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Biomedical subjects

C Wilson

Publications and source records attributed to C Wilson.

At least 325 records · Page 18Linked to original sources
PubMed1993

In vivo comparisons of the effects of quinpirole and the putative presynaptic dopaminergic agonists B-HT 920 and SND 919 on striatal dopamine and acetylcholine release.

The extent to which the putative dopamine (DA) autoreceptor agonists B-HT 920 (6-allyl-2-amino-5,6,7,8-tetrahydro-4H-thiazolo[4,5d]azepine dihydrochloride) and SND 919 (2-amino-4,5,6,7-tetrahydro-6-propylamino- benzthiazol dihydrochloride) and the potent D2 receptor agonist quinpirole have differential effects on pre- and postsynaptic DA receptors was determined by using in vivo microdialysis to monitor the effects of these compounds on extracellular concentrations of DA and acetylcholine (ACh) in the striata of freely moving rats. B-HT 920 and SND 919 reduced interstitial concentrations of DA, but not ACh, when administered s.c. at doses of 0.05 and 0.1 mg/kg. Quinpirole (0.05 and 0.2 mg/kg) decreased extracellular concentrations of both DA and ACh. Hence, relative to its effects on DA, quinpirole was more potent than the other drugs at DA receptors controlling ACh release. These results are consistent with the hypothesis that B-HT 920 and SND 919 have preferential actions on DA autoreceptors. Local application of the selective D2 receptor antagonist raclopride produced similar dose-dependent increases in DA and ACh release. It is unlikely therefore that differences in the degree to which endogenous DA inhibits transmitter release from nigrostriatal terminals and cholinergic neurons can account for the greater sensitivity of the former to the depressant actions of systemically administered B-HT 920 and SND 919. As was the case with systemic administration, local striatal application of B-HT 920 produced larger decreases in extracellular DA than ACh.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1993

The AHEC libraries.

Explore the source record for details and available documents.

Area Health Education Centers↗
PubMed1993

Independent guidance of retinal axons in the developing visual system of Drosophila.

The development of the adult visual system of Drosophila requires the establishment of precise retinotopic connections between retinal photoreceptor cell axons and their synaptic partners in the optic lobe of the brain. To assess the role of axon-axon interactions in retinal axon guidance, we used genetic methods to disrupt the normal spatiotemporal order of retinal axon ingrowth. We examined retinal axon projections to the developing first optic ganglion, the lamina, in two mutants in which reduced numbers of ommatidia develop in the eye imaginal disk. We find that in the developing lamina of these mutants, sine oculis and Ellipse, retinal axons project to proper dorsoventral positions despite the absence of the usual array of neighboring retinal axons. In a second approach, we examined animals that were somatic mosaics for the mutation, glass. In glass- animals, retinal axons project aberrantly and the larval optic nerve is absent. We find that in the developing lamina of glass mosaic animals, wild-type retinal axons project to proper dorsoventral positions despite the misrouted projections of neighboring glass- retinal axons. In addition, wild-type retinal axons project normally in the absence of the larval optic nerve, indicating that the latter is not an essential pioneer for retinal axon navigation. Our observations support the proposal that axon fascicles can make at least some pathfinding decisions independently of other retinal axon fascicles. We suggest that positional guidance cues that might label axon pathways and target destinations contribute to retinotopic pattern formation in the Drosophila visual system.

Animals↗
PubMed1993

Metabolism of apoB-100-containing lipoproteins in familial hyperchylomicronemia.

The metabolism of apolipoprotein B-100 was studied in three patients with familial hyperchylomicronemia (type I hyperlipoproteinemia) using a very low density lipoprotein (VLDL) dual-tracer technique. Radioiodinated VLDL1 (Sf 60-400) and VLDL2 (Sf 20-60) were injected and their catabolism and rate of the transfer of apoB into VLDL2, intermediate density lipoprotein (IDL) (Sf 12-20), and low density lipoprotein (LDL) (Sf 0-12) were compared in patients and in five normolipidemic controls. The rates of delipidation of large triglyceride-rich VLDL1 to VLDL2 (0.26-0.54 pools/day vs. 2.5-5.2 pools/day in controls) and VLDL1 direct catabolism (0.33-0.92 pools/day vs. 4.2-14.7 pools/day in controls) were found to be significantly reduced in type I patients resulting in a tenfold increase of VLDL1 pool size. ApoB synthesis into this density interval was, however, normal as was that into smaller VLDL2. the circulating apoB mass in VLDL2 was not increased. In fact, apart from a modest decrease in the rate of VLDL2 delipidation to IDL and LDL, the behavior of apoB in this density interval was similar in hyperchylomicronemic and normal subjects. Likewise, the transfer of apoB through the IDL and LDL density ranges was not significantly different from normal. Pool sizes of these fractions, however, were reduced, the latter significantly (354-491 mg vs. 1,160-2,505 mg in controls) due to increased direct catabolism in hyperchylomicronemic patients. The results of this study indicate that lipoprotein lipase deficiency primarily affects VLDL1 metabolism, both its delipidation and direct removal from plasma. Lipolysis further down the delipidation cascade is not dependent on this enzyme. Hypercatabolism rather than a failure of synthesis of IDL and LDL was responsible for the decreased pools for both lipoproteins.

Adult↗
PubMed1993

Vulvar involvement in autoimmune bullous diseases.

The autoimmune blistering diseases are characterized by involvement of the skin and mucous membranes. On mucosal surfaces, although the initial lesion is often a blister, friction results in erosions. We report on 140 female patients with a variety of blistering diseases examined in the bullous disease clinic. Vulval involvement was found in 5 of 55 adult patients and in 2 of 3 girls with bullous pemphigoid. Sexual abuse was initially suspected in one child. Twenty-six women had cicatricial pemphigoid; of these, 14 had vulval involvement, often with severe scarring. Chronic bullous disease of childhood was identified in 20 girls; perineal involvement was present in 16 causing initial misdiagnosis of herpes simplex in one case and sexual abuse in another. Vulval involvement was less frequent in linear IgA disease (the adult counterpart of chronic bullous disease of childhood), occurring in 9 of 22 patients. One of two adults and two of three girls with epidermolysis bullosa acquisita had vulval involvement. Finally, of nine female patients with pemphigus, four had vulval involvement, all of whom had pemphigus vulgaris. Blistering diseases are rare, but vulval involvement is common across the spectrum of these diseases. When mucosal involvement predominates, diagnostic difficulties can arise.

Adult↗
PubMed1992

A putative serine/threonine protein kinase gene on chromosome III of Saccharomyces cerevisiae.

We have sequenced a gene on chromosome III of Saccharomyces cerevisiae which codes for a putative serine/threonine protein kinase of 726 amino acids (calculated molecular weight 82 kDa). We have called this gene KIN82. The amino acid sequence of KIN82 is most similar to the cyclic nucleotide-dependent protein kinase subfamily and the protein kinase C subfamily. Gene disruption of KIN82 did not produce any phenotype when tested under a variety of conditions. Reduced stringency hybridizations revealed the presence of another genomic sequence with high homology to the carboxy-terminal catalytic domain of KIN82.

Amino Acid Sequence↗
PubMed1992

The complete sequence of a 6146 bp fragment of Saccharomyces cerevisiae chromosome III contains two new open reading frames.

As part of the EEC project to sequence the entire chromosome III of Saccharomyces cerevisiae we have sequenced a total of 11,040 bp from near the right end of the chromosome. A new protein kinase gene was found at one extremity of the sequenced region (Wilson et al., 1992), while the previously sequenced actin binding protein gene, ABP1, (Drubin et al., 1990) was found at the other extremity. We present here the sequence of the region between these two genes which has the potential to code for two new open reading frames (ORFs).

Amino Acid Sequence↗
PubMed1992

Hereditary hypotrichosis (Marie-Unna type) and juvenile macular degeneration (Stargardt's maculopathy).

Hypotrichosis of the Marie-Unna variety is a distinctive syndrome eponymously named following a publication in 1925 describing a family in which 27 individuals in seven generations were affected by a previously unreported type of hypotrichosis. Its inheritance is determined by an autosomal dominant gene and it usually occurs as an isolated abnormality. Hereditary macular degeneration (Stargardt's maculopathy) is also well recognized and has been reported in one family in association with alopecia areata but never in association with Marie-Unna hypotrichosis. Inheritance of Stargardt's maculopathy is autosomal recessive. Our patient demonstrates the co-existence of these two uncommon genetic disorders and it would appear that both defects have been independently inherited.

Child↗
PubMed1992

Sequence similarity between HLA-DR1 and DR4 subtypes associated with rheumatoid arthritis and proteus/serratia membrane haemolysins.

Rheumatoid arthritis (RA) is found more often in subjects carrying the HLA-DR1 antigen and some subtypes of the HLA-DR4 antigen than in those without these antigens. Analysis of probes specific for HLA-DR4 has shown that amino acids encoding positions 69-74 (EQRRAA) of the beta chain indicates susceptibility to RA. A hexamer sequence of proteus haemolysin spanning residues 32-37 (ESRRAL) has been identified which resembles biochemically, and discriminates by charge, between HLA types associated with RA (DR1, Dw4, Dw14, Dw15), and those not linked with the disease (Dw10, Dw13).

Amino Acid Sequence↗
PubMed1992

Recurrent ventricular arrhythmias complicating myocardial infarction in the presence of phaeochromocytoma.

After an acute myocardial infarction a 49 year old man developed late recurrent severe ventricular arrhythmias coincident with transient hypertensive episodes. A phaeochromocytoma was diagnosed on the basis of the urinary concentration of catecholamines and computerised tomography of the adrenal glands. After stabilisation of his cardiac rhythm and blood pressure with alpha and beta adrenergic blockade and anti-arrhythmic treatment the right adrenal gland, which contained the tumour, was successfully resected. The diagnosis of a phaeochromocytoma should be considered when recurrent ventricular arrhythmias are associated with intermittent hypertension after myocardial infarction.

Adrenal Gland Neoplasms↗
PubMed1992

[Risk of chronic oral anticoagulant treatment in elderly patients].

To assess age-related risks of long term anticoagulation, the records of 348 patients followed up at our university hospital outpatient anticoagulation clinic during a seven year period were reviewed. There were 129 patients, under 56 years of age, 144 from 56 to 69 and 75 over 70 years old. The total observation period was 1089 patient-years (3.3 yrs per pt). 64% of the patients had adequate anticoagulation level (prothrombin time < 35%, INR 2.2-4.5) 70 to 100% of the observation period. Prothrombin time was slightly, but significantly higher in the elderly group. During this period 21 patients developed major bleeding complications (1.84/100 pt yrs), 8 of them with fatal intracranial hemorrhages, and 20 embolic complications (1.93/100 pt yrs), 3 of them fatal. No significant differences in the incidence of both bleeding and embolic complications were observed in the three groups. The results of this retrospective follow-up study suggest that long term anticoagulation can be carried out in elderly pts with risk of hemorrhagic and embolic complications similar to those observed in the general population.

Acenocoumarol↗
PubMed1991

Chronic desipramine enhances the effect of locally applied amphetamine on interstitial concentrations of dopamine in the nucleus accumbens.

In vivo microdialysis was used to study the effect of chronic desipramine (DMI, 5 mg/kg, twice daily for 21 days) on increases in interstitial dopamine (DA) produced by local administration of d-amphetamine (1.0, 3.3 and 10.0 microM) in the nucleus accumbens. Locally applied amphetamine increased interstitial DA in a dose-dependent manner. The amphetamine-induced increase was significantly greater in the DMI treated animals. These data suggest that chronic DMI may directly influence the functional status of the DA terminals in the nucleus accumbens.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1991

Computational method for the design of enzymes with altered substrate specificity.

A combination of enzyme kinetics and X-ray crystallographic analysis of site-specific mutants has been used to probe the determinants of substrate specificity for the enzyme alpha-lytic protease. We now present a generalized model for understanding the effects of mutagenesis on enzyme substrate specificity. This algorithm uses a library of side-chain rotamers to sample conformation space within the binding site for the enzyme-substrate complex. The free energy of each conformation is evaluated with a standard molecular mechanics force field, modified to include a solvation energy term. This rapid energy calculation based on coarse conformation sampling quite accurately predicts the relative catalytic efficiency of over 40 different alpha-lytic protease-substrate combinations. Unlike other computational approaches, with this method it is feasible to evaluate all possible mutations within the binding site. Using this algorithm, we have successfully designed a protease that is both highly active and selective for a non-natural substrate. These encouraging results indicate that it is possible to design altered enzymes solely on the basis of empirical energy calculations.

Algorithms↗
PubMed1991

CD4 lymphocyte concentrations in patients with newly identified HIV infection attending STD clinics. Potential impact on publicly funded health care resources.

Since January 1990, human immunodeficiency virus (HIV)-infected patients attending two sexually transmitted disease clinics in Baltimore, Md, have been offered T-lymphocyte subset evaluations. From January through September, CD4+ lymphocyte concentrations were measured in 223 newly diagnosed HIV-infected patients; 50% had fewer than 500 CD4+ T cells and 12% had fewer than 200 CD4+ T cells per cubic millimeter. Most patients were asymptomatic, and, even among patients with fewer than 200 CD4+ T cells, 54% had no symptoms or signs suggestive of advanced HIV infection. Homosexually active men had significantly lower mean CD4+ lymphocyte concentrations than intravenous drug users. Given the substantial numbers of patients with CD4+ concentrations that qualified them for zidovudine therapy, we also assessed their mechanisms of paying for health care. Only 24% of HIV-infected patients had private insurance. Seventy-two percent of patients with fewer than 200 CD4+ T cells either had no insurance or relied on public assistance for health care. Thus, although 50% of asymptomatic individuals identified by routine voluntary HIV screening in an inner-city sexually transmitted disease clinic may benefit from therapy for their disease, 75% of those qualifying for presently recommended therapy either depend on publicly funded health care or have no means of payment for care.

Adolescent↗
PubMed1991

Three-dimensional structure of the LDL receptor-binding domain of human apolipoprotein E.

Human apolipoprotein E, a blood plasma protein, mediates the transport and uptake of cholesterol and lipid by way of its high affinity interaction with different cellular receptors, including the low-density lipoprotein (LDL) receptor. The three-dimensional structure of the LDL receptor-binding domain of apoE has been determined at 2.5 angstrom resolution by x-ray crystallography. The protein forms an unusually elongated (65 angstroms) four-helix bundle, with the helices apparently stabilized by a tightly packed hydrophobic core that includes leucine zipper-type interactions and by numerous salt bridges on the mostly charged surface. Basic amino acids important for LDL receptor binding are clustered into a surface patch on one long helix. This structure provides the basis for understanding the behavior of naturally occurring mutants that can lead to atherosclerosis.

Amino Acid Sequence↗
PubMed1991

Genetic evidence for the spread of agriculture in Europe by demic diffusion.

European agriculture originated in the Near East about 9,000 years ago. The Neolithic reached almost all areas suitable for agriculture by 5,000 yr BP (before present). The routes and times of the spread of agriculture through Europe are relatively well established, but not its manner of spreading. This could have been by cultural diffusion with few genetic consequences. By contrast, Ammerman and Cavalli-Sforza proposed that the spread of farming increased local population densities, causing demic expansion into new territory and diffusive gene flow between the neolithic farmers and mesolithic groups. We have now tested observed genetic patterns against expectations derived from the demic expansion hypothesis. We found significant partial correlations of genetic distances with a distance matrix especially designed to represent the spread of agriculture on that continent, when geographic distances are held constant. These findings support the hypothesis of Ammerman and Cavalli-Sforza and invite further investigation into Renfrew's hypothesis on the origin of the Indo-European languages.

Agriculture↗