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Biomedical subjects

D Brown

Publications and source records attributed to D Brown.

At least 451 records · Page 25Linked to original sources
PubMed1995

Cellular distribution of the aquaporins: a family of water channel proteins.

A group of transmembrane proteins that are related to the major intrinsic protein of lens fibers (MIP26) have been named "aquaporins" to reflect their role as water channels. These proteins are located at strategic membrane sites in a variety of epithelia, most of which have well-defined physiological functions in fluid absorption or secretion. However, some aquaporins have been localized in cell types where their role is at present unknown. Most of the aquaporins are delivered to the plasma membrane in a non-regulated (constitutive) fashion, but AQP2 enters the regulated exocytotic pathway and its membrane expression is controlled by the action of the antidiuretic hormone, vasopressin. These pathways of constitutive versus regulated delivery to the plasma membrane have been reconstituted in transfected LLC-PK1 epithelial cells, indicating that the information encoded within the protein sequence is sufficient to allow sorting of newly synthesized protein into distinct intracellular vesicles. Finally, different members of the aquaporin family can be targeted to apical, basolateral or both apical and basolateral plasma membrane domains of polarized epithelial cells. This implies that signals for the polarized targeting of these proteins also is located in non-homologous regions of these similar proteins. Thus, future investigations on the aquaporin family of proteins will provide important information not only on the physiology of membrane transport processes in many cell types, but also on the targeting and trafficking signals that allow proteins to enter distinct intracellular vesicular pathways in epithelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Detection of HCV-RNA in paraffin-embedded liver biopsies from patients with autoimmune hepatitis.

BACKGROUND/AIMS: There may be a relationship between autoimmune hepatitis and viral infection. To examine this relationship, 19 patients with autoimmune hepatitis and/or chronic hepatitis C were studied. METHODS: Patients were selected initially on the basis of having autoantibodies (anti-nuclear, anti-smooth muscle, or anti-liver-kidney microsomal) in serum. Formalin-fixed, paraffin-embedded liver biopsies from these patients were tested for HCV-RNA by polymerase chain reaction. The biopsies were examined histologically to detect features suggestive of chronic hepatitis C or autoimmune hepatitis. The results were correlated with serum anti-HCV and HCV-RNA, and with response to steroid therapy. RESULTS: Five of the nineteen patients had detectable HCV-RNA in their liver biopsies. In two of three patients from whom serum was available, HCV-RNA was detectable. The remaining 14 patients were negative for HCV-RNA by tissue polymerase chain reaction. Serum was available from 11 of these patients, and serum HCV-RNA was negative in all. All of the three HCV-RNA-positive patients who were treated with steroids showed a partial response; tissue positivity for HCV-RNA was significantly higher in partial responders than in complete responders (60% vs 0%, p = 0.01). Severe portal and periportal inflammation with prominent plasma cells together with bridging parenchymal necrosis were seen more often in HCV-negative biopsies. Mild portal and periportal inflammation with portal lymphoid aggregates, apoptosis and spotty parenchymal necrosis were seen more in HCV-positive biopsies. CONCLUSIONS: These results show that hepatitis C virus can be detected in some patients with circulating autoantibodies. The ability to detect HCV-RNA in paraffin-embedded archival material provides a valuable addition to the battery of available HCV tests.

Adolescent↗
PubMed1995

Detection of interleukin-1 signal transduction inhibitors: action of protein kinase inhibitors.

The dysregulated production of IL-1 has been shown to play an important role in many pathological processes. Despite the apparent value of compounds able to inhibit either the secretion of IL-1 or its signal transduction pathway in a specific manner, there are no such compounds suitable for clinical use. A major problem in identifying novel and specific inhibitors of signal transduction is the lack of knowledge of the intracellular events which mediate the cellular actions of IL-1. In this study a simple cellular assay has been established to screen natural product and synthetic compound libraries for low molecular weight inhibitors of the cytokine signalling pathways of potential therapeutic value. In addition, we have studied the action of several known modulators of signal transduction on the actions of IL-1.

Cell Division↗
PubMed1995

Aquaporin water channels: unanswered questions and unresolved controversies.

The long-standing biophysical question of how water crosses plasma membranes has been answered by the recent discovery of the aquaporins. Identification of this large family of membrane water-transport proteins has generated new questions about the physiological functions, tissue distributions, and regulatory mechanisms of individual aquaporins. The fast pace of developments in this field has also resulted in major discrepancies in published reports which warrant resolution.

Animals↗
PubMed1995

Storage-phosphor autoradiography: a rapid and highly sensitive method for spatial imaging and quantitation of radioisotopes.

This study evaluates a storage-phosphor imaging system for rapid autoradiography and quantitation of beta- and gamma-ray emitters in mice. Known quantities of authentic 3H, 14C, and 195mPt (0.06 to 31,714 DPM/mm2) were exposed to imaging plates of the storage-phosphor system for 0.5 min to 15 hr at room temperature. Immediately after exposure, the imaging plates were scanned and the autoradiograms were quantified. Radioactivity as low as 1.8 DPM/mm2 (3H), 0.06 DPM/mm2 (14C) and 3.1 DPM/mm2 (195mPt) was visualized and quantified in 8 hr (3H and 14C) and 6 min (195mPt), respectively. The system displayed a linear range of four to five orders of magnitude (14C: 0.5 to 6,914 DPM/mm2 for 2-hr exposure; 3H: 1.8 to 15,372 DPM/mm2 for 15-hr exposure; and 195mPt: 66 to 198,000 DPM 6 min-exposure). Variation from scan-to-scan was small (< 1% to 5%) and was more pronounced at the lower detection limits and exposure periods. Similar sensitivity, linearity, and variability were obtained in cryosections of murine tumors treated with 14C-fluorouracil or 3H-epinephrine and whole-body autoradiograms of mice treated with 195mPt-cisplatin via liver. The high sensitivity allowed noninvasive imaging of live unanesthetized mice treated with 195mPt with a short exposure time (105 sec). These results validate, for the first time, the high sensitivity, linearity, and wide dynamic range of storage-phosphor technology for quantitative autoradiography of 14C, 3H, and 195mPt isotopes. Storage-phosphor imaging will be useful in rapid quantitative autoradiographic disposition studies of radiolabeled drugs and excipients in vitro and in vivo.

Animals↗
PubMed1995

Uniform prehospital data elements and definitions: a report from the uniform prehospital emergency medical services data conference.

One of the district and universal aspects of emergency medical service (EMS) is the belief that before its implementation many people were dying or being killed by ill-equipped, poorly trained "hearse drivers" and that this tragic state of affairs has been rectified by the advances in the prehospital phase of care. Except for cases of nontraumatic, out-of-hospital cardiac arrest there is almost no convincing scientific evidence to prove that prehospital care has had an impact on morbidity or mortality. At the very foundation of this problem is the lack of a set of broad-based, well-conceived, accurate, reliable, uniform EMS data. Many attempts have been made to develop a uniform EMS data set, but without a national consensus these have not achieved wide distribution. In 1992, with the assistance of the National Highway Traffic Safety Administration, the national consensus process began with a series of meetings involving many EMS agencies and organizations. This culminated in August 1994 with the development of an 81-item uniform EMS data set. We detail the prior attempts at data set development and outline the process leading to the this uniform, national EMS data set.

Data Collection↗
PubMed1995

Expression of osteopontin, a urinary inhibitor of stone mineral crystal growth, in rat kidney.

Cultured mouse kidney cortical cells secrete osteopontin, a bone matrix protein that is also found in urine. Osteopontin is associated with cell proliferation/tumerogenesis and also inhibits kidney stone mineral crystal growth [1]. Using antibodies raised against osteopontin isolated from the culture medium, we localized osteopontin in normal rat kidney. Fluorescence, confocal and electron microscopy revealed osteopontin primarily in cells of the descending thin limb of the loop of Henle (DTL) and in papillary surface epithelium (PSE) in the area of the calyceal fornix. In situ hybridization with labeled RNA made from a cDNA that contains the entire coding sequence for mouse osteopontin revealed message at the same sites at which protein was demonstrated by immunocytochemistry. Immunogold labeling was localized to a population of dense vesicles distinct from lysosomes and endosomes. To examine the turnover of osteopontin, rats were injected with the protein synthesis inhibitor cyclohexamide, 14 mg/kg, six hours prior to kidney fixation. These kidneys no longer demonstrated osteopontin in DTL and the immunofluorescence in the papillary surface was attenuated. Thus, osteopontin is secreted at two sites in the kidney where urine is highly concentrated in stone mineral constituents. It has a relatively rapid turnover, suggesting that it could be subject to physiological regulation. Osteopontin may be important in the normal endogenous defense against kidney stone formation.

Animals↗
PubMed1995

Structure and function of kidney water channels.

There is now firm evidence that water transporting proteins are expressed in renal and extrarenal tissues. In the kidney, proximal-type (CHIP28) and collecting duct (WCH-CD) water channels have been identified. We have cloned three kidney cDNAs with homology to the water channel (aquaporin) family, including a mercurial-insensitive water channel (MIWC), and a glycerol-transporting protein (GLIP) in collecting duct basolateral membrane. To elucidate water transporting mechanisms, a series of molecular and spectroscopic studies were carried out on purified CHIP28 protein and expressed chimeric and mutated CHIP28 cDNAs. The results indicate that CHIP28 transports water selectively, that CHIP28 monomers are assembled in membranes as tetramers, but that individual monomers function independently. Monomers contain multiple membrane-spanning helical domains. Based on these data and recent electron crystallography results, a model for water transport is proposed in which water moves through narrow pores located within individual CHIP28 monomers.

Amino Acid Sequence↗
PubMed1995

The Claybury Community Psychiatric Nurse Stress Study: is it more stressful to work in hospital or the community?

The Claybury community psychiatric nurse (CPN) stress study collected data on stress levels in 250 CPNs and 323 ward-based psychiatric nurses (WBPN) in the North East Thames region. Four out of 10 CPNs were found to be experiencing high levels of psychological distress on GHQ scores. Whilst both CPNs and WBPNs scored highly on scores of occupational burnout, especially on emotional exhaustion scores, WBPNs scored worse on emotional detachment from their patients and were achieving less personal fulfilment from their work. Both groups of nurses were more satisfied with direct patient clinical work than with their employment conditions, particularly their working environments and, for CPNs, their relationships with their managers. The different patterns of coping skills are explored and discussed for both groups of nurses, especially the use of social support, time management and organization of tasks. The study concludes that whilst major changes are occurring in the psychiatric arena for both groups of nurses, stress is reaping its toll on mental health nurses, in terms of higher absence rates, lower self-esteem and personal unfulfilment. This could not only affect the quality of patient care but also future career prospects for nurses. The study invites serious consideration of introducing stress-reducing measures in the work-place as well as further research into specific stressors for different groups of nurses.

Adaptation, Psychological↗
PubMed1995

Pseudomemories: the standard of science and the standard of care in trauma treatment.

The pseudomemory (PM) debate has focused on individuals who do not remember sexual abuse and later recover these memories, often in therapy. This paper critically reviews experimental research on stress and memory and on suggestibility and memory in terms of its applicability to PM production in therapy. Three different kinds of suggestibility are identified--hypnotizability, postevent misinformation suggestibility, and interrogatory suggestibility. It is hypothesized that interrogatory suggestibility alone or the interaction of all three pose significant risk for PM production. It is argued that a better standard of science is needed before claims can be made about PM production in therapy, since no experimental studies have been conducted on memory performance or suggestibility effects in therapy. However, the findings derived from memory research on other populations, nevertheless, are useful to inform the standard of care in treating recovered memory patients.

Adult↗
PubMed1995

Sequence variation in the extreme 5' end of the human papillomavirus type 6a long control region.

A sequence analysis of human papillomavirus (HPV) type 6a isolates from 15 exophytic condylomata acuminata lesions was done to determine the prototype sequence for this region of HPV 6a, which sequences are conserved and which vary, and whether the variability might be useful in epidemiologic studies. The long control region (LCR) was amplified by the polymerase chain reaction and approximately 242 bp were directly sequenced. The data indicate that all isolates contain a 94-bp insertion relative to prototype HPV 6b and confirm that this insertion should be considered a part of the HPV 6 LCR. Seven of the 15 isolates were in 1 group, and the rest were distributed among 4 groups. There was no strong correlation between DNA group and location of lesion, sex of patient, or pregnancy status. In addition, although there was variation among isolates, a region implicated by deletional analysis to have transcriptional silencing activity was conserved.

Base Sequence↗
PubMed1995

Antibodies against viral nonstructural proteins in response to infection with poliovirus.

Sera from recent and past cases of poliomyelitis as well as from healthy subjects vaccinated with live attenuated poliovirus, all contain antibodies to poliovirus nonstructural proteins. Reactivity of these antisera with nonstructural protein antigens present in virus-infected HeLa cells or translated from cDNA transcripts in rabbit reticulocyte lysates was sometimes sensitive to denaturation of the antigens. The finding of antibodies to nonstructural proteins of poliovirus and other viruses should have applications in the development of diagnostic assays for virus infection and may have implications for future vaccine design.

Antibodies, Viral↗
PubMed1995

The utilization of lupin (Lupinus angustifolius) and faba bean globulins by rats is poorer than of soybean globulins or lactalbumin but the nutritional value of lupin seed meal is lower only than that of lactalbumin.

The effects of dietary sweet lupin (Lupinus angustifolius, Unicrop) seed meal or its insoluble fiber (nonstarch polysaccharides + lignin) on performance, digestibility and nitrogen utilization in growing rats were studied in four experiments. Globulin proteins isolated from lupin, faba bean (Vicia faba L. minor) or soybean (Glycine max) were also incorporated into purified diets as replacements for lactalbumin (control) and the nutritional effects were evaluated. Isocaloric, legume-based diets supplemented with amino acids were used. Final weight gain, gain:feed ratios, nitrogen retention and net protein utilization of the animals fed whole lupin meal-based diets for 10 d were inferior to those of controls. In contrast, adding lupin insoluble fiber to a control diet produced no adverse effects. Ileal starch and apparent nitrogen digestibilities, and fecal digestibility of starch in lupin-fed rats were higher than those of controls, but fecal true nitrogen digestibility was lower. Replacement of lactalbumin with globulin proteins from lupin or faba bean depressed food intake and protein utilization, but only performance was affected by consumption of soybean globulins. Rats consuming lupin or faba bean globulins excreted significantly more nitrogen, particularly as urea through the urine. This did not occur in rats fed soybean globulins. Urea concentration in plasma was higher in rats fed diets containing lupin meal or legume globulins. The concentrations of urea, arginine and ornithine in plasma increased significantly compared with control values after 3 to 9 h of a lupin diet. After 9 h, plasma lysine was also decreased. We concluded that the main reasons for the low nutritional value of sweet lupin seed meal are likely to be related to the chemical structure of the globulin proteins and their adverse effects on growth and nitrogen metabolism, and not to any known antinutritional factor or poor digestibility.

Amino Acids↗
PubMed1995

Stress and coping strategies in community psychiatric nurses: a Q-methodological study.

With the development of the concept of community care there has been a significant expansion of the community psychiatric nurse (CPN) profession. The present study attempts to examine which aspects of their work CPNs currently find stressful. The study also examines the various strategies which CPNs feel to be useful in attempting to cope with such occupational stress. Forty-four CPNs in four health districts participated in this Q-methodological study which provided the opportunity for CPNs to construct their own concepts of stressors and coping strategies. The results obtained indicated that CPNs identified nine distinct areas of stress within their work, along with 12 distinct coping strategies which they considered useful in attempting to deal with such stress. The implications of these findings are discussed.

Adaptation, Psychological↗
PubMed1995

Stress and the community mental health nurse: the development of a measure.

The issue of stress amongst health care professionals is currently a major concern within the British National Health Service. It is important for researchers to develop both reliable and valid psychometric measures to assess occupational stress. This paper outlines the development and piloting of a measure of professional stress for community mental health nurses, the CPN Stress Questionnaire (Revised). Data on the reliability and validity of this new measure are presented. It is concluded that this measure has good psychometric properties. A range of possible research applications is outlined.

Burnout, Professional↗
PubMed1995

Prediction of the severity of haemolytic disease of the newborn. Quantitative IgG anti-D subclass determinations explain the correlation with functional assay results.

Sera containing anti-D, taken from 44 RhD-negative women with RhD-positive infants, were tested in antibody-dependent cellular cytotoxicity (ADCC) and monocyte monolayer assays (MMA) which used similar target and effector cell populations. In addition, the anti-D concentration was measured in the Auto Analyzer and the number of IgG1 and IgG3 anti-D molecules bound to the target red cells was measured by flow cytometry. The results of the functional assays and Auto Analyzer quantitation were examined for correlation with IgG subclass quantitation and all results were compared for their ability to predict the severity of haemolytic disease of the newborn (HDN). ADCC correctly predicted HDN in 39/44 (88.6%) cases, Auto Analyzer quantitation in 35/44 (79.5%) and the MMA in 32/44 (72.7%). For all three assays, the number of correct predictions was highest when the maternal serum contained both IgG1 and IgG3 anti-D. ADCC activity and HDN were correlated with the number of cell-bound IgG1 molecules (r > or = 0.58), but MMA activity was most closely correlated with the number of cell-bound IgG3 molecules (r = 0.68). Hence the superior predictive value of ADCC is due to its ability to reflect the IgG1 component of maternal anti-D, which has a better correlation than IgG3 anti-D with the severity of HDN.

Autoanalysis↗