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Biomedical subjects

D R Brown

Publications and source records attributed to D R Brown.

At least 217 records · Page 12Linked to original sources
PubMed1995

Predictors of adopting leisure-time physical activity among a biracial community cohort.

Literature on the correlates and predictors of leisure-time physical activity among African-American population is sparse. This cohort study assessed correlates of leisure-time physical activity (specific large muscle activities during the past month at least three times a week) in a biracial population in 1987 and predictors for the adoption of this behavior 4 years later among those initially inactive. Random digit dialing methods were used to identify residents of two South Carolina communities in 1987. In 1991, 3,223 of these residents were resurveyed (62% response rate). In general, the correlates of leisure-time physical activity (education, > or = 12 years; nonsmoking; weight loss behaviors; and physician advice) were similar for each sex and race group. In 1987, the definition of leisure-time physical activity was not met by 831 (54% of 1,542) white women, 374 (76% of 489) African-American women, 586 (59% of 991) white men, and 126 (63% of 201) African-American men. Among those who were inactive in 1987, 22-24% of white adults and African-American men and 14% of African-American women adopted physical activity 4 years later. Twelve years or more of education was a predictor among white women (risk ratio = 1.7, 95% confidence interval 1.2-2.6) and African-American women (risk ratio = 3.1, 95% confidence interval 1.4-6.9), but not among men. Having a physician discuss physical activity was a predictor among white women (risk ratio = 1.9, 95% confidence interval 1.3-2.7), African-American women (risk ratio = 1.7, 95% confidence interval 0.9-3.2), white men (risk ratio = 2.0, 95% confidence interval 1.3-3.1), and African-American men (risk ratio = 2.7, 95% confidence interval 1.0-7.6). These results highlight the strong effect of educational attainment on adoption of healthy behaviors and support the involvement of physicians to promote physical activity among all race and sex groups.

Adult↗
PubMed1995

Sequence determination of human papillomavirus type 6a and assembly of virus-like particles in Saccharomyces cerevisiae.

Human papillomavirus 6a (HPV6a), the most abundant HPV6 subtype, was detected in a vulvar condyloma acuminatum. The complete genome of HPV6a was cloned, and its DNA sequence was shown to be over 97% identical to the HPV6b sequence. Of the eight open reading frames (ORFs) of HPV6a, only the imputed amino acid sequence of the major capsid protein L1 was identical to the corresponding HPV6b sequence; all other HPV6a ORFs showed amino acid changes compared to the HPV6b ORFs. The HPV6a L1 or the L1 + L2 ORFs were expressed in the yeast Saccharomyces cerevisiae. Self-assembly of the L1 capsid protein into virus-like particles (VLPs) was demonstrated both in the L1 as well as L1 + L2 coexpressing yeast strains. Copurification of the L1 and L2 proteins showed complex formation of the L1 and L2 proteins in the yeast-derived VLPs of coexpressing strains.

Adult↗
PubMed1995

Topographical reinnervation of the toad glutaeus muscle by axons of only one spinal nerve.

The toad glutaeus muscle is innervated by axons from two spinal nerves. Following regeneration from nerve lesion, axonal reinnervation from both spinal nerves remains topographically selective. The aim of the present experiments was to determine whether axons from one spinal nerve (nerve 9) would topographically reinnervate the glutaeus muscle in the absence of innervation from the other spinal nerve (nerve 8). Glycogen depletion of single motor units showed that nerve 9 axons are topographically selective when reinnervating the muscle alone. The synapses formed are stronger in topographically correct locations even in the absence of nerve 8 innervation. The distinction between the territory innervated by rostral and caudal nerve 9 axons arises independently of the presence of nerve 8 axons.

Animals↗
PubMed1995

N-terminal 130 amino acids of MDM2 are sufficient to inhibit p53-mediated transcriptional activation.

The human oncoprotein MDM2 binds with the tumor suppressor p53 and inhibits p53-directed transactivation. In this report we show that deletion of 336 amino acids from the C-terminus of human MDM2 does not decrease its efficiency to bind p53 in vivo and inhibit p53-directed transactivation. Even further deletion of MDM2 from the C-terminus up to amino acid 131 does not reduce its ability to inhibit p53-mediated transactivation. Since deletion up to amino acid 131 also deletes many antigenic sites of MDM2 and the truncated protein cannot be immunoprecipitated by the antibodies available to us, two internal deletions were made to define the p53-interaction domain. Internal deletion of four amino acids beginning at 110 residue (amino acids 110 to 113) did not reduce p53-binding or inhibition of p53-directed transactivation whereas internal deletion of amino acids 60 to 65 reduces but does not abolish these activities. Sequential deletion of amino acids from the N-terminus leads to sequential destruction of p53-binding and inhibition of transactivation capability of MDM2. Fourteen amino acids can be deleted from this end without any reduction of these activities. Deletion of 28 N-terminal amino acids residues drastically reduces, but does not abolish the p53-binding ability of the protein, as well as inhibition of p53-directed transactivation. Deletion of 58 amino acids from the N-terminus of the oncoprotein abolishes its ability to bind p53 in vivo and to inhibit p53-directed transactivation. These results locate the p53-binding domain of MDM2 within amino acids 14 to 154 and inhibition of transactivation domains of MDM2 within amino acid residues 14 to 130 suggesting possible p53-independent biological functions of the 491 amino acid long oncoprotein.

Humans↗
PubMed1995

Taxonomic analysis of the tortoise mycoplasmas Mycoplasma agassizii and Mycoplasma testudinis by 16S rRNA gene sequence comparison.

The nucleotide sequences of the 16S rRNA genes of two mycoplasmas, Mycoplasma agassizii (proposed sp. nov.) and Mycoplasma testudinis, isolated from tortoises were determined and used for taxonomic comparisons. Signature nucleotide sequence motifs and overall sequence similarities to other mollicutes positioned these mycoplasmas in the M. hyorhinis and M. pneumoniae phylogenetic groups, respectively. A third, previously unrecognized tortoise mycoplasma was detected by 16S rRNA gene amplification and sequence analysis and was positioned in the M. fermentans phylogenetic group. The 16S rRNA gene of Acholeplasma laidlawii was similarly detected in a tortoise isolate, showing that diverse mollicutes can share the same family of reptilian host.

Animals↗
PubMed1995

Taxonomy of the feline mycoplasmas Mycoplasma felifaucium, Mycoplasma feliminutum, Mycoplasma felis, Mycoplasma gateae, Mycoplasma leocaptivus, Mycoplasma leopharyngis, and Mycoplasma simbae by 16S rRNA gene sequence comparisons.

The nucleotide sequence of the 16S rRNA gene of eight mycoplasmas isolated from felids was determined and used for taxonomic comparisons. A signature nucleotide sequence motif and overall sequence similarity to other mollicutes positioned Mycoplasma felifaucium, Mycoplasma felis, Mycoplasma leocaptivus, Mycoplasma leopharyngis, and Mycoplasma simbae in the Mycoplasma fermentans phylogenetic group of mollicutes. Mycoplasma arginini and Mycoplasma gateae were positioned in the Mycoplasma hominis phylogenetic group of mollicutes, and Mycoplasma feliminutum was positioned in the phylogenetically distant Acholeplasma group of mollicutes, showing that host family preference does not necessarily derive from bacterial phylogenetic closeness.

Acholeplasma↗
PubMed1995

Protective vaccination with a recombinant fragment of Clostridium botulinum neurotoxin serotype A expressed from a synthetic gene in Escherichia coli.

A completely synthetic gene encoding fragment C, a approximately 50-kDa fragment, of botulinum neurotoxin serotype A was constructed from oligonucleotides. The gene was expressed in Escherichia coli, and full-sized product was produced as judged by Western blot (immunoblot) analysis. Crude extracts of E. coli expressing the gene were used to vaccinate mice and evaluate their survival against challenge with active toxin. Mice given three subcutaneous vaccinations were protected against an intraperitoneal administration of 10(6) 50% lethal doses (ID50) of serotype A toxin. The same mice survived when challenged with 3 LD50 of botulinum toxin serotype E but died when challenged with 10 LD50 of serotype E or 3 LD50 of serotype B. Purified fragment C was compared with the botulinum toxoid vaccine in a vaccination and challenge study. Fragment C was as efficacious in protecting against challenge with active botulinum neurotoxin serotype A as the toxoid vaccine. This recombinant protein product has many properties that make it a good candidate for human use to protect against botulinum toxin.

Animals↗
PubMed1995

Wild-type human p53 transactivates the human proliferating cell nuclear antigen promoter.

The wild-type p53 protein is a transcriptional activator implicated in the control of cellular growth-related gene expression. Here, using a number of different cell lines and transient-transfection-transcription assays, we demonstrate that at low levels, wild-type p53 transactivates the human proliferating cell nuclear antigen (PCNA) promoter. When expressed at a similar level, the tumor-derived p53 mutants did not transactivate the PCNA promoter. We identified a p53-binding site on the human PCNA promoter with which p53 interacts sequence specifically. When placed on a heterologous synthetic promoter, the binding site functions as a wild-type p53 response element in either orientation. Deletion of the p53-binding site renders the PCNA promoter p53 nonresponsive, showing that wild-type p53 transactivates the PCNA promoter by binding to the site. At a higher concentration, wild-type p53 inhibits the PCNA promoter but p53 mutants activate. Transactivation by p53 mutants does not require the p53-binding site. These observations suggest that moderate elevation of the cellular wild-type p53 level induces PCNA production to help in DNA repair.

3T3 Cells↗
PubMed1995

Neuromodulation of ion transport in porcine distal colon: NPY reduces secretory actions of leukotrienes.

Electrical transmural stimulation (ETS) was used to examine the neuroregulation of electrolyte transport in the porcine distal colon. ETS of the colonic mucosa-submucosa mounted in Ussing chambers produced rapid and transient increases in short-circuit current (Isc) that were inhibited 36% by serosal bumetanide, suggesting that a portion of the response may be attributed to Cl secretion. ETS actions were dependent upon stimulus intensity and frequency and were inhibited by tetrodotoxin and omega-conotoxin. Prazosin and pyrilamine had no effect on the mucosal responses to ETS, whereas atropine reduced the responses by 32%. Neuropeptide Y (NPY) also reduced the mucosal responses to ETS up to 60% (half-maximal effective concentration = 17 nM). In addition, the effects of leukotriene C4, previously shown to stimulate Cl secretion via a neuronal pathway, were also inhibited by NPY. These results indicate that cholinergic submucosal neurons play a role in the regulation of epithelial ion transport and that NPY acts as an inhibitory neuromodulator, particularly on leukotriene-sensitive neurons in the porcine distal colon.

Animals↗
PubMed1995

Apolipoprotein E deficiency in mice: gene replacement and prevention of atherosclerosis using adenovirus vectors.

Apolipoprotein E (apoE)-deficient mice develop marked hyperlipidemia as well as atherosclerosis and thus are an excellent animal model for evaluating the potential for gene therapy in human genetic dyslipoproteinemias. Recombinant adenovirus containing either human apoE (rAdv.apoE) or the reporter gene luciferase (rAdv.luc) were generated and infused intravenously in apoE-deficient mice with preinfusion plasma total cholesterol of 644 +/- 149 mg/dl an cholesterol rich VLDL/IDL. After a single infusion of rAdv.apoE, plasma concentrations of human apoE ranging from 1.5 to 650 mg/dl were achieved. Adenovirus-mediated apoE replacement resulted in normalization of the lipid and lipoprotein profile with markedly decreased total cholesterol (103 +/- 18mg/dl), VLDL, IDL, and LDL, as well as increased HDL. Measurement of aortic atherosclerosis 1 mo after adenoviral infusion demonstrated a marked reduction in the mean lesion area of mice infused with rAdv.apoE (58 +/- 8 x 10(3) microns2) when compared with control mice infused with rAdv.luc (161 +/- 10 x 10(3) microns2; P < 0.0001). Thus, apoE expression for 4 wk was sufficient to markedly reduce atherosclerosis, demonstrating the feasibility of gene therapy for correction of genetic hyperlipidemias resulting in atherosclerosis. The combined use of adenovirus vectors and the apoE-deficient mouse represents a new in vivo approach that will permit rapid screening of candidate genes for the prevention of atherosclerosis.

Adenoviridae↗
PubMed1995

Major depression in a community sample of African Americans.

OBJECTIVE: This study examined demographic, sociocultural, familial background, and health-related risk factors for major depression in a community sample of African Americans. METHOD: Data came from a probability sample of 865 urban African American adults, 20 years of age and older, who were given the structured National Institute of Mental Health Diagnostic Interview Schedule. RESULTS: The findings indicated a 1-year prevalence of 3.1% for major depression. While age, residential mobility, health status, and stressful life events were significantly associated with major depression, none of the sociocultural and family background factors were. The strongest predictors of major depression were poor or fair health and being 20-29 years of age. In terms of treatment for depression, persons with major depression were significantly more likely than those without to engage in help seeking. However, only 11.1% actually saw a psychiatrist or other mental health professional, and 7.4% saw no one. CONCLUSIONS: Young age and fair to poor physical health appear to be more powerful risk factors for major depression among African Americans than other demographic, sociocultural, and family background variables. Few African Americans with major depression actually receive clinical treatment for this illness. The results further suggest the need to increase awareness of major depression among general practitioners and to target outreach to African American communities.

Adult↗
PubMed1995

Oxandrolone therapy in constitutionally delayed growth and puberty. Bio-Technology General Corporation Cooperative Study Group.

BACKGROUND: Male adolescents with constitutional delay of growth and puberty may have significant psychosocial difficulties related to their sexual immaturity and short stature. The purpose of this study was to test the hypothesis that 1 year of oxandrolone therapy would increase growth velocity and thereby improve psychosocial functioning in boys with constitutional delay of growth and pubertal development. METHODS: Forty boys (ages 11 to 14.7 years) with delayed pubertal development and short stature were recruited from the pediatric endocrine clinics of 14 medical centers. The boys were randomized using a block design stratified for age to receive either oxandrolone (0.1 mg/kg daily for 1 year) or an identical-appearing placebo tablet, using a double-masked design. RESULTS: Growth velocity in the oxandrolone-treated boys was significantly greater than in the control boys (9.5 vs 6.8 cm/y). Likewise, the mean height SD score increased 0.41 in the oxandrolone group, whereas it decreased 0.03 in the control group. Those in the oxandrolone group gained 2.4 kg more than those in the placebo group. Mean predicted adult heights did not change in either group. The mean rates of pubertal progression were equivalent in both groups. Self-image (Piers-Harris Self Concept Scale) and social competence (Child Behavior Profile) were normal at baseline in both groups and did not change significantly over the course of the study in either group. No complications of oxandrolone therapy were identified. CONCLUSIONS: This randomized, placebo-controlled trial demonstrates that low-dose oxandrolone can increase both height and weight velocity in boys with delayed puberty safely. Under the conditions of this study, however, the increased growth velocity in the oxandrolone-treated boys was not associated with a greater improvement in psychosocial status compared with the control boys.

Adolescent↗
PubMed1995

Chronic psychological effects of exercise and exercise plus cognitive strategies.

Psychological changes associated with 16-wk moderate and low intensity exercise training programs, two of which possessed a cognitive component, were evaluated. Subjects were healthy, sedentary adults, 69 women (mean age = 54.8 +/- 8.3 yr) and 66 men (mean age = 50.6 +/- 8.0 yr). Participants were randomly assigned to a control group (C), moderate intensity walking group (MW), low intensity walking group (LW), low intensity walking plus relaxation response group (LWR), or mindful exercise (ME) group-a Tai Chi type program. Women in the ME group experienced reductions in mood disturbance (tension, P < 0.01; depression, P < 0.05; anger, P < 0.008; confusion, P < 0.02; and total mood disturbance, P < 0.006) and an improvement in general mood (P < 0.04). Women in the MW group noted greater satisfaction with physical attributes (body cathexis, P < 0.03), and men in MW reported increased positive affect (P < 0.006). No other differences were observed between groups on measures of mood, self-esteem, personality, or life satisfaction. Equivocal support is provided for the hypothesis that exercise plus cognitive strategy training programs are more effective than exercise programs lacking a structured cognitive component in promoting psychological benefits.

Adaptation, Psychological↗
PubMed1995

Isolation of mycoplasmas from prairie voles (Microtus ochrogaster).

A new species of mycoplasmas was isolated from the lungs and nasopharyngeal washings of prairie voles (Microtus ochrogaster). Clinical signs of disease and microscopic lesions were not observed at the time of this isolation. The organism was cultured in SP4 medium; it grew aerobically, anaerobically, and in 5% CO2 in 5 to 7 days, and fermented glucose. Transmission electron microscopy revealed the organism to lack a cell wall and to have typical mycoplasmal ultrastructural morphology. The complete nucleotide sequence of the 16S rRNA gene from an isolate was determined by amplification with polymerase chain reaction and by sequencing with the dideoxynucleotide chain termination method. The sequence did not match any known sequences in the GenBank of the National Institutes of Health. The 16S rRNA sequence of the organism, Mycoplasma volis (proposed species novum), is unique and most closely resembles that of M. muris and M. iowae. Because this vole colony will be housed in rooms with other rodents, pathogenicity studies of this new species of mycoplasmas in mice and rats are underway.

Animals↗
PubMed1994

Cell-type-specific induction of the UL9 gene of HSV-1 by cell signaling pathway.

The origin-binding protein, encoded by the UL9 gene of herpes simplex virus-1 (HSV-1), has the properties of an initiator of DNA replication. In this communication, we report that the UL9 promoter contains a cAMP-response element (CRE). Transient expression analyses show that dibutyryl cyclic AMP, known to elevate intracellular cAMP level, can induce the UL9 promoter in a rat pheochromocytoma cell line (PC12) but not in a non-neuronal human cell line (HeLa). Interestingly, a transcription factor that increases expression of a neuropeptide gene by interacting with CRE can also activate the UL9 promoter independent of cell type. Thus, our data suggest that extracellular stimuli, capable of interacting with the signaling pathway in neuronal cells, can activate UL9 gene expression, and different proteins may regulate UL9 expression in different cell types.

Animals↗
PubMed1994

Mouse cortical cells lacking cellular PrP survive in culture with a neurotoxic PrP fragment.

To elucidate whether the neurotoxic effect of a prion protein fragment (PrP106-126) is in some way mediated by the cellular isoform of the prion protein (PrPC), dissociated cortical cell cultures were prepared from mice in which the PrP gene had been disrupted (PrP0/0 mice). Cell survival after 10 days in culture was tested with an MTT assay. PrP106-126 applied every second day for 10 days in cultures from normal mice resulted in the death of 34% more cells than in untreated cells. When PrP106-126 was applied to cultures from mice lacking PrPC expression, survival was equal to or greater than that of untreated control cells. These results support the notion that expression of PrPC is required for the neurotoxic effect of PrP106-126.

Amino Acid Sequence↗
PubMed1994

Colocalization of human papillomavirus type 11 E1[symbol: see text]E4 and L1 proteins in human foreskin implants grown in athymic mice.

The most abundant viral mRNA species in tissues infected with HPV 11 consists of two exons, joining a short segment of open reading frame (ORF) E1 to ORF E4, potentially encoding an protein of 10 kDa. E4 gene products have previously been identified by immunohistochemistry in human tissues infected with HPV 1 and HPV 16, and in HPV 11-infected raft cultures. The E1[symbol: see text]E4 mRNA is produced in abundance in HPV 11-infected human foreskin implants grown in athymic mice. In contrast, the L1 mRNA is present at low levels and appears late in the course of infection. To characterize the relationship of these proteins, polyclonal rabbit antisera were produced against bacterially expressed HPV 11 trpE/E1[symbol: see text]E4 and trpE/L1 fusion proteins and tested in an immunohistochemical assay of paraffin-embedded sections of HPV 11-infected human foreskin tissue fixed with 10% buffered formalin phosphate or zinc formalin. In sections fixed with either fixative, the anti-L1 serum stained nuclei of cells in the upper spinous and granular layers. In contrast, the anti-E1[symbol: see text]E4 serum stained the cell membrane and, to a lesser degree, the cytoplasm of cells in the upper spinous and granular layers of tissue fixed with zinc formalin, but not 10% buffered formalin phosphate. In sections treated with both the E1[symbol: see text]E4 and L1 antisera, cell membrane staining occurred in the same cells that exhibited nuclear staining. The HPV 11 E1[symbol: see text]E4 protein appears to be a cell membrane-associated protein. Expression of the HPV 11 E1[symbol: see text]E4 and L1 proteins may be influenced by similar factors in differentiating cells.

Animals↗