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Biomedical subjects

O F James

Publications and source records attributed to O F James.

At least 109 records · Page 6Linked to original sources
PubMed1992

Bacterial contamination of the small bowel in elderly people: is it necessarily pathological?

Bacterial contamination of the small bowel is probably the commonest cause of occult malabsorption in the elderly. It may occur in patients without a 'blind loop' or suggestive symptoms of diarrhoea and weight loss. We have prospectively studied the apparent prevalence of presumed bacterial contamination of the small bowel and its effect on nutritional state. Subjects were divided into three groups: (A) 54 young fit subjects; (B) 103 fit community elderly subjects; (C) 73 elderly long-stay hospital patients. All subjects had simultaneous lactulose hydrogen breath test and 14C-glycocholic acid breath test. Nutritional state was assessed by anthropometry, haematology and biochemistry. There were significantly fewer positive 14C-glycocholic acid breath tests in the young than in the elderly subjects (3% vs. 20% and 17%, p less than 0.0001) but no difference in the number of positive hydrogen breath tests between groups. There was no association between positive breath tests and anthropometry, haematology and biochemistry except for a lower albumin in group B and a lower red blood cell folate in group C with positive breath tests. These abnormal breath tests indicate that bacterial contamination of the small bowel may be common in normal fit elderly people and in elderly long-stay hospital patients and may be a concomitant of 'normal' ageing, not necessarily leading to ill-health.

Adult↗
PubMed1992

The association of age with the activity of alcohol dehydrogenase in human liver.

Ethanol is principally oxidized in the liver by the cytosolic enzyme alcohol dehydrogenase (ADH). We have examined the effect of age and sex on alcohol dehydrogenase activities in human liver obtained from 16 healthy subjects, age range 45-88 years. There was no correlation between ADH activity, whether expressed as activity per mg cytosolic protein or per gram wet weight liver, and age. Activities were similar in men and women. These results suggest that, in common with activities of other hepatic drug metabolizing enzymes, age has no effect upon the activity of ADH in human liver.

Aged↗
PubMed1992

Light microscopic and ultrastructural distribution of type VI collagen in human liver: alterations in chronic biliary disease.

We have investigated the distribution of type VI collagen in normal human liver obtained from cadaveric renal transplant donors, using a peroxidase-antiperoxidase method for light microscopic visualization, and an immunogold labelling method for ultrastructural localization. The distribution was compared with that of the more abundant interstitial collagen type III, using antibodies to amino terminal procollagen type III. Staining for type VI collagen was identified in Glisson's capsule, in portal tract stroma and within the space of Disse. Perisinusoidal staining showed intra-acinar heterogeneity with the intensity in acinar zones 2 and 3 being greater than in zone 1. Type III collagen was also found in the space of Disse although no significant intra-acinar variation in staining intensity was noted. Immuno-gold labelling for type VI collagen was demonstrated on amorphous or microfilamentous material lying between, and occasionally appearing to interconnect, cross-striated collagen fibrils, whereas labelling for amino terminal procollagen type III was exclusively on fibrils. Intracellular staining for type VI collagen was noted in perisinusoidal (lto) cells. These results confirm that type VI collagen is a ubiquitous constituent of the normal hepatic extracellular matrix and suggest that it may be synthesized by perisinusoidal (lto) cells. The distribution of type VI collagen was also studied in biopsy material from patients with different histological stages of primary biliary cirrhosis. Intense staining was noted around proliferating bile ductules within developing fibrous septa and in established septa of cirrhotic liver. These observations indicate that this 'minor' matrix component may play an important role in hepatic fibrogenesis.

Chronic Disease↗
PubMed1992

Ageing and duodenal morphometry.

Small bowel morphometry was studied in 25 subjects under the age of 70 years and 22 over the age of 70. There was no evidence of malabsorption or malnutrition in either group. Two distal duodenal endoscopic biopsy specimens were examined morphometrically. There were no significant correlations between age and areas of duodenal surface epithelium, crypts and lamina propria, heights of villi and surface epithelium, depth of crypts, crypt to villus ratio, number of intraepithelial lymphocytes, duodenal architecture, enterocytes, brush border and Brunner glands. Contrary to previous reports there was no evidence for a significant effect of age on proximal small bowel morphometry.

Aged↗
PubMed1992

Snoring increases the risk of stroke and adversely affects prognosis.

In a case-controlled study we recruited 400 patients admitted to hospital with stroke and 400 community controls matched for age, gender and family practitioner. Snoring history was obtained from 326 patients and 345 controls. Odds ratio for admission to hospital with stroke was 3.2 (95 per cent confidence intervals 2.3-4.4) for regular snorers against those who did not snore regularly. This risk was independent for age, gender and other risk factors for stroke. Snoring did not increase the chances of stroke during sleep. Level of consciousness was reduced more frequently in snorers (p = 0.0003). As the frequency of snoring increased so did the mortality to 6 months (p = 0.0006). Snoring is an important risk factor for stroke and adversely affects the prognosis in patients admitted to hospital with stroke.

Adult↗
PubMed1991

Erythrocyte sodium, potassium and sodium fluxes with cell and subject ageing.

In young subjects erythrocyte sodium was lower in females than in males. In males juvenile erythrocyte sodium decreased with subject age whereas in females aged erythrocyte sodium increased with subject age. Therefore, the difference in erythrocyte sodium between young male and female subjects was not observed in the elderly. These differences in erythrocyte sodium appeared to be mainly due to differences in the sodium pump rate constant. In juvenile cells from young subjects the sodium pump rate constant was related to the ouabain sensitive sodium flux rate, but not in elderly subjects, suggesting disturbed control of cell sodium in the latter group. Juvenile erythrocytes had a higher potassium content in elderly than young subjects but this was mainly in the 'frail' hospitalised elderly and it decreased more rapidly with cell ageing. This could indicate more active erythrocytes entering the blood in elderly subjects and then ageing more rapidly. Differences between young and elderly subjects in erythrocyte sodium, potassium and sodium pump rate constant were more marked in the 'frail' hospitalised elderly.

Adult↗
PubMed1991

Investigation of the role of polymorphisms at the alcohol and aldehyde dehydrogenase loci in genetic predisposition to alcohol-related end-organ damage.

Little is known about factors determining individual susceptibility to the physical complications of alcohol abuse but genetically determined differences in ethanol metabolism may be important. The oxidative metabolism of alcohol is catalyzed by alcohol and aldehyde dehydrogenase. Polymorphisms have been observed at two of the five loci encoding alcohol dehydrogenase subunits: ADH2 (producing three beta subunits) and ADH3 (producing two tau subunits) and also at the locus encoding the metabolically important form of aldehyde dehydrogenase, ALDH2. We have compared ADH2, ADH3 and ALDH2 allele frequencies in patients with alcohol-related cirrhosis (n = 59) and chronic pancreatitis (n = 13) with 79 local healthy control subjects. The different alleles were detected with allele-specific oligonucleotide probes after amplification of leukocyte DNA by the polymerase chain reaction. All patients and all but one control subject were homozygous ADH2*1, encoding the beta 1 subunit. No ADH2*3 alleles were detected. All 34 patients and 39 control subjects tested were homozygous ALDH2*1 encoding the active enzyme. ADH3 allele frequencies were different in patients and control subjects. ADH3*1 frequency: control subjects, 55.1%; cirrhotic patients, 62.7%; chronic pancreatitis patients, 65.4%. The difference between the patient groups combined and the control subjects was significant (p less than 0.05; G-test of Sokal and Rohlf) if it was assumed that the allele frequency in our control population was a reasonable estimate of our local population allele frequency. These results suggest that genetically determined differences in alcohol metabolism may, in part, explain predisposition to alcohol-related end-organ damage.

Alcohol Dehydrogenase↗
PubMed1991

Clarification of the identity of the major M2 autoantigen in primary biliary cirrhosis.

1. In primary biliary cirrhosis, the major M2 autoantigen, reacting with antimitochondrial antibodies in sera from greater than 90% of patients, has been identified as the E2 component of the pyruvate dehydrogenase complex. However, two recent reports suggest that alternative polypeptides may be major autoantigens. 2. The evidence that a 75 kDa subunit of complex I of the respiratory chain is a major autoantigen (Frostell, Mendel-Hartvig, Nelson, Totterman, Bjorkland & Ragan, Scand. J. Immunol. 1988; 28, 157-65) is refuted. The findings of Frostell et al. can be explained by contamination of complex I with the pyruvate dehydrogenase complex, evidence for which is presented here. 3. Inspection of the partial amino acid sequence of an unidentified mitochondrial autoantigen (Muno, Kominami, Ishii, Usui, Saituku, Sakakibara & Namihisa, Hepatology 1990; 11, 16-23) shows that it is the E1 beta-subunit of the pyruvate dehydrogenase complex, previously identified as a major autoantigen, and not a 'new' alternative major autoantigen. 4. These findings substantiate previous work showing that the mitochondrial M2 autoantigens identified so far in primary biliary cirrhosis are all polypeptide components of the pyruvate dehydrogenase complex or the other related 2-oxo acid dehydrogenase complexes.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed1991

Long-term outcome for patients and carers following hospital admission for stroke.

Outcome was assessed in 82 3(+)-year survivors from a cohort of 229 patients admitted to hospital with acute stroke; 71% were independent or only mildly disabled, 76% were living at home. Institutionalized patients were significantly older, less often married, and had more cognitive impairment than those at home. No patient who produced normal picture drawings (house, man, clock) was in institutional care, only two patients living alone had abnormal drawings. Of patients at home 39% had not seen their general practitioner (GP) in the last 6 months. GPs were less likely to see patients who were more severely disabled (p less than 0.05). Targeting of services seemed poor, there was no relationship between level of dependence and level of support from voluntary or statutory services. Forty-four of 49 chief informal carers were also interviewed; 30% showed marked strain. Carers had more problems with emotional reactions, sleep and social isolation than expected.

Acute Disease↗
PubMed1991

Autoantibodies in primary biliary cirrhosis: analysis of reactivity against eukaryotic and prokaryotic 2-oxo acid dehydrogenase complexes.

Six components of the mammalian 2-oxo acid dehydrogenase complexes have previously been identified as M2 autoantigens in primary biliary cirrhosis. In this report, we present data showing that both polypeptide-specific and cross-reacting antibodies are present in patients' sera. Antibodies reacting with E2 of the pyruvate dehydrogenase complex cross-react with protein X but not with any other mammalian antigen. The main immunogenic region on protein X has been localized to within its single lipoyl domain. Polypeptide-specific antibodies bind to E1 alpha and E1 beta of the pyruvate dehydrogenase complex. Antibodies reacting with the E2 polypeptides of the 2-oxoglutarate dehydrogenase complex and branched-chain 2-oxo acid dehydrogenase complex show some cross-reactivity but do not recognize any of the antigens of the pyruvate dehydrogenase complex. Antibodies against the E2 component of the mammalian pyruvate dehydrogenase complex cross-react effectively with the corresponding protein from yeast but not with E2 from Escherichia coli. Antibody titer against mammalian antigens is significantly higher than against the bacterial antigens, arguing against a bacterial origin for primary biliary cirrhosis.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed1990

Low prevalence of antibody to hepatitis C virus in north east England.

The prevalence of antibodies to hepatitis C virus (anti-HCV) was studied in North East England in blood donors, local multiply transfused patients, local high risk individuals, and chronic liver disease patients. Anti-HCV was detected by enzyme-linked immunosorbent assay (ELISA) in 2/1120 (0.18%) blood donors; 1/84 chronic renal failure patients on haemodialysis who had received 1,992 units of blood (seroconversion rate of 0.05% per unit transfused), 1/207 cardiac patients 6 months post cardiac surgery transfused with 1,403 units of blood (1 anti-HCV pre-operatively, seroconversion rate 0.07%), 40/50 haemophilia A patients treated with commercial factor VIII, and 38/100 intravenous drug users. In addition anti-HCV was detected by ELISA in 5/35 cryptogenic chronic liver disease patients, 5/5 confirmed by recombinant immunoblot assay (RIBA) (14%); 3/30 patients with autoimmune chronic active hepatitis, 2/3 by RIBA (7%); 2/50 primary biliary cirrhosis patients, 1/2 by RIBA (2%); 0/30 alcoholic cirrhosis patients; and 2/9 patients with hepatocellular carcinoma, 1/2 by RIBA (11%). HCV is uncommon in North East England; it may be implicated in the aetiology of a minority of cases of cryptogenic liver disease and less than 5% of autoimmune chronic active hepatitis and primary biliary cirrhosis.

Factor VIII↗
PubMed1990

Primary biliary cirrhosis. Quantitation of autoantibodies to purified mitochondrial enzymes and correlation with disease progression.

Primary biliary cirrhosis is characterized by the presence of antimitochondrial antibodies. Recently, six of the autoantigens have been identified as components of the 2-oxo acid dehydrogenase multienzyme complexes located within mammalian mitochondria. Immunoblotting studies have shown that two of these components, namely E2 and protein X of pyruvate dehydrogenase complex, are the major antigenic polypeptides recognized by autoantibodies. This study shows the development of an enzyme-linked immunosorbent assay to detect and quantitate antibodies to these two purified antigens. Coded serum samples from 166 patients with primary biliary cirrhosis, 140 patients with other liver and/or autoimmune disease, and 52 normal women were analyzed for reactivity using this immunoassay. These results indicate that this rapid, simple method has a 93% sensitivity and 96% specificity in the diagnosis of primary biliary cirrhosis. The titer of immunoglobulin G autoantibodies correlated not only with antimitochondrial antibody titer measured by indirect immunofluorescence (P less than 0.0001) but also with histological stage of disease (P less than 0.04) and prognostic biochemical variables such as higher serum bilirubin and lower serum albumin levels (P = 0.038 and 0.028, respectively). There was no significant correlation between titer of autoantibodies and serum globulin or immunoglobulin G levels, indicating that the positive correlation with disease progression was not secondary to hypergammaglobulinemia.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed1990

Symptom development and prognosis in primary biliary cirrhosis: a study in two centers.

The prognosis of patients with asymptomatic primary biliary cirrhosis has been uncertain. Cases of primary biliary cirrhosis in 95 patients from two centers are presented: 70 patients from a regional referral center (Freeman Hospital, FH) and 25 from an international tertiary referral center (King's College Hospital, KCH) with similar mean age at diagnosis and duration of follow-up (median, 12 months). During follow-up, 19 of 70 FH patients and 15 of 25 KCH patients developed symptoms (P less than 0.001); the mean time to symptom appearance was 43 months at FH and 35 months at KCH (P = 0.0012). Twenty-five of 95 patients died, 15 of 34 subjects who had developed symptoms (all liver-related deaths) and 10 of 61 who remained asymptomatic (all non-liver-related deaths) (P less than 0.001). Hepatic mortality was worse than among the normal population (P less than 0.05). A comparison of those patients developing symptoms with 111 at FH and 165 at KCH who presented with symptoms suggests no difference in survival once hepatic symptoms appear. In both centers, hepatic mortality was strongly related to symptom appearance in asymptomatic primary biliary cirrhosis: patients developing symptoms resemble those with symptoms at presentation. Other differences between the centers may reflect different referral patterns.

Adult↗
PubMed1990

Polymerase chain reaction for detection of the alpha-1-antitrypsin Z allele in chronic liver disease.

The genetic locus for alpha-1-antitrypsin (alpha-AT) is highly polymorphic, but all protein variants are encoded by a single locus on chromosome 14. Periportal hepatocyte granules are described in association with chronic liver disease and the Z variant. A Z-specific point mutation in exon V of the alpha-AT gene, converting amino acid 342 from Glu to Lys, is thought to be responsible for the hepatocyte accumulation. We describe the use of the polymerase chain reaction (PCR) to amplify exon V of the alpha-AT gene and subsequent detection of the wild-type M- and Z-specific sequences by hybridisation to 32P-labelled-allele-specific oligonucleotides. We applied this technique to leucocyte DNA from 37 patients with suspected chronic liver disease, 25 of whom had hepatocyte alpha-AT inclusion granules on liver biopsy. All 25 were homozygous or heterozygous for the Z allele. One patient, phenotyped as PiS, was found to be PiSZ and another phenotyped as PiZ (presumed homozygous), was found to be a Z heterozygote. No Z allele was detected in any of the twelve patients without alpha-AT inclusion granules. This sensitive PCR technique could be used to assess the relative risk of chronic liver disease in PiZ heterozygotes and to determine whether individuals without the Z amino acid 342 substitution can developed periportal alpha-AT granules.

Alleles↗
PubMed1990

Effects of age and gender on in vitro properties of human liver microsomal monooxygenases.

Aging in humans is associated with marked declines in the disposition of numerous drugs and other xenobiotics that require hepatic biotransformation before elimination. Considerable pharmacokinetic evidence in humans, coupled with data on in vitro liver microsomal monooxygenase functions generated in inbred male rodent models, has implicated impaired liver phase I drug metabolism (i.e., diminished efficacy of microsomal monooxygenases) in reduced drug clearance in the elderly. This study (1) assessed the in vitro activities and amounts of liver microsomal monooxygenases as a function of donor age and gender in healthy humans and (2) provides the most extensive and comprehensive data to date demonstrating the absence of significant age- and gender-dependent differences in the activities and contents of human liver monooxygenases.

Adolescent↗
PubMed1990

Blood pressure, heart rate and neuroendocrine responses to a high carbohydrate and a high fat meal in healthy young subjects.

1. The responses of blood pressure, heart rate, autonomic function and plasma insulin to a high carbohydrate and a high fat meal of equivalent energy value were studied in nine young volunteers. 2. Neither meal produced a significant change in supine or erect blood pressure. The high carbohydrate meal, however, resulted in an overall rise in both supine (6 beats/min) and erect (6 beats/min; P less than 0.05) heart rate, no such changes being seen after the high fat meal. 3. Plasma noradrenaline levels increased by a maximum of 126% at 90 min (0.98 to 2.22 nmol/l) after the high carbohydrate meal but were virtually unchanged after the high fat meal (P less than 0.01). Parasympathetic function showed no between-meal differences. Plasma insulin and glucose levels were significantly higher after the high carbohydrate meal than after the high fat meal. No postprandial difference in packed cell volume was found between meal types. 4. We conclude that, in young subjects, the postprandial blood pressure after a high carbohydrate meal is maintained by an increase in heart rate associated with increased sympathetic nervous system activity. These changes are at variance with the blood pressure and heart rate responses seen in the elderly after a high carbohydrate meal. A high fat meal has no significant cardiovascular or neuroendocrine effects in the young or old. The nutrient composition of meals has to be taken into account when studying the postprandial cardiovascular and neuroendocrine responses in the young.

Adult↗