Patterns of population spread.
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Agriculture↗
Biomedical subjects
C Wilson
Publications and source records attributed to C Wilson.
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↗
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↗
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↗
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↗
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↗
[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↗
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↗
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↗
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↗
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↗
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↗
Role of the protease-antiprotease balance in peritoneal exudate during acute pancreatitis.
The peritoneal exudate formed during experimental pancreatitis is toxic when administered intraperitoneally or intravenously to other animals. Overwhelming of the peritoneal antiprotease defences by proteolytic enzymes released from the pancreas may be a key factor responsible for this toxicity and is examined in the current study. Human pancreatitis exudates possessed tryptic amidase activity indicating trypsinogen activation. The trypsin inhibitory capacities of exudates were reduced indicating a degree of consumption of the peritoneal antiproteases. Of 21 exudates examined, three showed marked reduction of their trypsin inhibitory capacity indicating almost complete consumption of their antiproteases. All three patients were shocked at the time of sampling, two dying of fulminant pancreatitis within 24 h. Overwhelming of the peritoneal antiproteases was not confirmed, but may occur in a few instances where proteolytic enzyme release or zymogen activation continues. Intraperitoneal administration of exogenous antiproteases prolongs survival in rats with pancreatitis and has been suggested as a therapy in man. The current data suggests that few patients are likely to benefit from such an approach.
Acute Disease↗
Distribution of mitochondrial r1-type introns and the associated open reading frame in the yeast genus Kluyveromyces.
We have sequenced the intron in the large subunit ribosomal RNA gene from the mitochondrion of Kluyveromyces lactis. It is a typical group I intron but, unlike the corresponding intron (r1) in Saccharomyces cerevisiae, it does not contain an open reading frame. This intron is widespread in the genus Kluyveromyces although intron-less strains were also found in some species of this genus. Sequences homologous to the open reading frame of the S. cerevisiae ribosomal intron were detected in some strains of K. waltii, K. thermotolerans and K. africanus.
Base Sequence↗
Platelet activating factor as a proinflammatory mediator in acetic-induced colitis in the rat.
Platelet activating factor (PAF) induces neutrophilia and produces a variety of gastrointestinal lesions. The role of PAF as a proinflammatory mediator was examined by measuring the production of PAF and the efficacy of the PAF antagonists WEB 2086 and Ro 24-0238 in acetic acid (HOAc)-induced colitis. PAF levels within the colonic mucosa, as measured by radioimmunoassay, increased from 259 +/- 119 ng/mg in control tissue, to 616 +/- 266 ng/mg in HOAc inflamed tissue. The accumulation of neutrophils within the mucosa was decreased by 53 +/- 10% by pretreatment with 3 mg/kg WEB 2086, and by 43 +/- 11% by 3 mg/kg Ro 24-0238. PAF-induced neutrophilia had no effect on the severity of HOAc-induced colitis, therefore, PAF my be involved in sustaining the chronic inflammation of colitis.
Acetates↗
Contact dermatitis in reaction to 2% topical minoxidil solution.
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Administration, Topical↗
Phosphoproteins of dentine extracellular matrix: silver colloid staining.
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Aging↗