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Biomedical subjects

T J Peters

Publications and source records attributed to T J Peters.

At least 235 records · Page 13Linked to original sources
PubMed1995

Activity and subcellular distribution of phosphatidate phosphohydrolase (EC 3.1.3.4) in alcoholic liver disease.

A micromethod was developed to assay the hepatic activity and subcellular distribution of phosphatidate phosphohydrolase (PAH, EC 3.1.3.4), an important regulatory enzyme in triacylglycerol synthesis, in human needle biopsy specimens. In normal liver PAH is predominantly cytosolic in distribution, but on treatment with oleic acid it shifts to the membranous compartments of the cell, its physiologically active site. The hepatic specific activity of PAH was similar in controls and patients with fatty liver but significantly more of the enzyme was associated with the membranous compartments in patients with severe alcoholic fatty liver. These observations may explain the enhanced rates of triacylglycerol synthesis observed in these patients and may be implicated in the pathogenesis of alcoholic fatty liver.

Adult↗
PubMed1994

Effect of alcohol on the activity and subcellular distribution of phosphatidate phosphohydrolase in rat liver.

The activity and subcellular distribution, before and after translocation with oleic acid, of hepatic phosphatidate phosphohydrolase (PAH: E.C.3.1.3.4) was measured following acute and chronic administration of ethanol with either 18% or 4.4% total calories as fat, to male Wistar rats. Acute injection produced a significant increase in PAH activity, without affecting the subcellular distribution or translocation of activity from the cytosol into the membraneous compartments induced by oleic acid. PAH activity, subcellular distribution and the translocation of activity by oleic acid was similar in all groups following chronic liquid feeding. Chronic ethanol feeding was associated with significantly increased plasma corticosterone in the ethanol-fed rats compared with controls, independent of the fat content of the diet. Plasma insulin was similar in chronic alcohol fed rats and controls. This suggests that enhanced PAH activity may contribute to triacylglycerol accumulation following acute alcohol injection, but activity normalises as hepatic lipid accumulation progresses and this effect is not due to attenuation of the hormonal effects of ethanol.

Animals↗
PubMed1994

Further characterisation of forms of haemosiderin in iron-overloaded tissues.

The biochemical and biophysical properties of isolated haemosiderins have been compared to that of another iron-containing protein, termed prehaemosiderin, which sediments through chaotropic potassium iodide only after 20 h of ultracentrifugation, in contrast to that of haemosiderin which is recovered after 2 h of ultracentrifugation. The iron/protein ratio and iron/phosphate ratio were less that that of the corresponding haemosiderin, while the elemental composition was also reduced in many of the prehaemosiderin samples. Mossbauer spectroscopy and electron diffraction identified the predominant presence of ferrihydrite in prehaemosiderin species even though the secondary haemochromatosis haemosiderin iron cores were essentially goethite-like. The majority of the prehaemosiderins isolated showed the presence of an additional peptide band at 17 kDa in addition to that at 21 kDa. Further Mossbauer studies of haemosiderin isolated from untreated secondary haemochromatosis patients showed that goethite was the predominant form of iron present, thereby indicating that the presence of this form of ferrihydrite was not wholly attributable to chelation therapy.

Animals↗
PubMed1994

Control of cellular iron homeostasis by iron-responsive elements in vivo.

It has recently been proposed that cellular iron homeostasis in mammalian cells is regulated at the post-transcriptional level by the reciprocal control of transferrin receptor and ferritin mRNA expression via an iron-regulatory factor. This iron-regulatory factor has been shown to be a cytoplasmic aconitase which can bind to iron-responsive elements in the corresponding mRNAs with greater or lesser affinity as a function of the iron status of the cell. In the present study, we show that in vivo the affinity of iron-regulatory factor for iron-responsive elements in liver reflects the long-term iron status of the tissue in animal models for iron overloading and iron deficiency, when combined with altered transferrin saturation and serum iron levels. In contrast hepatic iron overload achieved without altering such haematopoeitic indices, had a less pronounced effect. In both spleen and heart, the affinities of iron-regulatory factor changed in parallel with both altered iron status and haematological markers. In brain and duodenum, there were no consistent changes in iron-regulatory-factor activity with iron loading or depletion. Iron-regulatory-factor activity in kidney responded in an as yet unexplained manner.

Animals↗
PubMed1994

Alcoholic muscle disease: features and mechanisms.

Approximately 50 per cent of all chronic alcohol misusers have alcoholic muscle disease. Chronic alcoholic skeletal muscle myopathy is characterized by a selective atrophy of type II fibres, so that up to 20 per cent of the entire skeletal musculature is lost. The pathogenetic mechanism for the myopathy is currently unknown but a model has been described in which various anatomically-distinct skeletal muscles are employed to reflect type I and II fibres, i.e. the soleus and plantaris, respectively. In chronic studies, rats were fed nutritionally complete liquid diets containing either ethanol or glucose (controls) for up to 6 weeks. In acute studies, rats were given single boluses of ethanol and rates of protein synthesis were examined at 2.5 h. The results show that the myopathy is due to defective skeletal muscle protein synthesis. The information gained from these studies enhances our understanding of skeletal muscle diseases characterized by preferential effects on anaerobic fibres and should be applicable to disease processes in other toxic or metabolic myopathies.

Adult↗
PubMed1994

Alcohol and acetaldehyde dehydrogenase gene polymorphism and alcoholism.

Inherited variations in alcohol and aldehyde dehydrogenases, the principal enzymes of ethanol metabolism, have been implicated in determining susceptibility to alcoholism and alcohol-related organ damage. An association between an RFLP for the alcohol dehydrogenase-2 (ADH2) gene and alcohol-induced liver damage was demonstrated in a Caucasian population. Genotyping studies revealed an increase in the ADH3(2) allele in patients with alcohol-induced cirrhosis. PCR studies of the ALDH5 gene have demonstrated diverse polymorphism within a short segment of its coding region, with marked inter-racial variation in allele frequencies. In addition, the Caucasian alcohol-induced flushing reaction has been characterised and its relationship with phenotypic polymorphism of ALDH1 examined.

Alcohol Dehydrogenase↗
PubMed1994

Serum carnosinase activities in central nervous system disorders.

Serum carnosinase activity was assayed in five groups of patients with neurological disorders. Enzyme activities in patients with idiopathic epilepsy (mean +/- S.E.M., 148 +/- 11 nmol/ml per min) and motor neurone disease (155 +/- 15 nmol/ml per min) were similar to the control group (161 +/- 7 nmol/ml per min). Reduced serum carnosinase activity was observed in patients with Parkinson's disease (109 +/- 11 nmol/ml per min, P < 0.005), multiple sclerosis (82.5 +/- 10.0 nmol/ml per min, P < 0.005) and patients following a cerebrovascular accident (74.6 +/- 5.4 nmol/ml per min, P < 0.001) compared with the control group. Carnosinase activity, 5-10% of that found in serum, was detected in CSF samples. The cause of reduced serum carnosinase activities in central nervous system disorders is unclear, although anoxic damage to carnosinase-producing cells or disruption of the blood-brain barrier may be responsible.

Adult↗
PubMed1994

Risk factors for giardiasis: a case-control study in Avon and Somerset.

Giardia lamblia is a common and increasing cause of gastrointestinal illness in the UK. We report a case-control study that examined risk factors for giardiasis. Patients with giardiasis were identified from reports to the Consultants in Communicable Disease in Avon and Somerset, and age-sex matched controls were obtained from their general practitioners' lists. Details of travel history, water consumption and recreational water use were collected by postal questionnaire. Over the period July 1992 to May 1993, 74 cases and 108 matched controls were obtained. The data were analysed using conditional logistic regression. Swimming appeared to be an independent risk factor for giardiasis (odds ratio 2.4, 95% CI 1.0 to 6.1, P = 0.050). Travel (P = 0.001), particularly to developing countries, and type of travel (P = 0.004)--that is, camping, caravanning or staying in holiday chalets--were also observed to be significant risk factors. Other recreational water use and drinking potentially contaminated water were found to be not statistically significant after adjustment for other factors.

Adolescent↗
PubMed1994

Fatty acid synthesis by rat liver after chronic ethanol feeding with a low-fat diet.

1. Chronic alcohol feeding with a low-fat diet (4.4% total calories) produced a two- to three-fold increase in hepatic triacylglycerol and esterified cholesterol compared with pair-fed low-fat diet controls. Plasma lipids were similar in both groups. 2. Hepatic fatty acid synthesis rates measured in vivo with 3H2O were significantly lower in the alcohol-fed animals than in controls. Activities of hepatic fatty acid synthase (EC 2.3.1.85) and acetyl-CoA carboxylase (EC 6.4.1.2) were reduced in the alcohol-fed rats. 3. These results indicate that enhanced hepatic fatty acid synthesis does not occur in rats fed alcohol and a low-fat diet for 4 weeks, and is thus not implicated in the pathogenesis of alcohol-induced fatty liver.

Acetyl-CoA Carboxylase↗
PubMed1994

Upper respiratory tract illnesses and accidents.

Anecdotal accounts suggest that colds and influenza may increase human error. This view is supported by laboratory studies of the effects of upper respiratory tract illnesses (URTIs) on performance efficiency, which have shown that both experimentally induced and naturally occurring URTIs reduce aspects of performance efficiency. The present research examined the relationship between accidents and URTIs by studying 923 patients attending an Accident and Emergency department at a time of year when upper respiratory tract viruses were circulating. The results revealed no significant associations between URTIs and workplace accidents, and, similarly, no significant associations emerged when all accidents were compared with other attenders. The only effect which was close to statistical significance was a protective effect of influenza against workplace accidents, which could be explained in terms of a person with influenza or who has recently had influenza being less likely to work and therefore less likely to be at risk of experiencing a workplace accident. Further research must examine this topic with different methodologies, such as selecting controls from fellow workers of the index case, and these studies will provide us with a clearer view as to whether or not there is an association between URTIs and workplace accidents.

Accidents, Occupational↗
PubMed1994

Alcohol: the drug.

The purpose of this chapter is to bring together some of the recent research that has significantly increased our knowledge of the mechanisms underlying the actions of alcohol in the body, including absorption and metabolism. One particular field of growth is that of the actions of alcohol in the brain. In the past few years there have been a number of important advances in our understanding of the mechanisms by which alcohol produces sedation, intoxication and pleasure as well as those processes which contribute to its addictive properties. Progress has also been made in unravelling the mechanisms of tolerance and physical withdrawal and these studies have also thrown light on the basis of the neurotoxic effects of alcohol. Similarly in the periphery new ideas about the toxic tissue damaging properties of alcohol have been developed.

Biogenic Monoamines↗
PubMed1994

Chronic alcoholic myopathy: transcription and translational alterations.

Alcoholic myopathy is characterized by selective atrophy of type II fibers and affected subjects lose up to 20% of the entire musculature. Between one- and two-thirds of all alcohol abusers are affected. In acute studies, defective rates of translation occur and type II fiber-predominant muscles are more adversely affected than type I fiber-predominant muscles. Furthermore, acetaldehyde is also a potent modulator of translation, and contractile and noncontractile proteins are affected equally. In chronic ethanol feeding there is rapid and sustained loss of ribosomal RNA. Recent attention has focused on the observation that total messenger RNA (mRNA) falls after ethanol consumption, but mRNA for specific myofibrillary contractile proteins are unaffected, implicating a role for translational modifications in the initial stages of the myopathy. Clinical studies have also shown that chronic alcohol abusers have defective rates of muscle protein synthesis and whole-body protein metabolism. The modulations in transcription and translation are not mediated by availability of amino acids, the effects of endocrine dysfunction (cortisol and growth hormone), liver impairment, or malnutrition. Free radicals, however, may be contributory mediators. Receptor-mediated events and the putative roles of growth factors are generally unexplored, though a distinguishing feature of acute ethanol administration is a reduction in circulating IGF-I. Thus, ethanol may act directly on muscle, although other concordant processes may coexist.

Alcoholism↗
PubMed1994

Intestinal iron absorption studies in mouse models of iron-overload.

Three mouse strains have been evaluated as suitable models for investigations into the pathogenesis of iron-overload syndromes. Mice with hereditary heterozygous alpha-thalassaemia had moderately raised reticulocyte counts, but were not anaemic and showed little, if any, iron loading. In contrast, mice with homozygous beta-thalassaemia showed microcytic anaemia, reticulocytosis and splenomegaly. Iron-loading was marked, progressive with age and mainly confined to the spleen. Liver iron-loading increased until the age of 7-8 weeks, with no further increase over successive weeks. Although intestinal iron absorption was modestly increased due to enhanced mucosal uptake, the majority of the 'excess' liver and spleen iron could be accounted for by re-distribution of iron from the erythrocytic compartment. Homozygous hypotransferrinaemic mice, with approximately 1-2% of normal plasma transferrin levels, were markedly anaemic with hypochromic microcytic erythrocytes. Intestinal iron absorption increased 3-4-fold (predominantly due to changes in mucosal transfer), as compared to wild-type controls and heterozygotes, and was ascertained to be a major factor causing the marked hepatic iron overload. Heterozygous hypotransferrinamic mice, with over half normal plasma transferrin levels and a mild degree of hepatic iron loading, showed very similar characteristics to wild-type controls. Thus, of the three models, hpx/hpx mice showed the greatest enhancement in intestinal iron absorption and net iron-loading and provides a suitable animal model of spontaneous iron-overload. Comparison of iron absorption values between the models suggests that reticulocytes cannot account for the enhanced absorption seen in the hpx/hpx mice.

Animals↗
PubMed1994

Urinary symptoms in the community: how bothersome are they?

OBJECTIVES: To measure the level of reported urinary symptoms presumed to be associated with benign prostatic hyperplasia (BPH) among men aged 40 years and over in the community, and to assess how bothersome these symptoms are perceived to be. SUBJECTS AND METHODS: All ambulant men aged 40 years and over who were registered in a general practice (703) were invited to attend the health centre to complete a questionnaire containing the Maine prostatectomy scale and the International Continence Society-BPH questionnaire, and to undergo uroflowmetry. RESULTS: The prevalence of symptomatic BPH (as defined by a numerical score > or = 11 on the Maine score, a urinary peak flow of < 15 ml/s, and failure to void > or = 150 ml on three separate occasions) was 284/1000 for men aged 40 years and over. This prevalence increased from 179/1000 in men aged 40-49 to 500/1000 in men aged 70 years and over. The most commonly reported symptoms were those typically associated with BPH (terminal dribble, hesitancy, intermittency, urgency). The symptoms that caused men the greatest degree of bother were frequency, nocturia and those causing incontinence or social embarrassment. CONCLUSION: The high prevalence of urinary symptoms assumed to be related to BPH in men in the community does not necessarily suggest that these men will require treatment. Common symptoms, typically associated with BPH, were tolerated. Further research is required to investigate the natural history of urinary symptoms, the relationships between symptoms and bladder outflow obstruction secondary to BPH, and to determine the most appropriate management for men in the community, ranging from 'watchful waiting' (monitoring without treatment) to medical or surgical treatment.

Adult↗
PubMed1994

Enhancement of ethanol induced rectal mucosal hyper regeneration with age in F344 rats.

Experimental studies in rats have shown an independent stimulation of rectal cell turnover by either chronic ethanol consumption or age. In this study the combined effect of these two factors on colorectal cell regeneration has been investigated. Ninety male F344 rats aged 2, 12, and 22 months were pair fed nutritionally adequate liquid diets containing 36% of total energy either as ethanol or isoenergetic carbohydrates. After four weeks of feeding, colorectal crypt cell production rates were measured using a stathmokinetic technique with vincristine. While age by itself did not affect colorectal cell renewal, chronic ethanol consumption stimulated rectal, but not colonic crypt cell production rate in an age dependent manner. While no significant effect of ethanol was noted in young animals, cell proliferation was significantly enhanced in middle aged animals by 81% (4.1 (2.7-5.5) v 7.4 (6.0-8.7) cells/crypt/hour, p < 0.001) and in old animals by 138% (4.5 (3.3-5.6) v 10.7 (8.9-12.4) cells/crypt/hour, p < 0.001) after ethanol ingestion. Because acetaldehyde, the first and most toxic metabolite of ethanol, has been detected in the colorectal mucosa and may lead to tissue injury influencing cell regeneration, acetaldehyde concentrations have been measured in the colons of 15 male F344 rats of various ages after an acute intraperitoneal dose of ethanol (2.5 g/kg bodyweight). There was a significant positive correlation between crypt cell production rate and acetaldehyde concentrations measured in the distal and proximal colon after an acute dose of ethanol (r = 0.5955, p < 0.005). These data clearly show that the ethanol mediated stimulation of cell regeneration in the rectum is age dependent. As reported earlier, there was found indirect evidence that acetaldehyde participates in the pathogenesis of rectal hyperregeneration after chronic alcohol consumption. This hyperregeneration of the rectal mucosa after alcohol drinking could by itself favour carcinogenesis, which is especially relevant in old age.

Acetaldehyde↗