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Biomedical subjects

M R Brown

Publications and source records attributed to M R Brown.

At least 253 records · Page 14Linked to original sources
PubMed1986

CNS actions of calcitonin gene-related peptide on gastric acid secretion in conscious dogs.

To determine the mechanisms of action of calcitonin gene-related peptide (CGRP) in inhibiting gastric acid secretion, we studied awake male beagle dogs fitted with a chronic intracerebroventricular cannula and a gastric fistula. Synthetic rat CGRP (10 pmol/kg to 10 nmol/kg) given intracerebroventricularly or intravenously significantly inhibited pentagastrin-stimulated gastric acid secretion. CGRP (1 nmol/kg) given intracerebroventricularly decreased acid secretion stimulated by 2-deoxy-D-glucose but not by histamine. CGRP-(1-14), [Tyr23]CGRP-(23-37), and [acetamidomethyl-Cys2,7]CGRP, the linear peptide molecule devoid of the disulfide bridge, did not affect gastric secretion. Ganglionic blockade with chlorisondamine, a vasopressin antagonist, naloxone, and truncal vagotomy did not abolish the gastric inhibitory action of CGRP given intracerebroventricularly. CGRP administered intracerebroventricularly and intravenously decreased gastric acid secretion, but not plasma gastrin concentrations stimulated by an 8% peptone meal. It is concluded that CGRP given intracerebroventricularly or intravenously inhibits gastric acid secretion in conscious dogs; the intact molecule appears to be necessary for biological activity; and inhibition of gastric acid secretion by CGRP in the dog is not mediated by the autonomic nervous system or vasopressin-, opiate-, or gastrin-dependent pathways.

Animals↗
PubMed1985

Central nervous system effects of bombesin on the cardiovascular response to cold exposure.

The effects of cold exposure on mean arterial pressure (MAP), heart rate (HR) and oxygen consumption (VO2) were examined in conscious, unrestrained rats receiving intracerebroventricular (i.c.v.) injections of bombesin or appropriate control solutions. Cold exposure elicited significant elevations of MAP, HR and VO2 in control-treated rats. I.c.v. administration of bombesin produced dose-related suppressions of cold-induced elevations of HR and VO2, but not MAP. The central nervous system (CNS)-selective somatostatin analog, ODT8-SS, injected i.c.v., reversed the effects of bombesin on HR and VO2 during cold exposure. Intravenous administration of atropine methyl nitrate did not antagonize the effects of bombesin on HR and VO2 during cold exposure. HR and VO2 were strongly correlated in bombesin-treated rats suggesting that this peptide may prevent cold-induced elevations of VO2 through a CNS action on cardiac function.

Animals↗
PubMed1985

Corticotropin-releasing factor: a physiologic regulator of adrenal epinephrine secretion.

Pituitary adrenocorticotropic hormone (ACTH) secretion following stress is mediated primarily by the release of corticotropin-releasing factor (CRF) from the brain. We have hypothesized that stress-induced alterations of autonomic nervous system activity also may be dependent on CRF release within the brain because administration of CRF into the brain produces changes in autonomic nervous system function that are similar to those observed following exposure to various types of stress. We now report confirmation of this hypothesis with studies using a CRF receptor antagonist. The CRF receptor antagonist, alpha-helical CRF9-41, placed into the brains of rats suppressed stress-induced elevations of plasma epinephrine levels. Thus, CRF appears to be physiologically involved in coordinating the pituitary and autonomic nervous system responses to stress.

Adrenal Medulla↗
PubMed1985

Central nervous system actions of somatostatin-related peptides.

Somatostatin-related peptides act within the central nervous system to influence adrenomedullary epinephrine secretion and thermoregulation. Cysteamine-induced depletion of brain somatostatin-related peptides or central administration of a somatostatin receptor antagonist alters adrenomedullary epinephrine secretion and thermoregulation in a predictable manner. The actions of cysteamine and the somatostatin receptor antagonist are reversed by administration of somatostatins into the central nervous system, supporting the hypothesis that endogenous brain somatostatin-related peptides are involved in the regulation of adrenomedullary epinephrine secretion and thermoregulation.

Adrenal Medulla↗
PubMed1985

Central nervous system actions of calcitonin gene-related peptide on gastric acid secretion in the rat.

Calcitonin gene-related peptide (CGRP) and its messenger ribonucleic acid have been identified in brain regions that participate in the central nervous system regulation of gastrointestinal functions. The purpose of this study was to determine the central nervous system effect of CGRP on gastric acid secretion and to delineate the mechanism(s) of its action. Calcitonin gene-related peptide (1 pmol-1 nmol) injected intracerebroventricularly inhibited gastric acid secretion in awake, freely moving, pylorus-ligated rats and the secretory response after intracerebroventricularly administered thyrotropin-releasing hormone. Calcitonin gene-related peptide (rat) and calcitonin (salmon) inhibited gastric secretion similarly. Calcitonin gene-related peptide given intracerebroventricularly inhibited gastric acid secretion stimulated by pentagastrin, histamine, or bethanecol for 2 h in anesthetized rats. Adrenalectomy or noradrenergic blockade with bretylium tosylate did not affect the gastric inhibitory action of CGRP. After subdiaphragmatic truncal vagotomy, CGRP did not exhibit the inhibitory effect on gastric acid secretion stimulated by pentagastrin. These studies indicate that CGRP injected intracerebroventricularly is a potent inhibitor of gastric acid secretion in the rat. Calcitonin gene-related peptide decreases gastric secretion stimulated centrally by thyrotropin-releasing hormone and peripherally by pentagastrin, histamine, or bethanecol. Inhibition of gastric acid secretion by CGRP is not mediated by the sympathetic nervous system but may depend on intact vagus nerves.

Animals↗
PubMed1985

Ultrastructure of midgut endocrine cells in the adult mosquito, Aedes aegypti.

The ultrastructure of endocrine cells in the midgut of the adult mosquito, Aedes aegypti, resembled that of endocrine cells in the vertebrate gastro-intestinal tract. Midgut endocrine cells, positioned basally in the epithelium as single cells, were cone-shaped and smaller than the columnar digestive cells. The most distinctive characteristic of endocrine cells was numerous round secretory granules along the lateral and basal plasma membranes where contents of the granules were released by exocytosis. Secretory granules in each individual cell were exclusively of one type, either solid or 'haloed', and for all cells observed, the range in granule diameter was 60-120 nm. The cytoplasm varied in density from clear to dark. Lamellar bodies were prominent in the apical and lateral cellular regions and did not exhibit acid phosphatase activity. The basal plasma membrane was smooth adjacent to the basal lamina, whereas in digestive cells the membrane formed a labyrinth. Some endocrine cells reached the midgut lumen and were capped by microvilli; a system of vesicles and tubules extended from beneath the microvilli to the cell body. An estimated 500 endocrine cells were distributed in both the thoracic and abdominal regions of the adult midgut. In one midgut, we classified a sample of endocrine cells according to cytoplasmic density and granule type and size; endocrine cells with certain types of granules had specific distributions within the midgut.

Aedes↗
PubMed1985

Biological actions of human and rat calcitonin and calcitonin gene-related peptide.

We assessed the central and peripheral biological actions of human and rat calcitonin and calcitonin gene-related peptide (CGRP). After intravenous administration, human and rat calcitonin, but neither human nor rat CGRP significantly decreased plasma calcium and phosphorus concentrations in awake, freely moving rats. After intracerebroventricular as well as after intravenous administration, human and rat calcitonin and human and rat CGRP significantly inhibited gastric acid secretion in conscious rats. Intracerebroventricular administration of rat calcitonin did not alter plasma calcium and phosphorus concentrations. Linear, partially protected CGRP and calcitonin did not exhibit any biological effects. These studies indicate that calcitonin, but not CGRP, affects calcium and phosphorus homeostasis while both peptides decrease gastric acid secretion similarly. Furthermore, these studies support the hypothesis that the calcium and phosphorus lowering effects of calcitonin are peripheral while the gastric inhibiting actions of the calcitonin and CGRP are mediated by the central nervous system.

Amino Acid Sequence↗
PubMed1985

Chylous ascites in infants and children: a case report and literature review.

Successful treatment of an infant with chylous ascites secondary to "congenital leaky lymphatics" is described, followed by a literature review of cases of pediatric chylous ascites. The infant was placed on home total parenteral nutrition for 10 weeks, during which time the chylous ascites resolved and did not recur with the introduction of a normal diet. Forty cases of pediatric chylous ascites have been reported since 1960, with an age range from birth to 18 years. The presenting signs and symptoms were secondary to abdominal distension in over 80% of cases. The chylous ascites was secondary to trauma, which included child abuse (19%), obstruction (27%), or lymphatic abnormalities (54%). Most studies described were not helpful in making the diagnosis, except for lymphangiography and exploratory laparotomy. Many patients were treated with a high-protein, low-fat diet, with or without medium-chain triglycerides, with variable success. Total parenteral nutrition (TPN) was the primary therapeutic modality in five patients, and in all but one of the cases there was complete resolution of the chylous ascites over 3 to 10 weeks with no significant side effects. Total parenteral nutrition, including home TPN, is a safe and effective therapeutic modality for some cases of chylous ascites.

Adolescent↗
PubMed1985

Effect of subinhibitory concentrations of cephalosporins on surface properties and siderophore production in iron-depleted Klebsiella pneumoniae.

Subinhibitory MICs (sub-MICs) of several cephalosporins significantly reduced the enterochelin production of Klebsiella pneumoniae 327 grown under iron-depleted conditions and also reduced capsule formation regardless of iron availability. The surface hydrophobicity of K. pneumoniae 327 increased significantly when the bacteria were grown in either iron-sufficient or iron-depleted media in the presence of sub-MICs of all the cephalosporins used in this study. Antisera raised against a non-encapsulated K. pneumoniae strain caused rapid agglutination of K. pneumoniae 327 grown in the presence of sub-MICs of the cephalosporins but no agglutination of the same strain grown in drug-free media. The results indicated that the cephalosporins reduced enterochelin production and also capsule formation to the extent that noncapsular surface antigens were exposed, with possible significant consequences in vivo.

Bacterial Proteins↗
PubMed1985

Protein antigens of encapsulated Klebsiella pneumoniae surface exposed after growth in the presence of subinhibitory concentrations of cephalosporins.

It recently has been reported by us that cephalosporins, at a concentration below that influencing growth rate, reduced the production of enterochelin and capsule formation of iron-depleted Klebsiella pneumoniae. We now report on the antigenicity of the outer membrane components and surface-exposed protein antigens of iron-depleted cells grown in the presence or absence of cephalosporins. All major outer membrane proteins, including iron-regulated membrane proteins, were immunogenic. Encapsulated K. pneumoniae grown in antibiotic-free media had three protein antigens (60, 35.5, and 32.5 kilodaltons) exposed on the surface that were accessible to antibodies. Growth of the same cultures in the presence of subinhibitory concentrations of cephalosporins resulted in the exposure of a greater number of protein antigenic determinants, including iron-regulated membrane proteins, which become readily accessible to antibodies. It was also found that immunoblotting was generally more sensitive than conventional staining of the acrylamide gel with Coomassie blue in the detection of proteins.

Antigens, Bacterial↗
PubMed1985

In vivo evidence that bacteria in urinary tract infection grow under iron-restricted conditions.

The outer membrane protein composition of bacteria isolated directly and without subculturing from the urine of two patients with urinary tract infections was investigated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The results indicated that the bacteria grew under iron-restricted conditions, as revealed by the expression of several high-molecular-weight outer membrane proteins which could also be observed when the same isolates were grown under iron-depleted conditions in laboratory media. The antigenicity of outer membrane components of the bacteria isolated was studied by immunoblotting with serum samples from the patients. The results indicated that the sera from the patients contained antibodies against major outer membrane components of the bacteria present in the urine, including the iron-regulated membrane proteins.

Aged↗
PubMed1985

Calcitonin gene related peptide inhibits basal, pentagastrin, histamine, and bethanecol stimulated gastric acid secretion.

This study was designed to examine the effect of calcitonin gene related peptide on gastric acid secretion in the rat. Calcitonin gene related peptide (1 pmol-1 nmol/rat) injected intravenously inhibited basal gastric acid secretion in awake, freely moving rats. Calcitonin gene related peptide decreased gastric secretion stimulated by histamine, pentagastrin, or bethanecol in anaesthetised rats. The inhibitory effect was immediate and most pronounced in the first hour and diminished during the second hour. The N- and C-terminal fragments of calcitonin gene related peptide, CGRP1-14 and [Tyr23]CGRP23-37, did not affect gastric acid secretion. [acetamidomethyl-cys2,7]CGRP, the linear cysteine-protected molecule devoid of the disulphide bridge, was not biologically active. After truncal vagotomy or atropine sulphate, calcitonin gene related peptide did not inhibit gastric secretion. These studies indicate that calcitonin gene related peptide administered peripherally inhibits basal and stimulated gastric acid secretion in the rat. Both C- and N-terminal residues as well as the disulphide bridge are necessary for the inhibitory effect on gastric secretion. Inhibition of gastric acid secretion by calcitonin gene related peptide may depend on intact vagal cholinergic fibres.

Animals↗
PubMed1985

Central nervous system cardiovascular effects of bombesin in conscious rats.

The effects of intracerebroventricular administration of bombesin on mean arterial pressure and heart rate were studied in conscious, freely moving rats. Injection of bombesin produced dose-dependent elevations of mean arterial pressure and reductions of heart rate. These effects were not caused by leakage of bombesin into the peripheral circulation. Adrenalectomy abolished the pressor action of bombesin but did not alter bombesin-induced bradycardia. Systemic phentolamine pretreatment prevented bombesin-induced changes of mean arterial pressure, whereas rats treated intravenously with captopril or a vasopressin antagonist still exhibited pressor responses to bombesin administration. Bombesin-induced bradycardia was partially antagonized by intravenous atropine methyl nitrate administration, whereas systemic injections of propranolol did not modify this response. It is concluded that bombesin acts within the central nervous system to elevate mean arterial pressure through an adrenal-dependent mechanism involving alpha-adrenergic receptors and to reduce heart rate through an adrenal-independent mechanism involving, at least in part, cardiac parasympathetic nervous activation.

Animals↗
PubMed1985

Corticotropin-releasing factor, sauvagine, and urotensin I: effects on blood flow.

Corticotropin-releasing factor (CRF), sauvagine (SVG), and urotensin I (UI) were tested for their effects on superior mesenteric blood flow in conscious dogs. Intravenous (iv) administration of CRF, SVG, and UI induced an immediate rise of mesenteric blood flow that was associated with a decrease in mean arterial pressure and an increase in heart rate. Intracerebroventricular (ICV) injection of SVG and UI, but not CRF, rapidly (within 5 min after injection) elicited a long (90 min) elevation of mesenteric blood flow. Central administration of these peptides induced a delayed rise in heart rate and slightly elevated mean arterial pressure. The finding that CRF given ICV did not increase mesenteric blood flow could not be explained by the release of vasoactive agents such as vasopressin, epinephrine, or norepinephrine. After injection of CRF, SVG, and UI, plasma concentrations of CRF-, SVG-, and UI-like immunoreactivity did not increase as determined by radioimmunoassay. These results indicate that SVG and UI, but not CRF, administered ICV produce a long increase of mesenteric blood flow in conscious dogs. Because iv SVG and UI decrease mean arterial pressure and ICV SVG and UI increase mean arterial pressure and do not cause an increase in SVG- and UI-like immunoreactivity in the peripheral circulation, it is proposed that SVG and UI injected into the third cerebral ventricle act within the central nervous system to increase superior mesenteric blood flow in the dog.

Amphibian Proteins↗
PubMed1985

Corticotropin-releasing factor. Mechanisms to inhibit gastric acid secretion in conscious dogs.

Immunoreactivity similar to that of corticotropin-releasing factor (CRF) is found in regions of the central nervous system that modulate autonomic responses, including gastrointestinal functions. We examined the central nervous system effects of ovine CRF on gastric acid secretion in conscious dogs. Male beagle dogs (11-13 kg) were fitted with chronic intracerebroventricular cannulae and gastric fistulae. Gastric acid secretion in response to intravenously administered gastric secretory stimuli was measured by in vitro titration of gastric juice to pH 7.0 and in response to an intragastric meal by in vivo intragastric titration at pH 5.0. Plasma gastrin was determined by radioimmunoassay. CRF microinjected into the third cerebral ventricle decreased pentagastrin-stimulated gastric acid secretion for 3 h (P less than 0.01) dose-dependently (0.2-6.0 nmol X kg-1). CRF did not inhibit histamine-stimulated gastric secretion but significantly (P less than 0.01) decreased the secretory response after 2-deoxy-D-glucose for 3 h. The gastric inhibitory action of intracerebroventricularly administered CRF on pentagastrin-stimulated gastric acid secretion was completely abolished by ganglionic blockade with chlorisondamine. The opioid antagonist, naloxone, and the vasopressin antagonist, [1-deaminopenicillamine,2-(O-methyl) tyrosine,8-arginine]-vasopressin, significantly suppressed the inhibitory effect of CRF on gastric acid secretion stimulated by pentagastrin. In contrast, truncal vagotomy did not prevent the inhibition of gastric acid secretion induced by CRF. CRF (0.2-2.0 nmol X kg-1) administered intracerebroventricularly decreased gastric acid secretion stimulated by 200-ml liquid meals containing 8% peptone. CRF did not affect plasma gastrin concentrations. These results indicate that CRF microinjected into the third cerebral ventricle inhibits gastric acid secretion in conscious dogs. CRF-induced inhibition of gastric acid secretion appears to be mediated by the sympathetic nervous system and, in part, by opiate and vasopressin-dependent mechanisms.

Animals↗
PubMed1985

Corticotropin-releasing factor: effects on the autonomic nervous system and visceral systems.

Corticotropin-releasing factor (CRF) acts within the central nervous system to modify the activity of the sympathetic and parasympathetic nervous systems, cardiovascular function, endocrine-pancreatic function, and carbohydrate metabolism. These changes in animal physiology induced by CRF provide a tenable basis for hypothesizing that this peptide may be physiologically involved in integrating the neuroendocrine, autonomic, cardiovascular, and metabolic responses to stressful stimuli. This hypothesis is supported by studies demonstrating that glucocorticoids or CRF receptor antagonists alter both the neuroendocrine and autonomic responses to stress.

Adrenal Medulla↗