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Biomedical subjects

M R Brown

Publications and source records attributed to M R Brown.

At least 217 records · Page 12Linked to original sources
PubMed1988

Autonomic and cardiovascular effects of corticotropin-releasing factor in the spontaneously hypertensive rat.

Corticotropin-releasing factor (CRF) administered intracerebroventricularly (i.c.v.) produced a greater increase of plasma epinephrine and glucose concentrations in spontaneously hypertensive rats (SHR) than in Wistar-Kyoto (WKY) or Sprague-Dawley (SD) rats. In contrast, CRF given i.c.v. produced significant elevations of mean arterial pressure (MAP) and heart rate (HR) in WKY and SD rats, but not in SHRs. To determine whether the prominent rise of plasma epinephrine levels following CRF administration to SHRs was a unique response to this peptide, two other stimuli for epinephrine secretion were evaluated, i.e. bombesin given i.c.v., and insulin given intravenously (i.v.). In contrast to the apparent enhanced responsiveness of the SHR to CRF, plasma epinephrine levels following either bombesin or insulin administration were similar in SHR, WKY and SD rats. These results demonstrate that the adrenomedullary response to CRF administration in the SHR is of greater magnitude than in WKY or SD rats. In an effort to identify the mechanisms responsible for the differential cardiovascular and adrenomedullary responses to CRF in the SHR versus WKY rat, CRF binding studies were performed. No difference in binding affinity of [125I]CRF or CRF receptor number could be identified in brains from SHR and WKY rats. Thus, CRF influences cardiovascular and adrenomedullary functions in a qualitatively dissimilar fashion in SHR and WKY rats. These differences are not secondary to any measurable alteration in CRF receptor affinity and number in SHR and WKY rats.

Animals↗
PubMed1988

Effects of morphine and opioid peptides on plasma levels of atrial natriuretic peptide.

The effect of opiate ligand administration on plasma levels of atrial natriuretic peptide (ANP) was studied in awake, freely moving Sprague-Dawley rats. Prior to and following the intracerebroventricular (icv) or central venous (iv) injection of morphine (MS), leu-enkephalin (Leu-enk), dynorphin (Dyn) or beta-endorphin (B-endor), plasma samples were obtained for measurement of ANP concentrations by radioimmunoassay. MS was 10 times more potent when given icv than when given iv to increase plasma ANP levels. Icv injection of Leu-enk decreased plasma ANP concentrations. Dyn and B-endor administration (iv or icv) did not alter the plasma concentration of ANP. These effects of MS and Leu-enk on plasma concentrations of ANP appear to be mediated through actions on the central nervous system. MS, Leu-enk, B-endor, and Dyn given icv, produced elevations of plasma norepinephrine (NE) and epinephrine (Epi) concentrations. When MS was given icv, mean Epi and NE plasma levels increased 10-50 times the increases noted with B-endor, Leu-enk and Dyn. A role of catecholamines in mediating MS-stimulated ANP release is supported by the observation that ganglionic blockade with chlorisondamine significantly attenuated the increase of plasma ANP levels. MS, but not B-endor, Leu-enk and Dyn, acts within the brain to increase plasma levels of ANP. MS-induced elevations of plasma ANP levels may be dependent on an intact autonomic nervous system.

Animals↗
PubMed1988

Peptide injections into the amygdala of conscious rats: effects on blood pressure, heart rate and plasma catecholamines.

The central nucleus of the amygdala (Ce) mediates cardiovascular and autonomic changes associated with defense or fear responses. At least 16 different neuropeptides have been identified within nerve terminals within the Ce. The role that these peptides play in the Ce regulation of cardiovascular and autonomic function has been assessed. Neuropeptides were microinjected into the region of the Ce and mean arterial pressure (MAP), heart rate (HR) and plasma catecholamine concentrations were measured. Five of the 16 peptides caused changes of MAP and HR. Thyrotropin releasing factor (TRF) and calcitonin gene-related peptide (CGRP) induced increases of MAP and HR. Angiotensin-II (A-II) and somatostatin-28 (SS-28) injection produced increases of MAP and decreases of HR. Bombesin (Bom) injections into the Ce induced an increase of MAP but did not alter HR. Corticotropin releasing factor (CRF), TRF and CGRP were the only peptides found to increase plasma catecholamine concentrations. These results support the conclusion that the Ce contains several peptides that could be involved in the regulation of cardiovascular and autonomic nervous system function. A role of the amygdala in mediating the observed effects of CRF, TRF, CGRP, A-II, SS-28, and Bom is suggested by these studies.

Amygdala↗
PubMed1988

Arm muscle plus bone area: anthropometry and CAT scan compared.

Arm muscle plus bone (M + B) cross-sectional area of the arm estimated from area circumference and skinfold thickness was compared with that estimated from CAT scans. The anthropometric technique overestimated M + B area, and the degree of overestimation varied directly with arm adiposity.

Adolescent↗
PubMed1988

Outer membrane proteins of polymyxin resistant Pseudomonas aeruginosa: effect of magnesium depletion.

Pseudomonas aeruginosa strain PA01, which is normally sensitive to 10 units/ml of polymyxin, was adapted in eight successive steps to be resistant to polymyxin at 6000 units/ml. The polymyxin-resistant variant was very sensitive to all other antibiotics with which it was challenged, including hydrophobic antibiotics such as erythromycin. This increased sensitivity implies that the acquired polymyxin resistance had disrupted the permeability barrier of the outer membrane. Changes in the outer membrane protein profile of PA01 were studied at each adaption step using sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). At the third step (resistant to 80 units/ml) protein H1 was absent. At succeeding steps up to 6000 units/ml of polymyxin, protein H1 was still absent and the levels of OM proteins D, E, F (major porin) and G were all considerably reduced compared with the wild type. Overproduction of protein H1 by wild type P. aeruginosa under conditions of magnesium depletion has been proposed as a mechanism to explain polymyxin resistance. However, protein H1 remained absent from the outer membrane of the polymyxin-resistant variants even under magnesium depletion. Furthermore, protein H1 could not be induced by magnesium depletion when the resistant variant was repeatedly grown in concentrations of polymyxin as low as 10 units/ml yet, at this low concentration, the variant retained its resistance to 6000 units/ml. These observations make it unlikely that induction of protein H1 alone is a mechanism of polymyxin resistance in P. aeruginosa.

Bacterial Outer Membrane Proteins↗
PubMed1988

The neurohumoral response to burn injury in patients resuscitated with hypertonic saline.

Fourteen adult patients (mean age, 35 yrs) with 20-60% total body surface area (TBSA) burns (mean, 35%) were resuscitated using hypertonic sodium lactate (HSL: sodium = 250 mEq/L). Plasma concentrations of atrial natriuretic peptide (ANP), arginine vasopressin (AVP), angiotensin II (A-II), epinephrine (E) and norepinephrine (NE) were measured on admission and for 7 days following burn injury. Serum sodium concentrations and osmolalities were lowest on admission, and were persistently elevated following HSL resuscitation. Plasma AVP levels were highest on admission and correlated with the size of the burn injury. Between days 4 and 5 plasma ANP levels rose while plasma AVP levels returned to normal. Plasma concentrations of AVP and ANP did not correlate with serum osmolality or serum sodium concentrations on admission or after HSL resuscitation. Plasma levels of A-II, NE and E were elevated throughout the 7-day period and were unrelated to the size of the burn.

Adult↗
PubMed1988

Penetration of immunoglobulins through the Klebsiella capsule and their effect on cell-surface hydrophobicity.

The ability of antibodies to cell-surface components of Klebsiella to increase surface hydrophobicity and to gain access to antigens potentially masked by the capsule was investigated. Treatment of capsulate or non-capsulate strains with the respective autologous antiserum resulted in a marked increase in surface hydrophobicity. Antisera raised against a rough non-capsulate (K-O-) strain had little effect on the surface hydrophobicity of either of the capsulate strains K1+O1+ and K2+O1+, or of the non-capsulate K-O1+ strain. Whereas anti-K-O1+ sera or anti-K2+ sera increased the surface hydrophobicity of the K2+O1+ strain, only antisera containing anti-K1+ antibodies increased the hydrophobicity of the K1+O1+ strain. Immunoadsorption of anti-K-O1+ serum by whole capsulate cells revealed that neither the K1 nor the K2 capsular polysaccharide acted as a barrier to anti-O antibodies but that the K1 capsular polysaccharide masked the presence of the immunoglobulin at the cell surface. The Klebsiella capsular polysaccharide does not appear to present a permeability barrier to immunoglobulins although failure to detect outer-membrane proteins in the immune complexes of either of the capsulate strains or of the K-O1+ strain suggests that the O antigen may prevent access of antibodies to these antigens.

Antibodies, Bacterial↗
PubMed1988

Use of immunoblot detection of serum antibodies in the diagnosis of chronic Pseudomonas aeruginosa lung infection in cystic fibrosis.

Antibodies to Pseudomonas aeruginosa were investigated in serum from cystic fibrosis (CF) patients by immunoblotting (Western blotting). The results were compared with determinations of precipitating antibodies in serum by crossed immune electrophoresis (CIE). The number of CIE precipitins is a sensitive and specific indication of infection and is used, with sputum bacteriology, to distinguish between colonisation and invasive lung infection. Immunoblotting was considerably more sensitive than CIE for detecting antibodies to P. aeruginosa. Paired serum samples from 64 CF patients, taken before a diagnosis of P. aeruginosa lung infection and immediately afterwards, showed a marked increase in the number of serum antibodies with the onset of infection. The intensity of the reaction, as shown by the density of blotted bands, was also increased. Laser scanning densitometry of immunoblots, and of photographic negatives taken from them, was used to quantify the increases. Differences in the number and intensity of blotted bands were highly significant between the two groups. The reproducibility of the method was good. An immunoblot assay may be a sensitive and useful method for routine diagnosis of early P. aeruginosa lung infection in CF.

Adult↗
PubMed1988

Antibody response to Pseudomonas aeruginosa surface protein antigens in a rat model of chronic lung infection.

For an animal model of infection to be useful in immunological studies it is necessary to establish that the surface antigens expressed by bacteria growing in vivo in the experimental infection mimic those expressed by bacteria in the human infection. In this study, chronic infection was induced by inoculating the lungs of rats with agar beads containing mucoid Pseudomonas aeruginosa. P. aeruginosa was obtained from the lungs 14 days after infection and studied without subculture. Several high-mol.-wt proteins were expressed in the outer membranes (OM) of the bacteria from the rat lungs which could be induced by cultivating the same isolate in iron-depleted conditions in vitro. The pattern of iron-regulated membrane proteins (IRMP) was similar to that obtained in an earlier study with another mucoid isolate of P. aeruginosa examined directly, without subculture, from the sputum of a cystic fibrosis patient. Immunoblotting with LPS-absorbed serum from infected rats and also with serum from CF patients showed that IgG in these fluids reacted with the IRMPs and other major OM proteins (OMPs) of P. aeruginosa. Antisera from rats immunised with whole cells of P. aeruginosa grown in iron-depleted media reacted with all the major OMPs of P. aeruginosa, including the IRMPs, confirming their immunogenicity.

Animals↗
PubMed1988

Influence of cephalosporins and iron on surface protein antigens of Klebsiella pneumoniae in vivo.

The outer membrane protein (OMP) profiles of Klebsiella pneumoniae grown in a rabbit peritonitis model in the presence or absence of cephalosporins were investigated. Six high-molecular-weight OMPs (Mr 69,000 to 83,000) were induced under iron-depleted conditions in vitro. Three of these proteins (the 69,000-Mr protein [69K protein] and the 70K and 78K proteins) and trace amounts of the 73K and 75K proteins were induced in the OM of bacteria infecting the peritoneal cavity of rabbits. Addition of iron either to the growth medium in vitro or to the peritoneum in vivo repressed the expression of these proteins. Cephaloridine had no significant effect on the OMP profiles. An additional 56,000-Mr protein was observed in the OM of bacteria cultivated in vivo in the presence of CGP 17520 and also to a lesser extent in vivo under conditions of iron excess. A difference in recognition of OM antigens between cells grown in vitro and in vivo was observed by immunoblotting techniques. The 26K, 27.5K, and 28.5K antigens present in the OM of cells grown in vitro (but not in vivo) were recognized by antibodies raised against bacteria cultivated in vitro under conditions of iron depletion, but were not recognized by antisera raised against bacteria harvested directly from infections. Antisera raised against a nonencapsulated K. pneumoniae strain caused no agglutination of encapsulated K. pneumoniae grown in vivo in the absence of cephalosporins. Rapid agglutination was observed with this antiserum when the same encapsulated strain was grown in vivo in the presence of either cephalosporin, indicating less occlusion of critical antigens by the capsule.

Agglutination Tests↗
PubMed1988

Somatostatin-28 effects on central nervous system regulation of vasopressin secretion and blood pressure.

Somatostatin-28 (SS-28) acted within the central nervous system (CNS) to produce a dose-dependent elevation of mean arterial pressure (MAP), a reduction of heart rate (HR), and an elevation of the plasma concentration of vasopressin. SS-28 given intravenously did not affect MAP or HR. Furthermore, these changes of cardiovascular functions were not prevented by systemic passive immunization against SS-28, thus supporting a CNS site of action. Microinjections of SS-28, in amounts ineffective when given into the lateral cerebroventricle or other brain parenchymal areas, into the paraventricular nucleus of the hypothalamus produced significant elevations of MAP. Neither ganglionic blockade with chlorisondamine nor treatment with the alpha-adrenergic receptor antagonist, phentolamine, prevented SS-28-induced changes of cardiovascular function; however, treatment of animals with the vasopressin antagonist [1-deaminopenicillamine, 2-(0-methyl)Tyr]-vasopressin completely prevented SS-28-induced elevation of MAP and slowing of HR. These results suggest that SS-28 acts within the CNS to increase MAP and decrease HR by stimulating pituitary vasopressin secretion.

Animals↗
PubMed1988

Ultrastructure of the encapsulation of Plasmodium cynomolgi (B strain) on the midgut of a refractory strain of Anopheles gambiae.

Using transmission electron microscopy, we investigated the encapsulation of the simian malaria parasite, Plasmodium cynomolgi, in a refractory strain of the mosquito, Anopheles gambiae. After the ookinete penetrates the mosquito midgut epithelium and lodges between the basal membrane and the basal lamina, an electron-dense, melanin-like substance begins to coalesce around the parasite. Completely encapsulated parasites were found as early as 16 hr after the blood meal. Granules of the melanin-like substance often appeared to condense onto the parasite from the fluid in the extracellular spaces of the basal membrane labyrinth. Melanin granules also appeared to condense from the hemolymph onto the basal lamina underlying the parasite. In addition, groups of tubules, vesicles, and membranous whorls often were found in midgut cells that were located next to or were enclosing parasites. These structures were unusually electron-dense, and may have been associated with melanization. Hemocytes rarely were observed near completed capsules and neither hemocytes nor their remnants were components of the capsules. During later stages of encapsulation, parasites appeared abnormal and often were infiltrated with melanin. Although late-stage capsules were usually located basally, completed capsules enclosed by membranes were occasionally observed near the apical border of the midgut. Other capsules associated with cellular debris, were found in the lumen of the midgut from 1 to 6 days after the blood meal.

Animals↗
PubMed1987

Central nervous system actions of beta-endorphin on gastric acid secretion.

We assessed the central nervous system (CNS) actions of beta-endorphin on gastric acid secretion in awake dogs. Synthetic beta-endorphin (0.2-2.0 nmol X kg-1), but not Leu- or Met-enkephalin, microinjected into the third cerebral ventricle, significantly (P less than 0.01) decreased gastric acid secretion stimulated by pentagastrin. beta-Endorphin given intracerebroventricularly inhibited gastric acid secretion following 2-deoxy-D-glucose (P less than 0.01), but not after stimulation with histamine. Intravenous administration of beta-endorphin did not inhibit gastric acid secretion. beta-Endorphin decreased gastric acid secretion but not the concomitant release of gastrin stimulated by a 200-ml liquid meal containing 8% peptone. Pretreatment of the animals with the opioid antagonist, naloxone, prevented the gastric inhibitory effect of beta-endorphin. Furthermore, either ganglionic blockade with chlorisondamine or truncal vagotomy completely abolished the gastric inhibitory action of beta-endorphin. These findings indicate that beta-endorphin, but neither Leu- nor Met-enkephalin, acts within the CNS to inhibit gastric acid secretion in awake dogs. beta-Endorphin-induced inhibition of gastric acid secretion is mediated by an opiate-dependent pathway and by the autonomic (parasympathetic) nervous system.

Animals↗
PubMed1987

Intracerebroventricular administration of human calcitonin and human calcitonin gene-related peptide inhibits meal-stimulated gastric acid secretion in the dog.

This study was designed to assess the central nervous system actions of human calcitonin (hCalc) and human calcitonin gene-related peptide (hCGRP) on meal-stimulated gastric acid secretion in awake beagle dogs. hCalc (0.1-1.0 nmol/kg) and hCGRP (0.01-1.0 nmol/kg) injected into the third cerebral ventricle significantly inhibited gastric acid secretion stimulated by an 8% peptone meal. hCGRP was ten times more potent than hCalc in inhibiting gastric secretion. Neither hCalc nor hCGRP significantly altered plasma gastrin concentrations compared to control values. Truncal vagotomy did not prevent the gastric inhibitory actions of hCalc and hCGRP. Ganglionic blockade with chlorisondamine completely abolished the gastric inhibitory action of hCalc but had no effect on gastric acid inhibition induced by hCGRP. The results of this study indicate that intracerebroventricular administration of hCalc and hCGRP inhibits meal-stimulated gastric acid secretion in awake dogs. Inhibition of gastric acid secretion by hCalc and hCGRP in the dog is not mediated by inhibition of gastrin release or by the vagus nerves. Human Calc but not human CGRP appears to inhibit meal-stimulated gastric acid secretion in the dog by activation of the autonomic (sympathetic) nervous system.

Animals↗