Search PubMed⌕ Search

Biomedical subjects

J Brown

Publications and source records attributed to J Brown.

At least 523 records · Page 29Linked to original sources
PubMed1994

Effects of physiological increments in human alpha-atrial natriuretic peptide and human brain natriuretic peptide in normal male subjects.

1. Brain natriuretic peptide, closely related to atrial natriuretic peptide in structure, may be an important circulating hormone. Its physiological role is unclear. First, we studied the effects of incremental infusions of brain natriuretic peptide in six healthy men on plasma brain natriuretic peptide levels and the pharmacokinetics of brain natriuretic peptide. Synthetic human brain natriuretic peptide-32 was infused intravenously, at an initial rate of 0.4 pmol min-1 kg-1, doubling every 15 min until the dose rate reached 6.4 pmol min-1 kg-1, at which rate the infusion was maintained for 30 min. 2. The brain natriuretic peptide infusion raised the brain natriuretic peptide-like immunoreactivity from 1.4 +/- 0.5 pmol/l to 21.4 +/- 7.6 pmol/l. Brain natriuretic peptide-like immunoreactivity after the end of infusion was consistent with a bi-exponential decay, with half-lives of 2.1 min and 37 min. 3. Next, we studied the effects of low-dose infusion of brain natriuretic peptide to mimic physiological increments in the circulating levels in comparison with atrial natriuretic peptide. Six dehydrated male subjects received intravenous infusions of atrial natriuretic peptide and brain natriuretic peptide, separately and in combination, in a randomized double-blind, placebo-controlled, four-part cross-over design. Atrial natriuretic peptide and brain natriuretic peptide were given at the rate of 0.75 and 0.4 pmol min-1 kg-1, respectively, for 3 h. The control infusion consisted of the vehicle. 4. Analysis of variance showed that atrial natriuretic peptide and atrial natriuretic peptide plus brain natriuretic peptide, but not brain natriuretic peptide alone, increased urinary flow and decreased urinary osmolality significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Activity of Ca2+/calmodulin-dependent protein kinase II following ischemia: a comparison between CA1 and dentate gyrus in a hippocampal slice model.

Both CA1 and dentate gyrus regions of the hippocampal slice exhibit an irreversible loss of synaptic transmission after exposure to in vitro ischemic conditions (buffer without oxygen and glucose). However, after shorter durations of ischemia (8-10 min) the CA1 region shows an irreversible loss of synaptic responses, whereas the dentate gyrus region completely recovers synaptic responses upon reoxygenation. To determine biochemical mechanisms underlying this differential susceptibility, we have examined changes in Ca2+/calmodulin-dependent protein kinase II (CaM-KII) and cyclic AMP-dependent protein kinase activities in homogenates from CA1 and dentate gyrus regions of the hippocampal slice after increasing durations of in vitro ischemia. Time-dependent changes in CaM-KII activities were correlated with changes in electrophysiological responses. CA1 homogenates from slices exposed to 1 min of ischemia showed significant increases in CaM-KII activity, whereas there was no significant change in kinase activity in dentate homogenates after 1 min of ischemia. However, after longer durations of ischemia (5, 10, and 20 min) we found a time-dependent reduction in CaM-KII activity in both CA1 and dentate gyrus regions, whereas no change was detected in cyclic AMP-dependent protein kinase activity. Irreversible depression of CaM-KII activity was seen at shorter durations of ischemia (10 min) in the CA1 region than in dentate region (20 min), which correlated with irreversible effects on synaptic responses. Immunoblot analysis showed that the decrease in CaM-KII activity was not due to degradation of CaM-KII protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1994

Distribution of clindamycin in cortical bone during direct local infusion of the canine tibia.

The distribution of clindamycin in tibial cortical bone, administered via direct local infusion with an implantable pump, is described. Clindamycin concentrations in cortical bone were measured after 3, 7, and 21 days of intraosseous infusion. The tibia were divided into four quadrants relative to the outflow infusion catheter site located in the medial aspect of the mid-diaphysis. A gradient of 5-30 mm from the infusion site was documented in all four quadrants (proximal lateral, proximal medial, distal lateral, and distal medial). At all sampling times, clindamycin concentrations in all quadrants exceeded the minimum inhibitory concentrations for gram-positive aerobic bacteria, including Staphylococcus aureus and S. epidermidis, and both the gram-positive and gram-negative anaerobes, including Peptostreptococcus species and Bacteroides species. The data suggest that gravitational forces affect the diffusion of the clindamycin because concentrations in both distal quadrants were greater than in corresponding proximal quadrants.

Animals↗
PubMed1994

Recurrent erythema multiforme: tissue typing in a large series of patients.

Previous reports have shown an increased frequency of certain HLA antigens in association with erythema multiforme, including HLA-B15(B62), HLA-B35, HLA-A33, HLA-DR53 and, more recently, HLA-DQB1*0301. A strong association with HLA-DQ3 has been documented in patients with recurrent erythema multiforme. We have performed HLA typing in 39 patients with recurrent erythema multiforme, of whom 33 were associated with herpes simplex virus infection. The results were compared with 309 controls. In the recurrent erythema multiforme patients there was a statistically significant increase in HLA-B62 and HLA-B35. An increase in HLA-DR53 was also found, although this did not reach statistical significance. There was no increase in HLA-A33. The presence of HLA-DQ3 in the study population approached that in the controls. Finally, the study population demonstrated a trend towards a reduction in the HLA antigens A1, B8 and DR3. The study confirms the previously reported associations with HLA-B62 (B15), HLA-B35 and HLA-DR53. We have been unable to confirm an association of HLA-A33 or HLA-DQ3 with erythema multiforme. The HLA antigens A1, B8, and DR3 are associated with autoimmune disease, reflecting an increased host response to tissue self antigens. Their absence in patients with recurrent erythema multiforme (REM) may be an indicator of a poor host response to an antigen, which in the case of REM is the herpes simplex virus.

Adult↗
PubMed1994

Peripheral mononuclear cells of haemophiliacs with chronic liver disease are infected with replicating hepatitis C virus.

Most haemophiliacs treated with non-virally inactivated concentrates have been infected with the hepatitis C virus (HCV). 19/21 (90%) patients with HCV antibody were found to have HCV RNA in their serum and in 16 of these it was also detected in peripheral blood mononuclear cells (PBMC). We used specific primers to detect the negative (replicative) strand of this single positively stranded virus. The negative strand was detected in the serum or PBMC of 16 patients indicating active replication outside the liver. The detection of replicating HCV RNA in the cells of HIV negative haemophiliacs could explain at least some of the immunological abnormalities previously reported in these patients and attributed to clotting factor concentrates.

Chronic Disease↗
PubMed1994

Legionnaires' disease outbreak, Fairfield 1992: public health aspects.

An investigation of an outbreak of Legionnaires' disease in 1992 in Fairfield, a municipality of Sydney, was carried out to determine the source of the outbreak. Cases of Legionnaires' disease with onset of symptoms between 11 and 20 April 1992 were included. Definite cases were individuals with a history consistent with Legionnaires' disease, confirmed by direct fluorescent antibody testing plus serology or culture. There were two control groups: patients admitted to the same hospital as the cases, matched for age and sex, and patients admitted to hospital with a presumptive diagnosis of legionnaires' disease, in whom the diagnosis was subsequently excluded. There were 26 definite cases with onset of symptoms between 11 and 20 April 1992. Six (23 per cent) died. Twenty-two cases (85 per cent) reported visiting the Fairfield business district during the ten days prior to the onset of symptoms. They were 20 times more likely to have visited Fairfield than were matched controls. Matching of Legionella pneumophila serogroup 1 from environmental and clinical samples was achieved by cytogenetic fingerprinting. Fourteen cases were linked to a single environmental sample. The epidemiological findings were consistent with a point source of Legionella in the Fairfield business district. It is most likely that the exposure occurred on 10 April 1992.

Adult↗
PubMed1994

Biochemical characterization of a glutaryl-7-aminocephalosporanic acid acylase from Pseudomonas strain BL072.

Pseudomonas strain BL072 produces an acylase enzyme active in hydrolyzing glutaryl-7-aminocephalosporanic acid to 7-aminocephalosporanic acid. This acylase was purified by column chromatography and gel electrophoresis. The native acylase was composed of two subunits of approximately 65 and 24 kDa, though some heterogeneity was seen in both the native acylase and its small subunit. The isoelectric point of the acylase is approximately 8.5, and it has Km of 1.6 mM for glutaryl desacetoxy aminocephalosporanic acid. The acylase hydrolyzes the desacetoxy and desacetyl derivatives of glutaryl-7-aminocephalosporanic acid at rates similar to that of glutaryl-7-aminocephalosporanic acid. Cephalosporin C was hydrolyzed at a reduced rate. The pH optimum was found to be 8.0, and an activation energy of 9 kcal/mol (ca. 38 kJ/mol) was observed. The acylase has transacylase activity 10 times that of its hydrolytic activity. Eupergit C-immobilized acylase had a half-life of greater than 400 h.

Amidohydrolases↗
PubMed1994

Blepharophimosis sequence and diaphragmatic hernia associated with interstitial deletion of chromosome 3 (46,XY,del(3)(q21q23)).

A case of blepharophimosis, ptosis, and epicanthus inversus (BPES) associated with prenatally diagnosed diaphragmatic hernia and interstitial deletion of the long arm of chromosome 3, del(3)(q21q23), is reported. Comparison with other cases of BPES resulting from 3q rearrangements indicate that this disorder, previously assigned to 3q2, can now be more accurately mapped to 3q23.

Abnormalities, Multiple↗
PubMed1994

Receptor proteins and biological effects of C-type natriuretic peptides in the renal glomerulus of the rat.

Binding studies on rat glomeruli using 125I-labeled Tyr0-C-type natriuretic peptide-(1-22) [125I-Tyr0-CNP-(1-22)] and 125I-labeled alpha-atrial natriuretic peptide (alpha-125I-ANP), and the unlabeled ligands CNP-(1-22), alpha-ANP, and des-Gln18,Ser19,Gly20,Leu21,Gly22-ANP-(4-2 3)-NH2 (C-ANP) suggest that receptor-like sites that bind both alpha-ANP and C-ANP fall into two categories, one with high [dissociation constant (Kd) approximately 10(-9)M] and one with low (Kd approximately 10(-5)M) affinity for CNP-(1-22). Covalent attachment of 125I-Tyr0-CNP-(1-22) and alpha-125I-ANP to these sites identifies two membrane proteins with corresponding properties. The first, which can be labeled by both radioligands, is a disulfide-bridged approximately 140-kDa protein that is reduced by dithiothreitol to approximately 67 kDa. This protein binds C-ANP and has Kd approximately 10(-10) M for CNP-(1-22). The second protein, which is labeled only by alpha-125I-ANP, also binds C-ANP, but has Kd approximately 10(-5)M for CNP-(1-22). This approximately 77-kDa protein may also have a disulfide-bridged, high-molecular-mass form of approximately 140 kDa in the absence of dithiothreitol. Studies of glomerular function show that alpha-125I-ANP is internalized whereas 125I-Tyr0-CNP-(1-22) is not. C-ANP abolishes the specific internalization of alpha-125I-ANP. CNP-(1-22) inhibits internalization of 400 pM alpha-125I-ANP weakly, only approximately 60% being inhibited by 10 microM CNP-(1-22). This implies that the approximately 77-kDa protein, with its low affinity for CNP-(1-22), mediates internalization. Furthermore, CNP-(1-22), as well as alpha-ANP and C-ANP, inhibits glomerular levels of adenosine 3',5'-cyclic monophosphate (cAMP), and CNP-(1-22) does so with a high affinity, which corresponds to its affinity for the approximately 67-kDa protein. The results suggest that the approximately 67-kDa receptor is distinct from the natriuretic peptide clearance receptor and may control cAMP levels.

Amino Acid Sequence↗
PubMed1994

Diagnosing and managing unstable angina. Agency for Health Care Policy and Research.

This Quick Reference Guide for Clinicians contains recommendations on the care of patients with unstable angina based on a combination of evidence obtained through extensive literature reviews and consensus among members of an expert panel. Principal conclusions include the following. (1) Many patients suspected of having unstable angina can be discharged home after adequate initial evaluation. (2) Further outpatient evaluation may be scheduled for up to 72 hours after initial presentation for patients with clinical symptoms of unstable angina judged at initial evaluation to be at low risk for complications. (3) Patients with acute ischemic heart disease judged to be at intermediate or high risk of complications should be hospitalized for careful monitoring of their clinical course. (4) Intravenous thrombolytic therapy should not be administered to patients without evidence of ST segment elevation and acute myocardial infarction. (5) Assessment of prognosis by noninvasive testing often aids selection of appropriate therapy. (6) Coronary angiography is appropriate for patients judged to be at high risk for cardiac complications or death based on their clinical course or results of noninvasive testing. (7) Coronary artery bypass surgery should be recommended for almost all patients with left main disease and many patients with three-vessel disease, especially those with left ventricular dysfunction. (8) The discharge care plan should include continued monitoring of symptoms; appropriate drug therapy, including aspirin; risk-factor modification; and counseling.

Ambulatory Care↗
PubMed1994

UK cervical cancer screening programme: setting a research agenda.

The UK national cervical cancer screening programme aims at reducing the incidence of and mortality from carcinoma of the cervix. It is generally agreed that high grade cervical intraepithelial neoplasia should be treated aggressively, but the appropriate management strategies for women with lesser degrees of abnormality are uncertain because of the inability to distinguish lesions that are likely to progress to invasive disease from those that will regress spontaneously. The role of human papillomavirus (HPV) and the possible usefulness of HPV testing as a secondary screening tool in women with borderline or mild dyskaryosis is also unknown. This paper proposes an agenda for research into the uncertainties within the UK screening programme, suggesting that priority should be given to determining the most appropriate referral and management policies and the use of HPV DNA assay for women with borderline and mild dyskaryosis, so that those women at highest risk of developing invasive disease are treated. A randomised controlled trial is needed. The practical and methodological difficulties which would need to be considered and the need to convene a multidisciplinary research team to develop and implement the trial are highlighted.

Carcinoma↗
PubMed1994

Self-reporting of behavior problems in patients with tic disorders.

Self-awareness of behavioral or emotional problems was examined in 25 children and adolescents with tic disorders by comparing the Youth, Parent, and Teacher forms of the Child Behavior Checklist. In general, their parents reported a significant number of deviant behaviors which were denied by the patients.

Adult↗