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Biomedical subjects

C Wilson

Publications and source records attributed to C Wilson.

At least 361 records · Page 20Linked to original sources
PubMed1990

Dissecting the complexity of the nervous system by enhancer detection.

Enhancer detectors are DNA constructs which, when introduced into a eukaryotic genome, respond to nearby genomic transcriptional regulatory elements by means of a reporter gene, revealing the expression pattern of genes in their vicinity. Recent experiments in Drosophila suggest that enhancer detection is a powerful method to identify genes that are expressed in the nervous system. Since enhancer detectors allow a rapid molecular and genetic characterization of genes in their vicinity, the method will greatly facilitate the study of neural development and behavior.

Animals↗
PubMed1990

Changing patterns of incidence and mortality from acute pancreatitis in Scotland, 1961-1985.

Data on all discharges from hospitals in Scotland have been recorded since 1961 as the Scottish Hospital In-Patient Statistics and examination of these data has permitted analysis of the incidence and mortality trends from acute pancreatitis. The number of discharges recorded has increased 11-fold in males from 69 patients/year in 1961 to 750 patients/year in 1985, and fourfold in females from 112 patients/year to 484 patients/year respectively. This increase has occurred particularly amongst young and middle-aged males (20-59 years) and in elderly females (over 60 years), the most marked increases occurring in the health boards of the 'central belt' area of Scotland. Mortality rate did not show a corresponding change, increasing only two-fold in males from 15 patients/year to 30 patients/year and in females from 29 patients/year to 37 patients/year. As a consequence the case mortality rate has fallen from 17.8 per cent over the period 1961-65 to 5.6 per cent over the period 1981-85. An apparent increase in the incidence of acute pancreatitis may be inferred from these data, much of which is thought to be due to improved accuracy in diagnosis.

Acute Disease↗
PubMed1990

Effective intraperitoneal antiprotease therapy for taurocholate-induced pancreatitis in rats.

In canine pancreatitis, irreversible hypotension and death follow saturation of the antiprotease molecules in peritoneal exudate by activated proteolytic enzymes which are released from the pancreas. This study has examined, in rats with taurocholate-induced pancreatitis, the efficacy of removal of the peritoneal exudate by aspiration and a single lavage, followed by instillation of an exogenous antiprotease solution. Instillation of human fresh frozen plasma, containing alpha 2-macroglobulin and alpha 1-antiprotease, was associated with the longest median survival. Aprotinin, although possessing a much greater trypsin inhibitory capacity, just failed to significantly improve the median survival time compared with the control group. Intraperitoneal antiprotease therapy is simple to perform, has a beneficial effect on survival time in this model and merits investigation in man.

Acute Disease↗
PubMed1990

Prediction of outcome in acute pancreatitis: a comparative study of APACHE II, clinical assessment and multiple factor scoring systems.

The APACHE II severity of disease classification system has been examined prospectively in 160 patients with acute pancreatitis. Using clinical and simple laboratory data APACHE II was able to provide useful discrimination between uncomplicated, complicated and fatal attacks within a few hours of admission. Peak APACHE II scores (recorded during the first 3 days) had a prognostic accuracy similar to the multiple factor scoring systems, but then incurred a similar delay. Patients could be graded according to their risk of death or of developing a major complication; no deaths occurred in patients with a peak APACHE II score less than 10. APACHE II can be repeated daily, uncomplicated attacks demonstrating falling scores in association with clinical improvement, in contrast to the rising scores associated with clinical deterioration in those dying early. APACHE II appears to reflect any continuing disease activity and may prove a useful means of monitoring the course of the illness and response to therapy.

Acute Disease↗
PubMed1990

An immunocytochemical study of keratin reactivity during rat odontogenesis.

The cytokeratin distribution in the developing rat enamel organ from day 15 of gestation through to 11 days post partum was examined immunohistochemically using a panel of monoclonal antibodies. A temporo-spatial programme of keratin expression was observed during odontogenesis and positive reactivity of the enamel organ was seen with the pan keratin antibodies CK1 (clone LP34 - reacts with a number of keratins including 6 and 18) and AE1-3 (reacts with most acidic and basic keratins). No reactivity was observed in the enamel organ with the other antibodies examined (Ks 8.12 [reacts with keratins 13 and 16], Ks 8.60 [reacts with keratins 10 and 11) and MCA157 [reacts with rat liver antigen]), although these antibodies did stain other epithelial tissues. This study supports the view that the epithelial cells of the enamel organ synthesize a tissue-specific subset of keratins which are related to the differentiation of the cells.

Animals↗
PubMed1990

Renal vasodilatory response to intravenous glycine in the aging rat kidney.

Studies were performed in the awake, chronically catheterized male Sprague-Dawley rat to investigate renal hemodynamics in the baseline state and also in response to a large intravenous (IV) amino acid (glycine) load. Studies were performed in young adult rats (age 3 to 4 months), old rats (age 18 months), and senescent rats (age 22 to 24 months). Histologic evaluation of the kidney permitted a correlation between structural and functional changes with aging. Histology showed progressive glomerular damage (sclerosis) with aging. In 18-month-old rats, the glomerular filtration rate (GFR) was normal, which, considering the level of glomerular injury (only 64% normal glomeruli), must indicate heterogeneity of glomerular function, with some hyperfunctioning glomeruli. By 22 to 24 months of age (at which time approximately 50% mortality has occurred in males of this strain), GFR is substantially reduced, as is renal plasma flow rate (RPF). Severe glomerular damage was observed histologically (only 34% normal glomeruli), indicating widespread heterogeneity of glomerular function. Young adult rats displayed a substantial renal vasodilation in response to acute IV glycine infusion, which resulted in approximately 25% increases in GFR and RPF. The renal vascular responsivity to glycine was diminished at 18 months and was completely absent in 22- to 24-month-old rats. This altered renal vasodilatory response to glycine probably reflects both structural changes associated with aging and also the compensatory vasodilation of intact hyperfunctioning remnant nephrons as other nephrons are lost due to aging.

Aging↗
PubMed1990

Trypanocidal effects of catecholamines and indolealkylamines.

Catecholamines, indolealkylamines and their analogues are oxidized at neutral or alkaline pH, producing hydrogen peroxide, quinones and free radicals. Several of these amines were tested for trypanocidal effects on Trypanosoma brucei, which possess a well-documented vulnerability to such oxidation products. Dopamine, 5-hydroxydopamine (5-OHDA), 6-hydroxydopamine (6-OHDA), 5-hydroxytryptamine (5-HT), 5,6-dihydroxytryptamine (5,6-DHT) and 5,7-dihydroxytryptamine (5,7-DHT) killed the parasites in vitro, using a fibroblast feeder layer cell culture system, in four to 48 hours at concentrations of 10(-5)-10(-7) M. The 5-OHDA, 6-OHDA, 5,6-DHT and 5,7-DHT were also effective in vivo when tested by intraperitoneal injection of infected mice.

Animals↗
PubMed1990

Regulation of antigen-induced blastogenesis and interleukin-2 expression by adherent mononuclear cells in humans infected with Schistosoma mansoni.

The immune response and its regulation by adherent mononuclear cells were investigated in 39 Egyptians aged 13-30 (mean +/- SD, 16.2 +/- 3.6) with chronic Schistosoma mansoni infection (fecal egg excretion, 40-2480 eggs/g; mean, 709 +/- 612). Blastogenesis and production of interleukin-2 (IL-2) by peripheral blood mononuclear cells showed a significant correlation when streptolysin O but not when soluble worm antigenic preparation (SWAP) was used as stimulus. This suggested independent regulation of these responses to SWAP. Thirteen subjects showed SWAP-restricted suppression of blastogenesis but not IL-2 production by adherent cells. Compared with 24 other S. mansoni-infected subjects, they had depressed blastogenic responses to SWAP but comparable SWAP-induced IL-2 production and responsiveness to exogenous IL-2. This study indicates that IL-2 production is not the site of action of parasite antigen-restricted suppressor adherent cells in chronic S. mansoni infection.

Adolescent↗
PubMed1990

Prediction of possibly preventable death: a case-control study of postneonatal mortality in southern New Zealand.

The postneonatal mortality rate in three southern regions of New Zealand was 8.1 per 1000 live births for 1979-1984. The possibly preventable postneonatal mortality rate was 7.1 per 1000 live births and data on 377 possibly preventable deaths and 936 randomly selected controls were used to develop a two-stage risk-scoring system. Logistic regression analysis was undertaken separately on two sub-samples of the total sample. The data were used to evaluate three other previously published scoring systems. The four variables used in our birth score (mother's age, parity, marital status, and birth weight) have all appeared in other scoring systems, and this score could identify a group of infants in southern New Zealand with an estimated 1.7% mortality rate in the first year of life. It is suggested that currently the only valid use of risk-scoring in this region is for the definition of a high-risk population for the purpose of evaluating potential intervention strategies.

Case-Control Studies↗
PubMed1990

The site of an immune-selected point mutation in the transmembrane protein of human immunodeficiency virus type 1 does not constitute the neutralization epitope.

We previously reported the in vitro generation of a neutralization-resistant variant of the molecularly cloned isolate of human immunodeficiency virus type 1 (HIV-1), HXB2D. The molecular basis for the resistance was shown to be a point mutation in the env gene, causing the substitution of threonine for alanine at position 582 of gp41. Here, we show the variant to be resistant to syncytium inhibition as well as to neutralization by the immune-selecting serum. Moreover, 30% of HIV-positive human sera able to neutralize the parental virus have significantly decreased ability to neutralize the variant. As the A-to-T substitution thus has general relevance to the interaction of HIV-1 with the host immune system, we investigated further the biologic and immunologic bases for the altered properties. Synthetic peptides corresponding to the 582 region failed to compete in infectivity, neutralization, or syncytium inhibition assays and did not elicit neutralizing antibodies. Furthermore, human antibodies, affinity purified on synthetic peptide resins, bound to gp41 and peptides from the 582 region but did not possess neutralizing antibody activity. Some viral constructs in which the AVERY sequence in the 582 region was altered by site-directed mutagenesis were not infectious, indicating that the primary structure in this region is crucial for viral infectivity. Constructs predicted to possess a local secondary structure similar to that of the variant nevertheless behaved like the parental virus and remained neutralization sensitive. These results suggest that the requirements for neutralization resistance in this region are very precise. Our results with synthetic peptides show that the 582 region does not by itself constitute a neutralization epitope. Moreover, the degree of flexibility in amino acid substitution which allows maintenance of neutralization sensitivity suggests that position 582 does not form part of a noncontiguous neutralization epitope. The basis for neutralization resistance of the immune-selected variant is more likely a conformational change altering a neutralization epitope at a distant site.

Amino Acid Sequence↗
PubMed1990

Aberrant membrane insertion of a cytoplasmic tail deletion mutant of the hemagglutinin-neuraminidase glycoprotein of Newcastle disease virus.

The hemagglutinin-neuraminidase (HN) protein of Newcastle disease virus (NDV) is a type II glycoprotein oriented in the plasma membrane with its amino terminus in the cytoplasm and its carboxy terminus external to the cell. We have previously shown that the membrane insertion of HN protein requires signal recognition particle SRP, occurs cotranslationally, and utilizes the same GTP-dependent step that has been described for secretory proteins, type I proteins, and multispanning proteins (C. Wilson, R. Gilmore, and T. Morrison, Mol. Cell. Biol. 7:1386-1392, 1987; C. Wilson, T. Connolly, T. Morrison, and R. Gilmore, J. Cell Biol. 107:69-77, 1988). The role of the amino-terminal cytoplasmic domain in the faithful membrane insertion of this type II protein was explored by characterizing the membrane integration of a mutant lacking 23 of the 26 amino acids of the cytoplasmic domain. The mutant protein was able to interact with SRP, resulting in translation inhibition, membrane targeting, and membrane translocation, but the efficiency of translocation was considerably lower than for the wild-type HN protein. In addition, a significant proportion of the mutant protein synthesized in the presence of SRP and microsomal membranes was associated with the membrane in an EDTA- and alkali-insensitive manner yet integrated into membranes with its carboxy-terminal domain on the cytoplasmic side of membrane vesicles. Membrane-integrated molecules with this reverse orientation were not detected when the mutant protein was synthesized in the absence of SRP or a functional SRP receptor. Truncated mRNAs encoding amino-terminal segments of the wild-type and mutant proteins were translated to prepare ribosomes bearing arrested nascent chains. The arrested mutant nascent chain, in contrast to the wild-type nascent chain, was also able to insert into membranes in a GTP- and SRP-independent manner. Results suggest that the cytoplasmic domain plays a role in the proper membrane insertion of this type II glycoprotein.

Amino Acid Sequence↗
PubMed1990

Focal functional anatomy of dorsolateral frontocentral seizures.

We compared 6 patients with dorsolateral frontocentral seizures to 7 patients with temporal lobe seizures. We determined general seizure location by structural lesions in 7 patients, bilateral depth electrodes in 4, and EEG and semiology in 2. We then mapped seizure cortex and essential cortex using chronic ECoG arrays. Two ECoG patterns were similar in frontal and temporal seizures. Focal patterns were near lesions and resections. Regional patterns were distant from lesions but not associated with worse surgical outcome. "Dipolar" seizure patterns occurred in one-half of frontal patients with maps like somatosensory evoked responses, consistent with focal seizure anatomy and involvement of sensorimotor cortex. Dipole location estimates were near centers of seizure cortex determined by lesions, semiology, and outcome. Six temporal patients had focal excisions that gave significant seizure reduction in all. All frontocentral patients had focal excisions that significantly reduced seizures except in 1 patient with progressive disease. We conclude that dorsolateral frontocentral seizures have focal functional anatomy that can be predicted by ictal ECoG.

Adult↗
PubMed1990

P-element-mediated enhancer detection allows rapid identification of developmentally regulated genes and cell specific markers in Drosophila.

We have employed a new technique in Drosophila that allows in vivo detection of genomic regulatory elements using a beta-galactosidase reporter gene. A translational fusion of the reporter gene to the P-transposase gene, which is encoded by the P-transposon of Drosophila, places the expression of beta-galactosidase under the control of the weak P-transposase promoter. Flies carrying single insertions of this P-element construct at different locations in the Drosophila genome frequently stain for beta-galactosidase activity in a temporally and spatially restricted fashion in embryos, larvae and adult ovaries, reflecting the influence of nearby genomic regulatory elements on the P-transposase promoter. This technique is a powerful tool as it can be used to produce very many different cell markers and to isolate developmentally regulated genes in Drosophila. We discuss the implications of our results and the applications of the technique to further the study of Drosophila development.

Animals↗
PubMed1990

Teenage suicide in Zimbabwe.

The teenage suicide rate in Zimbabwe did not change much during the 1970s, though the rate rose for female teenagers. Female teenagers used poison as a method of suicide more often than did adults, and self-immolation had increased in frequency among young women by the mid-1980s.

Adolescent↗