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Biomedical subjects

S W Brown

Publications and source records attributed to S W Brown.

At least 73 records · Page 4Linked to original sources

Neonatal surgery at Waikato Hospital 1978-87.

A ten year (1 January 1978 to 31 December 1987) review of neonatal surgery at Waikato Hospital is reported. There were 367 operations performed on 296 infants aged 0-28 days, with 144 of the operations being classified as a major. Of the 31 deaths, three occurred preoperatively and 28 postoperatively, with diaphragmatic hernia (n = 8) and necrotising enterocolitis (n = 7) being the commonest causes. A significant increase in the number of operations (% major operations), infants with birthweights less than 1500 g, preoperative ventilation and the proportion of operations performed by paediatric surgeons and anaesthetists was seen in the five year period 1983-7, when compared with 1978-82. It is recommended that neonatal surgery only be undertaken at hospitals with level III neonatal intensive care facilities and only by paediatric surgeons and anaesthetists.

Humans↗

Purification and biochemical characterization of recombinant hirudin produced by Saccharomyces cerevisiae.

Recombinant hirudin was produced by the yeast Saccharomyces cerevisiae using the alpha-pheromone prepro sequence to direct its secretion into the culture medium. The secreted hirudin was isolated to greater than or equal to 95% purity as measured by 205-nm absorbance integration from a reverse-phase chromatogram. One major activity peak corresponding to the complete, correctly processed molecule and two minor activity peaks corresponding to C-terminally truncated forms were identified. The primary structure of the major peak, determined by N-terminal sequencing of tryptic peptides, was that predicted from the cDNA sequence, and the molecular mass analyzed by fast atom bombardment mass spectrometry (FAB-MS) was 6892.6 (calculated 6892.5). UV spectral analysis suggested that, in contrast to the natural molecule, recombinant hirudin produced by S. cerevisiae is not sulfated.

Amino Acid Sequence↗

Production and evaluation of recombinant hirudin.

Hirudin, a 65 amino acid polypeptide form the medicinal leech, is an extremely efficient and specific thrombin inhibitor whose therapeutic potential has been demonstrated in a number of animal models. We have developed protocols for the production of recombinant hirudin by secretion from S. cerevisiae and carried out a full biologic evaluation of the purified product. These studies showed that natural and recombinant hirudin was similar in structure and in biologic function in vitro. Moreover, the recombinant protein displayed strong antithrombotic activity in several experimental thrombosis models in vivo, confirming the molecule's promise in the therapy of thrombotic disorders.

Amino Acid Sequence↗

Evoked and psychogenic epileptic seizures. I. Precipitation.

The precipitation of seizures by external stimulation (evoked seizures) is well known. Less well known is the precipitation of seizures by a change in the patient's thinking or feelings. This artick uses Lockhart's monkey model of focal epilepsy to propose that there is a close relationship between seizures and ongoing brain activity. Thus, seizures precipitated by both voluntary and spontaneous changes in behaviour and thinking must commonly occur. Clinical examples of such seizure precipitation is described.

Adult↗

Evoked and psychogenic epileptic seizures: II. Inhibition.

The inhibition of seizure activity by behavioural methods is becoming more popular. Lockhart's monkey model of focal epilepsy suggests a theoretical approach to behavioural seizure inhibition. Behaviour, by changing the pattern of excitation and inhibition surrounding a focus, is thus able to inhibit seizure activity. This article describes single case studies in which the behavioural methods of cued arousal, covert desensitization and relaxation have brought about a decrease in seizure frequency.

Adult↗

Sequence of the Bacillus subtilis glutamine synthetase gene region.

The nucleotide sequence of the glutamine synthetase (GS) region of Bacillus subtilis has been determined and found to contain several unique features. An open reading frame (ORF) upstream of the GS structural gene is part of the same operon as GS and is involved in regulation. Two downstream ORFs are separated from glnA by an apparent Rho-independent termination site. One of the downstream ORFs encodes a very hydrophobic polypeptide and contains its own potential RNA polymerase and ribosome-binding sites. The derived amino acid (aa) sequence of B. subtilis GS is similar to that of several other prokaryotes, especially to the GS of Clostridium acetobutylicum. The B. subtilis and C. acetobutylicum enzymes differ from the others in the lack of a stretch of about 25 aa as well as the presence of extra cysteine residues in a region known to contain regulatory as well as catalytic mutations. The region around the tyrosine residue that is adenylylated in GS from many species is fairly similar in the B. subtilis GS despite its lack of adenylylation.

Amino Acid Sequence↗

The psychophysics of retrospective and prospective timing.

In two experiments, different groups of subjects heard four musical selections and then estimated the duration of each selection. Some groups made retrospective time estimates while others made prospective estimates. In both experiments, analyses of the psychophysical relation between perceived and actual duration showed that the slopes of straight-line fits were flatter and accounted for a smaller proportion of the variance under retrospective as compared with prospective conditions. In addition, in experiment 1, retrospective subjects were less accurate in rank ordering the selections from longest to shortest. There was also a serial-order effect, with selections estimated longer when they occurred early in the sequence. In experiment 2 the slopes decreased as the selections in a series became longer. Both retrospective and prospective estimates also exhibited a context effect, in that estimates of a given selection were influenced by the relative durations of the other three selections in the series. The results on inaccurate retrospective judgments raise questions about prior research on stimulus factors and retrospective timing. However, similarities under retrospective and prospective conditions suggest that timing under these conditions, although different in some respects, reflects a similar process.

Adult↗

Discrimination learning in a foraging situation.

Rats were allowed to forage in a simulated natural environment made up of eight food sources (patches) each containing a fixed number of pellets. Two of the eight contained an extra supply of peanuts. The peanut patches were signaled by an olfactory/visual cue located at the bottom of the ladder leading to the patch. In successive phases the number of sessions per day, height of the patches, and availability of peanuts were manipulated. Subjects showed evidence of discrimination learning under these conditions, although the degree of discriminatory behavior varied as a function of environmental manipulations. Assessment of behavior within foraging sessions showed that subjects systematically changed their patterns of utilization of patches across time. Sampling or exploration, as well as food reinforcement, seem implicated in these results.

Journal Article↗

Theophylline and antipyrine disposition in smoking and non-smoking epileptic subjects.

Theophylline and antipyrine disposition has been compared in smoking epileptic patients, non-smoking epileptic patients and non-smoking healthy volunteers. Although clear differences in drug clearance and half-life were evident as a result of anticonvulsant drug therapy, no effect of smoking was discernible. Thus, additive effects from induction of the hepatic microsomal monooxygenase system in man by anticonvulsant drugs and polycyclic aromatic hydrocarbons (in cigarette smoke) were not evident.

Adult↗

Behavioral effects of microwave reinforcement schedules and variations in microwave intensity on albino rats.

The objective of this exploratory investigation was to determine the interactive effects of fixed-ratio scheduling of microwave reinforcement in tandem with changes in microwave intensity. Nine albino rats were conditioned to regulate their thermal environment with microwave radiation while living in a Skinner (operant conditioning) Box in which the ambient temperature was about 27.13 degrees F at the beginning of the session. Each rat obtained a 6-sec. exposure of microwave radiation on a fixed-ratio schedule of MW reinforcement, the values of which varied from FR-1 to FR-30. Intensities of MW radiation were 62.5 W, 125 W, 250 W, and 437.5 W. Sessions lasted for 8 to 9 hr. over an approximate 13-mo. period. The effects of the intensity of microwave reinforcement varied as a function of the ratio value of the schedule used. Continuous reinforcement (FR-1) produced the lowest over-all rates, whereas FR-15, and FR-25 produced the highest over-all rates. Relatively higher thermal-behavior rates occurred under 62.5 W than under any of the other MW intensities for FR-1, FR-15, and FR-25, whereas FR-10 and FR-30 ratios produced intermediate rates of thermal responding which were constant for all values of MW intensity. These data are explained in terms of interactive effects between the "local" satiation or deprivation properties of the MW intensity and the ratio requirements of the schedule of MW reinforcement.

Animals↗

Environmental influences on incidents of alleged child abuse and neglect in New York State psychiatric facilities: toward an etiology of institutional child maltreatment.

In order to gain a better understanding of the etiology of institutional child maltreatment, 232 allegations of child abuse and neglect in New York State Office of Mental Health operated facilities were investigated with the hypothesis that environmental stresses placed on professional child care workers can precipitate incidents of child maltreatment in institutional settings in the same way that stress and anxiety experienced by a parent can contribute to incidents of abuse in the home. The study focused on administrative policy decisions, patient census and admissions, seasonal influences, staffing levels and identifiable one-time disruptions in daily routines as potential contributors to institutional abuse. A multivariate regression analysis revealed a significant four-variable model for predicting the number of reports of abuse and neglect per month, R2 = .585, F(4,21) = 7.41, p less than .01. Potential preventive measures based on this model were suggested.

Adolescent↗

Plasmid segregation into minicells is associated with membrane attachment and independent of plasmid replication.

The role of plasmid replication in the segregation of plasmids into Escherichia coli minicells was investigated with temperature-sensitive replication mutants derived from E. coli plasmids ColE1 and pSC101. For as long as six generations of growth, at permissive or nonpermissive temperatures (when greater than 80% of plasmid replication was inhibited), the same amount of previously 3H-labeled plasmid DNA segregated into minicells. Density gradient separations of wild-type and temperature-sensitive plasmid DNA from both replicons segregated into the minicells showed that about 20 to 25% was stably associated with the minicell membrane at both temperatures. Electron microscopy showed this DNA to consist of circular plasmid molecules attached to the minicell membrane. These combined findings suggest that segregation of plasmids into minicells and their association with the minicell membrane are interrelated and independent of plasmid replication.

Adhesiveness↗

The influence of seizure type and medication on psychiatric symptoms in epileptic patients.

The influence of type of seizure and medication on psychological disability was assessed using the Standard Psychiatric Interview in matched epileptic patients. In comparison to patients with idiopathic tonic-clonic seizures, those with temporal lobe epilepsy complained of more irritability and impaired concentration, and were rated as more depressed and slowed up. Compared to patients on phenytoin, those on carbamazepine complained of more sleep disturbance and were more likely to be taking an hypnotic.

Adult↗

Activation of plasma and amniotic prorenin by metalloprotease and trypsin.

Human renin occurs in a latent form as prorenin in blood and amniotic fluid. We found that the metalloprotease thermolysin is a more potent activator of amniotic and plasma prorenin than trypsin, provided the thermolysin alpha 2-macroglobulin plasma inhibitor was inactivated. Thermolysin fully activated amniotic prorenin at a 23-fold lower molar concentration than trypsin, and renin activated by thermolysin was more stable than when activated by trypsin. Thermolysin also activated plasma prorenin at a 16-fold lower concentration than trypsin in the presence of methylamine (100 mM). Thermolysin activated prorenin directly, because added inhibitors of other endogenous proteases did not block the activation. The maximum activation values obtained after incubation with trypsin or thermolysin in plasma samples from 17 normotensive and 58 hypertensive subjects were similar. The mean renin concentration did not differ significantly in normotensives and hypertensives, but after activation, total renin was significantly higher in hypertensive subjects (89.8 vs. 53.4 ng angiotensin I/h . ml). The Km of the substrate, angiotensinogen, was about the same with both active renin and activated prorenin (281-290 nM). The mol wt of prorenin was 60,000 after gel filtration; activation by thermolysin reduced it to 51,000. Thus, thermolysin, which has a different peptide bond specificity than trypsin, is another model for a prorenin activator.

Adult↗