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Biomedical subjects

C Wilson

Publications and source records attributed to C Wilson.

At least 397 records · Page 22Linked to original sources

Effect of cromakalim on contractions in rabbit isolated renal artery in the presence and absence of extracellular Ca2+.

1. The inhibitory effects of the K+ channel activator, cromakalim, upon contractions to noradrenaline, histamine and caffeine were examined in rabbit isolated renal artery. For comparison, the effects of pinacidil, dazodipine and sodium nitroprusside were also studied in some experiments. 2. In normal Krebs solution, cromakalim (1 microM) produced a 39.1% reduction in area under the curve (AUC) of the noradrenaline concentration-response, and a 61.8% reduction in the histamine AUC. Ca2+ removal (with EGTA 0.1 mM) gave an 80.0% reduction in the noradrenaline AUC and a 74.5% reduction in the histamine AUC. The combination of Ca2+ removal and cromakalim (1 microM) had no further effect on the noradrenaline responses (a reduction of 78.4% in AUC), but produced a significantly greater reduction in the histamine AUC (86.2%). 3. LaCl3 (1 mM) reduced the noradrenaline AUC by 74.8% and gave an 81.8% reduction in the response to a single (EC90) histamine concentration. LaCl3 (1 mM) plus cromakalim (1 microM) produced no further reduction in the noradrenaline AUC (71.9%) but gave a significant further reduction of the histamine response (94.6%). 4. Pinacidil (3 microM) reduced the noradrenaline AUC by 35.5%. Pinacidil (3 microM) plus LaCl3 (1 mM) produced the same reduction in the noradrenaline AUC (80.9%) as LaCl3 alone (80.9%). 5. In both normal and Ca2+-free Krebs solution, cromakalim (0.1, 1.0 and 10 microM) produced concentration-related inhibition of the contraction to caffeine (10 mM). This inhibition was antagonised by the K+ channel blocker, glibenclamide (3 microM). Similarly, pinacidil (0.3, 3.0 and 30 microM) produced a glibenclamide-sensitive inhibition of the caffeine contraction. At equi-vasorelaxant concentrations, dazodipine (0.01, 0.1 and 1.O microM) and sodium nitroprusside (0.03, 0.3 and 3.0 microM) had no significant effect on caffeine contractions. 6. The data show that the K+ channel activators, cromakalim and pinacidil, unlike the Ca2+ channel blocker, dazodipine, or the guanylate cyclase activator, sodium nitroprusside, can inhibit the contraction which results from caffeine-induced Ca2+ release. Cromakalim and pinacidil, however, inhibit only the component of the noradrenaline response resulting from Ca2+ influx (tonic component) and not that resulting from Ca2 + release (phasic component). Cromakalim may affect both components of the histamine contraction.

Animals↗

Factors Affecting Activity and Stability of the Kluyveromyces lactis Killer Toxin.

A number of physical parameters determining the activity and stability of the killer toxin produced by the yeast Kluyveromyces lactis have been investigated. The toxin was active over a relatively narrow pH range of 4.4 to 5.8, with a maximum at the lower end of the range. However, it was stable up to at least pH 8.0 but appeared to be irreversibly inactivated below pH 4.4. The toxin was stable at 40 degrees C but rapidly inactivated at 50 degrees C. Strong agitation caused the inactivation of the toxin in one medium but not another; this seemed to be due to oxygen-mediated disulfide bond formation, which could be prevented by sulfhydryl protecting agents.

Journal Article↗

Formation of infectious hybrid virions with gibbon ape leukemia virus and human T-cell leukemia virus retroviral envelope glycoproteins and the gag and pol proteins of Moloney murine leukemia virus.

The gibbon ape leukemia virus, SEATO strain, and human T-cell leukemia virus type I envelope glycoproteins can be functionally assembled with a Moloney murine leukemia virus core into infectious particles. The envelope-host cell receptor interaction is the major determinant of the host cell specificity for these hybrid virions.

Animals↗

Hepatobiliary complications in chronic pancreatitis.

Thirty nine patients undergoing surgery for chronic pancreatitis were investigated for evidence of hepatobiliary disease. In addition to pre-operative assessment by liver function tests, ultrasound, ERCP (in 33) and percutaneous transhepatic cholangiography (in five), all had peroperative liver biopsy. Common bile duct stenosis was diagnosed in 16 (62%) of the 26 patients with successful cholangiography. Features of extrahepatic biliary obstruction were found on biopsy in 11 patients, three of whom showed features of secondary sclerosing cholangitis. No patients had secondary biliary cirrhosis. Three had parenchymal liver disease (cirrhosis, resolving hepatitis and alcoholic hepatitis respectively) and two others had features suggestive of previous alcohol-induced injury. Five (83%) of the patients with clinical jaundice had biopsy features of extrahepatic biliary obstruction, as did eight (67%) with alkaline phosphatase above twice normal and seven (44%) with radiological common bile duct stenosis. Neither alkaline phosphatase rise, nor common bile duct stenosis alone or in combination, were a reliable indication of the need for biliary enteric bypass surgery. Pre-operative liver biopsy may be a valuable adjunct in the assessment of such patients.

Adult↗

Integration of ambulance staff trained in cardiopulmonary resuscitation with a medical team providing prehospital coronary care.

Ambulance staff with advanced training in cardiopulmonary resuscitation and equipped with monitor/defibrillators were used as the initial responders to collapse calls within a medically based prehospital coronary care system. During 21 months, in a population of approximately 120,000, ambulance staff successfully resuscitated six patients from ventricular fibrillation; there were four long term survivors. The median response time of emergency ambulances to collapse calls was eight minutes compared with 20 minutes for the medically manned mobile coronary care unit. None of the patients resuscitated by ambulance staff would have survived if they had been dependent on the mobile coronary care unit acting alone. Nineteen other patients with important arrhythmias were referred for earlier medical management which in some cases may have saved lives. An additional eight long term survivors of out of hospital ventricular fibrillation were resuscitated by medical staff. The integration of paramedical with medical prehospital coronary care improved survival after out of hospital cardiac arrest.

Adult↗

P-element-mediated enhancer detection applied to the study of oogenesis in Drosophila.

We have stained the ovaries of nearly 600 different Drosophila strains carrying single copies of a P-element enhancer detector. This transposon detects neighbouring genomic transcriptional regulatory sequences by means of a beta-galactosidase reporter gene. Numerous strains are stained in specific cells and at specific stages of oogenesis and provide useful ovarian markers for cell types that in some cases have not previously been recognized by morphological criteria. Since recent data have suggested that a substantial number of the regulatory elements detected by enhancer detection control neighbouring genes, we discuss the implications of our results concerning ovarian gene expression patterns in Drosophila. We have also identified a small number of insertion-linked recessive mutants that are sterile or lead to ovarian defects. We observe a strong correlation with specific germ line staining patterns in these strains, suggesting that certain patterns are more likely to be associated with female sterile genes than others. On the basis of our results, we suggest new strategies, which are not primarily based on the generation of mutants, to screen for and isolated female sterile genes.

Animals↗

The Uganda I/CDC strain of Plasmodium malariae in Aotus lemurinus griseimembra monkeys.

Two lines of the Uganda I/CDC strain of Plasmodium malariae were studied in splenectomized Aotus lemurinus griseimembra monkeys. A line initially adapted to these monkeys from an infected chimpanzee failed to produce high-level parasite counts or mosquito infection in 13 of this type of monkey during 16 linear passages. Another line, originally adapted from the chimpanzee to Aotus azarae boliviensis, after 7 linear passages in 3 different types of Aotus was then passaged to 14 splenectomized A. lemurinus griseimembra. Geometric mean maximum parasitemia in these monkeys was 18,400/mm3. Mosquito infections were readily obtained during the period just after the parasite count rose above 1,000/mm3. Anopheles freeborni, An. stephensi, An. dirus, and 2 strains of An. gambiae supported the development of the parasite to the presence of sporozoites in the salivary glands. Two attempts to transmit the strain to other splenectomized A. lemurinus griseimembra by sporozoite inoculation were unsuccessful.

Animals↗

Knowledge about AIDS among Zimbabwean teacher-trainees before and during the public awareness campaign.

Knowledge about AIDS was studied among 4,189 Zimbabwean teacher-trainees from January to March, 1988, about six months after a national AIDS awareness campaign began. Knowledge about AIDS among part of this sample of teacher-trainees surveyed after the AIDS campaign began was also compared with that displayed by 630 teacher-trainees studied in January, 1987, roughly six months before the AIDS campaign began. Over 85 percent of 1988 subjects knew that AIDS is fatal and incurable. More than 80 percent of 1988 respondents knew that a condom is an effective precaution against AIDS. However, among 1988 participants, 35 percent did not know that many people carrying the AIDS virus look healthy, 36 percent believed that many AIDS victims in Africa are homosexual, 36 percent did not know that one cannot contract AIDS from a toilet seat, 40 percent believed that kissing transmits AIDS and nearly half believed that mosquitoes transmit AIDS. Males and subjects from urban homes were better informed about AIDS than females and those from rural homes, respectively. Teacher-trainees surveyed in 1988 were generally more knowledgeable about AIDS than those studied in 1987. The implications of these results for further educational efforts are considered.

Acquired Immunodeficiency Syndrome↗

Surgical glove failure rate.

Surgical gloves were collected after day-time operations for a 4-week period. Glove punctures were located by inflating each glove with compressed air and immersing the inflated glove in water. During the period of the study 681 surgical operations were performed. A total of 3790 gloves was collected, 334 gloves (8.8%) had perforations at the end of the surgical procedure. Defects occurred in one or more gloves in 32.0% of all operations.

Equipment Failure↗

The mechanisms of proteinuria in aging rats.

Aging is associated with the appearance of a selective proteinuria which cannot be attributed to any specific underlying renal disease. The present studies were conducted in conscious, chronically catheterized young (3-4 months), non-proteinuric male rats and old (22-25 months), proteinuric males to determine the mechanism(s) of the proteinuria. Compared with young males, old proteinuric rats had increased blood pressure, reduced glomerular filtration rate (GFR) and renal plasma flow and heavy proteinuria. Fractional clearance of neutral dextran (D) and anionic dextran sulfate (DS) were both significantly increased at the 36 A molecular radius in old rats; the increase in DS fractional clearance being greater than the increase in D fractional clearance. The proteinuria of aging is therefore due to moderate increases in glomerular permeability and, more importantly, to loss of fixed glomerular polyanion. Striking glomerular morphologic changes were also evident in the old rats including thickening of the glomerular basement membrane and extensive glomerular sclerosis.

Aging↗

Comparative effects of K+ channel blockade on the vasorelaxant activity of cromakalim, pinacidil and nicorandil.

Three agents with K+ channel blocking activity, procaine, 4-aminopyridine (4-AP) and tetraethylammonium (TEA), were tested for inhibition of vasorelaxation and 86Rb+ efflux induced by cromakalim (BRL 34915), pinacidil and nicorandil in rabbit isolated mesenteric artery. The potency order for inhibition of vasorelaxation was procaine greater than 4-AP greater than TEA and for inhibition of efflux was procaine = 4-AP greater than TEA. The K+ channel blockers did not discriminate between cromakalim, pinacidil or nicorandil on efflux but demonstrated preferential inhibition of vasorelaxation to cromakalim greater than pinacidil greater than nicorandil. In addition, the maximum response to cromakalim was depressed but that to pinacidil and nicorandil was not. The results confirm the role of K+ channel activation in vasorelaxation to cromakalim, pinacidil and nicorandil, but suggest that additional mechanisms may be involved for pinacidil and, in particular, for nicorandil.

4-Aminopyridine↗

Generation of a neutralization-resistant variant of HIV-1 is due to selection for a point mutation in the envelope gene.

Transmission and growth of HIV-1 produced from the biologically active clone HTLV-III/HXB2D in the constant presence of a neutralizing antiserum yielded a viral population specifically resistant to neutralization by the same antiserum. Molecular clones MX-1 and -2, containing the entire envelope gene, were obtained from cultures of the resistant variant. The coding regions for the large envelope protein and most of the transmembrane envelope protein of two such clones were substituted for the homologous segment of HXB2D. Infectious viruses from these constructs were also specifically resistant to neutralization by the selecting antiserum. The exchanged fragment contained only one base change, resulting in an Ala----Thr replacement at position 582. When this substitution was introduced into HXB2D it conferred the resistant phenotype. Thus, small differences may be selected for in vivo by the host immune response and result in relatively large differences in susceptibility of the virus to such a response.

Antibodies, Viral↗

Surgical treatment of acute necrotizing pancreatitis.

Between January 1980 and June 1986, 21 patients required surgery for acute necrotizing pancreatitis. Four patients had been transferred from other hospitals; the remaining 17 patients had been treated from the outset at Glasgow Royal Infirmary, representing 3.7 per cent of the 456 patients treated for acute pancreatitis during this time. Necrosectomy was performed on 14 patients and 7 patients were treated by pancreatic resection, with 4 deaths in each group; thus 8 patients (38 per cent) died at a median time of 22 days from onset of their attack. Three of the four patients transferred to our care died, giving a mortality in our own patients of 29 per cent. Of the survivors, all but three had a prolonged and complicated hospital course. Our data confirm that acute necrotizing pancreatitis is still associated with a considerable mortality and morbidity. Early multi-organ failure, advanced age, underlying medical illness and the presence of infected necrosis were associated with a poor outcome. Necrosectomy delayed until the second or subsequent week appeared to be a suitable procedure for the majority of our patients, but shortcomings were apparent with the traditional methods of closed drainage of the pancreatic bed postoperatively. The many demands imposed by this small group of patients suggests that their management is best undertaken in centres in which there is special expertise and this should contribute to a further reduction in the mortality from this condition.

Acute Disease↗