. Since hair is so easily collected, stored, and analyzed it promises to be an ideal complement to serum and urine analysis as a diagnostic tool. (BB)

  5. Serum IL-17A in Behçet's disease

    PubMed Central

    Cengiz, Fatma Pelin; Erdem, Gul Bahar

    2015-01-01

    Introduction Behçet's disease is a chronic multisystem disease with spontaneous remissions and relapses. Several studies show that autoimmune mechanisms play an important role in the development of Behçet's disease. Activation of T cells and neutrophils is important in the pathogenesis of the disease. Interleukin 17 (IL-17) is a new cytokine that induces several types of cells to secrete proinflammatory cytokines in many inflammatory and autoimmune diseases. Aim This study evaluated the serum levels of IL-17A in active and stable Behçet's disease patients. Material and methods Seventy-six patients who had active clinic findings of Behçet's disease were enrolled in our study. Seventy age- and sex-matched controls were also enrolled. Serum IL-17 levels were studied in peripheral venous blood samples. Results No significant differences were found between active Behçet's disease patients and controls in terms of serum IL-17A (p > 0.05). Conclusions These results suggest that IL-17A serum levels do not play an important role in active Behçet's disease. PMID:26759544

  6. Mannose-Binding Lectin Serum Levels in Patients With Candiduria

    PubMed Central

    Moslem, Maryam; Zarei Mahmoudabadi, Ali; Fatahinia, Mahnaz; Kheradmand, Alireza

    2015-01-01

    Background: Candida species are normal mycoflora of human body which are capable to cause urinary tract infection (UTI). Mannose-binding lectin (MBL) is a kind of innate immune system and decreasing plasma levels of MBL may disrupt the natural immune response and increase susceptibility to infections. Objectives: The aim of the present study was to assess MBL in the serum of patients with candiduria and compare them with control. Patients and Methods: The blood and urine samples were collected from 335 patients (hospitalized in Golestan hospital, Ahvaz) using standard methods and the growing colonies on CHROMagar were identified using routine diagnostic tests. MBL activity in the serum of 45 patients with candiduria and 45 controls was measured using Eastbiopharm enzyme-linked immunosorbent assay (ELISA) kit. Results: In this study, 45 (13.4 %) urine samples were positive for Candida species (17 males and 28 females). The most common isolated yeast was Candida albicans (34%), followed by C. glabrata (32.1%), C. tropicalis (9.4%), other Candida species (22.6%), and Rhodotorula species (1.9%). The mean serum levels of MBL were 0.85 ± 0.01 ng/mL and 1.02 ± 0.03 ng/mL among candiduric patients and controls, respectively, and there was no significant difference between the two groups (P = 0.6). Conclusions: Our results showed that there was no significant relationship between MBL serum levels and candiduria. PMID:26870314

  7. NAA For Human Serum Analysis: Comparison With Conventional Analyses

    SciTech Connect

    Oliveira, Laura C.; Zamboni, Cibele B.; Medeiros, Jose A. G.; Azevedo, Maria R.

    2010-08-04

    Instrumental and Comparator methods of Neutron Activation Analysis (NAA) were applied to determine elements of clinical relevancy in serum samples of adult population (Sao Paulo city, Brazil). A comparison with the conventional analyses, Colorimetric for calcium, Titrymetric for chlorine and Ion Specific Electrode for sodium and potassium determination were also performed permitting a discussion about the performance of NAA methods for clinical chemistry research.

  8. Purification of folate binding factor in normal umbilical cord serum.

    PubMed Central

    Kamen, B A; Caston, J D

    1975-01-01

    Human umbilical cord serum was found to contain both free folate and folate complexed to a high-molecular weight factor. The complexed folate was bound to a very high affinity binder and was present in concentrations equivalent to as much as 60 ng of 5-methyltetrahydrofolic acid per ml of serum. Acidification of the serum caused disassociation of the folate-binder complex. Released folates were separated from binder by Sephadex gel filtration, zonal centrifugation through sucrose gradients, or adsorption onto activated charcoal. The separated binding factor, either saturated or unsaturated with folate, had a molecular weight of about 40,000 on Sephadex G-200 chromatography. Binding of [3H]pteroylglutamic acid was rapid and, as in the original endogenous folate-binder complex, was essentially irreversible at neutral pH. The affinity and specificity of the binder were examined by competition experiments using [3H]pteroylglutamic acid and nonradioactive folate derivatives. Oxidized folates were bound in preference to reduced derivatives, but only three to four times more unlabeled 5-methyltetrahydrofolic acid than pteroylglutamic acid was required to produce an equal level of competition. The strong affinity for 5-methyltetrahydrofolic acid, the main serum folate, suggests that the binder could be part of the mechanism by which the fetus concentrates maternally supplied folate for its growth and development. PMID:676

  9. Association between Serum 25-Hydroxyvitamin D Level and Rheumatoid Arthritis

    PubMed Central

    Cen, Xiaomin; Liu, Yuan; Yin, Geng; Xie, Qibing

    2015-01-01

    The objective of this study is to examine and evaluate whether serum 25(OH)D is associated with disease activity in patients with rheumatoid arthritis (RA). Our results suggested that serum 25(OH)D in RA groups has significant lower level (35.99 ± 12.59 nmol/L) than that in the normal groups (54.35 ± 8.20 nmol/L, P < 0.05). Based on the DAS28, patients with RA were divided into four subgroups, and no differences were found in the four groups (P > 0.05). The 25(OH)D levels in complete remission, low disease activity, middle disease activity, and high disease activity group were 32.86 ± 12.26, 33.97 ± 13.28, 38.41 ± 10.64, and 38.94 ± 13.35 nmol/L, respectively. Based on the serum 25(OH)D levels, patients with RA were divided into inadequate group and normal group, and there were no significant differences in baseline characteristics and disease activity in the two groups. Our results showed that serum 25(OH)D levels in the inadequate group are significantly lower than those in the normal group. However, no correlations were found between 25(OH)D levels and disease activity among 116 patients with RA. The present findings will help to understand the association between 25(OH)D and disease activity of RA. PMID:26064964

  10. Association Between Serum Osteocalcin and Markers of Metabolic Phenotype

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Osteocalcin has been recently reported to contribute to the regulation of glucose tolerance and insulin secretion and sensitivity in experimental animals; however, the data in humans are sparse. To examine the association between serum osteocalcin concentration and markers of dysmetabolic phenotype...

  11. Antiplasmin activity of electrophoretically separated human serum fractions

    PubMed Central

    Mann, R. D.; Cotton, Susan; Jackson, D.

    1966-01-01

    The antiplasmin which migrates electrophoretically with the alpha2 globulins preponderates in effect over that of the alpha1 migrating antiplasmin. This preponderance persists at physiological pH value in vitro and the significance of this finding is discussed. No evidence has been obtained of the existence of anti-urokinase activity in antiplasmin-free serum fractions. PMID:4160096

  12. Serum cortisol levels in patients with uncomplicated and cerebral malaria.

    PubMed

    Shwe, T; Khin, M; Min, H; Hla, K K; Win, Y Y; Htwe, K; Thu, T M

    1998-03-01

    Ten patients with uncomplicated malaria, ten with cerebral malaria and 37 controls (blood donors from blood bank) were included in the study. The serum cortisol levels of the patients were determined daily for 7 days while they were at the hospital. A radio-immunoassay method was used for quantitative measurement of cortisol in human serum. The mean serum cortisol level of patients with uncomplicated malaria was 528.2 +/- 123.9 nmol/l, with cerebral malaria was 516.0 +/- 80.5 nmol/l, and in controls was 393.8 +/- 141.0 nmol/l. There was a significant rise of serum cortisol levels in patients with malaria when compared to controls at the day of admission to hospital. There was no significant difference between uncomplicated malaria patients and those with cerebral malaria. There was also no significant difference between the different days of treatment up till day 7. We found no cortisol insufficiency in cases with falciparum malaria during acute and convalescent stages of illness. PMID:9740267

  13. 9 CFR 147.2 - The rapid serum test. 2

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false The rapid serum test. 2 147.2 Section 147.2 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF... incubated 48 hours at 37 °C., and the surface growth washed off with a very slight amount of 12...

  14. 9 CFR 147.2 - The rapid serum test. 2

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false The rapid serum test. 2 147.2 Section 147.2 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF... incubated 48 hours at 37 °C., and the surface growth washed off with a very slight amount of 12...

  15. 21 CFR 522.1079 - Serum gonadotropin and chorionic gonadotropin.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... freeze-dried powder to be reconstituted with 5 milliliters of sterile aqueous diluent. (b) Sponsor. See No. 000061 in § 510.600(c) of this chapter. (c) Conditions of use in swine—(1) Amount. 400 I.U. serum.... (i) Gilts. For induction of fertile estrus (heat) in healthy prepuberal (noncycling) gilts. (ii)...

  16. Lowering of serum cholesterol in hypercholesterolemic humans by tocotrienols (palmvitee).

    PubMed

    Qureshi, A A; Qureshi, N; Wright, J J; Shen, Z; Kramer, G; Gapor, A; Chong, Y H; DeWitt, G; Ong, A; Peterson, D M

    1991-04-01

    A double-blind, crossover, 8-wk study was conducted to compare effects of the tocotrienol-enriched fraction of palm oil (200 mg palmvitee capsules/day) with those of 300 mg corn oil/d on serum lipids of hypercholesterolemic human subjects (serum cholesterol 6.21-8.02 mmol/L). Concentrations of serum total cholesterol (-15%), LDL cholesterol (-8%), Apo B (-10%), thromboxane (-25%), platelet factor 4 (-16%), and glucose (-12%) decreased significantly only in the 15 subjects given palmvitee during the initial 4 wk. The crossover confirmed these actions of palmvitee. There was a carry over effect of palmvitee. Serum cholesterol concentrations of seven hypercholesterolemic subjects (greater than 7.84 mmol/L) decreased 31% during a 4-wk period in which they were given 200 mg gamma-tocotrienol/d. This indicates that gamma-tocotrienol may be the most potent cholesterol inhibitor in palmvitee capsules. The results of this pilot study are very encouraging. PMID:2012010

  17. Serum Glucose Level in First and Third Trimester of Pregnancy.

    PubMed

    Zannat, M R; Nessa, A; Hossain, M M; Das, R K; Asrin, M; Sufrin, S; Islam, M T; Tajkia, T; Nasreen, S

    2016-04-01

    In the present study serum glucose were estimated in pregnant women during the first trimester of pregnancy and third trimester of pregnancy to observe the frequency of hyperglycemia during pregnancy and to assess the incidence of gestational diabetes mellitus. This study was a cross sectional study, carried out in the Department of Physiology of Mymensingh Medical College, Mymensingh from July 2014 to June 2015. For this purpose, total 300 women with age ranged from 18 to 35 years were selected and divided into 100 healthy non pregnant women as control group and 200 normal pregnant women as study group. Study group was further divided into 100 pregnant women in first trimester of pregnancy and 100 pregnant women in third trimester of pregnancy. Diagnosed case of type I and type II diabetes, hypothyroidism, cushing's syndrome, polycystic ovary, antipsychotic drug users, regular steroid users were excluded from this study. Serum glucose was evaluated by the glucose-oxidase principle by GOD-PAP method in women with 1st trimester of pregnancy, 3rd trimester of pregnancy and in non pregnant women. Statistical analysis of data was done by unpaired student's t test. The results showed that the serum glucose levels increased significantly in third trimester and the value is not significant in first trimester. The increasing frequency of serum glucose level in third trimester may predispose the women to hyperglycemia of pregnancy or gestational diabetes mellitus. PMID:27277349

  18. Raised serum proinflammatory cytokines in Alzheimer's disease with depression.

    PubMed

    Khemka, Vineet Kumar; Ganguly, Anirban; Bagchi, Debajit; Ghosh, Arindam; Bir, Aritri; Biswas, Atanu; Chattopadhyay, Sita; Chakrabarti, Sasanka

    2014-06-01

    The purpose of the present study was to identify the changes in the levels of proinflammatory cytokines like IL-1β, IL-6 and TNF-α in peripheral circulation in Alzheimer's disease (AD) subjects and to correlate these with associated depression and cognitive deficit. Fifty five AD subjects and thirty seven age and sex matched controls were included in the study. The AD patients were grouped as AD with depression (n= 31) and AD without depression (n= 24). The serum levels of IL-1β, IL-6 and TNF-α were determined by immunoassay by commercially available kits. The serum levels of IL-6 and TNF-α were elevated in AD patients with depression compared to control (p<0.001) or AD without depression (p<0.001). The serum level of IL-1β was higher in AD patients with or without depression as compared to controls. Furthermore, a strong inverse correlation was observed between the MMSE scores and serum levels of IL-6 or TNF-α in AD subjects with depression. The study highlights the important role of peripheral IL-6 and TNF-α in AD associated depression and cognitive deficits. PMID:24900939

  19. 9 CFR 147.2 - The rapid serum test. 2

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... the composition of a satisfactory medium are described in § 147.1 (b) and (c). (c) Large 1-inch test... tightly stoppered bottles. (g) The tests should be conducted on a suitable, smooth plate. The serum... within 15 to 20 seconds. The final reading should be made at the end of 2 or 3 minutes. Heating the...

  20. Investigation of bovine serum albumin glycation by THz spectroscopy

    NASA Astrophysics Data System (ADS)

    Cherkasova, Olga P.; Nazarov, Maxim M.; Shkurinov, Alexander P.

    2016-04-01

    Protein glycation is accelerated under hyperglycemic conditions resulting to loss in the structure and biological functions of proteins. The transmission THz spectroscopy has been used for measuring of bovine serum albumin glycation dynamics. It was found that amplitude of albumin THz absorption depends on type of sugars and incubation time.

  1. Fasting Serum Glucose Level in Postmenopausal Bangladeshi Women.

    PubMed

    Tajkia, T; Nessa, A; Mia, M R; Das, R K; Sufrin, S; Zannat, M R; Naznin, R; Khanam, A; Akter, R; Nasreen, S

    2016-07-01

    The study was done to find out the causes that changes the fasting serum glucose level in postmenopausal women. This was descriptive type of cross sectional study carried out over a period of one year from July 2014 to June 2015 in the department of physiology, Mymensingh Medical College, Mymensingh. Women of reproductive age (25-45 years) and clinically diagnosed 100 menopausal women (45-70 years) were included for this study. Convenience type of sampling technique was used for selecting the study subjects. Measurement of fasting serum glucose was done by GOD-PAP method. Data were expressed as mean±SD and statistical significance of difference among the groups were calculated by unpaired student's 't' test. The mean±SD of serum glucose in menopausal women were significant at 1% level of probability than women of reproductive age. This study revealed that postmenopausal women showed higher levels of fasting serum glucose level. Fasting blood sugar level between the study & control group were 7.69±2.37 and 4.59±0.73 and the difference was statistically significant. PMID:27612883

  2. The Association of Cord Serum Cytokines with Neurodevelopmental Outcomes

    PubMed Central

    Varner, Michael W.; Marshall, Nicole E.; Rouse, Dwight J.; Jablonski, Kathleen A.; Leveno, Kenneth J.; Reddy, Uma M.; Mercer, Brian M.; Iams, Jay D.; Wapner, Ronald J.; Sorokin, Yoram; Thorp, John M.; Malone, Fergal D.; Carpenter, Marshall; O’Sullivan, Mary J.; Peaceman, Alan M.; Hankins, Gary D.V.; Dudley, Donald J.; Caritis, Steve N.

    2014-01-01

    OBJECTIVE To test whether elevated umbilical cord serum inflammatory cytokine levels predicted subsequent cerebral palsy (CP) or neurodevelopmental delay (NDD). STUDY DESIGN Nested case-control analysis within a clinical trial of antenatal magnesium sulfate (MgSO4) before anticipated PTB for prevention of CP, with evaluation of surviving children at age 2. NDD was defined as a Bayley Psychomotor Developmental Index (PDI) and/or Mental Developmental Index (MDI) <70. Controls, defined as surviving children without CP and with Bayley PDI and MDI ≥85, were matched by race and gestational age. Cord serum was analyzed for IL-8, IL-1 β and TNF-α levels. Elevated cytokine levels were defined as ≥75th percentile in placebo-exposed controls. Analyses compared case/control cytokine levels, adjusting for MgSO4 exposure, gestational age, race/ethnicity and sociodemographic differences. RESULTS Logistic regression analysis with 339 cases and 276 controls showed that elevated IL-8 and IL-1β were more common in cord blood serum from infants with subsequent low MDI compared with controls. After adjusting for additional confounders, the significant differences were no longer evident. Cytokine levels (IL-8, IL-1β, and TNF-α) were not elevated with CP or low PDI. CONCLUSION Cord serum IL-8, IL-1β, and TNF-α levels in preterm infants are not associated with subsequent CP or NDD. PMID:24936937

  3. Maternal Serum Screening Markers and Adverse Outcome: A New Perspective.

    PubMed

    Krantz, David; Hallahan, Terrence; Janik, David; Carmichael, Jonathan

    2014-01-01

    There have been a number of studies evaluating the association of aneuploidy serum markers with adverse pregnancy outcome. More recently, the development of potential treatments for these adverse outcomes as well as the introduction of cell-free fetal DNA (cffDNA) screening for aneuploidy necessitates a re-evaluation of the benefit of serum markers in the identification of adverse outcomes. Analysis of the literature indicates that the serum markers tend to perform better in identifying pregnancies at risk for the more severe but less frequent form of individual pregnancy complications rather than the more frequent but milder forms of the condition. As a result, studies which evaluate the association of biomarkers with a broad definition of a given condition may underestimate the ability of such markers to identify pregnancies that are destined to develop the more severe form of the condition. Consideration of general population screening using cffDNA solely must be weighed against the fact that traditional screening using serum markers enables detection of severe pregnancy complications, not detectable with cffDNA, of which many may be amenable to treatment options. PMID:26237472

  4. HPLC ANALYSIS OF VINCLOZOLIN AND ITS METABOLITES IN SERUM

    EPA Science Inventory


    HPLC ANALYSIS OF VINCLOZOLIN AND ITS METABOLITES IN SERUM. A Sierra-Santoyo1,2, H A Barton1 and M F Hughes1. 1US EPA, ORD, NHEERL, ETD, RTP, NC; 2Toxicology Section, CINVESTAV-IPN, Mexico City, Mexico.

    The fungicide vinclozolin (V) is used predominantly for treatment...

  5. Serum resistance associated with virulence in Yersinia enterocolitica.

    PubMed Central

    Pai, C H; DeStephano, L

    1982-01-01

    Yersinia enterocolitica strains that exhibited a calcium requirement for growth and autoagglutination at 37 degrees C were invariably virulent in rabbits, causing diarrhea and a high degree of lethality, and were capable of colonizing the intestinal lumen and establishing foci of infection on the Peyer's patches of mice. Strains that had lost the properties of calcium dependency and autoagglutinability were totally avirulent in rabbits and were quickly eliminated from the intestinal lumen and tissues of mice. Virulent and avirulent strains were shown to be equally invasive to HeLa cells. However, the virulent strains were resistant to the bactericidal action of normal serum, and this serum resistance was lost with the loss of virulence. Furthermore, the serum resistance of virulent strains was expressed, as were other properties, when strains were grown at 37 degrees C, but not at 27 degrees C. These results suggest that a virulence factor associated with serum resistance plays an essential role in the pathogenicity of Y. enterocolitica. PMID:7056577

  6. Serum DHEAS levels are associated with the development of depression.

    PubMed

    Zhu, Guang; Yin, You; Xiao, Chun-Lan; Mao, Rong-Jie; Shi, Bo-Hai; Jie, Yong; Wang, Zuo-Wei

    2015-09-30

    The aim of study was to evaluate the association between serum DHEAS levels and depression with a case-control study together with a meta-analysis. Radioimmunoassay (RIA) was performed to measure the serum DHEAS levels of all participants before and after treatment. Depression Patients were divided into mild depression and severe depression based on Hamilton depression scale (HAMD24) and received 5-hydroxytryptamine (5-HT) and citalopram (20mg/d) for 8 weeks. Case-control studies related to our study theme were enrolled for meta-analysis and Comprehensive Meta-analysis 2.0 (CMA 2.0) was used for statistical analysis. After treatment, DHEAS levels in depression patients were significantly increased, while before and after treatment, DHEAS levels were all lower in depression patients than in controls (all P<0.001); further analysis on age revealed that DHEAS levels were decreased with the rising of age. Meta-analysis results suggested that serum DHEAS levels (ng/mL) were significantly higher in healthy controls compared to depression patients (SMD=0.777, 95%CI=0.156-1.399, P=0.014). In conclusion, our study suggests that serum DHEAS levels are associated with the development of depression and it decreased with the rising of age. PMID:26205628

  7. Serum Dopamine Beta Hydroxylase and Maltreatment in Psychiatrically Hospitalized Boys.

    ERIC Educational Resources Information Center

    Galvin, Matthew; And Others

    1995-01-01

    Males (ages 7 to 17) in a psychiatric hospital were studied while off psychoactive medication to determine how serum dopamine beta hydroxylase (DBH) activity varies with childhood maltreatment experiences. Lowest DBH levels were found in boys maltreated before 72 months of age or with the principal diagnosis of conduct disorder solitary aggressive…

  8. INVESTIGATION OF SERUM MICROCYSTIN CONCENTRATIONS AMONG DIALYSIS PATIENTS, BRAZIL, 1996

    EPA Science Inventory

    Investigation of Serum Microcystin Concentrations Among Dialysis Patients, Brazil, 1996

    Elizabeth D. Hilborn 1, Wayne W. Carmichael 2, Sandra M.F.O. Azevedo 3
    1- USEPA/ORD/NHEERL, Research Triangle Park, NC
    2- Wright State University, Dayton, OH
    3- Federal Univers...

  9. Decreased serum prohepcidin concentration in patients with polycythemia vera*

    PubMed Central

    Kwapisz, Justyna; Żekanowska, Ewa; Jasiniewska, Joanna

    2009-01-01

    Objective: Iron deficiency is a common complication in patients with polycythemia vera (PV). Hepcidin is a principal regulator of iron homeostasis. The aim of our study was to assess prohepcidin, a hepcidin precursor, and other iron status parameters in the serum of PV patients. Methods: The study was performed in 60 patients (F/M 26/34) aged 38~84 (66±10) years. The control group consisted of 20 healthy volunteers, age and sex matched. The following parameters were determined in blood serum samples: prohepcidin concentration, iron content, unsaturated iron binding capacity (UIBC), total iron binding capacity (TIBC), transferrin saturation (TfS), and concentrations of ferritin and soluble transferrin receptor (sTfR). Results: All PV patients showed significantly lower levels of prohepcidin, higher levels of sTfR and TIBC compared to the control group. 40% of the patients from the study group showed concentrations of ferritin below the normal range and significantly lower levels of serum iron and TfS, and significantly higher levels of sTfR, UIBC and TIBC in comparison with the rest of the study group. In this group of patients, prohepcidin concentrations were significantly lower than those in other patients. Conclusion: The results indicate that PV patients suffer from iron metabolism disorders. The decreased serum level of prohepcidin in PV patients may be a result of iron deficiency. PMID:19882752

  10. SERUM VALUES OF ALKALINE PHOSPHATASE AND LACTATE DEHYDROGENASE IN OSTEOSARCOMA

    PubMed Central

    ZUMÁRRAGA, JUAN PABLO; BAPTISTA, ANDRÉ MATHIAS; ROSA, LUIS PABLO DE LA; CAIERO, MARCELO TADEU; CAMARGO, OLAVO PIRES DE

    2016-01-01

    ABSTRACT Objective: To study the relationship between the pre and post chemotherapy (CT) serum levels of alkaline phosphatase (AP) and lactate dehydrogenase (LDH), and the percentage of tumor necrosis (TN) found in specimens after the pre surgical CT in patients with osteosarcoma. Methods: Series of cases with retrospective evaluation of patients diagnosed with osteosarcoma. Participants were divided into two groups according to serum values of both enzymes. The values of AP and LDH were obtained before and after preoperative CT. The percentage of tumor necrosis (TN) of surgical specimens of each patient was also included. Results: One hundred and thirty seven medical records were included from 1990 to 2013. Both the AP as LDH decreased in the patients studied, being the higher in pre CT than post CT. The average LHD decrease was 795.12U/L and AP decrease was 437.40 U/L. The average TN was 34.10 %. There was no statistically significant correlation between the serums values and the percentage of tumoral necrosis. Conclusion: The serum levels values of AP and LDH are not good predictors for the chemotherapy-induced necrosis in patients with osteosarcoma. Level of Evidence IV, Case Series. PMID:27217815

  11. Serum antibodies to Escherichia coli in subjects with ulcerative colitis

    PubMed Central

    Heddle, R. J.; Shearman, D. J. C.

    1979-01-01

    It has been proposed that in ulcerative colitis the intestinal flora stimulates autoimmune reactions to colonic epithelium through shared specificities exposed in a `common antigen' found in most Enterobacteriaceae. The present experiments aimed to resolve conflicting data as to whether patients with ulcerative colitis have selectively increased serum antibody titres to enterobacterial common antigen or E. coli 014, which is rich in enterobacterial common antigen. Antibody titres to enterobacterial common antigen and lipopolysaccharides of E. coli 014 and of five serotypes of E. coli which occur frequently in human faeces were measured by passive haemagglutination. Sera were obtained from patients with ulcerative colitis, age- and sex-matched controls and subjects with other gastrointestinal disorders. Serum titres to enterobacterial common antigen and E. coli 014 lipopolysaccharide were not increased significantly in subjects with ulcerative colitis but significant increases were observed in subjects with chronic liver disease without colitis. Patients with active ulcerative colitis, patients with chronic liver disease and subjects convalescent from Salmonella or Shigella infections all had significantly increased serum titres to the antigens as a group. Class-specific enhancement of passive haemagglutination indicated that the class distribution of serum antibodies was similar in subjects with ulcerative colitis and controls. PMID:93528

  12. Identification of serum analytes and metabolites associated with aerobic capacity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Studies aimed at identifying serum markers of cellular metabolism (biomarkers) that are associated at baseline with aerobic capacity (V02 max) in young, healthy individuals have yet to be reported. Therefore, the goal of the present study was to use the standard chemistry screen and untargeted mass ...

  13. Serum IgE Concentration in Trisomy 21

    ERIC Educational Resources Information Center

    Lopez, Vicente

    1974-01-01

    Levels of serum IgE (an immunoglobulin carrying reaginic antibody activity) were investigated in 16 Down's syndrome adolescents (12-to 18-years old) and in an equal number of retardates matched for age and sex residing in the same institution. (CL)

  14. Storage of serum in plastic and glass containers may alter the serum concentration of polychlorinated biphenyls.

    PubMed Central

    Karmaus, Wilfried; Riebow, John F

    2004-01-01

    Valid exposure assessment and biomonitoring of toxicants rely on standardized specimen collection, handling, storage, and measurement. In a study designed to determine organochlorine concentrations in blood samples, we recruited participants from registered anglers in Michigan. After participants were interviewed, blood was collected from study subjects, either at home by a phlebotomist or in a commercial blood-draw station. The phlebotomists stored their samples in glass containers, but without our knowledge, the commercial laboratory transferred the specimens to plastic containers for freezing in its central facility. Samples were analyzed in the Analytical Chemistry Section Laboratory of the Michigan Department of Community Health. This laboratory also provided information on storage in glass (n = 28) versus plastic containers (n = 113). We conducted linear regression analyses to assess factors that may explain the concentrations of polychlorinated biphenyls (PCBs), dichlorodiphenyldichloroethylene (DDE), and polybrominated biphenyls (PBBs). Our results indicate that storage of serum in plastic containers altered the total concentrations of PCBs, in particular, the higher chlorinated PCBs (PCB-180 and PCB-199), but not DDE or PBBs. No other characteristics of the samples could explain the higher PCB values (0.75 micro g/L vs. 0.45 micro g/L; p = 0.025) of those stored in plastic containers. The proportion of PCB detects in both subsamples did not differ. Some preceding studies have provided information on whether specimens were stored in glass or plastic containers; however, a number of studies have not. We suggest the initiation of a new review process to determine whether these earlier reports were based on unbiased PCB determinations. We recommend standardizing specimen collection, handling, storage, and measurement, which is particularly necessary for newly emerging analytes. PMID:15121504

  15. Serum Copper and Zinc Levels Among Iranian Colorectal Cancer Patients.

    PubMed

    Khoshdel, Zahra; Naghibalhossaini, Fakhraddin; Abdollahi, Kourosh; Shojaei, Shahla; Moradi, Mostafa; Malekzadeh, Mahyar

    2016-04-01

    Alterations of trace element concentrations adversely affect biological processes and could promote carcinogenesis. Only a few studies have investigated the degree of changes in copper and zinc levels in colorectal cancer (CRC). The aim of the present study was to compare the serum copper (Cu) and zinc (Zn) concentrations in patients with CRC from Iran with those of healthy subjects. Cu and Zn concentrations in the serum of 119 cancer patients and 128 healthy individuals were measured by atomic absorption spectrometry. We found a significant decrease in the total mean serum Cu and Zn concentrations in CRC patients as compared with the control group (137.5 ± 122.38 vs. 160.68 ± 45.12 μg/dl and 81.04 ± 52.05 vs. 141.64 ± 51.75, respectively). However, the serum Cu/Zn ratio in the patient group was significantly higher than that measured in the control group (p = 0.00). There was no significant difference in the mean values of serum Cu and Zn concentrations between young (<60 years) and elderly (≥60 years) patients. However, the Cu/Zn ratio in <60-year cases was significantly higher than that in ≥60-year age group (p < 0.05). In addition, mean serum Cu level in normal weight patients was significantly higher than that in overweight/obese cases (132.31 ± 87.43 vs. 103.81 ± 53.72 μg/dl, respectively) (p < 0.05). There was no difference in mean serum Cu and Zn concentrations in patients stratified by the site, stage, or differentiation grade of tumors. Our findings suggest that imbalance in Cu and Zn trace element level is associated with CRC and might play an important role in cancer development among Iranian patients. PMID:26329996

  16. The Association Between Serum Selenium Levels with Rheumatoid Arthritis.

    PubMed

    Yu, Na; Han, Fang; Lin, Xiaojun; Tang, Chun; Ye, Jinghua; Cai, Xiaoyan

    2016-07-01

    There are conflicting reports on the correlation between serum selenium (Se) levels with rheumatoid arthritis (RA). Through a meta-analysis approach, the aim of the present study is to clarify the relationship between serum Se levels with RA. We searched literatures that met our predefined criteria in PubMed, ScienceDirect, and OVID published as of September 2015. Ten eligible articles with 14 case-control studies involving 716 subjects were identified. Overall, pooled analysis indicated that subjects with RA had lower serum levels of Se than the healthy controls (standardized mean difference (SMD) = -1.347, 95 % confidence interval (CI) = [-1.872, -0.823], p < 0.001). Further subgroup analysis indicated that subjects with RA had lower serum Se levels than healthy controls in Europe (SMD = -1.063, 95 % CI = [-1.571, -0.556], p < 0.001) and Asia (SMD = -3.254, 95 % CI = [-4.687, -1.821], p < 0.001) but not in USA (SMD = -0.322, 95 % CI = [-0.657, 0.012], p = 0.059). The serum Se levels were lower in RA than healthy controls measured by graphite furnace atom absorption spectrometry (GFAAS) (SMD = -1.026, 95 % CI = [-1.522, -0.530], p < 0.001), electrothermal absorption spectrometry (EAS) (SMD = -1.197, 95 % CI = [-2.373, -0.020], p < 0.05), flame atomic absorption spectrophotometry (FAAS) (SMD = -0.681, 95 % CI = [-1.049, -0.313], p < 0.001), and inductively coupled plasma-mass spectrophotometer (ICP-MS) (SMD = -11.707, 95 % CI = [-15.189, -8.224], p < 0.001) but not by neutron activation analysis (NAA) (SMD = -0.674, 95 % CI = [-1.350, 0.003], p = 0.051). In conclusion, this meta-analysis supports a significant association between low serum Se concentration with RA. However, this finding needs further confirmation by a trans-regional multicenter study to obtain better understanding of causal relationship between serum Se with RA of different human

  17. Serum concentrations of 25-hydroxyvitamin D and its association with bone mineral density and serum parathyroid hormone levels during winter in urban males from Guiyang, Southwest China.

    PubMed

    Zhang, Qiao; Shi, Lixin; Peng, Nianchun; Xu, Shujing; Zhang, Miao; Zhang, Song; Li, Hong; Zhuang, Huijun; Gong, Mingxian; Wu, Danrong; Wang, Rui

    2016-03-28

    Serum vitamin D (25-hydroxyvitamin D (25OHD)) may influence serum parathyroid hormone (PTH) levels and bone mineral density (BMD). In the present study, we assessed serum 25OHD concentration and its association with PTH and BMD in urban males from Guiyang (N26.57°), the capital city of Guizhou province, Southwest China. We recruited 634 males aged >20 years from the Guiyang Health Measures Survey, and stratified them into three groups according to age: young (20-39 years), middle aged (40-59 years) and older (60-79 years). We measured serum concentrations of 25OHD, PTH levels and BMD of the lumbar spine (L1-L4), femoral neck and total hip. In addition, we also explored the relationship between 25OHD and lifestyle, socio-economic characteristics and medical history by applying covariance analysis and locally weighted regression plots. The results showed that serum 25OHD was 75 nmol/l in 12·6 % of the subjects. Higher level of serum PTH was detected in relation to lower concentrations of serum 25OHD up to 50 nmol/l. A negative correlation between serum 25OHD and PTH concentrations was observed (r -0·207, P=0·003). Mean concentration of serum PTH increased gradually and plateaued while concentrations of serum 25OHD decreased to 50 nmol/l. Gradual increase in serum PTH was observed as 25OHD concentration was <25 nmol/l (P=0·004). BMD values at all sites were greater in the higher serum 25OHD concentration group. This study shows that low concentrations of serum 25OHD were common in males, and bone health was likely to be improved when serum 25OHD values were between 30 and 50 nmol/l. PMID:26843386

  18. Transforming growth factor-beta 1 stimulates glomerular mesangial cell synthesis of the 72-kd type IV collagenase.

    PubMed Central

    Marti, H. P.; Lee, L.; Kashgarian, M.; Lovett, D. H.

    1994-01-01

    Transforming growth factor-beta 1 (TGF-beta 1) is generally considered to exert positive effects on the accumulation of extracellular matrices. These occur as the net result of enhanced matrix protein synthesis, diminished matrix metalloproteinase (MMP) synthesis, and augmented production of specific inhibitors, including the tissue inhibitor of metalloproteinases (TIMP-1). Given that glomerular TGF-beta 1 synthesis is induced by inflammation, the effects of this cytokine on synthesis of the 72-kd type IV collagenase and TIMP-1 by cultured human mesangial cells were evaluated. Concentrations of TGF-beta 1 of 5 ng/ml and above specifically stimulated the synthesis of the 72-kd type IV collagenase. This effect was independent of the stimulatory effect of TGF-beta 1 on TIMP-1 synthesis, which was maximal in a lower concentration range (0.1 to 1 ng/ml). Most significantly, the net effect at the higher concentrations of TGF-beta 1 was an excess of enzyme over the TIMP-1 inhibitor. Northern blot analysis of TGF-beta 1-stimulated human mesangial cells demonstrated a specific increase in the abundance of the 3.1 kb mRNA transcript encoding the 72-kd type IV collagenase, presumably mediated by a direct stimulation of 72-kd type IV collagenase mRNA transcription observed as early as 3 hours after exposure to TGF-beta 1. These studies were extended to an analysis of the expression of TGF-beta 1 and 72-kd type IV collagenase mRNAs in normal and nephritic rats. In normal animals, basal TGF-beta 1 and 72-kd type IV collagenase mRNA expression was observed in a strictly mesangial distribution. After induction of acute immune complex-mediated glomerulonephritis, there was a major increase in TGF-beta 1 and 72-kd type IV collagenase mRNA expression, which was strictly limited to the expanded, hypercellular mesangial compartment. Enhanced synthesis of the mesangial type IV collagenase in response to TGF-beta 1 released during glomerular inflammatory processes could have an important

  19. Transforming growth factor-beta1 upregulates myostatin expression in mouse C2C12 myoblasts.

    PubMed

    Budasz-Rwiderska, M; Jank, M; Motyl, T

    2005-06-01

    Myostatin (MSTN) and transforming growth factor-beta1 (TGF-beta1) belong to the same TGF-beta superfamily of proteins. They are involved in regulation of skeletal muscle growth and development as well as muscle catabolism. The aim of the present study was to investigate the relationship between MSTN and TGF-beta1 expression in proliferating and differentiating mouse C2C12 myoblasts cultured in normal and catabolic conditions and to evaluate the effect of exogenous TGF-beta1 as well as "knock down" of TGF-beta1 receptor type II on MSTN expression in proliferating and differentiating myogenic cells. The direct effect of TGF-beta1 on myostatin was also examined. Myostatin expression increased gradually with cell confluency in proliferating cultures, while the level of TGF-beta1, detected in the form of a 100 kDa small latent complex diminished. Myostatin expression was accompanied by a partial cell cycle arrest. Three forms of myostatin were found: a 52 kDa precursor, a 40 kDa latency associated propeptide, and a 26 kDa active peptide. A decrease in myostatin and TGF-beta1 levels was observed during the first three days of differentiation, which was subsequently followed by significant increase of their expression during next three to four days of differentiation. Catabolic state induced by dexamethasone significantly increased the level of all forms of myostatin as well as latent (100 kDa) and active (25 kDa) forms of TGF-beta1 in differentiating myoblasts in a dose dependent manner. Exogenous TGF-beta1 (2 ng/ml) significantly increased myostatin levels both in proliferating and differentiating C2C12 myoblasts, whereas silencing of the TGF-beta1 receptor II gene significantly lowered myostatin level in examined cells. The presented results indicate that TGF-beta1 may control myostatin-related regulation of myogenesis through up-regulation of myostatin, predominantly in the course of terminal differentiation and glucocorticoid-dependent catabolic stimulation. PMID

  20. Serum Metabolite Biomarkers Discriminate Healthy Smokers from COPD Smokers

    PubMed Central

    Chen, Qiuying; Deeb, Ruba S.; Ma, Yuliang; Staudt, Michelle R.; Crystal, Ronald G.; Gross, Steven S.

    2015-01-01

    COPD (chronic obstructive pulmonary disease) is defined by a fixed expiratory airflow obstruction associated with disordered airways and alveolar destruction. COPD is caused by cigarette smoking and is the third greatest cause of mortality in the US. Forced expiratory volume in 1 second (FEV1) is the only validated clinical marker of COPD, but it correlates poorly with clinical features and is not sensitive enough to predict the early onset of disease. Using LC/MS global untargeted metabolite profiling of serum samples from a well-defined cohort of healthy smokers (n = 37), COPD smokers (n = 41) and non-smokers (n = 37), we sought to discover serum metabolic markers with known and/or unknown molecular identities that are associated with early-onset COPD. A total of 1,181 distinct molecular ions were detected in 95% of sera from all study subjects and 23 were found to be differentially-expressed in COPD-smokers vs. healthy-smokers. These 23 putative biomarkers were differentially-correlated with lung function parameters and used to generate a COPD prediction model possessing 87.8% sensitivity and 86.5% specificity. In an independent validation set, this model correctly predicted COPD in 8/10 individuals. These serum biomarkers included myoinositol, glycerophopshoinositol, fumarate, cysteinesulfonic acid, a modified version of fibrinogen peptide B (mFBP), and three doubly-charged peptides with undefined sequence that significantly and positively correlate with mFBP levels. Together, elevated levels of serum mFBP and additional disease-associated biomarkers point to a role for chronic inflammation, thrombosis, and oxidative stress in remodeling of the COPD airways. Serum metabolite biomarkers offer a promising and accessible window for recognition of early-stage COPD. PMID:26674646

  1. Elevated serum levels of Chromogranin A in hepatocellular carcinoma

    PubMed Central

    2012-01-01

    Background During the past three decades, the incidence of hepatocellular carcinoma in the United States has tripled. The neuroendocrine character has been observed in some tumor cells within some hepatocellular carcinoma nodules and elevated serum chromogranin A also been reported in patients with hepatocellular carcinoma. The aim of this work was to investigate the role of serum concentration of chromogranin A in patients with hepatocellular carcinoma at different stages. Methods The study population consisted of 96 patients (63 males and 33 females age range 52-84) at their first hospital admission for hepatocellular carcinoma. The control group consisted of 35 volunteers (20 males and 15 females age range 50-80). The hepatocellular carcinoma patients were stratified according the Barcelona-Clinic Liver Cancer classification. Venous blood samples were collected before treatment from each patients before surgery, centrifuged to obtain serum samples and stored at -80° C until assayed. Results The chromogranin A serum levels were elevated (> 100 ng/ml) in 72/96 patients with hepatocellular carcinoma. The serum levels of chromogranin A were significantly correlated (p<0.05) with alpha-fetoprotein. In comparison with controls, the hepatocellular carcinoma patients showed a significant increase (p<0.001) vs controls. The chromogranin A levels in the Barcelona staging of hepatocellular carcinoma was higher in stage D compared to stage C (p<0.01), to stage B (p<0.001), and to stage A (p<0.001). Conclusions Molecular markers, such as chromogranin A, could be very useful tools for hepatocellular carcinoma diagnosis. However the molecular classification should be incorporated into a staging scheme, which effectively separated patients into groups with homogeneous prognosis and response to treatment, and thus serves to aid in the selection of appropriate therapy. PMID:23173843

  2. Serum magnesium concentration in drug-addicted patients.

    PubMed

    Karakiewicz, Beata; Kozielec, Tadeusz; Brodowski, Jacek; Chlubek, Dariusz; Noceń, Iwona; Starczewski, Andrzej; Brodowska, Agnieszka; Laszczyńska, Maria

    2007-03-01

    Drug addiction is a complex problem which leads to many somatic, psychic and social diseases. It is accompanied by the disturbed metabolism of various macro and micronutrients. The aim of this study was to assess serum magnesium concentration in drug-addicted patients and analyze whether Human Immunodeficiency Virus (HIV) infection and methadone treatment affect the level of serum magnesium in these patients. The examination was conducted in a group of 83 people - patients of Szczecin-Zdroje Psychiatric Hospital (Poland). They were 21 to 49 years old, and the mean age was 32 +/- 7 years. The control group consisted of 81 healthy individuals. Flame atomic-absorption spectrometry method was used to determine the magnesium concentration. The total serum magnesium concentration was calculated for the whole patient group, subgroups of women and men, a subgroup of people infected with HIV, and a subgroup receiving methadone substitution treatment. How magnesium behaves depending on age and addiction period, was checked. The mean concentration of magnesium in blood serum of the patients examined was 0.57 mmol/L, which was significantly lower than in the control group. In the subgroup of men it was 0.57 mmol/L, and in the subgroup of women - 0.55 mmol/L; the differences were not statistically significant. In the patient group nobody had the appropriate magnesium concentration in blood serum. No significant correlation was found between the magnesium concentration, age of the patients and addiction period. In the subgroup of seropositive people the mean concentration of magnesium was 0.55 mmol/L, and in the subgroup of non-infected patients - 0.58 mmol/L; the difference was not statistically significant. The mean concentration of magnesium in the subgroup treated with methadone was 0.59 mmol/L, and in the subgroup not involved in this type of therapy - 0.55 mmol/L; it was not a statistically significant difference. PMID:17536489

  3. Free DNA in serum and plasma from normal adults.

    PubMed Central

    Steinman, C R

    1975-01-01

    Circulating DNA has been associated with several human disorders, including the nephritis of systemic lupus erythematosus (SLE), in which it is thought to play an etiological role. However, it remains unclear whether its appearance in the circulation is truly pathological. Several reports, each generally based on a single assay method, have disagreed as to whether DNA may circulate in normals. Some, but not all, of this disagreement may be explained by the recently described appearance of DNA in serum, but not plasma, apparently as the result of release from leukocytes in vitro. In the present report an attempt is made to clarify this problem. Normal plasma and serum samples were examined by four assays for DNA that were newly modified to enhance their specificity and/or sensitivity. Plasma DNA was undetectable by all four methods, the most sensitive of which could detect 0.05 mug/ml of native DNA (nDNA) or 0.1 mug/ml of single-stranded DNA (ssDNA). Serum DNA was present in 14 of 16 samples tested in variable concentrations with an estimated mean of 1.9 mug/ml. It is concluded that the appearance of DNA in adult human plasma is a pathological event. Presumably, previous reports describing detection of DNA in normal plasma were based on the measurement of non-DNAase-sensitive interfering substance. Furthermore, it is emphasized that the use of serum in studies dependent on sensitive assays for DNA (or anti-DNA antibody) introduces an ambiguity that may be avoided by substitution of carefully collected plasma for serum. PMID:1150882

  4. Associations between serum lipids and hepatitis C antiviral treatment efficacy

    PubMed Central

    Ramcharran, Darmendra; Wahed, Abdus S.; Conjeevaram, Hari S.; Evans, Rhobert W.; Wang, Tianyi; Belle, Steven H.; Yee, Leland J.

    2010-01-01

    Approximately one half of patients who undergo antiviral therapy for chronic hepatitis C virus (HCV) genotype 1 infection will not respond to treatment. African Americans (AAs) are less responsive to treatment than Caucasian Americans (CAs) and the reasons for this disparity are largely unknown. Recent studies suggest that serum lipids may be associated with treatment response. The aims of this study were to evaluate baseline and changes in serum lipids during therapy, determine if serum lipids are associated with virological response, and assess if these measures explain the racial difference in efficacy. Participants were from Virahep-C, a prospective study of treatment naïve participants with type 1 HCV infection who received peginterferon alfa-2a (PEG-IFN) plus ribavirin therapy for up to 48 weeks. Fasting serum lipids were analyzed at baseline, during, and after therapy in 160 AAs and 170 CAs. A relative risk (RR) model was employed to evaluate characteristics associated with sustained virological response (SVR). Antiviral therapy was associated with changes in serum lipids during and after antiviral therapy, with the changes differing by race and the amount of PEG-IFN taken. Baseline lipid measures independently associated with a higher rate of SVR were lower TG and higher LDLc, with an interaction between high density lipoprotein cholesterol (HDLc) and gender. Lipid measures did not contribute significantly to explaining the racial difference in SVR. Conclusion Lipid levels are associated with SVR, although lipid parameters did not explain the racial difference in treatment response. Results are compatible with proposed biological mechanisms of HCV entry, replication, and secretion, and may underscore new potential therapeutic targets for HCV eradication. PMID:20690192

  5. Serum Calcium Increase Correlates With Worsening of Lipid Profile

    PubMed Central

    Gallo, Luigia; Faniello, Maria C.; Canino, Giovanni; Tripolino, Cesare; Gnasso, Agostino; Cuda, Giovanni; Costanzo, Francesco S.; Irace, Concetta

    2016-01-01

    Abstract Despite the well-documented role of calcium in cell metabolism, its role in the development of cardiovascular disease is still under heavy debate. Several studies suggest that calcium supplementation might be associated with an increased risk of coronary heart disease, whereas others underline a significant effect on lowering high blood pressure and hyperlipidemia. The purpose of this study was to investigate, in a large nonselected cohort from South Italy, if serum calcium levels correlate with lipid values and can therefore be linked to higher individual cardiovascular risk. Eight-thousand-six-hundred-ten outpatients addressed to the Laboratory of Clinical Biochemistry, University of Magna Græcia, Catanzaro, Italy from January 2012 to December 2013 for routine blood tests, were enrolled in the study. Total HDL-, LDL- and non-HDL colesterol, triglycerides, and calcium were determined with standard methods. We observed a significant association between total cholesterol, LDL-cholesterol, HDL-cholesterol, non-HDL cholesterol, triglycerides, and serum calcium in men and postmenopause women. Interestingly, in premenopause women, we only found a direct correlation between serum calcium, total cholesterol, and HDL-cholesterol. Calcium significantly increased while increasing total cholesterol and triglycerides in men and postmenopause women. Our results confirm that progressive increase of serum calcium level correlates with worsening of lipid profile in our study population. Therefore, we suggest that a greater caution should be used in calcium supplement prescription particularly in men and women undergoing menopause, in which an increase of serum lipids is already known to be associated with a higher cardiovascular risk. PMID:26937904

  6. Serum Amyloid A (SAA): a Novel Biomarker for Endometrial Cancer

    PubMed Central

    Cocco, Emiliano; Bellone, Stefania; El-Sahwi, Karim; Cargnelutti, Marilisa; Buza, Natalia; Tavassoli, Fattaneh A.; Schwartz, Peter E.; Rutherford, Thomas J.; Pecorelli, Sergio; Santin, Alessandro D.

    2009-01-01

    Background We investigated the expression of Serum-Amyloid-A (SAA) in endometrial endometrioid carcinoma (EEC), and evaluated its potential as a serum biomarker. Methods SAA gene and protein expression levels were evaluated in EEC and normal endometrial tissues (NEC), by real time-PCR, immunohistochemistry (IHC) and flow cytometry. SAA concentration in 194 serum samples from 50 healthy-women, 42 women with benign diseases and 102 patients including 49 grade-1, 38 grade-2 and 15 grade-3 EEC was also studied by a sensitive bead-based-immunoassay. Results SAA gene expression levels were significantly higher in EEC when compared to NEC (mean-copy-number by RT-PCR = 182 vs 1.9; P=0.001). IHC revealed diffuse cytoplasmic SAA protein staining in poorly differentiated EEC tissues. High intracellular levels of SAA were identified in primary EEC cell lines evaluated by flow cytometry and SAA was found to be actively secreted in vitro. SAA concentrations (μg/ml) had medians of 6.0 in normal healthy females and 6.0 in patients with benign disease (P=0.92). In contrast, SAA values in the serum of EEC patients had a median of 23.7 significantly higher than those of the healthy group (P=0.001) and benign group (P=0.001). Patients harboring G3 EEC were found to have SAA concentrations significantly higher than G1/G2 patients. Conclusions SAA is not only a liver-secreted-protein but is also an EEC-cell product. SAA is expressed and actively secreted by G3-EEC and it is present in high concentration in the serum of EEC patients. SAA may represent a novel biomarker for EEC to monitor disease recurrence and response to therapy. PMID:20041483

  7. Probing peptide amphiphile self-assembly in blood serum.

    PubMed

    Ghosh, Arijit; Buettner, Christian J; Manos, Aaron A; Wallace, Ashley J; Tweedle, Michael F; Goldberger, Joshua E

    2014-12-01

    There has been recent interest in designing smart diagnostic or therapeutic self-assembling peptide or polymeric materials that can selectively undergo morphological transitions to accumulate at a disease site in response to specific stimuli. Developing approaches to probe these self-assembly transitions in environments that accurately amalgamate the diverse plethora of proteins, biomolecules, and salts of blood is essential for creating systems that function in vivo. Here, we have developed a fluorescence anisotropy app