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Biomedical subjects

J L Brown

Publications and source records attributed to J L Brown.

At least 55 records · Page 3Linked to original sources

Hormone secretion in the asian elephant (Elephas maximus): characterization of ovulatory and anovulatory luteinizing hormone surges.

In the elephant, two distinct LH surges occur 3 wk apart during the nonluteal phase of the estrous cycle, but only the second surge (ovLH) induces ovulation. The function of the first, anovulatory surge (anLH) is unknown, nor is it clear what regulates the timing of these two surges. To further study this observation in the Asian elephant, serum concentrations of LH, FSH, progesterone, inhibin, estradiol, and prolactin were quantified throughout the estrous cycle to establish temporal hormonal relationships. To examine long-term dynamics of hormone secretion, analyses were conducted in weekly blood samples collected from 3 Asian elephants for up to 3 yr. To determine whether differences existed in secretory patterns between the anLH and ovLH surges, daily blood samples were analyzed from 21 nonluteal-phase periods from 7 Asian elephants. During the nonluteal phase, serum LH was elevated for 1-2 days during anLH and ovLH surges with no differences in peak concentration between the two surges. The anLH surge occurred 19.9+/-1.2 days after the end of the luteal phase and was followed by the ovLH surge 20.8+/-0.5 days later. Serum FSH concentrations were highest at the beginning of the nonluteal phase and gradually declined to nadir concentrations within 4 days of the ovLH surge. FSH remained low until after the ovLH surge and then increased during the luteal phase. Serum inhibin concentrations were negatively correlated with FSH during the nonluteal phase (r = -0.53). Concentrations of estradiol and prolactin fluctuated throughout the estrous cycle with no discernible patterns evident. In sum, there were no clear differences in associated hormone secretory patterns between the anLH and ovLH surge. However, elevated FSH at the beginning of the nonluteal phase may be important for follicle recruitment, with the first anLH surge acting to complete the follicle selection process before ovulation.

Animals↗

The DNA-binding polycomb group protein pleiohomeotic mediates silencing of a Drosophila homeotic gene.

Polycomb group (PcG) proteins repress homeotic genes in cells where these genes must remain inactive during development. This repression requires cis-acting silencers, also called PcG response elements. Currently, these silencers are ill-defined sequences and it is not known how PcG proteins associate with DNA. Here, we show that the Drosophila PcG protein Pleiohomeotic binds to specific sites in a silencer of the homeotic gene Ultrabithorax. In an Ultrabithorax reporter gene, point mutations in these Pleiohomeotic binding sites abolish PcG repression in vivo. Hence, DNA-bound Pleiohomeotic protein may function in the recruitment of other non-DNA-binding PcG proteins to homeotic gene silencers.

Animals↗

Rates of lower-extremity amputation and arterial reconstruction in the United States, 1979 to 1996.

OBJECTIVES: This report describes trends in the rates of lower-extremity amputation and revascularization procedures and vascular disease risk factors. METHODS: We analyzed trends in National Hospital Discharge Survey data for 1979 through 1996 and in National Health Interview Study data for 1983 through 1994. RESULTS: Despite a decline between 1983/84 and 1991/92, by 1995/96 the rate of major amputation had increased 10.6% since 1979/80. The earlier 12-year decline was positively correlated with reductions in the prevalence of smoking (r = 0.88, P < .0001), hypertension (r = 0.65, P = .02), and heart disease (r = 0.73, P = .007), but not diabetes (r = -0.33, P = .29). During the 1980s, amputation and angioplasty rates were inversely correlated (r = -0.75, P = .001), but the decline in amputation rates occurred before the increase in angioplasty. The major amputation rate, which has increased since 1993, was 24.95 per 100,000 people in 1996. CONCLUSIONS: Major amputation rates fell in the years following the diffusion of distal bypass surgery but before the widespread use of peripheral angioplasty. Because disease prevalence and primary amputation rates are unknown, it is difficult to estimate the contribution of recent improvements in vascular surgery to limb preservation.

Adult↗

Effects of drainage and soil organic content on growth of Spartina alterniflora (Poaceae) in an artificial salt marsh mesocosm.

An artificial salt marsh mesocosm was constructed using 680-L polypropylene tanks to determine the effect of soil drainage depth and organic content on growth and rhizome proliferation of the salt marsh smooth cordgrass Spartina alterniflora. Soil drainage depth had no effect on accumulation of aerial or subsurface plant tissue, but tanks that had 2.5% soil organic content supported enhanced aerial tissue and rhizome growth compared to tanks that contained sand alone. We propose a mathematical model for predicting the mass of photosynthetically significant leaf tissue without cutting and drying leaves. Implications of these findings for salt marsh creation projects are discussed.

Journal Article↗

An integrated pharmacokinetic and pharmacodynamic study of arsenite action. 1. Heme oxygenase induction in rats.

Rat heme oxygenase (HO) activity was used as a specific (among forms of arsenic) and sensitive biomarker of effect for orally administered sodium arsenite in rats. Time course studies showed that HO was induced in rat liver from 2 to 48 h in both rat liver and kidney. Hepatic and renal inorganic arsenic (iAs) concentrations were high at times preceding a high degree of HO induction. At times following pronounced HO induction, tissue dimethylarsinic acid concentrations were high. Dose-response studies of arsenite showed substantial HO induction in liver at doses of 30 micromol/kg and higher and in the kidney at doses of 100 micromol/kg and higher. Doses of 10 (in liver) and of 30 micromol/kg (in kidney) sodium arsenite given by gavage did not significantly induce rat HO activity. Speciation of tissue total arsenic into iAs, methylarsonic acid (MMA), and dimethylarsinic acid (DMA) permits us to link tissue iAs and HO enzyme induction. There was a linear relationship between tissue inorganic arsenic (iAs) concentration and tissue HO in individual rats (r(2) = 0.780 in liver and r(2) = 0.797 in kidney). Nonlinear relationships were observed between administered arsenite dose and either liver or kidney iAs concentration. Overall, there was a sublinear relationship between administered arsenite and biological effect in rats. Teratogenesis Carcinog. Mutagen. 19:385-402, 1999. Published 1999 Wiley-Liss, Inc.

Administration, Oral↗

Fecal cortisol metabolite analysis for noninvasive monitoring of adrenocortical function in the cheetah (Acinonyx jubatus).

A radioimmunoassay was validated for quantifying excreted cortisol metabolites in cheetah (Acinonyx jubatus) feces. High-performance liquid chromatography analysis indicated that immunoreactivity was associated with a water-soluble metabolite in fecal extracts from males and females. None of the immunoreactivity corresponded with free cortisol or corticosterone but rather was associated with a more polar, unidentified metabolite. To determine the biologic relevance of excreted immunoreactive cortisol metabolites, cheetahs were exposed to a variety of situations anticipated to increase cortisol secretion. First, to assess acute changes in adrenal activity, adrenocorticotropic hormone (ACTH; 400 IU i.m.) was administered to two adult males and two adult females. Pre-ACTH baseline serum cortisol and fecal cortisol metabolite concentrations varied among individuals. Serum cortisol concentrations were elevated above baseline within 10 min of ACTH injection, followed by corresponding increases in fecal cortisol metabolite concentrations (690-4,194% above baseline) 48 hr later in three of four cheetahs. In the fourth cheetah, a smaller increase (334% above baseline) in fecal cortisol metabolite excretion was observed 96 hr after ACTH injection. Seven cheetah females also were subjected to a variety of potentially stressful manipulations, including immobilization, translocation, and introduction to a male to assess the ability of this technique to detect physiologic changes in adrenal activity. Increased fecal corticoid metabolite excretion was observed 24-72 hr after exposure to these exogenous stressors. Results indicate that adrenocortical activity can be monitored noninvasively in the cheetah through analysis of these metabolites. This technique could be valuable for evaluating, and thus optimizing, environmental and management conditions and for investigating the role of stress in disease pathogenesis and the usually poor reproductive performance of this species in captivity.

Acinonyx↗

Anesthesiology.

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Anesthesiology↗

Thrombospondin-1 is elevated with both intimal hyperplasia and hypercholesterolemia.

BACKGROUND: Thrombospondin-1 (TSP-1) is important in platelet adhesion and aggregation, inflammation, cell to cell interaction, angiogenesis, and smooth muscle cell (SMC) proliferation. TSP-1 expression increases rapidly with injury. Therefore, we hypothesize that TSP-1 may play a role in the development of intimal hyperplasia (IH). The purpose of this study is to examine the interaction between cholesterol and TSP-1 on SMC proliferation and to quantitatively assess TSP-1 expression in an established model of IH, with and without underlying cholesterol-induced atherosclerosis. MATERIALS AND METHODS: In vitro, rabbit aortic SMC culture studies were performed to see the effect of TSP-1 antibodies on PDGF and, separately, cholesterol-induced SMC proliferation. In vivo, 23 rabbits were fed either a regular or a high-cholesterol diet. Hypercholesterolemia was confirmed by measurement of serum levels. Subsets underwent intraluminal aortic injury. Aortas were harvested 8-10 weeks later. Arterial wall TSP-1 was evaluated immunohistochemically and quantified by computer image analysis. RESULTS: In vitro, TSP-1 antibodies were able to inhibit PDGF and cholesterol-induced SMC proliferation (P < 0.05). In vivo, TSP-1 was found predominantly in the extracellular matrix in the rabbit aorta. IH was uniformly seen status-post angioplasty. Hyperplasia was more prominent in samples from hypercholesterolemic animals. ANOVA and Student's t test analyses demonstrated significantly more TSP-1 in the high-cholesterol/angioplasty group than in all other groups (P = 0.0006 vs regular diet/no angioplasty group). CONCLUSIONS: These data are consistent with the hypothesis that TSP-1 contributes to the development of IH. This study suggests that injured arteries in hypercholesterolemic atherosclerotic rabbits overexpress TSP-1.

Animals↗

Yeast Skn7p activity is modulated by the Sln1p-Ypd1p osmosensor and contributes to regulation of the HOG pathway.

Activation and control of the yeast HOG (High Osmolarity Glycerol) MAP kinase cascade is accomplished, in part, by a two-component sensory-response circuit comprised of the osmosensing histidine protein kinase Sln1p, the phospho-relay protein Ypd1p, and the response regulator protein Ssk1p. We found that deletion of SLN1 and/or YPD1 reduces reporter gene transcription driven by a second two-component response regulator -- Skn7p. The effect of sln1delta and ypd1delta mutations upon Skn7p activity is dependent on a functional two-component phosphorylation site (D427) in Skn7p, suggesting that Sln1p and Ypd1p may act as phosphodonors for Skn7p. We also observed that loss of PTC1 (a protein serine/threonine phosphatase implicated in negative control of the HOG pathway) in a skn7delta background results in severely retarded growth and in morphological defects. Deletion of either PBS2 or HOG1 alleviates the slow growth phenotype of ptc1delta skn7delta cells, suggesting that Skn7p may participate, in concert with known regulatory components, in modulating HOG pathway activity. The contribution of Skn7p to HOG pathway regulation appears to be modulated by the receiver domain, since non-phosphorylatable Skn7pD427N is unable to fully restore growth to ptc1/skn7 cells.

Calcium-Calmodulin-Dependent Protein Kinases↗

The Drosophila Polycomb group gene pleiohomeotic encodes a DNA binding protein with homology to the transcription factor YY1.

Genes of the Polycomb group (PcG) of Drosophila encode proteins necessary for the maintenance of transcriptional repression of homeotic genes. PcG proteins are thought to act by binding as multiprotein complexes to DNA through Polycomb group response elements (PREs); however, specific DNA binding has not been demonstrated for any of the PcG proteins. We have identified a sequence-specific DNA binding protein that interacts with a PRE from the Drosophila engrailed gene. This protein (PHO) is a homolog of the ubiquitous mammalian transcription factor Yin Yang-1 and is encoded by pleiohomeotic, a known member of the PcG. We propose that PHO acts to anchor PcG protein complexes to DNA.

Amino Acid Sequence↗

Resolving conflict creatively: evaluating the developmental effects of a school-based violence prevention program in neighborhood and classroom context.

This study evaluated the short-term impact of a school-based violence prevention initiative on developmental processes thought to place children at risk for future aggression and violence and examined the influence of classroom and neighborhood contexts on the effectiveness of the violence prevention initiative. Two waves of developmental data (fall and spring) were analyzed from the 1st year of the evaluation of the Resolving Conflict Creatively Program (RCCP), which includes 5053 children from grades two to six from 11 elementary schools in New York City. Three distinct profiles of exposure to the intervention were derived from Management Information System (MIS) data on between classroom differences in teacher Training and Coaching in RCCP, Classroom Instruction in RCCP, and percentages of students who are Peer Mediators. Developmental processes that place children at risk were found to increase over the course of the school year. Children whose teachers had a moderate amount of training and coaching from RCCP and who taught many lessons showed significantly slower growth in aggression-related processes, and less of a decrease in competence-related processes, compared to children whose teachers taught few or no lessons. Contrary to expectation, children whose teachers had a higher level of training and coaching in the RCCP but taught few lessons showed significantly faster growth over time in aggressive cognitions and behaviors. The impact of the intervention on children's social cognitions (but not on their interpersonal behaviors) varied by context. Specifically the positive effect of High Lessons was dampened for children in high-risk classrooms and neighborhoods. Implications for future research on developmental psychopathology in context and for the design of preventive interventions are discussed.

Achievement↗

Immunochemical detection of hepatic cocaine-protein adducts in mice.

Cocaine is capable of producing hepatic necrosis in laboratory animals and humans. Studies in mice indicate that N-oxidative metabolism of cocaine is required for hepatotoxicity and have suggested that toxicity may result from the adduction of proteins by cocaine-reactive metabolites. To aid in identifying protein targets for cocaine-reactive metabolites, an antibody was raised in rabbits immunized with cocaine linked via the tropane nitrogen to a carrier protein (bovine serum albumin). Hepatic proteins from cocaine-treated mice (ICR males, 50 mg of cocaine/kg of body weight, ip) and saline-treated controls were prepared from whole liver homogenate or following subcellular fractionation, and Western blot analyses of hepatic proteins using this antibody were conducted following one- and two-dimensional SDS-PAGE. Analysis of liver homogenate from cocaine-treated mice revealed major protein targets with approximate molecular masses of 20 kDa (pI = 6.0), 44 kDa (two proteins with pI's of 5.0 and 7.0), 52-54 kDa (pI = 4.5), and 64 kDa (pI = 5.5). These specific protein targets were shown to be localized in the mitochondria and microsomes. Several minor bands of immunoreactivity were also seen in mice treated with cocaine, but not in saline-treated controls. Pretreatment of mice with the P450 inhibitor SKF 525A diminished or eliminated the formation of these cocaine-protein adducts. Liver sections from cocaine-treated mice immunostained using the antibody indicated the presence of cocaine-adducted proteins in the centrilobular and midzonal regions of the lobule, corresponding to areas of hepatocyte swelling and necrosis. This study indicates that reactive metabolites from cocaine bind to discrete proteins in specific regions of the liver, consistent with a role for protein adduction in cocaine hepatotoxicity.

Animals↗

Linkage and association between inflammatory bowel disease and a locus on chromosome 12.

Genetic epidemiological studies have shown that genetic factors are important in the pathogenesis of the idiopathic inflammatory bowel diseases (IBD), Crohn disease (CD), and ulcerative colitis (UC). A genome screen in the United Kingdom found linkage of IBD to a 41-cM region of chromosome 12, surrounding D12S83. We aimed to replicate this linkage and to narrow the region of interest. Nonparametric linkage analyses at microsatellites surrounding D12S83 were performed in 122 North American Caucasian families containing 208 genotyped IBD-affected relative pairs. Transmission/disequilibrium tests (TDTs) were also performed. We confirmed that IBD is linked to chromosome 12 (peak GENEHUNTER-PLUS LOD* score 2.76 [P = .00016] between D12S1724 and D12S90). The evidence for linkage is contributed by both the group of CD-affected relative pairs (peak GENEHUNTER-PLUS LOD* score 1.79 [P = .0021] between D12S1724 and D12S90) and the group of UC-affected relative pairs (peak GENEHUNTER-PLUS LOD* score 1.82 [P = .0019] at D12S335). The TDT is positive at the D12S83 locus (global chi2 = 16.41, 6 df, P = .012). In conclusion, we have independently confirmed linkage of IBD to the chromosome 12 region that we investigated. A positive TDT at D12S83 suggests that we have greatly narrowed the chromosome 12 region that contains an IBD locus.

Chromosomes, Human, Pair 12↗

Novel Cdc42-binding proteins Gic1 and Gic2 control cell polarity in yeast.

Cdc42p, a Rho-related GTP-binding protein, regulates cytoskeletal polarization and rearrangements in eukaryotic cells, but the effectors mediating this control remain unknown. Through the use of the complete yeast genomic sequence, we have identified two novel Cdc42p targets, Gic1p and Gic2p, which contain consensus Cdc42/Rac interactive-binding (CRIB) domains and bind specifically to Cdc42p-GTP. Gic1p and Gic2p colocalize with Cdc42p as cell polarity is established during the cell cycle and during mating in response to pheromones. Cells deleted for both GIC genes exhibit defects in actin and microtubule polarization similar to those observed in cdc42 mutants. Finally, the interaction of the Gic proteins and Cdc42p is essential, as mutations in the CRIB domain of Gic2p that eliminate Cdc42p binding disrupt Gic2p localization and function. Thus, Gic1p and Gic2p define a novel class of Cdc42p targets that are specifically required for cytoskeletal polarization in vivo.

Adaptor Proteins, Signal Transducing↗

Acid habituation of Escherichia coli and the potential role of cyclopropane fatty acids in low pH tolerance.

A reversible adaptive tolerance to low pH termed 'acid habituation' is demonstrated for five strains of Escherichia coli. Superimposed upon the intrinsic acid tolerance of individual strains, acid habituation significantly enhances the survival of exponential phase cultures exposed to a lethal acid challenge (pH 3.0), and minimises inter-strain variability in acid tolerance. The fatty acid composition of acid habituated, non-habituated, and de-habituated exponential phase cultures is also reported. During acid habituation, monounsaturated fatty acids (16:1 omega 7c and 18:1 omega 7c) present in the phospholipids of E. coli are either converted to their cyclopropane derivatives (cy17:0 and cy19:0), or replaced by saturated fatty acids. The acid tolerance of individual strains of E. coli appears to be correlated with membrane cyclopropane fatty acid content and, thus, it is postulated that increased levels of cyclopropane fatty acids may enhance the survival of microbial cells exposed to low pH. The results presented illustrate the remarkable capacity of E. coli to adapt to environmental challenges, and have significant implications for the survival of spoilage and pathogenic bacteria, and hence for food safety.

Adaptation, Physiological↗

Pharmacokinetics and ovarian-stimulatory effects of equine and human chorionic gonadotropins administered singly and in combination in the domestic cat.

Pregnancy success and embryo survival are low with the use of assisted reproduction in felids treated with exogenous gonadotropins. In this study, the pharmacokinetics and ovarian-stimulatory effects of eCG and hCG were evaluated in the domestic cat. Catheterized anestrual queens (n = 4 per treatment [Trt] group) were given 100 IU eCG i.v. (Trt 1), 100 IU eCG i.m. (Trt 2), 75 IU hCG i.v. (Trt 3), 75 IU hCG i.m. (Trt 4), or 100 IU eCG i.m. followed 80 h later by 75 IU hCG i.m. (Trt 5). Blood samples were collected at 0, 5, 30, and 60 min and 4, 8, 12, 24, 36, 48, 72, 96, 120, 144, and 168 h postinjection, and serum samples were analyzed for estradiol-17beta, progesterone, eCG, and hCG. Pharmacokinetic traits (volume of distribution, Vd; elimination half-life, t1/2beta; clearance rate, Clr) were calculated for eCG and hCG. When i.v. and i.m. administration were compared, no differences (p > 0.05) were observed in follicle or corpus luteum (CL) number or hormone concentrations for queens receiving eCG or hCG alone. Number of mature ovarian follicles (> or = 2 mm diameter) observed at 168 h postinjection did not differ (p > 0.05) for eCG (mean +/- SEM, 10.5 +/- 2.0) vs. hCG (11.1 +/- 3.0), indicating that these were equally effective in inducing follicular growth. In most queens (> 90%) given single gonadotropins (i.m. or i.v.), eCG and hCG persisted in circulation for at least 120 h and 96 h after injection, respectively, reflecting similar (p > 0.05) pharmacokinetic (i.v.) values for Vd (eCG, 91.4 +/- 24.8 ml/kg; hCG, 59.1 +/- 7.9 ml/kg), t1/2beta (eCG, 23.0 +/- 2.4 h; hCG, 22.9 +/- 4.1 h), and Clr (eCG, 2.7 +/- 0.5 ml/h per kg; hCG, 1.8 +/- 0.1 ml/h per kg). Sequential treatment with eCG+hCG did not affect (p > 0.05) the t1/2beta of individual gonadotropins. In summary, eCG and hCG have comparable pharmacokinetics and ovarian-stimulatory activity when administered alone to the domestic cat. These findings suggest that hCG promotes the ancillary follicle formation that is frequently observed after ovulation in cats treated with eCG+hCG regimens, possibly disrupting the maternal environment and decreasing fecundity following assisted reproductive procedures.

Animals↗