Search PubMed⌕ Search

Biomedical subjects

D Roberts

Publications and source records attributed to D Roberts.

At least 235 records · Page 13Linked to original sources
PubMed1993

The Wilms tumour gene WT1 is expressed in murine mesoderm-derived tissues and mutated in a human mesothelioma.

The tumour suppressor gene WT1 encodes a transcription factor expressed in tissues of the genito-urinary system. Inactivation of this gene is associated with the development of Wilms tumour a pediatric kidney cancer. We show that WT1 is also expressed at high levels in many supportive structures of mesodermal origin in the mouse. We also describe a case of adult human mesothelioma, a tumour derived from the peritoneal lining, that contains a homozygous point mutation within WT1. This mutation, within the putative transactivation domain, converts the protein from a transcriptional repressor of its target sequence to a transcriptional activator. The role of WT1 in normal development thus extends to diverse structures derived from embryonic mesoderm and disruption of WT1 function contributes to the onset of adult, as well as pediatric, tumours.

Adult↗
PubMed1993

Chorioamnionitis caused by Capnocytophaga: case report and review.

We report a case of pathologically demonstrated chorioamnionitis due to Capnocytophaga species. The mother had high fever and marked uterine tenderness, and the infant had poor Apgar scores, fever, and pulmonary infiltrates. Both recovered after receiving specific antibiotics. Pathological examination of the placenta revealed acute chorioamnionitis, subchorionitis, and vasculitis of the umbilical vein. The dramatic clinical and pathological features of this case are compared with those of the nine previously reported cases of infection due to Capnocytophaga species occurring in pregnancy.

Adult↗
PubMed1993

Examination of raw beef products for the presence of Vero cytotoxin producing Escherichia coli, particularly those of serogroup O157.

Fifty-four of 310 (17%) samples of raw beef products contained Vero cytotoxin (VT)-producing Escherichia coli (VTEC) detected by DNA probes for the VT genes. VTEC strains examined in detail from a selection of the positive samples belonged to several O serogroups, some of which have been associated with human diarrhoea or haemolytic uraemic syndrome. Some of the strains possessed properties that may contribute to virulence in man. None of the food samples contained VT-producing E. coli O157 when tested by a combination of VT probe tests and colony immunoblotting with commercially available anti-O157 serum. Quantification of the immunoblotting technique indicated that O157 VTEC could be recovered from artificially-inoculated meat samples at a level of less than one organism per gram. Five of the food samples carried E. coli O157 strains that did not produce VT and differed in other properties from O157 VTEC.

Animals↗
PubMed1993

Effect of reduced aprotinin dosage on blood loss and use of blood products in patients undergoing cardiopulmonary bypass.

High-dose aprotinin reduces bleeding after cardiac surgery, but has also evoked concern with regard to potential side effects and hospital costs. To evaluate the effects of reduced-dose aprotinin on blood loss and need for blood transfusion, 40 patients undergoing myocardial revascularization were studied (double-blind, placebo-controlled). Postoperative bleeding was reduced by 40% and erythrocyte infusion by 85% in the group given 3 x 10(6) KIU aprotinin (1 x 10(6) as a loading dose before cardiopulmonary bypass, 1 x 10(6) in the priming volume and 2.5 x 10(5)/hour intraoperatively) Aprotinin concentrations during the operation were monitored and maintained above the required level. There were no adverse effects of the drug. Hospital expenditure on blood products was reduced by 51% when aprotinin was used. Our study suggests that aprotinin in reduced dosage diminishes bleeding and requirements for blood products, and that it should be given before, during and after cardiopulmonary bypass.

Aged↗
PubMed1993

The influence of heparin-coated and uncoated extracorporeal circuits on blood rheology during cardiac surgery.

The effect of heparin-coated perfusion circuits on blood trauma during clinical cardiopulmonary bypass (CPB) was studied in order to find out if traumatic changes in the blood could be minimized. Twenty-four patients undergoing coronary artery bypass surgery were randomized prospectively to CPB with heparin-coated circuits (HCC) or non-coated circuits (NCC). The trauma to blood was assessed by measuring damage to blood cells by estimating red and white cell rheology changes. These were measured as red cell filtration rate (RFR) and white cell filtration rate (WFR) using standard microfiltration methods. Furthermore, changes in plasma hemoglobin (P-Hb), whole blood and plasma viscosity were simultaneously assessed. The RFR was significantly reduced in both groups during CPB by 10% in the HCC and 32% in the NCC groups (p less than 0.01). When comparing the HCC and NCC groups, a significant difference was first seen after 30 minutes of bypass (p less than 0.05) and increased at the end of CPB (p less than 0.01). Similar results were seen regarding WFR (15% and 36%, p less than 0.01). After 30 minutes of bypass, a significant difference was seen between HCC and NCC groups (p less than 0.05). Furthermore, a significant increase in P-Hb levels were seen during CPB in both patient groups. At the end of CPB, there was a significant difference in P-Hb levels (HCC 305+/-90 mg/L; NCC 455+/-78 mg/L, p less than 0.01) when comparing the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

The cycle of SEC4 function in vesicular transport.

Sec4 is a Ras-like GTP-binding protein required for exocytosis in yeast. Unlike Ras, it is the ability of Sec4 to cycle between the GTP- and GDP-bound forms rather than the absolute levels of the GTP-bound form that is critical for function. This cycle may be coupled to an observed cycle of Sec4 localization within the cell. Sec4 binds to secretory vesicles which then fuse with the plasma membrane in exocytosis. Sec4 can recycle from the plasma membrane through a soluble pool to rebind to a new round of vesicles. We have found an activity in yeast (Saccharomyces cerevisiae) comparable to that of the GDP dissociation inhibitor protein isolated from mammalian cells that releases GDP-bound Sec4 from membranes. DSS4-1, a dominant suppressor of the sec4-8 temperature-sensitive mutation, encodes a nucleotide exchange protein. The cycle of Sec4 may function to allow the assembly and subsequent disassembly of a set of proteins necessary for exocytosis. Candidates for members of this set of proteins are encoded by sec genes which show strong genetic interactions with sec4-8. Two of these (SEC8 and SEC15) encode large proteins which form a complex that is peripherally associated with the plasma membrane.

Biological Transport↗
PubMed1993

Detection of perioperative myocardial structural damage by the estimation of cardiac myosin light chain I.

The accurate estimation of myocardial damage is desirable for the assessment of myocardial protection and surgical treatments. The purpose of the study was to estimate myocardial damage by measuring cardiac myosin light chain I (CMLCI). Forty-nine patients undergoing cardiac surgery (for angina or valvular disease) were arbitrarily divided into four groups according to the maximum CMLCI level. Group 1: max CMLCI < 10 micrograms/L (37%); Group 2: max CMLCI 10-20 micrograms/L (39%); Group 3: max CMLCI 20-30 micrograms/L (16%); Group 4: max CMLCI > 30 micrograms/L (8%). Electrocardiogram (ECG) and serum creatine kinase MB isoenzyme (CK-MB) were conventionally used as standards of myocardial damage, and compared with CMLCI. Perioperative myocardial infarction, injury and minimum damage were determined by combinations of ECG pattern changes and CK-MB levels. The max CMLCI level was usually seen on the third postoperative day. None of the patients in group 1 had any ECG changes. The number of patients with ECG changes was much higher as the max CMLCI level increased, and evidently increased when the max CMLCI was over 20 micrograms/L. The number of patients with high CK-MB > 100 micrograms/L followed the same pattern. Furthermore, perioperative infarction was only seen when the max CMLCI was > 30 micrograms/L. The peak CMLCI level was significantly higher in the infarction group than injury and minimum damage groups. This study showed that CMLCI was able to estimate the actual extent and severity of the myocardial damage and enhanced the diagnosis of perioperative infarction.

Aged↗
PubMed1992

Cyclic AMP-independent secretion of mucin by SW1116 human colon carcinoma cells. Differential control by Ca2+ ionophore A23187 and arachidonic acid.

The regulation of mucin secretion by SW1116 human colon carcinoma cells has been studied using monoclonal antibody 19-9, which has previously been used to detect mucin in the serum of cancer and cystic fibrosis patients. We found that SW1116 cells constitutively secrete considerable amounts of mucin as the predominant glycoprotein. The secretion of mucin by these cells is independent of cyclic AMP levels, but can be further stimulated by the Ca2+ ionophore A23187. However, arachidonic acid and its metabolites inhibit mucin secretion. Electron microscope studies reveal that the mucin is located near the plasma membrane as well as in vesicular and lysosome-like structures. However, the secretion pathway of mucin is different than that of the lysosomal contents, since arachidonic acid, while inhibiting mucin secretion, actually activates the secretion of the lysosomal enzyme beta-glucuronidase. We suggest that the mechanism of mucin secretion by SW1116 cells occurs by a pathway different from common exocytosis, and possibly by more than one pathway. The response of mucin secretion by SW1116 cells to common secretagogues resembles that of epithelial cells obtained from cystic fibrosis patients. Thus SW1116 cells are an especially interesting system for studying processes related to pathological states associated with excessive constitutive secretion of mucin.

1-Methyl-3-isobutylxanthine↗
PubMed1992

Fetal echocardiography: accuracy and limitations in a population at high and low risk for heart defects.

OBJECTIVE: Our objective was to assess the accuracy of prenatal echocardiography in detecting congenital heart defects in patients at high and low risk for structural cardiac anomalies. STUDY DESIGN: Sixty-nine consecutive fetuses with congenital heart defects who had had prenatal ultrasonography at greater than or equal to 18 weeks' gestation were evaluated to determine the accuracy of prenatal ultrasonography in identifying structural cardiac defects. Thirty-nine patients were at high risk and 30 patients were at low risk for cardiac anomalies. All fetuses were scanned with standard four-chamber and outflow tract views. Data concerning extracardiac anomalies and karyotypic abnormalities were tabulated. The accuracy of the four-chamber view alone in identifying congenital heart defects was evaluated. RESULTS: Fifty-seven of 69 fetuses (83%) were prenatally identified ultrasonographically as having a heart defect. There was no difference in the sensitivity of detecting cardiac anomalies between high-risk and low-risk groups. When the four-chamber view was used, only 63% of fetuses were recognized as having an abnormal heart. Extracardiac anomalies were noted in 36% and karyotypic abnormalities in 17% of patients. CONCLUSION: The four-chamber and outflow tract views done routinely in an ultrasonography laboratory seeing a mixed population of patients was successful in detecting 83% of fetuses with structural cardiac malformations. Because 43% of the fetuses with heart defects were referred for low-risk indications, systematic ultrasonographic examination of the fetal heart should not be reserved only for those at high risk.

Chromosome Aberrations↗
PubMed1992

Influence of alprostadil on pulmonary dysfunction after a cardiac operation.

To test the effects of alprostadil on pulmonary dysfunction after cardiac operations, we studied 24 male patients undergoing aortocoronary bypass. Twelve were given an intravenous infusion of alprostadil (synthetic prostaglandin E1), 20 ng.kg-1.min-1, in a double-blind manner during operation; the other 12 were controls. Duration of artificial respirator use and frequent blood gas analyses were used to assess postoperative pulmonary function. Use of the artificial respirator postoperatively was significantly lower in the prostaglandin group (mean time. 5.25 +/- 1.81 hours) compared with the controls (mean time, 8.34 +/- 4.35 hours) (p = 0.047). The proportion of patients with hypercapnia and with hypoxia determined every 4 hours for the first 24 hours after extubation was significantly lower in the prostaglandin group compared with the controls (p less than 0.0001). These results indicate that synthetic prostaglandin E1 may play a role in protecting lung tissue during extracorporeal circulation.

Adult↗
PubMed1992

An outbreak of Salmonella dublin infection in England and Wales associated with a soft unpasteurized cows' milk cheese.

An outbreak of Salmonella dublin infection occurred in England and Wales in October to December 1989. Forty-two people were affected, mainly adults, and most lived in south-east England. Microbiological and epidemiological investigations implicated an imported Irish soft unpasteurized cows' milk cheese as the vehicle of infection. A case-control study showed a statistically significant association between infection and consumption of the suspect cheese (p = 0.001). Salmonella dublin was subsequently isolated from cheeses obtained from the manufacturer's premises. Initial control measures included the withdrawal of the cheese from retail sale and a Food Hazard Warning to Environmental Health Departments, as well as a press release, from the Department of Health. Subsequently, a decision was taken by the manufacturer to pasteurize milk used in the production of cheese for the UK market and importation of the cheese resumed in June 1990.

Adolescent↗