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Biomedical subjects

D R Brown

Publications and source records attributed to D R Brown.

At least 91 records · Page 5Linked to original sources
PubMed2000

Expression of nociceptin/OFQ receptor and prepro-nociceptin/OFQ in lymphoid tissues.

This study was undertaken to examine the presence of functional nociceptin/orphanin FQ (N/OFQ) receptors in the immune system. Receptor mRNA signals were detected by RT-PCR in porcine thymus, lymph nodes, spleen and freshly-isolated splenocytes; the distribution of prepro-nociceptin/-orphanin FQ (PP-N/-OFQ) mRNA was similar, with the exception of lymph nodes. However, specific [(3)H]nociceptin binding sites were not detected in rat or porcine lymphoid tissues, and 0.1-100 nM nociceptin had no effect on forskolin-stimulated cyclic AMP concentrations in porcine splenocytes. Thus, it appears that nociceptin/orphanin FQ receptor mRNA, but not a functional receptor protein is expressed in the immune system.

Animals↗
PubMed2000

Promoting physical activity in rural communities: walking trail access, use, and effects.

INTRODUCTION: Environmental and policy approaches to promote physical activity, such as walking trail construction and promotion, are being widely recommended, yet sparse data exist on their effectiveness. In conjunction with ongoing community-intervention projects in Missouri, walking trails are being built, promoted, and evaluated. Objectives include determining: (1) patterns and correlates of walking, (2) the availability of places to walk and perform other forms of physical activity, (3) the extent of walking trail use and possible effects on rates of physical activity, and (4) attitudes toward the trails and their uses. METHODS: In 12 rural counties in Missouri we used a cross-s ectional telephone survey to ask a population-based sample of residents aged >18 years (n=1269) some standard and specially developed questions about walking behaviors, knowledge, and attitudes. RESULTS: Only 19.5% of respondents were classified as regular walkers. About one third of respondents (36.5%) reported having access to walking trails in their area, and 50.3% reported having access to indoor facilities for exercise. Among persons with access to walking trails, 38.8% had used the trails. Groups who were more likely to have used the walking trails included women, persons with more education, those making $35,000 or more per year, and regular walkers. Among persons who had used the trails, 55.2% reported they had increased their amount of walking since they began using the trail. Women and persons with a high school education or less were more than twice as likely to have increased the amount of walking since they began using the walking trails. CONCLUSIONS: Walking trails may be beneficial in promoting physical activity among segments of the population at highest risk for inactivity, in particular women and persons in lower socioeconomic groups.

Adolescent↗
PubMed2000

Recruitment and retention of minority women in cancer screening, prevention, and treatment trials.

Researchers are giving greater attention to the recruitment and retention of minority women in clinical studies because of their historical underrepresentation, despite their greater morbidity and mortality for many conditions. Using findings from four studies, this article examines documented barriers to the recruitment and retention of minority women to clinical cancer research and discusses effective recruitment strategies. Among the major barriers to recruitment were lack of awareness, lack of transportation, interference with work/family responsibilities, financial costs, negative side effects, and burdensome procedures. Effective recruitment strategies focused on using culturally targeted mass mailings and media presentations based on acquiring an understanding of the minority community. Recommendations are made for further study and implementation.

Clinical Trials as Topic↗
PubMed2000

Trehalose expression confers desiccation tolerance on human cells.

Many organisms that withstand desiccation express the disaccharide trehalose. We have now expressed the otsA and otsB genes of Escherichia coli, which encode trehalose biosynthetic enzymes, in human primary fibroblasts using a recombinant adenovirus vector. Infected cells produced increased amounts of trehalose with increasing multiplicity of infection (MOI). Human primary fibroblasts expressing trehalose could be maintained in the dry state for up to five days. Fourier transform infrared spectroscopy indicated that dry, but viable, human cells contained no detectable water. This study shows that mammalian cells can be engineered to retain viability in the absence of water.

Bacterial Proteins↗
PubMed2000

Functional and structural differences between the prion protein from two alleles prnp(a) and prnp(b) of mouse.

The prion protein is a glycoprotein expressed by neurones and other cells. In its holo-form it binds copper and exhibits superoxide dismutase activity. Studies in mice have led to the description of two distinct alleles. Differences in these alleles are linked to long and short incubation times following infection with scrapie. We studied recombinant mouse protein corresponding to the products of either allele and two intermediates carrying single amino-acid residue substitutions. The different forms of the prion protein exhibited differences in superoxide dismutase (SOD) activity and conformation. Intermediates with single substitutions were less stable than either allelic product. The findings provide insight into the differences between the two alleles and might have consequences for understanding differences in susceptibility to prion disease.

Alleles↗
PubMed2000

Propagation of human papillomavirus type 59 in the athymic mouse xenograft system.

Studies of human papillomavirus (HPV) infection are hampered by the lack of an adequate culture system. The athymic mouse xenograft system permits propagation of HPV, but only a few HPV types have been grown in this manner. To produce an oncogenic type for studies of HPV pathogenesis, a condylomata acuminata lesion from an immunosuppressed patient was used to prepare an infectious extract. The patient's lesion was shown by PCR analysis to contain abundant HPV 59 (an oncogenic type) and a lesser amount of HPV 11, a nononcogenic type. The extract was used to infect human foreskin tissue which was subsequently implanted into athymic mice. Characterization of implants recovered after 3-4 months of growth revealed the presence of HPV 59 exclusively. A second extract was prepared from one of these implants and used in an additional experiment to demonstrate the passage of HPV 59. Compared to the histopathologic changes induced by the prototypic nononcogenic HPV 11, infection with HPV 59 caused a higher degree of basal cell crowding, less acanthosis, minimal papillomatosis and less pronounced koilocytosis.

Adult↗
PubMed2000

Perceived barriers to exercise and stage of exercise adoption in older women of different racial/ethnic groups.

The purpose of this study was to determine whether barriers to exercise differ among racial/ethnic groups at the same stage of exercise adoption and adjacent stages within racial/ethnic groups. Questions about stage of exercise adoption and perceived barriers to exercise were administered to a cross sectional sample of 745 African American, 660 Hispanic, 738 Native American/Native Alaskan, and 769 Caucasian U.S. women aged 40 years and older. Correlations between rankings of barriers among racial/ethnic groups within the same stage ranged from .43 to .89. For each racial/ethnic group, significant differences existed between adjacent stages in the percentage of women reporting barriers to interfere with exercise (p < .10). Barriers were not similar enough among racial/ethnic groups to recommend that the same barriers be addressed for all races/ethnicities.

Adult↗
PubMed2000

Mouse model of sublethal and lethal intraperitoneal glanders (Burkholderia mallei).

Sixty male BALB/c mice were inoculated intraperitoneally with either a sublethal or a lethal dose of Burkholderia mallei China 7 strain, then killed at multiple time points postinoculation. Histopathologic changes were qualitatively similar in both groups and consisted of pyogranulomatous inflammation. In sublethal study mice, changes were first seen at 6 hours in mediastinal lymph nodes, then in spleen, liver, peripheral lymph nodes, and bone marrow at day 3. These changes generally reached maximal incidence and severity by day 4 but decreased by comparison in all tissues except the liver. Changes were first seen in lethal study mice also at 6 hours in mediastinal lymph nodes and in spleens. At day 1, changes were present in liver, peripheral lymph nodes, and bone marrow. The incidence and severity of these changes were maximal at day 2. In contrast to sublethal study mice, the incidence and severity of the changes did not decrease through the remainder of the study. The most significant difference between the two groups was the rapid involvement of the spleen in the lethal study mice. Changes indicative of impaired vascular perfusion were more frequently seen in the sublethal study mice. Our findings indicate that mice are susceptible to B. mallei infection and may serve as an appropriate model for glanders infection in a resistant host such as human beings. Additionally, by immunoelectron microscopy, we showed the presence of type I O-antigenic polysaccharide (capsular) antigen surrounding B. mallei.

Animals↗
PubMed2000

Morbidity and mortality associated with a new mycoplasma species from captive American alligators (Alligator mississippiensis).

Nine of 74 American alligators (Alligator mississippiensis) from a captive Florida herd of 3-4-m-long, 200-350-kg, adult males greater than 30 yr of age died within a 10-day period during 1995. Nonspecific clinical signs included anorexia, lethargy, muscle weakness, paraparesis, bilateral white ocular discharge, and various degrees of periocular, facial, cervical, and limb edema. Pneumonia, pericarditis, and arthritis were found on postmortem evaluation of the spontaneously dead and euthanatized alligators. Rapidly growing mycoplasmas were identified by culture, and mycoplasma nucleotide sequences were identified by polymerase chain reaction testing of fresh lung and synovial fluid from an affected alligator. Culture of banked frozen lung from necropsy specimens and fresh lung and fresh synovial fluid from newly affected alligators confirmed the presence of a new mycoplasma species in seven of eight individuals. Oxytetracycline was administered, but related deaths continued for 6 mo until only 14 of the initial alligators remained. An enzyme-linked immunosorbent assay to detect antibody was developed, and the organism was transmitted experimentally to naive juvenile alligators, although the source of the organism, Mycoplasma sp. (ATCC 700619), has not been identified. The alligator isolate is a novel species in the mycoplasma family because its nucleotide sequence does not match those of over 75 characterized mycoplasma species. Such factors as population density, animal age, and mycoplasmal virulence likely contributed to the course of disease.

Alligators and Crocodiles↗
PubMed2000

Patterns and correlates of physical activity among US women 40 years and older.

OBJECTIVES: This study describes the patterns of physical activity among minority women by using a variety of definitions and determines sociodemographic and behavioral correlates of physical activity in this population. METHODS: A cross-sectional study was conducted in 1996 and 1997 among US women 40 years and older (n = 2912) of the following racial/ethnic groups: African American, American Indian/Alaskan Native, Hispanic, and White. RESULTS: Physical activity was lowest among African Americans and American Indians/Alaskan Natives (adjusted odds ratios [ORs] for no leisure-time activity were 1.35 [95% confidence interval (CI) = 1.08, 1.68] and 1.65 [95% CI = 1.33, 2.06], respectively). A much higher proportion of women were classified as being physically active when occupational activity rather than more traditional assessments of leisure activity were used to determine level of physical activity. On the basis of a composite definition of physical activity, 72% of respondents reported being physically active. Women living in rural regions (OR = 1.33; 95% CI = 1.12, 1.58) were more likely than urban inhabitants to be completely inactive during leisure time. CONCLUSIONS: Minority women are among the least active subgroups in American society, although not all groups are less active than White women when all domains of physical activity are taken into account.

Adult↗
PubMed2000

Evaluation of substance P as a neurotransmitter in equine jejunum.

OBJECTIVE: To determine whether substance P (SP) functions as a neurotransmitter in equine jejunum. SAMPLE POPULATION: Samples of jejunum obtained from horses that did not have lesions in the gastrointestinal tract. PROCEDURE: Jejunal smooth muscle strips, oriented in the plane of the circular or longitudinal muscle, were suspended isometrically in muscle baths. Neurotransmitter release was induced by electrical field stimulation (EFS) delivered at 2 intensities (30 and 70 V) and various frequencies on muscle strips that were maintained at low tension or were under contraction. A neurokinin-1 receptor blocker (CP-96,345) was added to baths prior to EFS to interrupt SP neurotransmission. Additionally, direct effects of SP on muscle strips were evaluated, and SP-like immunoreactivity was localized in intestinal tissues, using indirect immunofluorescence testing. RESULTS: Substance P contracted circularly and longitudinally oriented muscle strips. Prior treatment with CP-96,345 altered muscle responses to SP and EFS, suggesting that SP was released from depolarized myenteric neurons. Depending on orientation of muscle strips and stimulation variables used, CP-96,345 increased or decreased the contractile response to EFS. Substance P-like immunoreactivity was detected in the myenteric plexus and circular muscle layers. CONCLUSIONS AND CLINICAL RELEVANCE: Substance P appears to function as a neurotransmitter in equine jejunum. It apparently modulates smooth muscle contractility, depending on preexisting conditions. Effects of SP may be altered in some forms of intestinal dysfunction. Altering SP neurotransmission in the jejunum may provide a therapeutic option for motility disorders of horses that are unresponsive to adrenergic and cholinergic drugs.

Animals↗
PubMed2000

In vitro evaluation of intraluminal factors that may alter intestinal permeability in ponies with carbohydrate-induced laminitis.

OBJECTIVES: To study the in vitro effects of cecal contents incubated with corn starch on colonic permeability in horses. ANIMALS: 4 healthy adult ponies. PROCEDURE: Mucosal specimens were obtained from the right ventral colon and mounted in Ussing chambers. Changes in short circuit current, conductance, and large-molecule permeability in response to addition of cecal contents and cecal contents incubated with corn starch were evaluated for 120 minutes. RESULTS: Incubation of cecal contents with corn starch for 8 hours resulted in a decrease in cecal content pH and an increase in lactic acid concentration. These changes were similar to those reported in vivo for ponies given corn starch. Exposure of colonic mucosa to cecal contents incubated with corn starch resulted in an increase in tissue conductance and permeability of technetium Tc 99m pentetate, compared with mucosa exposed to cecal contents alone. CONCLUSIONS AND CLINICAL RELEVANCE: In vitro exposure of colonic mucosa to cecal contents incubated with starch resulted in increased paracellular permeability. Fermentation of excessive amounts of carbohydrate in the intestinal lumen of horses may directly induce increased intestinal permeability associated with carbohydrate-induced laminitis.

Animals↗
PubMed2000

Pathology of upper respiratory tract disease of gopher tortoises in Florida.

Between August 1993 and September 1995, 24 gopher tortoises (Gopherus polyphemus) were received for pathological evaluations from various locations in Florida (USA). All tortoises were examined for clinical signs of upper respiratory tract disease (URTD) including nasal and ocular discharge, palpebral edema, and conjunctivitis. Of the 24 tortoises, 10 had current or previously observed clinical signs of URTD and 14 did not. A blood sample was drawn for detection of anti-mycoplasma antibodies by ELISA, and nasal lavage samples were collected for culture and detection of Mycoplasma agassizii gene sequences by polymerase chain reaction (PCR). Of the 14 clinically healthy tortoises, eight were sero-, culture- and PCR-negative, and six were seropositive for antibodies against M. agassizii. Of those six, five were culture- and/or PCR-positive for M. agassizii, and one was culture- and PCR-negative. Of the 10 ill tortoises, nine were seropositive by the ELISA and one was in the suspect range. Nine of the ill tortoises, including the suspect tortoise, were culture- and/or PCR-positive for M. agassizii, and one was culture- and PCR-negative. For histologic evaluation and discussion, the eight sero-, culture-, and PCR-negative tortoises were designated URTD-negative, and the other 16 were classified as URTD-positive. Histologic evaluation of the upper respiratory tract (URT) indicated the presence of mild to severe inflammatory, hyperplastic, or dysplastic changes in 14 URTD-positive tortoises. Seven of eight URTD-negative tortoises had normal appearing nasal cavities; one had mild inflammatory changes. Transmission electron microscopy revealed an organism consistent with Mycoplasma spp. on the nasal mucosal surface of tortoises with clinical signs and lesions of URTD. Additionally, gram-negative bacteria were isolated more frequently from the nasal cavities of URTD-positive tortoises than URTD-negative tortoises. Because clinical signs of URTD were never observed in six of the URTD-positive tortoises, we also conclude that subclinical URTD can occur in gopher tortoises.

Animals↗
PubMed2000

Persistent infectivity of a disease-associated herpesvirus in green turtles after exposure to seawater.

Herpesviruses are associated with several diseases of marine turtles including lung-eye-trachea disease (LETD) and gray patch disease (GPD) of green turtles (Chelonia mydas) and fibropapillomatosis (FP) of green, loggerhead (Caretta caretta), and olive ridley turtles (Lepidochelys olivacea). The stability of chelonian herpesviruses in the marine environment, which may influence transmission, has not been previously studied. In these experiments, LETD-associated herpesvirus (LETV) was used as a model chelonian herpesvirus to test viral infectivity after exposure to seawater. The LETV virus preparations grown in terrapene heart (TH-1) cells were dialyzed for 24 to 120 hr against aerated artificial or natural seawater or Hank's balanced salt solution (HBBS). Fresh TH-1 cells were inoculated with dialyzed LETV, and on day 10 post-infection cells were scored for cytopathic effect. Virus samples dialyzed up to 120 hr were positive for the herpesvirus DNA polymerase gene by polymerase chain reaction. Electron microscopy revealed intact LETV nucleocapsids after exposure of LETV to artificial seawater or HBSS for 24 hr at 23 C. LETV preparations remained infectious as long as 120 hr in natural and artificial seawater at 23 C. Similar results were obtained with a second culturable chelonian herpesvirus, HV2245. LETV infectivity could not be detected after 48 hr exposure to artificial seawater at 30 C. Since LETV and HV2245 remain infectious for extended periods of time in the marine environment, it is possible that FP-associated and GPD-associated herpesviruses also may be stable. These findings are significant both for researchers studying the epidemiological association of herpesviruses with diseases of marine turtles and for individuals who handle turtles in marine turtle conservation efforts.

Animals↗
PubMed2000

Intestinal type 2 proteinase-activated receptors: expression in opioid-sensitive secretomotor neural circuits that mediate epithelial ion transport.

Trypsin and mast cell tryptase cleave within the extracellular N terminus of proteinase-activated receptor-2 (PAR-2), exposing a tethered ligand (SLIGRL) that binds and activates the cleaved receptor. We examined the neuronal expression of PAR-2 and its role in intestinal ion transport. Short-circuit current elevations in response to trypsin or the receptor-activating peptide SLIGRL-NH(2) were measured in sheets of mucosa-submucosa from porcine ileum. SLIGRL-NH(2) or trypsin rapidly elevated short-circuit current after their contraluminal application with respective 50% effective concentrations of 184 and 769 nM. Their actions were attenuated after contraluminal administration of the neuronal conduction blocker saxitoxin (0.1 microM); the cyclooxygenase inhibitor indomethacin (10 microM); or the Na(+)/K(+)/Cl(-) cotransport inhibitor furosemide (10 microM), but not by atropine (0.1 microM), a muscarinic cholinergic antagonist. In addition, soybean trypsin inhibitor (5 microgram/ml) reduced mucosal responses to trypsin. The delta-opioid agonist [D-Pen(2,5)]-enkephalin (0.1 microM) inhibited trypsin action, an effect that was prevented by naltrindole (0.1 microM), a delta-opioid antagonist. PAR-2 immunofluorescence was localized in the mucosa using a receptor-specific antibody. PAR-2-like immunoreactivity was detected in myenteric and submucosal neurons, nerve fibers innervating ileal smooth muscle and mucosa, and in enteroendocrine cells. Some neurons coexpressed PAR-2- and choline acetyltransferase-like immunoreactivity. These results indicate that PAR-2 is expressed on cholinergic and noncholinergic submucosal neurons in porcine ileum. PAR-2 agonists stimulate active anion secretion by a neurogenic mechanism that is modulated by prostanoids and opioids. These receptors may have a potentially important role in intestinal neuroimmunomodulation.

Animals↗
PubMed1999

Prion protein expression aids cellular uptake and veratridine-induced release of copper.

The function of the prion protein is unknown despite suggestions it binds copper. Radioactive copper (Cu(67)) was used to demonstrate that histidine-dependent uptake of copper by cerebellar cells in culture is related to the level of PrP(c) expression. Copper is released by neurones at the synapse. Veratridine-induced release from synapses was proportional to the level of PrP(c) expression. Veratridine-induced release can be abolished only from PrP(c) expressing cells by pretreatment with phosphatidyl-specific phospholipase C, an enzyme that cleaves PrP(c) from the cell surface. These results suggest that PrP(c) aids cellular copper uptake and may have a function at the synapse related to release of copper during transmission.

Animals↗
PubMed1999

Normal prion protein has an activity like that of superoxide dismutase.

We show here that mouse prion protein (PrP(C)) either as recombinant protein or immunoprecipitated from brain tissue has superoxide dismutase (SOD) activity. SOD activity was also associated with recombinant chicken PrP(C) confirming the evolutionary conserved phenotype suggested by sequence similarity. Acquisition of copper by PrP(C) during protein folding endowed SOD activity on the protein but the addition of copper following refolding did not. PrP(C) dependent SOD activity was abolished by deletion of the octapeptide-repeat region involved in copper binding. These results describe an enzymic function for PrP(C) consistent with its cellular distribution and suggest it has a direct role in cellular resistance to oxidative stress.

Animals↗