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Biomedical subjects

J M Gilbert

Publications and source records attributed to J M Gilbert.

At least 55 records · Page 3Linked to original sources
PubMed1990

Fusion of Rous sarcoma virus with host cells does not require exposure to low pH.

We investigated whether Rous sarcoma virus (RSV) infects cells through a pH-independent or a low-pH-dependent pathway. To do this, the effects of lysosomotropic agents and acid pretreatment on RSV infectivity of, and fusion with, chicken embryo fibroblasts (CEFs) were studied. High concentrations of lysosomotropic agents (ammonium chloride and monensin) did not inhibit virus infectivity: equal titers of RSV were produced in the presence and absence of these agents. Similarly, low-pH pretreatment did not inhibit RSV infectivity. In parallel experiments, lysosomotropic agents and acid pretreatment completely abolished the ability of influenza virus to infect CEFs. To monitor the fusion activity of RSV directly, the viral membrane was labeled with the fluorescent lipid probe octadecyl rhodamine at a self-quenching concentration. Upon fusion with a host cell, the probe is diluted in the cell membrane, resulting in fluorescence dequenching (D. Hoekstra, T. de Boer, K. Klappe, and J. Wilschut, Biochemistry 23:5675-5681, 1984). In this assay, fusion of RSV with CEFs was found to occur in both a time-dependent and a strictly temperature-dependent fashion. No fusion occurred unless cells with prebound virus were warmed to temperatures greater than 20 degrees C. Fusion, but not binding, was abolished if virus was pretreated with low concentrations of glutaraldehyde. High concentrations of ammonium chloride had no effect on fusion of RSV with CEFs but greatly diminished the ability of influenza virus and Semliki Forest virus to fuse with CEFs. Similarly, acid pretreatment of RSV had no effect on fusion with CEFs while markedly inhibiting fusion of both influenza and Semliki Forest viruses. Collectively, our results show that RSV fusion with and hence infection of CEFs does not require exposure of the virus to low pH. In this respect, RSV resembles another retrovirus, human immunodeficiency virus.

Animals↗
PubMed1990

Altered pituitary growth hormone (GH) regulation in streptozotocin-diabetic rats: a combined defect of hypothalamic somatostatin and GH-releasing factor.

Diabetes mellitus in the rat is associated with loss of pulsatile GH secretion. An interplay between hypothalamic GH-releasing factor (GRF) and inhibitory factor [somatostatin (SRIF)] secretion is thought to account for episodic pituitary GH release. An increase in SRIF tone/action or a decrease in GRF release/response in diabetic rats could account for the suppressed GH levels. Pituitaries from streptozotocin-diabetic rats contained less GH than controls (15.9 +/- 2.5 vs. 29.5 +/- 4.6 micrograms/mg; P less than 0.05) despite normal somatotrope representation, as demonstrated using immunofluorescence studies. Basal GH secretion from monolayer culture of dispersed anterior pituitary (AP) cells from diabetic rats was proportionately decreased (150 +/- 10 vs. 103 +/- 10 ng/10(5) cells; P less than 0.005). GRF (10(-11)-10(-8) M)-induced release of GH from AP cells was decreased in diabetic rats (maximum response to 10(-8) M GRF, 401 +/- 60 vs. 618 +/- 41 ng/10(5) cells; P less than 0.01); however, sensitivity to GRF was unchanged (EC50, 79 +/- 41 vs. 128 +/- 67 pM). By contrast, SRIF (10(-7)-10(-10)-induced inhibition of GRF (10(-8) M)-mediated GH release was impaired in AP cells of diabetic rats compared to that in controls (IC50, 112 +/- 33 vs. 55 +/- 31 pM; P less than 0.05) associated with a decrease in AP plasma membrane SRIF receptor concentration (63.4 +/- 15.6 vs. 160.3 +/- 13.7 fmol/mg protein; P less than 0.05), with no change in affinity. These findings are consistent with chronic exposure to increased hypothalamic SRIF influence. GH synthesis has been shown to be independent of SRIF regulation; however, insulin-like growth factor-I and GRF inhibit and stimulate GH synthesis, respectively. In diabetic rats insulin-like growth factor-I levels were decreased, appropriate to low GH status, in serum (290 +/- 66 vs. 1662 +/- 92 ng/ml; P less than 0.001) and hypothalamus (6.8 +/- 1.0 vs. 13.0 +/- 0.4 pg/mg wet wt; P less than 0.001) and, thus, did not seem to account for the low AP GH content. Hypothalamic GRF content in diabetic rats (1.11 +/- 0.10 ng/hypothalamus) did not differ from that in controls (1.16 +/- 0.17 ng/hypothalamus). GRF mRNA levels, however, were reduced by 80% in diabetic rats compared to controls. Taken together these data support a combined role for decreased hypothalamic GRF and increased SRIF in mediating alterations of GH synthesis and secretion in streptozotocin-induced diabetes.

Animals↗
PubMed1989

A comparison between amoxycillin/clavulanate and mezlocillin in abdominal surgical prophylaxis.

A randomized comparative study was conducted to evaluate the clinical efficacy of amoxycillin/clavulanate (Augmentin) compared with mezlocillin for the prevention of wound infection in patients undergoing abdominal surgery. There was no difference in overall wound infection rates between the amoxycillin/clavulanate treated group and the mezlocillin group. When sub-groups were examined for total infections no significant difference was seen between antibiotic groups in patients undergoing clean/potentially contaminated operations or contaminated operations, although more deep infections were encountered in the amoxycillin/clavulanate group in comparison with the mezlocillin group, in contaminated operations. The type of operation performed also failed to show any difference in those patients undergoing upper gastro-intestinal, appendiceal, colonic, or biliary operations. The infections in those receiving amoxycillin/clavulanate were largely of bowel origin and predominantly sensitive to amoxycillin/clavulanate. Those in the mezlocillin group were predominantly staphylococcal in origin. Amoxycillin/clavulanate appears to be an effective antibiotic for use as a single agent in surgical prophylaxis.

Abdomen↗
PubMed1988

Purification of homologous protein carboxyl methyltransferase isozymes from human and bovine erythrocytes.

We have purified the two major isozymes of the L-isoaspartyl/D-aspartyl protein methyltransferase from both human and bovine erythrocytes. These four enzymes all have polypeptide molecular weights of approximately 26,500 and appear to be monomers in solution. Each of these enzymes cross-reacts with antibodies directed against protein carboxyl methyltransferase I from bovine brain. Their structures also appear to be similar when analyzed by dodecyl sulfate gel electrophoresis for the large fragments produced by digestion with Staphylococcus aureus protease V8 or when analyzed by high-performance liquid chromatography (HPLC) for tryptic peptides. The structural relatedness of these enzymes was confirmed by sequence analysis of a total of 433 residues in 32 tryptic fragments of the human erythrocyte isozymes I and II and of the bovine erythrocyte isozyme II. We found sequence identify or probable identity in 111 out of 112 residues when we compared the human isozymes I and II and identities in 127 out of 134 residues when the human and bovine isozymes II were compared. These results suggest that the erythrocyte isozymes from both organisms may have nearly identical structures and confirm the similarities in the function of these methyltransferases that have been previously demonstrated.

Amino Acid Sequence↗
PubMed1988

Two major isozymes of the protein D-aspartyl/L-isoaspartyl methyltransferase from human erythrocytes.

We have been able to separate protein carboxyl methyltransferase activity from human erythrocyte cytosol into two major fractions by DEAE-cellulose chromatography. These isozymes, designated I and II, are characterized by their isoelectric points of approximately 6.6 and 5.5 as determined by isoelectric focusing in polyacrylamide gels. The ratio of the isozymes (II/I) was found to range from 0.52 to 1.2 in blood samples from 14 individuals. We did not detect differences in this ratio between males and females. We also found no differences between freshly drawn and outdated blood samples. Both isozymes catalyzed the methylation of proteins such as ovalbumin as well as synthetic L-isoaspartyl-containing peptides.

Adult↗
PubMed1988

Intraoperative testing of the integrity of left-sided colorectal anastomoses: a technique of value to the surgeon in training.

Left-sided colorectal anastomoses sometimes leak despite the best efforts of the surgeon. The cause is thought to be multifactorial but imperfections in the technique of performing the anastomosis must play some part. A method for testing the integrity of left-sided colorectal anastomoses has been developed using intraluminal distension. Twenty-one patients were studied and defects in the anastomosis were found in five (24%). These defects were rectified at the time of operation. We conclude that this method is useful for demonstrating imperfections in anastomotic technique and we suggest a distending pressure of 25 cm saline. We suggest that the method may be particularly useful for the surgeon in training.

Aged↗
PubMed1987

Cyclopia and congenital cytomegalovirus infection.

We describe the first documented association of congenital cytomegalovirus (CMV) infection and cyclopia. A previous report has suggested that any infant with congenital ocular defects should be investigated for CMV infection [Frenkel et al, 1980]. Our case underlines this suggestion and questions a teratogenic role for CMV in cyclopiaholoprosencephaly. More documented cases may help clarify the relationship of transplacental CMV infection to the holoprosencephaly developmental field defect, including cyclopia.

Abnormalities, Multiple↗
PubMed1987

Peritoneal closure after lateral paramedian incision.

The lateral paramedian incision has been advocated as the strongest incision for abdominal surgery. We have evaluated this incision and tested the necessity for closing the deep peritoneal layer by a prospective randomized trial. All 206 patients undergoing laparotomy in the Surgical Unit in 1984, both elective and emergency cases, were included. In patients undergoing laparotomy through unscarred tissue, a lateral paramedian incision was performed and they were randomized to have either the peritoneum closed (n = 77) or left open (n = 75). Patients in whom the laparotomy was performed through a previous incision (n = 51) and those in whom the abdomen had to be opened urgently (n = 3) were excluded from the trial but studied separately (n = 54). The rectus sheath was closed with monofilament nylon in all cases. Patients were assessed for wound integrity during the immediate postoperative period and at 1, 3, 6 and 12 months after operation. So far the patients have been followed up for between 1 and 2 years and follow-up is continuing as in some cases incisional hernia may not be detected until several years after operation. There have been no cases of burst abdomen. No incisional hernias have developed in patients in whom a lateral paramedian incision was performed and the peritoneum was closed, and one incisional hernia has occurred in the patients in whom the peritoneum was left open. Seven incisional hernias have occurred in patients excluded from the trial of the lateral paramedian incision (13 per cent). We conclude that the lateral paramedian incision successfully abolishes the burst abdomen and that incisional hernia is rare. It is not necessary to close the peritoneum with this incision.

Clinical Trials as Topic↗
PubMed1987

Experimental colorectal cancer as a model of human disease.

Colorectal cancer may now be induced consistently in experimental animals by the carcinogen 1,2-dimethylhydrazine (DMH). Adenomas and adenocarcinomas are produced in the large bowel and these resemble human colorectal cancer both macroscopically, and in their clinical behaviour. They are a close model of human disease and may be used for the evaluation of anti-cancer therapies and for the development of a diagnostic test for colorectal cancer.

Adenocarcinoma↗
PubMed1987

Psychosis and prenatal exposure to diethylstilbestrol.

Over the past 10 years, increasing evidence has demonstrated mammalian brain development to be influenced by prenatal exposure to sex hormones. It seems possible that human behavioral abnormalities may be associated with prenatal exposure to diethylstilbestrol (DES). Relevant basic science and clinical reports are reviewed and four case reports of psychotic patients who were prenatally exposed to DES are presented.

Adult↗
PubMed1986

The characterization of an acidic calmodulin-binding protein in brain cytoskeleton and membrane fractions.

One of the most abundant acidic proteins in rat brain has an Mr of 68,000 and a pI of 5.6 (68K 5.6 protein) when analysed by two-dimensional gel electrophoresis. The 68K 5.6 protein was found in large relative amounts in brain cytoskeleton preparations and in membrane and supernatant fractions. High-salt washing and proteolytic digestion did not remove this protein from the membrane elements. The 68K 5.6 protein was also found in the microtubule-associated protein fraction of purified microtubules and was present in large relative amounts in preparations of intermediate-filament proteins. The 68K 5.6 protein binds to calmodulin in the presence of Ca2+ ions, and we found it to be an abundant acidic calmodulin-binding protein in brain tissue.

Animals↗
PubMed1986

Surgery for peptic ulceration associated with hypergastrinaemia.

Between 1971 and 1983, 31 males and 13 females were found to have peptic ulceration associated with hypergastrinaemia. An antral G-cell lesion was present in 11 (25 per cent) and a gastrinoma in 14 (32 per cent). There were 11 patients with multiple endocrine adenomatosis (MEA) (25 per cent) and 4 (9 per cent) with primary hyperparathyroidism. Four patients (9 per cent) were unclassified. Length of history and level of gastrin did not differentiate between the groups and an average of 2.5 operations was performed per patient, while the overall mortality was 27.3 per cent. The patients with G-cell lesions were significantly younger than all the other groups (P less than 0.01). Partial gastrectomy adequately treated G-cell hyperplasia. Total gastrectomy was required to treat pancreatic gastrinomata but additional pancreatic resection did not improve the outcome. In MEA, parathyroidectomy did not influence the treatment of a gastrinoma. This is the first recorded experience of surgery for hypergastrinaemia in the United Kingdom and the outcome of such a retrospective study may be a guide to the future management of these conditions.

Adenoma, Islet Cell↗
PubMed1986

Randomized trial of oral adjuvant razoxane (ICRF 159) in resectable colorectal cancer: five-year follow-up.

Razoxane is one of the few agents which has shown activity in the treatment of advanced colorectal cancer. The drug has therefore been evaluated in a prospective randomized controlled trial as an adjuvant to surgery for resectable colorectal cancer. The results to median follow-up of 5 years are reported here. Accrual has ceased and a total of 272 patients entered the trial (133 control, 139 treatment). Treated patients received razoxane postoperatively on a continuous, long-term basis while control patients received identical clinical care but no adjuvant chemotherapy. Analysis of the results shows a significant prolongation of the time to recurrence for Dukes' C patients. All other groups including the overall analysis show no benefit although there is a consistent trend in favour of the treated patients except in Dukes' group 'D'. Razoxane is tolerated well by patients and causes minimal side-effects. However acute leukaemia occurred in three patients (2.45 per cent) after prolonged exposure to the drug and further evaluation should be in patients who are at high risk of developing recurrent cancer, in whom such a risk may be acceptable. It is concluded that razoxane is suitable for further evaluation in colorectal cancer and for incorporation into combination chemotherapy regimens.

Clinical Trials as Topic↗
PubMed1986

Controlled trial of transcutaneous electrical nerve stimulation (TENS) for postoperative pain relief following inguinal herniorrhaphy.

We have evaluated the effect of transcutaneous electrical nerve stimulation (TENS) on postoperative pain following inguinal herniorrhaphy in a prospective randomized controlled trial. Forty male patients undergoing unilateral inguinal herniorrhaphy for the first time were randomized to receive either active or inactive TENS. Electrical stimulation was delivered by electrodes placed along either side of the wound following operation. An identical apparatus, which did not deliver an electrical current, was applied to control patients. Pain was assessed over the first 3 postoperative days by visual analogue pain scores, expiratory peak flow rates and analgesic requirements. There was no difference between the two groups for pain scores, peak flow rates or analgesic requirements and we conclude that TENS as used in this trial does not reduce postoperative pain. However, TENS had considerable patient appeal and many patients believed that it was effective.

Adult↗