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Biomedical subjects

M R Brown

Publications and source records attributed to M R Brown.

At least 181 records · Page 10Linked to original sources
PubMed1990

Characterization of the type 1 fimbrial subunit gene (fimA) of Serratia marcescens.

The nucleotide sequence of a DNA fragment that contains the fimA gene, encoding the major fimbrial subunit, of Serratia marcescens IA506 and associated flanking sequences has been elucidated. In addition, the origin of transcription has been identified and is located 120 base pairs upstream of the fimA initiation codon. The predicted amino acid sequence of the FimA polypeptide exhibits some degree of sequence homology with the fimbrial subunits encoded by the fimA determinants of Klebsiella pneumoniae, Salmonella typhimurium, and Escherichia coli and also to Smf2, the major structural component of mannose-resistant (MR) fimbriae of S. marcescens. The Serratia adhesin that facilitates haemagglutination mediated by type 1 fimbriae is less susceptible to inhibition by D-mannose than has been observed to be the case in other type 1 fimbrial adhesins. The molecule conferring this adherence specificity has been shown to be distinct from the fimA gene product and, therefore, is analogous to the fimbrial systems reported in other species.

Amino Acid Sequence↗
PubMed1990

Possible involvement of the division cycle in dispersal of Escherichia coli from biofilms.

Growth rate control of adherent, sessile populations was achieved by the controlled perfusion of membrane-associated bacterial biofilms by the method of Gilbert et al. (P. Gilbert, D. G. Allison, D. J. Evans, P. S. Handley, and M. R. W. Brown, Appl. Environ. Microbiol. 55:1308-1311, 1989). Changes in cell surface hydrophobicity were evaluated with respect to growth rate for such sessile Escherichia coli cells and compared with those of suspended (planktonic) populations grown in a chemostat. Newly formed daughter cells shed at the various growth rates from the biofilm during its growth and development were also included in the study. Surface hydrophobicity decreased with growth rate similarly for both planktonic and sessile E. coli; no significant differences were noted between the two. Daughter cells dislodged from the biofilm, however, were significantly more hydrophilic than those remaining, indicating that hydrophobicity changed during the division cycle. Our data support the hypothesis that dispersal of cells from adhesive biofilms and recolonization of new surfaces reflect cell-cycle-mediated events.

Bacterial Adhesion↗
PubMed1990

Distinction of NPY receptors in vitro and in vivo. II. Differential effects of NPY and NPY-(18-36).

We have studied the hemodynamic effects of neuropeptide Y (NPY) and its COOH-terminal fragment NPY-(18-36) in conscious rats. Intra-arterial injection of NPY rapidly elevated systemic vascular resistance (SVR), which remained high for greater than 30 min. Cardiac output (CO) decreased, and it remained low for greater than 30 min. Accordingly, blood pressure rose only transiently and returned to base-line values within 5 min. The reduction of CO could be attributed to a decreased stroke volume with an only marginal reduction of heart rate. Thus a direct cardiodepressive effect of NPY rather than baroreflex activation appears to be the major cause of the reduced CO. In vitro experiments excluded the possibility that NPY has direct negative inotropic effects and suggest that its cardiodepressive action is caused by coronary vasoconstriction or by presynaptic inhibition of norepinephrine release. Intra-arterial injections of NPY-(18-36) caused different hemodynamic effects. NPY-(18-36) decreased CO in a manner similar to that seen with NPY but initially did not elevate SVR, resulting overall in a reduced blood pressure. Only later, when blood pressure was reduced, was an elevation of SVR observed, which could be associated with increased plasma levels of catecholamines, angiotensin II, vasopressin, and NPY. Thus NPY-(18-36) mimics the cardiac effects of NPY but does not elicit its vascular effects. As NPY-(18-36) discriminates between NPY receptor subtypes in vitro, we conclude that the cardiac and vascular effects of NPY are mediated by distinct receptor subtypes.

Animals↗
PubMed1990

Cerebroventricular calcitonin gene-related peptide inhibits rat duodenal bicarbonate secretion by release of norepinephrine and vasopressin.

Proximal duodenal bicarbonate secretion is an important factor in humans and animals protecting the mucosa against acid-peptic damage. This study examined the mechanisms responsible for the central nervous system regulation of duodenal bicarbonate secretion by calcitonin gene-related peptide (CGRP) in unrestrained rats. Cerebroventricular administration of rat CGRP significantly inhibited basal duodenal bicarbonate secretion as well as the stimulatory effects of vasoactive intestinal peptide, neurotensin, a luminal PGE1 analogue, misoprostol, and hydrochloric acid. The inhibitory effects of cerebroventricular CGRP were abolished by ganglionic blockade with chlorisondamine, significantly attenuated by noradrenergic blockade with bretylium, and enhanced by vagotomy. Inhibition of duodenal bicarbonate secretion induced by CGRP coincided with significant increases in plasma norepinephrine (NE) and vasopressin concentrations. The alpha adrenergic receptor antagonist, phentolamine, and the vasopressin V1 receptor antagonist, (1-deaminopenicillamine, 2-[O-methyl]Tyr, 8-Arg)-vasopressin, given intravenously reversed the central inhibitory effect of CGRP by approximately 50% each. Pretreatment of the animals with both phentolamine and the vasopressin antagonist completely abolished the central inhibitory effect of CGRP. Peripheral vasopressin and NE significantly decreased duodenal bicarbonate secretion, and their inhibitory effects were additive and prevented by phentolamine and the vasopressin antagonist, respectively. We conclude that cerebroventricular CGRP inhibits rat duodenal bicarbonate secretion by activation of sympathetic efferents and subsequent release of NE and vasopressin that act on alpha adrenergic and vasopressin receptors, respectively.

Adrenalectomy↗
PubMed1989

Outer membrane proteins of gentamicin induced small colony variants of Pseudomonas aeruginosa.

Small colony variants (SCVs) of Pseudomonas aeruginosa NCTC 6750 (WT) were repeatedly isolated in an in vitro kinetic model after exposure to gentamicin (GM). There were minor differences biochemically and in phage and serotyping between the wild type (WT) strain and SCVs. Changes in outer membrane protein profiles were found. SCVs were more resistant to polymixin and to a range of aminoglycosides (except kanamycin), but were more susceptible to a range of other antibiotics (hydrophilic and hydrophobic) with differing modes of action.

Bacterial Outer Membrane Proteins↗
PubMed1989

Elevation of plasma neuropeptide Y levels in congestive heart failure.

PURPOSE: Our objectives were to assess whether plasma neuropeptide Y (NPY) levels are elevated in patients with congestive heart failure (CHF) and whether or not NPY levels can serve as a reliable indicator of sympathetic activity in CHF. PATIENTS AND METHODS: Plasma levels of the sympathetic neurotransmitters norepinephrine and epinephrine and of the sympathetic co-transmitter NPY were measured in 17 patients with CHF and 14 healthy control subjects at rest and after maximal exercise. RESULTS: Under resting conditions, plasma NPY and norepinephrine levels were elevated in patients with CHF compared with control subjects (551 +/- 48 pg/ml versus 311 +/- 22 pg/ml, p less than or equal to 0.001 for NPY, and 306 +/- 73 pg/ml versus 124 +/- 22 pg/ml, p less than or equal to 0.02 for norepinephrine). Plasma NPY correlated better with plasma norepinephrine than with epinephrine, indicating its origin from sympathetic nerve terminals. Acute stimulation of sympathetic activity by dynamic exercise increased plasma norepinephrine levels in control subjects and patients with CHF, but did not significantly alter the mean plasma NPY value in the latter group. CONCLUSION: NPY may play a role in the pathophysiology of CHF.

Adult↗
PubMed1989

Purification and characterization of insect toxins derived from the mite, Pyemotes tritici.

Three low mol. wt proteins which have contracting-paralyzing activity in insects were isolated from extracts of the straw itch mite, Pyemotes tritici. One of these toxins, referred to as TxP-I, was purified to apparent homogeneity using the following sequence: ion-exchange, affinity, hydroxyapatite and reverse-phase chromatography. The other two toxins, referred to as TxP-II, remained as a mixture. Peptide mapping and immunoblot analysis suggest that TxP-I and TxP-II are probably isoproteins. The apparent mol. wt of native TxP-I and of the two components of TxP-II were 27,000, 28,000 and 29,000, respectively. The apparent mol. wt of the toxins after reductive carboxamidomethylation increased to 38,000, 41,000 and 43,000, respectively. The amino acid composition of TxP-I indicates a high content of Cys (8 mole%). Therefore, several disulfide bonds may impart a very compact tertiary structure to this protein which, upon denaturation, unfolds and increases its Stoke's radius resulting in retarded mobility on a polyacrylamide gel. The N-terminal sequence of TxP-I is not homologous with any other protein for which the sequence is known. The paralysis dose50 of TxP-I (PD50) in wax moth larvae is ca. 500 micrograms/kg and it is not toxic to mice at a dose of 50 mg/kg. A polyclonal antibody, raised against TxP-I, reacted with both TxP-I and TxP-II. The antibody neutralized the rapid, muscle-contracting paralysis of these toxins. Using this antibody and immunocytochemistry, we found the toxins localized in posterior glands which appear to be connected with the stylet through a series of ducts. We conclude that TxP-I and TxP-II are part of a complex mixture of neurotoxins which P. tritici utilizes to capture prey.

Amino Acid Sequence↗
PubMed1989

The cardiovascular actions of centrally administered neuropeptide Y.

The cardiovascular actions of intracerebroventricular (i.c.v.) administration of neuropeptide Y (NPY) were examined in conscious, unrestrained rats. A prolonged decrease in heart rate (HR) and a fall in mean arterial pressure (MAP) were obtained following i.c.v. administration of NPY (1 and 10 micrograms). Passive immunization with an antiserum directed against NPY confirmed that the slowing of HR following i.c.v. administration of NPY was mediated via a central nervous mechanism and not from leakage of NPY out of the brain. Administration of NPY into different brain parenchymal regions identified a putative site of action in the rostral region of the solitary tract. The mechanism of the decrease in HR caused by centrally administered NPY was investigated by i.c.v. administration of NPY to animals that were pretreated with agents that altered autonomic tone. Administration of NPY to atropine-treated animals produced a reversal of the atropine-induced tachycardia, suggesting that the NPY-induced decrease in HR was not due to augmented vagal tone. However, administration of NPY to animals pretreated with propranolol did not significantly lower HR below that obtained with propranolol alone. These data suggest that i.c.v. administration of NPY may cause a decrease in cardiac sympathetic outflow. The effects of centrally administered NPY on baroreflex function were studied. The changes in HR caused by NPY did not significantly alter baroreflex set-point or gain. These studies provide evidence that NPY acted within a brainstem region to decrease sympathetic nervous outflow, resulting in a decrease in HR and MAP.

Animals↗
PubMed1989

Iron depletion alters surface-associated properties of Staphylococcus aureus and its association to human neutrophils in chemiluminescence.

Staphylococcus aureus NCTC 6571 was grown in iron-depleted tryptone soya broth (Fe-TSB) to approximate to in vivo conditions, and in iron-rich TSB (Fe + TSB). Low iron effected a crucial decrease in surface hydrophobicity (SH) and a lack of supernatant Protein A (PrA). Iron availability did not affect PrA detection in immunoblotting and it was identified as a 35.5 kDa antigen in this strain. Fe-phenotypes lacked 34, 48 and 52 kDa antigens. In chemiluminescence, Fe-phenotypes appeared least vulnerable to phagocytosis despite opsonisation.

Antigens, Surface↗
PubMed1989

Desmopressin acetate following cardiopulmonary bypass: evaluation of coagulation parameters.

Desmopressin acetate (DDAVP) has been advocated as efficacious in reducing mediastinal bleeding following cardiopulmonary bypass (CPB), and has been shown to ameliorate platelet dysfunction; however, this has not been evaluated during routine coronary artery bypass grafting (CABG). In the present study, this therapy was evaluated utilizing the thromboelastograph (TEG), a rapid, on-line means of diagnosing a coagulopathy. During elective CABG, 20 patients received either DDAVP, 0.3 microgram/kg, intravenously, following heparin reversal after CPB, or a placebo infusion, in a randomized, double-blind fashion. Hemostasis was monitored with both the TEG and conventional coagulation tests. No significant differences between the two groups were found at induction, postprotamine, post-"study infusion," or 2 hours postoperatively, with the exception of the postoperative PTT (31.1 +/- 3.2 v 36.5 +/- 5.9 seconds for DDAVP v placebo, P = 0.03). Total blood products transfused intraoperatively, and in the first 8, 16, 24, or 48 postoperative hours, were also similar between the groups. No manifestations of hypercoagulability were seen, but hypotension during the infusion was noted in four patients receiving DDAVP, and in none of the controls. It is concluded that the expense and potential complications of DDAVP therapy do not justify its routine use in CABG.

Blood Coagulation↗
PubMed1989

Synthesis and hypertensive activity of neuropeptide Y fragments and analogues with modified N- or C-termini or D-substitutions.

Porcine neuropeptide Y (NPY), NPY fragments, and analogues with D-Xaan, Ala9, D-Ala9, and Met17 substitutions or modifications to the C- or N-termini were synthesized. The synthesis and purification of these peptides was achieved by using routine laboratory strategies and techniques. The ability of these peptides to alter mean arterial pressure (MAP) and heart rate (HR) in conscious rats was monitored for 15 min following intraarterial administration. Potencies and efficacies of these peptides relative to NPY were determined by comparison of dose-response curves. Administration of 40 micrograms/kg NPY resulted in a rapid, though short-lived, rise in mean arterial pressure from a basal value of 107.0 +/- 2.6 to 157 +/- 5.5 mmHg (means +/- sem, n = 13). The ED50 (+/- SE) for this response was 3.04 +/- 0.88 micrograms/kg. Peptide YY (PYY) elicited a response that was similar in magnitude but with an ED50 (+/- SE, n = 3) of 0.76 +/- 0.24 micrograms/kg while porcine pancreatic polypeptide (pPP) was inactive when tested at 40 micrograms/kg (n = 4). Relative potencies for [Ac-Tyr1]NPY, [Ac-D-Tyr1]NPY, [des-amino-Tyr1] NPY, and [Me-Tyr1]NPY ranged from 1.1 to 2.2. Potencies relative to NPY for D-substitutions at positions 2-6 and 8-13 inclusive ranged from 0.1 to 1.0. Analogues with D-substitutions at positions 1-3 exhibited an extended duration of action. Analogues with D-substitutions at positions 33-35 inclusive were inactive at 40 micrograms/kg, and [D-Tyr36]NPY was 10-fold less potent than NPY, suggesting that the integrity of the C-terminal region is critical to the overall biological action of NPY. This conclusion is supported by studies with C- and N-terminal deletion peptides. NPY2-36 showed full intrinsic activity at 40 micrograms/kg and retains 40% of the hypertensive potency of NPY. There was a sequential decrease in efficacy upon further N-terminal deletion. In contrast to the finding with NPY2-36, modification of the C-terminus either from the native carboxamide to the free carboxylic acid or by deletion of the C-terminal residue resulted in analogues which were inactive at 40 micrograms/kg. These data indicate that an essentially full-length, C-terminally amidated NPY structure is required for the hypertensive activity observed in conscious rats upon intraarterial administration of NPY and NPY analogues.

Animals↗