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Biomedical subjects

J A Higgins

Publications and source records attributed to J A Higgins.

At least 109 records · Page 6Linked to original sources
PubMed1983

The risk of gastric carcinoma after surgical treatment for benign ulcer disease. A population-based study in Olmsted County, Minnesota.

To determine the long-term risk of gastric cancer in benign peptic-ulcer disease, we studied 338 residents of Olmsted County, Minnesota, who had surgical treatment for benign peptic-ulcer disease in the 25-year period 1935-1959 and had no evidence of gastric cancer for five years after that surgery. These patients were subsequently followed for over 5635 person-years of observation. The risk of development of a gastric cancer in this group was compared with that expected on the basis of gastric-cancer incidence rates for the local population. Carcinomas in the gastric remnant developed in only two of these patients, as compared with an expected 2.6 primary gastric carcinomas (relative risk, 0.8 [95 per cent confidence interval, 0.1 to 2.7]). We conclude that there is no indication for endoscopic surveillance in asymptomatic patients with previous gastric surgery for benign peptic-ulcer disease.

Adult↗
PubMed1983

Capacitation and the acrosome reaction in guinea pig spermatozoa increase the availability of surface aminophospholipids for labelling by trinitrobenzene sulphonate.

Guinea pig spermatozoa isolated from the epididymis were capacitated by incubation in phosphate buffered saline at 37 degrees C for 5h. and the acrosome reaction induced by addition of calcium chloride (10mM). There was no significant difference between the phospholipid compositions of freshly prepared, capacitated or acrosome reacted spermatozoa. However, the % of the aminophospholipids available to trinitrobenzene sulphonate in the external medium was increased significantly in capacitated and acrosome reacted spermatozoa compared with freshly isolated spermatozoa. These observations are consistent with the morphological observations of others and suggest that on capacitation there is a change in the arrangement of phospholipids in the plasma membrane of spermatozoa to increase the concentration of fusogenic phospholipids in the outer leaflet.

Acrosome↗
PubMed1982

Asymmetric distribution of phosphatidylethanolamine in the endoplasmic reticulum demonstrated using trinitrobenzenesulphonic acid as a probe.

At pH 7.4 approximately one third of the phosphatidylethanolamine (PE) of rat liver microsomes is labelled by trinitrobenzenesulphonic acid (TNBS). The same fraction of the PE was labelled, when a fixed concentration of microsomes were incubated with concentrations of TNBS from 1.5 mM to 12 mM, or when the TNBS concentration was fixed at 3.0 mM and the microsomal protein varied between 1.2 and 12.0 mg. Microsomes incubated with TNBS remain closed indicated by retention of mannose-6-phosphatase latency, retention of labelled vesicular contents and by the appearance of the vesicles in the electron microscope. When the microsomal vesicles were opened by alkaline pH or after passage through the French pressure cell the % of PE labelled increased up to 90% of the total. The small % remaining unlabelled may be due to some vesicles remaining closed or to steric hindrance by the relatively bulky label on both phospholipid and protein. Phospholipase C hydrolyses approximately one third of the PE in closed microsomal vesicles. After treatment of microsomes with phospholipase C the % PE available for labelling by TNBS decreased and was inversely proportional to the % PE hydrolysed. These results suggest that the same pool of PE is available for either hydrolysis by phospholipase C or for labelling by TNBS, and that this pool is that of the outer leaflet of the microsomal membrane bilayer.

Animals↗
PubMed1982

Asymmetric synthesis followed by transmembrane movement of phosphatidylethanolamine in rat liver endoplasmic reticulum.

Studies with phospholipase C have indicated that two-thirds of the phosphatidylethanolamine of rat liver endoplasmic reticulum is located in the inner leaflet of the membrane bilayer. Phosphatidyl[14C]]ethanolamine is synthesised in microsomes incubated with CDP[14C]ethanolamine. Using phospholipase C as a probe we have observed that the labelled phospholipid is initially (1-2 min) concentrated in the "outer leaflet' of the membrane bilayer. The specific activity of this pool of phosphatidylethanolamine was 3.5 times that of the inner leaflet. If, however, the microsomes were opened with 0.4% taurocholate or the French pressure cell to make both sides of the bilayer available to phospholipase C, the phosphatidylethanolamine behaves as a single pool for hydrolysis. On longer incubation, up to 30 min, with CDP[14 C]ethanolamine the specific activity of the outer leaflet phosphatidylethanolamine becomes close to that of the inner leaflet. In chase experiments, in which microsomal phosphatidylethanolamine was labelled by incubation with CDP[14 C]ethanolamine for 1 min, the reaction stopped by addition of calcium, and the microsomes isolated by centrifugation and reincubated, labelled phosphatidylethanolamine was transferred from the "outer leaflet' to the "inner leaflet', so that both were equally labelled. These observations suggest that phosphatidylethanolamine is synthesised at the cytoplasmic leaflet of the endoplasmic reticulum and subsequently transferred across the membrane to the cisternal leaflet of the bilayer. Transmembrane movement is apparently temperature-dependent and independent of continued synthesis of phosphatidylethanolamine.

Animals↗
PubMed1982

The contribution of electron microscopic cytochemistry to an understanding of the biogenesis of the endoplasmic reticulum of rat hepatocytes.

The endoplasmic reticulum has the enzymic machinery for the synthesis of both protein and phospholipid and hence plays a central role in its own biogenesis and that of other cellular membranes. The evidence available concerning the biogenesis of the phospholipid bilayer of the endoplasmic reticulum, particularly from the application of the structural cytochemical methods for the localization of acyltransferases, is reviewed. The observations are consistent with a model in which phospholipid is synthesized in situ at the site of membrane growth. Synthesis is asymmetric, with most enzymes located at the cytoplasmic side of the membrane, and controlled transmembrane movement of phospholipid results in an asymmetric bilayer.

Acyltransferases↗
PubMed1982

Fine-structural changes in rat liver microsomes treated with phospholipase C.

Phospholipase C hydrolyses 50% of the phospholipids of rat liver microsomes. Our previous observations suggest that the hydrolysis is of the outer leaflet of the membrane bilayer. In the present investigation the products of hydrolysis and effect of phospholipase C treatment on the morphology of total, rough and smooth microsomes were investigated. The only product of phospholipase C treatment of microsomes was diglyceride. After hydrolysis of half the phospholipid, the microsomes retained their vesicular structure; however, the average diameter of total and smooth microsomes was reduced by approximately half, and that of rough microsomes by a third. Profiles were observed that suggested that small vesicles may form by pinching off from large vesicles. About 10-15% of the phospholipase-treated microsomes had associated with them an amorphous droplet yielding a 'signet-ring'-like structure. The rest of the vesicle membrane retained a bilayer structure. About 10-15% of the treated vesicles adhered in groups of two or three. In these groups the shared membrane was trilaminar. Freeze-fracture replicas of phospholipase C-treated microsomes exhibited a similar morphology to untreated microsomes having both concave and convex surfaces, the former exhibiting a greater density of intramembranous particles. These observations suggest that microsomal vesicles remain closed after treatment with phospholipase C and that the bilayer structure is retained. However, there are morphological changes that are possibly related to maintaining the stability of the membranes in which the outer leaflet consists essentially of diglyceride.

Animals↗
PubMed1981

Biogenesis of endoplasmic reticulum phosphatidylcholine. Translocation of intermediates across the membrane bilayer during methylation of phosphatidylethanolamine.

Phosphatidylethanolamine of rat liver microsomes is rapidly methylated by S-adenosyl[methyl-14C]methionine to produce phosphatidyl-N-monomethylethanolamine, phosphatidyl-N,N-dimethylethanolamine and phosphatidylcholine. Using phospholipase C as a probe, on both opened (0.4% taurocholate or French pressure cell treatment) and unopened microsomes, it is demonstrated that phosphatidylcholine is labelled in the inner leaflet of the bilayer and, to a greater extent, in the outer leaflet. Phosphatidyl-N,N-dimethylethanolamine is labelled in the outer leaflet and in a pool sequestered from phospholipase C in open and closed vesicles. Phosphatidyl-N-monomethylethanolamine is labelled in a similarly sequestered pool. When microsomes containing labelled phosphatidyl-N-monomethylethanolamine and phosphatidyl-N,N-dimethylethanolamine were incubated with unlabeled S-adenosylmethionine, these phospholipids were methylated to produce phosphatidylcholine in the outer leaflet. This metabolism was inhibited by S-adenosylhomocysteine. Trypsin treatment of unopened microsomes inhibited 95% of the incorporation of 14CH3 into the outer leaflet of the bilayer with no effect on incorporation into sequestered phosphatidyl-N-monomethylethanolamine, phosphatidyl-N,N-dimethylethanolamine and phosphatidylcholine. Therefore, sequestered phosphatidyl-N-monomethylethanolamine and phosphatidyl-N,N-dimethylethanolamine are apparently synthesized by enzymes located at the inner surface of the microsomal membranes. These observations suggest that initial methylation of phosphatidylethanolamine takes place at the inner surface of the microsomes and that phosphatidyl-N-monomethylethanolamine is transferred to the outer leaflet to produce phosphatidylcholine. However, phosphatidyl-N-monomethylethanolamine is also methylated at the inner leaflet to produce phosphatidylcholine which does not equilibrate with that of the outer leaflet. Phosphatidylcholine of both the inner and outer bilayer leaflets is uniformly labelled by injection of [14C]methionine, in vivo.

Animals↗
PubMed1981

Nutritional status of a group of alcoholics before and after admission to an alcoholism treatment unit.

The nutritional status of the alcoholic has been presumed to be less than adequate because of the large quantity of alcohol ingested. Most reports have focused on the derelict alcoholic. In contrast, the patients in this investigation are more representative of the usual alcoholic population. The pretreatment dietary histories of 58 alcoholics were compared with their actual dietary intake while they were hospitalized for the treatment of alcoholism. Comparisons were also made between dietary intake by history and Recommended Dietary Allowances. The mean calorie, protein, fat, and carbohydrate intake of the patients was adequate and was well within the Recommended Dietary Allowances ranges. After the patients stopped drinking, they increased their intake of all major nutrients, especially carbohydrates. A subgroup of 11 patients whose recent dietary intake by history was corroborated by their urinary nitrogen excretion had no change in total caloric intake after they stopped drinking.

Adolescent↗
PubMed1980

Phospholipid asymmetry in rough- and smooth-endoplasmic-reticulum membranes of untreated and phenobarbital-treated rat liver.

Phospholipase C was used as a probe for the distribution of phospholipids about the membrane of rough and smooth microsomal fractions from normal and phenobarbital-treated rat liver. All membranes exhibited an asymmetric distribution, with phosphatidylethanolamine and phosphatidylserine concentrated in the inner leaflet of the bilayer and phosphatidylcholine and sphingomyelin concentrated in the outer leaflet. The only phospholipid showing a significant difference in distribution between fractions was phosphatidylcholine, which was shifted towards the outer leaflet in the smooth microsomal fraction compared with the rough microsomal fraction, and towards the outer leaflet in both rough and smooth microsomal fractions from phenobarbital-treated liver compared with the same preparations from untreated rat liver. Apart from this small change, the asymmetric distribution of phospholipids was conserved in microsomal fractions which had proliferated in response to phenobarbital and in which the protein composition had changed.

Animals↗
PubMed1980

A rapid method for the separation of free and membrane-bound polysomes of rat liver by gel filtration on columns of sepharose 4B.

A rapid method is reported for the separation of free and bound polysomes from total microsomes of rat liver on columns of Sepharose 4B, in which the total procedure from sacrifice of the animal to final preparation takes less than five hours. Both forms of polysomes are active in the incorporation of amino acids into proteins, the free polysomes having approximately twice the activity of bound polysomes. Both preparations contain polysomes at least six ribosomes in length.

Amino Acids↗
PubMed1979

Asymmetry of the site of choline incorporation into phosphatidylcholine of rat liver microsomes.

[14C]Choline was incorporated into microsomal membranes in vivo, and from CDP-[14C]choline in vitro, and the site of incorporation determined by hydrolysis of the outer leaflet of the membrane bilayer using phospholipase C from Clostridium welchii. Labelled phosphatidylcholine was found to be concentrated in the outer leaflet of the membrane bilayer with a specific activity approximately three times that of the inner leaflet. During incorporation of CDP-choline and treatment with phospholipase C the vesicles retained labelled-protein contents indicating that they remained intact. When the microsomes were opened with taurocholate after incorporation of [14C]choline in vivo, the labelled phosphatidylcholine behaved as a single pool. Selective hydrolysis of labelled phosphatidylcholine in intact vesicles is not, therefore, a consequence of specificity of phospholipase C. These results indicate that the phosphatidylcholine of the outer leaflet of the microsomal membrane bilayer is preferentially labelled by the choline-phosphotransferase pathway and that this pool of phospholipid does not equilibrate with that of the inner leaflet.

Animals↗
PubMed1979

Transmural eosinophilic gastroenteritis with ascites.

An atopic patient with recurrent abdominal pain, diarrhea, and ascites was shown to have eosinophilic gastroenteritis. Transmural involvement was inferred from the findings of dense eosinophilic infiltrates in the jejunal mucosa and eosinophilia in the ascitic fluid. An impressive response to steroid treatment occurred. The reported cases of eosinophilic gastroenteritis with ascites are reviewed.

Adult↗
PubMed1977

Asymmetry of the phospholipid bilayer of rat liver endoplasmic reticulum.

The phospholipids of intact microsomal membranes were hydrolysed 50% by phospholipase C of Clostridium welchii, without loss of the secretory protein contents of the vesicle, which are therefore not permeable to the phospholipase. Phospholipids extracted from microsomes and dispersed by sonication were hydrolysed rapidly by phospholipase C-Cl. welchii with the exception of phosphatidylinositol. Assuming that only the phospholipids of the outside of the bilayer of the microsomal membrane are hydrolysed in intact vesicles, the composition of this leaflet was calculated as 84% phosphatidylcholine, 8% phosphatidylethanolamine, 9% sphingomyelin and 4% phosphatidylserine, and that of the inner leaflet 28% phosphatidylcholine, 37% phosphatidylethanolamine, 6% phosphatidylserine and 5% sphingomyelin. Microsomal vesicles were opened and their contents released in part by incubation with deoxycholate (0.098%) lysophosphatidycholine (0.005%) or treatment with the French pressure cell. Under these conditions, hydrolysis of the phospholipids by phospholipase C-Cl. welchii was increased and this was mainly due to increased hydrolysis of those phospholipids assigned to the inner leaflet of the bilayer, phosphatidylethanolamine and phosphatidylserine. Phospholipase A2 of bee venom and phospholipase C of Bacillus cereus caused rapid loss of vesicle contents and complete hydrolysis of the membrane phospholipids, with the exception of sphinogomyelin which is not hydrolysed by the former enzyme.

Animals↗
PubMed1976

Heterogeneity of phospholipid synthesis in rat liver endoplasmic reticulum during proliferation of smooth membranes.

During proliferation of smooth endoplasmic reticulum (SER) induced by phenobarbital the specific activity of acyltransferases of the smooth microsomes increases, there is a transient rise in the phospholipid/protein ratio of these membranes, and an increased incorporation of [14C]glycerol into smooth-membrane phospholipid. Microsomes separated into subfractions on 2 gradients exhibited a heterogeneous distribution of these characteristics, indicating a non-uniform distribution of the site of phospholipid synthesis in the ER under these conditions. Cytochemical localization of acyltransferases on whole liver and smooth and rough microsomes confirmed this heterogeneity, and indicated that the distribution of this activity was not restricted to any morphologically distinct site in the ER of the intact cell. After 4 days of phenobarbital treatment the increased membrane is restricted to lighter subfractions and is similar in distribution to that of increased acyltransferase activity. These results indicate that the synthesis of membrane phospholipid and the growth of the SER in response to phenobarbital is not uniform but occurs at randomly dispersed sites in the SER while proteins may be added preferentially at these sites resulting in a final uniform distribution.

Acyltransferases↗