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Biomedical subjects

M R Brown

Publications and source records attributed to M R Brown.

At least 145 records · Page 8Linked to original sources
PubMed1992

Effects of nonenzymatic glycation of subfragment-1 of myosin on interactions with actin.

Nonenzymatic bonding of reducing sugars to subfragment-1 of myosin (S-1) resulted in a reduction in actin-activated S-1 ATPase activity. Fructose caused a greater reduction than glucose. The Km for binding of actin to S-1 was significantly increased with sugar derivatization. In addition, sugar derivatization lowered the ability of S-1 to promote polymerization of G-actin. Western blot analysis demonstrated that glucose was nonenzymatically incorporated into the 50 and 20 kilodalton (kDa) fragments of S-1 with preponderance in the 20-kDa fragment. The reduced affinity of derivatized myosin for actin is indicated by the increased Km, the reduced ability to stimulate actin polymerization, and the positive Western blot reaction in the 20-kDa fragment.

Actins↗
PubMed1992

Involvement of cellular division cycle in the susceptibility of Escherichia coli to cold- and osmotic-shock.

Susceptibility of Escherichia coli to cold-shock, osmotic-shock and cold-osmotic-shock has been evaluated throughout the cellular division cycle for a variety of generation time. Two periods of sensitisation were detected. The first of these was towards cold-shock which occurred 60 min prior to cell division and might correspond to initiation of DNA replication. The second period of sensitisation was towards both cold-, osmotic- and cold-osmotic-shock and occurred immediately prior to and during cell division. Patterns and extents of sensitisation towards each of these three stresses during the second period were suggestive of a common sensitising event associated with constriction of the cell and separation.

Cell Cycle↗
PubMed1991

The antinociceptive effects of spinally administered neuropeptide Y in the rat: systematic studies on structure-activity relationship.

Neuropeptide Y (NPY) is a 36-amino-acid, C-terminal amidated peptide that is found in bulbospinal pathways and can inhibit the release of the primary afferent C-fiber neurotransmitter, substance P. Based on these observations, the present studies examined the possible antinociceptive effects of this peptide and several NPY fragments after intrathecal administration in rats prepared with chronic intrathecal catheters. In the 52 degrees C hot plate test, NPY produced a dose-dependent elevation in the nociceptive threshold with a median effective dose of 1.1 nmol. The ordering of fragments' activity was: NPY greater than NPY16-36 greater than or equal to NPY19-36 greater than or equal to NPY14-36 greater than or equal to NPY18-36 much greater than NPY1-36-OH = NPY18-36-OH = 0. In the paw pressure test, NPY was not active, even at the highest doses examined (median effective dose greater than 20 nmol), whereas the C-terminal fragments retained their potency and produced significant increases in the pressure required to evoke escape (NPY18-36: median effective dose = 18.7 nmol). The rank ordering of activity in the paw pressure test was: NPY19-36 greater than or equal to NPY14-36 greater than or equal to NPY18-36 greater than or equal to NPY16-36 much greater than NPY = NPY18-36-OH = 0. Peptide YY, human pancreatic polypeptide and avian pancreatic polypeptide behave similarly to NPY.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1991

Bombesin immunoreactive neurons in the hypothalamic paraventricular nucleus innervate the dorsal vagal complex in the rat.

Bombesin-like immunoreactivity has been localized within neuronal cell bodies of the hypothalamus and nerve terminals within the dorsal vagal complex. The possibility that the hypothalamus is a source for bombesin-like immunoreactive terminals within the dorsal vagal complex was examined using the combined retrograde tracing and immunohistochemical technique. After injections of retrograde tracer were made into the dorsal vagal complex, cells in the hypothalamus labeled with both retrograde tracer and bombesin immunoreactivity were localized in the parvocellular part of the paraventricular nucleus. In the paraventricular nucleus most of the vagal projecting bombesin immunoreactive neurons were located within the medial parvocellular subdivision. Approximately 30% of the bombesin immunoreactive neurons in this subnucleus projected to the dorsal vagal complex. The results suggest that the paraventricular hypothalamic nucleus is a major source of bombesin terminals within the dorsal vagal complex. This pathway may mediate some of the autonomic nervous system changes that are observed when bombesin is injected within the central nervous system. Additionally, this data adds to a growing amount of evidence supporting the role of bombesin as a peptide neurotransmitter.

Amidines↗
PubMed1991

Central nervous system site of action of bombesin to elevate plasma concentrations of catecholamines.

To identify the central nervous system site of action of bombesin to elevate plasma concentrations of catecholamines, this peptide has been injected into numerous brain ventricular and parenchymal sites. Low doses of bombesin (1-10 ng) injected into the region of the rostral nucleus tractus solitarius (NTS) elicited an elevation of plasma catecholamines greater than those observed following an injection of bombesin into other brain regions. Bombesin-induced (10 ng) elevation of plasma epinephrine but not norepinephrine was prevented by co-administration of somatostatin-28 (100 ng). Mean arterial pressure (MAP) and heart rate (HR) were measured following injection of bombesin into the NTS. Bombesin injected into the NTS resulted in prolonged decreases in HR without significantly altering MAP. These studies demonstrate that bombesin injected into the dorsal medulla resulted in significant changes of plasma catecholamine levels and HR. Based on these actions of bombesin and the neuroanatomic distribution of bombesin-like peptide, it is suggested that this peptide may play an important role in regulation of sympatho-adrenal and cardiac functions.

Animals↗
PubMed1991

Tissue specific expression of the Drosophila Adh gene: a comparison of in situ hybridization and immunocytochemistry.

The tissue specific patterns for Drosophila melanogaster alcohol dehydrogenase (Adh) mRNA and protein expression were determined using in situ hybridization and immunocytochemical techniques. Alcohol dehydrogenase mRNAs were localized in thin sections of frozen tissue using the hybridization of single stranded RNA probes. Alcohol dehydrogenase protein was identified in frozen tissue samples using ADH antisera, a biotinylated secondary antibody, and streptavidin conjugated to horseradish peroxidase. In tissues such as fat body, gastric caeca, and adult cardiac valve, the patterns of expression for ADH protein and mRNA were identical. Other tissues such as oocytes, nurse cells, imaginal disks, and brain show levels of Adh mRNA that are lower than or equivalent to those observed in the previously mentioned tissues, but they exhibit little or no ADH protein. The lack of concordance between Adh mRNA and ADH protein expression in oocytes and nurse cells may reflect the packaging of maternal mRNAs (but not ADH protein) for use in early development. The reason(s) for the other discrepancies in protein and mRNA expression are not known at this time but may be due to post-transcriptional regulation in these specific tissues.

Alcohol Dehydrogenase↗
PubMed1991

Protection of monkeys against the lethal effects of male funnel-web spider (Atrax robustus) venom by immunization with a toxoid.

A stable toxoid was prepared from robustoxin (the lethal polypeptide neurotoxin in the venom of the male funnel-web spider, Atrax robustus) by polymerization with glutaraldehyde. This material was non-toxic in new-born mice. Administration of the toxoid to three Macaca fascicularis monkeys (50-80 micrograms/kg s.c. at 14-day intervals for 8-12 weeks) produced no toxic effects; anti-robustoxin antibodies were detected in serum samples by immunodiffusion tests within 13-27 days. In vivo evidence of successful protection with the toxoid was obtained by challenging the monkeys with male A. robustus venom (50 micrograms/kg i.v.) under anaesthesia with pentobarbitone (one monkey), or with ketamine, halothane and nitrous oxide, 1-26 weeks after the last injection of the toxoid. Only minor respiratory, cardiovascular and skeletal motor disturbances were produced, and all monkeys recovered fully and uneventfully. Challenge with the same dose of venom in non-immunized or robustoxin N-terminal decapeptide ovalbumin conjugate-treated monkeys resulted in typical lethal neurotoxic effects, culminating in severe hypotension or death from circulatory and respiratory failure within 280 min.

Amino Acid Sequence↗
PubMed1991

Phenotypic variation in the outer membrane protein composition of Actinobacillus (Haemophilus) pleuropneumoniae: non-specific effect of exogenous pyridine nucleotide supply.

Actinobacillus pleuropneumoniae, grown in batch culture, was provided with pyridine nucleotides at concentrations that limited the final growth yield (pyridine nucleotide-deficient cultures) or did not determine the final extent of growth (pyridine nucleotide-sufficient cultures). Sarkosyl-extracted outer membranes from stationary phase, pyridine nucleotide-sufficient organisms contained 23,000 Mr and 43,000 Mr polypeptides that were absent (23,000 Mr) or barely detectable (43,000 Mr) in outer membranes from stationary phase, pyridine nucleotide-deficient organisms or exponential phase organisms. When growth ceased due to exhaustion of pyridine nucleotide, the ratio of the major outer membrane polypeptides (31,000, 38,000 and 69,000 Mr) was altered, becoming more like the ratio found with exponential phase organisms. Similar results were obtained when growth ceased due to glucose exhaustion at low biomass concentrations demonstrating that diverse nutrient deprivations can induce similar changes in outer membrane protein profile. All of these polypeptides were recognized by porcine immune sera indicating their production by A. pleuropneumoniae growing in vivo.

Actinobacillus pleuropneumoniae↗
PubMed1991

Central regulation of stress responses: regulation of the autonomic nervous system and visceral function by corticotrophin releasing factor-41.

Our understanding of the role of CRF in mediating integrated endocrine, autonomic and visceral stress responses is rudimentary at best. Delineating the large number of neurochemical factors that influence the activity of CRF-containing hypophyseotrophic neurones offers one direction for future research in this area. Another approach might be to examine the neuropharmacological actions of transmitters which are co-localized within CRF-containing neurones. For example, CRF and dynorphin-related peptides coexist within a subpopulation of paraventricular neurones (Roth et al, 1983), suggesting the potential for their simultaneous release and possible functional interactions between them. Interestingly, CRF and dynorphin-related peptides exhibit reciprocal actions on the release of each other in vitro and in vivo. CRF stimulates the release of immunoreactive dynorphin from rat hypothalamic slices (Nikolarakis et al, 1986) while dynorphin A1-17 inhibits the basal secretion of immunoreactive CRF from rat hypothalami (Yajima et al, 1986). In vivo experiments demonstrate that i.c.v. administration of dynorphin A1-13 reduces basal and hypotension-induced secretion of CRF into hypophyseal portal blood (Plotsky, 1986). Recent studies suggest that, in addition to their interactions at the level of release, these peptides may also modify the CNS actions of each other on autonomic and cardiovascular function (Overton and Fisher, 1989b). Thus, CRF-induced elevations of arterial pressure, heart rate and plasma catecholamine levels are attenuated by co-administration of low doses of dynorphin A1-17. The reciprocal release actions and neuropharmacological interactions between CRF and dynorphin A1-17 suggest that local integration or perhaps feedback regulation of stress-induced autonomic and cardiovascular responses may be achieved by the co-release of multiple neurotransmitters from a single source. In summary, the combined anatomical, pharmacological and physiological data provide support for the involvement of CRF neuronal systems in mediating the integration of endocrine, autonomic, and visceral functions, particularly in response to stress. Future research in this area may contribute to our understanding of the neurobiology of CRF as well as the CNS mechanisms governing homeostasis.

Animals↗
PubMed1991

Susceptibility of Pseudomonas aeruginosa and Escherichia coli biofilms towards ciprofloxacin: effect of specific growth rate.

Methods of cell culture which enable the control of specific growth rate and expression of iron-regulated membrane proteins within Gram-negative biofilms were employed for various clinical isolates of Pseudomonas aeruginosa taken from the sputum of cystic fibrosis patients and of a laboratory strain of Escherichia coli. Susceptibility towards ciprofloxacin was assessed as a function of growth-rate for intact biofilms, cells resuspended from the biofilms and also for newly formed daughter cells shed from the biofilm during its growth and development. Patterns of susceptibility with growth rate were compared to those of suspended cultures grown in a chemostat. In all instances the susceptibility of chemostat cultures was directly related to growth rate. Whilst little difference was observed in the susceptibility pattern for P. aeruginosa strains with different observed levels of mucoidness, such populations were generally more susceptible towards ciprofloxacin than those of E. coli. At fast rates of growth P. aeruginosa cells resuspended from biofilms were significantly more resistant than chemostat grown cells. Intact P. aeruginosa biofilms were significantly more resistant than cells resuspended from them. This is in contrast to E. coli, where cells resuspended from biofilm and intact biofilms were, at the slower rates of growth, equivalent and significantly more susceptible than chemostat-grown cells. At high growth rates all methods of E. coli culture produced cells of equivalent susceptibility. For all strains, daughter cells dislodged from the biofilms demonstrated a high level of susceptibility towards ciprofloxacin which was unaffected by growth rate. This sensitivity corresponded to that of the fastest grown cells in the chemostat.

Bacteriological Techniques↗
PubMed1991

Effects of iron depletion and sub-inhibitory concentrations of antibodies on siderophore production by Staphylococcus aureus.

The effect of various sub-MICs of oxacillin and amikacin, alone or in combination, on siderophore production by Staphylococcus aureus growing under iron-depleted conditions was evaluated. Siderophore production varied greatly from strain to strain, ranging from 3.0 to 383.4 microM of Desferal equivalents. Siderophore production by some S. aureus strains was reduced significantly (P less than 0.001) under some sets of conditions. However, siderophore excretion in cultures with amikacin was sometimes equal to or greater than control cultures. Thus, at some sub-MICs, the bacteria tested were able to increase siderophore production under metabolic stress. This phenomenon may be a secondary effect of the antibiotics upon intermediary metabolism as a consequence of inhibition of peptidoglycan or protein synthesis. Alternatively the antibiotics may decrease the cellular association of siderophore molecules.

Amikacin↗
PubMed1991

Effect of intraoperative low-dose dopamine on renal function in liver transplant recipients.

Patients undergoing orthotopic liver transplantation frequently receive dopamine infusions to preserve renal function. To test the benefit of such infusions on renal function, 48 nonanuric patients presenting for OLT were entered into a randomized double-blind protocol. After exclusion of 1 patient for intraoperative nephrectomy, 22 patients received dopamine at a rate of 3 micrograms.kg-1.min-1 during surgery and the first postoperative 48 h, and a control group of 25 patients received saline. Venovenous bypass was used in 45 of 47 patients. During the hepatic vascular anastomoses, the donor liver was flushed with cold saline. In 7 patients, the flush contained mannitol (50 g) as part of a surgical protocol to investigate its role as a potential free radical scavenger. Initially, it appeared that there was an increase in urine output during the neohepatic phase in those patients receiving dopamine versus controls (4.20 +/- 3.3 vs 2.10 +/- 1.3 ml.kg-1.h-1, respectively). Upon further statistical analysis, this increase was associated with inclusion of mannitol in the liver flush of 5 patients in the dopamine group. After excluding all patients receiving flush containing mannitol, there was no significant difference in urine output during the neohepatic phase between the dopamine group and controls (2.94 +/- 0.45 and 2.10 +/- 0.28 ml.kg-1.h-1, respectively). The glomerular filtration rates at 1 month after surgery were similar and decreased approximately 40% in each group. Although a beneficial effect of dopamine in all situations cannot be ruled out the authors conclude that routine perioperative use of dopamine is of little value in nonanuric patients presenting for orthotopic liver transplantation.

Acute Kidney Injury↗
PubMed1991

Fibroinflammatory tumor of the liver causing biliary cirrhosis in an infant.

We report the case of a 21-month-old child with a fibroinflammatory tumor of the liver causing biliary obstruction. The patient had fever, diarrhea, and jaundice. Abdominal ultrasonography, computerized tomography, and endoscopic retrograde cholangiopancreatography demonstrated the tumor to be in the porta hepatis. Growth of the mass resulted in destruction of the common hepatic duct, and chronic obstruction led to biliary cirrhosis over 4 months' time. Histologic study of the tumor revealed a fibrous stroma infiltrated by inflammatory cells. The patient was successfully treated with an orthotopic liver transplantation and is doing well 18 months following initial diagnosis without evidence of recurrence.

Fibroma↗