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Biomedical subjects

K Scott

Publications and source records attributed to K Scott.

At least 91 records · Page 5Linked to original sources

Crystallization and preliminary crystallographic studies of the precursor and mature forms of a neutral lipase from the fungus Rhizopus delemar.

A neutral lipase from the filamentous fungus Rhizopus delemar has been crystallized in both its proenzyme and mature forms. Although the latter crystallizes readily and produces a variety of crystal forms, only one was found to be suitable for X-ray studies. It is monoclinic (C2, a = 92.8 A, b = 128.9 A, c = 78.3 A, beta = 135.8) with two molecules in the asymmetric unit related by a noncrystallographic diad. The prolipase crystals are orthorhombic (P2(1)2(1)2(1), with a = 79.8 A, b = 115.2 A, c = 73.0 A) and also contain a pair of molecules in the asymmetric unit. Initial results of molecular replacement calculations using the refined coordinates of the related lipase from Rhizomucor miehei identified the correct orientations and positions of the protein molecules in the unit cells of crystals of both proenzyme and the mature form.

Crystallization↗

Cocaine and metabolites in amniotic fluid may prolong fetal drug exposure.

OBJECTIVE: Cocaine and metabolites can be found in the amniotic fluid after maternal use, presumably as a result of fetal urination. The fetus may be repeatedly exposed to the effects of these drugs through contact with amniotic fluid that contains these substances. The purpose of this study was to determine whether the naive fetal lamb generates detectable fetal blood levels of cocaine and metabolites when cocaine is placed directly into the amniotic fluid and, if so, whether fetal swallowing accounts for these findings. STUDY DESIGN: Six pregnant ewes with singleton fetuses of 120 to 125 days' gestation were chronically catheterized for daily sampling of cocaine and metabolite levels in maternal venous plasma, fetal venous plasma, and amniotic fluid over a 7-day period. Esophageal ligation was performed in three additional animals similarly instrumented to evaluate the role of fetal swallowing in the distribution of amniotic fluid cocaine and its metabolites. In each case, at the time of surgery, an Alzet osmotic pump delivering cocaine at 0.5 mg/kg estimated fetal weight per hour into the amniotic fluid was secured to the fetal back. Cocaine and metabolites (benzoylecgonine, ecgonine methyl ester, and norcocaine) were measured daily in material and fetal plasma, amniotic fluid, and meconium by solid-phase extraction and derivatization and quantified by high-performance gas chromatographic techniques. RESULTS: The concentrations of ecgonine methyl ester were highest in the amniotic fluid followed by cocaine and benzoylecgonine. In the normal and esophagus-ligated groups, cocaine, benzoylecgonine, and norcocaine were found in fetal plasma in concentrations of approximately 3% that of amniotic fluid. Ecgonine methyl ester was not detected in fetal plasma from either group. Meconium samples from sheep with and without esophageal ligation demonstrated high levels of norcocaine. CONCLUSION: We conclude that cocaine and metabolites in amniotic fluid enter the fetal circulation to produce detectable plasma levels through routes other than swallowing. Moreover, the results of meconium analyses in the two groups of fetuses suggest that fetal swallowing is not the primary mechanism by which cocaine and metabolites enter the intestine.

Absorption↗

An innovative course: 'vers l'Europe 1992'.

A course in using French in the consultation is described. This proved a popular exercise with many general practitioners wishing to attend. A previous knowledge of French was essential for acceptance. The course consisted of 10 meetings with homework. Both formal and informal assessment of the course showed the success both from a group and an individual point of view.

Education, Medical, Continuing↗

Unintended and unwanted pregnancy in St. Lucia.

Among 200 mothers interviewed in St. Lucia, 82.5% described their pregnancy as unintended and 44% as unwanted; 80% of women having an intended pregnancy and 94.6% having an unintended pregnancy were unmarried and 18.5% were teenagers. Mothers of unintended pregnancies were significantly younger, were of significantly higher parity and had begun sexual relations at a significantly earlier age than mothers of intended pregnancies; and, unlike mothers of planned pregnancies, their desired interpregnancy interval was significantly longer than the actual interval. These results and the sporadic and ineffective use of contraception in St. Lucia emphasize the need for improvements in fertility regulation in that country.

Demography↗

Cloning and characterization of the major hepatic glutathione S-transferase from a marine teleost flatfish, the plaice (Pleuronectes platessa), with structural similarities to plant, insect and mammalian Theta class isoenzymes.

A cDNA clone (PLGSTA) of 896 bp, containing an open reading frame encoding a 225-amino-acid polypeptide of M(r) 25,723, was isolated from a cDNA library constructed in lambda gt11 from the liver of a marine teleost flatfish, the plaice (Pleuronectes platessa). The identification of this cDNA as that coding for the subunit of the major cytosolic glutathione S-transferase of plaice liver, GST-A, was supported by its heterologous expression in and purification of its protein product from Escherichia coli. The recombinant-derived protein exhibited identical M(r) and immunoreactivity and a similar substrate specificity to GST-A previously isolated from plaice liver. Comparison of the deduced amino acid sequence of the plaice GST-A polypeptide with the primary structures of GSTs from other Phyla revealed that it showed the greatest similarity to plant, insect and mammalian Theta class GSTs. Southern blot analysis of plaice DNA hybridized to the PLGSTA cDNA showed a banding pattern indicative of the presence of a single gene. Northern blot analysis of a variety of plaice tissues showed hybridizing bands of approx. 1100 nucleotides in all tissues tested, with the highest relative amounts in liver and intestinal mucosa. A marked increase in hybridization intensity was observed in hepatic RNA samples from plaice treated with trans-stilbene oxide, suggesting that GST-A is induced by epoxides in this species.

Amino Acid Sequence↗

Does social deprivation during gestation and early life predispose to later schizophrenia?

We employed a case-control study design to investigate whether schizophrenic patients differed from non-psychotic psychiatric patients in terms of place of birth and paternal occupation. "Cases" were first-contact schizophrenic patients ascertained from the Camberwell Cumulative Psychiatric Case Register. "Controls" were the next (non-psychotic) patient on the Register matched for age and sex. In comparison with controls, cases were more likely to have: (1) been born in the deprived inner-city Camberwell catchment area (odds ratio 2.3), and (2) had fathers who had "manual" as opposed to "non-manual" occupations (odds ratio 2.1). The results were compatible with the notion that socio-economic deprivation during gestation and early life predisposes to later schizophrenia.

Case-Control Studies↗

Reactor modelling for electrochemical processes.

This paper presents a relatively straightforward approach to the modelling of electrochemical reactors operated in batch or continuous modes. The models are based on ideal flow assumptions of either well-mixed or plug flow and incorporate reaction rate models based on electrochemical kinetics and mass transport at one electrode. General characteristics of the reactor models are described, particularly with regard to the need for good mass transport in metal recovery applications. An example is given on the use of the model in the recovery of a heavy metal (Cd2+) from an acidified solution containing Cd(II) and Fe(III) ions. The reaction rate model is based on experimental data.

Cadmium↗

Enzymatic activity and immunoreactivity of extracellular phospholipase A2 in inflammatory synovial fluids.

Synovial fluid PLA2 concentration was measured by an ELISA technique using monoclonal antibodies raised against human recombinant "synovial-type" group II phospholipase A2. This ELISA was specific for synovial-type PLA2 and did not detect pancreatic (group I) PLA2. In all synovial fluids examined, including rheumatoid, osteoarthritic, psoriatic, and gouty fluids, synovial fluid PLA2 enzyme activity significantly correlated with PLA2 immunoreactivity (P < 0.001). Within the limits of the ELISA technique, there was no evidence for the presence of specific or nonspecific modulation of PLA2 activity by either putative PLA2 activating or inhibitory proteins.

Arthritis↗

Serum phospholipase A2 enzyme activity and immunoreactivity in a prospective analysis of patients with septic shock.

Massive elevations of serum phospholipase A2 activity have been documented in patients with septic shock. Serum PLA2 activity correlated to the degree and duration of circulatory collapse, while purified native PLA2 reproduced hypotension in experimental animals. In a prospective study of patients with septic shock, we have determined the relationship of PLA2 enzyme activity to PLA2 immunoreactivity using radiolabelled E. coli phospholipid substrate and an ELISA specific for group II human nonpancreatic PLA2. In all patients, there was a clear concordance of the two assays. Maximal PLA2 concentration was increased a mean of 554-fold over normal levels. We found no evidence to support the presence of activating or inhibitory proteins. These data confirm that the observed increase in serum PLA2 activity in septic shock is due to intravascular release of group II nonpancreatic PLA2.

Antibodies, Monoclonal↗

Induction of circulating group II phospholipase A2 expression in adults with malaria.

High levels of interleukin 1 and tumor necrosis factor are found in both cases of malaria and cases of septic shock. Since both interleukin 1 and tumor necrosis factor induce expression of the proinflammatory enzyme phospholipase A2 (PLA2), we examined serum PLA2 levels in 14 adults with malaria. Mean serum PLA2 activity was elevated 40-fold above normal (P less than 0.001). Serum PLA2 activity correlated with PLA2 immunoreactivity (r = 0.987; P less than 0.001) by an enzyme-linked immunosorbent assay specific for human group II PLA2, showing that serum PLA2 in cases of malaria is host derived. This article describes the novel finding of elevated PLA2 levels in cases of malaria, further strengthening the notion that mediators of the host response in cases of malaria are similar to those in cases of septic shock.

Adult↗