Search PubMed⌕ Search

Biomedical subjects

J L Brown

Publications and source records attributed to J L Brown.

At least 91 records · Page 5Linked to original sources
PubMed1996

Crew resource management: a simulator study comparing fixed versus formed aircrews.

BACKGROUND: Most airline and military transport planes are flown by crews that have been teamed together for a short amount of time before disbanding and becoming part of a different crew (formed crew concept). Some military operations use a fixed crew concept, pairing crewmembers together for an indefinite period. This research investigated the effect of crew formation policy on aircrew performance during missions in U.S. Air Force KC-135 (tanker) simulators. METHOD: The performance of fixed aircrews is compared to formed aircrews flying the same simulator mission scenario, which included an in-flight emergency. Cockpit resource management (CRM) behavioral data and error data were collected by trained observers for 17 crews (9 fixed and 8 formed). RESULTS: The results show that fixed crews committed more minor errors (4.4 per mission) than formed crews (2.6 per mission), t(14) = 2.32, p = 0.036. No differences were found concerning major errors or CRM behavioral indicators. CONCLUSIONS: The results suggest the possibility of a "familiarity decline," where aircrew performance declines when crewmembers become too familiar with each other and may affect flight safety.

Accidents, Aviation↗
PubMed1995

Incorporation of 5-iodo-2'-deoxyuridine and 5-bromo-2'-deoxyuridine into rodent DNA as determined by neutron activation analysis.

Using 5-iodo-2'-deoxyuridine (IdU) and 5-bromo-2'-deoxyuridine (BrdU) as DNA precursors, neutron activation analysis (NAA) of iodine and Br was developed as a quantitative method for determining DNA synthesis. Endogenous rodent tissue concentrations of bromine (Br) and iodine ranged 100-fold from a low of 0.06 microgram of iodine/g of rat gastrointestinal tract (GIT) to a high of 5.99 micrograms of Br/g of rat kidney. All 10 rodent tissues had concentrations of Br 4 to 76 times higher than those of iodine. Rat hepatic Br concentrations could be reduced 17-fold by dietary and pharmacological methods. Female Fischer 344 rats and male C57BL/6 mice were given 4-8 intraperitoneal injections of either IdU or BrdU as a DNA precursor. Tissue clearance of iodine in IdU-treated rodents was both faster and more complete (in mice 4 and in rats 17 h or less) than Br clearance from BrdU-treated rodents (at 162 h nonincorporated Br label still remains). In rat liver, lung, and kidney, the iodine label incorporated from IdU into DNA was stable for at least 162 h. The incorporation ratio is defined as the microgram halogen/tissue for either IdU- or BrdU-treated rodents divided by the microgram halogen/g tissue of untreated rodents. NAA-based studies of DNA synthesis gave high incorporation ratios in rat liver (5.3), rat lung (6.7), rat GIT (19.0), rat spleen (24.0), mouse GIT (10.1), and mouse spleen (25.8).

Animals↗
PubMed1995

Morphological characterization of substance P receptor-immunoreactive neurons in the rat spinal cord and trigeminal nucleus caudalis.

Although there is considerable evidence that primary afferent-derived substance P contributes to the transmission of nociceptive messages at the spinal cord level, the population of neurons that expresses the substance P receptor, and thus are likely to respond to substance P, has not been completely characterized. To address this question, we used an antibody directed against the C-terminal portion of the rat substance P receptor to examine the cellular distribution of the receptor in spinal cord neurons. In a previous study, we reported that the substance P receptor decorates almost the entire dendritic and somatic surface of a subpopulation of spinal cord neurons. In the present study we have taken advantage of this labeling pattern to identify morphologically distinct subpopulations of substance P receptor-immunoreactive neurons throughout the rostral-caudal extent of the spinal cord. We observed a dense population of fusiform substance P receptor-immunoreactive neurons in lamina I at all segmental levels. Despite having the highest concentration of substance P terminals, the substantia gelatinosa (lamina II) contained almost no substance P receptor-immunoreactive neurons. Several distinct populations of substance P receptor-immunoreactive neurons were located in laminae III-V; many of these had a large, dorsally directed dendritic arbor that traversed the substantia gelatinosa to reach the marginal layer. Extensive labeling was also found in neurons of the intermediolateral cell column. In the ventral horn, we found that labeling was associated with clusters of motoneurons, notably those in Onuf's nucleus in the sacral spinal cord. Finally, we found no evidence that primary afferent fibers express the substance P receptor. These results indicate that relatively few, but morphologically distinct, subclasses of spinal cord neurons express the substance P receptor. The majority, but not all, of these neurons are located in regions that contain neurons that respond to noxious stimulation.

Afferent Pathways↗
PubMed1995

Fibrosing cholestatic hepatitis in a renal transplant recipient associated with the hepatitis B virus precore mutant.

A patient with evidence of chronic infection with hepatitis B virus (seropositive for hepatitis B surface antigen, and with antibody to hepatitis B e antigen) underwent renal transplantation, which subsequently failed. The patient developed abnormal liver function tests and 8 months after the removal of the transplanted kidney, hepatitis B virus DNA was detected in the serum in the absence of hepatitis B e antigen. Liver biopsy revealed the presence of fibrosing cholestatic hepatitis. Sequence analysis of the serum hepatitis B virus DNA showed the presence of the pre-core mutant. This case shows that fibrosing cholestatic hepatitis can occur outside the setting of liver transplantation, and coincided with the development of the pre-core mutant of hepatitis B virus.

Base Sequence↗
PubMed1995

Glycosyl phosphatidylinositol-dependent cross-linking of alpha-agglutinin and beta 1,6-glucan in the Saccharomyces cerevisiae cell wall.

The cell adhesion protein alpha-agglutinin is bound to the outer surface of the Saccharomyces cerevisiae cell wall and mediates cell-cell contact in mating. alpha-Agglutinin is modified by addition of a glycosyl phosphatidylinositol (GPI) anchor as it traverses the secretory pathway. The presence of a GPI anchor is essential for cross-linking into the wall, but the fatty acid and inositol components of the anchor are lost before cell wall association (Lu, C.-F., J. Kurjan, and P. N. Lipke, 1994. A pathway for cell wall anchorage of Saccharomyces cerevisiae alpha-agglutinin. Mol. Cell. Biol. 14:4825-4833). Cell wall association of alpha-agglutinin was accompanied by an increase in size and a gain in reactivity to antibodies directed against beta 1,6-glucan. Several kre mutants, which have defects in synthesis of cell wall beta 1,6-glucan, had reduced molecular size of cell wall alpha-agglutinin. These findings demonstrate that the cell wall form of alpha-agglutinin is covalently associated with beta 1,6-glucan. The alpha-agglutinin biosynthetic precursors did not react with antibody to beta 1,6-glucan, and the sizes of these forms were unaffected in kre mutants. A COOH-terminal truncated form of alpha-agglutinin, which is not GPI anchored and is secreted into the medium, did not react with the anti-beta 1,6-glucan. We propose that extracellular cross-linkage to beta 1,6-glucan mediates covalent association of alpha-agglutinin with the cell wall in a manner that is dependent on prior addition of a GPI anchor to alpha-agglutinin.

Antibodies↗
PubMed1995

Policy implications of new scientific knowledge.

Recent research findings have augmented the nutrition variable to a higher category of importance than previously appreciated. Inadequate nutrition can impair cognitive development and is associated with educational failure among impoverished children. This suggests that poor nutrition interferes with the formation of human capital, the cornerstone of a nation's social and economic development. Even temporary food shortages can produce adverse outcomes in developed as well as developing countries. The long-held concept of a critical period of brain development has been modified in light of the new understanding that developmental and morphological plasticity are far greater than previously recognized. This knowledge does not mean that there are no lasting adverse outcomes, but that from a policy perspective, intervention and rehabilitation can play crucial roles. This article highlights the relevance of this evidence to social and health programs and policies.

Child↗
PubMed1995

Natural versus chorionic gonadotropin-induced ovarian responses in the clouded leopard (Neofelis nebulosa) assessed by fecal steroid analysis.

The clouded leopard (Neofelis nebulosa) is an endangered species difficult to propagate in captivity because of sexual incompatibility between paired individuals. Fecal estradiol (E2) and progesterone (P4) metabolites were quantified in 14 females to noninvasively monitor seasonal reproductive patterns and compare ovarian responses to natural mating vs. exogenous gonadotropins. Increased E2 excretion was associated with behavioral estrus or eCG treatment, whereas elevated P4 metabolites were observed during natural and hCG-induced pregnant and nonpregnant luteal phases. On the basis of fecal E2 profiles, duration of the estrous cycle was 24 +/- 2 days, with estrus lasting 6 +/- 1 days. Mean gestation length was 89 +/- 2 days, whereas duration of the nonpregnant luteal phase was 47 +/- 2 days. Females experienced a seasonal anestrus during the late summer and early fall. One female demonstrated a lactational anestrus after the birth of three cubs. On nine occasions, clouded leopards ovulated spontaneously (based on elevated fecal P4 metabolite concentrations) in the absence of mating. Patterns of eCG-stimulated E2 excretion were similar to those associated with natural estrus and were unaffected by eCG dosage (25, 50, or 100 IU). In contrast, post-hCG P4 metabolite profiles varied considerably, with responses including anovulation, attenuated luteal P4 metabolite production, and hyperstimulated luteal function. In some females, compromised luteal function after ovulation induction appeared to be due to the presence of mature CL from previous spontaneous (without copulation) ovulations at the time of gonadotropin treatment. Duration of post-hCG P4 metabolite excretion was reduced approximately 40% in these individuals compared to females with no evidence of active luteal activity. In sum, these are the first data describing the ovarian cycle of this endangered species. The information is important because it is based on the longitudinal assessment of multiple females using a completely atraumatic approach, thereby eliminating the potential confounding impact of stress. Data indicate that spontaneous ovulations and the presence of active luteal tissue on the ovary can profoundly affect ovarian responses to exogenous gonadotropin therapy. Therefore, fecal steroid monitoring can serve as a useful adjunct to developing assisted reproduction techniques, especially the hormonal induction of ovulation for planned artificial insemination.

Animals↗
PubMed1995

Relationship of circulating steroid hormones, luteal luteinizing hormone receptor and progesterone concentration, and embryonic mortality during early embryogenesis in the domestic cat.

Serum hormones, corpus luteum (CL) progesterone, and CL LH receptors were characterized and interrelated to ovarian follicle and CL number and preimplantation embryo quality/survival in the cat. Blood samples were collected from queens ovariohysterectomized at 64 (n = 7), 76 (n = 11), 100 (n = 8), 124 (n = 7), 148 (n = 6), or 480 (n = 8) h after first copulation (3-times-daily matings on Days 2 and 3 of estrus). Ovarian CL were enucleated, weighed, and bisected; one hemi-CL was assayed for progesterone and the other for LH receptors. Serum was assessed for estradiol-17 beta and progesterone. Serum estradiol-17 beta concentrations did not return (p > 0.05) to baseline approximately 20 pg/ml) until 124 h after first copulation, whereas serum progesterone began to increase (> 1 ng/ml) by 76 h, was elevated (p < 0.05) by 124 h, and continued to rise thereafter. Serum progesterone was highly correlated with CL mass and LH receptor and progesterone concentration (range, r = 0.69-0.82; p < 0.01). CL progesterone and LH receptor concentrations were similar (p > 0.05) at 64 and 76 h, and both increased (p < 0.05) at subsequent time intervals and were correlated closely (r = 0.65; p < 0.01). Although ovarian CL were distinct and well organized by 64 h, pronounced elevations in serum progesterone and CL LH receptors and progesterone did not occur until at least 36 h later. The rapid increase in serum progesterone concentrations between 100 and 148 h was related to accelerated LH receptor synthesis and CL progesterone production and not entirely to enhanced CL growth.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Chronic hepatitis C virus infections: predictive value of genotype and level of viraemia on disease progression and response to interferon alpha.

The effects of hepatitis C virus genotype and viraemia on disease outcome in patients with chronic hepatitis C virus infection were studied. Patients infected with genotype 1 tended to develop more severe disease, and to respond less well to interferon (IFN) treatment, but no pretreatment variable successfully predicted either the severity of the disease or the response to IFN. Failure to eliminate the virus during the first three months of therapy, however, predicted a failure to derive long term benefit from the current IFN regime. Hence pretreatment variables cannot be used to determine whether individual patients will respond to IFN, but observations during the first three months of therapy can be used to decide which patients will not respond to prolonged therapy. In these patients consideration should be given to changing the IFN dosing regime or using alternative treatments.

Base Sequence↗
PubMed1995

Imagination training: a tool with many uses.

Guided imagery, self-hypnosis, and related strategies can help improve patient comfort during medical procedures. Use them to relieve pain and nausea, control heightened anxiety and phobias, and generally make the office visit easier for everyone.

Anxiety↗
PubMed1995

Pseudomembranous colitis following clarithromycin therapy.

OBJECTIVE: To describe the association of clarithromycin, used to treat Helicobacter pylori infection and duodenal ulceration, with pseudomembranous colitis in two patients. SETTING: St Mary's Hospital, London, UK. PATIENTS: Two female patients aged 77 and 78 years, admitted with duodenal ulceration and H. pylori infection. INTERVENTION: Clarithromycin (500 mg three times daily) was administered concurrently with omeprazole (40 mg once daily). OUTCOME MEASURES: After an initial improvement in symptoms both patients experienced persistent Clostridium difficile-associated diarrhoea. CONCLUSIONS: High-dose clarithromycin should be used with caution for the treatment of H. pylori infection associated with gastroduodenal ulceration. The drug may induce antibiotic-associated colitis which can lead to morbidity and mortality, particularly in the elderly.

Aged↗
PubMed1994

Yeast Skn7p functions in a eukaryotic two-component regulatory pathway.

Previous analysis of the amino acid sequence of Skn7p, the product of the yeast SKN7 gene, revealed a potential 'receiver motif' homologous to that found in bacterial response regulators (signal-transducing effector proteins regulated by phosphorylation at a conserved aspartate residue corresponding to position D427 in Skn7p). We determined the effects of D427N and D427E mutations in Skn7p. The D427N substitution resulted in diminished activity in four independent in vivo assays of Skn7p function, while the D427E mutation enhanced Skn7p activity in these assays. Our results are consistent with predictions based on the bacterial two-component paradigm and provide experimental evidence that a receiver motif functions in regulating the activity of Skn7p in a eukaryote. Skn7p suppressed growth defects associated with a pkc1 delta mutation, raising the possibility that PKC1 might play a role in regulating Skn7p. However, epistasis experiments indicate that Skn7p does not appear to function directly downstream of the PKC1-MAP kinase pathway. Rather, Skn7p may function in a two-component signal transduction pathway that acts in parallel with the PKC1 cascade to regulate growth at the cell surface. We present evidence suggesting that Skn7p serves as a transcription factor in such a signaling pathway.

Amino Acid Sequence↗
PubMed1994

Study of the roles of proline 391 and a highly conserved sequence in the carboxyl-terminal region of members of the serpin family in the secretion of alpha 1-proteinase inhibitor.

Truncation of alpha 1-proteinase inhibitor prior to Pro391 prevents its secretion. This residue is the carboxyl terminus of a highly conserved sequence in serpins, suggesting that either Pro391 or the conserved sequence may serve as at least a part of a signal recognized by components of the secretory pathway. To evaluate these possibilities, we have determined the effects of replacement of Pro391 on the secretion of alpha 1-proteinase inhibitor and have examined the ability of the 9-residue conserved sequence to mediate secretion. We find that replacement of Pro391 with hydrophobic residues yields variants that are well secreted, but replacement with other classes of amino acids severely restricts secretion. These results show that while alpha 1-proteinase inhibitor is secreted most efficiently when proline occupies position 391, Pro391 is not an absolute requirement for its secretion. Our results show that the 9-amino acid conserved sequence found near the carboxyl termini of proteins of the serpin family is not sufficient to direct the secretion of alpha 1-proteinase inhibitor. We conclude that mutations affecting residue 391 and other positions in the conserved region lead to structural changes, possibly very minor, that influence the secretion of alpha 1-proteinase inhibitor.

Amino Acid Sequence↗
PubMed1994

Tagging secretory and membrane proteins with a tyrosine sulfation site. Tyrosine sulfation precedes galactosylation and sialylation in COS-7 cells.

Sulfation of proteins on tyrosines is a late Golgi modification that can be used to label proteins with [35S]sulfate for the analysis of post-Golgi transport. To extend the use of this modification to proteins not naturally sulfated, we fused a tyrosine sulfation site, the carboxyl-terminal nonapeptide of cholecystokinin precursor, to the carboxyl terminus of two normally unsulfated proteins: alpha 1-proteinase inhibitor, a secretory protein, and subunit H1 of the asialoglycoprotein receptor; a type II membrane protein. The tagged proteins were efficiently sulfated in transfected COS-7 and Madin-Darby canine kidney cells. Specifically in COS-7 cells, the proteins were sulfated before they were galactosylated and sialylated and were converted to the mature forms with a half-time of approximately 2-3 min. This is in contrast to other cell types in which tyrosine sulfation was found to be virtually the last modification of the Golgi apparatus. Our results suggest that tyrosine sulfation occurs before the trans-Golgi in transfected COS-7 cells.

Amino Acid Sequence↗
PubMed1994

Dose-response relationship for rat liver DNA damage caused by 49 rodent carcinogens.

An experimental approach was taken to the question of dose-response curves for chemical carcinogenesis. DNA damage in female rat liver was chosen as the experimental parameter because all chemicals found to damage hepatic DNA were rodent carcinogens. The lowest dose causing DNA damage was determined for the 12 active chemicals (1,2-dibromoethane, 1,2-dibromo-3-chloropropane, 1,2-dichloroethane, 1,4-dioxane, methylene chloride, auramine O, Michler's ketone, selenium sulfide, 1,3-dichloropropene, 1,2-dimethylhydrazine, N-nitroso-piperidine and butylated hydroxytoluene). The resulting dose-response curves for rat hepatic DNA damage were plotted versus log of the molar dose (all activity was in five orders of magnitude) and versus percent of chemicals' oral rat LD50 (most of the activity was in only two orders of magnitude). Dose-response studies of the active chemicals were analyzed by regression methods. With the exception of butylated hydroxytoluene, the dose-response curves fit a linear model well (r2 = 0.886) and a quadratic model even better (r2 = 0.947). Based on experimental data from 11 DNA-damaging carcinogens (a dose range of 6 orders of magnitude), an equation and graph of the dose-response relationship of an 'average DNA-damaging carcinogen' is presented over the x-axis dose range of eight orders of magnitude.

Animals↗