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Biomedical subjects

J Wells

Publications and source records attributed to J Wells.

At least 91 records · Page 5Linked to original sources
PubMed1994

Traumatic lesions and transplants of granule cells in the dentate gyrus alter the distribution of afferent fibers in the molecular layer.

The present experiments determined whether traumatic lesions of the dentate gyrus granule cells had a different effect on the afferents in the molecular layer (ML) than nontraumatic lesions. Nontraumatic lesions of the granule cells induced by colchicine, ibotenic acid, x-radiation, and adrenalectomy have been reported to reduce both the acetylcholinesterase (AChE)-positive fibers and entorhinal afferents in the ML. After the nontraumatic granule cell lesions, the laminar distribution of the entorhinal afferents was maintained in the ML, whereas the AChE laminar pattern was lost. In the present study, dentate granule cells were traumatically lesioned by a fluid injection into the infragranular cleavage plane (IGCP) of the dentate gyrus. The traumatic lesion resulted in an altered distribution of the afferents in the ML. The perforant path fibers, shown by injection of wheat germ agglutinin horseradish peroxidase into the entorhinal cortex, occupied a greater proportion of the ML in lesioned animals than in control animals. The normal laminar pattern of AChE-positive afferents was not present after the granule cell lesion. There was an initial increase in AChE-positive fibers in the ML that lasted several weeks but eventually returned to near normal levels. The altered distribution of afferents could in part be due to uneven shrinkage of the molecular layer and/or sprouting of the afferents. Granule cell suspension transplants into the IGCP also traumatically lesioned the host granule cells but immediately replaced the damaged host granule cells with immature granule cells. The distribution of afferents was similar to that found in lesioned-only animals. The traumatic lesion induced MAP2 immunoreactivity in the anisomorphic reactive astrocytes of the ML. At the longer survival times, MAP2 was not seen in either the astrocytes of the ML or in the isomorphic reactive astrocytes in CA3.

Acetylcholinesterase↗
PubMed1994

Observation and measurement of drooling by people with mental retardation.

Four brief observational surveys were used to score residents of a state institution for people with mental retardation as drooling/not drooling. An average of 14% of the population was identified as drooling on the occasion of any of the surveys; the accumulated proportion of clients reported as drooling was 28%. In a second study, the drooling of 2 of the clients identified in the first study was sampled within and across days. These clients drooled different amounts both within and between days, which validated their presence and classifications in the first study.

Adolescent↗
PubMed1994

Flumazenil in cirrhotic patients in hepatic coma: a randomized double-blind placebo-controlled crossover trial.

Previous reports have suggested that "endogenous" benzodiazepines could contribute to neural inhibition in hepatic encephalopathy. RO 15-1788 (flumazenil), a specific antagonist of brain benzodiazepine receptors, could thus reverse the neurological symptoms of hepatic encephalopathy. To test this possibility, we conducted a double-blind, placebo-controlled crossover trial of the efficacy of flumazenil in cirrhotic patients in hepatic coma. Seventy-seven cirrhotic patients in hepatic coma were evaluated. Fifty-six were excluded from the trial because of multiorgan failure or because coma was precipitated by prior use of benzodiazepines, and 21 patients were randomly assigned to the flumazenil group (11 patients) or the placebo group (10 patients). Treatment was administered intravenously as a 20-ml solution (placebo or 2 mg flumazenil); seven patients were crossed over. Clinical status was assessed blindly by two observers, using a modified Glasgow scale, every 15 min for 6 hr. Electroencephalogram tracings obtained before and after drug administration were evaluated blindly by two independent observers. Serum concentrations of benzodiazepines before treatment were measured by means of a fluorescence polarization immunoassay. Improvement in neurological symptoms was observed in six patients treated with flumazenil, whereas none in the placebo group showed improvement (p < 0.05; Fisher's exact test). Improvements in electroencephalogram tracings were demonstrated in four patients treated with flumazenil, compared with two patients in the placebo group (p = NS). Benzodiazepines were found in the serum of four patients treated with flumazenil (two responders and two nonresponders); all of these patients had received pharmaceutical benzodiazepines 4 to 6 days before the trial.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Insertional activation of mevalonate kinase by hepatitis B virus DNA in a human hepatoma cell line.

Insertional mutagenesis of growth related genes by hepatitis B virus (HBV) DNA is presumed to play a role in hepatocarcinogenesis. Here, we report on insertional activation of the mevalonate kinase (MK) gene in the human hepatoma cell line PLC/PRF/5. Integration of HBV DNA dissociated the promoter and upstream regulatory elements of the gene from its coding sequences. This led to the over-expression of hybrid transcripts arising from an HBV promoter and the consequent over-production of functionally active mevalonate kinase. MK phosphorylates mevalonate, a major intermediate in the branched cholesterol/isoprenoid biosynthetic pathway. Isoprenylation is crucial to the functions of cellular proteins related to growth control, including the proto-oncogene ras. As the enzymes of these biosynthetic pathways are regulated at multiple points by negative feedback, both transcriptionally and at the protein level, the results discussed here support the idea that aberrant growth could result from deregulated overexpression of MK and, perhaps, other enzymes in the cholesterol pathway. These results invoke novel mechanisms by which cell transformation might occur.

Amino Acid Sequence↗
PubMed1993

Site-directed mutagenesis of human thioredoxin. Identification of cysteine 74 as critical to its function in the "early pregnancy factor" system.

Thioredoxin has been identified as a key component of the "early pregnancy factor" system, a system of components present in pregnancy sera which expresses a lymphocyte modifying activity in an assay known as the rosette inhibition assay. Although thioredoxin alone is inactive, addition of thioredoxin to lymphocytes in combination with nonpregnancy sera or platelet-activating factor results in a positive response. We have changed several amino acids of human thioredoxin by site-directed mutagenesis to investigate the residues required for this cooperative function. Conversion of the two active site residues (cysteines 32 and 35) to serines results in a protein devoid of classical redox activity; however, this protein retained its ability to cooperate with non-pregnancy sera or platelet-activating factor in the rosette inhibition assay. Vertebrate thioredoxins contain an additional conserved pair of cysteine residues in the C-terminal portion of the protein. Changing both to serines resulted in no change in redox activity but completely abolished function in the rosette inhibition assay. Further study revealed this function was solely dependent on cysteine 74 as conversion of only cysteine 74 to serine abolished function, whereas replacement of only cysteine 70 with serine had no effect. The nonfunctional mutants counteracted the action of pregnancy serum in the assay strongly supporting the hypothesis that thioredoxin is an integral part of the early pregnancy factor system with residue cysteine 74 having an important role.

Amino Acid Sequence↗
PubMed1993

Mutations in the human retinal degeneration slow (RDS) gene can cause either retinitis pigmentosa or macular dystrophy.

Mutations in the RDS gene, which encodes the photoreceptor glycoprotein peripherin, have been sought in families with autosomal dominant retinal dystrophies. A cysteine deletion at codon 118/119 is associated with retinitis pigmentosa in one. Three families with similar macular dystrophy have mutations at codon 172, arginine being substituted by tryptophan in two and by glutamine in one. A stop sequence at codon 258 exists in a family with adult vitelliform macular dystrophy. These findings demonstrate that both retinitis pigmentosa and macular dystrophies are caused by mutations in RDS and that the functional significance of certain amino-acids in peripherin-RDS may be different in cones and rods.

Adult↗
PubMed1993

An approach to training and retaining primary care physicians in rural Appalachia.

The West Virginia School of Osteopathic Medicine (WVSOM) educated and retained more primary care physicians for practice in rural Appalachia than did any other U.S. medical school from 1978 through 1990. This article describes the most important methods used at WVSOM to place physicians in rural areas: (1) The school has a focused, achievable mission (to provide primary care physicians who are trained to meet the medical needs of rural Appalachia and to improve the health care of the rural Appalachian population) that is agreed upon by the administration, faculty, and students; (2) it participates in a multistate educational exchange program with a similar mission; (3) it emphasizes personalized and interactive recruiting, admission, and placement processes aimed to attract nontraditional, rural students; (4) it provides early and long-term clinical training in rural sites (both hospitals and physicians' offices); (5) it is dedicated primarily to the education of medical students rather than to research or other goals; and (6) it is a freestanding school in a rural environment. The authors state that although WVSOM is unusual in some respects, at least some of its methods may be useful to other medical schools as they seek to produce more primary care physicians for rural and other underserved areas.

Appalachian Region↗
PubMed1993

Neutrophilic eccrine hidradenitis with an unusual presentation.

Neutrophilic eccrine hidradenitis (NEH) is an eruption most commonly seen in patients undergoing chemotherapy, and is characterized histologically by a neutrophilic infiltrate around the eccrine coils, with associated necrosis of the sweat coils. The rash usually affects the trunk and extremities, and the morphology of the lesions is very variable. We describe a patient with neutrophilic eccrine hidradenitis who presented with symmetrical, erythematous, swollen ears, a manifestation of NEH which has not been previously reported.

Adolescent↗
PubMed1993

The effects of hydrogen peroxide on steroidogenesis in mouse Leydig tumor cells.

It has previously been reported that treatment of rat luteal cells and human granulosa luteal cells with hydrogen peroxide (H2O2) results in a significant inhibition of steroid production. The mechanism of inhibition in the former was found to be at the level of cholesterol transport into the mitochondria, whereas in the latter it was found to be a result of inhibition of one or more enzymes in the steroidogenic pathway. In the present study we examined the effects of H2O2 on hormone-stimulated steroid production in another steroidogenic cell type, the Leydig cell. Our results demonstrate that treatment of either LH- or cAMP analog [(Bu)2cAMP]-stimulated MA-10 mouse Leydig tumor cells with H2O2 results in a dose-dependent inhibition of the production of progesterone (the major steroid produced in MA-10 cells). It was also observed that similar concentrations of H2O2 resulted in a significant inhibition of protein synthesis, a finding which could in part be responsible for the observed decrease in steroid production. Furthermore, although H2O2 resulted in a dose-dependent inhibition of (Bu)2cAMP-stimulated pregnenolone production, addition of the hydroxylated intermediate 22R-hydroxycholesterol and inhibitors of further pregnenolone metabolism demonstrated that cholesterol side-chain cleavage complex activity was unaffected by H2O2. Conversely, incubation of H2O2-treated cells in the presence of pregnenolone resulted in a very significant inhibition of progesterone synthesis. These data indicate that H2O2 inhibits steroidogenesis in Leydig tumor cells primarily by inhibiting the activity of the 3 beta-hydroxysteroid dehydrogenase, but that other effects of H2O2 such as inhibition of protein synthesis and the transfer of cholesterol to the cholesterol side-chain cleavage complex may also be involved.

Animals↗
PubMed1993

Dose- and source-size-related changes in the late response of pig skin to irradiation with single doses of beta radiation from sources of differing energy.

Late radiation damage to pig skin has been assessed at 104 weeks after exposure to sources of 90Sr/90Y (Emax 2.2 MeV) and 170Tm (Emax 0.9 MeV). Damage was assessed from measurements of dermal thickness in histological sections of irradiated skin and was compared with that of unirradiated skin to establish the relative reduction in dermal thickness. The size of the source varied from 0.1 to 40.0 mm in diameter; this covered the range of source sizes designed to simulate exposure to radioactive "hot" particles (< or = 1.0 mm diameter) up to the lower range of field size that patients may be exposed to in radiotherapy treatments. Radiation doses were measured using an extrapolation chamber with a collecting electrode of 1.1 mm2, and thus the quoted doses represent an average dose over this area. For the larger 90Sr/90Y sources of > or = 5 mm diameter and the larger 170Tm sources of > or = 2 mm diameter there was no evidence, based on levels of damage consistent with a > or = 10, > or = 20, > or = 30, and > or = 40% reduction in relative dermal thickness, for any effect of source size on the ED50 value for each of these specified levels of effect. However, there was a marked effect of beta-particle energy; the skin surface doses associated with the ED50 values (+/- SE) for a > or = 20% reduction in relative dermal thickness were approximately 12 and approximately 40 Gy for 90Sr/90Y and 170Tm, respectively. This difference in skin surface dose for an equivalent level of dermal injury reflects the variation in the depth dose from these two beta-particle emitters. These skin surface doses, for what was considered to be a clinically detectable dermal effect, were below the ED10 for the early skin response of moist desquamation. This supports the selection of late dermal thinning as the effect on which to base dose limits in radiation protection for more generalized larger area skin exposures. In comparison, single exposures to a small area, from sources designed to simulate those from hot particles, reinforced the view that acute ulceration should be the effect on which dose limitation is based. Either the isoeffect doses for a clinically detectable reduction in relative dermal thickness of > or = 20%, following a single exposure to a small area, were higher than the ED10 for acute ulceration or the area of skin showing dermal thinning was so small that it was not considered to be detrimental.

Animals↗
PubMed1992

Long-term symptomless HIV-1 infection in recipients of blood products from a single donor.

There have been reported cases of long-term symptomless human immunodeficiency virus type 1 (HIV-1) infection, but it is not clear whether the benign course of infection was due to host, viral, or other unknown factors. During follow-up of subjects with transfusion-acquired HIV-1 infection in New South Wales, Australia, we identified a group of 6 subjects who had been infected through a single common donor. We were therefore able to study the contributions of various factors to the course of infection. Throughout follow-up (range 6.8-10.1 years after infection), 5 of the recipients and the donor (last follow-up 10.2 years after infection of the first recipient) remained clinically free of symptoms, with normal CD4 cell counts and no p24 antigenaemia. HIV-1 was isolated from only 1 recipient; the isolate did not induce syncytia in a SUPT1 co-culture assay and had a limited in-vitro host range. 1 infected recipient (who had received extensive immunosuppressive treatment for systemic lupus erythematosus) developed Pneumocystis carinii pneumonia and died 4.3 years after infection. The frequency of progression to AIDS or a CD4 cell count below 0.50 x 10(9)/l was significantly lower among the 6 subjects with a common donor (1/6) than among 101 other HIV-infected transfusion recipients for whom data from 7 years of follow-up were available (94/101; p less than 0.0001). These findings suggest that the subjects were infected by a less virulent strain of HIV-1. The identification of this group of subjects should stimulate a search for other similar groups, which will provide important information on the immunopathogenesis of HIV-1 disease.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Isomorphic activation of astrocytes in the somatosensory thalamus.

Structural recovery in the rat somatosensory thalamus after the loss of one of its major inputs provided a model for studying the changes in astrocytes associated with reactive synaptogenesis. The temporal separation of the initiation of Wallerian degeneration and reactive synaptogenesis permitted astrocytic changes to be correlated either with the removal of degeneration, early in the recovery sequence, or with synaptogenesis, later in recovery. Over a period of post-lesion times ranging from 3 days to 13.5 months, GFAP-positive astrocytic fibers were quantified and the population density of S-100-positive astrocytic cell bodies was determined in the ventral posterolateral nucleus (VPL). The relative area of astrocytic cell bodies was measured at an early peak of the increased GFAP immunoreactivity (4-5 days post-lesion). The normal side of VPL (c-VPL) was compared to the deafferented side of VPL (d-VPL) and the ratio d-VPL/c-VPL was determined. Astrocytes in d-VPL underwent a minimal isomorphic activation with little or no hypertrophy or proliferation but with a large increase in GFAP immunoreactivity. Prior to the initiation of synaptogenesis, there was a decrease both in GFAP immunoreactivity and in the population density of VPL astrocytes. The decreases in the recovery curves suggested that a suppression of the influence of astrocytes may have been important for sprouting and/or synaptogenesis. In other systems, where synaptogenesis was initiated early in the recovery sequence, the suppression of astrocytes that was related to synaptogenesis may have been masked by astrocytic changes related to the removal of degeneration.

Afferent Pathways↗
PubMed1992

Evaluation of a photodiode array/HPLC-based system for the detection and quantitation of basic drugs in postmortem blood.

A systematic analytical approach has been developed for liquid chromatography determination of a number of basic drugs in postmortem blood. Using selective extraction, that is, back extraction into 0.2N sulfuric acid and 6N hydrochloric acid after the initial extraction with toluene under basic conditions (from 2 mL of blood), basic and weakly basic drugs, such as propranolol and diazepam, can be simultaneously quantitated and identified with a high degree of confidence. A microcomputer-based photodiode array detector was used to evaluate peak purity and facilitate peak identification. An automatic library search was performed at the end of each analysis using the system software. The method was validated for within-day and between-day precision for ten basic drugs at two concentrations. The coefficient of variation for the between-day precision was less than 8.7%. Accuracy of the assay was tested at four concentrations using linear regression analysis. The coefficients of determination (r2) for all ten drugs were greater than 0.99, and their slopes were close to unity. The chromatographic conditions developed are suitable for the screening of several basic, acidic, amphoteric, and neutral drugs. Retention data and ultraviolet spectral data for 119 drugs on two reversed-phase columns, using acidic mobile phases, are also presented.

Blood Chemical Analysis↗
PubMed1992

HIV antibody testing in France: results of a national survey.

Data from a knowledge, attitudes, and behavior survey conducted at the end of 1988 suggest that 13% of the population in France, aged 16 to 50 years, had been tested for HIV antibodies. Geographical differences in testing were observed, with a greater number of respondents tested in the regions where AIDS is most prevalent. Important variations in the percentage of HIV antibody-tested persons were found in relation to age, education, and occupation, but not to gender. Multiple logistic regression analysis identified significant predictors of HIV antibody testing. Behavioral predictors were multiple partners (odds ratio = 2.4), anal intercourse (odds ratio = 1.8), and drug use. A positive relationship was demonstrated between HIV testing and condom use. These correlations could indicate that the opportunity for anonymous and free testing encourages high-risk individuals to be tested.

AIDS Serodiagnosis↗