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Biomedical subjects

R M Bell

Publications and source records attributed to R M Bell.

At least 217 records · Page 12Linked to original sources
PubMed1982

Patient-controlled analgesia: a new concept of postoperative pain relief.

This report concerns evaluation of patient-controlled analgesia (PCA) in the form of two preliminary investigations. In the first study, the patient-controlled analgesia device, which consists of a pump linked to a timer so that patients can activate intravenous administration of morphine sulfate to themselves during the postoperative period, was used in seven morbidly obese patients. The amount of morphine used during the first 36 hours was found to vary between 32 and 185 mg, with a significant difference in drug usage when related to weight as well as to body surface area. In the second study, morbidly obese patients undergoing gastric bypass operations were prospectively randomized into 12 patients who used the PCA device in the postoperative period and 12 patients who were given standard intramuscular dosages of morphine sulfate. An analgesia and sedation scale was then used to compare the two groups. The patients in the PCA group were able to maintain a state of adequate analgesia without sleep with a significantly greater frequency than were those in the intramuscular injection group. On the basis of answers to a questionnaire given to the patient after 60 hours of morphine analgesia, it was apparent that the PCA group was much more satisfied with that form of postoperative analgesia. It would appear that PCA is an efficacious and safe method of providing for postoperative pain relief.

Analgesia↗
PubMed1982

Diagnostic peritoneal lavage.

From the preceding review, it can be seen that diagnostic peritoneal lavage is a safe, reliable means of evaluating the various acute conditions of the abdomen. Patients who have sustained, blunt trauma of the abdomen, particularly with associated injuries, are prime candidates for the procedure. Children who have sustained injuries, either suspected abdominal injuries or multiple trauma, should be included. Other groups include paraplegic patients with possible abdominal disease and patients with findings which are suggestive of an acute condition of the abdomen but an uncertain diagnosis. Relative contraindications for peritoneal lavage include a distended abdomen, a history of previous surgical procedures of the abdomen and gravid uterus. Peritoneal lavage may be performed upon these patients but with modifications of technique. Patients for whom the diagnosis is certain and those patients upon whom exploration is planned are not candidates for lavage. Peritoneal lavage has been shown to be an effective adjunct in the evaluation of the abdomen in a wide variety of conditions. Its use has decreased the rate of unnecessary laparotomy both in patients with blunt trauma to the abdomen and in those with nontraumatic, acute disease of the abdomen. It can be used to arrive at an early decision for operative and nonoperative therapy and thereby reduce morbidity and mortality in patients with abdominal disease.

Abdomen, Acute↗
PubMed1982

Facile enzymatic synthesis of fatty acylcoenzyme A thioesters.

The fatty acid:CoA ligase (acyl-CoA synthetase, EC 6.2.1.3) of rat liver microsomes was solubilized with Triton X-100 and bound to Matrex Gel Red A. Fatty acid:CoA ligase immobilized on Matrex Gel Red A was active and proved useful for the synthesis of fatty acyl-CoA thioesters. The immobilized activity was characterized by a 3-fold higher apparent Km for ATP than the soluble activity, similar apparent Km values for CoA and palmitate, and a shift in the pH dependence. Quantitative incorporation of fatty acid or CoA was possible. Long chain-fatty acyl CoA thioesters were purified in a single step by hydrophobic chromatography on Octyl-Sepharose. In addition to producing the thioesters of typical fatty acids (e.g., myristic, palmitic, stearic, oleic, cis-vaccenic, linoleic, and arachidonic), analogs such as the fluorescent molecules beta-parinaroyl-CoA and palmitoyl-(1-N6-etheno-)CoA were easily synthesized. These procedures should be generally applicable for both the small-scale, i.e., 1 to 10 mumoles, and large-scale, i.e., 50 to 250 mumoles, scale preparation of numerous fatty acyl-CoA's and related compounds.

Acyl Coenzyme A↗
PubMed1981

Topography of glycerolipid synthetic enzymes. Synthesis of phosphatidylserine, phosphatidylinositol and glycerolipid intermediates occurs on the cytoplasmic surface of rat liver microsomal vesicles.

The topography of glycerolipid biosynthetic enzymes within the transverse plane of rat liver microsomal vesicles was investigated: (1) by use of the impermeant inhibitor, mercury-dextran; (2) by use of proteases; and (3) by determining whether the enzyme activities are latent. The seven enzyme activities investigated (dihydroxyacetone-phosphate acyltransferase, acyldihydroxyacetone-phosphate oxidoreductase, phosphatidic acid : CTPcytidyltransferase, CDPdiacylglycerol : inositol phosphatidyltransferase, 2-monoacylglycerol acyltransferase, diacylglycerol kinase, and the serine base exchange enzyme) function in phosphatidylinositol and phosphatidylserine synthesis and at intermediate levels in glycerolipid synthesis including steps of ether lipid synthesis. Mercury-dextran inhibited four of these enzymes greater than 60% in intact microsomal vesicles. One or more of the proteases employed (chymotrypsin, trypsin and pronase) inactivated each of the seven enzyme activities in intact microsomal vesicles. These two approaches indicate that each of these enzymes has important domains located on the cytoplasmic surface of microsomal vesicles. These enzyme activities could be assayed in intact microsomal vesicles. None appeared to be highly latent, indicating that substrates have free access to active sites. One substrate for each of these enzymes had been shown previously to be unable to cross the microsomal membrane. These data indicate that the active sites of these enzymes are located on the cytoplasmic surface of microsomal vesicles. It is concluded that the synthesis of phosphatidylserine and phosphatidylinositol, intermediates of ether lipid formation and other intermediates of glycerolipid synthesis occur asymmetrically on the cytoplasmic surface of the endoplasmic reticulum. These findings and our previous investigations on the topography of seven enzymes of triacylglycerol, phosphatidylcholine and phosphatidylethanolamine biosynthesis (Ballas, L.M. and Bell, R.M., Biochim. Biophys. Acta 602, (1980) 578-590) indicate that the synthesis of the major cellular glycerolipids occurs asymmetrically on the cytoplasmic surface of the endoplasmic reticulum.

Acyltransferases↗
PubMed1981

Bacterial endocarditis in the critically ill surgical patient.

The association of endocarditis with persistent intraperitoneal sepsis and right-sided heat catheterization (Swan-Ganz catheter and central venous catheter) was found in four (27%) of 15 patients with endocarditis identified at the University of Kentucky Medical Center, Lexington, during a 14-year period. These four patients had (1) intra-abdominal abscesses as a persistent source of sepsis, (2) documented septicemia, (3) long-term use of right sided heart catheters, and (4) prolonged hospitalization with a fatal outcome. In each case, endocarditis with persistent septicemia was considered a major factor contributing to a fatal outcome. Identification of a new cardiac murmur associated with septicemia was the most reliable means of diagnosis in these patients. The best form of treatment seems to be prevention by (1) eliminating septic foci, (2) using central catheters for specific indications for as short a period as possible, and (3) promptly discontinuing use of the catheter when septicemia is suspected.

Abscess↗
PubMed1981

Experiences with conversion of jejunoileal bypass to gastric bypass: its use for maintenance of weight loss.

Jejunoileal bypass for morbid obesity has been associated with a variety of long-term adverse sequelae, including excess diarrhea, electrolyte imbalance, kidney dysfunction, liver abnormalities, and polyarthropathy. Takedown of the bypass without providing a means of maintenance of weight reduction will lead to recurrence of morbid obesity. We studied 32 patients who underwent conversion of jejunoileal bypass to gastric bypass either in one procedure (27 patients) or more than one procedure (five patients). There were no operative deaths, but significant morbidity. Nevertheless, the conversion has maintained weight reduction and reversed the adverse effects of the small-bowel bypass. We concluded that conversion of the jejunoileal bypass to the gastric bypass, particularly with a Roux-en-Y anastomosis, in a single procedure is relatively safe, simple, and effective.

Adolescent↗
PubMed1981

Lipid topogenesis.

Investigations of the topography of glycerolipid synthetic enzymes within the transverse plane of microsomal vesicles indicated an exclusive cytoplasmic surface location of active sites. Evidence was derived from studies employing proteases and other impermeant inhibitors, from investigations of latency and substrate permeation, and from localization of products. These studies strongly suggest a total asymmetric synthesis of glycerolipids on the cytoplasmic surface of the endoplasmic reticulum. The data are critically reviewed, emphasizing the importance of appropriate controls for topographical studies of microsomal enzymes. The limited data on the location and topography of other enzymes of complex lipid metabolism in microsomes, peroxisomes, mitochondria, and other membranes are also reviewed. These new findings have important implications for the processes of "lipid topogenesis" which encompass complex lipid synthesis, the integration of lipids into membranes, and lipid translocation across membranes. Later events of lipid topogenesis involve lipid movement to other membranes and structures, the sorting of complex lipids from each other to assemble structures of distinct lipid composition, and the formation and maintenance of lipid asymmetry.

Animals↗
PubMed1980

Topography of phosphatidylcholine, phosphatidylethanolamine and triacylgycerol biosynthetic enzymes in rat liver microsomes.

The topography of phosphatidylcholine, phosphatidylethanolamine and triacylglycerol biosynthetic enzymes within the transverse plane of rat liver microsomes was investigated using two impermeant inhibitors, mercury-dextran and dextran-maleimide. Between 70 and 98% of the activities of fatty acid : CoA ligase (EC 6.2.1.3), sn-glycerol-3-phosphate acyltransferase (EC 2.3.1.15), phosphatidic acid phosphatase (EC 3.1.3.4), diacylglycerol acyltransferase (EC 2.3.1.20), diacylglycerol cholinephosphotransferase (EC 2.7.8.2) and diacylglycerol ethanolaminephosphotransferase (EC 2.7.8.1) were inactivated by mercury-dextran. Dextran-maleimide caused 52% inactivation of the sn-glycerol-3-phosphate acyltransferase. Inactivation of each of these activities except fatty acid : CoA ligase occurred in microsomal vesicles which remained intact as evidenced by the maintenance of highly latent mannose-6-phosphatase activity (EC 3.1.3.9). These glycerolipid biosynthetic activities were not latent, indicating that substrates have free access to the active sites. Moreover, ATP, CDP-choline and CMP appeared unable to penetrate the microsome membrane. These data indicate that the active sites of thease enzymes are located on the external surface of microsomal vesicles. It is concluded that the biosynthesis of phosphatidylcholine, phosphatidylethanolamine and triacylglycerol occurs asymmetrically on the cytoplasmic surface of the endoplasmic reticulum.

Acyltransferases↗
PubMed1980

Membrane phospholipid synthesis in Escherichia coli. Cloning of a structural gene (plsB) of the sn-glycerol-3-phosphate acyl/transferase.

Si+ hybrid ColE1 plasmids of the Clarke-Carbon collection (Clarke, C., and Carbon, J. (1976) Cell 9, 91-99) which eliminate the sn-glycerol 3-phosphate growth requirement of a mutant of Escherichia coli with a Km defect in sn-glycerol-3-phosphate acyltransferase (plsB) were identified. Marked overproduction of a plasmid-encoded sn-glycerol-3-phosphate acyltransferase with a wild type Km in a host plsB- background indicates that the hybrid plasmids carry a structural gene for this enzyme. In addition, all of these plasmids suppress the phenotype of a mutation in a second locus involved in phospholipid biosynthesis, dgk (diglyceride kinase), and one of them also bears the dnaB structural gene. Diglyceride kinase activity is also overproduced in these strains. The linkage of plsB, dgk and dnaB loci was confirmed by transduction analysis which demonstrated the clockwise gene order malB, dnaB, dgk, plsB, and uvrA near Minute 91 on the E. coli linkage map. This is in contrast to the previously reported co-transduction of plsB with dctA near Minute 78 (Cronan, J. E., Jr., and Bell, R. M. (1974) J. Bacteriol., 120, 227-233). Recloning of restriction endonuclease fragments and in vitro mutagenesis have localized the dgk, and plsB loci to a 2.2-megadalton DNA segment, and have demonstrated that diglyceride kinase and sn-glycerol-3-phosphate acyltransferase activities reside in separate polypeptides. Availability of these clones and mutationally altered derivatives has allowed the identification of a single polypeptide (Mr = 83,000) corresponding to the sn-glycerol-3-phosphate acyltransferase and purification of this membrane-bound enzyme to near homogeneity (Larson, T. J., Lightner, V. A., Green, P. R., Modrich, P., and Bell, R. M. (1980) J. Biol. Chem. 255, 9421-9426). The size of the plsB polypeptide indicates that a major fraction of the DNA segment to which this gene has been localized is involved in coding for the sn-glycerol-3-phosphate acyltransferase.

Acyltransferases↗
PubMed1980

Membrane phospholipid synthesis in Escherichia coli. Identification of the sn-glycerol-3-phosphate acyltransferase polypeptide as the plsB gene product.

A collection of hybrid plasmids bearing a structural gene, plsB, for the sn-glycerol-3-phosphate acyltransferase of Escherichia cole (Lightner, V. A., Larson, T. J., Tailleur, P., Kantor, G. D., Raetz, C. R. H., Bell, R. M., and Modrich, P. (1980) J. Biol. Chem. 255, 9413-9420) was employed to identify the membrane protein which is the sn-glycerol-3-phosphate acyltransferase. Strains containing these hybrid plasmids exhibited a marked increase in sn-glycerol-3-phosphate acyltransferase activity which was quantitatively extracted from membrane preparations with Triton X-100. Analysis of polypeptides present in detergent extracts of membranes from strains harboring the hybrid plasmids revealed a marked overproduction of a protein with an apparent molecular weight of 83,000, which was also the major protein labeled in minicells containing these hybrid plasmids. The labeled 83,000-dalton protein cochromatographed with sn-glycerol-3-phosphate acyltransferase activity on DEAE-cellulose. Utilization of three hybrid plasmids bearing amber mutations within the plsB gene demonstrated that the 83,000-dalton protein is the sn-glycerol-3-phosphate acyltransferase. Analysis of Bam HI deletion plasmids demonstrated that a 2.3-megadalton DNA fragment is necessary and sufficient for expression of the plsB gene. The sn-glycerol-3-phosphate acyltransferase was purified to near homogeneity from Triton X-100 extracts of membranes from overproducing strains. The preparations had reconstitutable specific activity of 2.5 micromol/min/mg and contained a single polypeptide with an apparent molecular weight of 83,000.

Acyltransferases↗
PubMed1980

Selective changes in enzymes of the sn-glycerol 3-phosphate and dihydroxyacetone-phosphate pathways of triacylglycerol biosynthesis during differentiation of 3T3-L1 preadipocytes.

Enzyme activities of the sn-glycerol 3-phosphate (glycerol-P) and of the dihydroxyacetone-phosphte (DHAP) pathway of glycerolipid biosynthesis were investigated during the differentiation of 3T3-L1 preadipocytes into adipocytes. Total particulate glycerol-P and DHAP acyltransferase activities increased 70- and 30-fold, respectively, during differentiation induced with methylisobutylxanthine and dexamethasone. The N-ethylmaleimide-sensitive (microsomal) glycerol-P and DHAP acyltransferase activities were virtually undetectable in nondifferentiated cells, and increased in parallel over 70-fold during differentiation. These and several kinetic observations are consistent with the induction of a single microsomal enzyme having dual activity. During differentiaion, the N-ethylmaleimide-resistant DHAP acyltransferase activity increased 10-fold, suggesting the presence of at least two DHAP acyltransferase isoenzymes. Qualitatively similar changes in microsomal glycerol-P and DHAP acyltransferase activities were observed when cell differentiation was induced with insulin or with insulin plus dexamethasone and methylisobutylxanthine. Acyl-DHAP oxidoreductase (EC 1.1.1.101) specific activity increased only 3- to 5-fold during adipocyte differentiation. Alkyl-DHAP synthase activity was not detected. These data demonstrate that selective changes in enzyme activities of the gycerol-P pathways of glycerolipid synthesis occur during the differentiation of 3T3-L1 preadipocytes.

1-Methyl-3-isobutylxanthine↗