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Biomedical subjects

J A Brown

Publications and source records attributed to J A Brown.

At least 37 records · Page 2Linked to original sources
PubMed2001

Circulating angiotensins in the river lamprey, Lampetra fluviatilis, acclimated to freshwater and seawater: possible involvement in the regulation of drinking.

Plasma angiotensin levels were measured for the first time in a cyclostome, the river lamprey. With the demonstration that angiotensins are present in the circulation, the possibility of a physiological role in the regulation of drinking was re-examined. Angiotensin II and III concentrations and plasma osmolalities were significantly higher in lampreys acclimated to 28 ppt seawater than in those acclimated to freshwater. No changes were found in angiotensin II and III levels 4 h after transfer from freshwater to 50% seawater, although plasma osmolality had started to rise by this time. There was a suggestion that plasma angiotensin II levels might be related to osmolality in the transfer experiment. Injection of Asp(1)Val(5)- or Asn(1)Val(5)-angiotensin II (40-169 microg/kg body wt.) did not stimulate drinking in freshwater-acclimated lampreys, even when they were still capable of drinking. The angiotensin-converting enzyme inhibitor captopril and the smooth muscle relaxant papaverine both reduced drinking rate in 50% seawater-acclimated lampreys. The data do not provide direct evidence for the involvement of the renin-angiotensin system in the control of drinking behaviour in the lamprey. Indirect evidence from the captopril effect is suggestive, but could have other explanations.

Adaptation, Physiological↗
PubMed2001

PD-L2 is a second ligand for PD-1 and inhibits T cell activation.

Programmed death I (PD-I)-deficient mice develop a variety of autoimmune-like diseases, which suggests that this immunoinhibitory receptor plays an important role in tolerance. We identify here PD-1 ligand 2 (PD-L2) as a second ligand for PD-1 and compare the function and expression of PD-L1 and PD-L2. Engagement of PD-1 by PD-L2 dramatically inhibits T cell receptor (TCR)-mediated proliferation and cytokine production by CD4+ T cells. At low antigen concentrations, PD-L2-PD-1 interactions inhibit strong B7-CD28 signals. In contrast, at high antigen concentrations, PD-L2-PD-1 interactions reduce cytokine production but do not inhibit T cell proliferation. PD-L-PD-1 interactions lead to cell cycle arrest in G0/G1 but do not increase cell death. In addition, ligation of PD-1 + TCR leads to rapid phosphorylation of SHP-2, as compared to TCR ligation alone. PD-L expression was up-regulated on antigen-presenting cells by interferon gamma treatment and was also present on some normal tissues and tumor cell lines. Taken together, these studies show overlapping functions of PD-L1 and PD-L2 and indicate a key role for the PD-L-PD-1 pathway in regulatingT cell responses.

Amino Acid Sequence↗
PubMed2000

Physiological status of wild European eels (Anguilla anguilla) infected with the parasitic nematode, Anguillicola crassus.

The effect of the parasitic swimbladder nematode, Anguillicola crassus, on the physiological status of wild European eels (Anguilla anguilla) was investigated during an 18 month survey (February 1995 until September 1996), and compared with that of wild uninfected eels collected over the same time-period. Despite the occurrence of up to 15 blood-feeding adults in the swimbladder lumen of the infected eels and as many as 25 additional larvae in the swimbladder wall, there were no major differences in hormonal, metabolic or osmoregulatory status of the 2 groups of eels. Wild European eels appear to adapt to chronic parasitism with Anguillicola crassus. The possible adverse effects of additional simultaneous stressors are discussed.

Air Sacs↗
PubMed2000

Low grade gastric MALT Lymphoma: radiographic findings.

AIMS: Gastric MALT (mucosa-associated lymphoid tissue) lymphoma is now recognized as a distinct entity within extranodal non-Hodgkin's lymphoma. The purpose of this study was to describe the radiographic findings in low grade gastric MALT lymphoma. MATERIALS AND METHODS: We retrospectively reviewed the radiographic findings in 22 cases of low-grade gastric MALT lymphoma. The study group consisted of 15 men and seven women (median age 68 years, range 41-91 years). Lesions were designated as infiltrative or polypoid by consensus of two radiologists. Polypoid lesions were categorized by number and size. Anatomical site within the stomach and presence of transpyloric or oesophagogastric extension was determined for each case. The presence of abdominal lymphadenopathy was categorized as regional or distant. The presence of Helicobacter pylori was determined from endoscopic and surgical biopsies. RESULTS: Computed tomography (CT) revealed abnormalities of the stomach in 19 cases of the 21 in which it was performed. There were 14 infiltrative lesions and five polypoid lesions. Of the 14 infiltrative lesions, the mean gastric wall thickness was 2.2 cm (range 0.8-6.0 cm). There were three single and two multiple polypoid lesions (mean size 2.2 cm, range 1. 5-2.7 cm). Transpyloric extension was observed in two cases and oesophagogastric extension in one. Abdominal lymphadenopathy was observed in 10 of 21 patients. Helicobacter pylori was found in 19 of 22 cases (86%). CONCLUSION: Low grade B cell gastric MALT lymphomas present with an infiltrative form on CT in about three-quarters of cases and a polypoid pattern in the remainder. Abdominal lymphadenopathy is seen in approximately one-half of cases. There is a high association with Helicobacter pylori.

Adult↗
PubMed2000

The Rib43a protein is associated with forming the specialized protofilament ribbons of flagellar microtubules in Chlamydomonas.

Ciliary and flagellar microtubules contain a specialized set of three protofilaments, termed ribbons, that are composed of tubulin and several associated proteins. Previous studies of sea urchin sperm flagella identified three of the ribbon proteins as tektins, which form coiled-coil filaments in doublet microtubules and which are associated with basal bodies and centrioles. To study the function of tektins and other ribbon proteins in the assembly of flagella and basal bodies, we have begun an analysis of ribbons from the unicellular biflagellate, Chlamydomonas reinhardtii, and report here the molecular characterization of the ribbon protein rib43a. Using antibodies against rib43a to screen an expression library, we recovered a full-length cDNA clone that encodes a 42,657-Da polypeptide. On Northern blots, the rib43a cDNA hybridized to a 1. 7-kb transcript, which was up-regulated upon deflagellation, consistent with a role for rib43a in flagellar assembly. The cDNA was used to isolate RIB43a, an approximately 4.6-kb genomic clone containing the complete rib43a coding region, and restriction fragment length polymorphism analysis placed the RIB43a gene on linkage group III. Sequence analysis of the RIB43a gene indicates that the substantially coiled-coil rib43a protein shares a high degree of sequence identity with clones from Trypanosoma cruzi and Homo sapiens (genomic, normal fetal kidney, and endometrial and germ cell tumors) but little sequence similarity to other proteins including tektins. Affinity-purified antibodies against native and bacterially expressed rib43a stained both flagella and basal bodies by immunofluorescence microscopy and stained isolated flagellar ribbons by immuno-electron microscopy. The structure of rib43a and its association with the specialized protofilament ribbons and with basal bodies is relevant to the proposed role of ribbons in forming and stabilizing doublet and triplet microtubules and in organizing their three-dimensional structure.

Algal Proteins↗
PubMed2000

Spontaneous mutation in the db gene results in obesity and diabetes in CD-1 outbred mice.

Five allelic mutants of the diabetes (db) gene have been previously described in mice and rats causing obesity, infertility, and varying degrees of diabetes. We have identified a new, spontaneous mutation resulting in obesity and diabetes in a colony of CD-1 outbred mice, Mus musculus domesticus. Genetic complementation studies indicated that the new mutation was an allele of the diabetes locus. Sequence analysis of cDNA fragments showed a deletion of one G residue located in exon 12 of the leptin receptor gene. The mutation, Lepr(db-NCSU), results in a frameshift and reduces Lepr transcript levels 10-fold. Mutant mice drank up to four times more water and were up to two times heavier than wild-type mice. Blood glucose and plasma insulin and leptin concentrations were sexually dimorphic among affected mice, suggesting an effect of sex steroids. Mortality of affected males was 100% by 5 mo, whereas affected females survived up to 10 mo of age.

Alleles↗
PubMed2000

Evidence for an intrarenal renin-angiotensin system in the rainbow trout, Oncorhynchus mykiss.

Physiological and molecular approaches were used to investigate the existence of an intrarenal renin-angiotensin system (RAS) in rainbow trout. Inhibition of angiotensin-converting enzyme by captopril (5 x 10(-4 )M) rapidly decreased vascular resistance of the trunk of the trout, perfused at 19 mmHg, resulting in an increased perfusate flow rate and a decreased intrarenal dorsal aortic pressure. A profound diuresis occurred in the in situ perfused kidney and reflected both increased glomerular filtration rates and decreased water reabsorption (osmolyte reabsorption was unchanged). Renal and vascular parameters recovered once captopril treatment was stopped. Diuretic and vascular effects of captopril on the in situ trout kidney concur with an inhibition of known vasoconstrictor and antidiuretic actions of angiotensin II. However, at a higher perfusion pressure (28 mmHg), captopril had no effect on intrarenal aortic pressure or perfusate and urine flow rates, suggesting that the trout intrarenal RAS is activated by low perfusion pressures/flows. Existence of the renal RAS in trout was further supported by evidence for angiotensinogen gene expression in kidney as well as liver.

Angiotensin II↗
PubMed1999

Novel mutations of the MET proto-oncogene in papillary renal carcinomas.

Hereditary papillary renal carcinoma (HPRC) is characterized by multiple, bilateral papillary renal carcinomas. Previously, we demonstrated missense mutations in the tyrosine kinase domain of the MET proto-oncogene in HPRC and a subset of sporadic papillary renal carcinomas. In this study, we screened a large panel of sporadic papillary renal carcinomas and various solid tumors for mutations in the MET proto-oncogene. Summarizing these and previous results, mutations of the MET proto-oncogene were detected in 17/129 sporadic papillary renal carcinomas but not in other solid tumors. We detected five novel missense mutations; three of five mutations were located in the ATP-binding region of the tyrosine kinase domain of MET. One novel mutation in MET, V1110I, was located at a codon homologous to an activating mutation in the c-erbB proto-oncogene. These mutations caused constitutive phosphorylation of MET when transfected into NIH3T3 cells. Molecular modeling studies suggest that these activating mutations interfere with the intrasteric mechanism of tyrosine kinase autoinhibition and facilitate transition to the active form of the MET kinase. The low frequency of MET mutations in noninherited papillary renal carcinomas (PRC) suggests that noninherited PRC may develop by a different mechanism than hereditary papillary renal carcinoma.

3T3 Cells↗
PubMed1999

IFN-gamma and CD8+ T cells restore host defenses against Pneumocystis carinii in mice depleted of CD4+ T cells.

Host defenses against infection are profoundly compromised in HIV-infected hosts due to progressive depletion of CD4+ T lymphocytes and defective cell-mediated immunity. Although recent advances in antiretroviral therapy can dramatically lower HIV viral load, blood CD4+ T lymphocytes are not restored to normal levels. Therefore, we investigated mechanisms of host defense other than those involving CD4+ T lymphocytes against a common HIV-related opportunistic infection, Pneumocystis carinii (PC) pneumonia. Using CD4-depleted mice, which are permissive for chronic PC infection, we show that up-regulation of murine IFN-gamma by gene transfer into the lung tissue results in clearance of PC from the lungs in the absence of CD4+ lymphocytes. This resolution of infection was associated with a >4-fold increase in recruited CD8+ T lymphocytes and NK cells into the lungs. The role of CD8+ T cells as effector cells in this model was further confirmed by a lack of an effect of IFN-gamma gene transfer in scid mice or mice depleted of both CD4+ and CD8+ T cells. Cytokine mRNA analysis revealed that recruited, lung-derived CD8+ T cells had greater expression of IFN-gamma message in animals treated with the IFN-gamma gene. These results indicate that CD8+ T cells are capable of clearing PC pneumonia in the absence of CD4+ T cells and that this host defense function of CD8+ T cells, as well as their cytokine repertoire, can be up-regulated through cytokine gene transfer.

Adenoviridae↗
PubMed1999

Angiotensin II-induced calcium signalling in isolated glomeruli from fish kidney (Oncorhynchus mykiss) and effects of losartan.

Glomeruli were isolated from the kidney of freshwater-adapted rainbow trout, Oncorhynchus mykiss, to qualitatively evaluate changes in cellular calcium associated with angiotensin II ([Asn1Val5]-Ang II) receptor stimulation and antagonism by the Ang II receptor antagonist losartan. Microspectrofluorometry using the fluorescent calcium indicator dye Calcium Green recorded fluorescence changes in isolated single glomeruli. Isolated glomeruli containing ester-loaded Calcium Green showed an Ang-II-induced transient rise in fluorescence. This transient rise showed an increased peak amplitude with increased Ang II concentration (10(-9) to 10(-6) M), but only a very small response was detectable in glomeruli exposed to 10(-9) M Ang II. The biphenylimidazole compound losartan (=DuP 753), an antagonist of the mammalian AT1 subtype Ang II receptor, initiated a transient agonistic rise in glomerular fluorescence at high concentration (10(-5), 10(-4), and 10(-3) M). However, the responses to 10(-6) 10(-7) M losartan were small or very low in each case. Losartan (10(-4) or 10(-7) M) antagonised the Ang-II-induced signalling in isolated glomeruli exposed to 10(-7) or 10(-6) M Ang II, respectively. This is the first evidence for functional AT1-like Ang II receptors coupled to cellular calcium signalling in the glomeruli of rainbow trout.

Angiotensin II↗
PubMed1999

Determinants of job stress and job satisfaction among supervisory and non-supervisory employees in a large Canadian teaching hospital.

This article explores the extent to which hospital workers at a large teaching hospital at different managerial/supervisory levels (designated and non-designated supervisors, and non-supervisory staff), experienced job stress and job satisfaction prior to the re-engineering of hospital services. For all groups, increased levels of job demands were associated with higher levels of stress. Lower levels of decision latitude were associated with increased job stress for designated supervisors. Increasing levels of decision latitude were associated with both job stress and satisfaction for the other two groups. Co-worker support and teamwork contributed to increased job satisfaction for all groups.

Adaptation, Psychological↗