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Biomedical subjects

M R Brown

Publications and source records attributed to M R Brown.

At least 199 records · Page 11Linked to original sources
PubMed1989

Glutathione peroxidase and selenium deficiency in patients receiving home parenteral nutrition: time course for development of deficiency and repletion of enzyme activity in plasma and blood cells.

The time course for the depletion of red blood cell (RBC) and plasma glutathione peroxidase (GSHPx) activity in five patients receiving home parenteral nutrition was documented. During the development of the RBC GSHPx deficiency, enzymatic activity and protein content decreased. Plasma and RBC selenium content were similarly decreased as was cellular metabolism of exogenous hydrogen peroxide. When the replacement of Se (selenious acid) began, there was a rapid increase (within 6 h) in plasma GSHPx activity. Platelet and granulocyte (PMN) GSHPx activity, which were low when Se replacement began, became normal within a time consistent with the kinetics of platelet and PMN production. RBC GSHPx did not become normal for 3-4 mo. This is consistent with the time course for RBC production. It appears that the repletion of blood cell GSHPx requires the formation of these cells in the presence of Se.

Adult↗
PubMed1989

Hormonal response to overfeeding.

We assessed the hormonal status of adult female volunteers before and during a 3-wk period of weight gain induced by mixed diet overfeeding. Forty-six percent of the 4.3-kg average weight gain experienced by these subjects consisted of lean body mass (LBM) and it is of interest that there were also increases in plasma Somatomedin-C/Insulin-like Growth Factor (SM-C/IGF-1) and testosterone concentrations as well as insulin. We suggest that it was the combined anabolic effect of these three hormones that facilitated the increase in LBM. Of the other assays done, increases were recorded for urinary 17-ketosteroids, 17-hydroxysteroids, epinephrine, and creatinine, whereas there were no changes in serum cortisol or triiodothyronine (T3), or urine norepinephrine; serum thyroxine (T4) fell slightly. Thus it appears that energy surfeit as well as energy deficit (reported by others) has an effect on blood hormone concentrations.

Adolescent↗
PubMed1989

Fatal multisystem disease with immune enteropathy heralded by juvenile rheumatoid arthritis.

The prognosis of juvenile rheumatoid arthritis (JRA) is generally good, although premature death occurs in a subset of children. Secondary infections, chronic amyloidosis, and heart disease have been reported as common causes. Our experience indicates that JRA can also herald the development of a severe immune enteropathy. In the case presented, typical JRA was followed by fulminant hepatitis; skin rashes; recurrent, severe, watery diarrhea; malabsorption; and ultimately death. Biopsies of the small bowel exposed to the patient's serum revealed deposition of complement and immunoglobulins in the epithelium. Although not widely appreciated, JRA can herald a multisystem syndrome characterized by severe immune enteropathy.

Arthritis, Juvenile↗
PubMed1989

Effect of iron depletion on cell-wall antigens of Candida albicans.

Cell walls were isolated from stationary-phase cultures of Candida albicans grown at 25 degrees C or 37 degrees C, in iron-depleted and iron-sufficient conditions. Proteins solubilised from cell-wall fractions were separated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. Approximately 40 protein bands were detected by Coomassie blue staining in all wall extracts, regardless of temperature or other growth condition. Sera from patients with oral or systemic candidosis, from whom the isolates were obtained, and pooled normal human serum were examined for the presence of IgG and IgM antibodies to cell-wall proteins by Western blotting. Patient sera recognised more antigens than pooled normal human serum. In particular, an antigen of 44 kda was detected by IgG antibodies in the sera of patients and two antigens of 41 and 14 kda were detected by their IgM antibodies when the sera were used as probes against walls from iron-depleted cells, but not from iron-sufficient cells, grown at 25 degrees C. Two antigens of 45 and 40 kda were detected by IgM antibodies in the sera of patients tested against walls from iron-depleted but not from iron-sufficient cells grown at 37 degrees C. IgG antibodies did not distinguish between these wall preparations from cells grown at 37 degrees C. These results suggest that the specific cell-wall proteins induced during growth in iron-depleted conditions, as well as other proteins, were immunogenic and were recognised by the patients' antibodies.

Antibodies, Fungal↗
PubMed1989

Growth rate control of adherent bacterial populations.

We report a novel in vitro method which, through application of appropriate nutrient limitations, enables growth rate control of adherent bacterial populations. Exponentially growing cells are collected by pressure filtration onto cellulose acetate membranes. Following inversion into the bases of modified fermentors, membranes and bacteria are perfused with fresh medium. Newly formed and loosely attached cells are eluted with spent medium. Steady-state conditions (dependent upon the medium flow rate) at which the adherent bacterial biomass is constant and proportional to the limiting nutrient concentrations are rapidly achieved, and within limits, the growth rate is proportional to the medium flow rate. Scanning electron microscopic studies showed that such populations consist of individual cells embedded within an extracellular polymer matrix.

Bacterial Adhesion↗
PubMed1989

Primary culture of secretagogue-responsive parietal cells from rabbit gastric mucosa.

A new procedure for isolation and primary culture of gastric parietal cells is described. Parietal cells from rabbit gastric mucosa are enriched to greater than 95% purity by combining a Nycodenz gradient separation with centrifugal elutriation. Cells are plated on the basement membrane matrix, Matrigel, and maintained in culture for at least 1 wk. Parietal cells cultured in this manner remain differentiated, cross-react with monoclonal H+-K+-ATPase antibodies, and respond to histamine, gastrin, and cholinergic stimulation with increased acid production as measured by accumulation of the weak base, [14C]aminopyrine. When stimulated, cultured cells undergo ultrastructural changes in which intracellular canaliculi expand and numerous microvilli are observed. These ultrastructural changes are similar to those previously found to occur in vivo and in acutely isolated parietal cells. Morphological transformations in living cells can also be observed with differential interference contrast optics in the light microscope. After histamine stimulation, intracellular canaliculi gradually expand to form large vacuolar spaces. When the H2 receptor antagonist, cimetidine, is added to histamine-stimulated cells, these vacuoles gradually disappear. The ability to maintain hormonally responsive parietal cells in primary culture should make it possible to study direct, long-term effects of a variety of agonists and antagonists on parietal cell secretory-related activity. These cultured cells should also prove to be useful for the study of calcium transients, ion fluxes, and intracellular pH as related to acid secretion in single cells, particularly since morphological transformations can be used to monitor "physiological" responses at the same time within the same cell.

Adenosine Triphosphatases↗
PubMed1989

Carbachol-induced protein phosphorylation in parietal cells: regulation by [Ca2+]i.

1,2-Bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester (BAPTA/AM), an intracellular calcium [( Ca2+]i) chelator, was used to investigate the role of [Ca2+]i in acid secretory activity and protein phosphorylation in parietal cells from rabbit. Chelation of extracellular calcium [( Ca2+]o) with ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid did not prevent the initial carbachol-induced elevation of [Ca2+]i as measured with the fluorescent Ca2+ probe, fura-2, and only partially inhibited [14C]-aminopyrine (AP) accumulation, an indirect indicator of acid secretory activity. [Ca2+]i chelation with BAPTA/AM eliminated carbachol-stimulated increases in [Ca2+]i and AP accumulation but only transiently reduced histamine stimulation of AP accumulation. Carbachol increased phosphorylation of a 36-kDa, pI approximately 7 protein (pp36) and transient phosphorylation of a 28-kDa, pI approximately 5 protein (pp28), whereas histamine increased phosphorylation of 40-kDa, pI approximately 6.5 (pp40) and 27-kDa, pI approximately 6.2 (pp27) proteins. Phosphorylation of pp36 and pp28 were mimicked by the protein kinase C activator, 12-O-tetradecanoylphorbol-13-acetate (TPA) and the calcium ionophore, ionomycin, respectively. Two other phosphoproteins with molecular weights of 66,000 and pIs of 5.7 and 5.9 were also phosphorylated in response to TPA and carbachol. Chelation of [Ca2+]i and [Ca2+]o blocked carbachol-induced phosphorylation of pp28 and pp36 and ionomycin phosphorylation of pp28 but not TPA-stimulated phosphorylation of pp36 or the two pp66s or histamine-stimulated phosphorylation of pp27 or pp40. Chelation of [Ca2+]i alone did not block increases in [Ca2+]i or phosphorylation of pp28 in response to ionomycin. Both pp28 and pp36 were localized in both microsomal and cytosolic fractions of cells, which suggests involvement in cytoskeleton-membrane interactions. These phosphoproteins could be common elements of Ca2+-dependent stimulus-secretion coupling as similar proteins were phosphorylated by carbachol and cholecystokinin (CCK) in chief cells. Based on data with TPA and ionomycin, both protein kinase C and an as yet unidentified Ca2+-dependent protein kinase(s) appear to be activated upon stimulation with cholinergic agonists and CCK.

Aminopyrine↗
PubMed1989

Thyrotropin-releasing factor-induced adrenocorticotropin secretion is mediated by corticotropin-releasing factor.

TSH-releasing factor (TRF), administered into the lateral cerebroventricle of adult male rats, elevated plasma concentrations of ACTH, epinephrine, and norepinephrine. TRF given iv was devoid of these activities. The CRF receptor antagonist, alpha-helical CRF9-41 (CRF9-41) given iv suppressed the TRF-induced increase in ACTH, but did not alter TRF-induced changes in plasma catecholamines. Intravenous administration of CRF antiserum totally blocked TRF-induced elevation of plasma ACTH concentrations. CRF receptor antagonists administered icv attenuated CRF-induced, but not TRF-induced elevation of plasma concentrations of ACTH, epinephrine, and norepinephrine. It is concluded from these results that TRF acts within the central nervous system to stimulate ACTH release through a CRF-dependent mechanism.

Adrenocorticotropic Hormone↗
PubMed1989

Ultrastructural localization of phenoloxidase in the midgut of refractory Anopheles gambiae and association of the enzyme with encapsulated Plasmodium cynomolgi.

A melanogenic enzyme, phenoloxidase, was localized ultrastructurally in the midgut epithelia of 2 strains of Anopheles gambiae, a refractory strain that melanotically encapsulates Plasmodium cynomolgi ookinetes on the midgut, and a susceptible strain that does not. Midguts were incubated with either dopa or dopamine, and the resultant electron-dense product of phenoloxidase activity was localized on the basal lamina (BL) and cellular basal membrane labyrinth (BML) in uninfected mosquitoes of both strains. In infected refractory mosquitoes, the reaction products still were observed on the BL and BML but were especially dense in the BML of midgut cells near encapsulated ookinetes and in the capsule itself. In infected susceptible mosquitoes, phenoloxidase localization was reduced or absent in the BL and BML and was not observed near parasites. Phenylthiourea (PTU) inhibited the phenoloxidase reaction, indicating that the reaction product deposited in the absence of PTU resulted from enzyme activity and not autooxidation of the substrates. It is concluded that higher levels of phenoloxidase in the refractory strain following a blood meal may contribute to the ability to encapsulate ookinetes.

Animals↗
PubMed1989

Decreased cholestasis with enteral instead of intravenous protein in the very low-birth-weight infant.

Thirty to 50% of very low-birth-weight infants have parenteral nutrition-associated cholestasis. To test the hypothesis that the incidence of cholestasis would be decreased if parenteral amino acids were avoided and protein given enterally, infants with a gestational age of less than 30 weeks were randomized to two groups. One group received amino acid-free parenteral nutrition and whey protein enterally with added premature infant formula. The control group received standard parenteral nutrition with amino acids and enteral premature formula. At the end of 3 weeks of parenteral nutrition, infants who had a direct serum bilirubin level of greater than 3 mg/dl were considered to have significant cholestasis. Twenty-nine infants required parenteral nutrition for 3 weeks, 17 in the whey group and 12 in the control group. No instances of significant cholestasis were observed in the whey group (0/17), whereas seven of 12 infants (58%) in the amino acid control group had cholestasis (p less than 0.001).

Amino Acids↗
PubMed1989

Efficacy of oral cyclosporine given prior to liver transplantation.

The bioavailability of oral cyclosporine (CYS) dissolved in a large quantity of milk given just before liver transplantation (LTX) was evaluated in 30 patients, given randomly timed oral CYS before LTX, by measurements of CYS blood levels at induction, 2 h later, and at the time of graft reperfusion. Adequate blood CYS levels, defined as greater than or equal to 500 ng/mL (FPIA), could reliably be achieved only when the drug was administered 4 to 7 h preoperatively. Patients receiving the drug less than 4 h preoperatively generally had low levels thereafter (two of seven patients had greater than or equal to 500 ng/mL in any sample, compared with 13 of 14 patients in the 4-7-h group, P less than 0.011); an interval of greater than 7 h yielded unpredictable results. Fluids and blood products transfused, and preoperative ascites or ICU care, were not related to blood CYS levels. Oral CYS should be given 4 to 7 h before LTX to achieve adequate levels.

Anesthesia↗
PubMed1989

Energy need for weight maintenance in human beings: effect of body size and composition.

We estimated energy requirement by determining the amount of food needed to maintain body weight in a controlled environment. In a study of 28 adolescents and adults of widely varying weight and body fat content, we found that the energy required for weight maintenance was directly proportional to body weight (r = 0.92). The increased energy requirement of the obese is due in part to their larger lean weight and in part to their greater burden of body fat; together these account for 87% of the variance. For these subjects, who were engaged in light physical activity, the ratio of total energy to basal metabolic rate was 1.52 +/- 0.16 (SD).

Adipose Tissue↗
PubMed1988

Novel modes of action of aminoglycoside antibiotics against Pseudomonas aeruginosa.

Several mucoid strains and one non-mucoid strain of Pseudomonas aeruginosa were grown in subinhibitory concentrations of various aminoglycosides, beta-lactams, and ciprofloxacin. At antibiotic concentrations that did not affect bacterial growth, aminoglycosides inhibited the excretion of alginate capsule and the production of the iron-chelating siderophores. The same concentrations also disturbed other aspects of the bacterium's iron metabolism, manifested by reduced cellular levels of cytochromes and catalase. beta-lactams, except for cefotaxime, and ciprofloxacin did not reduce alginate excretion. These effects on virulence factors are likely to contribute to the efficacy of aminoglycosides.

Alginates↗
PubMed1988

Role of somatostatin in the regulation of vasopressin secretion.

Intracerebroventricular (i.c.v.) administration of somatostatin-28 (SS-28) (30 ng-1 micrograms) resulted in a dose-dependent elevation of plasma concentrations of vasopressin. Continuous i.c.v. infusion of SS-28 produced a depletion of vasopressin-like immunoactivity within the paraventricular and supraoptic of the hypothalamus as determined by immunocytochemistry. To evaluate the role of endogenous brain somatostatin in the regulation of vasopressin secretion, animals were treated with cysteamine. Cysteamine (90 mg/kg) treatment given s.c. produced a 50% depletion of endogenous brain somatostatin-like peptide concentrations. Pretreatment of animals with cysteamine attenuated hemorrhage-induced elevation of plasma vasopressin levels. The elevation of plasma vasopressin concentrations following the i.v. administration of hypertonic saline or the i.c.v. administration of angiotensin-II were not altered by cysteamine treatment. These results are consistent with the conclusion that an endogenous brain somatostatin may be involved in the physiologic regulation of vasopressin secretion following hemorrhage.

Animals↗
PubMed1988

FMRFamide- and adipokinetic hormone-like immunoreactivity in the nervous system of the mosquito, Aedes aegypti.

As demonstrated with immunocytochemistry, specific cells and axons in the nervous system of female Aedes aegypti contain antigens immunologically related to FMRFamide (phenylalanine-methionine-arginine-phenylalanine-amide) and locust adipokinetic hormone I (AKH). In the supra-esophageal ganglion, including some medial neurosecretory cells, and in all ganglia of the ventral nerve cord, there are 100-120 cells immunoreactive to a FMRFamide antiserum. The same cells cross-react with a bovine pancreatic polypeptide antiserum, but when the latter antiserum is preabsorbed with FMRFamide, immunoreactivity is lost. However, immunoreactivity is maintained when FMRFamide antiserum is preabsorbed with pancreatic polypeptide, suggesting that the immunoreactive peptide is more closely related to FMRFamide. There are 6-12 cells in the supra- and subesophageal ganglia immunoreactive to an AKH antiserum, and some of the same cells are reactive to the FMRFamide antiserum. As well, unpaired cells in each of the abdominal ganglia are positive for both AKH and FMRFamide. Although the function of the FMRFamide- and AKH-like peptides in mosquitoes is unknown, this study, combined with previous reports on the localization of FMRFamide-like peptides in midgut endocrine cells, supports the concept of a brain-midgut neuroendocrine axis in this insect.

Aedes↗
PubMed1988

Amino acid sequence of versutoxin, a lethal neurotoxin from the venom of the funnel-web spider Atrax versutus.

The complete amino acid sequence of versutoxin, a lethal neurotoxic polypeptide isolated from the venom of male and female funnel-web spiders of the species Atrax versutus, was determined. Sequencing was performed in a gas-phase protein sequencer by automated Edman degradation of the S-carboxymethylated toxin and fragments of it produced by reaction with CNBr. Versutoxin consisted of a single chain of 42 amino acid residues. It was found to have a high proportion of basic residues and of cystine. The primary structure showed marked homology with that of robustoxin, a novel neurotoxin recently isolated from the venom of another funnel-web-spider species, Atrax robustus.

Amino Acid Sequence↗