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Biomedical subjects

P G Collins

Publications and source records attributed to P G Collins.

At least 19 recordsLinked to original sources
PubMed1995

The alpha subunit of the Saccharomyces cerevisiae oligosaccharyltransferase complex is essential for vegetative growth of yeast and is homologous to mammalian ribophorin I.

Oligosaccharyltransferase mediates the transfer of a preassembled high mannose oligosaccharide from a lipid-linked oligosaccharide donor to consensus glycosylation acceptor sites in newly synthesized proteins in the lumen of the rough endoplasmic reticulum. The Saccharomyces cerevisiae oligosaccharyltransferase is an oligomeric complex composed of six nonidentical subunits (alpha-zeta), two of which are glycoproteins (alpha and beta). The beta and delta subunits of the oligosaccharyltransferase are encoded by the WBP1 and SWP1 genes. Here we describe the functional characterization of the OST1 gene that encodes the alpha subunit of the oligosaccharyltransferase. Protein sequence analysis revealed a significant sequence identity between the Saccharomyces cerevisiae Ost1 protein and ribophorin I, a previously identified subunit of the mammalian oligosaccharyltransferase. A disruption of the OST1 locus was not tolerated in haploid yeast showing that expression of the Ost1 protein is essential for vegetative growth of yeast. An analysis of a series of conditional ost1 mutants demonstrated that defects in the Ost1 protein cause pleiotropic underglycosylation of soluble and membrane-bound glycoproteins at both the permissive and restrictive growth temperatures. Microsomal membranes isolated from ost1 mutant yeast showed marked reductions in the in vitro transfer of high mannose oligosaccharide from exogenous lipid-linked oligosaccharide to a glycosylation site acceptor tripeptide. Microsomal membranes isolated from the ost1 mutants contained elevated amounts of the Kar2 stress-response protein.

Amino Acid Sequence↗
PubMed1995

The essential OST2 gene encodes the 16-kD subunit of the yeast oligosaccharyltransferase, a highly conserved protein expressed in diverse eukaryotic organisms.

Oligosaccharyltransferase catalyzes the transfer of a preassembled high mannose oligosaccharide from a dolichol-oligosaccharide donor to consensus glycosylation acceptor sites in newly synthesized proteins in the lumen of the rough endoplasmic reticulum. The Saccharomyces cerevisiae oligosaccharyltransferase is an oligomeric complex composed of six non-identical subunits (alpha-zeta). The alpha, beta, gamma, and delta subunits of the oligosaccharyltransferase are encoded by the OST1, WBP1, OST3, and SWP1 genes, respectively. Here we describe the functional characterization of the OST2 gene that encodes the epsilon-subunit of the oligosaccharyltransferase. Genomic disruption of the OST2 locus was lethal in haploid yeast showing that expression of the Ost2 protein is essential for viability. Overexpression of the Ost2 protein suppresses the temperature-sensitive phenotype of the wbp1-2 allele and increases in vivo and in vitro oligosaccharyltransferase activity in a wbp1-2 strain. An analysis of a series of conditional ost2 mutants demonstrated that defects in the Ost2 protein cause pleiotropic underglycosylation of soluble and membrane-bound glycoproteins. Microsomal membranes isolated from ost2 mutant yeast show marked reductions in the in vitro transfer of high mannose oligosaccharide from exogenous lipid-linked oligosaccharide to a glycosylation site acceptor tripeptide. Surprisingly, the Ost2 protein was found to be 40% identical to the DAD1 protein (defender against apoptotic cell death), a highly conserved protein initially identified in vertebrate organisms. The protein sequence of ost2 mutant alleles revealed mutations at highly conserved residues in the Ost2p/DAD1 protein sequence.

Amino Acid Sequence↗
PubMed1993

Let the finger linger.

Retrorectal masses are rare and of insidious onset. We report a consecutive series of six such cases (males = 4, females = 2). The main presenting complaint was back pain and the most reliable physical sign was a palpable mass posteriorly on rectal examination (all cases). C T scan was the most radiologically informative investigation. Surgical intervention was undertaken using both anterior (trans-abdominal) and posterior (retrorectal) approaches. The majority of the masses excised were benign and all patients, to date, remain well.

Adult↗
PubMed1991

Ribosome binding to the endoplasmic reticulum: a 180-kD protein identified by crosslinking to membrane-bound ribosomes is not required for ribosome binding activity.

We have used the membrane-impermeable, thiol-cleavable, crosslinker 3,3'-dithio bis (sulfosuccinimidylpropionate) to identify proteins that are in the vicinity of membrane-bound ribosomes of the RER. A specific subset of RER proteins was reproducibly crosslinked to the ribosome. Immunoblot analysis of the crosslinked products with antibodies raised against signal recognition particle receptor, ribophorin I, and the 35-kD subunit of the signal sequence receptor demonstrated that these translocation components had been crosslinked to the ribosome, but each to a different extent. The most prominent polypeptide among the crosslinked products was a 180-kD protein that has recently been proposed to be a ribosome receptor (Savitz, A.J., and D.I. Meyer, 1990. Nature (Lond.). 346: 540-544). RER membrane proteins were reconstituted into liposomes and assayed with radiolabeled ribosomes to determine whether ribosome binding activity could be ascribed to the 180-kD protein. Differential detergent extraction was used to prepare soluble extracts of microsomal membrane vesicles that either contained or lacked the 180-kD protein. Liposomes reconstituted from both extracts bound ribosomes with essentially identical affinity. Additional fractionation experiments demonstrated that the bulk of the ribosome binding activity present in detergent extracts of microsomal membranes could be readily resolved from the 180-kD protein by size exclusion chromatography. Taken together, we conclude that the 180-kD protein is in the vicinity of membrane bound ribosomes, yet does not correspond to the ribosome receptor.

Animals↗
PubMed1991

Carcinoma of the head of the pancreas.

Optimal treatment for unresectable carcinoma of the pancreas remains controversial. This study was done to examine the relationship between perioperative jaundice and postoperative morbidity, and type of palliative biliary bypass and postoperative morbidity and jaundice clearance. Seventy-six patients with obstructive jaundice secondary to carcinoma of the head of the pancreas were studied. Forty-nine patients underwent one of four different types of palliative bypass: 1, cholecystojejunostomy (n = 22); 2, choledochojejunostomy (n = 11); 3, choledochoduodenostomy (n = 9), and 4, cholecystoduodenostomy (n = 7). Age, sex and preoperative health status were similar for all operative groups, as well as for those with and without postoperative morbidity. The postoperative complication rate was 33 per cent and there was one postoperative death. Length of preoperative jaundice and peak preoperative bilirubin levels were independent of morbidity. Postoperative morbidity was similar for each type of bypass used and no significant difference was found when cholecystoenteric (1 and 4) and choledochoenteric (2 and 3) bypass were compared. The results of this study support the view that postoperative morbidity is not directly related to the presence of jaundice preoperatively. Furthermore, the rate of jaundice clearance and the occurrence of postoperative complications are not dependent on the type of bypass used.

Adult↗
PubMed1988

Phaeochromocytoma--a presentation mimicking malignant hyperthermia.

A 52-year-old apparently healthy, normotensive woman who presented for elective cholecystectomy experienced intra-operative hypertension and tachycardia, which were controlled by propranolol. Oesophageal temperature increased, there was a metabolic and respiratory acidosis with hypoxaemia, and malignant hyperthermia was diagnosed. Severe cardiogenic pulmonary oedema ensued, and was treated with intravenous glyceryl trinitrate. Ventricular fibrillation caused cardiac arrest, and this was treated successfully. Postoperatively a phaeochromocytoma was discovered, and removed at a subsequent operation. The case illustrates the similarities in presentation of malignant hyperthermia and phaeochromocytoma, and the possibility that misdiagnosis may exacerbate the crisis.

Adrenal Gland Neoplasms↗
PubMed1988

The diagnosis and management of splenic artery aneurysms.

The presentation and course of 7 patients with splenic artery aneurysms is reviewed. Three presented with abdominal pain, 2 with collapse and rupture and in 2 it was an incidental finding. Four patients had elective ligation-excision of the aneurysm with splenectomy as had one patient operated on as an emergency, with no operative mortality. The aneurysm size ranged from 20 to 45 mm (mean 30 mm) and histology confirmed atheroma. One patient was managed as a myocardial infarct for 8 hours after admission and a ruptured splenic aneurysm was diagnosed at autopsy, an overall mortality of 14%. A 66-year-old woman in poor general health was managed expectantly and was asymptomatic when lost to follow-up after 2 years.

Adult↗
PubMed1987

Blunt injury of the neck of the pancreas: a report of nine patients.

Nine patients with injury of the neck of the pancreas following blunt abdominal injury are reported. Eight were sustained in road traffic accidents and only two victims had used seatbelts. Serious associated injuries were present in four patients and the pancreatic injury was missed in two patients. The diagnosis of this injury was made at laparotomy in six, while one patient had the diagnosis confirmed at endoscopic retrograde pancreatography (ERP). The neck of the pancreas was the site of injury in all nine cases. Pancreatic drainage (3), suture repair (1) and distal resection with splenectomy (2) were the operative procedures performed. Pseudocyst of the pancreas (2), pancreatic fistulas (2), pancreatitis (1) and ascites (1), which necessitated a further laparotomy, accounted for postoperative morbidity. There was one postoperative death from haemorrhage due to stress ulceration. This study emphasizes that the neck of the pancreas is at special risk following blunt abdominal injury.

Accidents, Traffic↗
PubMed1986

Surgery for Crohn's disease in Ireland.

Patients overall had a one in seven chance of having curative surgery in any of the first ten years following diagnosis. Cumulative surgical recurrence rates are similar to those in America. The higher cumulative surgical recurrence rates are similar to those in America. The higher cumulative risk of surgical recurrence in patients with macroscopic disease of the large bowel probably relates to a conservative surgical approach in such patients. There was no operative mortality.

Adolescent↗
PubMed1984

Iatrogenic biliary stricture: presentation and management.

Repair of iatrogenic biliary stricture was carried out in 38 patients of whom five are now dead, three causally related. Thirty-one patients were followed up between August 1983 and March 1984 (mean time since repair 7.9 years). Fifty reparative operations were carried out, six patients first having a temporary end fistula performed. Cholangiography during cholecystectomy had been performed in only eight patients (21 per cent). All but one patient had gastroscopy and barium meal examination and the incidence of duodenal ulceration was 6.7 per cent and of oesophageal varices 5.6 per cent. Liver biopsies taken during the first reparative operation were normal in 5 per cent, obstructive in 65 per cent and cirrhotic in 30 per cent. Intra-operative cultures were mainly coliforms (66.7 per cent). Liver function tests were normal in 19 (61.3 per cent) but there was no correlation between abnormal values and clinical status. Twenty-nine patients (93.5 per cent) are now completely well. 99mTc HIDA scans, liver ultrasonography, intravenous cholangiography and BSP excretion were of limited value in planning further surgery. The most useful investigation before reoperation was transhepatic cholangiography.

Adult↗
PubMed1983

Effect of vehicle on the pharmacokinetics and uptake of four halogenated hydrocarbons from the gastrointestinal tract of the rat.

A variety of low molecular weight aliphatic chlorinated hydrocarbons have a history of use in the processing of foods, and their presence in potable water supplies has also been demonstrated. In this study, the relative uptake of four different aliphatic chlorinated hydrocarbons (methylene chloride, dichloroethane, chloroform and trichloroethylene) was studied after administration, by intragastric intubation, at the same dose level as corn-oil or aqueous solutions. Serial blood samples were collected over a 5-h period and uptake was assessed as the calculated area under blood concentration-time curves. A significant decrease in the rate and extent of uptake was observed for the compounds when administered as an oil solution as compared with an aqueous solution. Lower peak concentrations and an increase in the time taken to reach peak concentration, after dosing with corn oil solutions, was also observed.

Animals↗