bluuebunny/crossref_metadata_2025_split huggingface dataset:
Working Capacity and Expression of Myosin Heavy Chain Isoforms in Skeletal Muscle of Chronic Alcoholic Men without Liver Disease after I Day and 4 Weeks of Alcohol Abstinence
Authors: Sestoft L. , Iversen P. , Nordgaard I. , Amris S. , Joen T. , Overgaard O. , Klitgaard H. 
Published: August 2015

1. The aim of this study was to examine the effect of chronic alcohol ingestion on working capacity and on the expression of myosin heavy chain isoforms in fibre types of human skeletal muscle.
2. Six alcoholic men having drunk more than 240 g of alcohol/day for more than 10 years underwent a test for working capacity and a muscle biopsy on the first day of alcohol abstinence (test 1) and again after 4 weeks of abstinence (test 2). The biopsies were analysed using histochemical, immunochemical and gel-electrophoretic techniques, and the results were compared with those from eight age-matched nonalcoholic control subjects.
3. The area of type IIB muscle fibres was decreased by 33% in the alcoholic patients compared with normal control subjects at both test 1 and test 2. The area of type IIA fibres was lower (13%) in alcoholic patients at test 1 than in the control group, and increased to the normal level at test 2.
4. The relative proportion of fibres expressing only myosin heavy chain type IIB isoforms was one-third of normal in the alcoholic patients at both tests 1 and 2. The relative proportion of fibres expressing only myosin heavy chain type IIA isoforms was the same in alcoholic patients at test 1 and in normal control subjects, but increased by 25% between test 1 and 2 in the alcoholic group.
5. The relative proportion of fibres showing co-expression of myosin heavy chain type IIA/IIB isoforms was about two-thirds of normal in alcoholic patients at both test 1 and test 2, whereas fibres with co-expression of myosin heavy chain type I/IIA were not seen in the control group, but were found in the alcoholic group, where they doubled from test 1 to test 2.
6. Thus, chronic heavy alcohol consumption modulates the expression of myosin heavy chain isoforms-in human skeletal muscle by decreasing the expression of myosin heavy chain type IIB and increasing the expression of myosin heavy chain type I. After 4 weeks of alcohol abstinence a shift in the expression of myosin heavy chain type I towards myosin heavy chain type IIA is evident, indicating that the effect of alcohol on myosin heavy chain expression is a reversible process. However, to obtain complete recovery with a normal level of myosin heavy chain type IIB expression, more than 4 weeks of abstinence is necessary.
7. Working capacity was low and unchanged by 4 weeks of alcohol abstinence. The low proportion of type IIB (fast twitch glycolytic) fibres at both test 1 and 2 coincided with a low lactate production during maximal exercise. The increased proportion of type I (slow twitch oxidative) fibres at test 1 coincided with an preferential lipid oxidation during the working period.
Inositol-Specific Phospholipase D Activity in Health and Disease
Authors: Raymond F. D. , Fortunato G. , Moss D. W. , Castaldo G. , Salvatore F. , Impallomeni M. 
Published: August 2015

1. We report the first demonstration of the pathophysiological importance and clinical applications of the relatively recently discovered circulating enzyme, phosphoinositol-specific phospholipase D. This enzyme is known to cleave the large variety of important cell-surface molecules linked to the cell membrane by glycan-phosphatidylinositol linkages (glycan-phosphatidylinositol anchors).
2. When measured in the sera of healthy individuals, phosphoinositol-specific phospholipase D activity was found to show a strong negative correlation with age, the degree of depreciation being greater than that measured for most other analytes.
3. Serum phosphoinositol-specific phospholipase D activity was considerably depressed in patients presenting with conditions leading to reduced liver synthetic reserve, such as hepatocellular carcinoma or liver cirrhosis caused by chronic viral hepatitis, and correlated with reduced albumin levels in these conditions, indicating that the liver is the site of phosphoinositol-specific phospholipase D synthesis and that phosphoinositol-specific phospholipase D may be used as an additional marker of liver synthetic reserve.
4. When measured in patients with acute liver disease, such as acute viral hepatitis, or in patients with bronchopneumonia, phosphoinositol-specific phospholipase D activity was found to be significantly raised, demonstrating features characteristic of an acute-phase reactant.
5. These findings indicate that, besides its pathophysiological importance, phosphoinositol-specific phospholipase D and the measurement of its activity in serum may have a useful place in the investigation of a range of clinical conditions, including tissue injury and inflammation.
Loop—Sheet Polymerization: The Structural Basis of Z α1-Anti Trypsin Accumulation in the Liver
Authors: Lomas David A. 
Published: August 2015

1. The Z deficiency variant of α1-antitrypsin predisposes the homozygote to early-onset panlobular emphysema and results in the accumulation of antitrypsin within the hepatocyte, which leads to hepatocellular damage and cirrhosis. The mechanism of this accumulation has been shown to be due to the Z mutation (Glu-342→Lys) perturbing the structure of the protein, allowing a unique interaction between the reactive-centre loop of one molecule and the A sheet of a second. This loop—sheet polymerization occurs spontaneously at 37°C in purified plasma Z but not M antitrypsin. The rate of polymerization is greatly accelerated at 41 C and is blocked by the insertion of a specific peptide into the A sheet of the antitrypsin molecule. Electron microscopy and circular dichroic spectral analysis confirm that the Z antitrypsin polymers formed in vitro have structural identity with those isolated from the liver of a Z homozygote.
2. That loop—sheet polymerization is a more general phenomenon was shown by the examination of a second deficiency variant, antitrypsin Siiyama (Ser-53→Phe), which is also associated with liver inclusions. Electron microscopy confirmed that isolated antitrypsin Siiyama from the plasma of a homozygote was present as long chains of polymers identical with those of Z antitrypsin.
Improvement of Ketoacidosis in the Diabetic Rat after the Administration of the Oral Antilipolytic Agent Gr 79236
Authors: Thompson Cecil S. , Strong Peter , Mikhailidis Dimitri P. 
Published: August 2015

1. We assessed the effect of a novel oral antilipolytic agent, N-[(1S, trans) − 2 – hydroxycyclopentyl] adenosine (GR 79236), in experimental diabetic ketoacidosis. Ketotic rats were gavaged with GR 79236 (1 mg/kg) or water (vehicle) and their blood/plasma/serum biochemistry and haematological profile was determined.
2. We found that GR 79236 reduced the plasma non-esterified fatty acid concentration. This effect was associated with the correction of blood/plasma/serum biochemical variables (β-hydroxybutyrate, acetoacetate, triacylglycerol) directly related to diabetic ketoacidosis, and of others (cholesterol, creatinine, creatine kinase and aspartate transaminase) which are not directly related to this metabolic abnormality.
3. There was, however, no evidence of GR 79236 lowering blood glucose in this model. One possible explanation for this observation is that GR 79236 stimulated gastric emptying leading to enhanced absorption of stomach contents when compared with untreated animals.
Sepsis Modifies the Contribution of Different Organs to Whole-Body Protein Synthesis in Rats
Authors: Breuille D. , Rose F. , Arnal M. , Melin C. , Obled C. 
Published: August 2015

1. Protein synthesis rate was measured in the liver, muscle, intestine and whole body of septic rats and pair-fed controls by administration of a large dose of l-[U14C]valine. Sepsis was induced by intravenous injection of live bacteria, and protein synthesis measurements were carried out 48 h later.
2. Septic rats exhibited a reduction in food intake to between 10 and 50% of the normal level on the 2 days after infection. Animals lost body weight and the relative organ weight was increased in liver, unchanged in intestine and decreased in skeletal muscle.
3. The fractional protein synthesis rate of the whole body excluding liver was increased by 19% in septic rats in comparison with pair-fed controls, but the absolute protein synthesis rate was similar in the two groups because of the low protein content of the infected group.
4. The fractional protein synthesis was increased in whole intestine and liver but was decreased in skeletal muscle. In muscle and liver, the difference between infected and pair-fed animals was more pronounced for the absolute than for the fractional protein synthesis rate. In intestine, the fractional protein synthesis rate was similarly increased in whole intestine and the muscular layer of ileum. This suggests different regulation of protein synthesis in skeletal and smooth muscles.
5. The present investigation shows a complete redistribution of protein synthesis in sepsis. Liver represents about a third of the whole-body protein synthesis instead of 15% and becomes predominant over synthesis of muscle.
Impaired Contraction and Endothelium-Dependent Relaxation in Isolated Resistance Vessels from Patients with Insulin-Dependent Diabetes Mellitus
Authors: McNally Paul G. , Watt Pamela A. C. , Rimmer Timothy , Burden Andrew C. , Hearnshaw John R. , Thurston Herbert 
Published: August 2015

1. An increase in capillary blood flow and pressure has been implicated in the pathogenesis of diabetic microangiopathy. Abnormal vascular reactivity of the resistance vasculature may play a contributory role by permitting alterations in regional haemodynamics.
2. We have studied the contractile behavior of isolated resistance arteries from normotensive patients with insulin-dependent diabetes mellitus and non-diabetic matched control subjects. Contractile responses to potassium (123 mmol/l), noradrenaline (10−8 to 3 × 10−5 mol/l) and angiotensin II (10−11 to 3 × 10−8 mol/l) were recorded. Relaxation studies were performed in maximally contracted vessels using acetylcholine (10−8 to 10−5 mol/l) and bradykinin (10−9 to 10−6 mol/l) (endothelium-dependent) and sodium nitroprusside (10−9 to 10−5 mol/l) (endothelium-independent).
3. The maximal contractile responses to potassium (P &lt; 0.05), noradrenaline (P &lt; 0.01) and angiotensin II (P &lt; 0.01) were depressed in diabetic patients. Relaxation to acetylcholine was impaired (P &lt; 0.05), but was normal with bradykinin and sodium nitroprusside.
4. These results suggest that there may be a defect in the endothelial cell acetylcholine receptor excitation-coupling in diabetes mellitus rather than a decreased ability to synthesize and release endothelium-derived relaxing factor. Impaired contraction and endothelium-dependent relaxation of resistance arteries in diabetic patients may contribute to the development of diabetic microangiopathy by causing an increase in tissue blood flow, a rise in capillary pressure and, as a result, an increase in vascular permeability.
Functional Relationship between Mast Cells and C-Sensitive Nerve Fibres Evidenced by Histamine H3-Receptor Modulation in Rat Lung and Spleen
Authors: Dimitriadou V. , Rouleau A. , Tuong M. Dam Trung , Newlands G. J. F. , Miller H. R. P. , Luffau G. , Schwartz J.-C. , Garbarg M. 
Published: August 2015

1. Mast cell populations in rat lung and spleen were characterized by the presence of two specific protease markers, rat mast cell protease I and II, using both histochemical and radioimmunoassay techniques. Three mast cell populations with different size, morphology and localization were found in lung and spleen and were identified according to the expression of rat mast cell protease I (RMCPI+) or rat mast cell protease II (RMCPII+) or of both proteases (RMCPI/II+).
2. All three mast cell types were in the vicinity of calcitonin-gene-related-peptide-immunoreactive (CGRP+) nerve fibres in controls as well as in rats infected by Nippostrongylus brasiliensis in which a large increase in the number of both RMCPII+ and RMCPI/II+ mast cells was found. Ablation of the CGRP+ fibres by neonatal treatment with capsaicin resulted in a marked increase in the number of RMCPII+ and RMCPI/II+ cells in lung and, even more, in spleen of adult rats.
3. The interaction of mast cells with CGRP+ C-fibres was assessed pharmacologically by evaluation of the effects of histamine H3-receptor ligands known to act on various types of nerve endings, including those of C-fibres. The effects of H3-receptor ligands were assessed in controls, nematode-infected rats and neonatally capsaicinized rats. Mast cell activity was evaluated by measurement of [3H]histamine synthesis from [3H]histidine. In control rats, administration of the H3-receptor agonist (R)-α-methylhistamine and antagonist thioperamide, decreased and enhanced respectively [3H]histamine synthesis in lung and spleen, indicating a tonic control of mast cell activity by histamine via H3-receptors. Such effects were not found in the jejunum, although RMCPII+ mast cells are in close apposition with neuropeptide-containing fibres. The effects of the H3-receptor agents were maintained in lung and spleen of nematode-infected rats, but were almost suppressed in capsaicinized rats. 4. It is concluded that the control of mast cells by histamine acting at H3-receptors involves neuropeptide-containing nerves and presumably reflects the operation of a local neuron-mast cell feedback loop controlling processes such as ‘neurogenic inflammation’. This loop still functions when mast cells proliferate in an inflammatory condition. These observations suggest that the use of histamine H3-receptor agonists may constitute a novel therapeutic approach to limit excessive inflammatory responses resulting from dysregulation of this feedback loop.
Effect of the Serine Protease Inhibitor, Aprotinin, on Systemic Haemodynamics and Renal Function in Patients with Hepatic Cirrhosis and Ascites
Authors: MacGilchrist Alastair , Craig Kathrine J. , Hayes Peter C. , Cumming Allan D. 
Published: August 2015

1. Previous studies have documented activation of protease enzymes, such as the plasma kallikrein-kinin system, in hepatic cirrhosis. Increased plasma kinin generation could contribute to pathological systemic vasodilatation in cirrhosis, and reduced systemic vascular resistance has been suggested as a trigger to renal sodium retention in this disease. We investigated the effect of aprotinin, a protease inhibitor which binds to plasma kallikrein, on systemic haemodynamics and renal function in patients with hepatic cirrhosis and ascites.
2. Aprotinin was infused intravenously in high dosage (2 × 106 kallikrein inhibitory units loading, 1 × 106 kallikrein inhibitory units/h).
3. Of 13 patients, 10 had a low systemic vascular resistance (&lt; 1200 dyn s cm−5) at baseline. In this group, eight showed an increase in systemic vascular resistance during aprotinin infusion. Overall, the increase in systemic vascular resistance was significant, and there was a small but significant increase in mean arterial pressure. In all patients, there were increases in renal plasma flow, glomerular filtration rate, and absolute and fractional urinary sodium excretion during aprotinin infusion.
4. Plasma renin activity, plasma angiotensin II and plasma aldosterone fell significantly during aprotinin infusion. Plasma prekallikrein, plasma noradrenaline and plasma atrial natriuretic peptide did not change. Plasma aprotinin concentration was 209 ± 11 kallikrein inhibitory units/ml at the end of the infusion.
5. Before and during the infusion, there was a significant negative correlation between systemic vascular resistance and plasma renin activity. There was a positive correlation between the change in systemic vascular resistance and the change in renal plasma flow during aprotinin infusion.
6. In patients with hepatic cirrhosis and ascites, treatment with aprotinin appears beneficial in relation to systemic and renal haemodynamics, sodium excretion and hormonal stimulation, with no evidence of adverse effects. The results are compatible with an association between plasma kallikrein-kinin activation, systemic vasodilatation, renin-angiotensin activation, and renal vasoconstriction and sodium retention in this condition.
Anti-Tumour Necrosis Factor-α Treatment Interferes with Changes in Lipid Metabolism in a Tumour Cachexia Model
Authors: Carbó Neus , Costelli Paola , Tessitore Luciana , Bagby Gregory J. , López-Soriano Francisco J. , Baccino Francesco M. , Argilés Josep M. 
Published: August 2015

1. Rats bearing the Yoshida ascites hepatoma AH-130 showed an important decrease in white adipose tissue lipoprotein lipase activity as compared with non-tumour bearing rats. This was associated with a lower adipose tissue mass, as estimated from the weight of the lumbar fat-pads. Conversely, lipoprotein lipase activity was markedly increased in brown adipose tissue and heart.
2. These changes were associated with a distinct hyperlipaemia, essentially manifested as an increase in circulating triacylglycerol levels, whereas no changes were observed in glycaemia.
3. Tumour-bearing rats were treated with a polyclonal anti-murine tumour necrosis factor-α antibody or with a non-immune IgG preparation. Control animals were either untreated or received a nonimmune IgG preparation. Anti-tumour necrosis factor-α treatment resulted in a significant increase in lipoprotein lipase activity in white adipose tissue in animals bearing a tumour growing exponentially (day 4 after inoculation) as compared with the animals receiving a non-immune goat IgG preparation. In addition, animals bearing an stationary tumour (day 7 after inoculation) and submitted to anti-tumour necrosis factor-α treatment had a higher adipose tissue lipoprotein lipase activity as compared with the IgG- or the non-treated groups. Correspondingly, circulating triacylglycerol levels were markedly decreased, with a lower hyperlipaemia than in control tumour-bearing rats.
4. These observations suggest that tumour necrosis factor-α is involved in activating the lipid metabolic changes that develop in rats after transplantation of a fast-growing tumour.
Sympathetic Overactivity in Subjects Complaining of Unexplained Fatigue
Authors: Pagani Massimo , Lucini Daniela , Mela Giuseppe Sandro , Langewitz Wolf , Malliani Alberto 
Published: August 2015

1. Theoretical and practical considerations suggest that in subjects complaining of fatigue, in the absence of evident organ dysfunction, an alteration in the autonomic nervous system might be present as a functional correlate.
2. Autoregressive spectral analysis of R-R interval variability from a surface ECG, was used in healthy control subjects (n = 24, age 45 ± 4 years) and in subjects complaining of unexplained fatigue (n = 53, age 46 ± 9 years) to obtain quantitative indices of the state of the sympathovagal balance, both at rest and during a mental stimulus (mental arithmetic), capable of enhancing sympathetic drive. Sympathetic and vagal modulations were inferred from the normalized powers of the low frequency and high frequency spectral components respectively.
3. We observed in patients, at rest, a prevailing low frequency component of R-R variability (patients low frequency = 73 ± 11, control subjects 51 ± 10 normalized units, P &lt; 0.05). The responsiveness to mental arithmetic was reduced in patients as compared with controls. Systolic blood pressure variability did not differ. This suggested a selective imbalance in autonomic control of the sinoatrial node, characterized by sympathetic predominance as well as by vagal withdrawal, at rest.
4. The possibility of discriminating patients from control subjects on the basis of simple non-invasive functional markers might provide a better understanding of the mechanisms, clinical evolution and outcome of conditions such as the chronic fatigue syndrome, which lack ordinary evidence of disease, but comprise, as physiopathological correlate, a quantitative alteration of autonomic control.
Effect of Oral Creatine Supplementation on Respiratory Gas Exchange and Blood Lactate Accumulation during Steady-State Incremental Treadmill Exercise and Recovery in Man
Authors: Stroud Michael A. , Holliman Dawn , Bell Doug , Green Allison L. , Macdonald Ian A. , Greenhaff Paul L. 
Published: August 2015

1. Oral creatine supplementation has been shown to increase muscle creatine and phosphocreatine concentrations with consequent benefits on performance during short-term maximal exercise. However, recently there have been anecdotal reports that creatine supplementation can also influence the pattern of substrate utilization and improve performance during more prolonged, submaximal exercise, which, based on recent experimental evidence, may have some scientific justification.
2. Eight men performed a continuous incremental exercise test running at 10 km/h on a motorized treadmill at predetermined workloads from 50% to 90% of maximal oxygen uptake, before and after 5 days of creatine supplementation (4 × 5 g daily). Exercise was performed for 6 min at each workload to achieve a steady state, and respiratory gas exchange and blood lactate concentrations were measured during the last 30s at each workload. Measurements were also made at 5-min intervals for the first 15 min of recovery.
3. The results showed no measurable effect of creatine supplementation on respiratory gas exchange and blood lactate concentrations during either incremental submaximal exercise or recovery. This suggests that creatine supplementation does not influence substrate utilization during and after this type of exercise.