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Sample records for serum tgf-beta1 se-cad

  1. Chronic treatment with angiotensin AT1 receptor antagonists reduced serum but not bone TGF-beta1 levels in ovariectomized rats.

    PubMed

    Li, Yong-Qi; Ji, Hui; Shen, Yang; Ding, Li-Ju; Zhuang, Pei; Yang, Yu-Lin; Huang, Qiu-Ju

    2009-01-01

    Approximately 50% of hypertensive patients are postmenopausal women; therefore, any antihypertensive therapy must not adversely affect bone loss in this population. Recently, however, concern has been raised that use of angiotensin AT1 receptor antagonists may increase the tendency to develop postmenopausal osteoporosis by decreasing transforming growth factor-beta1 (TGF-beta1), which has been implicated in bone mass maintenance. In the present study, we selected telmisartan and valsartan as representatives of angiotensin AT1 receptor antagonists and used ovariectomized (OVX) rats as a model of human postmenopausal osteoporosis. After 3 months treatment with telmisartan (5 mg/kg daily) or valsartan (10 mg/kg daily), OVX rats showed no signs of adverse effects on bone mineral density of the lumbar vertebrae (L1-L5) or the total femur, nor did treatment affect serum levels of osteocalcin and osteoclast-derived tartrate-resistant acid phosphatase (TRACP-5b). Bone TGF-beta1 content remained unchanged, although treatment with telmisartan and valsartan significantly reduced serum TGF-beta1 levels (p < 0.05). In conclusion, chronic treatment with angiotensin AT1 receptor antagonists reduced serum but not bone TGF-beta1 levels and did not accelerate ovariectomy-induced bone loss in rats.

  2. Endocrine expression of the active form of TGF-beta1 in the TGF-beta1 null mice fails to ameliorate lethal phenotype.

    PubMed

    Longenecker, Glenn; Thyagarajan, Tamizchelvi; Nagineni, Chandrasekharam N; Flanders, Kathleen C; Factor, Valentina; Miller, Georgina; Ward, Jerrold M; Nalca, Aysegul; Rangnekar, Vivek M; Thorgeirsson, Snorri; Kulkarni, Ashok B

    2002-04-01

    TGF-beta1 null mice die by 3 to 4 weeks of age due to a severe autoimmune-mediated multifocal inflammation resulting in multi-organ failure. To assess the therapeutic potential of circulating levels of active TGF-beta1, we generated mice with endocrine expression of active TGF-beta1 on a TGF-beta1 null background (TGF-beta1 (-/-/TG)) by crossing TGF-beta1(+/-) mice with transgenic mice (TG) that express recombinant TGF-beta1 specifically in the liver and secrete it in the blood. The TGF-beta1 (-/-/TG) mice exhibit a survival profile similar to the TGF-beta1 (-/-) mice indicating a failure to rescue the lethal phenotype. However, serum TGF-beta1 levels in the TGF-beta1 (-/-/TG) mice were restored to near normal levels with expression in all the tissues, notably in the kidney and spleen. Histopathology showed reduced inflammation in the target tissues, especially in the heart. Interestingly, unlike TGF-beta1 (-/-) mice, the TGF-beta1 (-/-/TG) mice have glomerulonephritis in their kidneys similar to the TG mice. Thus, the phenotype of TGF-beta1 (-/-/TG) animal model indicates the potential role of circulating active-TGF-beta1 in reducing inflammation, but its failure to rescue lethality in TGF-beta1 null mice indicates a critical autocrine role of TGF-beta1.

  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. 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

  5. Ursolic acid, an antagonist for transforming growth factor (TGF)-beta1.

    PubMed

    Murakami, Shigeru; Takashima, Hajime; Sato-Watanabe, Mariko; Chonan, Sumi; Yamamoto, Koji; Saitoh, Masako; Saito, Shiuji; Yoshimura, Hiromitsu; Sugawara, Koko; Yang, Junshan; Gao, Nannan; Zhang, Xinggao

    2004-05-21

    Transforming growth factor-beta (TGF-beta), a multifunctional cytokine which is involved in extracellular matrix modulation, has a major role in the pathogenesis and progression of fibrotic diseases. We now report the effects of ursolic acid on TGF-beta1 receptor binding and TGF-beta1-induced cellular functions in vitro. Ursolic acid inhibited [(125)I]-TGF-beta1 receptor binding to Balb/c 3T3 mouse fibroblasts with an IC(50) value of 6.9+/-0.8 microM. Ursolic acid dose-dependently recovered reduced proliferation of Minc Mv1Lu cells in the presence of 5 nM of TGF-beta1 and attenuated TGF-beta1-induced collagen synthesis and production in human fibroblasts. Molecular dynamics simulations suggest that ursolic acid may interact with the hydrophobic region of the dimeric interface and thereby inhibit the binding of TGF-beta1 to its receptor. All these findings taken together show that ursolic acid functions as an antagonist for TGF-beta1. This is the first report to show that a small molecule can inhibit TGF-beta1 receptor binding and influence functions of TGF-beta1.

  6. 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

  7. The effects of shockwave on bone healing and systemic concentrations of nitric oxide (NO), TGF-beta1, VEGF and BMP-2 in long bone non-unions.

    PubMed

    Wang, Ching-Jen; Yang, Kunder D; Ko, Jih-Yang; Huang, Chung-Cheng; Huang, Hsuan-Ying; Wang, Feng-Sheng

    2009-06-01

    This study investigated the effects of extracorporeal shockwave treatment (ESWT) on bone healing and the systemic concentrations of nitric oxide (NO), TGF-beta1, VEGF and BMP-2 in long bone non-unions. Forty-two patients with 42 established non-unions of the femur and tibia were enrolled in this study. Each long bone non-union was treated with 6000 impulses of shockwave at 28 kV in a single session. Ten milliliters of peripheral blood were obtained for measurements of serum NO level and osteogenic growth factors including TGF-beta1, VEGF and BMP-2; serum levels of calcium, alkaline phosphatase, calcitonin and parathyroid hormone before treatment and at 1 day, 1, 3 and 6 months after treatment. The evaluations for bone healing included clinical assessments and serial radiographic examinations. At 6 months, bony union was radiographically confirmed in 78.6%, and persistent non-union in 21.4%. Patients with bony union showed significantly higher serum NO level, TGF-beta1, VEGF and BMP-2 at 1 month after treatment as compared to patients with persistent non-union. Shockwave-promoted bone healing was associated with significant increases in serum NO level and osteogenic growth factors. The elevations of systemic concentration of NO level and the osteogenic factors may reflect a local stimulation of shockwave in bone healing in long bone non-unions.

  8. 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

  9. 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

  10. 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.

  11. ClC-5 regulates dentin development through TGF-beta1 pathway.

    PubMed

    Duan, Xiaohong; Mao, Yong; Yang, Ting; Wen, Xuan; Wang, Huan; Hou, Jin; Xue, Yang; Zhang, Rong

    2009-12-01

    ClC-5 is one of the voltage-dependent chloride channel (ClC) family members. Mutations involving CLCN5 cause an X-linked nephropathy associated with Dent's disease. Some Clcn5 gene knockout (ClC-5 KO) mice have abnormal growth of the teeth; however, the expression and function of ClC-5 during tooth development is still unknown. Herein we report abnormal dentin structure, decreased DSPP and increased TGF-beta1 protein level in ClC-5 KO teeth. In odontoblast-like MDPC-23 cells, the mRNA levels of Tgfb1, Dspp and Dmp-1 were upregulated with Clcn5 RNAi after 48h treatment; whilst there was no change in those of TGF-beta receptor Tgfbr1 and Tgfbr2. We suggest that the dentin changes in ClC-5 KO mice might be a result of increasing TGF-beta1, and the interplay between ClC-5 and TGF-beta1 needs further identified.

  12. TGF-beta1 regulates the expression of multiple max-interacting transcription factors in Balb/MK cells: implications for understanding the mechanism of action of TGF-beta1.

    PubMed

    Satterwhite, D J; White, R L; Aakre, M E; Moses, H L

    2001-07-01

    Appropriate transforming growth factor-beta1 (TGF-beta1) signaling is required to preserve homeostasis of diverse tissues during development. At the cellular level, one function of TGF-beta1 that is critical for preserving homeostasis is the ability to arrest cell growth. TGF-beta1 arrests growth by blocking the function of the c-myc proto-oncogene. c-myc function is determined by the level of c-myc expression relative to other Max-interacting transcription factors, and TGF-beta1 has been shown to inhibit c-myc expression by inhibiting c-myc transcription. However, whether TGF-beta1 might also increase the expression of a Max-interacting factor that blocks myc function by competing with myc for Max binding is not known. Therefore, we determined the effect of TGF-beta1 on the expression of Max-interacting transcription factors in Balb/MK cells. We found unexpectedly that Balb/MK cells express both N-myc and c-myc. The pattern of N-myc expression during the cell cycle differs from that of c-myc, indicating that mRNA accumulation is controlled by mechanisms specific to each gene. TGF-beta1 rapidly inhibits N-myc mRNA expression; thus N-myc is a novel target of TGF-beta1 in Balb/MK cells. More importantly, we found that TGF-beta1 induces the expression of the putative tumor suppressor genes Mad4 and Mxi1 in both the Balb/MK and Mv1Lu cell lines. Mad4 and Mxi1 are novel targets of TGF-beta1, known to inhibit cell growth by antagonizing the interaction of Myc with Max. Thus, our results suggest that the induction of Mad4 and Mxi1 may function in tandem with the inhibition of N-myc and c-myc to mediate the growth inhibitory function of TGF-beta1. PMID:11420421

  13. Increased proteasome-dependent degradation of estrogen receptor-alpha by TGF-beta1 in breast cancer cell lines.

    PubMed

    Petrel, Trevor A; Brueggemeier, Robert W

    2003-01-01

    Normal mammary epithelial cells are rapidly induced to G(1) arrest by the widely expressed cytokine, transforming growth factor beta (TGF-beta1). Studies in established breast cancer cell lines that express the estrogen receptor alpha (ERalpha) have demonstrated loss of this responsiveness. This inverse correlation suggests interpathway signaling important to cell growth and regulation. The adenocarcinoma breast cell line BT474, which was not growth arrested by TGF-beta1, was used as a model of estrogen-inducible growth to explore interpathway crosstalk. Although BT474 cells were not growth-arrested by TGF-beta1 as determined by flow cytometry analysis and 5'-bromo-3'-deoxyuridine incorporation into DNA, estrogen receptor protein levels were attenuated by 100 pM TGF-beta1 after 6 h. This decrease in ERalpha reached 50% of untreated control levels by 24 h of treatment and was further supported by a 50% decrease in estrogen-inducible DNA synthesis. Inspection of ERalpha transcripts suggested that this decrease was primarily the result of altered ERalpha protein stability or availability. Use of the proteasome inhibitor, MG132, abolished all effects on ERalpha by TGF-beta1. Collectively, this data supports a role for TGF-beta1 in regulating the growth of otherwise insensitive breast cancer cells through modulation of ERalpha stability. PMID:12461787

  14. Mechanisms of TGF-beta1-induced intimal growth: plasminogen-independent activities of plasminogen activator inhibitor-1 and heterogeneous origin of intimal cells.

    PubMed

    Otsuka, Goro; Stempien-Otero, April; Frutkin, Andrew D; Dichek, David A

    2007-05-11

    Transforming growth factor (TGF)-beta(1) is a potent stimulator of intimal growth. We showed previously that TGF-beta(1) stimulates intimal growth through early upregulation of plasminogen activator inhibitor-1 (PAI-1) and, subsequently, PAI-1-dependent increases in cell migration and matrix accumulation. We also showed that PAI-1 negatively regulates TGF-beta(1) expression in the artery wall. Here we use plasminogen-deficient mice to test whether TGF-beta(1)-stimulated, PAI-1-dependent intimal growth and PAI-1 suppression of TGF-beta(1) expression are mediated through inhibition of plasminogen activation by PAI-1. We also use lineage tracing to investigate the origin of cells in TGF-beta(1)-induced intimas. Surprisingly, both TGF-beta(1)-induced, PAI-1-dependent intimal growth and PAI-1 suppression of TGF-beta(1) expression are independent of plasminogen. Moreover, approximately 50% of cells that migrate into the intima of TGF-beta(1)-overexpressing arteries carry a smooth muscle lineage marker, <1% carry a bone marrow lineage marker, and the remaining cells carry neither marker. Therefore, PAI-1 stimulates intimal growth and suppresses TGF-beta(1) expression through activities other than inhibition of plasminogen activation. In addition, contrary to widely held models, our results do not support a role for plasmin (or thrombospondin) in TGF-beta(1) activation in the artery wall. Further identification of the molecular targets through which PAI-1 stimulates intimal formation and suppresses TGF-beta(1) expression in the artery wall may reveal new approaches for inhibiting intimal formation. Our studies also discount bone marrow as an important source from which TGF-beta(1) recruits intimal cells and suggest instead that TGF-beta(1) induces substantial cell migration either from the adventitia or from an extravascular, but nonhematopoietic source.

  15. 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.

  16. TGF-beta1 and WISP-1/CCN-4 can regulate each other's activity to cooperatively control osteoblast function.

    PubMed

    Inkson, Colette A; Ono, Mitsuaki; Kuznetsov, Sergei A; Fisher, Larry W; Robey, Pamela Gehron; Young, Marian F

    2008-08-01

    Wnt-induced secreted protein-1 (WISP-1), like other members of the CCN family, is expressed in skeletal tissues. Its mechanism of action remains unknown. Expression of WISP-1 was analyzed in human bone marrow stroma cells (hBMSC) by RT-PCR. We identified two major transcripts corresponding to those of full-length WISP-1, and of the splice variant WISP-1va which lacks a putative BMP/TGF-beta binding site. To investigate the function of WISP-1 in bone, hBMSC cultures were treated with recombinant human (rh)WISP-1 and analyzed for proliferation and osteogenic differentiation. WISP-1 treatment increased both BrdU incorporation and alkaline phosphatase (AP) activity. Considering the known functional synergy found between the TGF-beta super-family and members of the CCN family, we next tested the effect of WISP-1 on TGF-beta1 activity. We found that rhWISP-1 could reduce rhTGF-beta1 induced BrdU incorporation. Similarly, rhTGF-beta1 inhibited rhWISP-1 induction of AP activity. To explore functional differences between the WISP-1 variants, WISP-1 or WISP-1va were transfected into hBMSC. Both variants could strongly induce BrdU incorporation. However, there were no effects of either variant on AP activity without an additional osteogenic stimulus such as TGF-beta1. Taken together our results suggest a functional relationship between WISP-1 and TGF-beta1. To further define this relationship we analyzed the effect of WISP-1 on TGF-beta signaling. rhWISP-1 significantly reduced TGF-beta1 induced phosphorylation of Smad-2. Our data indicates that full-length WISP-1 and its variant WISP-1va are modulators of proliferation and osteogenic differentiation, and may be novel regulators of TGF-beta1 signaling in osteoblast-like cells.

  17. Transforming growth factor beta 1 (TGF beta 1) is an autocrine positive regulator of colon carcinoma U9 cells in vivo as shown by transfection of a TGF beta 1 antisense expression plasmid.

    PubMed

    Huang, F; Newman, E; Theodorescu, D; Kerbel, R S; Friedman, E

    1995-12-01

    A transforming growth factor beta1 (TGF beta1) antisense expression plasmid under constitutive control of the Rous sarcoma virus promoter was introduced into the highly tumorigenic and invasive colon carcinoma U9A cell line, which uses its autocrine TGF beta1 as a growth-stimulating factor. Stable transfectants were infrequent, and only the K6 transfectant exhibited 39 and 33%, respectively, of the levels of TGF beta1 mRNA and active, secreted TGF beta1 protein of the parental line. K6 exhibited no change in TGF beta2 expression, and TGF beta3 expression was not detected in either parental or transfectant cells. Compared to the parental line, the K6 antisense transfectant exhibited a 3-fold increase in lag time in anchorage-dependent colony formation. The parental line was 44 times as invasive through a collagen l-coated polycarbonate membrane in vitro as K6 cells and, after s.c. injection at low-cell inocula, U9A cells induced tumors 75 times as large in vivo as did the K6 antisense transfectant. The decreases in in vitro invasion and anchorage-dependent colony formation seen in K6 cells were largely reversed by the addition of TGF beta1. Tumors that did arise from the K6 antisense transfectant cells had lost antisense TGF beta1 expression and expressed the same TGF beta1 mRNA levels as controls. U9A cells were more metastatic to the liver after intrasplenic injection than K6 cells. These findings demonstrate a role for autocrine TGE beta1 in colon cancer tumorigenicity and invasion. They also show that a relatively small decrease in TGF beta1 levels was enough to markedly decrease colon carcinoma cell aggressiveness. This is not unprecedented, as we had found in an earlier study that a small, 2-4-fold increase in TGF beta1 protein levels in human colon cancers correlated with disease progression to metastases (E. Friedman et al., Cancer Epidemiol, Biomarkers & Prev., 4:549-554, 1995).

  18. Controlled release of TGF-beta 1 from RADA self-assembling peptide hydrogel scaffolds

    PubMed Central

    Zhou, Ao; Chen, Shuo; He, Bin; Zhao, Weikang; Chen, Xiaojun; Jiang, Dianming

    2016-01-01

    Bioactive mediators, cytokines, and chemokines have an important role in regulating and optimizing the synergistic action of materials, cells, and cellular microenvironments for tissue engineering. RADA self-assembling peptide hydrogels have been proved to have an excellent ability to promote cell proliferation, wound healing, tissue repair, and drug delivery. Here, we report that D-RADA16 and L-RADA16-RGD self-assembling peptides can form stable second structure and hydrogel scaffolds, affording the slow release of growth factor (transforming growth factor cytokine-beta 1 [TGF-beta 1]). In vitro tests demonstrated that the plateau release amount can be obtained till 72 hours. Moreover, L-RADA16, D-RADA16, and L-RADA16-RGD self-assembling peptide hydrogels containing TGF-beta 1 were used for 3D cell culture of bone mesenchymal stem cells of rats for 2 weeks. The results revealed that these three RADA16 peptide hydrogels had a significantly favorable influence on proliferation of bone mesenchymal stem cells and hold some promise in slow and sustained release of growth factor. PMID:27703332

  19. 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.

  20. 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.

  1. Interactions between TGF-beta1 and TGF-beta3 and their role in medial edge epithelium cell death and palatal fusion in vitro.

    PubMed

    Murillo, Jorge; Maldonado, Estela; Barrio, Maria Carmen; Del Río, Aurora; López, Yamila; Martínez-Sanz, Elena; González, Ignacio; Martín, Concepción; Casado, Inmaculada; Martínez-Alvarez, Concepción

    2009-02-01

    In recent decades, studies have shown that both TGF-beta(1) and TGF-beta(3) play an important role in the induction of medial edge epithelium (MEE) cell death and palatal fusion. Many of these experiments involved the addition or blockage of one of these growth factors in wild-type (WT) mouse palate cultures, where both TGF-beta(1) and TGF-beta(3) are present. Few studies have addressed the existence of interactions between TGF-beta(1) and TGF-beta(3), which could modify their individual roles in MEE cell death during palatal fusion. We carried out several experiments to test this possibility, and to investigate how this could influence TGF-beta(1) and TGF-beta(3) actions on MEE cell death and palatal shelf fusion. We double-immunolabelled developing mouse palates with anti-TGF-beta(1) or anti-TGF-beta(3) antibodies and TUNEL, added rhTGF-beta(1) or rhTGF-beta(3) or blocked the TGF-beta(1) and TGF-beta(3) action at different concentrations to WT or Tgf-beta(3) null mutant palate cultures, performed in situ hybridizations with Tgf-beta(1) or Tgf-beta(3) riboprobes, and measured the presence of TUNEL-positive midline epithelial seam (MES) cells and MES disappearance (palatal shelf fusion) in the different in vitro conditions. By combining all these experiments, we demonstrate great interaction between TGF-beta(1) and TGF-beta(3) in the developing palate and confirm that TGF-beta(3) has a more active role in MES cell death than TGF-beta(1), although both are major inductors of MES disappearance. Finally, the co-localization of TGF-beta(1), but not TGF-beta(3), with TUNEL in the MES allows us to suggest a possible role for TGF-beta(1) in MES apoptotic clearance.

  2. 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

  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. 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

  5. TGF-beta 1 downregulates CFTR expression and function in nasal polyps of non-CF patients.

    PubMed

    Prulière-Escabasse, Virginie; Fanen, Pascale; Dazy, Anne Catherine; Lechapt-Zalcman, Emmanuèle; Rideau, Dominique; Edelman, Aleksander; Escudier, Estelle; Coste, André

    2005-01-01

    Nasal polyposis is a chronic inflammatory disease of the upper airways. It has been suggested that ion transports and CFTR expression could be modified in epithelial cells from nasal polyps of non-cystic fibrosis patients. We compared human nasal epithelial cells from nasal polyps (NP) with control nasal mucosa (CM). The level of CFTR mRNA was studied by Northern blot analysis and protein expression was studied by immunoprecipitation both ex vivo and in vitro in primary cultures of human nasal epithelial cells at the air-liquid interface. Ion transports were evaluated by short-circuit measurements in vitro. CFTR gene and protein expressions were significantly decreased in NP native tissues and in culture on day 4, when a global defect of ion transports was observed in NP cultures, but not in CM. We evaluated the effect of transforming growth factor (TGF)-beta 1 on CFTR expression and function in NP cultures on day 14 and showed, for the first time, that TGF-beta 1 was able to significantly downregulate the level of CFTR mRNA and cAMP-dependent current in NP cultures. Finally, we showed that the effects of TGF-beta 1 on ion transports could be reversed after 48-h removal of TGF-beta1 in NP cultures. In conclusion, our data strongly suggest that chronic inflammation in nasal polyposis downregulates CFTR gene and protein expression.

  6. 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.

  7. 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.

  8. Regulation of the friction coefficient of articular cartilage by TGF-beta1 and IL-1beta.

    PubMed

    DuRaine, Grayson; Neu, Corey P; Chan, Stephanie M T; Komvopoulos, Kyriakos; June, Ronald K; Reddi, A Hari

    2009-02-01

    Articular cartilage functions to provide a low-friction surface for joint movement for many decades of life. Superficial zone protein (SZP) is a glycoprotein secreted by chondrocytes in the superficial layer of articular cartilage that contributes to effective boundary lubrication. In both cell and explant cultures, TGF-beta1 and IL-1beta have been demonstrated to, respectively, upregulate and downregulate SZP protein levels. It was hypothesized that the friction coefficient of articular cartilage could also be modulated by these cytokines through SZP regulation. The friction coefficient between cartilage explants (both untreated and treated with TGF-beta1 or IL-1beta) and a smooth glass surface due to sliding in the boundary lubrication regime was measured with a pin-on-disk tribometer. SZP was quantified using an enzyme-linked immunosorbant assay and localized by immunohistochemistry. Both TGF-beta1 and IL-1beta treatments resulted in the decrease of the friction coefficient of articular cartilage in a location- and time-dependent manner. Changes in the friction coefficient due to the TGF-beta1 treatment corresponded to increased depth of SZP staining within the superficial zone, while friction coefficient changes due to the IL-1beta treatment were independent of SZP depth of staining. However, the changes induced by the IL-1beta treatment corresponded to changes in surface roughness, determined from the analysis of surface images obtained with an atomic force microscope. These findings demonstrate that the low friction of articular cartilage can be modified by TGF-beta1 and IL-1beta treatment and that the friction coefficient depends on multiple factors, including SZP localization and surface roughness.

  9. 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

  10. 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.

  11. Downregulation of TGF-beta1 mRNA and protein in the muscles of patients with inflammatory myopathies after treatment with high-dose intravenous immunoglobulin.

    PubMed

    Amemiya, K; Semino-Mora, C; Granger, R P; Dalakas, M C

    2000-02-01

    We used reverse transcription-polymerase chain reaction to study the level of TGF-beta1 mRNA expression and immunocytochemistry to examine the immunoreactive TGF-beta1 in muscle biopsy specimens from five patients with dermatomyositis (DM) and five patients with inclusion body myositis (IBM) obtained before and after 3 months treatment with intravenous immunoglobulin (IVIg). At baseline, the mRNA expression of TGF-beta1 was increased up to fivefold in the muscles of DM patients compared to that of IBM patients. After IVIg, TGF-beta1 was downregulated and the TGF-beta1 mRNA decreased twofold in the muscles of patients with DM who had successfully responded to therapy, but remained unchanged in the muscles of patients with IBM who did not respond. The downregulation of TGF-beta1 in DM was associated with improvement of the muscle cytoarchitecture and reduction of the endomysial inflammation and connective tissue, suggesting that in DM the excess of TGF-beta1 may be involved in the pathogenesis of chronic inflammation, fibrosis, and accumulation of extracellular matrix proteins.

  12. 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

  13. 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.

  14. PPARdelta promotes wound healing by up-regulating TGF-beta1-dependent or -independent expression of extracellular matrix proteins.

    PubMed

    Ham, Sun Ah; Kim, Hyo Jung; Kim, Hyun Joon; Kang, Eun Sil; Eun, So Young; Kim, Gil Hyeong; Park, Myung Hyun; Woo, Im Sun; Kim, Hye Jung; Chang, Ki Churl; Lee, Jae Heun; Seo, Han Geuk

    2010-06-01

    Although the peroxisome proliferator-activated receptor (PPAR) delta has been implicated in the wound healing process, its exact role and mechanism of action have not been fully elucidated. Our previous findings showed that PPARdelta induces the expression of the transforming growth factor (TGF)-beta1, which has been implicated in the deposit of extracellular matrix proteins. Here, we demonstrate that administration of GW501516, a specific PPARdelta ligand, significantly promoted wound closure in the experimental mouse and had a profound effect on the expression of collagen types I and III, alpha-smooth muscle actin, pSmad3 and TGF-beta1, which play a pivotal role in wound healing processes. Activation of PPARdelta increased migration of human epidermal keratinocytes and dermal fibroblasts in in vitro scrape-wounding assays. Addition of a specific ALK5 receptor inhibitor SB431542 significantly suppressed GW501516-induced migration of human keratinocytes and fibroblasts. In these cells, activated PPARdelta also induced the expression of collagen types I and III and fibronectin in a TGF-beta1-dependent or -independent manner. The effect of PPARdelta on the expression of type III collagen was dually regulated by the direct binding of PPARdelta and Smad3 to a direct repeat-1 site and a Smad-binding element, respectively, of the type III gene promoter. Taken together, these results demonstrated that PPARdelta plays an important role in skin wound healing in vivo and that it functions by accelerating extracellular matrix-mediated cellular interactions in a process mediated by the TGF-beta1/Smad3 signaling-dependent or - independent pathway.

  15. Immunohistochemical identification of TGF-beta1 at the maxillaries in growing Sprague-Dawley rats and after muscle section.

    PubMed

    Rubert, A; Manzanares, M C; Ustrell, J M; Duran, J; Pérez-Tomás, R

    2008-04-01

    Growth factors are currently being extensively studied in the literature to ascertain their role during maxillofacial development. Taking into account that few investigations refer to the functions of growth in the maxillaries, our aim was to identify the TGF-beta1 immunohistochemical expression pattern in the maxillaries of growing rats. A secondary aim was to identify this pattern after orofacial function inhibition by muscle section. In the palate and the mandibular symphysis and body, we found that bone was formed through an endomembranous pathway with intense TGF-beta1 staining inside chondroid cells during the maximum development stages. At the midpalatal suture and the mandibular symphysis and condyle, endochondral ossification was detected with an intense expression of TGF-beta1 inside the chondrocytes when major growth occurred. After the muscle had been sectioned, at the mandible the maturation process was accelerated, this change being transitory until muscular function was recovered. However, at the palate, the intervention caused a greater disturbance of the growing pattern, which did not recover normality.

  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. Transforming growth factor-beta 1 (TGF-beta1) prevents the age-dependent decrease in bone formation in human osteoblast/implant cultures.

    PubMed

    Zhang, Hai; Aronow, Michael S; Gronowicz, Gloria A

    2005-10-01

    Titanium implants have been extensively used in orthopedic surgery and dentistry. Most of the patients who receive such implants are elderly with a compromised ability to heal and form new bone. By using an in vitro osteoblast/implant culture system, the potency of TGF-beta1 in enhancing mineralization of human osteoblast cultures from elderly subjects was investigated in this study. Primary human osteoblast (HOB) cells obtained from different age group human subjects [Young (Y), Middle (M), and Old (O)] were cultured on Ti alloy (Ti-6Al-4V) disks with or without continuous administration of 0.2 ng/mL TGF-beta1 in the medium for 2 or 4 weeks. TGF-beta1 significantly (p < 0.05) increased calcium content and the size of calcified nodules on implant disks in the O group, but had no effect on the Y or M groups. The number of calcified nodules was not different with or without TGF-beta1 in all age groups. As measured by Northern blot analysis and RT-PCR, TGF-beta1 significantly increased the expression of bone-specific extracellular matrix proteins, including alkaline phosphatase, Type I collagen, bone sialoprotein and osteocalcin, after both 2 and 4 weeks in the O group but not in the Y group. In conclusion, TGF-beta1 enhances mineralization on implant materials of osteoblast cultures from elderly human subjects.

  19. Disruption of anterior segment development by TGF-beta1 overexpression in the eyes of transgenic mice.

    PubMed

    Flügel-Koch, Cassandra; Ohlmann, Andreas; Piatigorsky, Joram; Tamm, Ernst R

    2002-10-01

    Previous experiments showed that transgenic mice expressing a secreted self-activating transforming growth factor (TGF) -beta1 did not show a phenotype in the lens and cornea until postnatal day 21, when anterior subcapsular cataracts, sporadic thickening of the corneal stroma, and thinning of the corneal epithelium were noted (Srinivasan et al., 1998). To examine the effects of higher concentrations of TGF-beta1 on the lens and cornea, we constructed transgenic mice harboring the strong, lens-specific chicken betaB1-crystallin promoter driving an activated porcine TGF-beta1 gene. In contrast to the earlier study, the transgenic mice had microphthalmic eyes with closed eyelids. Already at embryonic day (E) 13.5, the future cornea of the transgenic mice was threefold thicker than that of wild-type littermates due to increased proliferation of corneal stromal mesenchyme cells. Staining of fibronectin and thrombospondin-1 was increased in periocular mesenchyme. At E17.5, the thickened transgenic corneal stroma was vascularized and densely populated by abundant star-shaped, neural cell adhesion molecule-positive cells of mesenchymal appearance surrounded by irregular swirls of collagen and extracellular matrix. The corneal endothelium, anterior chamber, and stroma of iris/ciliary body did not develop, and the transgenic cornea was opaque. Fibronectin, perlecan, and thrombospondin-1 were elevated, whereas type VI collagen decreased in the transgenic corneal stroma. Stromal mesenchyme cells expressed alpha-smooth muscle actin as did lens epithelial cells and cells of the retinal pigmented epithelium. By E17.5, lens fiber cells underwent apoptotic cell death that was followed by apoptosis of the entire anterior lens epithelium between E18.5 and birth. Posteriorly, the vitreous humor was essentially absent; however, the retina appeared relatively normal. Thus, excess TGF-beta1, a mitogen for embryonic corneal mesenchyme, severely disrupts corneal and lens differentiation

  20. 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

  1. 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.

  2. Periprosthetic breast capsules contain the fibrogenic cytokines TGF-beta1 and TGF-beta2, suggesting possible new treatment approaches.

    PubMed

    Kuhn, A; Singh, S; Smith, P D; Ko, F; Falcone, R; Lyle, W G; Maggi, S P; Wells, K E; Robson, M C

    2000-04-01

    Periprosthetic breast capsules composed of fibrotic collagenous material with increased collagen production are not dissimilar to other fibrotic conditions occurring in other organs. Fibrosis in the lung, liver, kidney, and skin has been associated with overproduction of the fibrogenic isoforms of transforming growth factor beta (TGF-beta1 and TGF-beta2). If periprosthetic breast capsules contained high levels of these cytokines, possibly new treatment approaches for capsular contraction could be proposed. Breast implant capsules of 35 patients harvested at the time of explantation were examined using indirect immunohistochemistry. Staining intensity for TGF-beta1 and TGF-beta2 was measured in all specimens. Immunohistochemical staining for TGF-beta1 and TGF-beta2 revealed that these two cytokines were present in all capsules analyzed. Minimal TGF-beta1 and TGF-beta2 were found in normal breast tissue. Levels of control vs. TGF-beta1 and control vs. TGF-beta2 were significant (p = 0.004 and p < 0.001 respectively). The presence of TGF-beta isoforms that are known to be fibrogenic may suggest new therapeutic approaches, which are being investigated for other fibrotic conditions.

  3. Differential effects of histone deacetylase inhibitors on phorbol ester- and TGF-beta1 induced murine tissue inhibitor of metalloproteinases-1 gene expression.

    PubMed

    Young, David A; Billingham, Olivia; Sampieri, Clara L; Edwards, Dylan R; Clark, Ian M

    2005-04-01

    Expression of the tissue inhibitor of metalloproteinases-1 (Timp-1) gene can be induced by either phorbol myristate acetate (PMA) or transforming growth factor beta1 (TGF-beta1), although the signalling pathways involved are not clearly defined. Canonically, histone deacetylase inhibitors (HDACi) such as trichostatin A (TSA) or sodium butyrate (NaB) increase total cellular histone acetylation and activate expression of susceptible genes. Remarkably, PMA and TGF-beta1 stimulation of Timp-1 show a differential response to TSA or NaB. TSA or NaB potentiate PMA-induced Timp-1 expression but repress TGF-beta1-induced Timp-1 expression. The repression of TGF-beta1-induced Timp-1 by TSA was maximal at 5 ng.mL(-1), while for the superinduction of PMA-induced Timp-1 expression, the maximal dose is > 500 ng x mL(-1) TSA. A further HDACi, valproic acid, did not block TGF-beta1-induced Timp-1 expression, demonstrating that different HDACs impact on the induction of Timp-1. For either PMA or TGF-beta1 to induce Timp-1 expression, new protein synthesis is required, and the induction of AP-1 factors closely precedes that of Timp-1. The effects of the HDACi can be reiterated in transient transfection using Timp-1 promoter constructs. Mutation or deletion of the AP-1 motif (-59/-53) in the Timp-1 promoter diminishes PMA-induction of reporter constructs, however, the further addition of TSA still superinduces the reporter. In c-Jun-/- cells, PMA still stimulates Timp-1 expression, but TSA superinduction is lost. Transfection of a series of Timp-1 promoter constructs identified three regions through which TSA superinduces PMA-induced Timp-1 and we have demonstrated specific protein binding to two of these regions which contain either an avian erythroblastosis virus E26 (v-ets) oncogene homologue (Ets) or Sp1 binding motif.

  4. 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

  5. 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.

  6. Iron chelation and a free radical scavenger suppress angiotensin II-induced upregulation of TGF-beta1 in the heart.

    PubMed

    Saito, Kan; Ishizaka, Nobukazu; Aizawa, Toru; Sata, Masataka; Iso-o, Naoyuki; Noiri, Eisei; Mori, Ichiro; Ohno, Minoru; Nagai, Ryozo

    2005-04-01

    Long-term administration of angiotensin II causes myocardial loss and cardiac fibrosis. We previously found iron deposition in the heart of the angiotensin II-infused rat, which may promote angiotensin II-induced cardiac damage. In the present study, we have investigated whether an iron chelator (deferoxamine) and a free radical scavenger (T-0970) affect the angiotensin II-induced upregulation of transforming growth factor-beta1 (TGF-beta1). Angiotensin II infusion for 7 days caused a robust increase in TGF-beta1 mRNA expression in vascular smooth muscle cells, myofibroblast-like cells, and migrated monocytes/macrophages. T-0970 and deferoxamine suppressed the upregulation of TGF-beta1 mRNA and reduced the extent of cardiac fibrosis in the heart of rats treated with angiotensin II. These agents blocked the angiotensin II-induced upregulation of heme oxygenase-1, a potent oxidative and cellular stress-responsive gene, but they did not significantly affect systolic blood pressure or plasma levels of aldosterone. In addition, T-0970 and deferoxamine suppressed the angiotensin II-induced upregulation of monocyte chemoattractant protein-1 in the heart. These results collectively suggest that iron and the iron-mediated generation of reactive oxygen species may contribute to angiotensin II-induced upregulation of profibrotic and proinflammatory genes, such as TGF-beta1 and monocyte chemoattractant protein-1.

  7. A transforming growth factor. beta. (TGF-. beta. ) receptor from human placenta exhibits greater affinity for TGF-. beta. 2 than for TGF-. beta. 1

    SciTech Connect

    Mitchell, E.J.; O'Connor-McCourt, M.D. )

    1991-04-30

    Affinity-labeling techniques have been used to identify three types of high-affinity receptors for transforming growth factor {beta} (TGF-{beta}) on the surface of many cells in culture. Here the authors demonstrate that membrane preparations from tissue sources may also be used as an alternative system for studying the binding properties of TGF-{beta} receptors. Using a chemical cross-linking technique with {sup 125}I-TGF-{beta}1 and {sup 125}I-TGF-{beta}2 and bis(sulfosuccinimidyl)suberate (BS{sup 3}), they have identified and characterized two high-affinity binding components in membrane preparations derived from human term placenta. The larger species, which migrates as a diffuse band of molecular mass 250-350 kDa on sodium dodecyl sulfate-polyacrylamide electrophoresis gels, is characteristic of the TGF-{beta} receptor type III, a proteoglycan containing glycosaminoglycan (GAG) chains of chondroitin and heparan sulfate. The smaller species of molecular mass 140 kDa was identified as the core glycoprotein of this type III receptor by using the techniques of enzymatic deglycosylation and peptide mapping. Competition experiments, using {sup 125}I-TGF-{beta}1 or {sup 125}I-TGF-{beta}2 and varying amounts of competing unlabeled TGF-{beta}1 or TGF-{beta}2, revealed that both the placental type III proteoglycan and its core glycoprotein belong to a novel class of type III receptors that exhibit a greater affinity for TGF-{beta}2 than for TGF-{beta}1. This preferential binding of TGF-{beta}2 to placental type III receptors suggests differential roles for TGF-{beta}2 and TGF-{beta} 1 in placental function.

  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. 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.

  10. Effects of initial boost with TGF-beta 1 and grade of intervertebral disc degeneration on 3D culture of human annulus fibrosus cells

    PubMed Central

    2014-01-01

    Background Three-dimensional (3D) culture in porous biomaterials as well as stimulation with growth factors are known to be supportive for intervertebral disc cell differentiation and tissue formation. Unless sophisticated releasing systems are used, however, effective concentrations of growth factors are maintained only for a very limited amount of time in in vivo applications. Therefore, we investigated, if an initial boost with transforming growth factor-beta 1 (TGF-beta 1) is capable to induce a lasting effect of superior cartilaginous differentiation in slightly and severely degenerated human annulus fibrosus (AF) cells. Methods Human AF tissue was harvested during surgical treatment of six adult patients with lumbar spinal diseases. Grading of disc degeneration was performed with magnet resonance imaging. AF cells were isolated and expanded in monolayer culture and rearranged three-dimensionally in a porous biomaterial consisting of stepwise absorbable poly-glycolic acid and poly-(lactic-co-glycolic) acid and a supportive fine net of non-absorbable polyvinylidene fluoride. An initial boost of TGF-beta 1 or TGF-beta 1 and hyaluronan was applied and compared with controls. Matrix formation was assessed at days 7 and 21 by (1) histological staining of the typical extracellular matrix molecules proteoglycan and type I and type II collagens and by (2) real-time gene expression analysis of aggrecan, decorin, biglycan, type I, II, III, and X collagens as well as of catabolic matrix metalloproteinases MMP-2 and MMP-13. Results An initial boost with TGF-beta 1 or TGF-beta 1 and hyaluronan did not enhance the expression of characteristic AF matrix molecules in our 3D culture system. AF cells showed high viability in the progressively degrading biomaterial. Stratification by grade of intervertebral disc degeneration showed that AF cells from both, slightly degenerated, or severely degenerated tissue are capable of significant up-regulations of characteristic matrix

  11. 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

  12. 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.

  13. Immunohistochemical analysis of bFGF, TGF-beta1 and catalase in rectus abdominis muscle from cattle foetuses at 180 and 260 days post-conception.

    PubMed

    Orzechowski, A; Gajkowska, B; Wojewódzka, U; Cassar-Malek, I; Picard, B; Hocquette, J F

    2002-12-01

    The potential for muscle growth depends on myoblast proliferation, which occurs essentially during the first two thirds of the foetal period in cattle. Thereafter, myofibres acquire their contractile and metabolic properties. Proliferation is regulated by molecular growth factors and by the tissue oxidative activity. The aim of this study was the quantification by immunochemistry of basic fibroblast growth factor (bFGF) and transforming growth factor beta 1 (TGF-beta1) and also of enzyme catalase (CAT) activity in rectus abdominis muscle. Samples were collected from cattle foetuses of different growth potential at 180 and 260 days post-conception (dpc). One major conclusion from this work is that protein contents of the muscle tissue bFGF and, to a lower extent, CAT activity decreased with increasing age during the foetal life. No differences were found between the different genotypes of cattle. However, the CAT to bFGF ratio tended to be lower in fast-growing cattle and increased with foetal age. TGF-beta1 did not change with age and was localised mostly at the vascular bed. CAT was detected in smooth and rough reticulum in striated muscles at 180dpc, and additionally in mitochondria at 260dpc. In conclusion, the balance between intracellular growth factors (bFGF and TGF-beta1) and the activity of antioxidant enzyme CAT may participate in the regulation of the transition from myoblast proliferation to differentiation. Thus, increased ratio of CAT to bFGF might be a good index indicating initiation of muscle maturation in cattle foetus prior to birth.

  14. Osteoarthritis in the temporo-mandibular joint (TMJ) of aged mice and the in vitro effect of TGF-beta 1 on cell proliferation, matrix synthesis, and alkaline phosphatase activity.

    PubMed

    Livne, E; Laufer, D; Blumenfeld, I

    1997-05-15

    The temporo-mandibular joint of aged mice develops osteoarthritic (OA) degenerative lesions. Adult chondrocytes have a low rate of cell replication, and cartilage repair potential is very limited. One of the major problems in OA is the low rate of matrix synthesis and the inability of the chondrocytes to exceed the rate of matrix degradation. These combined factors lead to the overall destruction of the cartilage as seen in OA. Cartilage degradation is mediated by elevated proteolytic activity of enzymes. Among the enzymes degrading cartilage are the metalloproteinases, stromelysin and collagenase. Other proteinases that may potentially participate in matrix degradation are the lysosomal enzymes cathepsin B, D, and L, and acid phosphatase. On the other hand, alkaline phosphatase (ALP) is an enzyme that has been shown to be a marker for anabolic activity in skeletal tissues such as bone and cartilage. The cartilage of the mandibular condyle in the T-M-J from aged mice reveals OA lesions. An overall reduction of cell proliferation and sulfated proteoglycan synthesis has been also shown in this joint. In the present study the effects of hTGF-beta on the stimulation of DNA and sulfated GAG synthesis and ALP activity were studied. Mandibular condyle cartilage obtained from 12-month-old ICR male mice were cultured in BGJb serum-free medium for 24-72 hours, supplemented with 0.1-10 ng/ml hTGF-beta 1. 3H-thymidine and 35S-sulfate were added for the last 24 hours of the culture and their incorporation into DNA and sulfated GAGs respectively, as well as the activity of ALP, were determined. Results indicated that hTGF-beta 1 enhanced the incorporation of both 3H-thymidine and of 35S-sulfate into cartilage cultures of aged mice, and also induced ALP activity. It thus appeared that in OA degenerating articular cartilage, the chondrocytes could be stimulated in vitro to proliferate and to synthesize new matrix, thus indicating induced anabolic activity in the tissue.

  15. 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.

  16. 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

  17. TGF-beta1 enhances SDF-1alpha-induced chemotaxis and homing of naive T cells by up-regulating CXCR4 expression and downstream cytoskeletal effector molecules.

    PubMed

    Franitza, Susanne; Kollet, Orit; Brill, Alexander; Vaday, Gayle G; Petit, Isabelle; Lapidot, Tsvee; Alon, Ronen; Lider, Ofer

    2002-01-01

    The migration of immunocytes within the extracellular matrix (ECM) is influenced by the activation state of the incoming cell and its responses to the presence of chemokines and cytokines. We studied the regulatory role of TGF-beta1 on T cell homing to secondary lymphatic organs, such as the spleen, and chemotaxis within an ECM-like environment in using an ECM-like 3-dimensional gel system designed to follow the migration of individual leukocytes along chemokine gradients in real time. The numbers of migrating naive, but not memory T cells toward SDF-1alpha markedly increased after pre-incubating the cells with TGF-beta1 (0.25 ng/ml) for 24 h. The mechanisms underlying TGFbeta1-modulated migration involve the up-regulation of the expression of the SDF-1alpha receptor CXCR4, the enhancement of the SDF-1alpha-induced actin polymerization, and increased phosphorylation of Pyk2, a focal adhesion kinase involved in integrin-mediated lymphocyte migration, adhesion and interactions with ECM. Interestingly, priming of naive human T cells with TGF-beta1 increased homing of these cells to the spleen of NOD/SCID mice in a CXCR4-dependent manner. We propose that the effect of TGF-beta1 on the chemotaxis of naive T cells may be important in the locomotion of naive T cells toward SDF-1alpha-rich niches. PMID:11754360

  18. Collective review: bioactive implants coated with poly(D,L-lactide) and growth factors IGF-I, TGF-beta1, or BMP-2 for stimulation of fracture healing.

    PubMed

    Schmidmaier, Gerhard; Lucke, Martin; Schwabe, Philipp; Raschke, Michael; Haas, Norbert P; Wildemann, Britt

    2006-01-01

    Demographic data reveal that due to the increasing aging of the population, complications with the musculoskeletal system will increase in the next years. One major problem in orthopedic and trauma surgery are the delayed healing or non-unions of long bone fractures. The exogenous application of growth factors can stimulate the bone healing to reduce these complications. Beside the choice of the optimal growth factor the application system is important. Therefore, we developed a new bioactive coating method for implants, which is based on a biodegradable poly(D,L-lactide) (coating thickness: 10 mum). This coating allows the incorporation of growth factors and the controlled release of these factors during the healing process without the need for further devices. The effect of different growth factors (IGF-I, TGF-beta1, and BMP-2) locally released from coated intramedullary implants on fracture healing was investigated with biomechanical and histological analysis in rats. All investigated growth factors stimulated the fracture healing as assessed with biomechanical tests and histological analysis. The local application of combined IGF-I and TGF-beta1 had the most stimulating effect on fracture healing, followed by the effect of BMP-2, IGF-I, and TGF-beta1 alone. Bioactive coating of biomechanical well-established implants can on the one hand stabilize the fracture and on the other hand stimulate healing processes to increase healing and to reduce the rate of complications.

  19. Induction of chondrogenesis and expression of superficial zone protein (SZP)/lubricin by mesenchymal progenitors in the infrapatellar fat pad of the knee joint treated with TGF-beta1 and BMP-7.

    PubMed

    Lee, Sang Yang; Nakagawa, Toshiyuki; Reddi, A Hari

    2008-11-01

    Superficial zone protein (SZP) is a key mediator of boundary lubrication of articular cartilage in joints. In this investigation, we made the unexpected discovery that SZP was expressed in infrapatellar fat pad (IFP) from bovine knee. Quantitative analysis of secreted proteins in the medium of the IFP stromal cells demonstrated a significant stimulation by TGF-beta1 and BMP-7. Real-time PCR analysis revealed the SZP expression was up-regulated by TGF-beta1 and BMP-7. Chondrogenically differentiated IFP progenitor cells were stimulated by TGF-beta1 and BMP-7 to synthesize and secrete SZP. SZP mRNA was significantly up-regulated by chondrogenic induction for 21 days. These findings indicate that the stimulation of SZP expression by TGF-beta and BMP-7 may lead to functional improvement of damaged intraarticular tissues and that IFP progenitor cells may be a potential useful source for inducing superficial zone of articular cartilage by tissue engineering for regeneration of damaged articular cartilage due to osteoarthritis.

  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. Expression of transforming growth factor beta (TGF beta) receptors and expression of TGF beta 1, TGF beta 2 and TGF beta 3 in human small cell lung cancer cell lines.

    PubMed Central

    Damstrup, L.; Rygaard, K.; Spang-Thomsen, M.; Skovgaard Poulsen, H.

    1993-01-01

    A panel of 21 small cell lung cancer cell (SCLC) lines were examined for the presence of Transforming growth factor beta receptors (TGF beta-r) and the expression of TGF beta mRNAs. By the radioreceptor assay we found high affinity receptors to be expressed in six cell lines. scatchard analysis of the binding data demonstrated that the cells bound between 4.5 and 27.5 fmol mg-1 protein with a KD ranging from 16 to 40 pM. TGF beta 1 binding to the receptors was confirmed by cross-linking TGF beta 1 to the TGF beta-r. Three classes of TGF beta-r were demonstrated, type I and type II receptors with M(r) = 65,000 and 90,000 and the betaglycan (type III) with M(r) = 280,000. Northern blotting showed expression of TGF beta 1 mRNA in ten, TGF beta 2 mRNA in two and TGF beta 3 mRNA in seven cell lines. Our results provide, for the first time, evidence that a large proportion of a broad panel of SCLC cell lines express TGF beta-receptors and also produce TGF beta mRNAs. Images Figure 3 Figure 4 PMID:8388229

  2. 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

  3. Expression of TGF-beta1, TGF-beta2, TGF-beta3 and the receptors TGF-betaRI and TGF-betaRII in placentomes of artificially inseminated and nuclear transfer derived bovine pregnancies.

    PubMed

    Ravelich, S R; Shelling, A N; Wells, D N; Peterson, A J; Lee, R S F; Ramachandran, A; Keelan, J A

    2006-01-01

    Bovine nuclear transfer pregnancies are characterized by a high incidence of placental abnormalities, notably, increased placentome size and deficiencies in trophoblast cell function and establishment of placental vasculature. Alterations in gene expression during placental growth and development may contribute to the appearance of large placentomes in pregnancies derived from nuclear transfer. The placenta synthesizes a number of cytokines and growth factors, including the transforming growth factor-betas (TGF-betas) that are involved in the establishment, maintenance and/or regulation of pregnancy. All forms of TGF-beta and their receptors are present at the fetal-maternal interface of the bovine placentome, where they are thought to play an important role in regulating growth, differentiation, and function of the placenta. Using real-time RT-PCR, we have examined the expression of TGF-beta1, TGF-beta2, TGF-beta3 and the receptors TGF-betaRI and TGF-betaRII in placentomes of artificially inseminated (AI) and nuclear transfer (NT)-derived bovine pregnancies at days 50, 100 and 150 of gestation. TGF-beta1, TGF-beta2 and TGF-beta3 mRNA expression increased by 2.0-2.8-fold, while TGF-betaRI and TGF-betaRII mRNA expression decreased by 1.7-2.0-fold in NT placentomes compared to AI controls at all gestational ages examined. These findings indicate that NT placentomes may be resistant to the growth suppressive effects of TGF-betas and could contribute to the placental proliferative abnormalities observed in NT-derived placentas. Alternatively, deficiencies in placentation may provide a mechanism whereby TGF-betas are dysregulated in NT pregnancies.

  4. Glucose-induced serum- and glucocorticoid-regulated kinase activation in oncofetal fibronectin expression

    SciTech Connect

    Khan, Zia A.; Barbin, Yousef P.; Farhangkhoee, Hana; Beier, Norbert; Scholz, Wolfgang; Chakrabarti, Subrata . E-mail: subrata.chakrabarti@fmd.uwo.ca

    2005-04-01

    Preferential expression of oncofetal extra domain-B fibronectin (EDB{sup +} FN), a proposed angiogenic marker, has been shown in proliferative diabetic retinopathy. High levels of glucose also increase EDB{sup +} FN expression in endothelial cells (ECs) via transforming growth factor-{beta}1 (TGF-{beta}1) and endothelin-1 (ET-1). The present study was aimed at elucidating the role of serum- and glucocorticoid-regulated kinase (SGK-1) in glucose-induced EDB{sup +} FN expression. Using human macro- and microvascular ECs, we show that high levels of glucose, TGF-{beta}1, and ET-1 increase the EDB{sup +} FN expression via SGK-1 alteration at the mRNA, protein, and activity levels. Inhibition of TGF-{beta}1 and ET-1 prevented glucose-induced SGK-1 activation and the EDB{sup +} FN expression. Furthermore, using siRNA-mediated SGK-1 gene silencing, we show that glucose-induced EDB{sup +} FN expression can be completely prevented. These findings provide first evidence of glucose-induced SGK-1 activation in altered EDB{sup +} FN expression and provide novel avenues for therapeutic modalities.

  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. Serum leptin levels in relation to circulating cytokines, chemokines, adhesion molecules and angiogenic factors in normal pregnancy and preeclampsia

    PubMed Central

    2011-01-01

    Objective In this study, we determined circulating levels of C-reactive protein, several cytokines, chemokines, adhesion molecules and angiogenic factors along with those of leptin in healthy non-pregnant and pregnant women and preeclamptic patients, and investigated whether serum leptin levels were related to the clinical characteristics and measured laboratory parameters of the study participants. Methods Sixty preeclamptic patients, 60 healthy pregnant women and 59 healthy non-pregnant women were involved in this case-control study. Levels of leptin and transforming growth factor (TGF)-beta1 in maternal sera were assessed by ELISA. Serum levels of interleukin (IL)-1beta, IL-1 receptor antagonist (IL-1ra), IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p40, IL-12p70, IL-18, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, interferon-gamma-inducible protein (IP)-10, monocyte chemotactic protein (MCP)-1, intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 were determined by multiplex suspension array. Serum C-reactive protein (CRP) concentrations were measured by an autoanalyzer. Serum total soluble fms-like tyrosine kinase-1 (sFlt-1) and biologically active placental growth factor (PlGF) levels were determined by electrochemiluminescence immunoassay. For statistical analyses, non-parametric methods were applied. Results There were significant differences in most of the measured laboratory parameters among the three study groups except for serum IL-1beta and TGF-beta1 levels. Serum leptin levels were significantly higher in preeclamptic patients and healthy pregnant women than in healthy non-pregnant women. Additionally, preeclamptic patients had significantly higher leptin levels as compared to healthy pregnant women. Serum leptin levels were independently associated with BMI in healthy non-pregnant women. In healthy pregnant women, both BMI and serum CRP concentrations showed significant positive linear association with leptin

  8. Otosclerosis and TGF-beta 1 gene in black South Africans.

    PubMed

    Tshifularo, M; Joseph, C A

    2008-09-01

    Limited literature is available on the epidemiology and genetics of otosclerosis in South African blacks, among whom it is extremely rare. We undertook this study because we had documented and surgically confirmed cases of clinical oval window otosclerosis in this population.

  9. 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

  10. 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

  11. 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…

  12. Transforming growth factor-beta 1 does not relate to hypertension in pre-eclampsia.

    PubMed

    Hennessy, A; Orange, S; Willis, N; Painter, D M; Child, A; Horvath, J S

    2002-11-01

    1. Pre-eclampsia is a human disease of pregnancy characterized by high blood pressure, proteinuria and end-organ damage, if severe. Pre-eclampsia is thought to be related to changes in early placental development, with the formation of a shallower than normal placental bed. 2. Transforming growth factor (TGF)-beta1 is a multifunctional fibrogenic growth factor involved in immune regulation that is elevated in some populations with a high risk of hypertensive end-organ disease related to increases in endothelin release. Transforming growth factor-beta1 is also an important factor in placental implantation. Alterations in TGF-beta1 may be related to abnormal placental development in early pregnancy and, thus, are a candidate for the development of hypertension in pre-eclampsia. 3. The aim of the present study was to examine the placental distribution and serum concentration of TGF-beta1 in patients with pre-eclampsia compared with normal pregnancy. 4. Patients with pre-eclampsia (n = 12) were compared with patients with normal pregnancy (n = 14). Transforming growth factor-beta1 was determined by TGF-beta1 Max ELISA (Promega, Madsion, WI, USA) after serum dilution (1/150) and acid activation. Placental distribution was determined by immunostaining with TGF-beta1 (Santa Cruz, Santa Cruz, CA, USA; 20 ng/mL) and the villi and decidual trophoblast were scored for intensity and extent of staining. 5. Patients with pre-eclampsia had a mean gestational age of 36 weeks, whereas those with a normal pregnancy had a mean gestational age of 39.0 +/- 0.4 weeks. There was no difference in TGF-beta1 concentration between the two groups (mean (+/-SEM) 27.1 +/- 1.0 vs 26.4 +/- 0.7 pg/mL for normal pregnancy and pre-eclampsia, respectively; P = 0.73, Mann-Whitney U-test). There was no correlation between systolic or diastolic blood pressure and TGF-beta1 concentration (regression analysis P = 0.4 and 0.2). Immunostaining was absent in the villous trophoblast cells and endovascular and

  13. Serum sickness

    MedlinePlus

    Drug allergy - serum sickness; Allergic reaction - serum sickness; Allergy - serum sickness ... penicillin, cefaclor, and sulfa) can cause a similar reaction. Injected proteins such as antithymocyte globulin (used to ...

  14. Identification of Retinoic Acid in a High Content Screen for Agents that Overcome the Anti-Myogenic Effect of TGF-Beta-1

    PubMed Central

    Krueger, Chateen; Hoffmann, F. Michael

    2010-01-01

    Background Transforming growth factor beta 1 (TGF-β1) is an inhibitor of muscle cell differentiation that is associated with fibrosis, poor regeneration and poor function in some diseases of muscle. When neutralizing antibodies to TGF-β1 or the angiotensin II inhibitor losartan were used to reduce TGF-β1 signaling, muscle morphology and function were restored in mouse models of Marfan Syndrome and muscular dystrophy. The goal of our studies was to identify additional agents that overcome the anti-myogenic effect of TGF-β1. Methodology/Principal Findings A high-content cell-based assay was developed in a 96-well plate format that detects the expression of myosin heavy chain (MHC) in C2C12 cells. The assay was used to quantify the dose-dependent responses of C2C12 cell differentiation to TGF-β1 and to the TGF-β1 Type 1 receptor kinase inhibitor, SB431542. Thirteen agents previously described as promoting C2C12 differentiation in the absence of TGF-β1 were screened in the presence of TGF-β1. Only all-trans retinoic acid and 9-cis retinoic acid allowed a maximal level of C2C12 cell differentiation in the presence of TGF-β1; the angiotensin-converting enzyme inhibitor captopril and 10 nM estrogen provided partial rescue. Vitamin D was a potent inhibitor of retinoic acid-induced myogenesis in the presence of TGF-β1. TGF-β1 inhibits myoblast differentiation through activation of Smad3; however, retinoic acid did not inhibit TGF-β1-induced activation of a Smad3-dependent reporter gene in C2C12 cells. Conclusions/Significance Retinoic acid alleviated the anti-myogenic effect of TGF-β1 by a Smad3-independent mechanism. With regard to the goal of improving muscle regeneration and function in individuals with muscle disease, the identification of retinoic acid is intriguing in that some retinoids are already approved for human therapy. However, retinoids also have well-described adverse effects. The quantitative, high-content assay will be useful to screen for less-toxic retinoids or combinations of agents that promote myoblast differentiation in the presence of TGF-β1. PMID:21152098

  15. Calcium input potentiates the transforming growth factor (TGF)-beta1-dependent signaling to promote the export of inorganic pyrophosphate by articular chondrocyte.

    PubMed

    Cailotto, Frederic; Reboul, Pascal; Sebillaud, Sylvie; Netter, Patrick; Jouzeau, Jean-Yves; Bianchi, Arnaud

    2011-06-01

    Transforming growth factor (TGF)-β1 stimulates extracellular PP(i) (ePP(i)) generation and promotes chondrocalcinosis, which also occurs secondary to hyperparathyroidism-induced hypercalcemia. We previously demonstrated that ANK was up-regulated by TGF-β1 activation of ERK1/2 and Ca(2+)-dependent protein kinase C (PKCα). Thus, we investigated mechanisms by which calcium could affect ePP(i) metabolism, especially its main regulating proteins ANK and PC-1 (plasma cell membrane glycoprotein-1). We stimulated articular chondrocytes with TGF-β1 under extracellular (eCa(2+)) or cytosolic Ca(2+) (cCa(2+)) modulations. We studied ANK, PC-1 expression (quantitative RT-PCR, Western blotting), ePP(i) levels (radiometric assay), and cCa(2+) input (fluorescent probe). Voltage-operated Ca(2+)-channels (VOC) and signaling pathways involved were investigated with selective inhibitors. Finally, Ank promoter activity was evaluated (gene reporter). TGF-β1 elevated cCa(2+) and ePP(i) levels (by up-regulating Ank and PC-1 mRNA/proteins) in an eCa(2+) dose-dependent manner. TGF-β1 effects were suppressed by cCa(2+) chelation or L- and T-VOC blockade while being mostly reproduced by ionomycin. In the same experimental conditions, the activation of Ras, the phosphorylation of ERK1/2 and PKCα, and the stimulation of Ank promoter activity were affected similarly. Activation of SP1 (specific protein 1) and ELK-1 (Ets-like protein-1) transcription factors supported the regulatory role of Ca(2+). SP1 or ELK-1 overexpression or blockade experiments demonstrated a major contribution of ELK-1, which acted synergistically with SP1 to activate Ank promoter in response to TGF-β1. TGF-β1 promotes input of eCa(2+) through opening of L- and T-VOCs, to potentiate ERK1/2 and PKCα signaling cascades, resulting in an enhanced activation of Ank promoter and ePP(i) production in chondrocyte.

  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. TGF-beta 1 inhibits both endotoxin-induced prostaglandin synthesis and expression of the TIS10/prostaglandin synthase 2 gene in murine macrophages.

    PubMed

    Reddy, S T; Gilbert, R S; Xie, W; Luner, S; Herschman, H R

    1994-02-01

    Activated macrophages produce substantial quantities of paracrine mediators, including cytokines, nitric oxide, and prostaglandins. Transforming growth factor beta 1 (TGF-beta) is a potent modulator of immune function. TGF-beta inhibits the cytotoxic activity of endotoxin/lipopolysaccharide (LPS)-activated macrophage cell lines and primary macrophage cultures, reducing their expression of cytokines and nitric oxide. In this report we demonstrate that TGF-beta also attenuates the LPS-induced synthesis and secretion of prostaglandin E2 in murine RAW 264.7 macrophage cells. Macrophage activation also induces accumulation of the recently described ligand-responsive prostaglandin synthase (PGS) TIS10/PGS-2. While TGF-beta alone has no effect on expression from the TIS10/PGS-2 gene, this cytokine inhibits LPS-induced TIS10/PGS-2 protein accumulation and synthesis, as well as LPS-induced TIS10/PGS-2 message accumulation in RAW 264.7 cells. TGF-beta concentrations in the range of 0.1-1.0 ng/ml (4-40 pM) maximally inhibit LPS-induced TIS10/PGS-2 message accumulation. In contrast, neither LPS nor TGF-beta has any effect on the level of PGS-1 (EC 1.14.99.1) message. TGF-beta also attenuates LPS-induced accumulation of unspliced TIS10/PGS-2 transcripts in RAW 264.7 cells, suggesting that this cytokine exerts its effects on TIS10/PGS-2 expression at the transcriptional level. TGF-beta inhibits the LPS-induced accumulation of TIS10/PGS-2 protein and message in cultured murine peritoneal macrophages, as well as in macrophage cell lines.

  18. 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.

  19. Effects of transforming growth factor-beta 1 and interleukin-1 alpha on matrix synthesis in osteoarthritic cartilage of the temporo-mandibular joint in aged mice.

    PubMed

    Blumenfeld, I; Laufer, D; Livne, E

    1997-04-01

    Osteoarthritic lesions were observed in the mandibular condyle cartilage of mice aged 7 months and older. These lesions appeared as fibrillations along the articular surface and were accompanied by reduced extracellular matrix synthesis and chondrocyte proliferation. Explants of mandibular condyle cartilage were cultured in serum-free BGJb medium supplemented with ascorbic acid (300 micrograms/ml), penicillin (100 U/ml) and streptomycin (100 micrograms/ml) for up to 72 h. Cultures were further supplemented with either hTGF-beta 1 (0.1-5.0 ng/ml) or human IL-1 alpha (40 U/ml). [3H]thymidine (2 microCi/ml) and [35S]SO4 (10 microCi/ml) were added to the culture medium for the last 24 h of culture and incorporation into DNA and sulfated proteoglycans, respectively, studied. The results indicated that protein and DNA contents, [3H]thymidine and [35S]SO4 incorporation, as well as the specific activity of alkaline phosphatase, were increased by TGF-beta 1. Addition of 1.0 or 5.0 ng/ml hTGF-beta 1 to the cultures for 48 h, had the most stimulatory effect on matrix synthesis and cell proliferation, whereas 0.1 ng/ml hTGF-beta 1 appeared to be inhibitory when compared to controls. Increased [35S]SO4 labeling of chondrocyte clusters was observed by autoradiography in tissue sections from cultures treated with TGF-beta 1 (1.0 and 5.0 ng/ml). In contrast, IL-1 alpha exerted inhibitory effects on cell proliferation and matrix synthesis. However, it induced the activity of acid phosphatase in these cultures. The results of the present study show that IL-1 alpha had catabolic effect on his tissue, while TGF-beta 1 enhanced proliferation and induced synthetic activity of the cartilage cells. Such action by TGF-beta suggests the existance of a possible repair process in osteoarthritic cartilage of the temporo-mandibular joint of aged mice.

  20. 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

  1. Pro-inflammatory cytokine production in chagasic mothers and their uninfected newborns.

    PubMed

    Cuna, Washington R; Choque, Ana Gabriela Herrera; Passera, Roberto; Rodriguez, Celeste

    2009-08-01

    The levels of IFN-gamma, TNF-alpha, IL-10, and TGF-beta1 cytokines associated with Trypanosoma cruzi during pregnancy were determined by enzyme-linked immunosorbent assay (ELISA) in serum samples from peripheral, placental, and cord blood of chronic infected mothers with detectable and undetectable parasitemia, and in their uninfected newborns. Compared to uninfected pregnant women and mothers with undetectable parasitemia, the concentrations of IFN-gamma were higher at the 3 sites in mothers with detectable parasitemia. In these mothers and their newborns, the TNF-alpha concentrations were higher in the periphery and cord in comparison to serum samples from non-chagasic pregnant women. TNF-alpha levels were higher in newborns of mothers with detectable parasitemia than in newborns of mothers with undetectable parasitemia. IL-10 and TGF-beta1 levels at the 3 sites were unchanged and diminished, respectively, in samples from infected mothers with patent parasitemia in comparison with uninfected pregnant women. Cytokine concentrations did not change significantly in all samples from mothers with undetectable parasitemia; however, the concentration of TGF-beta1 was significantly reduced in their peripheral samples but significantly higher in the placenta in comparison with uninfected mothers and mothers with detectable parasitemia, respectively. These results suggest that elevated numbers of circulating parasites in vivo elicit production of pro-inflammatory cytokines that control congenital T. cruzi infection.

  2. 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 ...

  3. 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 ...

  4. 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

  5. Regulation of serum phosphate

    PubMed Central

    Lederer, Eleanor

    2014-01-01

    The regulation of serum phosphate, an acknowledged risk factor for chronic kidney disease and cardiovascular mortality, is poorly understood. The discovery of fibroblast growth factor 23 (FGF23) as a key regulator of renal phosphate handling and activation of vitamin D has revolutionized our comprehension of phosphate homeostasis. Through as yet undetermined mechanisms, circulating and dietary phosphate appear to have a direct effect on FGF23 release by bone cells that, in turn, causes renal phosphate excretion and decreases intestinal phosphate absorption through a decrease in vitamin D production. Thus, the two major phosphaturic hormones, PTH and FGF23, have opposing effects on vitamin D production, placing vitamin D at the nexus of phosphate homeostasis. While our understanding of phosphate homeostasis has advanced, the factors determining regulation of serum phosphate level remain enigmatic. Diet, time of day, season, gender, age and genetics have all been identified as significant contributors to serum phosphate level. The effects of these factors on serum phosphate have major implications for what is understood as ‘normal’ and for studies of phosphate homeostasis and metabolism. Moreover, other hormonal mediators such as dopamine, insulin-like growth factor, and angiotensin II also affect renal handling of phosphate. How the major hormone effects on phosphate handling are regulated and how the effect of these other factors are integrated to yield the measurable serum phosphate are only now beginning to be studied. PMID:24973411

  6. [The National Serum Bank].

    PubMed

    Magos-López, C; Sánchez-Villarreal, F; Gutiérrez, G; Tapia-Conyer, R

    1992-01-01

    A National Serum Bank was established to store sera obtained during the National Seroepidemiological Survey performed in Mexico in 1987. More than 70,000 serum samples were obtained from subjects of either sex 1-99 years of age in each of the 32 states of the country. The current collection of sera includes 28,704 male samples and 40,629 female samples. This paper describes the procedures for handling serum samples, including reception registry, storage and distribution to several laboratories for detection of measles, rubella, poliomyelitis, AIDS, diphtheria, pertussis, tetanus, brucella, salmonella, amoeba, toxoplasma, American trypanosomiasis and cysticercus. Determinations of total cholesterol were also made in order to describe its distribution and to identify the prevalence of hypercholesterolemia.

  7. The Human Serum Metabolome

    PubMed Central

    Psychogios, Nikolaos; Hau, David D.; Peng, Jun; Guo, An Chi; Mandal, Rupasri; Bouatra, Souhaila; Sinelnikov, Igor; Krishnamurthy, Ramanarayan; Eisner, Roman; Gautam, Bijaya; Young, Nelson; Xia, Jianguo; Knox, Craig; Dong, Edison; Huang, Paul; Hollander, Zsuzsanna; Pedersen, Theresa L.; Smith, Steven R.; Bamforth, Fiona; Greiner, Russ; McManus, Bruce; Newman, John W.; Goodfriend, Theodore; Wishart, David S.

    2011-01-01

    Continuing improvements in analytical technology along with an increased interest in performing comprehensive, quantitative metabolic profiling, is leading to increased interest pressures within the metabolomics community to develop centralized metabolite reference resources for certain clinically important biofluids, such as cerebrospinal fluid, urine and blood. As part of an ongoing effort to systematically characterize the human metabolome through the Human Metabolome Project, we have undertaken the task of characterizing the human serum metabolome. In doing so, we have combined targeted and non-targeted NMR, GC-MS and LC-MS methods with computer-aided literature mining to identify and quantify a comprehensive, if not absolutely complete, set of metabolites commonly detected and quantified (with today's technology) in the human serum metabolome. Our use of multiple metabolomics platforms and technologies allowed us to substantially enhance the level of metabolome coverage while critically assessing the relative strengths and weaknesses of these platforms or technologies. Tables containing the complete set of 4229 confirmed and highly probable human serum compounds, their concentrations, related literature references and links to their known disease associations are freely available at http://www.serummetabolome.ca. PMID:21359215

  8. 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

  9. 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.

  10. Interpreting serum risperidone concentrations.

    PubMed

    Boerth, Joel M; Caley, Charles F; Goethe, John W

    2005-02-01

    Risperidone is an atypical antipsychotic commonly used for treatment of schizophrenia and other psychotic disorders. Although therapeutic drug monitoring is not routine for any of the atypical antipsychotics, serum antipsychotic concentrations are measured routinely to assess treatment nonadherence. In humans, risperidone is metabolized by cytochrome P450 2D6 to 9-hydroxyrisperidone; together these constitute the active moiety. Dose-proportional increases in serum concentrations have not been reported for the parent drug, but have been reported for 9-hydroxyrisperidone and the active moiety (i.e., the combined concentrations of risperidone and 9-hydroxyrisperidone). We describe a 34-year-old Caucasian man of Sicilian descent with a history of schizophrenia, disorganized type. He was suspected to be noncompliant with his risperidone therapy. Initially, active moiety risperidone concentrations increased linearly with prescribed dosage increases. However, with continued increases, active moiety concentrations adjusted downward and remained 17-36% below anticipated levels. We propose a method for estimating target active moiety concentrations of risperidone based on dosage-a method that may be used to guide clinicians in assessing nonadherence to risperidone treatment.

  11. 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.

  12. Fluid shear stress induces endothelial transforming growth factor beta-1 transcription and production. Modulation by potassium channel blockade.

    PubMed Central

    Ohno, M; Cooke, J P; Dzau, V J; Gibbons, G H

    1995-01-01

    The endothelium has the capacity to modulate vascular structure in response to hemodynamic stimuli. We tested the hypothesis that exposure of the endothelium to increased laminar shear stress induces the expression of TGF beta 1 via a signal transduction pathway modulated by K+ channel currents. Although TGF beta 1 is normally secreted in a latent, inactive form, exposure of cultured endothelial cells to steady laminar shear stress (20 dynes/cm2) induced increased generation of biologically active TGF beta 1. This increase in active TGF beta 1 was associated with a sustained increase in TGF beta 1 mRNA expression within 2 h of stimulation. TGF beta 1 mRNA levels increased in direct proportion to the intensity of the shear stress within the physiologic range. The effect of shear stress on TGF beta 1 mRNA expression was regulated at the transcriptional level as defined by nuclear run-off studies and transient transfection of a TGF beta 1 promoter-reporter gene construct. Blockade of endothelial K+ channels with tetraethylammonium significantly inhibited: activation of TGF beta 1 gene transcription; increase in steady state mRNA levels; and generation of active TGF beta 1 in response to shear stress. These data suggest that endothelial K+ channels and autocrine-paracrine TGF beta 1 may be involved in the mechanotransduction mechanisms mediating flow-induced vascular remodeling. Images PMID:7883983

  13. 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

  14. 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

  15. Changes in circulating immunosuppressive cytokine levels of cancer patients after high intensity focused ultrasound treatment.

    PubMed

    Zhou, Qiang; Zhu, Xue-Qiang; Zhang, Jun; Xu, Zhong-Lin; Lu, Pei; Wu, Feng

    2008-01-01

    Immunosuppression in a patient with malignant tumor is a major obstacle in cancer treatment. In this study, we investigated changes in the circulating level of all measured immunosuppressive cytokines in patients with malignancy before and after high intensity focused ultrasound (HIFU) treatment. Fifteen patients with solid malignancy were enrolled in this study and an enzyme-linked immunoabsorbent assay (ELISA) method was used to measure serum level of vascular endothelial growth factor (VEGF), transforming growth factor-beta1 (TGF-beta1), transforming growth factor-beta2 (TGF-beta2), interleukin 6 (IL-6) and interleukin 10 (IL-10), respectively before and 1 wk after HIFU treatment. Among them, seven patients had distant metastasis and the remaining eight had no metastasis. All patients received one-session HIFU treatment for primary cancer, including complete ablation in eight patients without metastasis, and partial ablation in seven patients with metastases. The results showed that serum immunosuppressive cytokine levels decreased after HIFU treatment, and there were significant decreases of VEGF, TGF-beta1, and TGF-beta2 before and after HIFU treatment. Compared with the values in the metastatic patients, serum levels of immunosuppressive cytokines were significantly lower in the nonmetastatic patients after HIFU treatment. It is concluded that HIFU can decrease tumor-secreted immunosuppressive cytokine production in addition to its direct tumor destruction. This change may lessen tumor-induced immunosuppression and renew antitumor immunity after HIFU in cancer patients.

  16. Serum bile acids in hepatobiliary disease.

    PubMed Central

    Bouchier, I A; Pennington, C R

    1978-01-01

    We review the estimation of total and individual serum bile acids to detect the presence and nature of hepatobiliary disease. The different methods for measuring serum bile acids are discussed. PMID:355064

  17. 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

  18. [Serum sclerostin levels and metabolic bone diseases].

    PubMed

    Yamauchi, Mika; Sugimoto, Toshitsugu

    2013-06-01

    Serum sclerostin levels are being investigated in various metabolic bone diseases. Since serum sclerostin levels are decreased in primary hyperparathyroidism and elevated in hypoparathyroidism, parathyroid hormone (PTH) is thought to be a regulatory factor for sclerostin. Serum sclerostin levels exhibit a significant positive correlation with bone mineral density. On the other hand, a couple of studies on postmenopausal women have shown that high serum sclerostin levels are a risk factor for fracture. Although glucocorticoid induced osteoporosis and diabetes are both diseases that reduce bone formation, serum sclerostin levels have been reported to be decreased in the former and elevated in the latter, suggesting differences in the effects of sclerostin in the two diseases. Serum sclerostin levels are correlated with renal function, and increase with reduction in renal function. Serum sclerostin level may be a new index of bone assessment that differs from bone mineral density and bone metabolic markers.

  19. SERUM PROTEIN PROFILES IN COCCIDIOIDOMYCOSIS

    PubMed Central

    Reed, William B.; Heiskell, Charles L.; Holeman, Charles W.; Carpenter, Charles

    1962-01-01

    Serum protein analysis is a valuable addition to the present methods for evaluating the status of the individual patient with coccidioidomycosis. The albumin protein and albumin glycoprotein decrease and gamma protein increases in relation to severity of infection. In 40 patients with coccidioidomycosis, changes in individual protein fractions could be significantly correlated with conventional laboratory tests, such as the complement fixation test, erythrocyte sedimentation rate and hematocrit. Changes in the alpha, glycoprotein concentration, the erythrocyte sedimentation rate and the hematocrit value appear to be related to the degree of inflammation, while the changes in the gamma protein and the beta, glycoprotein appear to be related to the specific antibody response. PMID:13973566

  20. Serum protein profiles in coccidioidomycosis.

    PubMed

    REED, W B; HEISKELL, C L; HOLEMAN, C W; CARPENTER, C

    1962-12-01

    Serum protein analysis is a valuable addition to the present methods for evaluating the status of the individual patient with coccidioidomycosis. The albumin protein and albumin glycoprotein decrease and gamma protein increases in relation to severity of infection. In 40 patients with coccidioidomycosis, changes in individual protein fractions could be significantly correlated with conventional laboratory tests, such as the complement fixation test, erythrocyte sedimentation rate and hematocrit. Changes in the alpha, glycoprotein concentration, the erythrocyte sedimentation rate and the hematocrit value appear to be related to the degree of inflammation, while the changes in the gamma protein and the beta, glycoprotein appear to be related to the specific antibody response.

  1. 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.

  2. Neptunium uptake by serum transferrin.

    PubMed

    Llorens, Isabelle; Den Auwer, Christophe; Moisy, Philippe; Ansoborlo, Eric; Vidaud, Claude; Funke, Harld

    2005-04-01

    Although of major impact in terms of biological and environmental hazards, interactions of actinide cations with biological molecules are only partially understood. Human serum transferrin (Tf) is one of the major iron carriers in charge of iron regulation in the cell cycle and consequently contamination by actinide cations is a critical issue of nuclear toxicology. Combined X-ray absorption spectroscopy (XAS) and near infrared absorption spectrometry were used to characterize a new complex between Tf and Np (IV) with the synergistic nitrilotriacetic acid (NTA) anion. Description of the neptunium polyhedron within the iron coordination site is given.

  3. Serum enzyme activities after cardioversion

    PubMed Central

    Mandecki, Tadeusz; Giec, Leszek; Kargul, Włodzimierz

    1970-01-01

    Serum aspartate aminotransferase (SGOT), alanine aminotransferase (SGPT), creatinine phosphokinase (CPK), and butyric acid dehydrogenase (BDH) were determined in 94 patients before, 1½ hours, and 24 hours after cardioversion. An increase in SGOT and CPK activity was observed 24 hours after cardioversion in the group of patients treated with two or more DC shocks. The importance of this enzyme activity increase is discussed. It originates in the skeletal muscles and probably has no clinical significance, as no other signs of myocardial damage were observed simultaneously in a large group of patients. PMID:5470040

  4. International Reference Preparation of Rheumatoid Arthritis Serum

    PubMed Central

    Anderson, S. G.; Bentzon, M. W.; Houba, V.; Krag, P.

    1970-01-01

    The National Institute for Medical Research, London, England, was requested by the WHO Expert Committee on Biological Standardization to arrange a collaborative study of the serum pool they had obtained, to determine its suitability to serve as an international reference preparation of rheumatoid arthritis serum. A batch of this serum was assayed by 11 laboratories in 7 countries against 30 test preparations. On the basis of the results obtained, the serum has been established as the International Reference Preparation of Rheumatoid Arthritis Serum and the International Unit of Rheumatoid Arthritis Serum has been defined as the activity contained in 0.171 mg of the international reference preparation. A description is also given of the British reference preparation of rabbit antibody to sheep red blood cells (amboceptor) and this material was also tested in the collaborative study. PMID:5310143

  5. Effect of Pregnancy Serum on Experimental Inflammation

    PubMed Central

    Persellin, R. H.; Vance, S. E.; Peery, A.

    1974-01-01

    Experimental inflammation induced in the rat by injection of carrageenin was suppressed by prior administration of pooled serum obtained from pregnant human females. Inflammatory oedema in the rat hind paw measured by a plethysmograph was inhibited 81% by 10 ml of pregnancy serum pool and the effect was dose related. Non-pregnant female serum was inhibitory to a lesser degree and no anti-inflammatory action was detected using cord serum. Although adrenal corticosteroid hormones could modify this inflammatory model, their presence in the serum pools could not account for the effects observed. Since carrageenin is sequestered within phagolysosomes and provokes release of their inflammation-inducing contents, it is suggested that the protective effect of pregnancy serum on carrageenin inflammation is mediated via lysosomal stabilization. PMID:4835795

  6. Pediatric bupropion-induced serum sicknesslike reaction.

    PubMed

    Hack, Sabine

    2004-01-01

    This reports the first 2 cases of serum sicknesslike reaction to bupropion in children (age 12 and 14). Serum sicknesslike reactions are an example of immune-complex medicated disease. The cardinal symptoms of serum sickness are fever, lymphadenopathy, arthralgias or arthritis, and urticaria. Symptoms usually resolve without long-term sequela following discontinuation of the exogenous antigen. It is likely that serum sicknesslike reactions to bupropion are either relatively rare or underrecognized and underreported. Between May 1998 and May 2001, GlaxoSmith Kline received 172 reports of seizures (a well-known adverse drug reaction) and only 37 reports of serum sicknesslike reactions (Wooltorton 2002). We do not know if children and adolescents are more prone than adults to develop serum sicknesslike reactions to bupropion. Luckily, the reported cases of serum sicknesslike reactions to bupropion have not caused irreversible morbidity or mortality. Nevertheless, the symptoms are painful, temporarily disfiguring and disabling, and warrant prompt medical attention. Parents and patients should be educated about this potential side effect at the onset of treatment, because symptoms are similar to many infectious childhood illnesses, and the treatment of serum sicknesslike reactions to bupropion should include the discontinuation of bupropion.

  7. 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.

  8. Altered regulation of Src tyrosine kinase by transforming growth factor beta1 in a human hepatoma cell line.

    PubMed

    Fukuda, K; Kawata, S; Tamura, S; Matsuda, Y; Inui, Y; Igura, T; Inoue, S; Kudara, T; Matsuzawa, Y

    1998-09-01

    Transforming growth factor betas (TGF-betas) are the potent growth inhibitors for various cell types. Certain transformed cells, however, show poor response to TGF-beta-induced growth inhibition, which contributes to their uncontrolled proliferation. Recently, we have reported that TGF-beta1 induces degradation of activated Src tyrosine kinase in rat fibroblasts. To elucidate the alteration in TGF-beta signaling pathway in tumor cells that cannot respond to the cytokine, we compared the effects of TGF-beta1 on Src kinase in two human hepatoma cell lines, TGF-beta1-insensitive Mahlavu cells and TGF-beta1-sensitive HepG2 cells. TGF-beta1 decreased Src kinase activity in HepG2 cells, but increased cellular Src levels and Src kinase activity in Mahlavu cells. Co-incubation of Mahlavu cells with TGF-beta1 and 12-O-tetradecanoyl phorbol 13-acetate (TPA) decreased Src protein levels and Src kinase activity, inducing TGF-beta1 sensitivity. TGF-beta1 induced tyrosine dephosphorylation of Ras guanosine triphosphatase-activating protein (Ras-GAP) and Ras inactivation in HepG2 cells, but induced Ras-GAP phosphorylation and Ras activation in Mahlavu cells. The Src kinase inhibitor abolished the increase of Src kinase activity in TGF-beta1-treated Mahlavu cells, and induced TGF-beta1 sensitivity. These findings suggest that regulation of Src kinase by TGF-beta1 is altered in Mahlavu cells. The altered regulation of Src may contribute to TGF-beta1 insensitivity in this cell line, at least in part through activation of Ras.

  9. Smoking, alcohol drinking and serum carotenoids levels.

    PubMed

    Aoki, K; Ito, Y; Sasaki, R; Ohtani, M; Hamajima, N; Asano, A

    1987-10-01

    Serum carotenoids concentrations in healthy inhabitants, aged 40-79 years, of a community were measured. The results are as follows. 1. The alpha- and beta-carotene and lycopene levels in serum were significantly higher in females than males. The alpha- and beta-carotene concentrations tended to increase with advancing age, this being especially marked for serum beta-carotene levels in males. However, beta-carotene levels were high in females throughout the age range of 50-69 years. There was no significant change in serum level of lycopene with age. 2. There was no significant difference in intake frequency of foods containing large amounts of carotenoids among the groups with or without smoking and drinking, as serum alpha- and beta-carotene levels were closely associated with intake frequency of green-yellow vegetables. 3. Regular alcohol drinkers or current smokers showed lower serum beta-carotene concentrations, and the effect of alcohol drinking on serum carotene level seemed to be larger than that of smoking. A synergistic lowering action of smoking and drinking on serum beta-carotene level was suggested. Among the alcohol drinkers, the more cigarettes consumed per day, the lower the serum beta-carotene level was, but this was not the case among the non-drinkers. Ex-smokers showed intermediate values between current smokers and non-smokers. The results suggest that alcohol drinking and smoking habit might be associated with lower serum beta-carotene level, which in turn may be related to excess incidence of cancer among smokers or drinkers.

  10. Role of Rabbit Lysozyme in In Vitro Serum and Plasma Serum Bactericidal Reactions Against Bacillus subtilis

    PubMed Central

    Carroll, Stephen F.; Martinez, Rafael J.

    1979-01-01

    The antibacterial activity of purified rabbit lysozyme was kinetically investigated at concentrations comparable to those in normal rabbit serum and plasma serum. The bactericidal capability, lysozyme content, and electrophoretic composition of “purified β-lysin,” fractionated from normal rabbit serum, were also examined. In contrast to the extensive antibacterial activity of dilute normal rabbit serum observed in vitro, rabbit lysozyme was only weakly bactericidal for Bacillus subtilis. Inhibition of lysozyme enzymatic and bactericidal activities in normal rabbit serum by antilysozyme immunoglobulin G slightly reduced the initial rate of killing. The addition of neutralizing antibody or histamine (another lysozyme inhibitor) to partially purified bactericidal serum fractions had no effect on killing kinetics. Increasing the ionic strength of reaction mixtures containing normal serum or partially purified bactericidal fractions to levels which completely inhibited lysozyme activity resulted in stimulation of their respective killing kinetics. The addition of inhibitors to normal rabbit plasma serum completely eliminated its bactericidal activity. With regard to the killing of B. subtilis by rabbit and human blood fractions, these analyses clearly demonstrated that (i) although lysozyme is not a significant antibacterial component of normal rabbit serum, it represents the principal factor in normal rabbit plasma serum; (ii) different primary bactericidal mechanisms which are not detectable by singlepoint analyses operate in the sera of different species; and (iii) purified β-lysin isolated from normal rabbit serum by the classical procedure is a heterogenous mixture of components. Images PMID:115789

  11. [Serum iron and serum copper balance in the early diagnosis of metastases of breast cancer].

    PubMed

    Wöllgens, P; Kuhne-Velte, H J; Franke-Lompa, C

    1980-02-01

    In a study made in the follow-up clinic on 684 patients with mammary carcinoma it was found that there were 64 cases of local recurrence and 244 cases of distant metastases. In both groups the serum iron and the serum copper balance in blood tests, in relation to the clinical proof of local recurrence and/or distant metastases, was investigated. It was found that there were 43.7% pathological serum iron and serum copper findings with local recurrences and 62.7% with distant metastases. The drift apart tendency of the blood serum values in patients with distant metastases could be proved in 78.7% of the cases and in 77.5% of the cases before any clinical proof. Thus, these observations allow the statement that the blood serum iron and serum copper imbalance in blood tests is of very real value in the early diagnosis of distant metastases.

  12. [Alternative tests to PSA for prostate cancer diagnosis].

    PubMed

    Defilippi, Elio; Zitella, Andrea; Tizzani, Alessandro

    2011-01-01

    Prostate specific antigen (PSA) is still the most useful tool to select the population requiring prostatebiopsy. The main downsides of PSA are an inadequate sensitivity to be used in screening and a low specificity for cancer detection. So far, a limited value for PSA derivates (velocity, density, free, proisoforms and doubling time) has been recognised. We present a short review of the literature describing a selection of the most promising alternatives to PSA being studied currently: PCA3, serum kallikreins, serum detectable prostate specific membrane antigen, the nuclear matrix protein EPCA, EPCA-2, prostatic acid phosphatase, urine detectable GSTP1, anti-AMACR antibodies, sarcosine, plasminogen activating urokinase, IGFBP, TGF beta 1,PSP94, IL6, plasmatic DNA, serum autoantibodies, neuroendocrine markers, proteomic analysis.

  13. 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

  14. Serum and Urinary NGAL in Septic Newborns

    PubMed Central

    Suchojad, Anna; Majcherczyk, Malgorzata; Jadamus-Niebroj, Danuta; Owsianka-Podlesny, Teresa; Brzozowska, Aniceta

    2014-01-01

    Neutrophil gelatinase-associated lipocalin (NGAL) is postulated to be a potentially new and highly specific/sensitive marker of acute kidney injury (AKI). The aim of this study was to assess the impact of inflammation on serum and urine NGAL in newborns that were treated due to infection. We determined serum and urine NGAL concentrations in 73 infants (51 with sepsis; 22 with severe sepsis) admitted to the Intensive Care Unit in the first month of life, for three consecutive days during the course of treatment for infection. 29 neonates without infection served as the control group. Septic patients, in particular, severe sepsis patients, had increased serum and urinary NGAL levels in the three subsequent days of observation. Five septic patients who developed AKI had elevated serum and urinary NGAL values to a similar extent as septic neonates without AKI. A strong correlation was found between the concentration of serum and urinary NGAL and inflammatory markers, such as CRP and procalcitonin. Serum and urinary NGAL levels were also significantly associated with NTISS (neonatal therapeutic intervention scoring system) values. We conclude that increased serum and urinary NGAL values are not solely a marker of AKI, and more accurately reflect the severity of inflammatory status. PMID:24579085

  15. Killing of Brucella abortus by bovine serum.

    PubMed

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

    1988-12-01

    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.

  16. Serum bile acids in patients with hyperlipidaemia.

    PubMed Central

    Pennington, C R; Ross, P E; Bateson, M C; Bouchier, I A

    1978-01-01

    Individual serum bile acids were analysed by an improved gas liquid chromatography method in 12 patients with primary hyperlipidaemia. Total serum bile acid concentrations were raised in 10 subjects. Ursodeoxycholic acid was found in all 12 patients. It was present in significantly greater concentrations, accounted for a greater proportion of the total serum bile acids, and occurred more frequently than in patients with various forms of hepatobiliary disease. Patients with hyperlipidaemia had proportionately less deoxycholic acid than controls but more than patients with liver disease. There was proportionately less chenodeoxycholic acid in patients with hypercholesterolaemia, in whom the primary bile acid ratio was raised. PMID:627619

  17. Serum nickle estimation in acute myocardial infarction.

    PubMed

    Narang, N K; Goyal, R K; Gupta, A K; Balwani, S

    1989-11-01

    Serum nickle was estimated by atomic absorption spectrometer in 20 healthy controls and in 25 cases of acute myocardial infarction at 12 hourly intervals upto 48 hours, after the onset of chest pain. The mean serum nickel was 0.27 micrograms/dl in healthy controls and 0.40,050,049 and 0.30 micrograms/dl in patients of acute myocardial infarction. The serum nickel values were significantly (P less than 0.001) raised upto 36 hours in acute myocardial infarction when compared with controls.

  18. Improved ultraviolet spectrophotometry of serum theophylline.

    PubMed

    Carter, P; Wallace, J E; Blum, K

    1978-02-01

    We present an improved method for ultraviolet spectrophotometry of theophylline in serum. We studied various extraction techniques aimed at eliminating interferences from co-extractable serum constituents. In the resulting modified procedure, 1 ml of serum is required and a salt-solvent pair of ammonium sulfate and chloroform/hexane is used for extraction. The solvent forms the top phase after extraction, the lower phase after back-extraction, thereby permitting easy removal of the appropriate phase from culture tubes. The use of ammonium sulfate coupled with the added specificity of the extraction solvent results in an extract with low background absorption and a well-defined spectrum for the extracted theophylline.

  19. The Second International Standard for Serum Gonadotrophin*

    PubMed Central

    Bangham, D. R.; Woodward, Patricia M.

    1966-01-01

    In 1961 the WHO Expert Committee on Biological Standardization asked the National Institute for Medical Research, London, to collect and study material to replace the first International Standard for Serum Gonadotrophin, stocks of which were running low. This paper describes the material that was contributed, its distribution into ampoules and the international collaborative assay to compare its biological activity with that of the first International Standard. On the basis of the results obtained the material has been established as the second International Standard for Serum Gonadotrophin, with a potency of 1600 International Units per ampoule. The International Unit for Serum Gonadotrophin is thus defined as the activity contained in 0.003569 mg of the second International Standard for Serum Gonadotrophin. PMID:5297810

  20. 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

  1. Serum ferritin in juvenile chronic polyarthritis.

    PubMed Central

    Craft, A W; Eastham, E J; Bell, J I; Brigham, K

    1977-01-01

    Six children with juvenile chronic polyarthritis were studied and their disease activity correlated with haematological values including serum ferritin. The latter is often raised above reference values, but even when within them appears to fluctuate significantly and correlates more closely with disease activity than any of the other parameters measured. We conclude that the serial measurement of serum ferritin may be a useful guide to the management of such children. PMID:879866

  2. Moving past serology: Diagnostic options without serum.

    PubMed

    Reichel, Michael P; Lanyon, Sasha R; Hill, Fraser I

    2016-09-01

    Detecting antibodies formed in serum in response to infection is the traditional function of serology. Diagnostic modalities have included complement fixation tests, agar gel immune-diffusion, radioimmunoassay, ELISA and immunofluorescence. More recent technology now allows for the direct detection of pathogens by PCR. This review details the options for diagnostic testing using specimen types other than serum, identifying the advantages and disadvantages of these options and providing evidence for more widespread use of these techniques and specimen types. PMID:27160006

  3. [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

  4. 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.

  5. Serum vitamin B12 in renal failure

    PubMed Central

    Matthews, D. M.; Beckett, A. Gordon; Maxwell, Patricia

    1962-01-01

    The serum vitamin B12 level was abnormally high in 14 out of 32 cases of renal failure. This was probably due to impaired excretion of the vitamin, but the results of measurements of the rate of excretion of radioactive vitamin B12 did not provide unequivocal evidence on this point; other possible explanations are discussed. Renal failure must be added to the causes of high serum B12 levels. PMID:13933867

  6. (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.

  7. 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

  8. 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

  9. Serum concentrations of haptoglobin and serum amyloid A in water buffaloes (Bubalus bubalis) with abomasal ulcer.

    PubMed

    Tajik, Javad; Nazifi, Saeed; Heidari, Mahdi; Babazadeh, Marzieh

    2012-01-01

    To evaluate the serum concentrations of haptoglobin (Hp) and serum amyloid A (SAA) in water buffaloes with abomasal ulcers, the abomasums of 100 randomly selected water buffaloes were examined after slaughter. Type I abomasal ulcers were found in 56 out of 100 buffaloes. Serum concentrations of Hp and SAA were measured. There was no significant difference between affected and non-affected buffaloes in the serum concentrations of Hp and SAA. The serum concentrations of Hp and SAA had no significant correlation with age and the serum SAA revealed no significant correlation with the number of abomasal ulcers. A significant correlation was found between the serum Hp and the number of abomasal ulcers (r =0.29, p = 0.04). There was no significant difference in the serum concentrations of Hp and SAA between buffaloes with different ulcer locations in the abomasums. Although more work on a larger number of animals is required in this area, it seems that the measurement of the serum Hp can be used to predict the abundance of type I abomasal ulcers.

  10. 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.

  11. Induction of apoptosis in cultured hepatocytes and in regressing liver by transforming growth factor beta 1.

    PubMed Central

    Oberhammer, F A; Pavelka, M; Sharma, S; Tiefenbacher, R; Purchio, A F; Bursch, W; Schulte-Hermann, R

    1992-01-01

    In previous studies hepatocytes undergoing cell death by apoptosis but not normal hepatocytes in rat liver showed immunostaining for transforming growth factor beta 1 (TGF-beta 1). Staining was much stronger with antibodies recognizing the pro-region of TGF-beta 1 than the mature peptide itself. Therefore we investigated the ability of both forms of TGF-beta 1 to induce apoptosis in primary cultures of rat hepatocytes. Mature TGF-beta 1 induced rounding up of the cells and fragmentation into multiple vesicles. As revealed by the DNA-specific stain H33258, the chromatin of these cells condensed and segregated into masses at the nuclear membrane; this was obviously followed by fragmentation of the nucleus. Ultrastructurally the cytoplasm was well preserved, as demonstrated by the presence of intact cell organelles. These features strongly suggest the occurrence of apoptosis. Quantification of nuclei with condensed chromatin revealed that mature TGF-beta 1 was 30-fold more effective than the TGF-beta 1 latency-associated protein complex. Finally, we administered TGF-beta 1 in vivo using an experimental model in which regression of rat liver was initiated by a short preceding treatment with the hepatomitogen cyproterone acetate. Two doses of TGF-beta 1, each 1 nM/kg, augmented the incidence of apoptotic hepatocytes 5-fold. Equimolar doses of TGF-beta 1 latency-associated protein complex were ineffective. These studies suggest that TGF-beta 1 is involved in the initiation of apoptosis in the liver and that the mature form of TGF-beta 1 is the active principle. Images PMID:1608949

  12. Peptidomic Identification of Serum Peptides Diagnosing Preeclampsia

    PubMed Central

    Wu, Shuaibin; Stevenson, David K.; Sheng, Guojun; Butte, Atul J.; Ling, Xuefeng B.

    2013-01-01

    We sought to identify serological markers capable of diagnosing preeclampsia (PE). We performed serum peptide analysis (liquid chromatography mass spectrometry) of 62 unique samples from 31 PE patients and 31 healthy pregnant controls, with two-thirds used as a training set and the other third as a testing set. Differential serum peptide profiling identified 52 significant serum peptides, and a 19-peptide panel collectively discriminating PE in training sets (n = 21 PE, n = 21 control; specificity = 85.7% and sensitivity = 100%) and testing sets (n = 10 PE, n = 10 control; specificity = 80% and sensitivity = 100%). The panel peptides were derived from 6 different protein precursors: 13 from fibrinogen alpha (FGA), 1 from alpha-1-antitrypsin (A1AT), 1 from apolipoprotein L1 (APO-L1), 1 from inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4), 2 from kininogen-1 (KNG1), and 1 from thymosin beta-4 (TMSB4). We concluded that serum peptides can accurately discriminate active PE. Measurement of a 19-peptide panel could be performed quickly and in a quantitative mass spectrometric platform available in clinical laboratories. This serum peptide panel quantification could provide clinical utility in predicting PE or differential diagnosis of PE from confounding chronic hypertension. PMID:23840341

  13. Serum growth factors in asbestosis patients.

    PubMed

    Li, Yongliang; Karjalainen, Antti; Koskinen, Heikki; Vainio, Harri; Pukkala, Eero; Hemminki, Kari; Brandt-Rauf, Paul W

    2009-02-01

    Various growth factors, including platelet-derived growth factor (PDGF) and transforming growth factor (TGF)-beta, have been implicated in the pathogenesis of asbestos-induced disease. PDGF and TGF-beta levels were determined by enzyme-linked immunosorbent assays in the banked serum samples of a cohort of workers with asbestosis, and the relationships of the growth factor levels to the subsequent development of cancer and to the radiographic severity and progression of asbestosis in the cohort were examined. Serum levels of PDGF and TGF-beta were found to be unrelated to the development of cancer, and serum levels of PDGF were found to be unrelated to the severity and progression of asbestosis. However, serum levels of TGF-beta were found to be statistically significantly related to disease severity (p = 0.01), increasing approximately 2.4-fold from ILO radiographic category 0 to category 3, and they were marginally related to disease progression (p = 0.07), in multivariate analysis controlling for other contributory factors including cumulative asbestos exposure. This suggests that serum TGF-beta may be a useful biomarker for asbestos-induced fibrotic disease. PMID:19283526

  14. Serum albumin and risk of venous thromboembolism

    PubMed Central

    Folsom, Aaron. R.; Lutsey, Pamela L.; Heckbert, Susan R.; Cushman, Mary

    2010-01-01

    Summary The incidence of venous thromboembolism (VTE) is increased in patients with albuminuria. However, whether a low serum albumin concentration is associated with increased risk of VTE has been a matter of controversy. We determined the association of serum albumin with VTE incidence in two large, prospective, population-based cohorts: the Atherosclerosis Risk in Communities (ARIC) Study (n = 15,300) and the Cardiovascular Health Study (CHS) (n = 5,400). Validated VTE occurrence (n=462 in ARIC and n=174 in CHS) was ascertained during follow-up. In both studies, after adjustment for age, sex, race, use of hormone replacement therapy, estimated GFR, history of cancer, and diabetes, serum albumin tended to be associated inversely with VTE. The adjusted hazard ratio per standard deviation lower albumin was 1.18 (95% CI = 1.08, 1.31) in ARIC and 1.10 (95% CI = 0.94, 1.29) in CHS. The hazard ratio for albumin below (versus above) the fifth percentile was 1.28 (95% CI = 0.90, 1.84) in ARIC and 1.80 (95% CI = 1.11, 2.93) in CHS. In conclusion, low serum albumin was a modest marker of increased VTE risk. The observed association likely does not reflect cause and effect, but rather that low serum albumin reflects a hyperinflammatory or hypercoagulable state. Whether this association has clinical relevance warrants further study. PMID:20390234

  15. 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.

  16. Serum cytokine changes in systemic vasculitis.

    PubMed Central

    Grau, G E; Roux-Lombard, P; Gysler, C; Lambert, C; Lambert, P H; Dayer, J M; Guillevin, L

    1989-01-01

    Cytokines are known to alter a number of vascular tissue cell functions. The aim of this retrospective study was to determine serum cytokine levels in patients with vasculitis and to analyse the possible relation to the severity of the disease. Tumour necrosis factor alpha (TNF alpha), interleukin-1 (IL-1)beta, IL-2, interferon (IFN)- and IFN-gamma were assayed in 33 patients with polyarteritis nodosa (PAN) or Churg and Strauss angiitis (CSA), and three with Wegener granulomatosis (WG). Serum cytokine changes were observed in most patients with active disease, i.e. before treatment was started. In the majority of patients with PAN or CSA, there was a marked increase in serum IFN-alpha and IL-2 levels, while TNF-alpha and IL-beta levels were moderately elevated. Serum IFN-gamma remained undetectable in all but one of these patients. In patients with WG, serum IFN-alpha and IL-2 levels were also elevated, whereas IL-1 beta, IFN-gamma and TNF alpha levels remained within normal limits. In paired samples of patients with PAN, IFN-alpha and IL-2 levels were significantly higher before than after treatment. These preliminary data suggest that a particular pattern of cytokine changes is associated with vasculitis and that cytokines might be involved in the pathogenesis of PAN/CSA and WG. Prospective studies are warranted to determine whether cytokines could be considered for the monitoring of disease activity and therapy. PMID:2478451

  17. Interpretation of the serum digoxin concentration.

    PubMed

    Weintraub, M

    1977-01-01

    Significant problems exist in the interpretation of serum digoxin concentration data. Failure to distinguish between results that do not require precise clinical correlation (proof of absorption, presence of drug, etc) and those which depend upon clinical correlation for their meaning ('toxicity' or 'effectiveness') can result in interpretive errors. Problems relating to the source of the serum digoxin concentration can also confound interpretation. Such difficulty may be controllable (obtaining the sample at the proper time, haemolysis, etc) or related to the laboratory technique (cross-reactivity with digoxin metabolites or other medications, technical errors, or lack of precision). Variation within the same patient over time or between patients related to disease (alterations in electrolytes, adrenergic or parasympathomimetic tone, or other medications) may prevent the direct attribution of an observed phenomenon to a particular digoxin concentration. Techniques for determining the effect of digoxin do exist and can be used to gather data for clinical correlations. Ways of improving the interpretaion of serum digoxin concentrations also exist and should be used to improve their value in patient management. The serum digoxin concentration seems to have an important future role. However, we need to know how better to interpret and exploit serum digoxin concentration data.

  18. Circulating DNA in plasma or serum.

    PubMed

    Anker, P; Stroun, M

    2000-01-01

    Small amounts of DNA circulate in both healthy and diseased human plasma/serum, and increased concentrations of DNA are present in the plasma of cancer patients. Characteristics of tumor DNA have been found in genetic material extracted from the plasma of cancer patients. These features include decreased strand stability, the presence of specific oncogene or tumor suppressor gene mutations, microsatellite alterations, Ig rearrangements and hypermethylation of several genes. The results obtained in many different cancers have opened a new research area indicating that plasma DNA might eventually be a suitable target for the development of noninvasive diagnostic, prognostic and follow-up tests for cancer. Following the discovery of tumor derived DNA in plasma or serum, cell-free fetal DNA has also been found in maternal plasma and serum. This discovery provides an easily accessible source of fetal genetic material for prenatal diagnosis.

  19. Clinical importance of thrombomodulin serum levels.

    PubMed

    Califano, F; Giovanniello, T; Pantone, P; Campana, E; Parlapiano, C; Alegiani, F; Vincentelli, G M; Turchetti, P

    2000-01-01

    Thrombomodulin is a glycoprotein that can bind to thrombin and activate protein C, thus mitigating the effects of cytokines produced by inflammatory and immunological processes. The molecule exerts a protective function on endothelial cells. Thrombomodulin is cleaved to its soluble form by neutrophil elastase and by other substances produced during acute and chronic inflammatory responses, immunologic reactions and complement activation. ELISA technique yields normal serum levels of 3.1 +/- 1.3 ng/ml; in males these levels are higher; TM levels also rise during menopause. Other circumstances associated with an increase of serum TM levels are smoking, disseminated intravascular coagulation (DIC), cardiac surgery, atherosclerosis, ARDS, liver cirrhosis, diabetes mellitus, cerebral and myocardial infarction, and multiple sclerosis. Serum levels of TM represent an useful prognostic index, because they are associated with an increase in mortality rate, or however a progression of the underlying pathological condition. PMID:11558626

  20. Iohexol in serum determined by capillary electrophoresis.

    PubMed

    Shihabi, Z K; Constantinescu, M S

    1992-10-01

    Iohexol, a nonionic compound used as a contrast medium for angiography and as a measure of the glomerular filtration rate, was quantified in serum by capillary electrophoresis. Comparable results were obtained for serum samples deproteinized with acetonitrile or analyzed directly after 50-fold dilution with borate buffer. Serum samples were electrophoresed for 2.6 min at 12 kV in a borate buffer with detection at 254 nm and with 3-isobutyl-1-methylxanthine as internal standard. Acetonitrile deproteinization gave a greater sensitivity than did sample dilution. Between-run CVs were between 4.7% and 6.7%, and within-run CVs were between 2.5 and 3.2%. Analytical recoveries were 95-105%. Results of the method compared well with those by high-performance liquid chromatography (slope 0.96, intercept 0.005 g/L). This method demonstrates the potential of capillary electrophoresis for rapid and simple quantification of small molecules.

  1. Serum adenosine deaminase activity in cutaneous anthrax

    PubMed Central

    Sunnetcioglu, Mahmut; Karadas, Sevdegul; Aslan, Mehmet; Ceylan, Mehmet Resat; Demir, Halit; Oncu, Mehmet Resit; Karahocagil, Mustafa Kasım; Sunnetcioglu, Aysel; Aypak, Cenk

    2014-01-01

    Background Adenosine deaminase (ADA) activity has been discovered in several inflammatory conditions; however, there are no data associated with cutaneous anthrax. The aim of this study was to investigate serum ADA activity in patients with cutaneous anthrax. Material/Methods Sixteen patients with cutaneous anthrax and 17 healthy controls were enrolled. We measured ADA activity; peripheral blood leukocyte, lymphocyte, neutrophil, and monocyte counts; erythrocyte sedimentation rate; and C reactive protein levels. Results Serum ADA activity was significantly higher in patients with cutaneous anthrax than in the controls (p<0.001). A positive correlation was observed between ADA activity and lymphocyte counts (r=0.589, p=0.021) in the patient group. Conclusions This study suggests that serum ADA could be used as a biochemical marker in cutaneous anthrax. PMID:24997584

  2. How does whisky lower serum urate level?

    PubMed

    Lu, Yang; Nakanishi, Takeo; Fukazawa, Miki; Tamai, Ikumi

    2014-05-01

    Clinical studies have shown that moderate whisky consumption increased renal excretion of urate into urine and decreased serum urate level, but the mechanism involved has not been established. Because renal reabsorption influences serum urate level, the effects of the whisky congeners on urate transporters, urate transporter 1 (URAT1), and voltage-driven urate transporter (URATv1) involved in reabsorptive transport of urate were examined. In transporter-expressing Xenopus oocytes, 12-year-old and 18-year-old whisky congeners inhibited urate uptake by URAT1 with IC50 values of 0.08 ± 0.01 and 0.04 ± 0.01 mg/mL, respectively, while urate uptake by URATv1 was inhibited only at 1 mg/mL. Decreased serum urate level after whisky consumption may be mainly due to inhibition of URAT1 by the congeners.

  3. 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

  4. 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.

  5. [Cold sterilization of serums with peracetic acid].

    PubMed

    Sprössig, M; Wutzler, P; Schweizer, H; Mücke, H

    1976-01-01

    On the basis of broad antimicrobic effect including also bacterial spores, mycoplasmas and viruses, the peracetic acid suits to sterilize in cold. By means of the final 0,1 to 0.02% concentration of the peracetic acid acting for 30 min. up to 5 days, it succeeded in sterilizing the serum used to prepare culture medium for bacteria, mycoplasmas and tissue cultures. Growth controls shown at least as good results as were those in using filtered sera. Chemical sterilization by means of the peracetic acid leads to significant diminution of neutralization and complementfixation antibodies in serum. PMID:823257

  6. Dietary phosphorus, serum phosphorus, and cardiovascular disease.

    PubMed

    Menon, Madhav C; Ix, Joachim H

    2013-10-01

    Recent epidemiologic studies have linked higher serum phosphorus concentrations to cardiovascular disease (CVD) events and mortality. This association has been identified in the general population and in those with chronic kidney disease (CKD). The risk of adverse outcomes appears to begin with phosphorus concentrations within the upper limit of the normal reference range. Multiple experimental studies have suggested pathogenetic mechanisms that involve direct and indirect effects of high phosphorus concentrations to explain these associations. Drawing from these observations, guideline-forming agencies have recommended that serum phosphorus concentrations be maintained within the normal reference range in patients with CKD and that dietary phosphorus restriction or use of intestinal phosphate binders should be considered to achieve this goal. However, outside the dialysis population, the links between dietary phosphorus intake and serum phosphorus concentrations, and dietary phosphorus intake and CVD events, are uncertain. With specific reference to the nondialysis populations, this review discusses the available data linking dietary phosphorus intake with serum phosphorus concentrations and CVD events.

  7. EFFECT OF LITHIUM ON SERUM ELECTROLYTES

    PubMed Central

    Geetha, P.R.; Channabasavanna, S.M.; Rama Rao, B.S. Sridhara

    1983-01-01

    SUMMARY 26 patients diagnosed as manic depressive psychosis were treated with lithium for three months and serum levels of calcium, magnesium, phosphates and proteins were estimated repeatedly. There were no significant changes in the levels of these electrolytes and proteins during the three months of study period. PMID:21847255

  8. 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...

  9. 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)

  10. 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 ...

  11. Removal of transferrin from fetal bovine serum.

    PubMed

    Huebers, E; Nelson, N J; Huebers, H A; Rasey, J S

    1987-12-01

    An antiserum against purified fetal bovine serum (FBS) transferrin was produced in rabbits. The isolation of anti-bovine transferrin IgG fraction was achieved by ammonium sulfate precipitation of rabbit hyperimmune plasma followed by ion exchange chromatography on diethylaminoethanol (DEAE) cellulose, at both an acidic and basic pH. The various antibody fractions were analyzed by fast protein liquid chromatography (FPLC) on a high-resolution mono-Q column. The specificity and efficiency of the antibody fractions obtained were tested by titration of a constant amount of fetal bovine serum with increasing amounts of antibody. The completeness of removal of the fetal bovine serum transferrin resulting from the formation of the highly stable antibody antigen complex was monitored by immunologic and radioisotope methods. The removal of FBS transferrin by this antibody precipitation technique did not interfere with the ability of added iron 59-tagged human transferrin to deliver iron to rat reticulocytes, as shown in an in vivo incubation model. The method proved to be effective for the fast and complete removal of bovine transferrin from fetal bovine serum in vitro and will be a prerequisite for more detailed studies of the interaction of transferrin of different species with tissue receptors on cell lines in culture without resorting to completely defined culture media. PMID:3681114

  12. 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.

  13. 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

  14. Serum Polyunsaturated Fatty Acids and Endometriosis.

    PubMed

    Hopeman, Margaret M; Riley, Joan K; Frolova, Antonina I; Jiang, Hui; Jungheim, Emily S

    2015-09-01

    Polyunsaturated fatty acids (PUFAs) are fatty acids containing 2 or more double bonds, and they are classified by the location of the last double bond. Omega 3 (n-3) and omega 6 (n-6) PUFAs are obtained through food sources including fatty fish and seed/vegetable oils, respectively, and they are important to a number of physiologic processes including inflammation. Previous work demonstrates suppressive effects of n-3 PUFAs on endometriotic lesions in animal models and decreased risk of endometriosis among women with high n-3 PUFA intake. Thus, we sought to determine the relationship between circulating levels of PUFAs and endometriosis in women. To do this, we performed a cross-sectional study of serum PUFAs and clinical data from 205 women undergoing in vitro fertilization (IVF). Serum PUFAs were measured using liquid chromatography coupled to tandem mass spectroscopy and included n-3 PUFAs such as α-linolenic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid and n-6 PUFAs such as linoleic acid and arachidonic acid. Multivariable logistic regression was used to determine relationships between specific and total serum PUFAs and patient history of endometriosis. Women with high serum EPA levels were 82% less likely to have endometriosis compared to women with low EPA levels (odds ratio = 0.18, 95% confidence interval 0.04-0.78).

  15. 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.

  16. Serum levels of pancreatic enzymes in lean and obese subjects.

    PubMed

    Kondo, T; Hayakawa, T; Shibata, T; Sato, Y; Toda, Y

    1988-05-01

    Serum amylase and trypsin, but not lipase, were significantly lower in obese subjects than in lean subjects. Serum amylase and trypsin, but not lipase, had significant inverse correlation with body weight. Low serum amylase was associated with low protein, fat and carbohydrate intakes per kg body weight, whereas low serum trypsin was associated with low carbohydrate intake per kg body weight. Low serum pancreatic enzymes readily increased with diet therapy. It is assumed that lowered serum pancreatic enzymes in obese subjects are somehow related to their diet intake. The mechanism through which pancreatic enzymes in the blood reflect the composition of food is unclear.

  17. Serum cholesterol concentrations among Navajo Indians.

    PubMed

    Sugarman, J R; Gilbert, T J; Percy, C A; Peter, D G

    1992-01-01

    Navajo Indians have been reported by earlier investigators to have low concentrations of serum lipids and a low prevalence of hyperlipidemia, as well as low rates of ischemic heart disease. However, no data on serum lipid concentrations among Navajos have been reported for more than two decades. The authors conducted a study to determine the distribution of concentrations of serum total cholesterol (TC), high density lipoprotein cholesterol, low density lipoprotein cholesterol, and triglyceride among persons 25-74 years old living in a representative community on the Navajo Indian reservation. Data are reported for 255 subjects, 105 men and 150 women, ages 25-74 years. The authors compared these data to those for the general population as determined by the second National Health and Nutrition Examination Survey (NHANES II). TC concentrations among Navajo men were similar to those from NHANES II. TC concentrations among younger Navajo women were similar to those for women younger than 55 years from NHANES II, but were significantly lower among older Navajo women. While 27.6 percent of men ages 25-74 years studied in NHANES II had TC concentrations greater than 240 milligrams per deciliter, 33.8 percent of Navajo men had similarly elevated TC. However, the prevalence of serum TC concentrations greater than 240 milligrams per deciliter among Navajo women (17.5 percent) was about half that among women studied in NHANES II (32.9 percent). A similar pattern was found for low density lipoprotein cholesterol. The researchers concluded that Navajo Indians are no longer characterized by low serum lipid concentrations, that increased cholesterol concentrations may be a harbinger of increasing rates of atherosclerotic coronary heart disease among Navajos, and that attention should be directed to primary prevention of hyperlipidemia in Navajo Indian communities. PMID:1738814

  18. 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

  19. 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.

  20. Immunohistochemical localization of transforming growth factor-beta 1 in the lungs of patients with systemic sclerosis, cryptogenic fibrosing alveolitis and other lung disorders.

    PubMed

    Corrin, B; Butcher, D; McAnulty, B J; Dubois, R M; Black, C M; Laurent, G J; Harrison, N K

    1994-02-01

    To study the role of transforming growth factor-beta 1 (TGF-beta 1) in the pathogenesis of pulmonary fibrosis we have examined lung biopsies from nine patients with systemic sclerosis and interstitial lung disease, eight with 'lone' cryptogenic fibrosing alveolitis, two with cystic fibrosis, two with extrinsic allergic alveolitis, two with Langerhans' cell histiocytosis, one with lymphangioleiomyomatosis, one with giant cell interstitial pneumonia, and one adenocarcinoma of the lung. In cryptogenic fibrosing alveolitis, both 'lone' and associated with systemic sclerosis alveolar macrophages, bronchial epithelium and hyperplastic type II pneumonocytes expressed intracellular TGF-beta 1. Extracellular TGF-beta 1 was found in the fibrous tissue immediately beneath the bronchial and hyperplastic alveolar epithelium. In normal lung, however, the alveolar epithelium and alveolar interstitium were negative for both forms of TGF-beta 1. There was strong expression of TGF-beta 1 in hyperplastic mesothelium and its underlying connective tissue and in Langerhans' cells in the two cases of histiocytosis. In the organizing pneumonia in cystic fibrosis, the intraalveolar buds of granulation tissue reacted strongly for the extracellular form of TGF-beta 1 and the overlying hyperplastic epithelium expressed the intracellular form. In lymphangioleiomyomatosis, the aberrant smooth muscle cells strongly expressed intracellular TGF-beta 1 and the extracellular form was expressed in the adjacent connective tissue. In giant cell interstitial pneumonia, the numerous alveolar macrophage including the multinucleate forms, expressed intracellular TGF-beta 1, as did the hyperplastic alveolar epithelium.(ABSTRACT TRUNCATED AT 250 WORDS)

  1. Adenovector-mediated gene transfer of active transforming growth factor-beta1 induces prolonged severe fibrosis in rat lung.

    PubMed Central

    Sime, P J; Xing, Z; Graham, F L; Csaky, K G; Gauldie, J

    1997-01-01

    Transforming growth factor (TGF)-beta1 has been implicated in the pathogenesis of fibrosis based upon its matrix-inducing effects on stromal cells in vitro, and studies demonstrating increased expression of total TGF-beta1 in fibrotic tissues from a variety of organs. The precise role in vivo of this cytokine in both its latent and active forms, however, remains unclear. Using replication-deficient adenovirus vectors to transfer the cDNA of porcine TGF-beta1 to rat lung, we have been able to study the effect of TGF-beta1 protein in the respiratory tract directly. We have demonstrated that transient overexpression of active, but not latent, TGF-beta1 resulted in prolonged and severe interstitial and pleural fibrosis characterized by extensive deposition of the extracellular matrix (ECM) proteins collagen, fibronectin, and elastin, and by emergence of cells with the myofibroblast phenotype. These results illustrate the role of TGF-beta1 and the importance of its activation in the pulmonary fibrotic process, and suggest that targeting active TGF-beta1 and steps involved in TGF-beta1 activation are likely to be valuable antifibrogenic therapeutic strategies. This new and versatile model of pulmonary fibrosis can be used to study such therapies. PMID:9259574

  2. Tyrosine dephosphorylation of nuclear proteins mimics transforming growth factor {beta}1 stimulation of {alpha}2(I) collagen gene expression

    SciTech Connect

    Greenwel, P.; Hu, Wei; Ramirez, F.; Kohanski, R.A.

    1995-12-01

    This report describes how the transforming growth factor {beta}1 (TGF-{beta}1) stimulates the transcription of the gene coding for collagen I (COL1A2). The report goes on to correlate tyrosine dephosphorylation, increased binding of a transcriptional complex and TGF-{beta}1 stimulation of gene expression. 33 refs., 8 figs., 1 tab.

  3. The JCR:LA-cp rat: a novel model for impaired wound healing.

    PubMed

    Bauer, Barbara S; Ghahary, Aziz; Scott, Paul G; Iwashina, Takashi; Demare, Jack; Russell, James C; Tredget, Edward E

    2004-01-01

    JCR:LA-cp/cp obese rats and their lean controls were evaluated as a type 2 diabetic wound healing model and the healing quality was characterized. This model of insulin resistance has been used extensively to study atherosclerosis but has not previously been used to study wound healing. Six circular excisional wounds were made on the dorsum of each rat and followed to day 21. Tracings of the wounds were made and used to assess the rate of wound closure. Planimetry showed a significantly diminished contraction of wounds in obese rats, but no significant difference in reepithelialization was observed. Collagen content was determined from the hydroxyproline content in wounded and unwounded skin. There were significantly lower levels of hydroxyproline in the wounds of obese compared to lean animals at day 21. Histology showed adipose tissue in place of dermal tissue in the JCR:LA-cp/cp rat in both unwounded tissue and in the wound at day 21. Active transforming growth factor-beta 1 (TGF-beta 1) was measured in the serum using the plasminogen activator inhibitor-1/luciferase assay and serum total TGF-beta was measured using an enzyme-linked immunosorbent assay. Active TGF-beta was significantly higher in the serum of obese animals compared with lean animals, while total TGF-beta 1 was not significantly different between the groups. Both active and total TGF-beta was measured in tissue sections using the plasminogen activator inhibitor-1/luciferase assay. There was no significant difference in active TGF-beta between genotypes, while obese rats had significantly higher levels of total TGF-beta at day 21. These results indicate a deficiency in wound healing in obese animals characterized by decreased wound contraction, decreased collagen production, and changes in histology. The JCR:LA-cp rat develops insulin resistance, atherosclerosis and early type 2 diabetes and may be a good model for impairment of wound healing in humans with metabolic syndrome.

  4. Relationships between serum serotonin and serum lipid levels, and aggression in horses.

    PubMed

    Meral, Y; Cakiroğlu, D; Sancak, A A; Cýftcý, G; Karabacak, A

    2007-01-01

    Levels of serum serotonin and serum lipids--triglyceride, total cholesterol, low-density lipoprotein, high-density lipoprotein and very low-density lipoprotein, were determined in normal horses and horses diagnosed with aggression on the basis of a questionnaire survey. Blood serotonin levels in aggressive horses were found to be significantly lower than in non-aggressive horses (P < 0.01), but no association was found with respect to blood lipids. PMID:17252934

  5. Genome-wide serum microRNA expression profiling identifies serum biomarkers for Alzheimer's disease.

    PubMed

    Tan, Lin; Yu, Jin-Tai; Tan, Meng-Shan; Liu, Qiu-Yan; Wang, Hui-Fu; Zhang, Wei; Jiang, Teng; Tan, Lan

    2014-01-01

    Recent findings that human serum contains stably expressed microRNAs (miRNAs) have revealed a great potential of serum miRNA signature as disease fingerprints to diagnosis. Here we used genome-wide serum miRNA expression analysis to investigate the value of serum miRNAs as biomarkers for the diagnosis of Alzheimer's disease (AD). Illumina HiSeq 2000 sequencing followed by individual quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) assays was used to test the difference in levels of serum miRNAs between 50 AD patients and 50 controls in the screening stages. The detected serum miRNAs then were validated by qRT-PCR in 158 patients and 155 controls. MiR-98-5p, miR-885-5p, miR-483-3p, miR-342-3p, miR-191-5p, and miR-let-7d-5p displayed significantly different expression levels in AD patients compared with controls. Among the 6 miRNAs, miR-342-3p has the best sensitivity (81.5%) and specificity (70.1%) and was correlated to Mini-Mental State Examination score. This study identified six serum miRNAs that distinguish AD patients from healthy controls with high sensitivity and specificity. Serum miRNA panel (or miR-342-3p alone) may serve as a novel, noninvasive biomarker for AD.

  6. 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.

  7. [Modified albumin in harp seal blood serum].

    PubMed

    Erokhina, I A

    1999-01-01

    The content of modified albumin (Am) in harp seal (Pagophilus groenlandica Erxleben, 1777) blood serum was studied. Am was determined by paper electrophoresis by means of re-precipitation in the trichloroacetic acid-ethanol system. Modified albumin content in normal seal pups' blood serum increased from 1990 to 1994. The Am level in undernourished pups was stable from year to year and higher than in normal pups. In oceanarium investigations it was revealed a low albumin resistance to denaturation and the dependence of Am content on the animals' physiological state. Thus there is a possibility to regard modified albumin content as one of the significant parameters in biomonitoring of harp seal population and, moreover, as a supplementary criterion for estimation of seals' health state in captivity.

  8. 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.

  9. 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…

  10. Serum Antibody Repertoire Profiling Using In Silico Antigen Screen

    PubMed Central

    Liu, Xinyue; Hu, Qiang; Liu, Song; Tallo, Luke J.; Sadzewicz, Lisa; Schettine, Cassandra A.; Nikiforov, Mikhail; Klyushnenkova, Elena N.; Ionov, Yurij

    2013-01-01

    Serum antibodies are valuable source of information on the health state of an organism. The profiles of serum antibody reactivity can be generated by using a high throughput sequencing of peptide-coding DNA from combinatorial random peptide phage display libraries selected for binding to serum antibodies. Here we demonstrate that the targets of immune response, which are recognized by serum antibodies directed against sequential epitopes, can be identified using the serum antibody repertoire profiles generated by high throughput sequencing. We developed an algorithm to filter the results of the protein database BLAST search for selected peptides to distinguish real antigens recognized by serum antibodies from irrelevant proteins retrieved randomly. When we used this algorithm to analyze serum antibodies from mice immunized with human protein, we were able to identify the protein used for immunizations among the top candidate antigens. When we analyzed human serum sample from the metastatic melanoma patient, the recombinant protein, corresponding to the top candidate from the list generated using the algorithm, was recognized by antibodies from metastatic melanoma serum on the western blot, thus confirming that the method can identify autoantigens recognized by serum antibodies. We demonstrated also that our unbiased method of looking at the repertoire of serum antibodies reveals quantitative information on the epitope composition of the targets of immune response. A method for deciphering information contained in the serum antibody repertoire profiles may help to identify autoantibodies that can be used for diagnosing and monitoring autoimmune diseases or malignancies. PMID:23826227

  11. Serum Antibody Repertoire Profiling Using In Silico Antigen Screen.

    PubMed

    Liu, Xinyue; Hu, Qiang; Liu, Song; Tallo, Luke J; Sadzewicz, Lisa; Schettine, Cassandra A; Nikiforov, Mikhail; Klyushnenkova, Elena N; Ionov, Yurij

    2013-01-01

    Serum antibodies are valuable source of information on the health state of an organism. The profiles of serum antibody reactivity can be generated by using a high throughput sequencing of peptide-coding DNA from combinatorial random peptide phage display libraries selected for binding to serum antibodies. Here we demonstrate that the targets of immune response, which are recognized by serum antibodies directed against sequential epitopes, can be identified using the serum antibody repertoire profiles generated by high throughput sequencing. We developed an algorithm to filter the results of the protein database BLAST search for selected peptides to distinguish real antigens recognized by serum antibodies from irrelevant proteins retrieved randomly. When we used this algorithm to analyze serum antibodies from mice immunized with human protein, we were able to identify the protein used for immunizations among the top candidate antigens. When we analyzed human serum sample from the metastatic melanoma patient, the recombinant protein, corresponding to the top candidate from the list generated using the algorithm, was recognized by antibodies from metastatic melanoma serum on the western blot, thus confirming that the method can identify autoantigens recognized by serum antibodies. We demonstrated also that our unbiased method of looking at the repertoire of serum antibodies reveals quantitative information on the epitope composition of the targets of immune response. A method for deciphering information contained in the serum antibody repertoire profiles may help to identify autoantibodies that can be used for diagnosing and monitoring autoimmune diseases or malignancies. PMID:23826227

  12. Serum proteomic profiling of major depressive disorder

    PubMed Central

    Bot, M; Chan, M K; Jansen, R; Lamers, F; Vogelzangs, N; Steiner, J; Leweke, F M; Rothermundt, M; Cooper, J; Bahn, S; Penninx, B W J H

    2015-01-01

    Much has still to be learned about the molecular mechanisms of depression. This study aims to gain insight into contributing mechanisms by identifying serum proteins related to major depressive disorder (MDD) in a large psychiatric cohort study. Our sample consisted of 1589 participants of the Netherlands Study of Depression and Anxiety, comprising 687 individuals with current MDD (cMDD), 482 individuals with remitted MDD (rMDD) and 420 controls. We studied the relationship between MDD status and the levels of 171 serum proteins detected on a multi-analyte profiling platform using adjusted linear regression models. Pooled analyses of two independent validation cohorts (totaling 78 MDD cases and 156 controls) was carried out to validate our top markers. Twenty-eight analytes differed significantly between cMDD cases and controls (P<0.05), whereas 10 partly overlapping markers differed significantly between rMDD cases and controls. Antidepressant medication use and comorbid anxiety status did not substantially impact on these findings. Sixteen of the cMDD-related markers had been assayed in the pooled validation cohorts, of which seven were associated with MDD. The analytes prominently associated with cMDD related to diverse cell communication and signal transduction processes (pancreatic polypeptide, macrophage migration inhibitory factor, ENRAGE, interleukin-1 receptor antagonist and tenascin-C), immune response (growth-regulated alpha protein) and protein metabolism (von Willebrand factor). Several proteins were implicated in depression. Changes were more prominent in cMDD, suggesting that molecular alterations in serum are associated with acute depression symptomatology. These findings may help to establish serum-based biomarkers of depression and could improve our understanding of its pathophysiology. PMID:26171980

  13. Serum ferritin levels in hemoglobin H disease.

    PubMed

    Galanello, R; Melis, M A; Paglietti, E; Cornacchia, G; de Virgiliis, S; Cao, A

    1983-01-01

    This study shows that hemoglobin H disease patients aged between 0.5 and 44 years, usually (27 out of 30) have normal serum ferritin levels according to age. This reconfirms that in this disease there are usually normal iron stores. However, in a few patients (3 out of 30) increased levels were found. This may be due to inappropriate iron medication, transfusions or associated idiopathic hereditary hemocromatosis gene.

  14. 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.

  15. (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.

  16. 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

  17. 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

  18. Serum protein concentrations in Plasmodium falciparum malaria.

    PubMed

    Graninger, W; Thalhammer, F; Hollenstein, U; Zotter, G M; Kremsner, P G

    1992-12-01

    In patients with uncomplicated Plasmodium falciparum infection cytokine-mediated serum protein levels of C-reactive protein (CRP), coeruloplasmin (COE), beta 2-microglobulin (B2M), alpha 1-acid glycoprotein (AAG), alpha 1-antitrypsin (AAT), haptoglobin (HPT), prealbumin (PRE), retinol binding protein (RBP), albumin (ALB) and transferrin (TRF) were measured in an endemic area of the Amazonian rain forest. Semi-immune (SI) and nonimmune (NI) patients were investigated. In both patient groups the serum concentrations of CRP, COE and B2M were elevated on admission. In addition AAG and AAT concentrations were increased in NI patients compared to control subjects. Significantly lower serum concentrations of HPT, PRE, RBP, ALB and TRF were seen in both patient groups during the acute phase of the disease, and were more pronounced in NI patients. After a 28-day follow-up, AAT and B2M were normal in SI patients but HPT, AAT and B2M were still significantly altered in NI patients.

  19. The anti-fibrotic effect of liver growth factor is associated with decreased intrahepatic levels of matrix metalloproteinases 2 and 9 and transforming growth factor beta 1 in bile duct-ligated rats.

    PubMed

    Díaz-Gil, Juan J; García-Monzón, Carmelo; Rúa, Carmen; Martín-Sanz, Paloma; Cereceda, Rosa M; Miquilena-Colina, María E; Machín, Celia; Fernández-Martínez, Amalia; García-Cañero, Rarael

    2008-05-01

    Liver growth factor (LGF), a mitogen for liver cells, behaves as an anti-fibrotic agent even in extrahepatic sites, but its mechanistic basis is unknown. We aimed to determine the intrahepatic expression pattern of key modulators of liver fibrosis in bile duct-ligated rats (BDL) after injection of LGF. BDL rats received either LGF (4.5 microg/ratXdose, two doses/week, at time 0 or 2 or 5w after operation, depending on the group (BDL+LGF groups, n=20) or saline (BDL+S groups, n=20). Groups were compared in terms of fibrosis (histomorphometry), liver function (aminopyrine breath test), matrix metalloproteinases MMP-2 and MMP-9, transforming growth factor beta 1 (TGF-beta1) and liver endoglin content (Western blotting), and serum tissue inhibitor of metalloproteinases 1 (TIMP-1) levels (ELISA). In BDL+LGF rats, the fibrotic index was significantly lower at 5w, p=0.006, and at 8w, p=0.04, than in BDL+S rats. Liver function values in BDL+LGF rats were higher than those obtained in BDL+S rats (80% at 5w and 79% at 8w, versus 38% and 29%, p<0.01, taking healthy controls as 100%). Notably, in BDL+LGF rats the intrahepatic expression levels of both MMPs were lower at 2w (MMP-2, p=0.03; MMP-9, p=0.05) and 5w (MMP-2, p=0.05, MMP-9, p=0.04). In addition, the hepatic TGF-beta1 level in BDL+LGF rats was lower at 2w (36%, p=0.008), 5w (50%) and 8wk (37%), whereas intrahepatic endoglin expression remained constant in all BDL rats studied. LGF ameliorates liver fibrosis and improves liver function in BDL rats. The LGF-induced anti-fibrotic effect is associated with a decreased hepatic level of MMP-2, MMP-9 and TGF-beta1 in fibrotic rats.

  20. 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.

  1. 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

  2. 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

  3. Circulating serum xenoestrogens and mammographic breast density

    PubMed Central

    2013-01-01

    Introduction Humans are widely exposed to estrogenically active phthalates, parabens, and phenols, raising concerns about potential effects on breast tissue and breast cancer risk. We sought to determine the association of circulating serum levels of these chemicals (reflecting recent exposure) with mammographic breast density (a marker of breast cancer risk). Methods We recruited postmenopausal women aged 55 to 70 years from mammography clinics in Madison, Wisconsin (N = 264). Subjects completed a questionnaire and provided a blood sample that was analyzed for mono-ethyl phthalate, mono-butyl phthalate, mono-benzyl phthalate, butyl paraben, propyl paraben, octylphenol, nonylphenol, and bisphenol A (BPA). Percentage breast density was measured from mammograms by using a computer-assisted thresholding method. Results Serum BPA was positively associated with mammographic breast density after adjusting for age, body mass index, and other potentially confounding factors. Mean percentage density was 12.6% (95% confidence interval (CI), 11.4 to 14.0) among the 193 women with nondetectable BPA levels, 13.7% (95% CI, 10.7 to 17.1) among the 35 women with detectable levels below the median (<0.55 ng/ml), and 17.6% (95% CI, 14.1 to 21.5) among the 34 women with detectable levels above the median (>0.55 ng/ml; Ptrend = 0.01). Percentage breast density was also elevated (18.2%; 95% CI, 13.4 to 23.7) among the 18 women with serum mono-ethyl phthalate above the median detected level (>3.77 ng/ml) compared with women with nondetectable BPA levels (13.1%; 95% CI, 11.9 to 14.3; Ptrend = 0.07). No other chemicals demonstrated associations with percentage breast density. Conclusions Postmenopausal women with high serum levels of BPA and mono-ethyl phthalate had elevated breast density. Further investigation of the impact of BPA and mono-ethyl phthalate on breast cancer risk by using repeated serum measurements or other markers of xenoestrogen exposure are needed. PMID:23710608

  4. 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.

  5. 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.

  6. Regulation of intestinal epithelial cell growth by transforming growth factor type. beta

    SciTech Connect

    Barnard, J.A.; Beauchamp, R.D.; Coffey, R.J.; Moses, H.L. )

    1989-03-01

    A nontransformed rat jejunal crypt cell line (IEC-6) expresses transforming growth factor type {beta}1 (TGF-{beta}1) mRNA, secretes latent {sup 125}I-labeled TGF-{beta}1 to specific, high-affinity cell surface receptors. IEC-6 cell growth is markedly inhibited by TGF-{beta}1 and TGF-{beta}2 with half-maximal inhibition occurring between 0.1 and 1.0 ng of TGF-{beta}1 per ml. TGF-{beta}1-mediated growth inhibition is not associated with the appearance of biochemical markers of enterocyte differentiation such as alkaline phosphatase expression and sucrase activity. TGF-{beta}1 increases steady-state levels of its own mRNA expression within 8 hr of treatment of rapidly growing IEC-6 cells. In freshly isolated rat jejunal enterocytes that are sequentially eluted from the crypt villus axis, TGF-{beta}1 mRNA expression is most abundant in terminally differentiated villus tip cells and least abundant in the less differentiated, mitotically active crypt cells. The authors conclude that TGF-{beta}1 is an autoregulated growth inhibitor in IEC-6 cells that potentially functions in an autocrine manner. In the rat jejunal epithelium, TGF-{beta}1 expression is most prominently localized to the villus tip--i.e., the region of the crypt villus unit that is characterized by the terminally differentiated phenotype. These data suggest that TGF-{beta}1 may function in coordination of the rapid cell turnover typical for the intestinal epithelium.

  7. Differential response of nontumorigenic and tumorigenic human papillomavirus type 16-positive epithelial cells to transforming growth factor beta 1.

    PubMed

    Braun, L; Dürst, M; Mikumo, R; Gruppuso, P

    1990-11-15

    The transforming growth factor (TGF) beta s are multifunctional polypeptide growth factors with diverse biological effects, including inhibition of epithelial cell proliferation both in vitro and in vivo. To investigate the possible role of TGF beta 1 in the regulation of papillomavirus infection and papillomavirus-associated transformation, we compared the response to TGF beta 1 of normal keratinocytes, human papillomavirus, type 16 (HPV 16)-positive-immortalized keratinocytes (nontumorigenic), and HPV 16-positive cervical carcinoma cells (tumorigenic) with respect to DNA synthesis and protooncogene expression. All HPV 16-immortalized cell lines were nearly as inhibited by TGF beta 1 as normal keratinocytes, whereas two cervical carcinoma cell lines (Caski and Siha) were refractory to growth inhibition by TGF beta 1. Cell surface receptors for TGF beta 1 were present on both normal and carcinoma cell lines. In all cases, growth inhibition by TGF beta 1 was accompanied by suppression of Steady-state levels of c-myc mRNA. In contrast, TGF beta 1 induced the expression of c-jun mRNA transcripts in normal, immortalized, and tumorigenic cells. We also studied the effect of TGF beta 1 on HPV 16 mRNA expression. Steady-state levels of HPV 16 mRNA transcripts were suppressed by TGF beta 1 in the nontumorigenic HPK cells but were unaffected in the tumorigenic lines. These findings suggest that TGF beta 1 may be an in vivo modulator of HPV infection and that loss of responsiveness to this growth inhibitory signal may be involved in HPV-associated malignant transformation. PMID:2171761

  8. SURFACE TENSION OF SERUM : X. ON THE THICKNESS OF THE MONOMOLECULAR LAYER OF SERUM.

    PubMed

    du Noüy, P L

    1924-06-30

    An attempt was made to apply the assumption that a monolayer of serum exists at a certain dilution, in order to calculate the thickness of this layer or, that is to say, the mean value of one of the dimensions of the molecules of the serum proteins. The criterion taken for the existence of such a monolayer was the existence at a given concentration (1/11,000 for rabbit serum) of a maximum drop in the surface tension of serum solutions kept in watch-glasses. A series of preliminary experiments showed: 1. That the maximum drop in 2 hours took place, for the material used, at a concentration of 1/11,000, and that it always corresponded to an absolute minimum value of the surface tension of the solution, this minimum being quite sharp and well defined. 2. That adsorption took place on the glass as well as on the free surface of the liquid, and that apparently the same part of the molecule, in both cases, was drawn toward the water. 3. That the specific gravity of the anhydrous proteins of the rabbit serum studied was 1.275, whence it followed, on the basis of 6.51 per cent protein content, that the mean thickness of the protein molecules was 35.4 x 10(-8) cm. The same method applied to crystalline egg albumin, pH 6.8, in water, gave 52.8 x 10(-8) cm. for the probable molecular length. PMID:19868899

  9. 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.

  10. 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.

  11. Serum amyloid A inhibits osteoclast differentiation to maintain macrophage function.

    PubMed

    Kim, Jiseon; Yang, Jihyun; Park, Ok-Jin; Kang, Seok-Seong; Yun, Cheol-Heui; Han, Seung Hyun

    2016-04-01

    Serum amyloid A is an acute phase protein that is elevated under inflammatory conditions. Additionally, the serum levels of serum amyloid A are associated with the progression of inflammatory arthritis; thus, serum amyloid A might be involved in the regulation of osteoclast differentiation. In the present study, we examined the effects of serum amyloid A on osteoclast differentiation and function. When bone marrow-derived macrophages, as osteoclast precursors, were stimulated with serum amyloid A in the presence of M-CSF and receptor activator of nuclear factor-κB ligand, osteoclast differentiation and its bone-resorption activity were substantially inhibited. TLR2 was important in the inhibitory effect of serum amyloid A on osteoclast differentiation, because serum amyloid A stimulated TLR2. The inhibitory effect was absent in bone marrow-derived macrophages obtained from TLR2-deficient mice. Furthermore, serum amyloid A inhibited the expression of c-Fos and nuclear factor of activated T cells c1, which are crucial transcription factors for osteoclast differentiation, but prevented downregulation of IFN regulatory factor-8, a negative regulator of osteoclast differentiation. In contrast, serum amyloid A sustained the endocytic capacity of bone marrow-derived macrophages and their ability to induce the proinflammatory cytokines, IL-6, IL-1β, and TNF-α. Taken together, these results suggest that serum amyloid A, when increased by inflammatory conditions, inhibits differentiation of macrophages to osteoclasts, likely to maintain macrophage function for host defense.

  12. Low serum alkaline phosphatase activity in Wilson's disease.

    PubMed

    Shaver, W A; Bhatt, H; Combes, B

    1986-01-01

    Low values for serum alkaline phosphatase activity were observed early in the course of two patients with Wilson's disease presenting with the combination of severe liver disease and Coombs' negative acute hemolytic anemia. A review of other cases of Wilson's disease revealed that 11 of 12 patients presenting with hemolytic anemia had values for serum alkaline phosphatase less than their respective sex- and age-adjusted mean values; in eight, serum alkaline phosphatase activity was less than the lower value for the normal range of the test. Low values for serum alkaline phosphatase were much less common in Wilson's disease patients with more chronic forms of presentation. Copper added in high concentration to serum in vitro did not have an important effect on serum alkaline phosphatase activity. The mechanism responsible for the decrease in serum alkaline phosphatase activity in patients is uncertain.

  13. 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

  14. 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

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

    PubMed

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

    2016-03-01

    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.

  16. Serum proteomic profiles of depressive subtypes.

    PubMed

    Lamers, F; Bot, M; Jansen, R; Chan, M K; Cooper, J D; Bahn, S; Penninx, B W J H

    2016-01-01

    Depression is a highly heterogeneous disorder. Accumulating evidence suggests biological and genetic differences between subtypes of depression that are homogeneous in symptom presentation. We aimed to evaluate differences in serum protein profiles between persons with atypical and melancholic depressive subtypes, and compare these profiles with serum protein levels of healthy controls. We used the baseline data from the Netherlands Study of Depression and Anxiety on 414 controls, 231 persons with a melancholic depressive subtype and 128 persons with an atypical depressive subtype for whom the proteomic data were available. Depressive subtypes were previously established using a data-driven analysis, and 171 serum proteins were measured on a multi-analyte profiling platform. Linear regression models were adjusted for several covariates and corrected for multiple testing using false discovery rate q-values. We observed differences in analytes between the atypical and melancholic subtypes (9 analytes, q<0.05) and between atypical depression and controls (23 analytes, q<0.05). Eight of the nine markers differing between the atypical and melancholic subtype overlapped with markers from the comparison between atypical subtype and controls (mesothelin, leptin, IGFBP1, IGFBP2, FABPa, insulin, C3 and B2M), and were mainly involved in cellular communication and signal transduction, and immune response. No markers differed significantly between the melancholic subtype and controls. To conclude, although some uncertainties exist in our results as a result of missing data imputation and lack of proteomic replication samples, many of the identified analytes are inflammatory or metabolic markers, which supports the notion of atypical depression as a syndrome characterized by metabolic disturbances and inflammation, and underline the importance and relevance of subtypes of depression in biological and genetic research, and potentially in the treatment of depression. PMID:27404283

  17. 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

  18. Molecular Sex Differences in Human Serum

    PubMed Central

    Ramsey, Jordan M.; Schwarz, Emanuel; Guest, Paul C.; van Beveren, Nico J. M.; Leweke, F. Markus; Rothermundt, Matthias; Bogerts, Bernhard; Steiner, Johann; Ruta, Liliana; Baron-Cohen, Simon; Bahn, Sabine

    2012-01-01

    Background Sex is an important factor in the prevalence, incidence, progression, and response to treatment of many medical conditions, including autoimmune and cardiovascular diseases and psychiatric conditions. Identification of molecular differences between typical males and females can provide a valuable basis for exploring conditions differentially affected by sex. Methodology/Principal Findings Using multiplexed immunoassays, we analyzed 174 serum molecules in 9 independent cohorts of typical individuals, comprising 196 males and 196 females. Sex differences in analyte levels were quantified using a meta-analysis approach and put into biological context using k-means to generate clusters of analytes with distinct biological functions. Natural sex differences were established in these analyte groups and these were applied to illustrate sexually dimorphic analyte expression in a cohort of 22 males and 22 females with Asperger syndrome. Reproducible sex differences were found in the levels of 77 analytes in serum of typical controls, and these comprised clusters of molecules enriched with distinct biological functions. Analytes involved in fatty acid oxidation/hormone regulation, immune cell growth and activation, and cell death were found at higher levels in females, and analytes involved in immune cell chemotaxis and other indistinct functions were higher in males. Comparison of these naturally occurring sex differences against a cohort of people with Asperger syndrome indicated that a cluster of analytes that had functions related to fatty acid oxidation/hormone regulation was associated with sex and the occurrence of this condition. Conclusions/Significance Sex-specific molecular differences were detected in serum of typical controls and these were reproducible across independent cohorts. This study extends current knowledge of sex differences in biological functions involved in metabolism and immune function. Deviations from typical sex differences were

  19. Interaction of Citrinin with Human Serum Albumin.

    PubMed

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

    2015-12-01

    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.

  20. [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

  1. Effect of cyproheptadine on serum leptin levels.

    PubMed

    Calka, Omer; Metin, Ahmet; Dülger, Haluk; Erkoç, Reha

    2005-01-01

    Leptin is a 167 amino acid protein encoded by the obesity gene that is synthesized in adipose tissue and interacts with receptors in the hypothalamus linked to the regulation of appetite and metabolism. It is known to suppress appetite and increase energy expenditure. Cyproheptadine is a piperidine antihistamine that increases appetite through its antiserotonergic effect on 5-HT2 receptors in the brain. Although both leptin and cyproheptadine are effective in controlling appetite, their interaction has not been addressed in clinical studies. This study evaluated serum leptin concentrations in patients who received cyproheptadine to treat a variety of disorders. Sixteen patients aged 7 to 71 years (mean, 26.25 years) were given cyproheptadine 2 to 6 mg/day for a minimum of 7 days. Body weight was measured and blood samples were obtained at baseline and after 1 week of treatment. Serum leptin levels were determined by leptin radioimmunoassay. The mean body weight at baseline (52.59 kg) did not differ significantly from that at 1 week after treatment (52.84 kg; P > .05), but the mean leptin level after 1 week of treatment with cyproheptadine (3.14 ng/mL) was 14.2% higher than that at baseline (2.75 ng/mL; P < .05). This increase may suggest that both leptin and cyproheptadine may affect appetite via similar receptors and that cyproheptadine does not impair leptin activity through these receptors. Further study will be necessary to clarify this relationship.

  2. Serum PDGF-AB in pleural mesothelioma.

    PubMed

    Filiberti, Rosa; Marroni, Paola; Neri, Monica; Ardizzoni, Andrea; Betta, Pier Giacomo; Cafferata, Mara A; Canessa, Pier Aldo; Puntoni, Riccardo; Ivaldi, Giovanni Paolo; Paganuzzi, Michela

    2005-01-01

    Overexpression of platelet-derived growth factor (PDGF) has been observed in lung and pleural tumors. The aim of this study was to evaluate the diagnostic and prognostic role of serum PDGF in pleural mesothelioma (PM). Four groups of subjects were studied: 93 malignant PM patients, 33 primary non small cell lung cancer patients, 51 subjects exposed to asbestos, defined as high-risk controls, and 24 healthy controls. PDGF-AB mean concentration was higher in PM patients (45.8 ng/ml) than in high-risk controls (33.1 ng/ml) and healthy controls (26.8 ng/ml). Using the cut-off level of 49.8 ng/ml, corresponding to the mean+2SD of PDGF-AB in healthy controls, 43% of PM patients showed positive PDGF-AB levels. Survival was evaluated in 82 PM patients. At the end of the follow-up (median 9.8 months) 80.5% of patients had died. Median survival was 13.1 and 7.9 months for patients with PDGF-AB lower and higher than the cut-off, respectively. Adjusting for age, sex, histology and platelet count, positive PDGF-AB levels were associated with lower survival (OR=1.2, 95%CI: 0.9-1.6), even if not significantly so. In conclusion, serum PDGF may represent a useful additional parameter to prognostic factors already available for PM.

  3. 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

  4. Serum prolactin concentrations are elevated after syncope.

    PubMed

    Oribe, E; Amini, R; Nissenbaum, E; Boal, B

    1996-07-01

    The distinction between syncope and epileptic seizures is a common clinical diagnostic problem. Elevated serum prolactin (PRL) concentrations are used to help differentiate epileptic from nonepileptic attacks such as pseudoseizures. Reports of PRL concentrations following syncope have been variable. To determine whether PRL rises after syncope, we measured serum PRL concentrations during a 45-minute passive 60-degree head-up tilt in 21 patients with a history of near-fainting or syncope. Head-up tilt triggered hypotension (mean arterial pressure 51 mm Hg, 95% CI = 45-57) with syncope in 11 patients. PRL concentrations were elevated ( > 19 ng/mL) and reached a maximum within the first 30 minutes after tilt-induced syncope in nine patients (PRL supine: 11 ng/mL, 95% CI = 7-15, vs. PRL after syncope: 52 ng/mL, 95% CI = 36-67; a greater than fourfold rise), while they remained unchanged in 10 patients who had a normal response to head-up tilt (PRL supine: 6 ng/mL, 95% CI = 5-8, vs. maximum PRL while upright: 8 ng/mL, 95% CI = 6-10). The findings indicate that elevated PRL concentrations are present after hypotensive syncope and are of little use in differentiating such syncope from epileptic seizures.

  5. Inorganic pyrophosphate generation by transforming growth factor-beta-1 is mainly dependent on ANK induction by Ras/Raf-1/extracellular signal-regulated kinase pathways in chondrocytes.

    PubMed

    Cailotto, Frederic; Bianchi, Arnaud; Sebillaud, Sylvie; Venkatesan, Narayanan; Moulin, David; Jouzeau, Jean-Yves; Netter, Patrick

    2007-01-01

    ANK is a multipass transmembrane protein transporter thought to play a role in the export of intracellular inorganic pyrophosphate and so to contribute to the pathophysiology of chondrocalcinosis. As transforming growth factor-beta-1 (TGF-beta1) was shown to favor calcium pyrophosphate dihydrate deposition, we investigated the contribution of ANK to the production of extracellular inorganic pyrophosphate (ePPi) by chondrocytes and the signaling pathways involved in the regulation of Ank expression by TGF-beta1. Chondrocytes were exposed to 10 ng/mL of TGF-beta1, and Ank expression was measured by quantitative polymerase chain reaction and Western blot. ePPi was quantified in cell supernatants. RNA silencing was used to define the respective roles of Ank and PC-1 in TGF-beta1-induced ePPi generation. Finally, selective kinase inhibitors and dominant-negative/overexpression plasmid strategies were used to explore the contribution of several signaling pathways to Ank induction by TGF-beta1. TGF-beta1 strongly increased Ank expression at the mRNA and protein levels, as well as ePPi production. Using small interfering RNA technology, we showed that Ank contributed approximately 60% and PC-1 nearly 20% to TGF-beta1-induced ePPi generation. Induction of Ank by TGF-beta1 required activation of the extracellular signal-regulated kinase (ERK) pathway but not of p38-mitogen-activated protein kinase or of protein kinase A. In line with the general protein kinase C (PKC) inhibitor calphostin C, Gö6976 (a Ca2+-dependent PKC inhibitor) diminished TGF-beta1-induced Ank expression by 60%, whereas a 10% inhibition was observed with rottlerin (a PKCdelta inhibitor). These data suggest a regulatory role for calcium in TGF-beta1-induced Ank expression. Finally, we demonstrated that the stimulatory effect of TGF-beta1 on Ank expression was inhibited by the suppression of the Ras/Raf-1 pathway, while being enhanced by their constitutive activation. Transient overexpression of Smad 7, an

  6. [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

  7. Reference intervals for serum cystatin C and serum creatinine in adults.

    PubMed

    Erlandsen, E J; Randers, E; Kristensen, J H

    1998-06-01

    The aim of this study was to establish reference intervals for cerum cystatin C and serum creatinine in adults. Blood samples were collected from 270 healthy blood donors (135 men and 135 women between 20 and 65 years old with 15 men and 15 women in each five-year-interval). Serum cystatin C was analyzed using an automated particle-enhanced immunoassay (DAKO Cystatin C PET kit) on the Cobas Mira S analyzer. Serum creatinine was analyzed using the Vitros Creatinine Slide, an enzymatic method on the Vitros 950 chemistry analyzer. The calculated reference intervals for serum cystatin C were 0.62-1.15 mg/l in women (median 0.84 mg/l, range 0.56-1.29 mg/l) and 0.51-1.25 mg/l in men (median 0.87 mg/l, range 0.42-1.39 mg/l). The Mann-Whithey U-test revealed no gender-related difference for cystatin C (p = 0.48). A common reference interval in women and men was calculated to be 0.54-1.21 mg/l (median 0.85 mg/l, range 0.42-1.39 mg/l). The non-parametric reference interval for serum creatinine was 57-95 mumol/l in women (median 72 mumol/l, range 44-105 mumol/l) and 69-111 mumol/l in men (median 89 mumol/l, range 58-123 mumol/l).

  8. Serum-stimulated cyclic-AMP production in S49 lymphoma cells grown in serum-free medium.

    PubMed

    Darfler, F J; Mullen, M D; Insel, P A

    1984-03-23

    Growth of S49 lymphoma cells with horse serum leads to an increase in cellular cAMP phosphodiesterase activity and a resultant loss of hormone- and cholera-toxin-stimulated cAMP accumulation. We now show that the serum requires protein synthesis to produce these effects. Further, we show that acute addition of serum to wild-type S49 cells, grown in serum-free medium, rapidly (under 2 min) and transiently (under 30 min) stimulates cellular cAMP, 10-fold over basal levels. This 'acute' effect of serum was not observed in UNC S49 cells, suggesting that a functional Ns, the guanine nucleotide regulatory component that mediates stimulation of adenylate cyclase, is required for the serum-mediated stimulation of cellular cAMP. Serum added acutely to wild-type S49 cells also augmented cAMP accumulation in response to isoproterenol and forskolin. The half-maximally effective concentrations of horse serum that acutely stimulated or more slowly decreased the cAMP accumulation were approx. 0.2% and 2.0%, respectively. Preliminary attempts to characterize further the serum factor indicate that it has a high (250 000-300 000) molecular weight and is insensitive to boiling; chromatography on Sepharose CL-6B yields a 100-fold purification. Thus, the serum contains one or more components that activate adenylate cyclase, increase cellular cAMP levels and ultimately induce cAMP phosphodiesterase in S49 lymphoma cells. PMID:6322858

  9. Differentiation of adipose-derived stem cells into Schwann-like cells: fetal bovine serum or human serum?

    PubMed Central

    Younesi, Elham; Hashemitabar, Mahmoud; Azandeh, Seyyed Saeed; Bijannejad, Dariush; Bahreini, Amin

    2015-01-01

    Access to autologous Schwann cells is limited due to lack of donor site and its difficult isolation and culture. Therefore, one of the possible ways to obtain to Schwann cells is to differentiate mesenchymal stem cells into glial pathway using various materials and protocols. The aim of this study was to compare the effects of fetal bovine serum and human serum on Schwann cell differentiation of adipose-derived stem cells to choose the best serum for use in future research. For this purpose, after isolation of human adipose-derived stem cells, it was characterized and differentiated into Schwann cell lineage using two protocols which one of them contained fetal bovine serum and the other human serum. At the end, morphological evaluation declared an increased detachment of cells in response to human serum. On the other side, immunocytochemistry showed that there was a significant increase in the number of cells expressing glial fibrillary acidic proteins and S100 in fetal bovine serum-treated group when compared to human serum-treated one (P<0.05). It was concluded that fetal bovine serum was more effective than allogeneic human serum in Schwann cell differentiation of adipose-derived stem cells. PMID:26417476

  10. Immunoassay of serum muramidase (lysozyme) in ocular diseases.

    PubMed

    Sen, D K; Sarin, G S

    1987-01-01

    Serum levels of muramidase activity were measured in 162 patients with different ocular diseases and 84 healthy subjects by electro-immuno-diffusion technique. We demonstrated for the first time that electro-immuno-diffusion technique could be successfully applied for the estimation of serum muramidase concentrations. Serum muramidase was found to be high in significant number of cases with granulomatous uveitis, tuberculous keratitis, central serous retinopathy and Eales' disease. Tuberculosis was presumed to be the cause in them by the process of exlusion. Patients with high serum muramidase activity were subjected to anti-tubercular treatment with a marked clinical improvement. It is suggested that high serum muramidase could be an useful parameter in deciding the line of treatment in patients with ocular diseases of uncertain etiology. Serum muramidase concentrations showed return to normal levels with the clinical improvement of the diseases with treatment. It increased again with the re-appearance of the activity of the diseases.

  11. Serum gamma-glutamyl transpeptidase activity in normal children.

    PubMed

    Shore, G M; Hoberman, L; Dowdey, B C; Combes, B

    1975-02-01

    Serum gamma-glutamyl transpeptidase (GGT) activities of 82 healthy neonates (aged 9 hours to 11 days) and 106 healthy children (aged 2 months to 15 years) were determined. Serum GGT activity of 47 neonates (51%) was higher than the accepted upper limit of normal for adults. By three months of age, all of the children had serum GGT activities that were within the accepted normal range for adults. Thereafter there was only minimal variation in serum GGT activities of older children. Although mean serum GGT activity was higher in male children than in female children, there was no significant difference between the values for male and female neonates. That after the neonatal period serum GGT activity is constant in the adult range and is not affected by bone growth as is alkaline phosphatase suggests that GGT may be of value in the evaluation of hepatobiliary disease in children.

  12. 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

  13. Farm animal serum proteomics and impact on human health.

    PubMed

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

    2014-09-01

    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.

  14. 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.

  15. Hexachlorobenzene triggers apoptosis in rat thyroid follicular cells.

    PubMed

    Chiappini, Florencia; Alvarez, Laura; Lux-Lantos, Victoria; Randi, Andrea S; Kleiman de Pisarev, Diana L

    2009-04-01

    Hexachlorobenzene (HCB) is a widespread environmental pollutant. Chronic exposure of humans to HCB produces a number of effects, such as triggering of porphyria, increased synthesis of liver microsomal enzymes, neurological symptoms, immunological disorders and thyroid dysfunctions. In rats, HCB induced hepatic porphyria, neurotoxic effects, and toxic effects on the reproductive system, thyroid function, and immune system. HCB is also known to cause tumors of the liver, thyroid and mammary gland in laboratory animals. The aim of this study was to investigate parameters of thyroid growth regulation, mainly cell proliferation and apoptosis in thyroid tissue from HCB (0.1, 1, 10, 100, and 500 mg/kg body weight)-treated female Wistar rats. The current study demonstrates that only the exposure to the highest HCB dose for 30 days, has adverse effects on thyroid endpoints examined related to thyroid gland morphology, and 3,3'5,5'-tetraiodothyronine (T(4), thyroxine) serum levels, without changes in thyroid-stimulating hormone concentrations or in thyroid gland weight. Morphological changes, included flattened epithelium and increased colloid size compared with control tissue. Transforming growth factor (TGF-beta1) mRNA levels, evaluated by RT-PCR, revealed a significant upregulation after exposure to HCB (1, 10, 100 mg/kg body weight). Cell proliferation evaluated by 5'-Br deoxiuridine incorporation into DNA, was not altered at any dose. HCB (1, 10, 100 mg/kg body weight) induces apoptosis, evaluated by in situ end labeling of fragmented DNA, terminal deoxynucleotidyl transferase-mediated deoxy uridine triphosphate nick-end labeling, in rat thyroid glands. This process is associated with dose-dependent increases in cytochrome c release from the mitochondria and procaspase-9 processing to its active product. Caspase-8 was not activated. These studies indicate that doses of HCB that do not disrupt thyroid economy induce TGF-beta1 expression and apoptosis in the thyroid

  16. Hydrogen sulfide suppresses migration, proliferation and myofibroblast transdifferentiation of human lung fibroblasts.

    PubMed

    Fang, Li-Ping; Lin, Qing; Tang, Chao-Shu; Liu, Xin-Min

    2009-12-01

    We previously reported that hydrogen sulfide (H(2)S) was implicated in the pathogenesis of bleomycin-induced pulmonary fibrosis in rat, but the cellular mechanisms underlying the role it played were not well characterized. The present study was undertaken to investigate the role of the exogenous H(2)S in human lung fibroblast (MRC5) migration, proliferation and myofibroblast transdifferentiation induced by fetal bovine serum (FBS) and growth factors in vitro, to elucidate the mechanisms by which H(2)S inhibits pathogenesis of pulmonary fibrosis. We found that H(2)S incubation significantly decreased the MRC5 cell migration distance stimulated by FBS and basic fibroblast growth factor (bFGF), inhibited MRC5 cell proliferation induced by FBS and platelet-derived growth factor-BB (PDGF-BB), and also inhibited transforming growth factor-beta1 (TGF-beta1) induced MRC5 cell transdifferentiation into myofibroblasts. Moreover, preincubation with H(2)S decreased extracellular signal-regulated kinase (ERK1/2) phosphorylation in MRC5 cells induced by FBS, PDGF-BB, TGF-beta1, and bFGF. However, the inhibition effects of H(2)S on MRC5 cell migration, proliferation and myofibroblast transdifferentiation were not attenuated by glibenclamide, an ATP-sensitive K(+) channel (K(ATP)) blocker. Thus, H(2)S directly suppressed fibroblast migration, proliferation and phenotype transform stimulated by FBS and growth factors in vitro, which suggests that it could be an important mechanism of H(2)S-suppressed pulmonary fibrosis. These effects of H(2)S on pulmonary fibroblasts were, at least in part, mediated by decreased ERK phosphorylation and were not dependent on K(ATP) channel opening.

  17. 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

  18. [Increased serum PIVKA-II levels in hyperthyroidism].

    PubMed

    Morimoto, M; Takeda, K; Ohara, E; Nishimori, Y; Hisahara, T; Nishida, M; Sugiura, T

    2001-11-01

    PIVKA-II has been practically used as a tumor marker of hepatocellular carcinoma. On the other hand, increased serum PIVKA-II concentration was reported in a Japanese patient who had hyperthyroidism without liver diseases. To evaluate whether thyroid hormone is related with serum PIVKA-II, we examined serum PIVKA-II concentrations in patients with various thyroid diseases. Eight patients with Hashimoto disease, 24 patients with Graves' disease, and 8 healthy subjects were studied. There was no significant difference of serum PIVKA-II levels among the three groups. However, serum PIVKA-II concentrations(mean +/- SD mAU/ml) in hyperthyroidism(37 +/- 27) were significantly higher than those in hypothyroidism(16 +/- 9) and normal controls(12 +/- 4) (p < 0.05 and p < 0.01, respectively). When hyperthyroid patients were treated by antithyroid drug or isotope, serum PIVKA-II concentrations decreased in accordance with the decrease of serum FT4 concentrations. Our data indicate that serum PIVKA-II concentration was increased in patients with hyperthyroidism, but further in vivo studies are necessary to clarify the mechanism related to increased serum PIVKA-II by thyroid hormone.

  19. Elevation of serum acid phosphatase in cancers with bone metastasis

    SciTech Connect

    Tavassoli, M.; Rizo, M.; Yam, L.T.

    1980-05-01

    In patients with nonprostatic cancer, serum acid phosphatase activity is usually elevated when bone metastasis is present but not when bone metastasis is absent. The fraction responsible for serum enzyme elevation is a normal component of serum; it appears in gel electrophoresis as band 5; and is tartrate-resistant. It is suggested that the origin of acid phosphatase elevation is bone osteoclasts rather than cancer tissue, as is the case with prostatic carcinoma. Determination of serum acid phosphatase activity may be useful in the detection of bone metastasis.

  20. Serum Endocan Levels in Children with Febrile Neutropenia.

    PubMed

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

    2016-03-17

    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.

  1. 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

  2. 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

  3. Serum enzyme and ferritin concentrations in acute leukaemia.

    PubMed

    Stark, A N; Gailor, K; Langdale, P I; Roberts, B E; Scott, C S

    1987-03-01

    Serum ferritin concentrations were determined in 142 untreated cases of acute leukaemia. No correlation between type of leukaemia as defined by morphology and immunology and the level of serum ferritin was found. Samples were also tested for lactate dehydrogenase (LDH), phosphohexose isomerase (PHI), B-glucuronidase (B-gluc), leucine aminopeptidase (LAP), and C-reactive protein (CRP) levels. Serum ferritin was significantly correlated with serum PHI, LAP, and LDH concentrations but not with leukaemic mass as assessed by total white blood cell count (WBC). Ferritin and CRP levels were also significantly correlated suggesting that ferritin may behave to some extent like an acute phase reactant in acute leukaemia. PMID:3502981

  4. 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.

  5. The nature of human serum insulin-like activity (ILA): characterization of ILA in serum and serum fractions obtained by acid-ethanol extraction and adsorption chromatography

    PubMed Central

    Poffenbarger, Philip L.; Ensinck, John W.; Hepp, Dieter K.; Williams, Robert H.

    1968-01-01

    Studies were undertaken in an attempt to clarify the apparent heterogeneous nature of human serum insulin-like activity. Methods of preparative zone electrophoresis on Pevikon, acid-ethanol extraction of trichloroacetic acid serum protein precipitates, adsorption chromatography on DEAE-cellulose and Dowex 50, gel filtration chromatography, and insulin antiserum immunoreactivity were used. The results establish the presence of a substance in serum with in vitro biological properties similar to insuln but with different physicochemical properties. The major portion of serum ILA measured by bioassay techniques can be attributed to the effects of this substance. Whereas the in vitro biological effects of this substance on muscle and adipose cells were similar to those of crystalline insulin, the substance is distinguished from insulin by: (1) the failure of insulin antiserum to inhibit its in vitro biological effect; (2) a slower electrophoretic mobility (in the gamma-beta globulin zone); and (3) a larger molecular weight, between 40,000 and 50,000 in these studies. It is similar to insulin since both are soluble in acid-ethanol. The results further indicate that previously described insulin-like activity in gamma-beta globulin preparations, the major portion of total serum insulin activity described in acid-ethanol extracts of serum, “bound” insulin, “atypical” insulin, and antibody nonsuppressible insulin-like activity bioassayed in diluted serum are all one and the same substance. PMID:4170389

  6. Acromegalic gigantism with low serum level of growth hormone and elevated serum insulin-like growth factor-I.

    PubMed

    Miyazaki, R; Yoshida, T; Sakane, N; Yasuda, T; Umekawa, T; Kondo, M; Shimatsu, A; Hizuka, N; Sano, T

    1995-03-01

    In a case of acromegalic gigantism with hyperprolactinemia is reported, the basal serum growth hormone (GH) levels ranged from 1.2 to 1.9 ng/ml. Serum GH response to either insulin-induced hypoglycemia or GH-releasing hormone was blunted. Frequent blood sampling showed non-pulsatile GH secretion. Serum prolactin and insulin-like growth factor-I (IGF-I) levels were elevated. After unsuccessful surgery, bromocriptine treatment normalized serum prolactin without affecting serum GH and IGF-I levels. Combined administration of octreotide with bromocriptine reduced serum GH and IGF-I levels. In this case, non-pulsatile GH secretion and enhanced tissue sensitivity to GH may induce hypersecretion of IGF-I and cause clinical acromegalic gigantism. PMID:7787324

  7. Hyperimmune goat serum for amyotrophic lateral sclerosis.

    PubMed

    Mackenzie, R; Kiernan, M; McKenzie, D; Youl, B D

    2006-12-01

    The authors report a patient with amyotrophic lateral sclerosis (ALS) who showed a lessening of deterioration in respiratory muscle strength during treatment with hyperimmune goat serum (HGS) (Aimspro). Respiratory function tests (RFTs) were measured by established protocols, and all measurements were expressed as a percentage of normal predicted values. The rate of decline was calculated by linear regression analysis. Respiratory muscle strength decline was less during 13 months of treatment with HGS (mean 1.3% per month, range 0.8-1.7%) compared to the preceding 13 months (mean 2.3% per month, range 1.2-3.1%), while a greater decline would be expected with disease progression. Comparison with similarly affected patients in the literature suggest that a decline of 4-5% per month of predicted values may be expected during the treatment phase.

  8. 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.

  9. Serum Dioxin Concentrations and Age at Menopause

    PubMed Central

    Eskenazi, Brenda; Warner, Marcella; Marks, Amy R.; Samuels, Steven; Gerthoux, Pier ario; Vercellini, Paolo; Olive, David L.; Needham, Larry; Patterson, Donald G.; Mocarelli, Paolo

    2005-01-01

    2,3,7,8-Tetrachlorobenzo-p-dioxin (TCDD), a halogenated compound that binds the aryl hydrocarbon receptor, is a by-product of numerous industrial processes including waste incineration. Studies in rats and monkeys suggest that TCDD may affect ovarian function. We examined the relationship of TCDD and age at menopause in a population of women residing near Seveso, Italy, in 1976, at the time of a chemical plant explosion. We included 616 of the women who participated 20 years later in the Seveso Women’s Health Study. All women were premenopausal at the time of the explosion, had TCDD levels measured in serum collected soon after the explosion, and were ≥ 35 years of age at interview. Using proportional hazards modeling, we found a 6% nonsignificant increase in risk of early menopause with a 10-fold increase in serum TCDD. When TCDD levels were categorized, compared with women in the lowest quintile (< 20.4 ppt), women in quintile 2 (20.4–34.2 ppt) had a hazard ratio (HR) of 1.1 (p = 0.77), quintile 3 (34.3–54.1 ppt) had an HR of 1.4 (p = 0.14), quintile 4 (54.2–118 ppt) had an HR of 1.6 (p = 0.10), and quintile 5 (> 118 ppt) had an HR of 1.1 (p = 0.82) for risk of earlier menopause. The trend toward earlier menopause across the first four quintiles is statistically significant (p = 0.04). These results suggest a nonmonotonic dose-related association with increasing risk of earlier menopause up to about 100 ppt TCDD, but not above. PMID:16002373

  10. 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

  11. Binding of transforming growth factor-beta (TGF-beta) to pregnancy zone protein (PZP). Comparison to the TGF-beta-alpha 2-macroglobulin interaction.

    PubMed

    Philip, A; Bostedt, L; Stigbrand, T; O'Connor-McCourt, M D

    1994-04-15

    Pregnancy zone protein (PZP) is quantitatively the most important pregnancy-associated plasma protein and it has strong similarity to alpha 2-macroglobulin. Since alpha 2-macroglobulin is a binding protein for transforming growth factors-beta (TGF-beta), it was of interest to test whether the related protein, PZP, also binds to these growth-regulatory proteins. Using affinity-labelling methods, we demonstrate that PZP binds both TGF-beta 1 and TGF-beta 2 and that the binding characteristics are similar to those of the TGF-beta-alpha 2-macroglobulin interaction. TGF-beta 2 and TGF-beta 1 bind to PZP in a predominantly noncovalent manner in vitro. TGF-beta 1 and TGF-beta 2 bind to both the dimeric and tetrameric forms of PZP. Our studies also indicate that PZP binds TGF-beta 2 with higher affinity than TGF-beta 1. Finally, we demonstrate that PZP inhibits the binding of TGF-beta 1 and TGF-beta 2 to their cell surface receptors. The increased level of PZP during pregnancy may affect the action of TGF-beta by regulating the distribution, clearance and/or general availability of TGF-beta. The preferential binding of TGF-beta 2 over TGF-beta 1 by PZP implies that PZP may differentially regulate the action of TGF-beta 1 and TGF-beta 2.

  12. Proteoglycan expression in bleomycin lung fibroblasts: role of transforming growth factor-beta(1) and interferon-gamma.

    PubMed

    Venkatesan, Narayanan; Roughley, Peter J; Ludwig, Mara S

    2002-10-01

    Bleomycin (BM)-induced pulmonary fibrosis involves excess production of proteoglycans (PGs). Because transforming growth factor-beta(1) (TGF-beta(1)) promotes fibrosis, and interferon-gamma (IFN-gamma) inhibits it, we hypothesized that TGF-beta(1) treatment would upregulate PG production in fibrotic lung fibroblasts, and IFN-gamma would abrogate this effect. Primary lung fibroblast cultures were established from rats 14 days after intratracheal instillation of saline (control) or BM (1.5 units). PGs were extracted and subjected to Western blot analysis. Bleomycin-exposed lung fibroblasts (BLF) exhibited increased production of versican (VS), heparan sulfate proteoglycan (HSPG), and biglycan (BG) compared with normal lung fibroblasts (NLF). Compared with NLF, BLF released significantly increased amounts of TGF-beta(1). TGF-beta(1) (5 ng/ml for 48 h) upregulated PG expression in both BLF and NLF. Incubation of BLF with anti-TGF-beta antibody (1, 5, and 10 microg/ml) inhibited PG expression in a dose-dependent manner. Treatment of BLF with IFN-gamma (500 U. ml(-1) x 48 h) reduced VS, HSPG, and BG expression. Furthermore, IFN-gamma inhibited TGF-beta(1)-induced increases in PG expression by these fibroblasts. Activation of fibroblasts by TGF-beta(1) promotes abnormal deposition of PGs in fibrotic lungs; downregulation of TGF-beta(1) by IFN-gamma may have potential therapeutic benefits in this disease. PMID:12225958

  13. Charged gold nanoparticles with essentially zero serum protein adsorption in undiluted fetal bovine serum.

    PubMed

    Murthy, Avinash K; Stover, Robert J; Hardin, William G; Schramm, Robert; Nie, Golay D; Gourisankar, Sai; Truskett, Thomas M; Sokolov, Konstantin V; Johnston, Keith P

    2013-05-29

    The adsorption of even a single serum protein molecule on a gold nanosphere used in biomedical imaging may increase the size too much for renal clearance. In this work, we designed charged ~5 nm Au nanospheres coated with binary mixed-charge ligand monolayers that do not change in size upon incubation in pure fetal bovine serum (FBS). This lack of protein adsorption was unexpected in view of the fact that the Au surface was moderately charged. The mixed-charge monolayers were composed of anionic citrate ligands modified by place exchange with naturally occurring amino acids: either cationic lysine or zwitterionic cysteine ligands. The zwitterionic tips of either the lysine or cysteine ligands interact weakly with the proteins and furthermore increase the distance between the "buried" charges closer to the Au surface and the interacting sites on the protein surface. The ~5 nm nanospheres were assembled into ~20 nm diameter nanoclusters with strong near-IR absorbance (of interest in biomedical imaging and therapy) with a biodegradable polymer, PLA(1k)-b-PEG(10k)-b-PLA(1k). Upon biodegradation of the polymer in acidic solution, the nanoclusters dissociated into primary ~5 nm Au nanospheres, which also did not adsorb any detectable serum protein in undiluted FBS.

  14. Isolation of human anti-serum albumin Fab antibodies with an extended serum-half life.

    PubMed

    Kang, Hyeon-Ju; Kim, Hye-Jin; Cha, Sang-Hoon

    2016-01-01

    The serum albumin (SA) has been exploited to generate long-acting biotherapeutics by taking advantage of the FcRn-mediated recycling mechanism in a direct or an indirect way. Since Fab fragments have been proven to be clinically safe for human usage, we assumed that human anti-SA Fab antibodies could have a great potential as a carrier molecule to extend the serum half-life of therapeutic proteins. We, herein, had attempted to isolate anti-SA Fab antibodies from HuDVFab-8L antibody library via a phage display technology, and identified eight discrete human Fab antibodies. One of the Fab antibodies, SL335, showed the strongest binding reactivity to human SA with nM range of affinity at both pH 6 and pH 7.4, and cross-reacted to SAs from various species including rat, mouse, canine and monkey. The in vivo pharmacokinetic assay using a rat model indicated that SL335 has approximately 10 fold longer serum half-life and 26 to 44-fold increase in AUC0 → ∞ compared to the negative control Fab molecule in both intravenous and subcutaneous administrations. Knowing that Fabs have proven to be safe in clinics for a long time, SL335 seems to have a great potential in generating long-acting protein drugs by tagging effector molecules with either chemical conjugation or genetic fusion.

  15. 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

  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.

  17. 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... GENERAL BIOLOGICAL PRODUCTS STANDARDS General Provisions § 610.16 Total solids in serums. Except as... solids....

  18. 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...

  19. Nutrition education improves serum retinol concentration among adolescent school girls.

    PubMed

    Lanerolle, Pulani; Atukorala, Sunethra

    2006-01-01

    Dietary diversification has been identified as a sustainable intervention method in developing countries where subclinical vitamin A deficiency exists. Nutrition education is central to all methods of nutrition intervention including dietary diversification. The paucity of available data currently limits the effective use of nutrition education in national programs in Sri Lanka. We assessed the effect of nutrition education on nutrition related knowledge, food consumption patterns and serum retinol concentrations among 229 adolescent school girls, aged between 15-19 years. Knowledge on nutrition, food consumption patterns and serum retinol concentration was assessed at baseline. Intervention included nutrition education as lecture discussions, interactive group discussions and four different methods of reinforcement. Knowledge, food consumption patterns and serum retinol concentrations were reassessed after a ten week period of intervention. Educational intervention resulted in a significant increase in knowledge (P < 0.001) and consumption of local vitamin A rich foods. The percentage of subjects with low serum retinol concentrations (<20 microg/dL) decreased from 17% to 4.8%. The effect of nutrition education on serum retinol concentration was highly significant (P<0.001) in subjects with baseline serum retinol concentrations below 20 microg/L. Nutrition education was effective in improving knowledge and food consumption patterns among these girls. Effectiveness was of biological significance, as a positive change in serum retinol concentration was observed in subjects with initially low concentrations, and not in subjects with initially normal serum concentrations.

  20. 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

  1. 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... GENERAL BIOLOGICAL PRODUCTS STANDARDS General Provisions § 610.16 Total solids in serums. Except as... solids....

  2. 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... GENERAL BIOLOGICAL PRODUCTS STANDARDS General Provisions § 610.16 Total solids in serums. Except as... solids....

  3. 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... GENERAL BIOLOGICAL PRODUCTS STANDARDS General Provisions § 610.16 Total solids in serums. Except as... solids....

  4. [Creation and organization of an antivenomous serum bank in France].

    PubMed

    Darsonval, Astrid; Boels, David; Clerc, Marie-Anne; De Haro, Luc; Penot-Ragon, Christine; Moal, Fréderic; Quistinic, Pierre; Lourdais, Olivier; Harry, Patrick

    2010-09-01

    For several years exotic snakes have been bred in France. In view of the increased risk of envenomation from some of these species, the Poison Centre in Angers has joined forces with several private licensed snake breeders to create an Anti-venom Serum Bank. The main objective of the new organization is to provide an effective means of dealing with bites and subsequent envenomation by exotic snakes by managing a stock of anti-venom serums in a hospital pharmacy, so that cases can be treated as quickly as possible. The hospital pharmacy has the authority to purchase and supply the anti-venom serums. The selection and purchase of the serums is done in conjunction with the French Ministry of Ecology, the French Drug Agency and specialist doctors. At the time of writing, the Antivenom Serum Bank has the capacity to treat about thirty different kinds of envenomation, compared to the 135 exotic venomous snake species officially registered. In the long term the Anti-venom Serum Bank will help eradicate the use of serums from unauthorized sources, evaluate the safety and efficacy of new serums and reduce transport times.

  5. 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.

  6. Serum Bilirubin and Disease Progression in Mild COPD

    PubMed Central

    Apperley, Scott; Park, Hye Yun; Holmes, Daniel T.; Wise, Robert A.; Connett, John E.

    2015-01-01

    BACKGROUND: COPD is a chronic inflammatory disorder associated with oxidative stress. Serum bilirubin has potent antioxidant actions, and higher concentrations have been shown to protect against oxidative stress. The relation between serum bilirubin and COPD progression is unknown. METHODS: Serum bilirubin was measured in 4,680 smokers aged 35 to 60 years old with mild to moderate airflow limitation. The relationship of serum bilirubin to postbronchodilator FEV1 and rate of FEV1 decline over 3 to 9 years was determined using regression modeling. Total and disease-specific mortality were also ascertained. RESULTS: Serum bilirubin was positively related to FEV1 (P < .001). Serum bilirubin was also negatively related to the annual decline in FEV1 when adjusted for baseline demographics, pack-years smoked, and baseline measures of lung function (P = .01). Additionally, serum bilirubin was negatively associated with risk of death from coronary heart disease (P = .03); however, the relationships between bilirubin and other mortality end points were not statistically significant (P > .05). CONCLUSIONS: Bilirubin is inversely related to COPD disease severity and progression. Higher serum bilirubin concentration was associated with a higher FEV1 and less annual decline in FEV1. Bilirubin was also associated with less coronary heart disease mortality. These data support the hypothesis that bilirubin has a protective effect on COPD disease progression, possibly through its antioxidant actions. Bilirubin may prove useful as an easily accessible and readily available blood-based COPD biomarker. PMID:25539285

  7. 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

  8. Cancer risk in relation to serum copper levels.

    PubMed

    Coates, R J; Weiss, N S; Daling, J R; Rettmer, R L; Warnick, G R

    1989-08-01

    A nested, matched case-control study was conducted to assess the relationship between serum levels of copper and the subsequent risk of cancer. One hundred thirty-three cases of cancer were identified during 1974-1984 among 5000 members of a northwest Washington State employee cohort from whom serum specimens had been previously obtained and stored. Two hundred forty-one controls were selected at random from the cohort and were matched to the cases on the basis of age, sex, race, and date of blood draw. Serum copper levels were measured by atomic absorption spectrometry. Risk of a subsequent diagnosis of cancer was positively associated with serum copper levels, but only among those cases diagnosed within 4 years of the time the serum specimens were collected. Among cases diagnosed more than 4 years after specimen collection, there was no consistent association between serum copper levels and risk. Adjustment for age, sex, race, occupational status, cigarette smoking, family history of cancer, alcohol consumption, and, among females, use of exogenous hormones had no appreciable effect on these relationships. The findings suggest that the presence of cancer may increase serum copper levels several years prior to its diagnosis. They are less supportive of the hypothesis that serum copper levels affect cancer risk.

  9. [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.

  10. Association of serum pentraxin 3 concentrations with diabetic nephropathy.

    PubMed

    Wang, Rui; Zhang, Jietao; Hu, Wenchao

    2016-08-01

    Pentraxin 3 (PTX3), a member of a superfamily of conserved proteins, attenuates renal damage in diabetic mice. This study aims to determine whether serum PTX3 concentrations are correlated with the presence of diabetic nephropathy (DN). A total of 160 patients with type 2 diabetes mellitus (T2DM) and 54 healthy subjects were enrolled in this study. Patients with T2DM were divided into three groups in accordance with the levels of urinary albumin excretion (UAE). Serum PTX3 concentrations were determined using an ELISA kit. Serum PTX3 concentrations were significantly higher in patients with T2DM compared with the controls. Patients with T2DM with macroalbuminuria showed higher serum PTX3 concentrations compared with the other three groups. However, there were no significant differences of serum PTX3 concentrations between patients with T2DM with normoalbuminuria and microalbuminuria. Furthermore, a simple regression analysis has shown that serum PTX3 concentrations in patients with T2DM were negatively correlated with body mass index, and positively correlated with blood urea nitrogen, serum creatinine, and UAE. Serum PTX3 concentrations are correlated with DN.

  11. 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...

  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... GENERAL BIOLOGICAL PRODUCTS STANDARDS General Provisions § 610.16 Total solids in serums. Except as... solids....

  13. 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...

  14. 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.

  15. Prognostic significance of serum cystatin C in multiple myeloma.

    PubMed

    Nückel, Holger; Langer, Christian; Herget-Rosenthal, Stefan; Wichert, Marc; Assert, Roland; Döhner, Hartmut; Dührsen, Ulrich; Liebisch, Peter

    2012-05-01

    Multiple myeloma (MM) is frequently complicated by renal insufficiency, which is associated with an unfavorable prognosis. Serum cystatin C is a new and accurate marker of glomerular filtration rate. Global gene expression analysis has revealed serum cystatin C as one of the most highly upregulated genes in MM. Recent data have shown serum cystatin C as an independent prognostic marker in MM. To further elucidate the prognostic significance of serum cystatin C, we investigated pretreatment serum cystatin C levels in 68 newly diagnosed patients homogeneously treated with high-dose melphalan followed by autologous stem cell transplantation. Median serum cystatin C level in MM patients was significantly higher than in the 66 healthy controls (1.07 vs. 0.74 mg/L [p = 0.002]). Median serum cystatin C levels significantly increased with higher International Staging System (ISS) stages (stage I 0.72 mg/L; stage II 0.89 mg/L; stage III 1.28 mg/L; p < 0.0001). Higher serum cystatin C was positively correlated with higher serum levels of creatinine (r = 0.84; p < 0.0001), β2-microglobulin (r = 0.72; p < 0.0001), LDH (r = 0.43; p = 0.0003), white blood cell counts (r = 0.61; p < 0.0001) and calcium (r = 0.29; p = 0.016), and negatively correlated with lower serum albumin levels (r = 0.44; p < 0.0001) and hemoglobin levels (r = 0.31; p = 0.01). Using ROC analysis, patients with serum cystatin C levels ≥0.95 mg/L (n = 24) had a significantly shorter event-free survival (EFS) and overall survival (OS) than patients with serum cystatin C levels <0.95 mg/L (median EFS: 26 vs. 44 months, p < 0.0001; median OS: 54 vs. 68 months, p = 0.05). Moreover, the combination of serum cystatin C level and genomic aberrations further refined the prognostic information (EFS and OS) provided by either one of the factors. The level of serum cystatin C is not only a sensitive marker of renal function, but also reflects tumor burden and delivers prognostic information in MM.

  16. Altered Serum Uric Acid Level in Lichen Planus Patients

    PubMed Central

    Chakraborti, Goutam; Biswas, Rabindranath; Chakraborti, Sandip; Sen, Pradyot Kumar

    2014-01-01

    Background: Lichen planus (LP) is a common disorder whose etiopathogenesis is not clear. Recently, it has been suggested that increased reactive oxygen species (ROS) play important roles in the underlying mechanism of LP. Objectives: The principal aim of this study was to evaluate serum uric acid (UA) levels as a measure of the antioxidant defense status in LP patients. Methods: Serum UA levels were determined in 58 LP patients and 61 controls. Results: Serum UA levels were significantly decreased in patients with respect to controls. Moreover, serum UA level was decreased according to increasing duration of disease. Conclusions: The results of our study suggest that LP is associated with decrease of UA levels in serum. UA may be a potential, useful biomarker of antioxidant status in LP for elaboration of treatment strategy and monitoring. PMID:25484383

  17. The binding of antituberculous drugs to normal and kwashiorkor serum.

    PubMed

    Buchanan, N; van der Walt, L A

    1977-09-17

    The protein binding of 6 antituberculous drugs--ethambutol, ethionamide, isoniazid, para-aminosalicylic acid, rifampicin and streptomycin--to normal and kwashiorkor serum has been investigated. The binding of these drugs was mildly decreased in kwashiorkor serum, but not to such an extent as to be of therapeutic importance, except for streptomycin and possibly para-aminosalicylic acid (PAS). With streptomycin there was a 15% increase in the free component in kwashiorkor serum, while with PAS there was a 12% increase in the free component. Of interest is the observation that rifampicin is predominantly bound to the gamma-globulin fraction, both in normal and in kwashiorkor serum. Secondary binding, predominantly to the alpha 1-, alpha 2-and gamma-globulin fractions, was seen quite commonly in kwashiorkor serum in association with diminished albumin binding.

  18. [Effect of freezing on cord blood serum proteins].

    PubMed

    Nardid, E O; Rozanova, E D; Tsymbal, L V; Zinchenko, A V; Nardid, O A; Grishchenko, V I

    2009-01-01

    The effect of freezing regimes and storage temperatures on protein conformation and the spectrum of cord blood serum has been investigated. Changes in the parameters of ESR spectra of spin probes in cord blood serum after slow freezing and subsequent thawing were established, indicating protein conformational changes characterized by loosening. This fact is confirmed by an earlier process, the first stage of albumin heat denaturation, as indicated by calorimetric data. It was shown that slow cooling results in the aggregation of serum protein in which serum albumin and immunoglobulins play an important role. It was concluded that, for retaining the properties, of cord blood serum proteins, it is preferable to perform cooling at a rate not lower than 100 degrees C/min and a storage temperature of -80 degrees C and lower. PMID:19894629

  19. Spectroscopic imaging of serum proteins using quantum cascade lasers.

    PubMed

    Mukherjee, Anadi; Bylund, Quentin; Prasanna, Manu; Margalit, Yotam; Tihan, Tarik

    2013-03-01

    First measurements of biomedical imaging using quantum cascade lasers (QCL) are presented. We report spectroscopic imaging of serum proteins using QCLs as an example for monitoring surface biocontamination. We found that dry smears of human serum can be spectroscopically imaged, identified, and quantified with high sensitivity and specificity. The core parts of the imaging platform consist of optically multiplexing three QCLs and an uncooled microbolometer camera. We show imaging of human serum proteins at 6.1, 9.25, and 9.5 μm QCLs with high sensitivity and specificity. The sensitivity limit of 3  μg/cm² of the human serum spot was measured at an S/N=3.The specificity of human serum detection was measured at 99% probability at a threshold of 77  μg/cm². We anticipate our imaging technique to be a starting point for more sophisticated biomolecular diagnostic applications.

  20. 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

  1. Regulation of transglutaminase type II by transforming growth factor-beta 1 in normal and transformed human epidermal keratinocytes.

    PubMed

    George, M D; Vollberg, T M; Floyd, E E; Stein, J P; Jetten, A M

    1990-07-01

    This study examines the effect of transforming growth factor-beta 1 (TGF-beta 1) on the expression of Type I and II transglutaminase in normal human epidermal keratinocytes (NHEK cells). Treatment of undifferentiated NHEK cells with 100 pM TGF-beta 1 caused a 10- to 15-fold increase in the activity of a soluble transglutaminase. Based on its cellular distribution and immunoreactivity this transglutaminase was identified as Type II (tissue) transglutaminase. TGF-beta 1 did not enhance the levels of the membrane-bound Type I (epidermal) transglutaminase activity which is induced during squamous cell differentiation and did not increase Type II transglutaminase activity in differentiated NHEK cells. Several SV40 large T antigen-immortalized NHEK cell lines also exhibited a dramatic increase in transglutaminase Type II activity after TGF-beta 1 treatment; however, TGF-beta 1 did not induce any significant change in transglutaminase activity in the carcinoma-derived cell lines SCC-13, SCC-15, and SQCC/Y1. Half-maximal stimulation of transglutaminase Type II activity in NHEK cells occurred at a dose of 15 pM TGF-beta 1. TGF-beta 2 was about equally effective. This enhancement in transglutaminase activity was related to an increase in the amount of transglutaminase Type II protein as indicated by immunoblot analysis. Northern blot analyses using a specific cDNA probe for Type II transglutaminase showed that exposure of NHEK cells to TGF-beta 1 caused a marked increase in the mRNA levels of this enzyme which could be observed as early as 4 h after the addition of TGF-beta 1. Maximal induction of transglutaminase Type II mRNA occurred between 18 and 24 h. The increase in Type II transglutaminase mRNA levels was blocked by the presence of cycloheximide, suggesting that this increase in mRNA by TGF-beta 1 is dependent on protein synthesis. PMID:1972706

  2. Transforming growth factor-beta 1 stimulates vascular smooth muscle cell L-proline transport by inducing system A amino acid transporter 2 (SAT2) gene expression.

    PubMed Central

    Ensenat, D; Hassan, S; Reyna, S V; Schafer, A I; Durante, W

    2001-01-01

    Transforming growth factor-beta1 (TGF-beta 1) is a multifunctional cytokine that contributes to arterial remodelling by stimulating vascular smooth muscle cell (SMC) growth and collagen synthesis at sites of vascular injury. Since l-proline is essential for the synthesis of collagen, we examined whether TGF-beta 1 regulates the transcellular transport of l-proline by vascular SMCs. l-Proline uptake by vascular SMCs was primarily sodium-dependent, pH-sensitive, blocked by neutral amino acids and alpha-(methylamino)isobutyric acid, and exhibited trans-inhibition. Treatment of SMCs with TGF-beta 1 stimulated l-proline transport in a concentration- and time-dependent manner. The TGF-beta 1-mediated l-proline uptake was inhibited by cycloheximide or actinomycin D. Kinetic studies indicated that TGF-beta 1-induced l-proline transport was mediated by an increase in transport capacity independent of any changes in the affinity for l-proline. TGF-beta 1 stimulated the expression of system A amino acid transporter 2 (SAT2) mRNA in a time-dependent fashion that paralleled the increase in l-proline transport. Reverse transcriptase PCR failed to detect the presence of SAT1 or amino acid transporter 3 (ATA3) in either untreated or TGF-beta 1-treated SMCs. These results demonstrate that l-proline transport by vascular SMCs is mediated predominantly by the SAT and that TGF-beta 1 stimulates SMC l-proline uptake by inducing the expression of the SAT2 gene. The ability of TGF-beta 1 to induce SAT2 expression may function to provide SMCs with the necessary levels of l-proline required for collagen synthesis and cell growth. PMID:11716780

  3. Molecular characterisation of sea bream (Sparus aurata) transforming growth factor beta1.

    PubMed

    Tafalla, C; Aranguren, R; Secombes, C J; Castrillo, J L; Novoa, B; Figueras, A

    2003-05-01

    A transforming growth factor beta1 (TGF beta1) full length cDNA was characterised and sequenced from the head kidney of sea bream (Sparus aurata) previously challenged with a nodavirus. The cloned cDNA of 1778bp contains a predicted open reading frame of 379 amino acids, which includes the mature peptide region of 112 amino acids. The regulating region of the peptide possesses four potential N-linked glycosylation sites (N-X-T/S), as well as an RGD integrin binding site, an RKKR tetrabasic cut site and nine conserved cysteines all characteristic of the TGF beta superfamily. Compared to other teleost TGF beta1 genes, the sea bream TGF beta1 is most closely related to hybrid striped bass (Moronesaxatilis xM. chrysops) TGF beta1 (80% amino acid identity). The genomic organisation of TGF beta1 was determined through the generation of contiguous PCR clones. The sea bream TGF beta1 gene is approximately 3.6kb in length and consists of five coding regions. Two introns are absent in comparison to the genomic organisation of rainbow trout Oncorhynchus mykiss TGF beta1, whilst an additional intron not present in other sequenced TGF beta genes, but present in the trout TGF beta1 gene, is conserved in sea bream.A reverse transcription polymerase chain reaction (RT-PCR) assay was developed to study TGF beta expression in different sea bream tissues. Constitutive TGF beta1 expression was detected in the liver, brain, muscle, kidney, heart, gills and spleen of sea bream, as well as in head kidney macrophages and blood leucocytes.

  4. 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.

  5. 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.

  6. Differential serum protein markers and the clinical severity of asthma

    PubMed Central

    Meyer, Norbert; Nuss, Sarah Janine; Rothe, Thomas; Siebenhüner, Alexander; Akdis, Cezmi A; Menz, Günter

    2014-01-01

    Background Asthma is a heterogeneous disease characterized by different clinical phenotypes and the involvement of multiple inflammatory pathways. During airway inflammation, many cytokines and chemokines are released and some are detectable in the sera. Objective Serum chemokines and cytokines, involved in airway inflammation in asthma patients, were investigated. Methods A total of 191 asthma patients were classified by hierarchical cluster analysis, including the following parameters: forced expiratory volume in 1 second (FEV1), eosinophil cationic protein (ECP) serum levels, blood eosinophils, Junipers asthma symptom score, and the change in FEV1, ECP serum levels, and blood eosinophils after 3 weeks of asthma therapy. Serum proteins were measured by multiplex analysis. Receiver operating characteristic (ROC) curves were used to evaluate the validity of serum proteins for discriminating between asthma clusters. Results Classification of asthma patients identified one cluster with high ECP serum levels, increased blood eosinophils, low FEV1 values, and good FEV1 improvement in response to asthma therapy (n=60) and one cluster with low ECP serum levels, low numbers of blood eosinophils, higher FEV1 values, and no FEV1 improvement in response to asthma therapy (n=131). Serum interleukin (IL)-8, eotaxin, vascular endothelial growth factor (VEGF), cutaneous T-cell-attracting chemokine (CTACK), growth-related oncogene (GRO)-α, and hepatocyte growth factor (HGF) were significantly different between the two clusters of asthma patients. ROC analysis for serum proteins calculated a sensitivity of 55.9% and specificity of 75.8% for discriminating between them. Conclusion Serum cytokine and chemokine levels might be predictors for the severity of asthmatic inflammation, asthma control, and response to therapy, and therefore might be useful for treatment optimization. PMID:24851055

  7. Are There Any Promising Biochemical Correlates of Achievement Behavior and Motivation? The Evidence for Serum Uric Acid and Serum Cholesterol

    ERIC Educational Resources Information Center

    Kasl, Stanislav V.

    1974-01-01

    This review examines the available evidence in support of the argument that serum uric acid (SUA) possesses considerable promise as an indicator of one type of biochemical influence on achievement behavior. The evidence arguing for further research into the role of serum cholesterol in achievement behavior is also examined. (Author/JR)

  8. Relationship among serum taurine, serum adipokines, and body composition during 8-week human body weight control program.

    PubMed

    You, Jeong Soon; Park, Ji Yeon; Zhao, Xu; Jeong, Jin Seok; Choi, Mi Ja; Chang, Kyung Ja

    2013-01-01

    Human adipose tissue is not only a storage organ but also an active endocrine organ to release adipokines. This study was conducted to investigate the relationship among serum taurine and adipokine levels, and body composition during 8-week human body weight control program in obese female college students. The program consisted of diet therapy, exercise, and behavior modification. After the program, body weight, body fat mass, percent body fat, and body mass index (BMI) were significantly decreased. Serum triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels were significantly decreased. Also serum adiponectin level was significantly increased and serum leptin level was significantly decreased. There were no differences in serum taurine and homocysteine levels. The change of serum adiponectin level was positively correlated with change of body fat mass and percent body fat. These results may suggest that body fat loss by human body weight control program is associated with an increase in serum adiponectin in obese female college students. Therefore, further study such as taurine intervention study is needed to know more exact correlation between dietary taurine intake and serum adipokines or body composition.

  9. BARIUM SULPHATE ABSORPTION AND THE SERUM DIAGNOSIS OF SYPHILIS.

    PubMed

    Noguchi, H; Bronfenbrenner, J

    1911-02-01

    The so-called syphilitic antibodies can be removed from a serum by means of absorption with barium sulphate. The removal is due either to an adsorption or a mechanical absorption. The activity of the syphilitic antibodies is thereby unimpaired. The readiness with which the absorption is accomplished with barium sulphate varies considerably with different syphilitic sera. That barium sulphate exerts the same absorbing effect upon non-syphilitic serum components is made evident by the interfering property which the latter manifest in the absorption experiment of the syphilitic antibodies. The selective removal of the serum components, other than the syphilitic antibodies, by means of barium sulphate absorption is, therefore, impossible. On the other hand, a partial removal of these components, with but little removal of the syphilitic antibodies, may be effected when the content of a given serum is poor in syphilitic antibodies and comparatively rich in the indifferent serum components. But this is impossible if the conditions are reversed. The main reasons why some negative syphilitic sera may be so modified by the barium sulphate treatment as to give positive reactions, are explained below, but these apply only to those methods in which inactivated serum is employed. The inactivation reduces the antibody content to about one-fourth to one-fifth of the original. When the serum is very rich in antibodies, this does not affect the result of the fixation test. But when the amount of the antibodies is small, the process of inactivation creates conditions quite unexpected. It may produce such a condition that a given amount of the serum contains, after inactivation, only one or two antibody units, while the other serum components remain undiminished. Here one must not lose sight of the vital fact that these apparently indifferent serum constituents are not at all indifferent in the fixation processes. They may possess affinities which are similar to those of complement

  10. Serum proteins in heavily burnt patients.

    PubMed

    Miskulin, M; Moati, F; Robert, A M; Monteil, R; Guilbaud, G

    1978-01-01

    Several serum proteins, such as prealbumin, protease inhibitors, immunoglobulins, metalloproteins and inflammatory glycoproteins were determined in the sera of heavily burnt patients by radial immunodiffusion. An increase of acute phase reactant glycoproteins (orsomucoid, haptoglobin, haemopexin, C-reactive protein), C3-complement, immunoglobulins, prealbumin and of the protease inhibitors (a1-antitrypsin, a2-macroglobulin) was found. For some proteins, such as prealbumin, haemopexin, immunoglobulins, this increase was preceeded by a decrease on days 3 to 5 post-burn. The time course of the increase was variable, faster for some patients and slower for others: orosomucoid, C-reactive protein, C3-complement reached peak values between days 6 and 8; immunoglobulins and hemopexin decreased then towards normal values. No significant increase was found for ceruloplasmin, transferrin, beta2-glycoprotein, a2-SH glycoprotein and GC-globulin. It is proposed that the selective overproduction of the above mentioned proteins may be related to the stimulation of acute-phase reactant protein synthesis by the liver as a result of tissue breakdown produced by the circulating proteases and especially by elastases and collagenases as was shown previously (Miskulin et al., 1978; Moati et al., 1978a).

  11. Origin of serum estradiol in postmenopausal women.

    PubMed

    Judd, H L; Shamonki, I M; Frumar, A M; Lagasse, L D

    1982-06-01

    In postmenopausal women, the circulating levels of estrone (E1) and estradiol (E2) may be of clinical importance. The origin of E1, but not of E2, has been defined. To examine the source of the latter, the serum concentrations, metabolic clearance rates, conversion ratios, and production rates of testosterone (T), androstenedione (A), E2, and E1 were measured in 20 postmenopausal subjects. For E2, the mean +/- SE CRTE2 was 0.0014 +/- 0.0005; thus, the contribution of circulating T to the circulating E2 pool was minimal (2.5%). The contribution of circulating A to E2 was also insignificant, whereas the CRE1E2 was appreciable (0.065 +/- 0.011), accounting for 21.5% of the E2 pool. For E1, the major contribution was the peripheral conversion of A, accounting for 24.6% of circulating E1. The contribution of peripheral conversion of T (unmeasurable) and E2 (2.9%) to the E1 pool were minimal. These data are consistent with the concept that in postmenopausal women the major contribution of peripheral conversion to the circulating E2 pool is from E1, which in turn is the product of peripheral aromatization of circulating A. PMID:7078905

  12. 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.

  13. 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

  14. Women's experience of maternal serum screening.

    PubMed Central

    Carroll, J. C.; Brown, J. B.; Reid, A. J.; Pugh, P.

    2000-01-01

    OBJECTIVE: To explore the ideas, opinions, feelings, and experiences of women regarding prenatal genetic screening, specifically maternal serum screening (MSS). DESIGN: Qualitative technique of focus groups. SETTING: Northern, rural, inner-city, urban, and suburban communities in Ontario. PARTICIPANTS: Women who had given birth to babies from January 1994 to May 1996, but who were not currently pregnant (n = 60). METHOD: Six focus groups composed of women living in various communities who had recently given birth to babies explored the experience of MSS. MAIN FINDINGS: Women want informed choice about prenatal genetic screening. Three factors influenced women's decisions to undergo or decline prenatal genetic screening: their personal values, including their philosophy of life, moral, and religious values, and attitudes regarding Down syndrome and disability; social support including their partners, families, and friends; and quality of information from health care providers. Women want their providers to give them information personally; they want to receive the information as early as possible in prenatal care to allow time for reflection; and they want unbiased, accurate information in order to make a decision that is in keeping with their personal values and beliefs. CONCLUSIONS: Knowledge of women's ideas, opinions, feelings, and experiences regarding MSS suggests specific ways health care providers can facilitate informed decision making in prenatal screening. Providing information about genetic testing needs to be individualized, with women actively participating in the decision-making process. Information needs described by these women could apply to other prenatal genetic tests that might be available in the future. PMID:10752000

  15. 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.

  16. Increased serum prolactin in borderline personality disorder.

    PubMed

    Atmaca, Murad; Korkmaz, Sevda; Ustundag, Bilal; Ozkan, Yusuf

    2015-01-01

    Although there is an important interaction between serotonergic system, prolactin and suicidal behavior, and impulsivity, no investigation examined the prolactin values in borderline personality disorder in which suicidal behavior and impulsivity are core symptom dimensions. In this context, in the present investigation, we planned to measure serum prolactin levels in the patients with borderline personality disorder. The study comprised 15 patients with borderline personality disorder and 15 healthy controls. Prolactin values were measured in both patients and control subjects. The patients had abnormally higher mean value of prolactin compared to those of healthy controls (48.66 ± 36.48 mg/dl for patients vs. 15.20 ± 7.81 mg/dl for healthy controls). There was no correlation between prolactin values and any demographic variables for both the patients and control subjects. In conclusion, our present results suggest that prolactin values increased in the patients with borderline personality disorder and are required to be replicated by more comprehensive and detailed further studies to decipher the exact roles of prolactin increase.

  17. Large fragments of human serum albumin.

    PubMed

    Geisow, M J; Beaven, G H

    1977-03-01

    Large fragments of human serum albumin were produced by treatment of the native protein with pepsin at pH3.5. Published sequences of human albumin [Behrens, Spiekerman & Brown (1975) Fed. Proc. Fed. Am. Soc. Exp. Biol. 34, 591; Meloun, Moravek & Kostka (1975) FEBSLett.58, 134-137]were used to locate the fragments in the primary structure. The fragments support both the sequence and proposed disulphide-linkage pattern (Behrens et al., 1975). As the pH of a solution of albumin is lowered from pH4 to pH3.5, the protein undergoes a reversible conformational change known as the N-F transition. The distribution of large fragments of human albumin digested with pepsin in the above pH region was critically dependent on pH. It appeared that this distribution was dependent on the conformation of the protein at low pH, rather than the activity of pepsin. The yields of the large fragments produced by peptic digestion at different values of pH suggested that the C-terminal region of albumin unfolds or separates from the rest of the molecule during the N-F transition. The similarity of peptic fragments of human and bovine albumin produced under identical conditions supports the proposed similar tertiary structure of these molecules.

  18. Study of the cross-reaction between rabbit anti-bovine serum albumin antibodies and equine serum albumin

    PubMed Central

    Rangel, H.

    1965-01-01

    Cross-reactions between bovine serum albumin and equine serum albumin were studied using heterologous soluble complexes and specifically purified cross-reacting antibody. Experiments with soluble complexes showed that homologous antigen can displace heterologous antigen specifically bound to antibody but heterologous antigen cannot displace homologous antigen. On gel precipitation tests a specific precipitation resulted when heterologous soluble complex reacted with homologous antigen. By using equine serum albumin conjugated to polyaminopolystyrene the cross-reacting antibodies from anti-bovine serum albumin imune sera could be isolated. These are divalent 7S, γ-globulin antibodies. A figure of cross-reaction was obtained when these purified antibodies were tested by double diffusion in agar with bovine and equine serum albumins. The results obtained both with soluble complexes and with purified antibody support the view that cross-reacting antibody is more avid for the homologous than for the heterologous antigen. ImagesFIG. 3FIG. 4FIG. 5 PMID:14245318

  19. Serum bactericidal resistance of faecal Escherichia coli and bactericidal competence of serum from patients with ulcerative colitis.

    PubMed

    Burke, D A; Clayden, S A; Axon, A T

    1990-04-01

    A microtitre method was developed to screen Escherichia coli from 48 patients with ulcerative colitis and 25 controls for serum resistance. Bactericidal resistance was indicated by a change in colour of indicator due to acid production by viable organisms and quantitated by a change in absorbance. The method clearly differentiated between organisms confirmed as resistant or sensitive by conventional techniques. Twenty four (50%) disease and 14 (56%) control E coli specimens showed serum resistance. Bactericidal competence of sera from patients with ulcerative colitis was assessed by incubating sensitive E coli with sera from 10 patients with ulcerative colitis and pooled normal serum. All sera effectively reduced viable counts to less than 6% of original inoculum. This study shows that serum samples from patients with ulcerative colitis are bactericidally competent and that there is no increase in the number of serum resistant E coli in patients with ulcerative colitis.

  20. Transforming growth factor-beta1 induces activation of Ras, Raf-1, MEK and MAPK in rat hepatic stellate cells.

    PubMed

    Reimann, T; Hempel, U; Krautwald, S; Axmann, A; Scheibe, R; Seidel, D; Wenzel, K W

    1997-02-10

    The transdifferentiation of hepatic stellate cells into myofibroblast-like cells and the proliferation of the transdifferentiated cells are controlled by TGF-beta1. Little is known about the intracellular signal transducers of TGF-beta1. In this paper we show that in cultured hepatic stellate cells TGF-beta1 induces activation of Ras, Raf-1, MEK and MAPK p42 and p44. The activation of MAPK depends on the activation of MEK. Our data exclude that the observed effects are mediated by a bFGF or PDGF autocrine loop. PMID:9038360

  1. Levels of transforming growth factor beta and transforming growth factor beta receptors in rat liver during growth, regression by apoptosis and neoplasia.

    PubMed

    Grasl-Kraupp, B; Rossmanith, W; Ruttkay-Nedecky, B; Müllauer, L; Kammerer, B; Bursch, W; Schulte-Hermann, R

    1998-09-01

    Transforming growth factor beta1 (TGF-beta1) has been implicated as inhibitor of cell proliferation and a potent inducer of apoptosis in vitro and in vivo after the administration of high doses. To assess the role of endogenous TGF-beta1, we quantitated the cytokine and its receptors in rat liver during regenerative and hyperplastic growth, regression by apoptosis, and in hepatocellular carcinoma (HCC). This was accomplished by Northern blot analysis and by RNase protection assay of the messenger RNA (mRNA) of TGF-beta1 and TGF-beta receptors (TbetaR) types I to III and by an activity bioassay of the TGF-beta proteins. Untreated rat livers were found to contain 15.6 +/- 4.8 ng TGF-beta1 protein/g tissue; TGF-beta2 protein was not detected. To induce toxic cell death and subsequent regenerative DNA synthesis in the liver, rats were treated with a necrogenic dose of carbon tetrachloride (CCl4). After 24 and 48 hours, there was an upregulation of TGF-beta1 (mRNA, up to tenfold; protein, about twofold) and of TbetaRs (mRNA: two- to fourfold); that indicates an overall enhanced production of and sensitivity to TGF-beta1, which may serve to confine the regenerative response. Hyperplastic liver growth and regression of the hyperplasia were induced by treatment with cyproterone acetate (CPA) or nafenopin (NAF) followed by withdrawal; neither mRNAs of TGF-beta1 and TbetaR types I to III nor TGF-beta1 protein exhibited significant changes during the growth phase or during regression by apoptosis. We also studied neoplastic growth. HCC, obtained after long-term treatment with NAF, exhibited high rates of cell replication and apoptosis. The majority of lesions contained mRNA and protein of TGF-beta1 and mRNA of TbetaR types I to III at concentrations similar to those of the surrounding tissue. In conclusion, during liver regeneration there is a pronounced upregulation of expression of both TGF-beta1 and TbetaRs I to III, but not during mitogen-induced liver growth or

  2. 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.

  3. [Determination of serum proteins by high performance capillary zone electrophoresis].

    PubMed

    Zhang, N; Tang, Y; Hao, D M; Zheng, L; Qiu, G B

    1999-11-01

    The separation method of serum proteins was established with an untreared 50 microns i.d. x 47 cm (40 cm to detector) capillary and detection of absorbance at 200 nm. Analysis was performed by pressure injectction 17.23 kPa.s and by applying 23 kV in the constant voltage mode. Serum samples were diluted 40-folds with assay buffer (12.5 mmol/L sodium borate, 1 mmol/L calcium lactate, 0.7 mmol/L magnesium sulfate, 1 mmol/L EDTA were mixed). A normal control serum protein was separated into 6 fractions. In pregnant serum, the alpha 0 was an additionally unknown fraction. Comparison of capillary electrophoresis with conventional cellulose acetate electrophoresis for analysis of serum proteins from normal control, pregnant women multiple myeloma and tonic rachitis patients indicates that capillary clectrophoresis is a new technique for the analysis of serum proteins because of its high efficiency, on-line data processing and automation. Capillary electrophoresis is the reliable technique for clinical diagnosis of serum protein abnormalities.

  4. Serum Selenium and Ceruloplasmin in Nigerians with Peripartum Cardiomyopathy

    PubMed Central

    Karaye, Kamilu M.; Yahaya, Isah A.; Lindmark, Krister; Henein, Michael Y.

    2015-01-01

    The study aimed to determine if selenium deficiency, serum ceruloplasmin and traditional birth practices are risk factors for peripartum cardiomyopathy (PPCM), in Kano, Nigeria. This is a case-control study carried out in three hospitals, and PPCM patients were followed up for six months. Critically low serum selenium concentration was defined as <70 µg/L. A total of 39 PPCM patients and 50 controls were consecutively recruited after satisfying the inclusion criteria. Mean serum selenium in patients (61.7 ± 14.9 µg/L) was significantly lower than in controls (118.4 ± 45.6 µg/L) (p < 0.001). The prevalence of serum selenium <70 µg/L was significantly higher among patients (76.9%) than controls (22.0%) (p < 0.001). The mean ceruloplasmin and prevalence of socio-economic indices, multiparity, pregnancy-induced hypertension, obesity and twin pregnancy were not different between the groups (p > 0.05). Logistic regression showed that rural residency significantly increased the odds for serum selenium <70 µg/L by 2.773-fold (p = 0.037). Baseline serum levels of selenium and ceruloplasmin were not associated with six-month mortality. This study has shown that selenium deficiency is a risk factor for PPCM in Kano, Nigeria, and is related to rural residency. However, serum ceruloplasmin, customary birth practices and some other characteristics were not associated with PPCM in the study area. PMID:25853263

  5. 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.

  6. Serum ferritin and anemia in trained female athletes.

    PubMed

    Ashenden, M J; Martin, D T; Dobson, G P; Mackintosh, C; Hahn, A G

    1998-09-01

    The aim of this study was to establish whether extremely low serum ferritin values in female athletes were associated with indications of iron deficiency anemia and whether serum ferritin values were influenced by the type of training or participants' body size. Hematological data collected during 6 years at the Australian Institute of Sport were reviewed to quantify changes in serum ferritin concentration associated with training and to establish whether decrements in serum ferritin were associated with any change in hemoglobin concentration, mean corpuscular volume, or mean corpuscular hemoglobin concentration. Mean serum ferritin concentrations of 7.5 microg x L(-1) were not associated with any indication of iron-deficiency anemia. Serum ferritin declined by approximately 25% with the onset of rigorous daily training (p < .01) whether training was predominantly weight-bearing or non-weight-bearing. Rowers had significantly higher ferritin concentrations than basketball players of similar stature (p=.02). We conclude that considerable background information such as the stage of training, specific sport, and previous blood results should be sought when interpreting serum ferritin concentrations in female athletes.

  7. Prognostic value of serum angiogenic activity in colorectal cancer patients

    PubMed Central

    Gonzalez, Francisco-Jesus; Quesada, Ana-Rodriguez; Sevilla, Isabel; Baca, Juan-Javier; Medina, Miguel-Angel; Amores, Jose; Diaz, Juan Miguel; Rius-Diaz, Francisca; Marques, Eduardo; Alba, Emilio

    2007-01-01

    Abstract Angiogenesis, resulting from an imbalance between angiogenic activator factors and inhibitors, is required for tumour growth and metastasis. The determination of the circulating concentration of all angiogenic factors (activators and inhibitors) is not feasible at present. We have evaluated diagnostic and prognostic values of the measurement of serum angiogenic activity in colorectal carcinoma (CRC) patients. Serum proliferative activity (PA) on human umbilical vein endothelial cells (HUVEC) in vitro, and serum vascular endothelial growth factor (VEGF) levels were determined by ELISA in 53 patients with primary CRC, 16 subjects with non-neoplastic gastrointestinal disease (SC) and 34 healthy individuals. Data were compared with clinical outcome of the patients. Although serum from CRC patients significantly increased the PA of HUVEC, compared to culture control (HUVEC in medium + 10% foetal bovine serum (FBS); P < 0.001); our results indicate that serum PA in CRC patients was similar to that of SC or healthy individuals. There was no correlation between serum PA and circulating VEGF concentrations. Surgery produced a decrease of PA at 8 hrs after tumour resection in CRC patients compared to pre-surgery values (186 ± 47 versus 213 ± 41, P < 0.001). However, an increase in serum VEGF values was observed after surgery (280 [176–450] versus 251 [160–357] pg/ml, P = 0.004). Patients with lower PA values after surgery showed a worse outcome that those with higher PA values. Therefore, this study does not support a diagnostic value for serum angiogenic activity measured by proliferative activity on HUVEC but suggests it could have a prognostic value in CRC patients. PMID:17367506

  8. Serum Renalase Levels Correlate with Disease Activity in Lupus Nephritis

    PubMed Central

    Zhang, Minfang; Shao, Xinghua; Chang, Xinbei; Fan, Zhuping; Cao, Qin; Mou, Shan; Wang, Qin; Yan, Yucheng; Desir, Gary; Ni, Zhaohui

    2015-01-01

    Introduction Lupus nephritis (LN) is among the most serious complications of systemic lupus erythematosus (SLE), which causes significant morbidity and mortality. Renalase is a novel, kidney-secreted cytokine-like protein that promotes cell survival. Here, we aimed to investigate the relationship of serum renalase levels with LN and its role in the disease progression of LN. Methods For this cross-sectional study, 67 LN patients and 35 healthy controls were enrolled. Seventeen active LN patients who received standard therapies were followed up for six months. Disease activity was determined by the SLE Disease Activity–2000 (SLEDAI-2K) scoring system and serum renalase amounts were determined by ELISA. Predictive value of renalase for disease activity was assessed. Furthermore, the expression of renalase in the kidneys of patients and macrophage infiltration was assessed by immunohistochemistry. Results Serum renalase amounts were significantly higher in LN patients than in healthy controls. Moreover, patients with proliferative LN had more elevated serum renalase levels than Class V LN patients. In proliferative LN patients, serum renalase levels were significantly higher in patients with active LN than those with inactive LN. Serum renalase levels were positively correlated with SLEDAI-2K, 24-h urine protein excretion, ds-DNA and ESR but inversely correlated with serum albumin and C3. Renalase amounts decreased significantly after six-months of standard therapy. The performance of renalase as a marker for diagnosis of active LN was 0.906 with a cutoff value of 66.67 μg/ml. We also observed that the amount of renalase was significantly higher in glomerular of proliferative LN along with the co-expression of macrophages. Conclusion Serum renalase levels were correlated with disease activity in LN. Serum renalase might serve as a potential indicator for disease activity in LN. The marked increase of glomerular renalase and its association with macrophages suggest

  9. 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

  10. Optimal serum phenylalanine for adult patients with phenylketonuria.

    PubMed

    Okano, Yoshiyuki; Nagasaka, Hironori

    2013-12-01

    High serum phenylalanine in adult patients with phenylketonuria (PKU) causes neuropsychological and psychosocial problems that can be resolved by phenylalanine-restricted diet. Therefore, PKU patients must continue to adhere to phenylalanine-restricted diet for life, although the optimal serum phenylalanine level in later life has yet to be established. The purpose of this review was to establish the optimal serum phenylalanine level in later life of PKU patients. We evaluated oxidative stress status, nitric oxide metabolism, cholesterol-derived oxysterols, vitamin D and bone status, and magnetic resonance imaging (MRI) in adult PKU patients according to serum phenylalanine level. Oxidative stress increased markedly at serum phenylalanine of 700-800 μmol/L. Serum phenylalanine higher than 700-850 μmol/L correlated with the disturbance of nitric oxide regulatory system. Adult PKU patients had poor vitamin D status and exhibited predominance of bone resorption over bone formation. In the brain, the levels of 24S-hydroxycholesterol, a marker of brain cholesterol elimination, were low at serum phenylalanine levels exceeding 650 μmol/L. MRI studies showed high signal intensity in deep white matter on T2-weighted and FLAIR images of PKU patients with serum phenylalanine greater than 500 μmol/L, with decreased apparent diffusion coefficients. Changes in most parameters covering the entire body organs in adult PKU were almost acceptable below 700-800 μmol/L of phenylalanine level. However, the optimal serum phenylalanine level should be 500 μmol/L or less in later life for the brain to be safe.

  11. Rapamycin selectively alters serum chemistry in diabetic mice.

    PubMed

    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

  12. Clinical significance of serum thymus and activation-regulated chemokine in gastric cancer: Potential as a serum biomarker

    PubMed Central

    Lim, Jong-Baeck; Kim, Do-Kyun; Chung, Hye Won

    2014-01-01

    Thymus and activation-regulated chemokine (TARC) can stimulate cancer cell proliferation and migration. The present study evaluated the clinical significance of serum TARC in gastric cancer (GC). We measured serum TARC, macrophage-derived chemokine, monocyte chemotactic protein-1 and stem cell factor (SCF) levels using a chemiluminescent immunoassay along the GC carcinogenesis (normal, high-risk, early GC [EGC] and advanced GC [AGC]) in both training (N = 25 per group) and independent validation datasets (90 normal, 30 high-risk, 50 EGC and 50 AGC). Serum levels were compared among groups using one-way analysis of variance. To evaluate the diagnostic potential of serum TARC for GC, receiver operating characteristic curve and logistic regression analyses were performed. Correlations between serum TARC and GC clinicopathological features were analyzed using Spearman's correlation. In the training dataset, serum TARC correlated with serum MDC, MCP-1 and SCF. However, only serum TARC and SCF were significantly higher in cancer groups than non-cancer groups (P < 0.001). In the validation dataset, serum TARC also increased along the GC carcinogenesis; the AGC group (167.2 ± 111.1 ng/mL) had significantly higher levels than the EGC (109.1 ± 67.7 ng/mL), the high-risk (66.2 ± 47.7 ng/mL) and the normal (67.5 ± 36.2 ng/mL) groups (Bonferroni, all P < 0.001). Receiver operating characteristic curves and logistic regression demonstrated the remarkable diagnostic potential of serum TARC as a single marker (72.0% sensitivity and 71.1% specificity; cutoff point, 0.37; logistic regression) and in a multiple-marker panel (72.6% sensitivity and 88.2% specificity; cutoff point, 0.54). Spearman's correlation showed that serum TARC was closely correlated with tumor size (γs = 0.227, P = 0.028), T-stage (γs = 0.340, P = 0.001), N-stage (γs = 0.318, P = 0.002) and M-stage (γs = 0.346, P = 0.001). Serum TARC is a promising serum biomarker for GC

  13. Are serum bile salt concentrations raised in hyperlipidaemia?

    PubMed Central

    Beckett, G J; Douglas, J G; Finlayson, N D; Percy-Robb, I W

    1980-01-01

    We have studied serum fasting and postprandial primary bile salt concentrations in a group of 10 consecutive hyperlipidaemic subjects. The efficiency of hepatic bile salt clearance in the same subjects was aslo studied using an injected dose of sodium glycocholate. No increase in serum fasting or postprandial concentrations of the primary bile salts were observed and hepatic bile salt clearance was only marginally abnormal in one subject. The presence of hyperlipidaemia does not invalidate the use of serum conjugated bile salt analysis for the detection of liver diseases. PMID:7399323

  14. Training volume, androgen use and serum creatine kinase activity.

    PubMed

    Häkkinen, K; Alén, M

    1989-09-01

    Serum creatine kinase (CK) activities were investigated in elite male strength athletes (n = 20) during normal weight training and bodybuilding training (one training session per day), during high volume strength training (two sessions per day) and during strength training (one session per day) with the use of high dose synthetic androgens (five athletes in each subgroup). The findings demonstrated that the increase in serum CK was highest in the subgroup using androgens. These results suggest that strength training with the use of androgenic steroids leads to higher serum CK activities than normal strength training.

  15. 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.

  16. 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

  17. Serum cortisol concentrations in horses with colic.

    PubMed

    Mair, T S; Sherlock, C E; Boden, L A

    2014-09-01

    Few studies have evaluated cortisol concentrations in horses with colic. In humans with septic shock, high cortisol levels are associated with an increased risk of death. The objectives of this study were to compare the serum total cortisol concentrations (STCCs) in horses with colic to those without colic, and to assess whether the STCC relates to the pathological nature or outcome of the disease. STCCs were determined at presentation in horses with colic and in systemically healthy 'control' horses. Horses with colic were grouped based on clinical and clinico-pathological parameters at admission, treatment, lesion type and location, and outcome. Univariable and multivariable logistic regression were performed using two different outcome measures: (a) whether the horse had colic or not (yes vs. no), and (b) horse STCC (≥200 nmol/L vs. <200 nmol/L). Horses were more likely to have colic if they presented with high STCCs (≥200 nmol/L compared with <200 nmol/L). Horses with colic and with STCCs ≥200nmol/L were more likely to have moderate or severe colic signs (compared with mild colic) and heart rates >45 beats per min (compared with ≤45 beats per min). It was concluded that colic in horses is associated with elevated STCCs, and increased STCC in horses with colic appears to relate to the severity of the disease. STCCs may provide additional decision-making and prognostic information in horses with colic but further studies are required to avoid misinterpretations associated with the wide variation in STCCs.

  18. 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

  19. Association between serum pepsinogen A and C levels, serum gastrin concentrations and Helicobacter pylori antibodies.

    PubMed

    Kullich, W; Pöllmann, G; Czerwenka, C; Klein, G

    1999-01-01

    Pepsinogen A and C as well as gastrin were measured in the serum of 117 patients with rheumatic diseases. Moreover, the patients were divided up in groups by aids of a semiquantitative, rapid enzyme immunoassay for detection of Helicobacter pylori: 20 patients without H. pylori antibodies (AB) negative, 18 positive + (= weak AB-titre), 21 positive +2 (medium AB-titre), and 58 positive +3 (high AB-titre). The semiquantitative determinations of H. pylori-AB correlated with pepsinogen A, C and gastrin. Patients with H. pylori-AB positive +3 showed significantly higher values of pepsinogen C (p < or = 0.01) as well as pepsinogen A and gastrin (p < or = 0.05) than H. pylori-AB negative patients. Significantly increased levels of pepsinogen A (> 150 ng/ml) and C (> 25 ng/ml) were found to occur in 39% and 100% of patients with high H. pylori-AB titres. The measurement of serum pepsinogen C concentrations may provide additional diagnostic information of the extent of mucosal lesions in patients with positive H. pylori-AB titres treated with antirheumatic drugs. Our findings suggest that the semi-quantitative classification of positive AB-results can be useful in cases determining H. pylori infection and mucosal irritation if other investigations are not available.

  20. The association between serum ApoE genetic polymorphism and serum lipid level in hemodialysis patients.

    PubMed

    Zhang, Yong; Zhang, Linlin; Cao, Bo

    2015-02-01

    Growing evidence indicates that apolipoprotein E (ApoE) is one of the most important candidate genes for influencing the development of hemodialysis (HD). This study aims to detect the potential association between serum ApoE genetic polymorphism and serum lipid level in HD. A total of 485 subjects were enrolled in this case-control study. The created restriction site polymerase chain reaction and DNA sequencing methods were used to investigate ApoE c.109G>A genetic polymorphism. Our data suggested that there were significant differences in the distribution of allelic and genotypic frequencies between HD patients and healthy controls. The levels of total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, ApoA-I, ApoB, ApoE, and lipoprotein (a) for genotype AA were different from genotype GG in HD patients and healthy controls. Our findings support that the ApoE c.109G>A genetic polymorphism might influence the development of HD and could be a risk factor for assessing HD.

  1. 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.

  2. 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.

  3. Establishment of enzyme immunoassay for measuring serum sultopride levels.

    PubMed

    Someya, T; Shimoda, K; Muratake, T; Nakajima, E; Shirai, A; Funaoka, H; Yashiki, T; Ishii, H; Sunahara, N; Takahashi, S

    2001-06-01

    Measurement of serum sultopride levels was performed using an enzyme immunoassay. Little or no cross-reactivity with metabolites of sultopride and other drugs was found. The results of reproducibility, recovery, and dilution testing were all good enough for clinical use. A comparison between the measurement values of this method (y) with that of high-performance liquid chromatography (x) showed high correlation (n = 211, r = 0.991, p < 0.0001, y = 0.99x + 107.5). In a comparison between the sultopride dose and serum levels in 161 patients, interindividual differences were large (19 times for same doses), implying that the serum level cannot be predicted from the dosage. The method was found to be reliable for serum level measurements of sultopride and useful for monitoring compliance and assessing the optimal dose.

  4. Study on Serum Albumin in Third Trimester of Pregnancy.

    PubMed

    Sufrin, S; Nessa, A; Islam, M T; Das, R K; Rahman, M H

    2015-07-01

    Various hormones can cause marked changes in pregnant woman's appearance. Decreased level of serum albumin occurs in third trimester of pregnancy, which may be associated with increased maternal and infant mortality and morbidity. So, this study was carried out to evaluate and assess the level of serum albumin in third trimester of pregnancy. This cross-sectional study was carried out in the Department of Physiology Mymensingh Medical College, Mymensingh. This study enrolled 100 pregnant women of third trimester of pregnancy and 100 aged matched non-pregnant women from Mymensingh district. In this study serum albumin level in study group were 33.41 ± 4.62gm/l and in control group were 37.09 ± 4.21 gm/l, which was statistically decreased. The lower level of serum albumin in third trimester of pregnancy is the major concern of development of physiological edema during pregnancy and may be associated with pre-eclampsia.

  5. Association of serum lipids and obesity with cardiovascular mortality.

    PubMed Central

    Pelkonen, R; Nikkilä, E A; Koskinen, S; Penttinen, K; Sarna, S

    1977-01-01

    Serum lipid concentrations, relative body weight, and smoking habits were assessed in a cohort of 1648 middle-aged Finnish men who were subsequently followed for seven years. Multivariate analysis showed that serum triglyceride and cholesterol concentrations and smoking were all independently associated with cardiovascular mortality. High serum triglyceride concentrations increased the risk of cardiovascular death only when they exceeded 1.7 mmol/l (150 mg/100 ml), but this occurred at all cholesterol and relative body weight levels. Obesity influenced death rates only in men with raised serum lipid levels, while smoking was associated with increased mortality when any combination of the other factors was present. Men who had raised triglyceride concentrations combined with smoking or obesity had the highest risk of cardiovascular death. PMID:589076

  6. 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

  7. Increased serum thymidine kinase activity in acute sarcoidosis.

    PubMed

    Tajima, Syunji; Sando, Yoshichika; Maeno, Toshitaka; Sagawa, Naoki; Nara, Mami; Maeno, Yuri; Nakagawa, Junichi; Ito, Toshio; Hoshino, Yoichi; Suga, Tatsuo; Arai, Masashi; Kurabayashi, Masahiko

    2002-02-01

    This is the first case report of acute sarcoidosis with increased serum thymidine kinase (TK) activity. A 43-year-old male presented fever, swelling of parotid glands, lymphadenopathy, and peripheral neuropathy. Sarcoidosis was pathologically diagnosed by lung and parotid gland biopsy. His serum TK, which was increased to 11.2 U/l at diagnosis (normal <5 U/l), normalized after glucocorticoid therapy. Serum TK has been considered as a good marker of the proliferative activity of various types of neoplasms. Its rise in sarcoidosis has, however, not been described. Because acute sarcoidosis sometimes resembles malignant lymphoma, the possible rise of serum TK in sarcoidosis may be worthy of note. PMID:11868600

  8. 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...

  9. Serum hormone levels in men with severe acne.

    PubMed

    Aizawa, H; Niimura, M

    1992-07-01

    In order to evaluate the hormonal milieu in young men with severe acne, we measured serum estradiol (E2), total testosterone (T), free testosterone (FT), dihydrotestosterone (DHT), dehydroepiandrosterone sulfate (DHEA-S), and sex hormone binding globulin (SHBG) levels in sixteen male patients aged 20-30 years with severe acne, including twelve cases of nodular-cystic acne, and in seventeen age-matched normal controls. There were no significant differences in the serum levels of T, FT, DHT, DHEA-S, or SHBG between the patients and the controls, but serum E2 was significantly higher in the patient population. Thus, the hemodynamics of serum androgens in male patients with acne do not seem to differ significantly from that of normal controls. Elevated E2 levels might affect the inflammatory response of acne vulgaris through the release of thymic hormones, as reported in the literature. PMID:1401498

  10. 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.

  11. [Adverse reaction to cefonicid analogous to serum sickness].

    PubMed

    Ortega Calvo, M; Méndez Mora, J L; Soriano Crespo, E; Fernández Martínez, D; Torello Iserte, J; Castillo Ferrando, J R

    1995-06-01

    We report a case of a male who was treated with cephonicid because of a surgical complication. Serum-sickness like symptoms were diagnosed two weeks later. Medical references are discussed. PMID:7548647

  12. A simple UV spectrophotometric method for theophylline serum level determination.

    PubMed

    Plavsić, F

    1978-09-15

    A brief, simple and unexpensive UV spectrophotometric method for theophylline serum level determination is described. Charcoal extraction was performed for theophylline isolation from biological fluids. Coefficients of variation and recovery are similar to other parallel methods.

  13. Prognostic value of preoperative serum lactate dehydrogenase in thymic carcinoma

    PubMed Central

    Yuan, Zu-Yang; Gao, Shu-Geng; Mu, Ju-Wei; Xue, Qi; Mao, You-Sheng; Wang, Da-Li; Zhao, Jun; Gao, Yu-Shun; Huang, Jin-Feng

    2016-01-01

    Background The prognostic value of serum lactate dehydrogenase (LDH) has been demonstrated in various solid tumors. We attempted to determine whether serum LDH was predictive of survival in thymic carcinoma after surgical resection. Methods Ninety-five patients with thymic carcinoma treated in our hospital between January 2005 and December 2015 were retrospectively enrolled. Serum LDH was measured before surgery and categorized as low or high relative to the upper limit of normal (ULN) (225 U/L). The relationships of serum LDH level and other clinical variables with survival were estimated by Cox regression and Kaplan-Meier survival analysis. Results Serum LDH levels were found to be significantly associated with overall survival (OS) and progression-free survival (PFS) of these patients. The 1-, 3-, and 5-year PFS were 76%, 51%, and 38%, and the 1-, 3- and 5-year OS were 97%, 75%, and 46%, respectively. Univariate analysis found that high serum LDH (>225 U/L) was associated with both lower OS [hazard ratio (HR) =2.710; 95% confidence interval (CI): 1.363–1.5.391; P=0.004] and PFS (HR =3.365; 95% CI: 1.776–6.374; P<0.001). Multivariate analysis found that high serum LDH was associated with lower PFS (HR =2.122; 95% CI: 1.056–4.267; P=0.035). Moreover, high LDH was significantly associated with advanced Masaoka stage (P=0.001). Conclusions High serum LDH (>225 U/L) was an independent predictor of decreased PFS in thymic carcinoma patients. It was also significantly associated with reduced OS, but was not an independent predictor of death in those patients. PMID:27746998

  14. [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

  15. Serum silicon concentrations in pregnant women and newborn babies.

    PubMed

    Jugdaohsingh, Ravin; Anderson, Simon H C; Lakasing, Lorin; Sripanyakorn, Supannee; Ratcliffe, Sarah; Powell, Jonathan J

    2013-12-14

    Earlier studies in animals have suggested an essential role for Si in connective tissues, but such works have not been replicated per se. Nonetheless, a study conducted in 2000 has reported that Si may be essential during pregnancy for the growing fetus, since serum Si concentrations in infants were approximately 300 % higher than those in older children and adults and serum Si concentrations in pregnant women were approximately 300 % lower than those in age-matched non-pregnant controls. To reproduce these potentially important findings, in the present study, serum Si concentrations were measured in fourteen pregnant women (15-24 weeks of gestation) and compared with those of seventeen non-pregnant, non-lactating female controls. Serum Si concentrations were also measured in fourteen full-term mothers at the time of delivery and in the umbilical cord (UC) vein and artery where possible. Fasting serum Si concentrations in pregnant women were not significantly different from those of the female controls and showed little change with advancing gestation (r 0·2). Mean serum Si concentrations in the UC vein samples were 52 % higher, while those in the UC artery samples were 235 % higher than those in the maternal forearm vein samples, although data were widely spread and differences were not significant. Mean maternal forearm vein Si concentrations at delivery were 50 % lower than those of pregnant women and female controls, but, again, these were not significant. Overall, we note that there are significant analytical challenges in comparing baseline Si levels between different groups; notwithstanding, our findings cannot confirm a reduction in fasting serum Si levels during pregnancy, but, equally, we cannot rule out higher serum Si levels in newborns than in their mothers, and further work is required. PMID:23702224

  16. Serum Calcium Concentration Is Inversely Associated With Radiographic Knee Osteoarthritis

    PubMed Central

    Li, Hui; Zeng, Chao; Wei, Jie; Yang, Tuo; Gao, Shu-Guang; Li, Yu-Sheng; Luo, Wei; Xiao, Wen-Feng; Xiong, Yi-Lin; Lei, Guang-Hua

    2016-01-01

    Abstract To examine the relationship between serum calcium (Ca) concentration and radiographic knee osteoarthritis (OA). This study covered a total of 2855 subjects. The serum Ca concentration was detected by the Arsenazo III method. The radiographic OA of the knee was defined as changes equivalent to Kellgren–Lawrence grade 2 on 1 side at least. The serum Ca concentration was categorized into 4 quartiles, which are ≤2.27, 2.28–2.34, 2.35–2.41, and ≥2.42 mmol/L, respectively. The relationship between serum Ca and radiographic knee OA was examined using the multivariable logistic analysis after adjusting a series of potential confounding factors. For each quartile of the relationship between serum Ca concentration and radiographic knee OA, the OR with 95% CI was calculated, and the one with the lowest value was considered to be the reference. An inverse association existed between serum Ca concentration and radiographic OA of the knee in the multivariable model and the model where the factors of age, sex, and BMI were adjusted. The multivariable-adjusted OR (95% CI) for radiographic knee OA in the second, third, and fourth quartiles of serum Ca concentration were 1.05 (95% CI: 0.83–1.31), 1.01 (95% CI: 0.80–1.27), and 0.79 (95% CI: 0.62–1.00), respectively, in comparison with the reference (first) quartile. A trend approaching to statistical significant (P = 0.06) was observed. Meanwhile, the relative odds of radiographic OA of the knee were decreased by 0.79 times in the fourth quartile in comparison with the reference. There is likely to be an inverse association between serum Ca concentration and radiographic OA of the knee. PMID:26871857

  17. Serum zinc and pneumonia in nursing home elderly

    PubMed Central

    Meydani, Simin N.; Barnett, Junaidah B.; Dallal, Gerard E.; Fine, Basil C.; Jacques, Paul F.; Leka, Lynette S.; Hamer, Davidson H.

    2008-01-01

    Background Zinc plays an important role in immune function. The association between serum zinc and pneumonia in the elderly has not been studied. Objective To determine if serum zinc concentrations in nursing home elderly are associated with incidence and duration of pneumonia, total and duration of antibiotic use, and pneumonia-associated and overall deaths. Design This observational study was conducted in residents from 33 nursing homes in Boston, MA, who participated in a one-year randomized, double-blind, and placebo controlled vitamin E supplementation trial; all were given daily doses of ½ RDA of essential vitamins and minerals including zinc. Participants with baseline (N=578) or final (N=420) serum zinc concentrations were categorized as having low (<70 μg/dL) or normal (≥70 μg/dL) serum zinc concentrations. Outcome measures included incidence and number of days with pneumonia, number of new antibiotic prescriptions, days of antibiotic use, death due to pneumonia, and, all-cause mortality. Results Subjects with normal final serum zinc concentrations had lower pneumonia incidence, total antibiotic use (by almost 50%), and shorter duration of pneumonia and antibiotic use (by 3.9 and 2.6 days, respectively) (all p-values ≤0.004) relative to those with low zinc concentrations. Normal baseline serum zinc concentrations were associated with decreased all-cause mortality (p=0.049). Conclusion Normal serum zinc concentrations in nursing home elderly were associated with decreased incidence and duration of pneumonia, and decreased use and duration of antimicrobial therapy. Zinc supplementation to maintain normal serum zinc concentrations in the elderly may help reduce pneumonia incidence and associated morbidity. PMID:17921398

  18. Serum Liver Enzyme Pattern in Birth Asphyxia Associated Liver Injury

    PubMed Central

    Chhavi, Nanda; Zutshi, Kiran; Singh, Niranjan Kumar; Awasthi, Ashish

    2014-01-01

    Purpose To study temporal pattern of serum liver enzymes levels in newborns with hepatic injury associated with birth asphyxia (BA). Methods Singleton term newborns with BA and ≤72 hours of age admitted to neonatal intensive care unit were prospectively enrolled. Term newborns with physiological jaundice and without BA were studied as controls. Serum liver enzymes were measured at <24 hours, 24-72 hours, and at 6-12 days of age for cases and at 1-6 days of age for controls. BA was defined by 1 minute Apgar score <7 or delayed or absent cry with hypoxic ischemic encephalopathy. BA-associated liver injury was defined as serum alanine aminotransferase (ALT) elevation beyond +2 standard deviation (ALT > +2 SD) above the mean of control subjects at any of the three time points. Results Sixty controls and 62 cases were enrolled. Thirty-five cases (56%) developed BA-associated liver injury (ALT>81 IU/L). They had higher serum levels of ALT, aspartate aminotransferase, lactate dehydrogenase than the control infants, with peak at 24-72 hours. In controls, serum liver enzyme levels were significantly higher in appropriate-for-date (AFD) babies than small-for-date (SFD) babies. Serum enzyme pattern and extent of elevation were comparable between SFD and AFD babies. Degree of serum liver enzyme elevation had no relationship with severity of hypoxic encephalopathy. Conclusion Serum liver enzyme elevation is common in BA; it peaks at 24-72 hours followed by a sharp decline by 6-12 days of age. Pattern and extent of enzyme elevation are comparable between SFD and AFD babies. PMID:25349832

  19. 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

  20. Serum copper concentration as an index of experimental lung injury

    SciTech Connect

    Ward, W.F.; Molteni, A.; Ts'ao, C.; Ischiropoulos, H. )

    1989-01-01

    Serum copper (Cu) concentration was evaluated as an index of lung injury in two rat models of pneumotoxicity: hemithoracic irradiation and monocrotaline ingestion. In both models there was a dose- and time-dependent increase in serum Cu concentration. This hypercupremia paralleled the development of pulmonary endothelial dysfunction (decreased lung plasminogen activator activity and increased prostacyclin production) and pulmonary fibrosis (hydroxyproline accumulation). In the radiation model, lung injury and hypercupremia persisted for at least 6 months, and were spared similarly when the total dose was delivered in multiple daily fractions as compared to single doses. In irradiated rats, the elevated serum Cu concentration was accompanied by increases in plasma ceruloplasmin, lung Cu concentration, and lung Cu/Zn superoxide dismutase (SOD) activity. In monocrotaline-treated rats, lung damage and hypercupremia also were accompanied by a reduction in liver Cu concentration, and by a direct correlation between the concentrations of Cu and SGOT in the serum. In both models, some but not all modifiers of lung damage (penicillamine, angiotensin converting enzyme inhibitors, pentoxifylline) also partially prevented the insult-induced hypercupremia. In contrast, serum iron concentration was largely independent of treatment in all experiments. These data suggest that elevated serum copper concentration is an accurate and minimally invasive index of lung injury in irradiated and monocrotaline-treated rats.

  1. Evaluation of serum ceruloplasmin in aggressive and chronic periodontitis patients

    PubMed Central

    Harshavardhana, B.; Rath, S. K.; Mukherjee, Manish

    2013-01-01

    Background: Pro-inflammatory markers are seen to increase in inflammatory diseases like periodontitis. Detecting an increase in these markers is one of the diagnostic modality. One such marker, which can be detected, is the ceruloplasmin. Ceruloplasmin induces hypoxia and generates oxygen radicals at the site of aggressive periodontitis. It also causes a state of hypoferremia leading to increase in the natural resistance of the body. The aim of this study was to evaluate the serum levels of cerruloplasmin in both aggressive and chronic periodontitis patients. Materials and Methods: Blood samples were collected from aggressive periodontitis patients (n = 20), chronic periodontitis patients (n = 20) and periodontally healthy patients (n = 20). The serum was extracted from all the blood samples and ceruloplasmin levels were spectroscopically evaluated through a new kinetic method, which used a norfloxacin based reagent. Results: Serum ceruloplasmin levels were found to be significantly higher in aggressive periodontitis patients (P > 0.05) than in chronic periodontitis patients (P > 0.05) even though increase in the level of ceruloplasmin was found in chronic periodontitis. Periodontally healthy patients did not show increase in the levels of serum ceruloplasmin. The levels of serum ceruloplasmin also increased with the disease severity whose manifestations were increased bleeding on probing, increased pocket depth and increased attachment loss. Conclusion: Serum ceruloplasmin levels increased in both aggressive and chronic periodontitis patients, but more in aggressive periodontitis patients making it a potential marker for diagnosis of periodontitis. PMID:24049334

  2. A new aspect of serum protein binding of tolbutamide.

    PubMed

    Ayanoğlu, G; Uihlein, M; Grigoleit, H G

    1986-02-01

    Tolbutamide is known to bind highly to serum proteins. Quite different values have, however, been reported for binding, ranging from 80 to 99 percent. In this study, in vivo and in vitro binding of increasing concentrations of tolbutamide to human serum proteins were evaluated. In vitro studies were done serum from three healthy males and for in vivo studies serum samples from eight healthy males who had received 1,000 mg tolbutamide were used. Protein binding was determined by equilibrium dialysis, using DIANORM system. Tolbutamide concentrations were determined by HPLC method of Uihlein and Hack. The results suggest that there is an increase in percent tolbutamide bound with increasing concentrations of tolbutamide. Generally, an inverse relationship between the total concentration of a drug in serum and its bound fraction is observed. Our findings seem to be contrary to this, at least within the concentration range studied. There exist at least two binding sites on albumin with different affinities for tolbutamide and most probably, at low concentrations, the drug binds mainly to the high affinity sites, whereas at higher concentrations additional drug will bind to the lower affinity sites leading to the observed increase in fraction bound with concentration. In conclusion it may be said that serum protein binding is a much more complicated phenomenon than generally stated and that the normal observations are only true for some ideal compounds where only one site of adsorption has to be taken into account.

  3. Isolation and characterization of serum albumin from Camelus dromedarius

    PubMed Central

    MALIK, AJAMALUDDIN; AL-SENAIDY, ABDULRAHMAN; SKRZYPCZAK-JANKUN, EWA; JANKUN, JERZY

    2013-01-01

    Serum albumin constitutes 35–50 mg/ml of plasma proteins and performs various physiological activities including the regulation of osmotic pressure on blood, maintaining buffering of the blood pH, carrying different fatty acids and other small molecules, such as bilirubin, hormones, drugs and metal ions, as well as participating in immunological responses. Serum albumin is an extensively used protein in biotechnological and pharmaceutical industries. The camel (Camelus dromedarius) is well tailored to successfully survive in extremely hot and dry climates. Plasma osmolality in the camel increases during water-deprived conditions. In such circumstances serum albumin is crucial in the regulation of blood pressure. The study of biochemical, biophysical and immunological aspects of camel serum albumin (CSA) are likely to provide molecular insights into camel physiology and may render it an alternative to human serum albumin (HSA) and bovine serum albumin (BSA) in all cases. However, these proteins are currently not available or cannot be utilized due to a variety of considerations. In this study, 12 mg of highly pure CSA was obtained from 1 ml plasma. Coomassie Brilliant Blue staining of SDS-PAGE yielded one band and RP-HPLC results revealed a single sharp peak, indicating homogenous preparation of the CSA. The charge/mass ratio and surface hydrophobicity of the CSA was similar to that of BSA. Mass spectrometry analysis of the purified protein confirmed the identity of CSA. PMID:24137219

  4. 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.

  5. 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

  6. 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.

  7. Serum Leptin and Insulin Hormone Level in Recurrent Pregnancy Loss

    PubMed Central

    Baban, Rayah S.; Ali, Noor M.; Al-Moayed, Hala A.

    2010-01-01

    Objective To measure serum leptin and insulin levels in women with recurrent pregnancy loss using modified methods of High Performance Liquid Chromatography (HPLC), and to examine their influence on recurrent loss at different pregnancy trimesters. Methods A case control study was conducted from, 1 September 2008 to 30 December 2009 in the Obstetric and Gynecological Department-Al-Khadimiya Teaching Hospital. HPLC technique with new modified method was used to estimate serum leptin and insulin hormones in samples of women with recurrent pregnancy loss (patients group, n=64) and healthy pregnant women at the end of the third gestational trimester as a control group (n=51). Results Both serum leptin and insulin levels were high in women with pregnancy loss in their three trimesters. A significant correlation was found between age (r=0.535, p<0.018) and serum total leptin in women with RPL during the first trimester. Also, a highly significant correlation was found between serum total leptin and insulin in women with RPL during the first, second and third trimesters (r=0.894, r=0.931, and r =0.995) respectively. The number of women who lost their pregnancy during the first trimester was higher than those losing during other trimesters. Conclusion It can be concluded that recurrent pregnancy loss in women at different trimester is associated with endocrine abnormalities where serum leptin and insulin levels increase in a different way compared with normal healthy pregnant women. PMID:22043338

  8. 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

  9. Serum cholesterol selectively regulates glucocorticoid sensitivity through activation of JNK.

    PubMed

    Yang, Nan; Caratti, Giorgio; Ince, Louise M; Poolman, Toryn M; Trebble, Peter J; Holt, Cathy M; Ray, David W; Matthews, Laura C

    2014-11-01

    Glucocorticoids (Gc) are potent anti-inflammatory agents with wide clinical application. We have previously shown that increased serum concentration significantly attenuates regulation of a simple Gc-responsive reporter. We now find that glucocorticoid receptor (GR) regulation of some endogenous transactivated but not transrepressed genes is impaired, suggesting template specificity. Serum did not directly affect GR expression, activity or trafficking, implicating GR crosstalk with other signalling pathways. Indeed, a JNK inhibitor completely abolished the serum effect. We identified the Gc modulating serum component as cholesterol. Cholesterol loading mimicked the serum effect, which was readily reversed by JNK inhibition. Chelation of serum cholesterol with methyl-β-cyclodextrin or inhibition of cellular cholesterol synthesis with simvastatin potentiated the Gc response. To explore the effect in vivo we used ApoE(-/-) mice, a model of hypercholesterolaemia. Consistent with our in vitro studies, we find no impact of elevated cholesterol on the expression of GR, or on the hypothalamic-pituitary-adrenal axis, measured by dexamethasone suppression test. Instead we find selective Gc resistance on some hepatic target genes in ApoE(-/-) mice. Therefore, we have discovered an unexpected role for cholesterol as a selective modulator of Gc action in vivo. Taken together these findings reveal a new environmental constraint on Gc action with relevance to both inflammation and cancer.

  10. Status of Serum Zinc in Multidrug Resistant Tuberculosis.

    PubMed

    Barman, N; Haque, M A; Uddin, M N; Ghosh, D; Rahman, M W; Islam, M T; Rahman, M Q; Rob, M A; Hossain, M A

    2016-01-01

    Zinc plays a vital role in the immune status. Its deficiency affects host defense by reducing the number of circulating T cells and phagocytosis activity of other cells which ultimately impair cell mediated immunity. The cell-mediated immunity plays a major role in the causation of pulmonary tuberculosis. The present study was carried out to estimate serum zinc level in newly detected multidrug resistant tuberculosis (MDR-TB) in adult population. In this study total fifty (50) MDR-TB patients were enrolled conveniently from the in-patients departments of National Institute of Diseases of the Chest Hospital (NIDCH), Bangladesh. Serum zinc was estimated by atomic absorption spectrophotometry method from early morning fasting blood sample. Serum zinc level was assessed according to normal cut-off value 70-120 μgm/dl and 76% studied population were found lower than this value. The mean±SD serum zinc level was observed 60.40±8.91 μgm/dl. No associations were found between serum zinc level with age (p=0.11) and with sex (p=0.085) of the study population respectively. The low level of serum zinc in MDR-TB patients suggested impaired immune status of our study population.

  11. Analysis of serum copper and zinc concentrations in cancer patients.

    PubMed

    Zowczak, M; Iskra, M; Torliński, L; Cofta, S

    2001-01-01

    Several studies have shown that plasma copper concentrations are increased in various carcinomas. Zinc acts as a cellular growth protector, including growth of neoplastic cells, and its deficiency was demonstrated to be involved in several stages of malignant transformation. However, the usefulness of the serum zinc and copper determinations in cancer prevention, detection, monitoring treatment, and prognosis requires further investigations. The aim of the present study was to compare the serum copper and zinc levels in patients with cancer of the lung (PC), breast (BC), gastrointestinal tract (GIC), and gynecological (GYNC) malignancy with progress of the disease. The results of the study have shown a significant increase in the mean total serum Cu levels and the serum Cu/Zn ratio in all patient groups with cancer compared to a control group. Increased mean serum concentrations and Cu/Zn ratios were found in the whole group (ALLC), and for the GIC and GYNC groups with local as well as metastasized (Meta) disease in comparison with the control group. The mean serum concentrations of Zn were decreased only in metastasized ALLC and GYNC groups.

  12. 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

  13. Prevalence of Thrombocytopenia and Its Association with Serum Magnesium.

    PubMed

    Lu, Leihong; Zhan, Yiqiang; Yu, Jinming; Sui, Lihong

    2016-01-01

    The present study aimed to investigate the prevalence of thrombocytopenia and its association with serum magnesium in a nationally representative cohort. A total of 8478 participants aged 18 years and over were recruited in a cross-sectional survey. Thrombocytopenia was defined as platelet count less than 150 × 10(9)/L. Multivariable logistic regression models were applied to examine the association between serum magnesium and thrombocytopenia. The prevalence of thrombocytopenia in total was 16.5% with 18.8% for men and 14.4% for women (P < 0.0001), respectively. Compared with men in the first quartile of serum magnesium, the odds ratios (ORs) and 95% confidence intervals (CIs) for those in the second, third, and fourth quartiles of serum magnesium were 0.96 (0.75, 1.21), 0.78 (0.62, 0.98), and 0.82 (0.65, 1.04), respectively, after adjusting for multiple confounders. Likewise, the corresponding ORs (95% CIs) were 0.80 (0.63, 1.01), 0.79 (0.62, 0.99), and 0.65 (0.51, 0.84) in women. When serum magnesium was treated as a continuous variable, each one standard deviation increase of magnesium was associated with 12 and 8% lower risk of thrombocytopenia in men and women, respectively. Serum magnesium was inversely associated with thrombocytopenia, and the association was slightly different in men compared with that in women.

  14. Biosensor immunoassay for flumequine in broiler serum and muscle.

    PubMed

    Haasnoot, Willem; Gerçek, Hüsniye; Cazemier, Geert; Nielen, Michel W F

    2007-03-14

    Flumequine (Flu) is one of the fluoroquinolones most frequently applied for the treatment of broilers in The Netherlands. For the detection of residues of Flu in blood serum of broilers, a biosensor immunoassay (BIA) was developed which was fast (7.5 min per sample) and specific (no cross-reactivity with other (fluoro)quinolones). This inhibition assay was based on a rabbit polyclonal anti-Flu serum and a CM5 biosensor chip coated with Flu which could be detected in the range of 15-800 ng mL(-1). For the detection of Flu in muscle, an easy extraction procedure in buffer was selected and the measuring range was from 24 to 4000 ng g(-1). Average recoveries of 66 till 75% were found with muscle samples spiked at 0.5, 1 and 2 times the maximum residue limit (MRL in muscle = 400 ng g(-1)) and the decision limit (CCalpha) and the detection capability (CCbeta) were determined as 500 and 600 ng g(-1), respectively. Incurred muscle samples were analysed by the BIA and by LC-MS/MS and a good correlation was found (R2 = 0.998). Serum and muscle samples from with Flu treated broilers were analysed and the concentrations found in serum were always higher than those found in muscle (average serum/muscle ratio was 3.5) and this proved the applicability of the BIA in serum as predictor of the Flu concentration in muscle.

  15. 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.

  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 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

  18. Labile neurotoxin in serum of calves with "nervous" coccidiosis.

    PubMed Central

    Isler, C M; Bellamy, J E; Wobeser, G A

    1987-01-01

    Mouse inoculation was used to test for the presence of a toxin in the serum, cerebrospinal fluid, and intestinal contents collected from cases of bovine enteric coccidiosis, with and without neurological signs, and from control calves. Intravenous inoculation of mice with 10 mL/kg of serum from calves showing nervous signs caused effects significantly different from those caused by the inoculation of serum from calves not showing nervous signs and from control calves. The effect was particularly evident in female mice. At this dosage severe neurological signs such as loss of righting reflex, seizures and death occurred only with serum from calves with "nervous coccidiosis". The results suggest that serum from the calves with neurological signs contains a neurotoxin. This toxin appears to be highly labile. It was not present in the cerebrospinal fluid at levels comparable to those in the serum. The significance of this labile neurotoxin with respect to the pathogenesis of the neurological signs associated with bovine enteric coccidiosis is unknown. PMID:2955865

  19. Variant Prostate Carcinoma and Elevated Serum CA-125

    PubMed Central

    Bilen, Mehmet Asim; Reyes, Adriana; Bhowmick, Deb; Maa, April; Bast, Robert; Pisters, Louis L.; Lin, Sue-Hwa; Logothetis, Christopher J.; Tu, Shi-Ming

    2015-01-01

    Introduction About 10% of tumors derived from nongynecologic, noncoelomic tissues react with the OC125 antibody. Some patients with advanced prostate cancer were found to have elevated serum CA-125 level. Materials and Methods We examined the clinical history of 11 patients with castration-resistant prostate cancer and an elevated serum CA-125 level. Pathological review and immunohistochemical staining were performed on tumors from 8 of these patients. Results Patients with advanced prostate cancer and an elevated serum CA-125 level responded to androgen ablative therapy (median duration, 27 months). They were predisposed to develop persistent or recurrent urinary symptoms and visceral metastases. Eight of 11 patients had a low or undetectable serum prostate-specific antigen level (≤4 ng/ml) or an elevated serum carcinoembryonic antigen level (>6 ng/ml). In 3 of 7 patients whose specimens were available for further review, the tumors contained histologic features compatible with a diagnosis of ductal or endometrioid adenocarcinoma of the prostate. Conclusions Patients with prostate cancer and an elevated serum CA-125 level have unique clinical and pathologic characteristics. Some of these patients possess tumors compatible with a subtype of prostate cancer known as ductal adenocarcinoma. Additional studies need to be performed to elucidate the biologic basis of the various subtypes of prostate cancer. PMID:25347368

  20. Distinction of leukemia patients' and healthy persons' serum using FTIR spectroscopy

    NASA Astrophysics Data System (ADS)

    Sheng, Daping; Liu, Xingcun; Li, Weizu; Wang, Yuchan; Chen, Xianliang; Wang, Xin

    2013-01-01

    In this paper, FTIR spectroscopy was applied to compare the serum from leukemia patients with the serum from healthy persons. IR spectra of leukemia patients' serum were similar with IR spectra of healthy persons' serum, and they were all made up of proteins, lipids and nucleic acids, etc. In order to identify leukemia patients' serum and healthy persons' serum, the H1075/H1542, H1045/H1467, H2959/H2931 ratios were measured. The H2959/H2931 ratio had the highest significant difference among these ratios and might be a useful factor for identifying leukemia patients' serum and healthy persons' serum. Furthermore, from curve fitting, the RNA/DNA (A1115/A1028) ratios were observed to be lower in leukemia patients' serum than those in healthy persons' serum. The results indicated FTIR spectroscopic study of serum might be a useful tool in the field of leukemia research and diagnosis.

  1. Serum fatty acids in 8-year-old Finnish boys: correlations with qualitative dietary data and other serum lipids.

    PubMed

    Nikkari, T; Räsänen, L; Viikari, J; Akerblom, H K; Vuori, I; Pyörälä, K; Uhari, M; Dahl, M; Lähde, P L; Pesonen, E; Suoninen, P

    1983-05-01

    To survey risk factors in coronary heart disease in Finnish children, fasting serum specimens from 244 healthy 8-yr-old boys were analyzed for the fatty acid composition of cholesterol esters (CE), triglycerides (TG), free fatty acids (FFA), and phospholipids (PL). A qualitative dietary survey was made by asking parents to answer a questionnaire including, among others, a question on the kind of fat usually used on bread by the child. The mean percentages of linoleate (18:2) in serum cholesterol esters, triglycerides, free fatty acids, and phospholipids were 53.1, 13.5, 11.5, and 22.7%, respectively, which represent an international average. The quality of dietary fat had a clear influence on serum fatty acids, eg, the content of 18:2 in CE was 56.8 +/- 3.6% in boys using soft vegetable margarine and 50.5 +/- 3.6% in those using butter. The former had also a marginally lower serum total cholesterol (4.87 +/- 0.86 mmol/l) than the latter (5.08 +/- 0.80 mmol/l). Serum total cholesterol showed significant negative correlations with the percentage of 18:2 in all four lipid fractions, the highest r values being with PL-18:2 (-0.41) and CE-18:2 (-0.24). Accordingly, serum cholesterol was lower in the highest CE-18:2 quartile (4.67 +/- 0.76 mmol/l) compared with the lowest (5.30 +/- 0.70 mmol/l; p less than 0.001). The results indicate that when serum fatty acids are used as indicators of the quality of dietary fat, a negative association between polyunsaturated fat and serum cholesterol may be demonstrable even within a free-living population.

  2. Serum α-1 acid glycoprotein and serum amyloid A concentrations in cats receiving antineoplastic treatment for lymphoma.

    PubMed

    Winkel, Valter M; Pavan, Tatiana L R; Wirthl, Vera A B F; Alves, Ana L N; Lucas, Silvia R R

    2015-11-01

    OBJECTIVE To characterize serum α-1 acid glycoprotein (AGP) and serum amyloid A (SAA) concentrations at diagnosis and during treatment in cats with lymphoma. ANIMALS 16 cats with various anatomic forms of lymphoma and 25 healthy cats. PROCEDURES Blood samples were collected from healthy cats once and from cats with lymphoma at diagnosis and 2-week intervals until the 12th week of antineoplastic treatment. Serum harvested from blood samples was assessed for AGP and SAA concentrations. Differences in serum AGP and SAA values were investigated between healthy cats and cats with lymphoma (at diagnosis) and, for cats with lymphoma, between diagnosis and various points during treatment. RESULTS Serum AGP and SAA concentrations were higher in cats with lymphoma at diagnosis (median, 832.60 and 1.03 μg/mL, respectively), compared with those in healthy cats (median, 269.85 and 0.10 μg/mL). Treatment resulted in a gradual decrease in serum AGP concentration after 4 weeks and in SAA concentration after 8 weeks of treatment, and these concentrations returned to values comparable with those of healthy cats by 12 weeks of treatment, by which point all cats had achieved complete remission of the disease. CONCLUSIONS AND CLINICAL RELEVANCE Serum AGP and SAA concentrations in cats with lymphoma were higher at diagnosis than after antineoplastic treatment. Decreases to values established for healthy cats corresponded with achievement of complete disease remission. Serum AGP and SAA may be useful protein markers for monitoring of antineoplastic treatment in cats with lymphoma.

  3. Serum Glycated Albumin to Guide the Diagnosis of Diabetes Mellitus.

    PubMed

    Wu, Wan-Chen; Ma, Wen-Ya; Wei, Jung-Nan; Yu, Tse-Ya; Lin, Mao-Shin; Shih, Shyang-Rong; Hua, Cyue-Huei; Liao, Ying-Jhu; Chuang, Lee-Ming; Li, Hung-Yuan

    2016-01-01

    In the diagnosis of diabetes mellitus, hemoglobin A1c (HbA1c) is sometimes measured to determine the need of an oral glucose tolerance test (OGTT). However, HbA1c does not accurately reflect glycemic status in certain conditions. This study was performed to test the possibility that measurement of serum glycated albumin (GA) better assesses the need for OGTT. From 2006 to 2012, 1559 subjects not known to have diabetes or to use anti-diabetic medications were enrolled. Serum GA was measured, and a 75-g OGTT was then performed to diagnose diabetes. Serum GA correlated significantly to age (r = 0.27, p<0.001), serum albumin (r = -0.1179, age-adjusted p = 0.001), body mass index (r = -0.24, age-adjusted p<0.001), waist circumference (r = -0.16, age-adjusted p<0.001), and plasma GA (r = 0.999, p<0.001), but was unaffected by diet (p = 0.8). Using serum GA at 15% for diagnosis of diabetes, the sensitivity, specificity, and area under the receiver-operating characteristic curve were 74%, 85%, and 0.86, respectively. Applying a fasting plasma glucose (FPG) value of < 100 mg/dL to exclude diabetes and of ≥ 126 mg/dL to diagnose diabetes, 14.4% of the study population require an OGTT (OGTT%) with a sensitivity of 78.8% and a specificity of 100%. When serum GA value of 14% and 17% were used to exclude and diagnose diabetes, respectively, the sensitivity improved to 83.3%, with a slightly decrease in specificity (98.2%), but a significant increase in OGTT% (35%). Using combined FPG and serum GA cutoff values (FPG < 100 mg/dL plus serum GA < 15% to exclude diabetes and FPG ≥ 126 mg/dL or serum GA ≥ 17% to diagnose diabetes), the OGTT% was reduced to 22.5% and the sensitivity increased to 85.6% with no change in specificity (98.2%). In the diagnosis of diabetes, serum GA measurements can be used to determine the need of an OGTT.

  4. 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

  5. Bovine serum albumin (BSA) can replace patient serum as a protein source in an in vitro fertilization (IVF) program.

    PubMed

    Benadiva, C A; Kuczynski-Brown, B; Maguire, T G; Mastoianni, L; Flickinger, G L

    1989-06-01

    Alternate protein sources have been suggested to replace the commonly used cord or patient serum for in vitro fertilization (IVF) procedures. During an 11-month period 127 patients treated for in vitro fertilization had either their serum (N = 71) or bovine serum albumin (BSA; N = 56) used as the protein source in the insemination and growth media. Ham's F-10 + 0.5% BSA was used for sperm swim-up and insemination media and 1% BSA was used for the growth media. Patient's serum was added to Ham's F-10 culture media at concentrations of 7.5 and 15% for insemination and growth, respectively. Embryo transfer was performed with Ham's F-10 containing 90% maternal serum in both groups. Fertilization rate of 259 oocytes inseminated in medium containing patient's serum did not differ when compared with 200 oocytes inseminated in medium containing BSA. Likewise, rates of abnormal fertilization, cleavage, and pregnancy were similar in both groups. In a second experiment, 148 normally fertilized oocytes were transferred after 24 hr in culture to growth media containing two different concentrations of BSA (0.5 or 1%). Cleavage rates for the two groups were similar and the percentage of embryos developed to greater than or equal to 4 cells did not differ significantly. We conclude that a single concentration of BSA can safely be used to supplement culture media in human IVF with several practical and economical benefits.

  6. Serum ferritin and serum iron changes after cross-country and roller ski endurance races.

    PubMed

    Pattini, A; Schena, F; Guidi, G C

    1990-01-01

    We have studied the variations induced in iron status parameters by four endurance races of different lengths. A comprehensive group of 48 healthy, non-iron deficient, endurance athletes were evaluated before and after four different cross-country and roller ski races: I = Skirollonga, roller ski race for individuals (n = 10), mean duration (MD) = 1 h 48 min; II = Marcialonga, cross-country ski race for individuals (n = 9) MD = 3 h 10 min; III = 12-h of Caldonazzo (Trento-Italy) roller ski relay race (n = 13) MD = 12 h; IV = 24-h of Pinzolo (Trento-Italy) cross-country ski relay race (n = 16) MD = 24 h. In the relays the MD includes both exercise and recovery times. Blood samples were taken before and after every race for the determination of the following haematological parameters: red blood count, haemoglobin, and packed cell volume, serum iron concentration [SI], serum ferritin concentration [FERR] and total iron binding capacity (TIBC). The results showed a constant significant increase of [FERR] after the races (+44.9% in I, +50.5% in II, +51.2% in III and +36.5% in IV, P less than 0.01) while [SI] increased only in the first two races (+28.2% in I and +19.7% in II, P less than 0.01) and showed a remarkable decrease in the longer races (-46.1% in III and -39% in IV, P less than 0.01). The TIBC increased in all the races (except II) to the same extent (range 10%-12%).(ABSTRACT TRUNCATED AT 250 WORDS)

  7. 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

  8. 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

  9. Serum Uric Acid Level among Acute Stroke Patients.

    PubMed

    Mohsin, M; Das, S N; Haque, M F; Shikha, S S; Bhuiyan, A S; Saha, P L; Das, B R; Chowdhury, M; Jahan, M K; Rahman, M M

    2016-04-01

    Stroke is one of the leading causes of death and disability in developed as well as developing countries like Bangladesh. Elevated serum uric acid levels may predict an increased risk for cerebro-vascular (CV) events including stroke. Aim of the study was to measure the serum uric acid level among stroke patients and determine the relationship between serum uric acid level and stroke. This descriptive, cross-sectional study was carried out in Department of Medicine, Mymensingh Medical College Hospital, Mymensingh, Bangladesh to measure serum uric acid level among 102 stroke patients in a period of one year by using non-probability sampling procedure. Finally, collected data were analyzed using SPSS software Version 17.0. It was observed that the mean age of patients was 60.87±8.05 years, of them 80(78.43%) patients were male and the rest 22(21.57%) were female. About 66(64.70%) of respondents were in age group 60 years and above, while 36(35.30%) were in age group 59 years and below. At least 23(22.55%) of stroke patients had elevated serum uric acid with a mean serum uric acid level of 5.18mg/dl and standard deviation 1.26mg/dl. About 23(27.38%) patients in ischemic stroke had elevated serum uric acid whereas 18(100%) patients in hemorrhagic stroke had normal uric acid level. Uric acid level was elevated in ischemic stroke than haemorrhagic stroke patients (p<0.001). High uric acid level may be considered as a risk factor in patients with acute ischemic stroke. PMID:27277350

  10. 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

  11. Serum Resistance in an Invasive, Nontypeable Haemophilus influenzae Strain

    PubMed Central

    Williams, Bryan J.; Morlin, Gregory; Valentine, Nathan; Smith, Arnold L.

    2001-01-01

    A common feature of many different organisms causing bacteremia is the ability to avoid the bactericidal effects of normal human serum. In Haemophilus influenzae encapsulated strains are particularly serum resistant; however, we found that a nonencapsulated strain (R2866) isolated from the blood of an immunocompetent child with meningitis who had been successfully immunized with H. influenzae type b conjugate vaccine was serum resistant. Since serum resistance usually involves circumventing the action of the complement system, we defined the deposition of various complement components on the surfaces of this H. influenzae strain (R2866), a nonencapsulated avirulent laboratory strain (Rd), and a virulent type b encapsulated strain (Eagan). Membrane attack complex (MAC) accumulation correlated with the loss of bacterial viability; correspondingly, the rates of MAC deposition on the serum-sensitive strain Rd and the serum-resistant strains differed. Analysis of cell-associated immunoglobulin G (IgG), C1q, C3b, and C5b indicated that serum-resistant H. influenzae prevents MAC accumulation by delaying the synthesis of C3b through the classical pathway. Among the initiators of the classical pathway, IgG deposition contributes most of the C3 convertase activity necessary to start the cascade ending with MAC deposition. Despite similar IgG binding, strain R2866 delays C3 convertase activity compared to strain Rd. We conclude that strain R2866 can persist in the bloodstream, in part by inhibiting or delaying C3 deposition on the cell surface, escaping complement mediated killing. PMID:11159957

  12. Serum adipokine levels modified by donepezil treatment in Alzheimer's disease.

    PubMed

    Pákáski, Magdolna; Fehér, Agnes; Juhász, Anna; Drótos, Gergely; Fazekas, Orsike Csilla; Kovács, János; Janka, Zoltán; Kálmán, János

    2014-01-01

    Neurotransmitter enhancement therapy with acetylcholinesterase inhibitors (AChEIs) is a clinically proven approach for patients with Alzheimer's disease (AD). Donepezil is one of the three currently approved AChEIs for treating AD symptoms delaying the decline in cognitive function. In addition to cholinergic hypofunction, there are several factors in AD pathogenesis. For example, adipocytokines released from adipose tissue are also thought to play a role in the progress of dementia. Adipokines, i.e., leptin and adiponectin, are involved in the modulation of certain cognitive functions in the brain. The goal of our study was to elucidate effects of donepezil therapy on the serum levels of certain adipokines, such as leptin and adiponectin in AD patients. Clinically diagnosed mild-to-moderate AD patients (n = 26) were involved in this open-labeled, single-center, prospective self-control study. ApoE polymorphism, serum adiponectin, leptin, LDL, HDL, triglyceride levels, and BMI were determined before and at 12 and 24 weeks intervals of donepezil treatment, respectively. Twenty-four weeks of donepezil treatment induced a linear decrease of serum leptin levels (p = 0.013) and a linear elevation of serum adiponectin levels (p = 0.007). BMI (p < 0.001) and abdominal circumference (p = 0.017) were significantly lower at 24 weeks as compared to control values. None of the other examined metabolic parameters were changed during the treatment period. This previously unrecognized serum adipokine regulating potential of donepezil may be relevant in its therapeutic, disease modifying effect in AD by transferring protective (by increasing serum adiponectin levels) and detrimental (by decreasing serum leptin levels) effects onto the neurodegenerative process at the same time.

  13. Identification and Insilico Analysis of Retinoblastoma Serum microRNA Profile and Gene Targets Towards Prediction of Novel Serum Biomarkers

    PubMed Central

    Beta, Madhu; Venkatesan, Nalini; Vasudevan, Madavan; Vetrivel, Umashankar; Khetan, Vikas; Krishnakumar, Subramanian

    2013-01-01

    Retinoblastoma (RB) is a malignant tumor of the retina seen in children, and potential non invasive biomarkers are in need for rapid diagnosis and for prognosticating the therapy. This study was undertaken to identify the differentially expressed miRNAs in the serum of children with RB in comparison with the normal age matched serum, to analyze its concurrence with the existing RB tumor miRNA profile, to identify its novel gene targets specific to RB, and to study the expression of a few of the identified oncogenic miRNAs in the advanced stage primary RB patient’s serum sample. MiRNA profiling was performed on 14 pooled serum from children with advanced RB and 14 normal age matched serum samples, wherein 21 miRNAs were found to be upregulated (fold change ≤ −2.0, P ≤ 0.05) and 24 to be downregulated (fold change ≥ +2.0, P ≤ 0.05). Furthermore, intersection of 59 significantly deregulated miRNAs identified from RB tumor profiles with that of miRNAs detected in serum profile revealed that 33 miRNAs had followed a similar deregulation pattern in RB serum. Later we validated a few of the miRNAs (miRNA 17-92) identified by microarray in the RB patient serum samples (n = 20) by using qRT-PCR. Expression of the oncogenic miRNAs, miR-17, miR-18a, and miR-20a by qRT-PCR was significant in the serum samples exploring the potential of serum miRNAs identification as noninvasive diagnosis. Moreover, from miRNA gene target prediction, key regulatory genes of cell proliferation, apoptosis, and positive and negative regulatory networks involved in RB progression were identified in the gene expression profile of RB tumors. Therefore, these identified miRNAs and their corresponding target genes could give insights on potential biomarkers and key events involved in the RB pathway. PMID:23400111

  14. 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

  15. Serum amino acid profiles and their alterations in colorectal cancer.

    PubMed

    Leichtle, Alexander Benedikt; Nuoffer, Jean-Marc; Ceglarek, Uta; Kase, Julia; Conrad, Tim; Witzigmann, Helmut; Thiery, Joachim; Fiedler, Georg Martin

    2012-08-01

    Mass spectrometry-based serum metabolic profiling is a promising tool to analyse complex cancer associated metabolic alterations, which may broaden our pathophysiological understanding of the disease and may function as a source of new cancer-associated biomarkers. Highly standardized serum samples of patients suffering from colon cancer (n = 59) and controls (n = 58) were collected at the University Hospital Leipzig. We based our investigations on amino acid screening profiles using electrospray tandem-mass spectrometry. Metabolic profiles were evaluated using the Analyst 1.4.2 software. General, comparative and equivalence statistics were performed by R 2.12.2. 11 out of 26 serum amino acid concentrations were significantly different between colorectal cancer patients and healthy controls. We found a model including CEA, glycine, and tyrosine as best discriminating and superior to CEA alone with an AUROC of 0.878 (95% CI 0.815-0.941). Our serum metabolic profiling in colon cancer revealed multiple significant disease-associated alterations in the amino acid profile with promising diagnostic power. Further large-scale studies are necessary to elucidate the potential of our model also to discriminate between cancer and potential differential diagnoses. In conclusion, serum glycine and tyrosine in combination with CEA are superior to CEA for the discrimination between colorectal cancer patients and controls.

  16. 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.

  17. 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.

  18. 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

  19. Effects of polychlorinated biphenyls and lipemia on serum analytes

    SciTech Connect

    Steinberg, K.K.; Freni-Titulaer, L.W.J.; Rogers, T.N.; Burse, V.W.; Mueller, P.W.; Stehr, P.A.; Miller, D.T.; Steele, G.

    1986-01-01

    Twelve serum analytes (triglycerides, cholesterol, total and conjugated bilirubin, high-density-lipoprotein cholesterol (HDL-C) alkaline phosphatase (AP), gammaglutamyl transferase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), ..beta..-glucoronidase (..beta..-glu), alanine aminopeptidase (AAP), and 5'-nucleotidase (5'nuc)) were measured to investigate their correlation with exposure to polychlorinated biphenyls (PCBs) and 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT). The relationship between serum lipids, lipophilic toxicants, and the analytes was also evaluated. The ..beta..-glue, 5'nuc, triglycerides, cholesterol, and total bilirubin correlated positively and significantly with log concentrations of serum total PCBs and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE), a metabolite of DDT. The more highly chlorinated PCBs had significant, positive correlations with several serum analytes, but the less chlorinated PCBs correlated significantly and negatively only with HDL-cholesterol. Triglyercide- and cholesterol-rich lipoproteins were added to serum to determine the effects of lipids on these assays. Several were spuriously elevated. AP and ..beta..-glu were not affected by lipoprotein addition with the methods used in this study. AAP was increased significantly only at triglyceide concentrations exceeding 400 mg/dl.

  20. Serum ferritin concentrations in Africans with low dietary iron.

    PubMed

    Moyo, Victor M; Mvundura, Elisha; Khumalo, Hlosukwazi; Gangaidzo, Innocent T; Saungweme, Thokozile; Nouraie, Mehdi; Rouault, Tracey A; Gomo, Zvenyika A R; Gordeuk, Victor R

    2009-11-01

    In the setting of high dietary, several studies have provided evidence for a strong effect of both high dietary iron and an unidentified genetic locus on iron stores in Africans. To investigate whether these effects are discernible in the setting of low dietary iron, serum ferritin concentrations were measured in 194 Zimbabwean men >30 years of age and 299 postmenopausal women who consumed a non-iron-fortified diet and who did not drink iron-rich traditional beer or other alcoholic beverages. Comparisons were made with non-alcohol drinking African-Americans studied in the third National Health and Nutritional Examination Survey (NHANES III) who consume an iron-fortified diet. As stratified by age and sex, serum ferritin concentrations were significantly lower in the 493 Zimbabweans studied than in 1,380 comparable African-Americans (P < 0.0005). Nevertheless, nine Zimbabwean subjects (1.8% of all cases) had modestly elevated serum ferritin concentrations not associated with evidence of inflammation or hepatic dysfunction. These data suggest that mild serum ferritin concentration elevations may occur among Zimbabweans not exposed to high dietary iron and that iron fortification of the diet may have substantial effects on serum ferritin concentration.

  1. Method for microRNA isolation from clinical serum samples.

    PubMed

    Li, Yu; Kowdley, Kris V

    2012-12-01

    MicroRNAs are a group of intracellular noncoding RNA molecules that have been implicated in a variety of human diseases. Because of their high stability in blood, microRNAs released into circulation could be potentially utilized as noninvasive biomarkers for diagnosis or prognosis. Current microRNA isolation protocols are specifically designed for solid tissues and are impractical for biomarker development utilizing small-volume serum samples on a large scale. Thus, a protocol for microRNA isolation from serum is needed to accommodate these conditions in biomarker development. To establish such a protocol, we developed a simplified approach to normalize sample input by using single synthetic spike-in microRNA. We evaluated three commonly used commercial microRNA isolation kits for the best performance by comparing RNA quality and yield. The manufacturer's protocol was further modified to improve the microRNA yield from 200μl of human serum. MicroRNAs isolated from a large set of clinical serum samples were tested on the miRCURY LNA real-time PCR panel and confirmed to be suitable for high-throughput microRNA profiling. In conclusion, we have established a proven method for microRNA isolation from clinical serum samples suitable for microRNA biomarker development.

  2. Serum calprotectin: a new potential biomarker for thyroid papillary carcinoma.

    PubMed

    Tabur, S; Korkmaz, H; Özkaya, M; Elboğa, U; Tarakçıoglu, M; Aksoy, N; Akarsu, E

    2015-09-01

    The aim of this study was to evaluate serum calprotectin levels and oxidative stress status in patients with papillary thyroid carcinoma (PTC) and the changes in their levels after total thyroidectomy. The study involved 30 patients with PTC and 30 healthy controls. Blood samples were obtained from the PTC patients before and 1 month after the operation. Preoperative and postoperative serum samples from PTC patients and healthy controls were analysed for calprotectin, total antioxidant status (TAS), total oxidant status (TOS) and lipid hydroperokside (LOOH). The preoperative calprotectin, TOS, OSI and LOOH levels of the patients with PTC were significantly higher compared to those of the control group (p < 0.001, for each). The levels of calprotectin decreased significantly in patients with PTC after the operation (p < 0.001), while TAS, TOS and OSI levels remained unchanged (p = 0.313, p = 0.085 and p = 0.163, respectively). Preoperative serum calprotectin levels were positively correlated with TOS, OSI and LOOH levels and negatively correlated with TAS levels in patients with PTC. In conclusion, serum calprotectin levels is increased in patients with PTC, and calprotectin is positively correlated with TOS and LOOH. Serum calprotectin levels is significantly decreased after total thyroidectomy.

  3. 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.

  4. 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

  5. Eating a healthy lunch improves serum alanine aminotransferase activity

    PubMed Central

    2013-01-01

    Background Nutritional guidance and diet control play important roles in the treatment of obesity and non-alcoholic fatty liver. However, in Japan, nutritional guidance is difficult to provide in practice. Therefore, we evaluated the effects of providing the ‘once-a-day’ intervention of a healthy lunch on various metabolic parameters. Methods For a 1-month preparatory period, 10 subjects generally consumed the lunches that were provided by the worksite cafeteria. This was followed by a 1-week washout period, after which, the subjects consumed healthy, low-calorie, well-balanced lunches for a 1-month test period. After the preparatory and test periods, blood samples were obtained from all subjects. The serum levels of indices relevant to metabolic syndrome and fatty liver were measured. Results Serum alanine aminotransferase activity significantly decreased by 20.3% after the healthy intervention. However, the indices of metabolic syndrome did not significantly change. Analysis of the relationship between serum alanine aminotransferase activity and nutrient content indicated that the improvement of serum alanine aminotransferase status was due to the higher vegetable content and lower animal-source protein of the meals provided. Conclusions In summary, the ‘once-a-day’ intervention of providing a healthy lunch improved serum alanine aminotransferase status. A diet high in vegetables and low in animal-based protein is important in maintaining a healthy condition. PMID:24034595

  6. 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

  7. [Detection of autoantibodies to polymerized human serum albumin].

    PubMed

    Manns, M; Müller, M; Meyer zum Büschenfelde, K H

    1984-11-01

    Binding activity of antibodies against polymerized human serum albumin (pHSA) was measured in the serum of 348 patients with various hepatic and non-hepatic diseases and in the serum of 108 control persons. The methods used were passive hemagglutination (PH) with antigen loaded human erythrocytes and radial immunodiffusion (ID). In the PH-method only HBsAg-positive sera reacted. Blocking experiments with pHSA, polymerized bovine serum albumin (pBSA) and monomeric human serum albumin (mHSA) showed, that the PH-method measures HBsAG associated receptors for pHSA. In HBeAG-positive cases titers were significantly higher than in anti-HBe-positive sera. Using the ID-method it could be shown, that 40% of sera of patients with liver diseases (n = 272), 37% of patients with LED (n = 27), 72% of patients with rheumatoid arthritis (n = 32), 6% of patients with glomerulonephritis (n = 17) and 2% of normal persons (n = 108) reacted. These sera reacted in the immunodiffusion assay with pHSA and pBSA but not with mHSA. Autoantibodies against non species specific determinants of pHSA which are not specific for liver diseases and possibly due to disturbed immunoregulation can be demonstrated by immunodiffusion. They may possibly be modulators of the pHSA mediated binding of hepatitis B-virus to hepatocytes.

  8. Immunoradiometric assay for human serum amyloid P component.

    PubMed

    Millar, David J; Hutchinson, Winston L; Pepys, Mark B

    2011-08-31

    Human serum amyloid P component (SAP) is of increasing interest for its possible pathogenic role in amyloidosis and Alzheimer's disease, and as a therapeutic target in these conditions. We have developed and validated a robust and reproducible immunoradiometric assay (IRMA) for human SAP in serum, plasma and cerebrospinal fluid, and characterized the notable stability of human SAP immunoreactivity during storage of undiluted serum at 4°C and 37°C as well as frozen at -30°C. SAP values were also stable after repeated freeze thawing of highly diluted serum samples. The 100 fold dynamic range of the assay, 0.5-50 μg/L, encompassed all values seen in blood and cerebrospinal fluid, when tested at suitable dilutions, from both normal healthy individuals and patients, including subjects receiving the SAP-depleting drug, CPHPC. Furthermore by comparing the IRMA values in the presence and absence of calcium, the new assay revealed interference due to the binding of CPHPC by SAP, which was markedly enhanced in heparinized plasma. It is therefore essential that SAP assays in samples from patients on CPHPC be conducted in the absence of free calcium, in order to completely abrogate interference and determine the actual total SAP concentration. Estimates by the IRMA of SAP concentration in 49 serum samples from amyloidosis patients corresponded closely with those obtained by the established standard electro-immunoassay method and by a newly developed commercial ELISA kit (Hycult Biotechnology).

  9. 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

  10. 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.

  11. 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

  12. Serum chemical values in hypothermic and rewarmed young calves.

    PubMed

    Olson, D P; South, P J; Hendrix, K

    1983-04-01

    Serum chemical values were determined in cold-stressed Holstein bull calves ranging from 1 to 7 days of age. The animals were anesthetized and cold-stressed until their core body temperature (colonic) was lowered 10 C. Animals were then rewarmed in warm water, with heat pads or heat lamps, or were allowed to recover naturally (unassisted) at room temperature. Blood samples were collected at selected intervals during cooling and recovery. Increases (P less than 0.05) were observed in the concentrations of glucose, calcium, phosphorus, iron, alkaline phosphatase, aspartate aminotransferase, lactate dehydrogenase, total protein, albumin, total globulin, serum urea nitrogen, uric acid, total bilirubin, indirect bilirubin, and cholesterol in the cold-stressed calves during cooling. Concentrations of chloride and insulin decreased (P less than 0.05) during the same period. Changes observed in many of the serum chemical values during rewarming were generally the reverse of the respective changes that occurred during cooling, although insulin values became exceedingly high in some cases midway or near the end of recovery. Serum enzyme values also remained high during most of recovery. Data did not indicate a clear advantage of one method of rewarming over the other methods used in terms of return of the serum chemical values to normal.

  13. Serum cardiac troponin response in adolescents playing basketball.

    PubMed

    Nie, J; Tong, T K; Shi, Q; Lin, H; Zhao, J; Tian, Y

    2008-06-01

    Cardiac troponin release is generally found in adult athletes after continuous-type endurance exercises or sport competitions. The purpose of this study was to investigate whether the physical stress experienced by adolescents while playing basketball, an intense, intermittent-type sport, could induce transient elevations of the serum cardiac troponin T (cTnT) and I (cTnI). Serum cTnT and cTnI levels in 10 male adolescent players (age 15.0 +/- 0.7 yr) were assessed immediately before and at 2, 4 and 24 h after a game randomly selected from a preseason basketball-training program. At 4 h following the game, serum cTnT levels in four of the ten subjects were above the cutoff of 0.01 ng . ml (-1) for myocardial injury. Two of these four subjects had values higher than the acute myocardial infarction cutoff of 0.05 ng . ml (-1). In three of the four subjects, the serum cTnI was above the cutoff of 0.06 ng . ml (-1) for myocardial injury. Nevertheless, serum cardiac troponins at 24 h had returned to pre-exercise levels. These findings suggest that the physical stress encountered during intense, intermittent-type sports could cause release of cardiac troponins in some adolescents at low risk for cardiac disease.

  14. Serum total antioxidant capacity in oral carcinoma patients

    PubMed Central

    Rathan Shetty, K. S.; Kali, Arunava; Rachan Shetty, K. S.

    2015-01-01

    Context: Oxidative stress is a major determinant in carcinogenesis and serum total antioxidant capacity (TAC) indirectly reflects the level of oxidative stress. Although oral cancer is the third most frequent cancer in Indian population, there are no standard noninvasive marker for early detection and monitoring therapeutic response in oral cancer patients. Aims: This study was carried out to investigate implications of serum TAC in oral cancer by evaluating pre- and post-operative levels in oral cancer patients. Settings and Designs: It was a prospective single blinded study. Subjects and Methods: Serum TAC was measured using ferric-reducing antioxidant power assay. Pre- and post-operative values were estimated and compared in 30 oral cancer patients who underwent surgery. Statistical Analysis Used: Paired t-test was used to compare pre- and post-operative values. Results: Compared to the normal value, both pre- and post-operative serum TAC were significantly low in oral cancer patients. However, there was no statistically significant difference between pre- and postoperative levels. Conclusions: In this study, low mean serum TAC was detected in oral cancer patients. However, its diagnostic and prognostic significance in oral cancer needs further investigation. PMID:25829792

  15. Transforming growth factor beta 1 null mutation in mice causes excessive inflammatory response and early death.

    PubMed Central

    Kulkarni, A B; Huh, C G; Becker, D; Geiser, A; Lyght, M; Flanders, K C; Roberts, A B; Sporn, M B; Ward, J M; Karlsson, S

    1993-01-01

    To delineate specific developmental roles of transforming growth factor beta 1 (TGF-beta 1) we have disrupted its cognate gene in mouse embryonic stem cells by homologous recombination to generate TGF-beta 1 null mice. These mice do not produce detectable amounts of either TGF-beta 1 RNA or protein. After normal growth for the first 2 weeks they develop a rapid wasting syndrome and die by 3-4 weeks of age. Pathological examination revealed an excessive inflammatory response with massive infiltration of lymphocytes and macrophages in many organs, but primarily in heart and lungs. Many lesions resembled those found in autoimmune disorders, graft-vs.-host disease, or certain viral diseases. This phenotype suggests a prominent role for TGF-beta 1 in homeostatic regulation of immune cell proliferation and extravasation into tissues. Images PMID:8421714

  16. 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

  17. 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.

  18. 1,25-dihydroxyvitamin D3 stimulates transforming growth factor-beta1 synthesis by mouse renal proximal tubular cells.

    PubMed

    Weinreich, T; Landolt, M; Booy, C; Wüthrich, R; Binswanger, U

    1999-01-01

    1,25-dihydroxyvitamin D3 [1,25-(OH)2 D3] is a secosteroid hormone with effects on cell growth, differentiation and immunoregulatory functions in a number of tissues not primarily involved in mineral metabolism. We recently demonstrated growth-regulating effects of 1, 25-(OH)2 D3 on human mesangial cells and proximal tubular cells. To investigate whether 1,25-(OH)2 D3 might also affect the synthesis of cytokines and growth factors in proximal tubular cells, we assessed in the present study the expression and secretion of transforming growth factor-beta1 (TGF-beta1) in a mouse proximal tubular cell line (MCT) in vitro. TGF-beta1 synthesis was measured by a monospecific ELISA in culture supernatant. The secreted TGF-beta1 was proven to be biologically active by means of a bioassay system (CCL-64 mink lung epithelial cell proliferation assay). TGF-beta1 gene expression was assessed by RT-PCR. To analyze whether TGF-beta1 expression mediates the 1,25-(OH)2 D3-induced antiproliferative actions in MCT, proliferation studies in the absence or presence of a blocking monoclonal anti TGF-beta1-3 antibody were performed. 1, 25-(OH)2 D3 (10(-11) to 10(-7) M) specifically increased the TGF-beta1 protein secretion in MCT with a maximum at 10(-8) M. No detectable effect was found with 25 D3 at 10 times higher concentrations. A synthetic 20-epi analogue, MC 1288, increased TGF-beta1 secretion up to similar amounts at equimolar concentrations as the natural hormone 1,25-(OH)2 D3. Steady-state TGF-beta1 mRNA concentration in MCT was transiently increased by 1, 25-(OH)2 D3 between 12 and 24 h, returning to control values at 48 h. Blocking TGF-beta1 did not reduce or abrogate the antiproliferative effect of 1,25-(OH)2 D3. In conclusion, 1,25-(OH)2 D3 stimulates TGF-beta1 expression in renal proximal tubular cells, a growth factor with anti-inflammatory and profibrotic actions which plays an important role in the development and progression of nephrosclerosis. PMID:10394107

  19. 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

  20. Serum chemistry of the collared peccary (Tayassu tajacu).

    PubMed

    Lochmiller, R L; Grant, W E

    1984-04-01

    Values of serum biochemistry were obtained for 33 adult (16 male and 17 female) and six juvenile (four male and two female) collared peccaries collected by trapping and drugging animals from southern Texas during the period July through September 1982. Only cholesterol and aspartate aminotransferase concentrations differed significantly with respect to sex. Juvenile peccaries had significantly lower concentrations of total protein and globulins, but had higher concentrations of glucose, triglycerides, alkaline phosphatase, alanine aminotransferase, and calcium, and a higher albumin/globulin ratio than did adults. Effects of method of capture on biochemical attributes of serum from five gunshot and nine trapped adult peccaries collected from a single herd during March 1983 also were examined. Trapped peccaries had significantly higher levels of serum urea nitrogen, urea nitrogen/creatinine ratio, glucose, and chloride concentrations. Levels of uric acid, calcium, and potassium were significantly lower among the trapped animals.

  1. Serum gastrin in canine chronic lymphocytic-plasmacytic enteritis

    PubMed Central

    2005-01-01

    Abstract This study evaluates serum gastrin concentrations in dogs with chronic lymphocytic-plasmacytic enteritis, as well as its possible relationship with the severity of lesions present in the stomach. To achieve this aim, 5 dogs without gastrointestinal disease and 15 dogs with chronic lymphocytic-plasmacytic enteritis were included. Serum gastrin concentrations were significantly increased in dogs with chronic lymphocytic-plasmacytic enteritis compared with those in dogs without gastrointestinal disease. Also, there was a positive correlation between the severity of the gastric lesion and the serum gastrin concentration. Our findings indicate the possibility that gastrin plays a role in the etiology of an accompanying chronic antral gastritis in canine chronic lymphocytic-plasmacytic enteritis. PMID:16152719

  2. Inhibition of lymphocyte blastogenesis by serum leachates of fly ash

    SciTech Connect

    Harris, W.R.; Shifrine, M.

    1987-01-01

    Samples of 8 ashes were leached with canine serum for 24 h to remove metal ions from the particle surfaces. The particles were removed by filtration, and the concentrations of 11 metal ions in the serum leachates were determined by atomic absorption spectrophotometry. The leachate samples were evaluated using the canine whole-blood lymphocyte stimulation test (WB/LST). The serum extracts of oil-related ashes were highly inhibitory, while lower biological activity was observed for the extracts of coal ashes. The observed inhibition in the WB/LST was correlated with the concentration of each metal ion using Kendall's rank correlation test. The highest correlations were observed for Mn and V. The results are compared with previous WB/LST studies on pure metal salts.

  3. The role of serum vitamin D levels in vitiligo

    PubMed Central

    Karagün, Ebru; Baysak, Sevim; Erden, Gönül; Aktaş, Habibullah; Ekiz, Özlem

    2016-01-01

    Introduction Vitiligo is a common acquired pigmentary skin disorder. Vitamin D is responsible for skin pigmentation, increases tyrosinase activity and melanogenesis, and exhibits immunoregulatory functions. Low levels of vitamin D are associated with many autoimmune diseases, including systemic lupus, diabetes mellitus, rheumatoid arthritis, multiple sclerosis and alopecia areata. Few reports have evaluated serum vitamin D levels in vitiligo patients, and their results are conflicting. Aim To evaluate serum vitamin D levels of vitiligo patients and compare the results with controls. Material and methods In total, 50 vitiligo patients and 47 controls were enrolled in the study. Vitamin D levels were measured from blood samples. Group comparisons were performed using appropriate statistical methods. Results The patients had lower serum vitamin D levels than the controls, but this difference was not significant (p = 0.570). Conclusions It remains unknown whether vitamin D deficiency causes vitiligo. Larger controlled studies are required to prove whether low circulating vitamin D is a causative factor in vitiligo.

  4. Determination of drug levels in human serum by circular dichroism.

    PubMed

    Gortázar, P; Roën, A; Vázquez, J T

    1998-01-01

    A study of the applicability of circular dichroism (CD) for the determination of drug levels in human serum is described and a new method for the quantitative determination of optically active absorbing drugs having Cotton effects at wavelengths about 250 nm in human serum and/or plasma is proposed. The principal advantages of this method are speed, economy, and simplicity, no derivatization or chromatographic separation steps being needed. The validity of the CD determination was confirmed by analysis of variance, beta-lactam antibiotics being chosen as model drugs. In addition, the validation studies performed confirm the accuracy and precision of the proposed method. For beta-lactam antibiotics lacking Cotton effects above 250 nm, an alternative method based on the extraction of the drug from serum is considered.

  5. 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.

  6. Effect of ethanol on serum electrolytes and osmolality

    SciTech Connect

    Mahboob, T.; Haleem, M.A.

    1988-01-01

    Rats and rabbits were injected ethanol 2 g/kg intraperitoneally. One hour after injection blood was analyzed for serum electrolytes and osmolality. Administration of ethanol caused decrease in serum sodium, potassium, calcium, chloride, magnesium, phosphorus and glucose in rabbits. Further studies of intraperitoneal administration of ethanol in rats showed decrease in concentration of sodium, potassium, calcium, chloride, magnesium, phosphorus and glucose. Administration of ethanol caused an increase in serum osmolality in both rabbits and rats. It is concluded that ethanol ingestion is probably the commonest cause of the hyperosmolar state. Although the osmotic and sedative effects of ethanol are pharmacologically unrelated, the presence of ethanol should be considered in comatose patients whom the measured plasma osmolality appreciably exceeds that predicted on the basis of plasma glucose, urea and electrolytes concentration.

  7. 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

  8. Analysis of human serum from women affected by cervical lesions.

    PubMed

    Barba de la Rosa, Ana P; Lugo-Melchor, Ofelia Y; Briones-Cerecero, Erika P; Chagolla-López, Alicia; De León-Rodríguez, Antonio; Santos, Leticia; Vázquez-Ortiz, Guelaguetza; Salcedo, Mauricio

    2008-01-01

    Cervical cancer is one of the first causes of death in Mexican women population. The plasma proteome has a wide dynamic range concentrations of different protein and their alterations reflect the physiological state of the individual's health. The aim of this study was to characterize the 2D-PAGE serum patterns from healthy women and with different levels of cervical lesions. Changes in haptoglobin, apolipoproteins, and transthyretin, when comparing the serum from healthy women and serum from patients with different levels of cervical lesion were found. The Western blot analysis showed increasing concentrations of metalloproteinases (MMP's), proteins with important biological roles in tumor development and metastasis. Protein profiles in conjunction with MS, bioinformatics, and Western blot analysis, allow us to compile information for the acquisition of results to proposed candidates biomarkers of cervical cancer among Mexican women population.

  9. Circulating nucleic acids in plasma and serum: an overview.

    PubMed

    Lo, Y M

    2001-09-01

    The recent interest in nucleic acids in plasma and serum has opened up numerous new areas of investigation and new possibilities for molecular diagnosis. In oncology, tumor-derived genetic changes, epigenetic alterations, and viral nucleic acids have been found in the plasma/serum of cancer patients. These findings have important implications for the detection, monitoring, and prognostication of many types of malignancies. In prenatal diagnosis, the discovery of fetal DNA in maternal plasma and serum has provided a noninvasive source of fetal genetic material for analysis. This development has important implications for the realization of noninvasive prenatal diagnosis and has provided new methods for the monitoring of pregnancy-associated disorders. Plasma DNA technology has also found recent applications in the fields of organ transplantation, posttrauma monitoring, and infectious agent detection. Future areas of study include circulating RNA in plasma and the elucidation of the biology of release, clearance, and possible functionality of plasma nucleic acids.

  10. [A diagnostic serum with antibodies to virulent Yersinia].

    PubMed

    Smirnov, I V; Gorokhov, V I

    1990-01-01

    A diagnostic agglutinating adsorbed rabbit serum with antibodies to Yersinia strains containing virulence plasmid with molecular mass of 40-50 mD was prepared. Trials of this serum in agglutination test on the glass with 69 Yersinia strains (Y. enterocolitica, Y. frederiksenii, Y. intermedia, Y. kristensenii, Y. pseudotuberculosis) and with 42 other Enterobacteriaceae strains have confirmed the specificity and sufficiently high activity of the agent in respect of virulent Yersinia strains. Experiments have demonstrated the possibility of using this serum in tests for the detection of yersiniasis agents and for rapid assessment of individual Yersinia clones in respect of the presence of plasmid with a molecular mass of 40-50 mD.

  11. Serum amylase isozymes in patients with chronic pancreatitis with hyperamylasemia.

    PubMed

    Wakabayashi, A; Saeki, M; Mori, R; Oshiba, S

    1977-01-01

    In order to clarify the relationship between hyperamylasemia and clinical states in chronic pancreatitis, serum amylase isozymes were studied in 39 cases of chronic pancreatitis including 13 cases of alcoholic pancreatitis. Hyperamylasemia in chronic pancreatitis is generally due to high pancreatic type isoamylase (P-amylase) activity in acute exacerbation, sometimes accompanied by a transient elevation in salivary type isoamylase (S-amylase). On remission, however, hyperamylasemia due to high S-amylase activity has been found. These were cases of advanced alcoholic pancreatitis, which exhibited a characteristic pattern of low serum P-amylase and high serum S-amylase activities while the clearance ratio (Cam/Ccr) was normal despite high S-amylase activity. It should be noted that hyperamylasemia in chronic pancreatitis may be caused by high S-amylase activity in addition to high P-amylase activity, especially in alcoholic pancreatitis.

  12. 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

  13. [Serum lipid spectrum in patients with obstructive jaundice].

    PubMed

    Makarov, V K; Mokhov, E M; Mosiagin, A V

    2007-11-01

    The study was undertaken to determine the serum lipid profile in patients with obstructive jaundice (OJ) of various genesis versus those with chronic viral hepatitis B (CVHB). The serum lipid profile was studied in 50 patients with OJ whose cause was cancer diseases and calculous cholecystitis in 20 and 30 patients, respectively. Thirty patients with CVHB were examined as a control group. In patients with OJ, the relative serum content of phospholipids was found to be twice less than that in patients with CVHB. In patients with OJ, hyperlipemia was mainly caused by free cholesterol or cholesterol esters. As compared with the patients with calculous cholecystitis and CVHB, the patients with cancer diseases had low sphingomyelin levels; this fact may be used as an additional measure in detecting OJ of cancer genesis. PMID:18228656

  14. 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

  15. 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

  16. Measurements of C-reactive protein in serum and lactate dehydrogenase in serum and synovial fluid of patients with osteoarthritis.

    PubMed

    Hurter, K; Spreng, D; Rytz, U; Schawalder, P; Ott-Knüsel, F; Schmökel, H

    2005-03-01

    Diagnosis of osteoarthritis (OA) is based upon the clinical orthopaedic examination and the radiographic assessment, both of which can be non-specific and insensitive in early joint disease. The aim of our study was to investigate if there is an increase in serum levels of C-reactive protein (CRP) in degenerative joint disease (DJD) and if CRP could be used to help diagnose OA. We also wished to investigate whether it was possible to distinguish a joint with clinically and radiographically confirmed OA from a healthy joint by comparing lactate dehydrogenase (LDH) levels within the synovial fluid and the serum. We have shown a difference in synovial LDH levels between diseased and healthy joints (P<0.0001). There was also a significant difference between LDH in arthritic synovial fluid and serum, with no correlation between the values. Despite the fact that the values of our clinical patients tended to be higher than the values of our control group (P=0.05) all measured values were within the normal limits of previous publications. From these data, we conclude that single measurements of serum CRP do not permit detection of OA in clinical patients and that serum LDH is not a reliable marker for osteoarthritis. LDH levels in the synovial fluid could be of diagnostic value for identifying osteoarthritis. PMID:15727922

  17. 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

  18. 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

  19. Serum Reactive Oxygen Metabolite Levels Predict Severe Exacerbations of Asthma

    PubMed Central

    Nakamoto, Keitaro; Watanabe, Masato; Sada, Mitsuru; Inui, Toshiya; Nakamura, Masuo; Honda, Kojiro; Wada, Hiroo; Mikami, Yu; Matsuzaki, Hirotaka; Horie, Masafumi; Noguchi, Satoshi; Yamauchi, Yasuhiro; Koyama, Hikari; Kogane, Toshiyuki; Kohyama, Tadashi; Takizawa, Hajime

    2016-01-01

    Background and Purpose Bronchial asthma (BA) is a chronic airway disease characterized by airway hyperresponsiveness and remodeling, which are intimately linked to chronic airway inflammation. Reactive oxygen species (ROS) such as hydrogen peroxide are generated by inflammatory cells that are involved in the pathogenesis of BA. However, the role of ROS in the management of BA patients is not yet clear. We attempted to determine the role of ROS as a biomarker in the clinical setting of BA. Subjects and Methods We enrolled patients with BA from 2013 through 2015 and studied the degrees of asthma control, anti-asthma treatment, pulmonary function test results, fractional exhaled nitric oxide (FeNO), serum reactive oxygen metabolite (ROM) levels, and serum levels of interleukin (IL)-6 and IL-8. Results We recruited 110 patients with BA. Serum ROM levels correlated with white blood cell (WBC) count (rs = 0.273, p = 0.004), neutrophil count (rs = 0.235, p = 0.014), CRP (rs = 0.403, p < 0.001), and IL-6 (rs = 0.339, p < 0.001). Serum ROM levels and IL-8 and CRP levels negatively correlated with %FEV1 (rs = -0.240, p = 0.012, rs = -0.362, p < 0.001, rs = -0.197, p = 0.039, respectively). Serum ROM levels were significantly higher in patients who experienced severe exacerbation within 3 months than in patients who did not (339 [302–381] vs. 376 [352–414] CARR U, p < 0.025). Receiver-operating characteristics analysis showed that ROM levels correlated significantly with the occurrence of severe exacerbation (area under the curve: 0.699, 95% CI: 0.597–0.801, p = 0.025). Conclusions Serum levels of ROM were significantly associated with the degrees of airway obstruction, WBC counts, neutrophil counts, IL-6, and severe exacerbations. This biomarker may be useful in predicting severe exacerbations of BA. PMID:27776186

  20. 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

  1. 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

  2. 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

  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. 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

  5. Serum nitric oxide in children with dengue infection.

    PubMed

    Trairatvorakul, Pon; Chongsrisawat, Voranush; Ngamvasinont, Direk; Asawarachun, Duangporn; Nantasook, Jutarat; Poovorawan, Yong

    2005-01-01

    One hundred and ten patients (M/F = 67/43) from King Chulalongkorn Memorial Hospital and the provincial hospitals of Uttaradit, Ayudhaya, and Sakonnakorn, who were clinically diagnosed with dengue infection and serologically confirmed by ELISA anti-Dengue IgM and IgG were recruited. Their serum NO level was measured using commercially available assay kits to investigate its correlation with the severity of the dengue infection: dengue fever (DF), DHF I/II, and DHF III/IV or dengue shock syndrome (DSS). Serum NO levels were also measured in 38 healthy controls (M/F = 19/19). Serum NO levels in dengue patients were lower than those of the controls (control = 168.18 +/- 24.10 micromol/l, DF = 124.94 +/- 36.79 micromol/l, DHF I/II = 99.69 +/- 33.42 micromol/l, and DHF III/IV = 120.63 +/- 46.26 micromol/l; p < 0.05). Serum NO levels in patients with DHF I/II were significantly lower than in those with DHF III/IV. These preliminary data revealed that levels of serum NO in dengue patients were significantly lower than those of normal controls. Patients with DSS had higher NO levels than those with DHF I/II. The decreased NO in dengue patients could be due to endothelial damage rendering the endothelium incapable of producing NO. Endothelial function seems to play a role in the pathogenesis of dengue infection. Further studies are required to see whether serum NO levels could play a role in the course of the disease and could help predict the severity of dengue infection.

  6. 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.

  7. 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

  8. Plasmid DNA encoding transforming growth factor-beta1 suppresses chronic disease in a streptococcal cell wall-induced arthritis model.

    PubMed Central

    Song, X Y; Gu, M; Jin, W W; Klinman, D M; Wahl, S M

    1998-01-01

    Transforming growth factor beta is a potent immunomodulator with both pro- and antiinflammatory activities. Based on its immunosuppressive actions, exogenous TGF-beta has been shown to inhibit autoimmune and chronic inflammatory diseases. To further explore the potential therapeutic role of TGF-beta, we administered a plasmid DNA encoding human TGF-beta1 intramuscularly to rats with streptococcal cell wall-induced arthritis. A single dose of 300 microg plasmid DNA encoding TGF-beta1, but not vector DNA, administered at the peak of the acute phase profoundly suppressed the subsequent evolution of chronic erosive disease typified by disabling joint swelling and deformity (articular index = 8.17+/-0. 17 vs. 1.25+/-0.76, n = 6, day 26, P < 0.01). Moreover, delivery of the TGF-beta1 DNA even as the chronic phase commenced virtually eliminated subsequent inflammation and arthritis. Both radiologic and histopathologic as well as molecular evidence supported the marked inhibitory effect of TGF-beta1 DNA on synovial pathology, with decreases in the inflammatory cell infiltration, pannus formation, cartilage and bone destruction, and the expression of proinflammatory cytokines that characterize this model. Increases in TGF-beta1 protein were detected in the circulation of TGF-beta1 DNA-treated animals, consistent with the observed therapeutic effects being TGF-beta1 dependent. These observations provide the first evidence that gene transfer of plasmid DNA encoding TGF-beta1 provides a mechanism to deliver this potent cytokine that effectively suppresses ongoing inflammatory pathology in arthritis. PMID:9637694

  9. Proteomic Profiling of Mesenchymal Stem Cell Responses to Mechanical Strain and TGF-B1

    SciTech Connect

    Kurpinski, Kyle; Chu, Julia; Wang, Daojing; Li, Song

    2009-10-12

    Mesenchymal stem cells (MSCs) are a potential source of smooth muscle cells (SMCs) for constructing tissue-engineered vascular grafts. However, the details of how specific combinations of vascular microenvironmental factors regulate MSCs are not well understood. Previous studies have suggested that both mechanical stimulation with uniaxial cyclic strain and chemical stimulation with transforming growth factor {beta}1 (TGF-{beta}1) can induce smooth muscle markers in MSCs. In this study, we investigated the combined effects of uniaxial cyclic strain and TGF-{beta}1 stimulation on MSCs. By using a proteomic analysis, we found differential regulation of several proteins and genes, such as the up-regulation of TGF-{beta}1-induced protein ig-h3 (BGH3) protein levels by TGF-{beta}1 and up-regulation of calponin 3 protein level by cyclic strain. At the gene expression level, BGH3 was induced by TGF-{beta}1, but calponin 3 was not significantly regulated by mechanical strain or TGF-{beta}1, which was in contrast to the synergistic up-regulation of calponin 1 gene expression by cyclic strain and TGF-{beta}1. Further experiments with cycloheximide treatment suggested that the up-regulation of calponin 3 by cyclic strain was at post-transcriptional level. The results in this study suggest that both mechanical stimulation and TGF-{beta}1 signaling play unique and important roles in the regulation of MSCs at both transcriptional and post-transcriptional levels, and that a precise combination of microenvironmental cues may promote MSC differentiation.

  10. Cellular localization of transforming growth factor-beta expression in bleomycin-induced pulmonary fibrosis.

    PubMed Central

    Zhang, K.; Flanders, K. C.; Phan, S. H.

    1995-01-01

    Bleomycin-induced pulmonary fibrosis is associated with increased lung transforming growth factor-beta (TGF-beta) gene expression, but cellular localization of the source of this expression has not been unequivocally established. In this study, lung fibrosis was induced in rats by endotracheal bleomycin injection on day 0 and, on selected days afterwards, lungs were harvested for in situ hybridization, immunohistochemical and histochemical analyses for TGF-beta 1 mRNA and protein expression, and cell identification. The results show that control lungs express essentially no detectable TGF-beta 1 mRNA or protein in the parenchyma. Before day 3 after bleomycin treatment, scattered bronchiolar epithelial cells, mononuclear cells, and eosinophils expressed elevated levels of TGF-beta 1. Between days 3 and 14, there was a major increase in the number of eosinophils, myofibroblasts, and fibroblasts strongly expressing TGF-beta 1 mRNA and protein. TGF-beta 1-producing cells were predominantly localized within areas of injury and active fibrosis. After day 14, the intensity and number of TGF-beta 1-expressing cells significantly declined and were predominantly found in fibroblasts in fibrotic areas. The expression of TGF-beta 1 protein was generally coincident with that for mRNA with the exception of bronchiolar epithelial cells in which strong protein expression was unaccompanied by a commensurate increase in mRNA. The study demonstrates that myofibroblasts, fibroblasts, and eosinophils represent the major sources of increased lung TGF-beta 1 expression in this model of pulmonary fibrosis. Images Figure 2 Figure 3 Figure 4 PMID:7543734

  11. Transforming growth factor-beta activation in irradiated murine mammary gland.

    PubMed Central

    Barcellos-Hoff, M H; Derynck, R; Tsang, M L; Weatherbee, J A

    1994-01-01

    The biological activity of TGF-beta, an important modulator of cell proliferation and extracellular matrix formation, is governed by dissociation of mature TGF-beta from an inactive, latent TGF-beta complex in a process that is critical to its role in vivo. So far, it has not been possible to monitor activation in vivo since conventional immunohistochemical detection does not accurately discriminate latent versus active TGF-beta, nor have events associated with activation been defined well enough to serve as in situ markers of this process. We describe here a modified immunodetection method using differential antibody staining that allows the specific detection of active versus latent TGF-beta. Under these conditions, we report that an antibody raised to latency-associated peptide detects latent TGF-beta, and we demonstrate that LC(1-30) antibodies specifically recognize active TGF-beta 1 in tumor xenografts overproducing active TGF-beta 1, without cross-reactivity in tumors expressing similar levels of latent TGF-beta 1. We previously reported that TGF-beta immunoreactivity increases in murine mammary gland after whole-body 60Co-gamma radiation exposure. Using differential antibody staining we now show that radiation exposure specifically generates active TGF-beta 1. While latent TGF-beta 1 was widely distributed in unirradiated tissue, active TGF-beta 1 distribution was restricted. Active TGF-beta 1 increased significantly within 1 h of irradiation concomitant with decreased latent TGF-beta immunoreactivity. This rapid shift in immunoreactivity provides the first evidence for activation of TGF-beta in situ. This reciprocal pattern of expression persisted for 3 d and was accompanied by decreased recovery of latent TGF-beta 1 from irradiated tissue. Radiation-induced activation of TGF-beta may have profound implications for understanding tissue effects caused by radiation therapy. Images PMID:8113421

  12. Expression of transforming growth factor-beta isoforms in small round cell tumors of childhood. An immunohistochemical study.

    PubMed Central

    McCune, B. K.; Patterson, K.; Chandra, R. S.; Kapur, S.; Sporn, M. B.; Tsokos, M.

    1993-01-01

    The transforming growth factor (TGF)-betas are a highly conserved group of potent multifunctional cell regulatory proteins with variable effects on cell growth and differentiation. Most of the small round cell group of childhood tumors are thought to arise from either primitive mesenchyme or neuroectoderm and show evidence of skeletal muscle or neural differentiation, and rarely both. To investigate the possibility that the TGF-betas have a role in the growth or differentiation of these neoplasms, we used antibodies specific for peptide sequences of the three known mammalian TGF-beta isoforms (TGF-betas 1, 2, and 3) to probe for TGF-beta protein expression in a total of 49 cases. TGF-beta 1 immunoreactivity was present in 16/17 (94%) of rhabdomyosarcomas, and the staining intensity was usually strong. TGF-beta 1 was also present in three of three ectomesenchymomas. In contrast, TGF-beta 1 was absent in all but one out of nine poorly differentiated neuroblastomas. Differentiating neuronal cells of ganglioneuroblastomas, however, were strongly positive for TGF-beta 1. Ewing's sarcomas and peripheral primitive neuroectodermal tumors had a less consistent, but usually positive, staining pattern. TGF-beta 3 staining patterns were very similar to those of TGF-beta 1. TGF-beta 2 immunoreactivity was only rarely detected in this group of tumors. The results suggest different roles for TGF-betas 1 and 3 in neuroblastoma and rhabdomyosarcoma. Expression of TGF-betas 1 and 3 is associated with neuronal differentiation of neuroblastoma. In contrast, these proteins may promote the growth of rhabdomyosarcoma by suppressing differentiation. Images Figure 1 Figure 2 Figure 3 PMID:8380955

  13. 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.

  14. Preparation and Characterization of 125I Labeled Bovine Serum Albumin

    PubMed Central

    Ashwitha Rai, K. S.; Jyothi; Rasmi, R. R.; Sarnaik, Jayula; Kadwad, V. B.; Shenoy, K. B.; Somashekarappa, H. M.

    2015-01-01

    Bovine serum albumin is a model protein, which has been conventionally used as protein standard and in many areas of biochemistry, pharmacology and medicine. Radioiodination procedure for bovine serum albumin employing chloramine-T as an oxidant with slight modification was evaluated critically to establish the optimal conditions for the preparation of radiolabeled tracer (125I-BSA) with required specific activity without impairing the immune reactivity and biological activity. Optimized radioiodination procedure involving 10 µg of chloramine-T along with 20 µg of sodium metabisulphite with 60 seconds incubation at 2° yielded 125I-BSA with high integrity. PMID:25767326

  15. [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

  16. Serum bactericidal activity in the horseshoe crab, Limulus polyphemus.

    PubMed Central

    Pistole, T G; Furman, R M

    1976-01-01

    Serum from the horseshoe crab, Limulus polyphemus, was examined for bactericidal activity against five species of bacteria. Greatest activity was found against Pseudomonas putida and Flavobacterium sp.; with the former, serum dilutions as high as 1:20 were capable of reducing viable counts by 50% within 2 h. Bactericidal activity of a significantly lesser magnitude was demonstrated against Serratia marcesencs and Salmonella minnesota. No killing was seen when the lobster pathogen Aerococcus viridans (formerly Gaffkya homari) was used. The cidal activity against Flavobacterium sp. remained relatively consistent for 6 months. PMID:11188

  17. Serum bactericidal activity in the horseshoe crab, Limulus polyphemus.

    PubMed

    Pistole, T G; Furman, R M

    1976-10-01

    Serum from the horseshoe crab, Limulus polyphemus, was examined for bactericidal activity against five species of bacteria. Greatest activity was found against Pseudomonas putida and Flavobacterium sp.; with the former, serum dilutions as high as 1:20 were capable of reducing viable counts by 50% within 2 h. Bactericidal activity of a significantly lesser magnitude was demonstrated against Serratia marcesencs and Salmonella minnesota. No killing was seen when the lobster pathogen Aerococcus viridans (formerly Gaffkya homari) was used. The cidal activity against Flavobacterium sp. remained relatively consistent for 6 months.

  18. Automated conductimetric assay of human serum cholinesterase activity.

    PubMed

    Duffy, P; Wallach, J M

    1989-01-01

    Serum cholinesterase activity was determined by conductimetry using samples in the microliter range. Butyrylcholine iodide was demonstrated to be a convenient substrate for the conductimetric assay. Validation of the microassay was made by using either purified enzyme or control serum. In the range of 0-60 U/l, a linear relationship was demonstrated. Correlation with a reference spectrophotometric method was obtained with a slope of 1.18. An explanation of this value is proposed, as different hydrolysis rates were obtained with human sera, depending on the substrate used (butyrylthio- or butyryl-choline ester).

  19. Serum copper levels in patients with lung cancer.

    PubMed

    Huhti, E; Poukkula, A; Uksila, E

    1980-01-01

    An increased mean serum copper level was found in 149 patients with lung cancer when compared with 19 healthy people and 23 patients with non-malignant lung diseases. The level seemed to reflect the stage of disease, with asymptomatic patients showing the lowest values, and patients with metastatic symptoms the highest. In spite of significant differences between the groups of subjects the scatter in the values was large. Hence serum copper determinations can be of only limited importance for differential diagnosis or in assessing the clinical stage of cancer. No differences in copper levels were found between the groups of patients with different histological types of lung cancer.

  20. Heterogeneity of serum activities of matrix metalloproteinases in chronic endometritis.

    PubMed

    Sukhikh, G T; Soboleva, G M; Silantyeva, E S; Shagerbieva, E A; Serov, V N

    2007-04-01

    Matrix metalloproteinases belong to the key molecules of tissue remodeling involved in physiological and pathological processes of the female reproductive system. Adequate levels of their expression in the endometrium are essential for effective implantation and uneventful pregnancy. Chronic inflammatory process in the endometrium is associated with low tissue expression of metalloproteinase-9. Histologically verified chronic endometritis is associated with low serum activities of metalloproteinases 2 and 9, which are restored after combined etiotropic therapy. We measured serum levels of metalloproteinases in patients with chronic endometritis concomitant with sterility and its changes during the first days after magnetotherapy. PMID:18214304

  1. 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.

  2. Westernization of diet and serum lipids in Ethiopians.

    PubMed

    Ostwald, R; Gebre-Medhin, M

    1978-06-01

    The dietary pattern, physical work output, and blood lipids were studied in three groups of healthy, young, urban Ethiopian men differing in the degree of "Westernization." The results showed striking increases in serum lipids that were associated with the degree of Westernization of the diet. These changes could not be accounted for by differences in other group characteristics such as age, weight, smoking, or length of residence in Addis Ababa. The effects of the level of physical work output on serum lipids were equivocal because the methods used for the assessment of energy output yielded crude approximations only.

  3. 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

  4. 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.

  5. 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.

  6. RAST with animal dander, urine, saliva and serum.

    PubMed

    Berrens, L; van Dijk, A G; Bollebakker-Baars, A; Huizinga, M

    1983-11-01

    Binding of specific IgE antibodies from the sera of patients allergic to animals was investigated by direct RAST, using the animal's dander, urine, saliva or blood serum as insolubilized allergens. In allergy to rat, mouse, guinea pig, dog, cat or horse, the RAST results with the excretions of a particular animal were mutually well correlated. RAST with the animal blood serum was positive less often, and only in cases of a positive dander RAST. It is concluded that a RAST with animal dander precludes the use of other animal products. PMID:6638617

  7. [Serum sterilization in the cold with peracetic acid].

    PubMed

    Sprössig, M; Wutzler, P; Schweizer, H; Mücke, H

    1976-01-01

    On the basis of broad antimicrobic effect including also bacterial spores, mycoplasmas and viruses, the peracetic acid suits to sterilize in cold. By means of the final 0,1 to 0.02% concentration of the peracetic acid acting for 30 min. up to 5 days, it succeeded in sterilizing the serum used to prepare culture medium for bacteria, mycoplasmas and tissue cultures. Growth controls shown at least as good results as were those in using filtered sera. Chemical sterilization by means of the peracetic acid leads to significant diminution of neutralization and complementfixation antibodies in serum. PMID:987107

  8. Effect of medroxyprogesterone acetate contraception on human serum enzymes.

    PubMed

    Mukherjea, M; Mukherjee, P; Biswas, R; Chakraborty, A S; Kushari, J

    1981-01-01

    Activities of five enzymes were determined biochemically in the serum of a woman taking the injectable contraceptive, depo-medroxyprogesterone acetate (DMPA), 150 mg every 3 months for 2 years. The specific activities of SGOT, SGPT, and alkaline phosphatase (AP)-the enzymes commonly discerned in tests on the function of the liver-do not show any change with long-term treatment of this steroid contraceptive. Activities of serum acid phosphatase (ACP) and acetylcholinesterase (AChE) in red cells show significant increase. DMPA contraception has no apparent harmful effect on liver function, although the rise in ACP and AChE activities may be related to some pathological condition.

  9. 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

  10. Determination of pindolol in human serum by HPLC.

    PubMed

    Chmielowiec, D; Schuster, D; Gengo, F

    1991-01-01

    A method for determining pindolol from human serum by high-performance liquid chromatography (HPLC) is presented. Pindolol is extracted into methylene chloride from 1 mL of alkalinized serum with a recovery of 87%. The organic layer is evaporated and the residue is reconstituted in mobile phase for injection into the column. Samples are eluted from a 5-micron C18 column (250 x 4.6 mm) with acetonitrile-water containing 0.1% triethylamine, pH adjusted to 3.5 with phosphoric acid (20:80 v/v). Samples as low as 2 ng/mL have been detected.

  11. Serum theophylline analysis by high-pressure liquid chromatography.

    PubMed

    Evenson, M A; Warren, B L

    1976-06-01

    We have developed and evaluated a rapid, high-pressure liquid-chromatographic method for theophylline in serum. Only 0.2 ml of serum is required for each determination, and the sensitivity of this method is 0.5 mg/liter. This method, involving liquid extraction and silica adsorption chromatography, provides adequate selectivity, accuracy, and precision for routine or research applications. Little sample preparation is required before chromatography. We found no endogenous or exogenous interferences. Use of beta-hydroxypropyl theophylline as the internal standard provides reproducible results for this micro-scale method.

  12. 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

  13. Effects of serum-isolated vs synthetic bilirubin-albumin complexes on dye-binding methods for estimating serum albumin.

    PubMed

    Ihara, H; Nakamura, H; Aoki, Y; Aoki, T; Yoshida, M

    1991-07-01

    Bush and Reed reported (Clin Chem 1987;33:821-3) that the reaction of albumin with bromcresol purple but not with bromcresol green underestimated the concentration of albumin in synthetically obtained bilirubin-albumin (Bd) by 29%. Their unproven assumption was that chemically synthesized Bd behaved in a manner indistinguishable from the natural Bd in icteric serum. Here we verify that Bd, whether synthetically obtained or isolated from serum, causes an underestimation of albumin in the bromcresol purple but not in the bromcresol green method. The molar ratio of Bd from either source to underestimated albumin approximates 1.0, suggesting that one molecule of Bd would react equivalently to a molecule of albumin in the bromcresol purple method. This underestimation might falsely suggest hypoalbuminemia in patients with increased serum Bd. PMID:1855300

  14. Defective Wound-healing in Aging Gingival Tissue

    PubMed Central

    Cáceres, M.; Oyarzun, A.; Smith, P.C.

    2014-01-01

    Aging may negatively affect gingival wound-healing. However, little is known about the mechanisms underlying this phenomenon. The present study examined the cellular responses associated with gingival wound-healing in aging. Primary cultures of human gingival fibroblasts were obtained from healthy young and aged donors for the analysis of cell proliferation, cell invasion, myofibroblastic differentiation, and collagen gel remodeling. Serum from young and old rats was used to stimulate cell migration. Gingival repair was evaluated in Sprague-Dawley rats of different ages. Data were analyzed by the Mann-Whitney and Kruskal-Wallis tests, with a p value of .05. Fibroblasts from aged donors showed a significant decrease in cell proliferation, migration, Rac activation, and collagen remodeling when compared with young fibroblasts. Serum from young rats induced higher cell migration when compared with serum from old rats. After TGF-beta1 stimulation, both young and old fibroblasts demonstrated increased levels of alpha-SMA. However, alpha-SMA was incorporated into actin stress fibers in young but not in old fibroblasts. After 7 days of repair, a significant delay in gingival wound-healing was observed in old rats. The present study suggests that cell migration, myofibroblastic differentiation, collagen gel remodeling, and proliferation are decreased in aged fibroblasts. In addition, altered cell migration in wound-healing may be attributable not only to cellular defects but also to changes in serum factors associated with the senescence process. PMID:24776985

  15. Studying the proliferation of human peripheral blood T lymphocytes in serum-free medium.

    PubMed

    Tabakov, V U; Litvina, M M; Schepkina, J V; Jarilin, A A; Chestkov, V V

    2009-01-01

    We compared the cultivation of human peripheral blood lymphocytes in serum-free medium Hybris-2 and RPMI 1640 medium with 10% fetal bovine serum in the presence of phytohemagglutinin and interleukin-2. The optimal concentration of phytohemagglutinin significantly differed in serum-free and serum-containing media (0.5 and 5 microg/ml, [corrected] respectively). Both mitogens were more potent in stimulating the proliferation of lymphocytes in serum-free medium than in serum-containing medium. Strong proliferation of CD3(+) and CD4(+) T lymphocytes was observed in both media. The dynamics of other markers was similar in serum-free and serum-containing media. However, significant differences were revealed between individual donors. Our results indicate that the developed serum-free medium may be used in lymphocyte cultivation for scientific, diagnostic, and therapeutic purposes.

  16. Effect of recombinant adeno-associated virus mediated transforming growth factor-beta1 on corneal allograft survival after high-risk penetrating keratoplasty.

    PubMed

    Zhou, Lianhong; Zhu, Xiangxiang; Tan, Jinquan; Wang, Jiong; Xing, Yiqiao

    2013-06-01

    Corneal transplantation is one of the most common and successful transplant surgeries performed around the world. However, the high-risk corneal transplantation remains a high level of corneal graft failure. Gene transfer of immunomodulatory molecules is considered as one potential strategy in preventing allograft rejection. It is worthy evaluating the effects of the immunemodulating agent on corneal allograft rejection. The purpose of this paper is to investigate the effects and mechanisms of recombinant adeno-associated virus mediated transforming growth factor-beta1 (rAAV-TGF-beta1) on corneal allograft survival using a high-risk rat model after penetrating keratoplasty (PKP). The mean survival time (MST) of corneal grafts was observed and immuno-histochemical staining of TGF-beta1 and Ox-62 was performed in the study. The MST showed significant prolongation in the rAAV-TGF-beta1 group compared to the allograft group. The rejection index (RI) at day 10 revealed was significantly greater in the allograft group than that of the other two groups. Besides the increase of TGF-beta1, the expression of Ox-62 decreasing in rAAV-TGF-beta1 transplanted recipients was detected after transplantation. In short, treatment with rAAV-TGF-beta1 prolongs corneal allograft survival and inhibits the Ox-62 expression in grafts after high-risk PKP.

  17. Transforming growth factor beta 1 enhances expression of 50 kDa protein related to 2'-5' oligoadenylate synthetase in human sperm cells.

    PubMed

    Naz, R K; Kumar, R

    1991-01-01

    Human cellular polypeptide factors, namely interferon-alpha, interferon-gamma transforming growth factor (TGF)-alpha, and TGF-beta 1, were analyzed for their effect on motility of human sperm cells. Both interferons caused an inhibition of sperm cell motility due to direct cytotoxic effects without inducing 2'-5' oligoadenylate [2-5(A)]synthetase activity. TGF-alpha affected neither motility nor the levels of 2-5(A) synthetase in sperm cells. TGF-beta 1 had no affect on sperm motility, yet it caused an induction of 2-5(A)synthetase activity. Western immunoblot analysis of TGF-beta 1-treated sperm indicated an enhancement of a 50 kDa protein. Metabolic labeling of sperm cells revealed biosynthesis of one major protein of 50 kDa and at least five minor proteins in the range of 30-92 kDa; the level of 50 kDa protein increased after treatment with TGF-beta 1. The treatment of sperm cells with TGF-beta 1 did not affect their penetration in zona-free hamster eggs (SPA). These results indicate that TGF-beta 1 enhances expression of a 50 kDa protein related to 2-5(A) synthetase in human sperm cells along with other minor proteins, and this increase does not affect sperm motility and SPA.

  18. Reorganization of endothelial cord-like structures on basement membrane complex (Matrigel): involvement of transforming growth factor beta 1.

    PubMed

    Kuzuya, M; Kinsella, J L

    1994-11-01

    The formation of capillary-like network structures by cultured vascular endothelial cells on reconstituted basement membrane matrix, Matrigel, models endothelial cell differentiation, the final step of angiogenesis (Kubota et al., 1988; Grant et al., 1989). When endothelial cells derived from bovine aorta and brain capillaries were plated on Matrigel, DNA synthesis was suppressed and a network of capillary-like structures rapidly formed in 8-12 h. With time, the network broke down, resulting in dense cellular cords radiating from multiple cellular clusters in 16-24 h. Finally, multicellular aggregates of cells were formed as the network underwent further retraction. Network regression was prevented when either dithiothreitol (DTT) or anti-TGF-beta 1 antibodies were added during the assay. The addition of exogenous TGF-beta 1 promoted the regression of endothelial cells into the clusters. This response to TGF-beta 1 was blocked by potent serine threonine protein kinase inhibitors, H-7 and HA100. TGF-beta 1 was released from polymerized Matrigel by incubation with Dulbecco's modified eagle's medium (DMEM) in the absence of cells. The Matrigel-conditioned DMEM inhibited endothelial DNA synthesis even in the presence of anti-TGF-beta 1 antibodies. These results suggest that TGF-beta 1 and possibly other soluble factors from Matrigel may be important for differentiation and remodeling of endothelial cells in a capillary network with possible implications for wound healing and development.

  19. Serum leptin concentrations are not related to dietary patterns but are related to sex, age, body mass index, serum triacylglycerol, serum insulin, and plasma glucose in the US population

    PubMed Central

    Ganji, Vijay; Kafai, Mohammad R; McCarthy, Erin

    2009-01-01

    Background Leptin is known to play a role in food intake regulation. The aim of this study was to investigate the relation between serum leptin concentrations and dietary patterns and demographic, lifestyle, and health factors in the US population. Methods Data from the third National Health and Nutrition Examination Survey, 1988–1994 were used to study the association between fasting serum leptin and dietary patterns, sex, race-ethnicity, smoking, age, energy and alcohol intakes, body mass index (BMI), plasma glucose, serum triacylglycerol, and serum insulin in 4009 individuals. Factor analysis was used to derive three principle factors and these were labeled as Vegetable, Fruit, and Lean Meat, Western, and Mixed dietary patterns. Results Serum leptin concentrations were significantly higher in Vegetable, Fruit, and Lean Meat (8.5 fg/L) and Mixed patterns (8.0 fg/L) compared to Western pattern (6.29 fg/L) (P < 0.0001). When analysis was adjusted for confounding variables, no significant association was observed between serum leptin and dietary patterns (P = 0.22). Multivariate adjusted serum leptin concentrations were significantly associated with sex (higher in women than in men; β = -1.052; P < 0.0001), age (direct relation, β = 0.006, P < 0.0001), BMI, (direct relation, β = 0.082, P < 0.0001), fasting plasma glucose (inverse relation, β = -0.024, P = 0.0146), serum triacylglycerol (direct relation, β = 0.034, P = 0.0022), and serum insulin (direct relation, β = 0.003, P < 0.0001) but not with race-ethnicity (P = 0.65), smoking (P = 0.20), energy intake (P = 0.42), and alcohol intake (P = 0.73). Conclusion In this study, serum leptin was not independently associated with dietary patterns. Sex, age, BMI, serum triacylglycerol, plasma glucose, and serum insulin are independent predictors of serum leptin concentrations. PMID:19144201

  20. 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)

  1. 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 AGRICULTURE LIVESTOCK IMPROVEMENT AUXILIARY PROVISIONS ON NATIONAL POULTRY IMPROVEMENT PLAN Blood...

  2. 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...

  3. 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 AGRICULTURE LIVESTOCK IMPROVEMENT AUXILIARY PROVISIONS ON NATIONAL POULTRY IMPROVEMENT PLAN Blood...

  4. 9 CFR 147.2 - The rapid serum test. 2

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 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...

  5. 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...

  6. 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

  7. Serum Leptin Is a Biomarker of Malnutrition in Decompensated Cirrhosis

    PubMed Central

    Rachakonda, Vikrant; Borhani, Amir A.; Dunn, Michael A.; Andrzejewski, Margaret; Martin, Kelly; Behari, Jaideep

    2016-01-01

    Background and Aims Malnutrition is a leading cause of morbidity and mortality in cirrhosis. There is no consensus as to the optimal approach for identifying malnutrition in end-stage liver disease. The aim of this study was to measure biochemical, serologic, hormonal, radiographic, and anthropometric features in a cohort of hospitalized cirrhotic patients to characterize biomarkers for identification of malnutrition. Design In this prospective observational cohort study, 52 hospitalized cirrhotic patients were classified as malnourished (42.3%) or nourished (57.7%) based on mid-arm muscle circumference < 23 cm and dominant handgrip strength < 30 kg. Anthropometric measurements were obtained. Appetite was assessed using the Simplified Nutrition Appetite Questionnaire (SNAQ) score. Fasting levels of serum adipokines, cytokines, and hormones were determined using Luminex assays. Logistic regression analysis was used to determine features independently associated with malnutrition. Results Subjects with and without malnutrition differed in several key features of metabolic phenotype including wet and dry BMI, skeletal muscle index, visceral fat index and HOMA-IR. Serum leptin levels were lower and INR was higher in malnourished subjects. Serum leptin was significantly correlated with HOMA-IR, wet and dry BMI, mid-arm muscle circumference, skeletal muscle index, and visceral fat index. Logistic regression analysis revealed that INR and log-transformed leptin were independently associated with malnutrition. Conclusions Low serum leptin and elevated INR are associated with malnutrition in hospitalized patients with end-stage liver disease. PMID:27583675

  8. 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

  9. 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.

  10. The Unexplored Roles of Human Serum IgA

    PubMed Central

    Leong, Ka Wai

    2014-01-01

    The roles of human serum IgA, in contrast to that of mucosal IgA, are relatively unexplored. Previous studies have shown that IgA mediates either pro- or anti-inflammatory effects in innate immune cells. Serum IgA has been shown to interact with many proteins and glycoproteins of which the functions and mechanisms are not fully characterized. Here, we present fresh perspectives into the roles of serum IgA, describing novel IgA–protein interactions, the importance of its glycosylation status in normal functions, and the plausible role of IgA as a driver and regulator of autoimmune diseases/immune overactivation. Other potential roles, including the regulation of cytokines, effector cell function, and homeostasis, are considered in view of the maintenance of immune function. We anticipate future research to uncover new anti-inflammatory or pro-inflammatory roles of human serum IgA in immune functions and dysfunctions, with implications on systemic lupus erythematosus (SLE). PMID:25188736

  11. 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

  12. 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.

  13. Evaluation of serum immunoglobulin E levels in bronchial asthma

    PubMed Central

    Sandeep, Thirunavukkarasu; Roopakala, Mysore Subrahmanyam; Silvia, Chickballapur Rayappa Wilma Delphine; Chandrashekara, Srikantaiah; Rao, Mohan

    2010-01-01

    Background: Immunoglobulin E and associated cellular responses are responsible for allergic airway diseases. A hypersensitivity reaction initiated by immunologic mechanisms, mediated by IgE antibodies occurs in allergic asthma Aim: To estimate and compare serum IgE levels in mild, moderate, and severe asthmatics and in normal subjects and to obtain a mathematical model describing the relationship between serum IgE levels and severity of asthma. Materials and Methods: A stratified sample of 60 patients within age group of 18-60 years and 31 male and 29 female asthmatic patients and 13 healthy controls within 18-60 years were included in this study and classified according to GINA classification. Serum IgE levels were estimated by using ELISA kit. Results: Mean IgE levels ranged from 151.95 IU/ml in normal subjects to 1045.32 IU/ml in severe asthmatics. The model developed was 27% efficient. Conclusion: Serum Immunoglobulin E levels were high in asthmatics as compared to normal subjects. On an average, the levels increased as the severity of asthma increased. However, there was no statistically significant correlation since the variability in each level of asthma was very large PMID:20931031

  14. 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...

  15. 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

  16. 21 CFR 522.1079 - Serum gonadotropin and chorionic gonadotropin.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 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. Immunological basis of serum resistance of Neisseria gonorrhoeae.

    PubMed

    Schneider, H; Griffiss, J M; Williams, G D; Pier, G B

    1982-01-01

    The immunological basis for resistance of certain strains of Neisseria gonorrhoeae to the bactericidal action of normal human serum was studied by investigating the potential role of factors which are known to interfere with each of the sequential steps that result in immune lysis of Gram-negative bacteria. Strains of N. gonorrhoeae were characterized as serum-sensitive (sers) or serum-resistant (serr) on the basis of their sensitivity to lysis by the sera of six normal individuals. Neither intrinsic resistance to the lytic action of activated human complement nor inaccessibility of the cell membrane to C5b accounted for serr. Outer membrane lipopolysaccharide (LPS) was the target antigen for lytic antibody in normal human sera. The gross chemical composition and molecular size of the LPS of the strains were heterogeneous and no consistent patterns of differences between those extracted from serr and from sers strains were found. Neither IgA nor IgG 'blocking' antibody in normal human serum was responsible for serr. We conclude that serr results from the absence from the LPS of the strains of antigenic loci for the lytic antibody in most normal human sera, or, expressed as a function of the host, the absence from the sera of most normal humans of lytic antibody directed against LPS antigenic loci for immune lysis.

  18. Fluorometric measurement of serum magnesium with a centrifugal analyzer.

    PubMed

    Pesce, M A; Bodourian, S H; Hills, L P

    1984-01-31

    We developed a rapid fluorometric assay for measurement of serum magnesium using the ligand, 8-hydroxy-quinoline-5-sulfonate and adapted the procedure to the Multistat Fluorescence Light Scattering Centrifugal Analyzer. The standard curve extends from 0.26 to 4.11 mmol/l. There was no interference from calcium or inorganic phosphorus at concentrations of 4.95 and 5.0 mmol/l, lead, iron, zinc or copper at twice the normal levels found in serum, bilirubin at concentrations of 10 mg/dl, or lipemic samples with triglyceride concentrations of 2400 mg/dl. Citrate and EDTA lowered magnesium concentrations in serum. Analytical recovery of magnesium added to four serum specimens averaged 97%. Between-run and within-run precision of the assay gave CVs which ranged from 2.9 to 7.6%. Magnesium concentrations, measured by our fluorometric procedure, were compared with those obtained by atomic absorption and colorimetric procedures. Correlation coefficients of 0.91 and 0.88 were obtained.

  19. 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...

  20. A third type of serum cholinesterase deficiency in Eskimos.

    PubMed Central

    Scott, E M; Wright, R C

    1976-01-01

    A new type of serum cholinesterase deficiency with less than 10% of the normal activity was found in an Alaskan Eskimo. The new type of deficiency appeared to be allelic with two types previously described in this population. Images Fig. 2 PMID:1266852

  1. 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 ...

  2. 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)

  3. Amyloid-related serum component (protein ASC) IN LEPROSY PATIENTS.

    PubMed Central

    Kronvall, G; Husby, G; Samuel, D; Bjune, G; Wheate, H

    1975-01-01

    The presence of amyloid-related serum component, protein ASC, in serum samples from 63 leprosy patients was investigated. Protein ASC was detected in 38% of the patients. A correlation to the disease spectrum of leprosy was apparent: polar lepromatous cases, 64% positive; borderline lepromatous, 50%; borderline tuberculoid, 36%; subpolar tuberculoid, 17%; and polar tuberculoid, negative. Antibody activity against the a antigen of Mycobacterium leprae was also determined, showing a similar correlation to the disease spectrum. Serum samples from 23 apparently healthy Ethiopians serving as controls showed a protein ASC incidence of 22%. This figure is significantly higher than the frequency found by others among healthy Norwegian blood donors. Immunoglobulin M levels among patients were elevated in the borderline lepromatous and poplar lepromatous groups. The three tuberculoid groups did not differ in this respect from the control group but were all elevated as compared to a normal Caucasian serum pool. Although raised immunoglobulin M levels seemed to parallel increased frequencies of protein ASC in the patient groups as well as in controls, this correlation might be only secondary to a primary derangement in T-cell function. PMID:804451

  4. 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.

  5. 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…

  6. [Serum leptin concentration and some lipid parameters in vegetarian children].

    PubMed

    Laskowska-Klita, Teresa; Ambroszkiewicz, Jadwiga; Klemarczyk, Witold

    2004-04-01

    Leptin, a hormone from adipose tissue, regulates feeding behavior, satiation rate, energy expenditure and also plays an important role in maturation and reproduction. Recent studies support the concept that several factors such as a diet may influence on leptin levels. The aim of this study was to investigate serum concentration of leptin and lipids status in prepubertal children aged from 2 to 10 years with two different nutritional habits: vegetarian (n = 24) and omnivorous diet (n = 20). Serum leptin concentration was determined by immunoenzymeassay (ELISA). Serum lipids (cholesterol, HDL- and LDL-cholesterol, triglyceride) were measured by enzymatic and apolipoproteins by immunoturbidimetric methods. We noticed that in vegetarian diet there is a high rate of fiber (nearly twice as high as in omnivorous diet) and polyunsaturated acids (35% as much). In our study vegetarian children had lower total cholesterol and cholesterol in fractions HDL and LDL than meat eaters did. Also the apolipoproteins levels in vegetarian children were significantly below that of nonvegetarians. There is no differences in triglyceride concentration between the two groups of children. The mean serum leptin level in vegetarian children was significantly lower (3.1 +/- 1.2 ng/mL) as compared with the omnivores (5.6 +/- 2.1 ng/mL) (p < 0.0001).

  7. Serum YKL-40 levels are altered in endometriosis.

    PubMed

    Tuten, Abdullah; Kucur, Mine; Imamoglu, Metehan; Oncul, Mahmut; Acikgoz, Abdullah Serdar; Sofiyeva, Nigar; Ozturk, Zeynep; Kaya, Baris; Oral, Engin

    2014-05-01

    Endometriosis is traditionally defined as the presence of endometrial glands and stroma in ectopic locations, especially the pelvic peritoneum, ovaries and rectovaginal septum. YKL-40, a new biomarker of inflammation, is secreted by activated macrophages and neutrophils in different tissues with inflammation. Serum concentrations of YKL-40 are elevated in patients with diseases characterized by inflammation. We aimed to investigate the possible association between serum YKL-40 levels and endometriosis. A total number of 88 women were recruited for this case-control study. About 53 patients with surgically proven endometriosis were included, while 35 patients without endometriosis comprised the control group. Patients were classified as having minimal, mild, moderate and severe disease in accordance with the severity. Two new groups were formed by combining patients with minimal and mild disease (Stage 1-2) and with moderate and severe disease (Stage 3-4). Serum YKL-40 levels were statistically higher in the endometriotic group compared to control group (p:0.001). YKL-40 levels were significantly higher in Stage 3-4 group compared to Stage 1-2 group (p values 0.001) as well. Correlation analysis revealed a positive correlation between serum YKL-40 levels and the stage of the disease. YKL-40 may be utilized as a marker for determining the severity of endometriosis.

  8. Serum digoxin concentrations in canine congestive heart failure.

    PubMed

    Tobias, A H; Bland-van den Berg, P; Kruse, M M; Tubbesing, U H; Berry, W L

    1989-03-01

    Digoxin was administered to dogs (n = 10) in congestive heart failure, at an oral dosage rate of 0.01 mg kg-1 lean body mass twice daily. Lean body mass was determined by reducing gross mass by the estimated degree of ascites and body fat. The dose was further adjusted for factors such as renal and hepatic function, the bioavailability of different formulations, and the size of the patient. Trough and peak serum digoxin concentrations were determined after 10 days of digitalisation, or when signs of toxicity became apparent. Serum digoxin concentrations in 6 of the 10 dogs were found to be partially or completely in the toxic or subtherapeutic range. This indicates that an oral digoxin dosage rate of 0.01 mg kg-1 lean body mass administered twice daily, even when adjusted appropriately for factors that affect digoxin pharmacokinetics, provides no more than a rough approximation of the precise dose required to provide serum digoxin concentrations within the therapeutic range. The observations also lend support to a recent recommendation that the digoxin dosage rate should be based on body surface area, although even when administered on this basis, serum digoxin concentrations outside of the therapeutic range could be anticipated. PMID:2724277

  9. Serum copper levels in different stages of carcinoma cervix uteri.

    PubMed

    Singh, M; Dwivedi, S; Singh, G; Bajpai, M

    1990-01-01

    Copper is a normal constituent of the diet and is present in all living matter. It is an important trace metal required for different metabolic processes. Detecting alterations in serum copper has an important role in the early detection and diagnosis of malignancy. Serum copper estimation was conducted on 95 women aged 32-60 using the P.P. Doxidase method. 62 women of varying age and parity had different stages of carcinoma cervix uteri and comprised the study group, while the control group was comprised of 33 non-pregnant women of different ages and parity. Approximately 40% of women in both groups were aged 41-45 years. In the control group, the mean serum copper level of reproductive age women was 118.3 ug% and 111.2 ug% among women of menopausal age. A linear progressive increase of serum copper levels was found in the study group with increasing stages of cervical malignancy. The mean values of stages I, II, III, and IV were 162.2 ug%, 190.64 ug%, 201.78 ug%, and 220.8 ug%, respectively.

  10. Quantitation of fluphenazine in equine serum following fluphenazine decanoate administration.

    PubMed

    Costello, Sara; Heffron, Brendan; Taddei, Lisa; Benoit, Marc; Hurt, Laura; Simpson, Lindsay; Bishop, Jennifer; Folker-Calderon, Dawn; Negrusz, Adam

    2013-10-01

    Fluphenazine, a potent antipsychotic used to treat schizophrenia in humans, is used in racehorses as a performance-enhancing drug, and for that reason it has been banned by the Association of Racing Commissioners International. A liquid chromatography-tandem mass spectrometry method for detecting and quantitating fluphenazine in equine serum was developed and validated. The method was then employed to quantitate fluphenazine in serum samples collected from three study horses after intramuscular injection of fluphenazine decanoate. Stability testing showed that fluphenazine is stable in unextracted and processed samples as well as samples that have been subjected to up to three freeze-thaw cycles. The limit of detection and lower limit of quantitation of fluphenazine were determined to be 0.05 and 0.1 ng/mL, respectively. Precision was evaluated based on one-way analysis of variance of replicate quality control samples and was determined to be 27.2% at the 0.2 ng/mL level and 18.1% at the 2 ng/mL level. Bias was determined to be 0.55% at the 0.2 ng/mL level and 3.66% at the 2 ng/mL level. In two of three horses, fluphenazine was detected in serum up to 14 days post-administration. The highest detected concentration of fluphenazine in serum was 1.4 ng/mL.

  11. Recurrence prediction in oral cancers: a serum Raman spectroscopy study.

    PubMed

    Sahu, Aditi; Nandakumar, Nikhila; Sawant, Sharada; Krishna, C Murali

    2015-04-01

    High mortality rates associated with oral cancers can be primarily attributed to the failure of current histological procedures in predicting recurrence. Identifying recurrence related factors can lead to improved prognosis, optimized treatment and enhanced overall outcomes. Serum Raman spectroscopy has previously shown potential in the diagnosis of cancers, such as head and neck, cervix, breast, oral cancers, and also in predicting treatment response. In the present study, serum was collected from 22 oral cancer subjects [with recurrence (n = 10) and no-recurrence (n = 12)] before and after surgery and spectra were acquired using a Raman microprobe coupled with a 40× objective. Spectral acquisition parameters were as follows: λex = 785 nm, laser power = 30 mW, integration time: 12 s and averages: 3. Data was analyzed in a patient-wise approach using unsupervised PCA and supervised PC-LDA, followed by LOOCV. PCA and PC-LDA findings suggest that recurrent and non-recurrent cases cannot be classified in before surgery serum samples; an average classification efficiency of ∼78% was obtained in after-surgery samples. Mean and difference spectra and PCA loadings indicate that DNA and protein markers may be potential spectral markers for recurrence. RS of post surgery serum samples may have the potential to predict the probability of recurrence in clinics, after prospective large-scale validation.

  12. Identification of Immunogenic and Serum Binding Proteins of Staphylococcus epidermidis

    PubMed Central

    Sellman, Bret R.; Howell, Alan P.; Kelly-Boyd, Cari; Baker, Steve M.

    2005-01-01

    Staphylococcus epidermidis is a commensal of human skin and a leading cause of nosocomial bloodstream infections. Limited information is available about S. epidermidis proteins that are expressed upon transition to the bloodstream or those involved in host-pathogen interactions. A cell surface fraction from S. epidermidis 0-47 grown in rabbit serum to mimic environmental signals encountered during a bloodstream infection was separated by two-dimensional (2D) gel electrophoresis. Following 2D separation, the proteins were transferred to nitrocellulose and detected with either pooled sera generated in rabbits immunized with live S. epidermidis 0-47 or with biotin-labeled serum proteins eluted from the surface of bacteria grown in rabbit serum. Twenty-nine immunoreactive or serum binding proteins of S. epidermidis were identified by mass spectrometry. Twenty-seven of the corresponding genes were expressed in Escherichia coli, and the purified recombinant proteins were used to immunize mice. In a preliminary screen, 12 of the 27 recombinant proteins induced a response that reduced the number of bacteria recovered from the spleen or bloodstream of infected mice. In subsequent vaccination studies, 5 of the 12 proteins resulted in a statistically significant reduction in the number of bacteria. The identification of five candidate vaccine antigens from the initial screen of only 29 proteins demonstrates the utility of this approach. PMID:16177335

  13. Effect of dietary calcium on serum BGP (osteocalcin).

    PubMed

    Kusuhara, R; Katayama, S; Itabashi, A; Maruno, Y; Inaba, M; Akabane, S; Tanaka, K; Morita, K; Shibuya, M; Kawazu, S

    1991-04-01

    The present study was designed to clarify the effects of dietary calcium (Ca) intake on serum BGP (osteocalcin) levels. Twelve women with a mean age of 21.2 years participated in the study. After one week of normal Ca intake (mean +/- SE, 535 +/- 2 mg/day), a low-Ca diet (163 +/- 1 mg/day) was given for one further week. Additional asparagine Ca (3 g as Ca/day) was also given to half of the subjects. Serum total and ionized Ca concentrations as well as BGP, PTH and 1,25(OH)2D3 were measured at the end of each period. Amounts of Ca and hydroxyproline excreted in urine were also determined. The plasma level of ionized Ca was significantly increased without any change in total Ca in either group. Low and high Ca intake decreased and increased urinary Ca excretion by 28% and 56%, respectively. Serum levels of BGP and 1,25(OH)2D3 were significantly augmented along with a transient increase in urinary hydroxyproline excretion after Ca deprivation. These results suggest that serum BGP is increased after one week of Ca restriction in healthy subjects.

  14. Serum Vitamin D in patients with alopecia areata

    PubMed Central

    Bakry, Ola Ahmed; El Farargy, Shawky M; El Shafiee, Maathir K; Soliman, Amira

    2016-01-01

    Background: Alopecia areata (AA) is a common, recurrent, autoimmune hair disorder. It has been found that vitamin D deficiency is associated with many autoimmune diseases. Aims: The current study aimed to estimate serum levels of 25-hydroxy vitamin D in patients with AA. Materials and Methods: This case–control study included 60 patients with AA and 60 age, gender, skin phototype, and body mass index-matched healthy subjects as a control group. Levels of serum 25-hydroxy vitamin D were estimated using ELISA technique. Results: Serum 25-hydroxy vitamin D levels were significantly lower in AA cases when compared with healthy controls (P < 0.001). The least values were significantly associated with alopecia totalis/universalis compared with patchy AA (P < 0.001) and ophiasis (P = 0.04). Severe AA showed significantly the lowest vitamin D levels compared with cases with mild (P = 0.002) and moderate disease (P = 0.03). A significant inverse correlation was found between 25-hydroxy vitamin D levels and age of the patients (r = −0.38; P = 0.03). There was no significant association between serum 25-hydroxy vitamin D levels and gender, disease duration, disease recurrence, nail affection, duration of sun exposure/day, or positive family history of AA. Conclusion: AA patients have lower levels of 25-hydroxy vitamin D than healthy subjects. More studies are required to assess the value of vitamin D supplementation in the treatment of that disease. PMID:27730032

  15. 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

  16. 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.

  17. Changes in serum sodium concentration after transurethral procedures.

    PubMed

    Georgiadou, Th; Vasilakakis, I; Meitanidou, M; Georgiou, M; Filippopoulos, K; Kanakoudis, F; Radopoulos, D

    2007-01-01

    The aim of this study is to evaluate the changes in serum sodium concentration and the degree of correlation with factors such as the amount of intravenous fluid intake, the kind and the amount of irrigating fluids and the duration of the procedure. In this framework, 98 male patients who underwent transurethral procedure were studied and the correlation between the magnitude of hyponatraemia and the above-mentioned parameters was evaluated. All procedures were performed under spinal anesthesia and a solution of either manitol-sorbitol or sterilized water was used as irrigation fluid. Serum sodium concentration was measured before and after the procedure, while the kind and amount of the irrigating fluids, the amount of fluid intake and the duration of the procedure were also recorded. The patients were divided into three groups according to the duration of the procedure (i) <30 min, (ii) 30-60 min, and (iii) >60 min. Significant reduction in serum sodium concentration was found postoperatively (P < 0.001) and this was more profound in procedures longer than 1 h. This reduction was strongly correlated only with the duration of the transurethral procedure (P < 0.01). In conclusion, in transurethral procedures the reduction in serum sodium is postoperatively related to the duration of the procedure, while the intravenous and irrigating fluids to play no role on it. PMID:17390229

  18. Testing of serum atherogenicity in cell cultures: questionable data published

    PubMed Central

    Jargin, Sergei V.

    2012-01-01

    In a large series of studies was reported that culturing of smooth muscle cells with serum from atherosclerosis patients caused intracellular lipid accumulation, while serum from healthy controls had no such effect. Cultures were used for evaluation of antiatherogenic drugs. Numerous substances were reported to lower serum atherogenicity: statins, trapidil, calcium antagonists, garlic derivatives etc. On the contrary, beta-blockers, phenothiazines and oral hypoglycemics were reported to be pro-atherogenic. Known antiatherogenic agents can influence lipid metabolism and cholesterol synthesis, intestinal absorption or endothelium-related mechanisms. All these targets are absent in cell monocultures. Inflammatory factors, addressed by some antiatherogenic drugs, are also not reproduced. In vivo, relationship between cholesterol uptake by cells and atherogenesis must be inverse rather than direct: in familial hypercholesterolemia, inefficient clearance of LDL-cholesterol by cells predisposes to atherosclerosis. Accordingly, if a pharmacological agent reduces cholesterol uptake by cells in vitro, it should be expected to elevate cholesterol in vivo. Validity of clinical recommendations, based on serum atherogenicity testing in cell monocultures, is therefore questionable. These considerations pertain also to the drugs developed on the basis of the cell culture experiments. PMID:22355278

  19. 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

  20. 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

  1. The features of skin inflammation induced by lupus serum.

    PubMed

    Liu, Lena; Xu, Guangqion; Dou, Hui; Deng, Guo-Min

    2016-04-01

    We recently developed a model of lupus serum-induced skin inflammation, which was used to study the pathogenesis of skin injury in systemic lupus erythematosus (SLE). We further characterized the features of lupus serum-induced skin inflammation. This skin inflammation was evident within 3h and lasted for at least two weeks. The skin inflammation was characterized by an influx of monocytic, CD11b+cells and by a scarcity of T and B lymphocytes. Depletion of IgG from the serum abrogated the skin inflammatory response. The skin inflammation was related to lupus patients' skin history but not to SLE disease activity and type of autoantibody. The expression of TNFR1, NF-kB and MCP-1 was increased locally in skin lesions. The TLR9 ligand and lupus serum act synergistically to trigger skin inflammation. These findings suggest that this novel model is valuable for the study of the pathogenesis and therapy of skin injury in SLE.

  2. Effect of raised serum prolactin on breast development.

    PubMed Central

    Stringer, B M; Rowson, J; Williams, E D

    1989-01-01

    The effect of serum prolactin elevation on the growth and development of the rat breast was investigated. Oral administration of the dopamine antagonist, perphenazine, led to a 5-10-fold elevation of serum prolactin after two days of treatment which was maintained for the 54 days of study. A significant (P less than 0.01) 3.4-fold increase in total breast volume was seen by Day 4 of serum prolactin elevation. Breast volume continued to rise up to Day 14 reaching an 8.9-fold peak (P less than 0.001) which was maintained for the duration of the experiment. Epithelial, myoepithelial, lumen and stromal volume changes in the ductular and alveolar compartments were quantified separately. Highly significant (P less than 0.01) volume increases were seen in all components within the first few days of prolactin elevation. Similar time courses of the growth response to elevated serum prolactin were seen in the ductal tissues reaching an approximate 3-fold peak by 7 days in duct epithelium, myoepithelium and duct stroma. Time coordinated growth responses were also seen in the alveolar tissues with larger (7-15-fold) increases in alveolar epithelium, alveolar myoepithelium and alveolar stroma, reaching a peak by 14 days. Images Fig. 1 Fig. 2 Fig. 3 PMID:2808120

  3. Clinical features of serum sickness after Australian snake antivenom.

    PubMed

    Ryan, Nicole M; Downes, Michael A; Isbister, Geoffrey K

    2015-12-15

    Serum sickness is a delayed immune reaction in which the immune system responds to a protein in antiserum as a potentially harmful substance and mounts an IgG-mediated antibody response. A 32 year-old female patient had systemic envenoming following a bite by a red-bellied black snake (Pseudechis porphyriacus). She was treated with Tiger snake antivenom and recovered over 24 h and did not develop myotoxicity. She then presented with local pain, itching and swelling, which was partially treated with antihistamines. Eleven days after the bite she presented again with symptoms of worsening serum sickness including rash on the upper legs, joint and muscle pain in arms, ankles and knees, and nausea. The patient was prescribed five days of prednisone 50 mg/day, antihistamine 10 mg/day and analgesia 1000 mg/day and improved over 2 days. She had no further problems on follow up at 4 months. This case highlights that serum sickness can cause significant effects after the treatment of snake envenoming. It develops 5-14 days after antivenom administration and has characteristic clinical and laboratory features. Severe cases of serum sickness can result in morbidity but it appears to respond well to corticosteroid treatment. PMID:26525657

  4. Autoimmune anti-androgen-receptor antibodies in human serum.

    PubMed Central

    Liao, S; Witte, D

    1985-01-01

    Circulating autoantibodies to human and rat androgen receptors are present at high titers in the blood sera of some patients with prostate diseases. The antibodies from some serum samples were associated with a purified IgG fraction and interacted with the 3.8S cytosolic androgen-receptor complexes of rat ventral prostate to form 9- to 12S units. Other serum samples, however, formed 14- to 19S units, suggesting that other immunoglobulins might be involved. In the presence of an anti-human immunoglobulin as a second antibody, the androgen-receptor-antibody complexes could be immunoprecipitated. The antibodies interacted with the nuclear and the cytosolic androgen-receptor complexes, either the DNA-binding or the nonbinding form, but not with receptors for estradiol, progestin, or dexamethasone from a variety of sources. Human testosterone/estradiol-binding globulin, rat epididymal androgen-binding protein, or rat prostate alpha-protein (a nonreceptor steroid-binding protein) also did not interact with the antibodies to form immunoprecipitates. About 37% of male and 3% of female serum samples screened had significant antibody titer. The chance of finding serum with a high titer is much better in males older than 66 years than in the younger males or females at all ages. The presence of the high-titer antibodies may make it possible to prepare monoclonal antibodies to androgen receptors without purification of the receptors for immunization. PMID:3866227

  5. 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

  6. Storage of serum in plastic and glass containers may alter the serum concentration of polychlorinated biphenyls.

    PubMed

    Karmaus, Wilfried; Riebow, John F

    2004-05-01

    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.

  7. Probing Cocaine-Antibody Interactions in Buffer and Human Serum

    PubMed Central

    Ramakrishnan, Muthu; Alves De Melo, Fernando; Kinsey, Berma M.; Ladbury, John E.; Kosten, Thomas R.; Orson, Frank M.

    2012-01-01

    Background Despite progress in cocaine immunotherapy, the kinetic and thermodynamic properties of antibodies which bind to cocaine and its metabolites are not well understood. It is also not clear how the interactions between them differ in a complex matrix such as the serum present in the human body. In the present study, we have used microscale thermophoresis (MST), isothermal titration calorimetry (ITC), and surface plasmon resonance (SPR) we have evaluated the affinity properties of a representative mouse monoclonal (mAb08) as well as those of polyclonal antibodies purified from vaccinated mouse and human patient serum. Results MST analysis of fluorescently tagged mAb08 binding to cocaine reveals an approximately 15 fold decrease in its equilibrium dissociation constant in 20–50% human serum compared with that in saline buffer. A similar trend was also found using enriched polyclonal antibodies purified from vaccinated mice and patient serum, for which we have used fluorescently tagged bovine serum albumin conjugated to succinyl norcocaine (BSA-SNC). This conjugate closely mimics both cocaine and the hapten used to raise these antibodies. The ITC data also revealed that cocaine has a moderate affinity of about 2 µM to 20% human serum and very little interaction with human serum albumin or nonspecific human IgG at that concentration range. In a SPR inhibition experiment, the binding of mAb08 to immobilized BSA-SNC was inhibited by cocaine and benzoylecgonine in a highly competitive manner, whereas the purified polyclonal antibodies from vaccinated humans and mice, revealed preferential selectivity to pharmacologically active cocaine but not to the inactive metabolite benzoylecgonine. We have also developed a simple binding model to simulate the challenges associated with cocaine immunotherapy using the variable quantitative and kinetic properties of the antibodies. Conclusions High sensitivity calorimetric determination of antibody binding to cocaine and its

  8. Candidates for reference swine serum with anti-Trichinella antibodies.

    PubMed

    Gómez-Morales, Maria Angeles; Ludovisi, Alessandra; Amati, Marco; Pozio, Edoardo

    2015-03-15

    Serology to monitor Trichinella spp. infection in pigs reared in controlled system has been claimed as a possible diagnostic tool. However, no international biological standards or reference materials exist to validate in house tests or commercial kits, and to improve the inter-laboratory comparability for the serological detection of anti-Trichinella IgG in pigs. In this work, potential reference sera have been prepared from four experimentally infected pigs. Sera were tested, aliquot, lyophilized, and maintained at +4°C. Since one of the prerequisites for the development of any reference material is to plan and execute stability studies, isochronous studies for short and long term stability testing were carried out to evaluate the possible degradation effects of transportation and storage. The stability of the lyophilized serum samples at +4°C, was arbitrarily assumed. For the short term stability study, two units were stored at -20°C, +4°C, +20°C, and +50°C for 0, 1, 2, and 4 weeks, and then tested in duplicate. For the long term stability study, the same number of units and replicates per unit were stored at -80°C, -20°C, and +4°C for 0, 6, 12, 18 and 24 months. In both studies, unit samples were selected randomly and tested on the same day under repeatability conditions. The linear regression versus time for each serum at each studied temperature was analyzed and then slopes were tested for significance. Further, uncertainty of the short and long term stability was calculated for a shelf life period of one week and three years, respectively. For all sera but one, and for all the studied temperatures but +50°C, the data from the short term stability study indicate the absence of a significant trend that would hint at degradation. The slopes of the regression lines did not significantly vary from zero. Even if the uncertainty of the short term stability was variable among serum samples, the rate of degradation was considered acceptable. For the long

  9. The Associations of Serum Lipids with Vitamin D Status

    PubMed Central

    Liu, Junli; Wang, Zongye; Jia, Haiying; Feng, Kai; Sun, Lili

    2016-01-01

    Aims Vitamin D deficiency has been associated with some disorders including cardiovascular diseases. Dyslipidemia is a major risk factor for cardiovascular diseases. However, data about the relationships between vitamin D and lipids are inconsistent. The relationship of vitamin D and Atherogenic Index of Plasma (AIP), as an excellent predictor of level of small and dense LDL, has not been reported. The objective of this study was to investigate the effects of vitamin D status on serum lipids in Chinese adults. Methods The study was carried out using 1475 participants from the Center for Physical Examination, 306 Hospital of PLA in Beijing, China. Fasting blood samples were collected and serum concentrations of 25(OH)D, total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) were measured. AIP was calculated based on the formula: log [TG/HDL-C]. Multiple linear regression analysis was used to estimate the associations between serum 25(OH)D and lipids. The association between the occurrences of dyslipidemias and vitamin D levels was assessed by multiple logistic regression analysis. Confounding factors, age and BMI, were used for the adjustment. Results The median of serum 25(OH)D concentration was 47 (27–92.25) nmol/L in all subjects. The overall percentage of 25(OH)D ≦ 50 nmol/L was 58.5% (males 54.4%, females 63.7%). The serum 25(OH)D levels were inversely associated with TG (β coefficient = -0.24, p < 0.001) and LDL-C (β coefficient = -0.34, p < 0.001) and positively associated with TC (β coefficient = 0.35, p < 0.002) in men. The associations between serum 25(OH)D and LDL-C (β coefficient = -0.25, p = 0.01) and TC (β coefficient = 0.39, p = 0.001) also existed in women. The serum 25(OH)D concentrations were negatively associated with AIP in men (r = -0.111, p < 0.01) but not in women. In addition, vitamin D deficient men had higher AIP values than vitamin D sufficient men

  10. High concentrations of horse serum inhibit growth of corn stunt spiroplasma.

    PubMed Central

    Igwegbe, E C

    1978-01-01

    Corn stunt spiroplasma (CSS) grew faster and achieved higher titers in liquid or agar medium containing 5 or 10 percent horse serum than it did in medium containing 20 percent horse serum. When growth in liquid medium was initiated with a small inoculum, CSS achieved excellent growth in the presence of 5 percent serum but did not grow in medium containing 0 or 20 percent serum. Addition of arginine to liquid or agar medium supplemented with 20 percent serum stimulated CSS growth, but addition to that containing 5 percent serum did not. Images PMID:564163

  11. A comparative fluorescent beacon-based method for serum microRNA quantification.

    PubMed

    Beta, Madhu; Krishnakumar, Subramanian; Elchuri, Sailaja V; Salim, Bindu; Narayanan, Janakiraman

    2015-01-01

    Circulating serum microRNAs (miRNAs) are promising biomarkers for disease diagnosis. The quantification of the serum miRNA copy number is a challenge due to the presence of low levels in the serum. Here, we report on a direct measurement of the miRNA copy number from human serum using a locked nucleic acid (LNA) modified beacon probe with a single step using fluorescence spectroscopy and microscopy. We had used a minimum volume of 0.1 μL healthy human serum and retinoblastoma serum to show the biological variation of the miRNA copy number.

  12. Serum thyrotropin (TSH) levels in patien