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Biomedical subjects

C Wilson

Publications and source records attributed to C Wilson.

At least 415 records · Page 23Linked to original sources

Cytoskeletal actin gene families of Xenopus borealis and Xenopus laevis.

We have sequenced the coding and leader regions, as well as part of the 3' untranslated region, of a Xenopus borealis type 1 cytoskeletal actin gene [defined according to the arrangement of acidic residues at the N-terminus; Vandekerckhove et al. (1981) J Mol Biol 152:413-426]. The encoded amino acid sequence is the same as the avian and mammalian beta (type 1) cytoskeletal actins, except for an isoleucine at position 10 (as found in the mammalian gamma cytoskeletal actins), and an extra amino acid, alanine, after the N-terminal methionine. Five introns were found, in the same positions as those of the rat and chicken beta-actin genes. The 5' and 3' untranslated regions resemble those of the human gamma (type 8) cytoskeletal actin gene more closely than the mammalian beta genes. Primer extension showed that this type 1 gene is transcribed in ovary and tadpole. Sequencing of primer extension products demonstrated two additional mRNA species in X. borealis, encoding type 7 and 8 isoforms. This contrasts with the closely related species Xenopus laevis, where type 4, 5, and 8 isoforms have been found. The type 7 isoform has not previously been found in any other species. The mRNAs of the X. borealis type 1 and 8 and X. laevis type 5 and 8 isoforms contain highly homologous leaders. The X. borealis type 7 mRNA has no leader homology with the other mRNA species and, unlike them, has no extra N-terminal alanine codon. The evolutionary implications of these data are discussed.

Actins↗

Deaths from acute pancreatitis: why do we miss the diagnosis so frequently?

Review of acute pancreatitis deaths between 1974 and 1984 revealed 126 patients, 53 (42%) of whom were first diagnosed at autopsy. Pancreatitis was undiagnosed in life in 13 (33%) of the patients with a gallstone aetiology, 8 (40%) of those with an alcohol aetiology, 21 (42%) of those of unknown aetiology and 17 (74%) of those with pancreatitis due to other identified aetiological factors. These patients more commonly died within the first week of their illness, more often had significant underlying medical disease and tended to have less severe degrees of pancreatic parenchymal destruction. Only 7 (13%) of the 53 patients undiagnosed in life had presented with abdominal pain. The majority (68%) presented atypically with known or suspected medical conditions, often to internists, or post-operatively (19%). Failure to diagnose these patients in life was most often due to a lack of consideration of the diagnosis, usually because of the atypical presentation, and consequent omission of an amylase determination--made in only 5 (9%) of the patients.

Acute Disease↗

Integration of membrane proteins into the endoplasmic reticulum requires GTP.

We have examined the requirement for ribonucleotides and ribonucleotide triphosphate hydrolysis during early events in the membrane integration of two membrane proteins: the G protein of vesicular stomatitis virus and the hemagglutinin-neuraminidase (HN) glycoprotein of Newcastle disease virus. Both proteins contain a single transmembrane-spanning segment but are integrated in the membrane with opposite orientations. The G protein has an amino-terminal signal sequence and a stop-transfer sequence located near the carboxy terminus. The HN glycoprotein has a single sequence near the amino terminus that functions as both a signal-sequence and a transmembrane-spanning segment. Membrane insertion was explored using a cell-free system directed by transcribed mRNAs encoding amino-terminal segments of the two proteins. Ribosome-bound nascent polypeptides were assembled, ribonucleotides were removed by gel filtration chromatography, and the ribosomes were incubated with microsomal membranes under conditions of defined ribonucleotide content. Nascent chain insertion into the membrane required the presence of both the signal recognition particle and a functional signal recognition particle receptor. In the absence of ribonucleotides, insertion of nascent membrane proteins was not detected. GTP or nonhydrolyzable GTP analogues promoted efficient insertion, while ATP was comparatively ineffective. Surprisingly, the majority of the HN nascent chain remained ribosome associated after puromycin treatment. Ribosome-associated HN nascent chains remained competent for membrane insertion, while free HN chains were not competent. We conclude that a GTP binding protein performs an essential function during ribosome-dependent insertion of membrane proteins into the endoplasmic reticulum that is unrelated to protein synthesis.

Cell Membrane↗

Klebsiella antibodies in ankylosing spondylitis and Proteus antibodies in rheumatoid arthritis.

Antibodies to Klebsiella, but not to other bacteria, have been shown to be present in patients with active ankylosing spondylitis (AS) by seven different techniques. Antibodies to Proteus, but not to E. coli or Klebsiella, have been shown to be present in patients with active rheumatoid arthritis (RA) by three different techniques. It is suggested AS and RA are forms of reactive arthritis, to Klebsiella and Proteus respectively, probably mediated by cross-reactivity to HLA antigens.

Animals↗

Chrysiasis: transmission electron microscopy, laser microprobe mass spectrometry and epipolarized light as adjuncts to diagnosis.

Two patients receiving gold therapy for rheumatoid arthritis developed skin pigmentation, chrysiasis, which in one appeared 4 months after cessation of the therapy. The diagnosis was confirmed by transmission electron microscopy and mass spectrometry laser microprobe analysis of paraffin sections and its extent demonstrated by epipolarized light. The condition is poorly reported and clinically may be confused with silver and mercury impregnation. Tissue diagnosis requires ancillary methods and of these, transmission electron microscopy and laser microprobe mass spectrometry are excellent examples. The transmission electron microscopy findings differ from previous reports and raise doubts on the hypothesis on the role of the skin in gold excretion. Because of the renewed interest in crysotherapy and the latent period that can separate this from chrysiasis, an increase in chrysiasis and the need for its diagnosis can be anticipated.

Arthritis, Rheumatoid↗

Fatal acute pancreatitis.

Review of all deaths from acute pancreatitis recorded at Glasgow Royal Infirmary between 1974 and 1984 identified 126 patients, 53 (42%) of whom had pancreatitis first diagnosed at necropsy. Aetiologies of the fatal attacks of pancreatitis included gall stones (30%), alcohol (15%), other identified aetiological factors (17%), and was unknown (38%). Overall mortality fell from 14.9% in the early half of the study to 10.8% in the latter half although in the 73 patients in whom the diagnosis of acute pancreatitis was made during life, the mortality rate was unchanged throughout. Within the group of 73 patients diagnosed during life deaths from gall stone pancreatitis have fallen by almost 50% suggesting that improved treatment of this subgroup may have occurred. The findings of this study lend support to the concept of early, complete clearance of calculi from the biliary tree, either by an endoscopic or surgical approach.

Acute Disease↗

Morphological evidence for the presence of arteries in human prolactinomas.

This study was undertaken to clarify the vascular anatomy of human prolactinomas and specifically to determine whether arteries were present. Sixteen prolactinomas were studied by electron microscopy. The presurgical diagnosis of the tumors as prolactinomas was based on the findings of hyperprolactinemia and radiographic abnormalities, and was confirmed by the electron microscopic features of the specimens as well as by immunocytochemical staining for PRL. In addition to the presence of fenestrated endothelial cells, which are characteristic of the normal capillaries of the anterior pituitary, 13 of the 16 prolactinomas contained arteries. These arteries ranged from well formed vessels with multiple layers of smooth muscle cells to abnormal terminal arterioles, i.e. vessels with fenestrated endothelium surrounded by a variable number of smooth muscle cells. Arteries were not found in anterior pituitaries from 8 patients with no pituitary disease. In the prolactinomas, smooth muscle cells also were found, either isolated in the pericapillary connective tissue space or in small cords some distance from the vessel lumen. The results suggest that vascular changes, including arteriogenesis, occur in prolactinomas (and possibly other types of pituitary tumor). The arteries entering the anterior pituitary directly could be congenital or develop during formation of the tumor. An arterial blood supply to a region of the anterior pituitary could result in the escape of that area from hypothalamic regulation, since systemic blood contains negligible levels of hypothalamic hormones. In the case of PRL-secreting cells, which are tonically inhibited by the hypothalamic hormone dopamine, this would result in hypertrophy, hyperplasia, and possibly tumorigenesis.

Adult↗

Cromakalim, a potassium channel activator: a comparison of its cardiovascular haemodynamic profile and tissue specificity with those of pinacidil and nicorandil.

Studies have been performed to compare the cardiovascular haemodynamic profiles of the potassium channel activator, cromakalim (BRL 34915), with those of pinacidil and nicorandil. In conscious renal hypertensive cats, cromakalim was 10 times more potent than pinacidil as an antihypertensive agent while nicorandil was 10 times less potent than pinacidil. Cromakalim and pinacidil had a similar duration of action while nicorandil was short acting. In anaesthetised cats, hypotension evoked by intravenous infusions of cromakalim, pinacidil, or nicorandil was associated with a decrease in mesenteric vascular resistance but only cromakalim produced a marked reduction in renal vascular resistance. Cromakalim, pinacidil, and nicorandil were highly specific as inhibitors of tension in vascular (rabbit portal vein) (IC50 = 2.1 x 10(-8), 4.6 x 10(-8), and 1.3 x 10(-6)M, respectively,) rather than cardiac (rabbit papillary muscle), tissue. In view of its antihypertensive efficacy, specificity for vascular tissue, and beneficial effect upon renal haemodynamics, the potassium channel activator, cromakalim, has advantages in its profile of activity compared to pinacidil and nicorandil.

Animals↗

Antihypertensive and angiotensin converting enzyme inhibitory activities of a novel dihydrobenzofuran analogue.

1. The biochemical and pharmacological profiles of the novel, orally active angiotensin converting enzyme (ACE) inhibitor, N-[N-[[4-(2, 3-dihydro-2-benzofuranyl)-1-(ethoxycarbonyl)]butyl]-(s)-alanyl]- (s)-proline (BRL 36378), have been compared with those of enalapril and captopril. 2. In the conscious sodium deficient spontaneously hypertensive rat, BRL 36378 and enalapril (0.3-10 mg/kg orally) produced comparable falls in blood pressure; at 3 mg/kg orally, captopril was less active than BRL 36378 and enalapril. 3. In the anaesthetised spontaneously hypertensive rat, enalapril was slightly more potent than BRL 36378 as an inhibitor of angiotensin I (AI) pressor responses whilst BRL 36378 was about twice as potent as captopril in this test (i.v. route used). BRL 36378 and enalapril were equipotent as potentiators of bradykinin depressor responses. 4. In the anaesthetised Wistar rat, the maximum inhibition of AI pressor responses by 0.1 microgram/kg i.v. BRL 36378 and captopril was achieved sooner than after the same dose of enalapril. The inhibitory effect of captopril subsided completely by 40-50 min but the maximum effects of BRL 36378 and enalapril persisted for at least 60 min. 5. In the conscious renal hypertensive cat, captopril was slightly more potent than BRL 36378 or enalapril as a blood pressure lowering agent, over 1-10 mg/kg orally. BRL 36378 was more potent than enalapril as an inhibitor of AI induced pressor responses in this model. Captopril possessed similar inhibitory activity to BRL 36378 although minor differences in time course were apparent.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗

Transmission of the OS strain of Plasmodium inui to Saimiri sciureus boliviensis and Aotus azarae boliviensis monkeys by Anopheles dirus mosquitoes.

Eight Saimiri and 7 Aotus monkeys were exposed to infection with the OS strain of Plasmodium inui via the bites of from 2 to 7 Anopheles dirus mosquitoes. All Saimiri monkeys developed high-level infections of from 152,000 to 500,000/mm3 after prepatent periods of from 14 to 17 days. Only 1 Aotus monkey developed a patent infection after a period of 28 days. Feeding on these animals failed to result in infection of An. dirus mosquitoes.

Animals↗

Beta-adrenoceptor sensitivity of brown and white adipocytes after chronic pretreatment of rats with reserpine.

The effect of pretreatment with reserpine (1.0 mg/kg i.p. daily for 7 days) on beta-adrenoceptor-mediated responses has been measured in epididymal white and interscapular brown adipocytes, left atria and vas deferens of rats in order to investigate the classification of the receptors and whether they are innervated. Lipolysis was measured in adipocytes, and from the same rats, the beta 1-adrenoceptor-mediated positive inotropic responses of isolated paced left atria and beta 2-adrenoceptor-mediated inhibition of field stimulation-induced contraction of the vas deferens were examined. The agonists used were isoprenaline, oxyfedrine (atria only) and (except in brown adipocytes) ritodrine, which was a partial agonist in white adipocytes, atria and vas deferens. Atria and brown adipocytes exhibited beta-adrenoceptor supersensitivity after reserpine pretreatment, whereas vas deferens and white adipocytes did not. Reserpine-induced reductions in food intake and body weight did not appear to influence beta-adrenoceptor-mediated lipolysis, since restriction of the diet equivalent to that of reserpine-treated rats produced no change in white adipocyte sensitivity. Responses mediated via beta 1-, but not beta 2-adrenoceptors, display supersensitivity after chronic depletion of neuronal catecholamines with reserpine and this is evidence for innervation of this receptor subtype. Thus, atrial beta 1-adrenoceptors are assumed to be innervated, whereas vas deferens beta 2-adrenoceptors are not. The present results are consistent with histochemical evidence that brown, but not white, adipocyte beta-adrenoceptors are innervated. However, they are not compatible with conventional receptor classification studies, which suggest that rat brown and white beta-adrenoceptors are similar--either both beta 1 or both atypical.

Adipose Tissue↗

Acute superior mesenteric ischaemia.

A review of case records and post-mortem reports from Glasgow Royal Infirmary over the past 12 years identified 102 patients with acute superior mesenteric ischaemia, 53 (52 per cent) of whom were first diagnosed at post mortem. Overall mortality was 92 per cent and mortality in the 49 patients diagnosed in life was 84 per cent. Fourteen patients (14 per cent) underwent exploratory laparotomy only with no survivors, 26 (25 per cent) had bowel resection alone with 7 surviving, and 9 (9 per cent) had a revascularization procedure, 5 requiring additional bowel resection, with only one surviving. Survivors were usually younger, had a shorter history and less extensive bowel infarction. Improvements in intensive care and nutritional support with the greater use of revascularization procedures in the past 6 years have barely influenced mortality. Delays in diagnosis and treatment contribute to the poor results. Earlier diagnosis might be aided by measuring serum inorganic phosphate and, coupled with the more widespread use of emergency angiography and revascularization procedures, holds out the best hope for future improvement.

Acute Disease↗