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Biomedical subjects

J Yeh

Publications and source records attributed to J Yeh.

At least 73 records · Page 4Linked to original sources

Incidence of renal failure in NIDDM. The Oklahoma Indian Diabetes Study.

The incidence of and risk factors for renal failure were determined in 912 Oklahoma Indians with non-insulin-dependent diabetes mellitus in a follow-up study conducted between 1987 and 1990. The incidence rate was 15.7/1,000 person-years after an average follow-up time of 10.2 years. Among those who had no qualitatively positive proteinuria at baseline, the incidence of renal failure was 10.3/1,000 person-years compared with 19.3- and 56.2/1,000 person-years, respectively, in those with slight and heavy proteinuria at baseline. Fasting plasma glucose (FPG) > or = 11.1 mM (200 mg/dl) increased the risk of renal failure to 2.9-fold (95% confidence interval [CI] = 1.9-4.6) higher than a level < 7.8 mM (140 mg/dl), and twofold (95% CI = 1.4-3.1) higher than a level between 7.8 (140 mg/dl) and 11.1 mM (200 mg/dl). The hypertensive patient had twice the incidence of renal failure than the normotensive subject (rate ratio = 2.1, 95% CI = 1.4-3.0). Patients with a lower blood pressure under antihypertensive medication had a lower incidence of renal failure than those whose hypertension remained uncontrolled with or without use of medication. Significant independent risk factors for renal failure, identified from Cox's proportional hazards model, were duration of diabetes, FPG, age, hypertension, and insulin use (P < 0.05). In patients without proteinuria at baseline, FPG and hypertension were significant predictors of renal failure as identified by multivariate analyses, whereas in patients who had proteinuria at baseline, insulin use was significant. Thus, hyperglycemic and hypertension control are suggested strongly for diabetic Oklahoma Indians as potential strategies to prevent the development of renal failure.

Adult↗

Effects of cytokines on epidermal growth factor receptor expression by malignant trophoblast cells in vitro.

Trophoblastic cells abundantly express epidermal growth factor (EGF) receptors, which, when activated by EGF or transforming growth factor-alpha, can influence cellular growth and metabolism. Various lymphocyte and macrophage cytokines have been found to influence the proliferation of human choriocarcinoma (CCA) cells in vitro. In the current study we investigated the possibility that certain cytokine effects are mediated by changes in EGF receptor expression. JEG-3 human CCA cells were incubated with varying concentrations of interleukin 1-alpha (IL-1 alpha), interleukin 1-beta (IL-1 beta), interleukin 2, gamma-interferon, granulocyte-macrophage colony stimulating factor and tumor necrosis factor-alpha (TNF), and the expression of EGF receptor was measured by radioimmunoassay using a murine monoclonal antibody with specificity for the EGF receptor. Proliferative or growth suppressive effects of the cytokines were assessed by quantitative analysis of the DNA in the cell culture wells. Macrophage-derived cytokines IL-1 alpha, IL-1 beta and TNF significantly suppressed cell growth; this was associated with a significant increase in EGF receptor expression. The other cytokines had no significant effect on either EGF receptor expression or cell growth. We also studied the expression of EGF mRNA in JEG-3, Jar and BeWo CCA cell lines. By reverse transcription followed by polymerase chain reaction, low levels of EGF mRNA were detected in all three cell lines. Therefore, EGF may be synthesized by JEG-3, Jar and BeWo CCA cell lines to participate in an autocrine growth pathway. Our findings support the concept that cytokines may act as paracrine mediators of autocrine processes involved in CCA cell growth regulation by modulating growth factor receptor expression.

Blotting, Northern↗

Ligand-dependent changes in intrinsic fluorescence of S-adenosylhomocysteine hydrolase: implications for the mechanism of inhibitor-induced inhibition.

Different forms of S-adenosylhomocysteine (AdoHcy) hydrolase (NAD+, apo, and NADH forms) were prepared, and the effects of ligand binding on the intrinsic tryptophan fluorescence were investigated. Binding of AdoHcy hydrolase (NAD+ form) with its mechanism-based inhibitors [e.g., (1'R,2'S,3'R)-9-(2',3'-dihydroxycyclopentan-1'-yl)adenine] caused significant quenching (35%) of the intrinsic tryptophan fluorescence of the enzyme. A ligand-induced conformational change in the tertiary structure of the enzyme accounted for an initial 10% quenching of the fluorescence, with further fluorescence quenching occurring in a time-dependent manner. This time-dependent quenching of fluorescence was consistent with the time-dependent inactivation of the enzyme and the time-dependent reduction of the enzyme-bound NAD+ to NADH. The time-dependent quenching of the intrinsic tryptophan fluorescence is largely the result of resonance energy transfer from tryptophan(s) in the enzyme to the enzyme-bound NADH. This interpretation is supported by the observations that the formation of enzyme-bound NADH quenched the intensity of the intrinsic tryptophan fluorescence and that the enzyme-bound NADH fluorescence was excited by light at wavelengths consistent with the absorption spectrum of tryptophan. Additional support for the involvement of NADH in the time-dependent tryptophan fluorescence quenching came from the observation that this quenching could only be observed when binding caused simultaneous reduction of the enzyme-bound NAD+ to NADH.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosylhomocysteinase↗

Mechanism of inactivation of S-adenosylhomocysteine hydrolase by (Z)-4',5'-didehydro-5'-deoxy-5'-fluoroadenosine.

S-Adenosyl-L-homocysteine (AdoHcy) hydrolase, an enzyme important in the regulation of biological methylation reactions, was shown by McCarthy et al. (McCarthy, J.R., Jarvi, E.T., Matthews, D.P., Edwards, M.L., Prakash, N.J., Bowlin, T.L., Mehdi, S., and Bey, P. (1989) J. Am. Chem. Soc. 111, 1127-1128) to be inactivated by (Z)-4',5'-didehydro-5'-deoxy-5'-fluoroadenosine (ZDDFA). In this study we have shown that the mechanism of this inactivation of AdoHcy hydrolase (NAD+ form) includes a rapid addition of water to the 5'-position of ZDDFA and elimination of fluoride ion, resulting in the formation of the 5'-carboxaldehydes 3 and 4. The 5'-carboxaldehydes 3 and 4 are then oxidized in a slower step to the 3'-keto-5'-carboxaldehydes 5 and 6 by reduction of the enzyme-bound NAD+ to NADH. Evidence in support of this mechanism includes the observation that the first step in this mechanism (i.e. elimination of fluoride ion and formation of the 5'-carboxaldehydes 3 and 4) can be catalyzed by apo-AdoHcy hydrolase and the NADH form of AdoHcy hydrolase. Incubation of ZDDFA with either the apo or NADH form of AdoHcy hydrolase resulted in rapid release of fluoride ion (determined by 19F NMR) and formation of the 5'-carboxyaldehydes 3 and 4 (determined by high performance liquid chromatography). The carboxaldehydes 3 and 4 were synthesized independently and were shown to be potent inhibitors of the NAD+ form of the enzyme. When the relative first-order rates of fluoride ion release (determined by 19F NMR) from ZDDFA, NAD+ reduction to NADH, and inactivation of the NAD+ form of the enzyme were compared, the release of fluoride ion was found to be approximately 20 times faster than NAD+ reduction or enzyme inactivation. Incubation of ZDDFA with the NAD+ form of AdoHcy hydrolase was shown to afford the 3'-keto-5'-carboxaldehydes 5 and 6, which were also formed upon incubation of the enzyme with the 5'-carboxaldehydes 3 and 4. The 3'-keto-5'-carboxaldehydes 5 and 6 were shown to be tightly (but not covalently) bound to the enzyme, since these products could be released by treatment of the ZDDFA-inactivated enzyme with HClO4 or other denaturing agents.

Adenosine↗

Refined structures of the ligand-binding domain of the aspartate receptor from Salmonella typhimurium.

The aspartate receptor is a transmembrane-signalling protein that mediates chemotaxis behaviour in bacteria. Aspartate receptors in Salmonella typhimurium and Escherichia coli exist as dimers of two subunits in the presence as well as in the absence of aspartate. We have previously reported the three-dimensional structures of the external ligand-binding domain of the S. typhimurium aspartate receptor with and without bound aspartate. The external or periplasmic region of the aspartate receptor is a dimer of four-alpha-helical bundle subunits; a single aspartate molecule binds to one of two sites residing at the subunit interface, increasing the affinity of the subunits for one another. Here we report the results of a detailed analysis of the aspartate receptor ligand-binding domain structure (residues 25 to 188). The dimer interface between the twofold related subunits consists primarily of contacts mediated by the side-chains of the N-terminal helix of each four-alpha-helical bundle subunit. The N-terminal helices pack approximately 20 degrees from parallel as an approximate coiled-coil super-secondary structure. We have refined aspartate receptor ligand-binding domain structures in the presence and in the absence of a bound aromatic compound, 1,10-phenanthroline, to 2.2 A and 2.3 A resolution, respectively, as well as crystal structures in the presence of specifically bound Au(I), Hg(II) and Pt(IV) complex ions at 2.4 A, 3.0 A and 3.3 A resolution, respectively. The possible biological relevance of the aromatic ligand-binding site and the metal ion-binding sites is discussed. The dimer of four-alpha-helical bundle subunits composing the periplasmic region of the S. typhimurium aspartate receptor provides a basis for understanding the results of mutational analyses performed on related chemotaxis transmembrane receptors. The crystal structure analysis provides an explanation for the way in which mutations in the E. coli aspartate receptor affect its binding to the periplasmic maltose-binding protein and how mutations in the more distantly related E. coli Trg chemotaxis receptor affect its binding to the periplasmic ribose and glucose-galactose binding proteins.

Aspartic Acid↗

JHM virus-specific cytotoxic T cells derived from the central nervous system.

Spleen cells cultured from Balb/c mice immunized with the JHM strain of mouse hepatitis virus (JHMV) have CD8+ cytotoxic T cells (CTL) specific for both the S and N proteins, but not the M or HE proteins. T cell lines were established from the brains of Balb/c mice infected with JHMV. The majority of the lines (20 of 22) were specific for JHMV. Analysis of the viral structural proteins which served as target structures indicate that most (15 of 20) were specific for the N protein. One line was specific for the S protein and four lines were specific for JHMV but the protein recognized could not be determined. These data suggest that early during infection there is a preferential recruitment of N protein specific CTL into the CNS of infected mice.

Animals↗

Expression of messenger ribonucleic acid for epidermal growth factor receptor and its ligands, epidermal growth factor and transforming growth factor-alpha, in human first- and second-trimester fetal ovary and uterus.

OBJECTIVES: The epidermal growth factor receptor, a 170 kd polypeptide with tyrosine kinase activity, is used as the common receptor by two homologous polypeptide growth factors, epidermal growth factor and transforming growth factor-alpha. The activation of the epidermal growth factor receptor results in effects including deoxyribonucleic acid synthesis and cellular differentiation. Epidermal growth factor, transforming growth factor-alpha, and the epidermal growth factor receptor are reported to be associated with adult reproduction. However, the pattern of gene expression for the epidermal growth factor receptor and its ligands in human fetal reproductive tissues has not been detailed previously. STUDY DESIGN: We studied the expression of messenger ribonucleic acid encoding three polypeptides, epidermal growth factor receptor, epidermal growth factor, and transforming growth factor-alpha, in 10-, 15-, 19-, and 22-week human fetal ovaries and uteri. Ribonucleic acid was prepared from the fetal tissues and made into complementary deoxyribonucleic acid by reverse transcription. The complementary deoxyribonucleic acid was amplified by polymerase chain reaction, using primers specific for the human epidermal growth factor receptor, epidermal growth factor, and transforming growth factor-alpha. RESULTS: We found that epidermal growth factor receptor messenger ribonucleic acid was present in all stages of ovarian and uterine tissues studied. In addition, both epidermal growth factor and transforming growth factor-alpha messenger ribonucleic acid was found in all four stages of ovarian development. Epidermal growth factor messenger ribonucleic acid was detected in all four stages of fetal uterine development. CONCLUSIONS: This is the first demonstration, to our knowledge, of epidermal growth factor receptor, epidermal growth factor, and transforming growth factor-alpha messenger ribonucleic acid expression in human first- and second-trimester uterus and ovary.

Base Sequence↗

Acute adrenocorticotropin stimulation of postmenopausal cigarette smokers and nonsmokers: effects on steroidogenesis.

Cigarette smoking has been associated with elevated levels of A and DHEAS in postmenopausal women. One possible mechanism postulated for this effect is enzymatic blockage by components of cigarette smoke. In this study, acute ACTH stimulation of postmenopausal cigarette smokers did not result in abnormal elevations of precursor steroids. Other possible mechanisms may be operative in vivo to account for the previously reported findings.

Adrenocorticotropic Hormone↗

Human fetal ovaries and uteri: developmental expression of genes encoding the insulin, insulin-like growth factor I, and insulin-like growth factor II receptors.

OBJECTIVE: To study the messenger ribonucleic acid (mRNA) expression of receptors for insulin, insulin-like growth factor I (IGF-I), and insulin-like growth factor II (IGF-II) in human fetal ovaries and uteri at 10, 15, 19, and 22 weeks' gestation. Insulin, IGF-I, and IGF-II are postulated to have paracrine and autocrine functions in the development of fetal tissues, but receptors for these growth factors have never been studied in reproductive organs of the human female fetus. DESIGN: Ribonucleic acid extracted from human fetal reproductive tissues underwent reverse transcription and polymerase chain reaction (PCR) amplification. The amplified complementary deoxyribonucleic acid (cDNA) fragments were analyzed by gel electrophoresis and restriction enzyme mapping. RESULTS: Messenger RNA expression consistent with both known forms of the insulin receptor, the IGF-I receptor, and the IGF-II receptor was observed in human fetal ovaries and uteri at 10, 15, 19, and 22 weeks' gestation. The identity of the PCR amplified ovarian and uterine DNA fragments were confirmed by digestion with the restriction endonucleases AvaII, DdeI, and BamHI, respectively. CONCLUSIONS: This study demonstrates that mRNA for receptors for insulin, IGF-I, and IGF-II are expressed in the fetal human female genital tract. These receptors may have roles in fetal reproductive tract development.

Base Sequence↗

Presence of transforming growth factor-alpha messenger ribonucleic acid (mRNA) and absence of epidermal growth factor mRNA in rat ovarian granulosa cells, and the effects of these factors on steroidogenesis in vitro.

Granulosa cell steroidogenesis has been reported to be modulated by transforming growth factor-alpha (TGF alpha) and its biochemical and physiological analog, epidermal growth factor (EGF). In this report, we studied whether TGF alpha or EGF mRNA is produced by granulosa cells, examined the morphological effects of TGF alpha or EGF on granulosa cell cultures, and measured the changes in granulosa cell progesterone production in cells cultured with TGF alpha or EGF. RNA from fresh granulosa cells and from those incubated overnight and for 4, 7, and 10 days with FSH was studied with reverse transcription-polymerase chain reaction for TGF alpha and for EGF. Only TGF alpha mRNA appeared to be present in the granulosa cells. Phase-contrast microscopy revealed that the combination of FSH plus TGF alpha or EGF resulted in cell shape changes and an increase in lipid droplets in the granulosa cells. Electron microscopy revealed that the endoplasmic reticulum increased in the granulosa cells incubated with either EGF or FSH plus EGF. Mitochondria of granulosa cells incubated with growth factors possessed ultrastructural features consistent with those found in preovulatory granulosa cells. Culture of the granulosa cells with FSH plus TGF alpha or with FSH plus EGF resulted in significantly elevated progesterone and 20 alpha-hydroxyprogesterone levels. The highest level of progesterone production was on the eighth day of culture. We conclude that TGF alpha mRNA is produced by granulosa cells and that granulosa cell differentiation, as defined by morphological and biochemical criteria, is significantly stimulated in vitro by the combination of FSH and TGF alpha.

20-alpha-Dihydroprogesterone↗

beta-Amyloid neurotoxicity in human cortical culture is not mediated by excitotoxins.

beta-Amyloid is a metabolic product of the amyloid precursor protein, which accumulates abnormally in senile plaques in the brains of patients with Alzheimer's disease. The neurotoxicity of beta-amyloid has been observed in cell culture and in vivo, but the mechanism of this effect is unclear. In this report, we describe the direct neurotoxicity of beta-amyloid in high-density primary cultures of human fetal cortex. In 36-day-old cortical cultures, beta-amyloid neurotoxicity was not inhibited by the broad-spectrum excitatory amino acid receptor antagonist kynurenate or the NMDA receptor antagonist D-2-amino-5-phosphonovaleric acid under conditions that inhibited glutamate and NMDA neurotoxicity. In 8-day-old cortical cultures, neurons were resistant to glutamate and NMDA toxicity but were still susceptible to beta-amyloid neurotoxicity, which was unaffected by excitatory amino acid receptor antagonists. Treatment with beta-amyloid caused chronic neurodegenerative changes, including neuronal clumping and dystrophic neurites, whereas glutamate treatment caused rapid neuronal swelling and neurite fragmentation. These results suggest that beta-amyloid is directly neurotoxic to primary human cortical neurons by a mechanism that does not involve excitatory amino acid receptors.

Amino Acids↗

Expression of messenger ribonucleic acids encoding for basic fibroblast growth factor (FGF) and alternatively spliced FGF receptor in human fetal ovary and uterus.

Basic fibroblast growth factor (bFGF) is an angiogenic and mitogenic peptide that may have modulatory effects in the adult ovary and uterus. The FGF receptor is a tyrosine kinase and has similar affinity for both acidic FGF and bFGF. The ligand-binding portion of the receptor has three immunoglobulin-like domains. bFGF and the FGF receptor have been localized in the fetal rat ovary and Mullerian duct. bFGF is a proliferative agent recently shown to be vital for long term cultures of mouse fetal primordial germ cells. Expression of bFGF and FGF receptor mRNA have not heretofore been reported in human fetal ovary and uterus. We prepared RNA from whole human fetal ovaries and uteri at 10, 15, 19, and 22 weeks gestation. After reverse transcription of the RNA into cDNA, we used polymerase chain reaction (PCR) primers directed to specific portions of bFGF and the FGF receptor and performed PCR amplification using the fetal cDNA. We found mRNA expression of bFGF and two forms of FGF receptor in all fetal ovaries and uteri at these developmental stages. One of the PCR products for the FGF receptor was the sequence that contained three immunoglobulin-like domains, whereas a second PCR-amplified fragment was consistent with a FGF receptor mRNA that has a 267-basepair deletion in the first immunoglobulin-like loop. We conclude that bFGF and two forms of the FGF receptor mRNA are expressed in human fetal ovary and uterus. The finding that both bFGF and the FGF receptor are concurrently expressed suggests that bFGF may serve as an autocrine or paracrine modulator during early development of the human reproductive tract.

Base Sequence↗

Mouse hepatitis virus nucleocapsid protein-specific cytotoxic T lymphocytes are Ld restricted and specific for the carboxy terminus.

Infection of mice with the JHM strain of mouse hepatitis virus (MHV) results in an acute encephalomyelitis associated with primary demyelination of the central nervous system. Efforts at understanding the components of the immune response in the development of chronic MHV-induced demyelination have implicated the antibody response and both the CD4+ and CD8+ T cell responses. In this report, we demonstrate that Balb/c (H-2d) mice immunized with the JHM (JHMV) strain of MHV develop a CD8+ cytotoxic T lymphocyte (CTL) response. One population of these virus-specific CTL recognize the nucleocapsid (N) protein. Recombinant vaccinia viruses expressing either the entire N protein or carboxy-terminal deletions were used to determine the number and location of the epitope(s) recognized. The CTLs were found to recognize a peptide contained within the carboxy-terminal 149 amino acids of the N protein. Analysis of infected cell lines expressing transfected major histocompatibility genes demonstrated that the anti-N protein CTLs were restricted exclusively to the Ld molecule. These data provide the first definition of a MHV-specific CTL response directed to a viral protein and suggest that the anti-N protein CTL response is one potential mechanism used by the host to clear JHMV from the central nervous system.

Animals↗

Messenger ribonucleic acid for transforming growth factor-alpha, but not for epidermal growth factor, is expressed in fetal and neonatal mouse brain.

OBJECTIVE: Little is known concerning the presence of transforming growth factor-alpha in fetal and neonatal tissues. Our objective was to analyze messenger ribonucleic acid expression for transforming growth factor-alpha and epidermal growth factor, the structural and biochemical analog of transforming growth factor-alpha in fetal and neonatal murine brain. STUDY DESIGN: Messenger ribonucleic acid was prepared from whole brains of mice from these developmental stages: embryonic days 14, 15, and 17, postnatal days 0, 4, 10, and adult. Polymerase chain reaction was performed on the complementary deoxyribonucleic acid obtained from reverse transcription of messenger ribonucleic acid with transforming growth factor-alpha and epidermal growth factor primers. In addition, ribonuclease protection assay was used to identify transforming growth factor-alpha transcripts. RESULTS: We found messenger ribonucleic acid encoding transforming growth factor-alpha in all stages of development used. Epidermal growth factor messenger ribonucleic acid was not found in any stage. Ribonuclease protection assay confirmed transforming growth factor-alpha transcripts in these tissues. CONCLUSION: Transforming growth factor-alpha may play an autocrine or paracrine role in the differentiation or maintenance of murine fetal and neonatal brains.

Aging↗

Risk factors for coronary heart disease in diabetic and nondiabetic Native Americans. The Strong Heart Study.

The Strong Heart Study is a study of cardiovascular disease and its risk factors among diabetic and nondiabetic Native Americans. The study includes 12 tribes in Arizona, Oklahoma, and North and South Dakota. Phase I, initiated in October 1988, included a mortality survey to determine CVD death rates in individuals 35-74 yr old between 1984 and 1988, and a medical record review to determine rates of myocardial infarction and stroke for individuals ages 45-74 during the same time. In addition, a physical examination was performed on persons 45-74 yr old to measure the prevalence of cardiovascular and peripheral vascular diseases and known and suspected risk factors. In Phase II, CVD mortality and morbidity rates will be determined in the examined cohort by surveillance. CVD risk factors, changes in risk factors over time, and the relationship between risk factors and CVD incidence will be assessed longitudinally. This study provides data on the relative importance of cardiovascular risk factors in nondiabetic and diabetic Native Americans and will provide insight into possible variations in the quantitative or qualitative importance of CVD risk factors among diverse population groups.

Adult↗