bluuebunny/crossref_metadata_2025_split huggingface dataset:
Four-Component Model of Body Composition in Chronic Renal Failure Comprising Dual-Energy X-ray Absorptiometry and Measurement of Total Body Water by Deuterium Oxide Dilution
Authors: Woodrow Graham , Oldroyd Brian , Turney John H. , Davies Peter S. W. , Day Janice M. E. , Smith Michael A. 
Published: August 2015

1. Assessment of nutrition in patients with chronic renal failure by body composition measurement techniques may be affected by variable hydration.
2. This study aimed to derive a four-component model of body composition (consisting of fat, protein, total body water and body mineral) from a combination of dual-energy X-ray absorptiometry and total body water measured by deuterium oxide dilution, allowing assessment of body protein stores without the effect of variation in hydration. Patients with chronic renal failure on haemodialysis, peritoneal dialysis and conservative treatment and a control group were studied. Patients with chronic renal failure were at an ‘ideal’ state of hydration on clinical assessment.
3. Hydration was defined by total body water as a percentage of fat-free mass measured by dual-energy X-ray absorptiometry, and no differences were found between chronic renal failure subgroups and control subjects (except in the female undialysed chronic renal failure subgroup). Hydration was significantly correlated with percentage total body fat in the control groups but not in patients with chronic renal failure.
4. Lean tissue measured by dual-energy X-ray absorptiometry was significantly reduced in three of the six chronic renal failure groups compared with control subjects (male and female patients on haemodialysis and female patients on peritoneal dialysis). Protein estimated from the four-component model failed to detect these abnormalities.
5. Lean tissue measured by dual-energy X-ray absorptiometry in normal subjects strongly correlated with fat-free mass measured by total body potassium in normal subjects (male r = 0.91; female r = 0.89, both P &lt; 0.0001). The correlation of protein estimated from the four-component model with fat-free mass measured by total body potassium was far weaker in male control subjects (r = 0.51, P &lt; 0.05) and not significant in female control subjects (r = 0.38, P not significant). In the normal subjects protein estimated from the four-component model showed a much greater variation from protein estimated by total body potassium than did protein estimated simply as 27% of dual-energy X-ray absorptiometry fat-free mass minus total body mineral.
6. Hydration in patients with chronic renal failure in whom fluid balance is believed to be normal on clinical criteria does not differ from that in normal subjects. The combined model of dual-energy X-ray absorptiometry and total body water is not a useful method for the measurement of body protein.
Studies on the Interaction of T-Cells with Major Histocompatibility Complex Class II Antigens
Authors: Warrens Anthony N. 
Published: August 2015

1. Major histocompatibility complex class II antigens have the central role in the immune response of ‘presenting’ antigenic peptide to CD4+ T-cells. This interaction with a T-cell's receptor may result in activation, but, if recognition occurs without collateral molecular interactions which cause ‘co-stimulation’, these T-cells will be tolerized.
2. In the light of current interest in muscle cell transplantation, a transformed myoblast, TE671, phenotypically comparable to untransformed cells, transfected to express class II, was studied as a stable model of antigen presentation by muscle cells. These cells failed to activate T-cells but induced tolerance.
3. The DRα chain is unusual being the only non-polymorphic classical class II polypeptide, raising the question of its functional contribution. To this end, several single polypeptide constructs were generated with contributions from different class II α-chains. On this basis, it was established that DRα makes significant contributions to peptide binding and that its α2 domain is also important in T-cell recognition, possibly through CD4 binding.
4. One implication of the lack of polymorphism of DRα may be that it has a wider range of pairing partners, possibly including β chains of different isotypes. To address this, it is planned to use transfectants expressing only a mixed isotype pair to generate T-cell clones in vitro. These reagents would be useful tools to detect whether such mixed pairs exist physiologically. In this paper, the development of a system is described which will allow this question to be addressed.
Urinary Albumin Excretion and Atherosclerosis in Essential Hypertension
Authors: Pedrinelli Roberto , Undpaintner Klaus , Dell'omo Giulia , Napoli Vinicio , Di Bello Vitantonio , De Caterina Raffaele , Petrucci Roberto 
Published: August 2015

1. Increased urinary albumin excretion is common in patients with essential hypertension and is at least to some extent correlated with prevailing blood pressure levels. However, the generalized vascular dysfunction present in advanced atherosclerotic disease may independently influence this parameter.
2. To evaluate this possibility, we assessed blood pressure, ultrasonographic carotid thickness, cardiac mass, minimum forearm vascular resistances, metabolic parameters and the angiotensin-converting enzyme genotype in patients with untreated essential hypertension and atherosclerotic peripheral vascular disease (n = 11). The results were compared with similar data obtained in matched groups of patients with uncomplicated hypertension and with normotensive control subjects (n = 11 per group).
3. Urinary albumin excretion was higher in hypertensive patients with atherosclerosis than in those without complications; carotid thickness was higher in atherosclerotic patients and a positive, statistically significant correlation existed between this parameter and urinary albumin excretion. In the same patient group, systolic blood pressure, fasting insulin and triacylglycerol levels were elevated and correlated with urinary albumin levels. However, differences in urinary albumin excretion persisted after taking into account the influence of those parameters by analysis of covariance. The distribution of angiotensin-converting enzyme genotype patterns and values of cardiac mass and minimum forearm vascular resistances did not differ significantly among the experimental groups.
4. The data suggest that vascular status may influence urinary albumin excretion in patients with essential hypertension, while confirming the importance of systolic blood pressure levels as a determinant of the raised urinary albumin excretion.
Pathogenesis of Liver Fibrosis
Authors: Alcolado R. , Arthur M. J. P. , Iredale J. P. 
Published: August 2015

1. Liver fibrosis is a common sequel to diverse liver injuries. It is characterized by an accumulation of interstitial collagens and other matrix components. The hepatic stellate cell is pivotal to the pathogenic process. Fibrotic liver injury results in activation of the hepatic stellate cell which undergoes a phenotypic change to a proliferative myofibroblast-like cell which synthesizes excess interstitial collagens and other matrix components.
2. The process of initiation of activation and its perpetuation result from complex, often interrelated series of signalling mechanisms which converge on this effector cell. Such mechanisms include alterations in matrix resulting in changed cell—matrix interactions and stimulation by cytokines released from damaged hepatocytes, infiltrating inflammatory cells, Kupffer cells and matrix. Foremost among the profibrotic cytokines is transforming growth factor β1.
3. Once the hepatic stellate cell is activated the preceding matrix changes and recurrent injurious stimuli will perpetuate the activated state.
4. Despite the accumulation of excess collagens, the liver retains a capacity for matrix degradation. This capacity may be overwhelmed and any secreted matrix remodelling enzymes may be inhibited by the concurrently secreted tissue inhibitors of metallo-proteinase-1 and α2-macroglobulin.
5. Our understanding of the molecular pathogenesis of liver fibrosis is increasing. It is anticipated that this knowledge will provide novel therapeutic avenues to treat this disease process.
Postural Vasoconstriction and Leg Ulceration in Homozygous Sickle Cell Disease
Authors: Mohan J. S. , Marshall J. M. , Reid H. L. , Thomas P. W. , Serjeant G. R. 
Published: August 2015

1. Chronic leg ulceration is a major cause of morbidity in patients with homozygous sickle cell disease; the ulcers commonly resolve on bed rest. We have therefore compared the cutaneous vascular response to dependency in three groups of eight patients with sickle cell disease (those with an active ulcer, with an ulcer scar and with no history of ulceration) and in eight subjects with normal haemoglobin and no history of leg ulceration.
2. We monitored, with a laser Doppler flowmeter, the change in red cell (erythrocyte) flux induced in the skin of the leg, at two sites proximal to the malleoli, with the leg horizontal and 5 and 10 min after moving the leg to the dependent position.
3. With the leg horizontal, mean cutaneous red cell flux was substantially higher in normal skin of patients with sickle cell disease than in normal subjects and was higher still at the site of the ulcer or scar. On dependency, red cell flux fell not only in normal subjects but also in the patients with sickle cell disease, both in the normal skin and at the site of the ulcer or scar; there was no difference in any group between the 5- and 10-min values. The fall in red cell flux in normal skin of patients with sickle cell disease was smaller than in normal subjects when considered as a percentage of the control values (32%, 36%, 30% and 61% respectively in sickle cell patients with an active ulcer, with an ulcer scar and with no history of ulceration and in normal subjects), but in absolute terms the falls in red cell flux were similar in sickle cell patients and normal subjects. By contrast, the fall in red cell flux at the ulcer or scar site was greater than in normal skin from sickle cell patients whether considered as a percentage of the control value (48% and 49% respectively in those with an active ulcer or ulcer scar) or in absolute terms.
4. We propose that high resting perfusion is important in patients with sickle cell disease to maintain normal integrity of cutaneous tissue and that pronounced vasoconstriction on dependency hinders the healing and encourages recurrence of leg ulcers.
Modulation of Neurocardiac Function by Oesophageal Stimulation in Humans
Authors: Tougas Gervais , Kamath Markad , Watteel Geena , Fitzpatrick Debbie , Fallen Ernest L. , Hunt Richard H. , Upton Adrian R. M. 
Published: August 2015

1. The heart and the oesophagus have similar sensory pathways, and sensations originating from the oesophagus are often difficult to differentiate from those of cardiac origin. We hypothesized that oesophageal sensory stimuli could alter neurocardiac function through autonomic reflexes elicited by these oesophageal stimuli. In the present study, we examined the neurocardiac response to oesophageal stimulation and the effects of electrical and mechanical oesophageal stimulation on the power spectrum of beat-to-beat heart rate variability in male volunteers.
2. In 14 healthy volunteers, beat-to-beat heart rate variability was compared at rest and during oesophageal stimulation, using either electrical (200 μs, 16 mA, 0.2 Hz) or mechanical (0.5 s, 14 ml, 0.2 Hz) stimuli. The power spectrum of beat-to-beat heart rate variability was obtained and its low- and high-frequency components were determined.
3. Distal oesophageal stimulation decreased heart rate slightly (both electrical and mechanical) (P &lt; 0.005), and markedly altered heart rate variability (P &lt; 0.001). Both electrical and mechanical oesophageal stimulation increased the absolute and normalized area of the high-frequency band within the power spectrum (P &lt; 0.001), while simultaneously decreasing the low-frequency power (P &lt; 0.005).
4. In humans, oesophageal stimulation, whether electrical or mechanical, appears to amplify respiratory-driven cardiac vagoafferent modulation while decreasing sympathetic modulation. The technique provides access to vagoafferent fibres and thus may yield useful information on the autonomic effects of visceral or oesophageal sensory stimulation.
Contraction Failure of Skeletal Muscle of Rats Recovering from Critical Illness
Authors: Rooyackers Olav E. , Hesselink Matthijs K. C. , Wagenmakers Anton J. M. 
Published: August 2015

1. Most patients recovering from critical illness experience enhanced fatiguability. Previously we have shown that zymosan-induced critical illness in rats is attended by a decreased mitochondrial content (maximal aerobic capacity) in skeletal muscle. We investigated whether this decrease results in an increased reduction in high-energy phosphates and a subsequent loss of contractility during in situ electrical stimulation in rats recovering from zymosan treatment.
2. Plantar-flexor muscles of the hindlimb were electrically stimulated via the innervating nerve to develop maximal isometric tetanic contraction.
3. Decreased concentrations of ATP were measured in gastrocnemius muscle of zymosan-treated rats, both at rest and after stimulation, in comparison with ad libitum-fed and pair-fed control rats. However, no differences in the stimulation-induced decreases in high-energy phosphate levels and changes in other metabolites, except ADP, were observed between the groups. Tension development in the zymosan-treated rats was, however, about 85% less compared with the pair-fed controls during the whole stimulation period.
4. We conclude that the primary cause of the loss of muscle tension in zymosan-treated rats is an insensitivity of skeletal muscle to stimulation via the nerve. An additional derangement in ATP production is, however, indicated by the comparable decreases in energy substrates during development of a dramatically lower tension.
Mitochondrial DNA Defects: A Widening Clinical Spectrum of Disorders
Authors: Sherratt Emma J. , Thomas Andrew W. , Alcolado John C. 
Published: August 2015

1. Mitochondrial DNA has a number of interesting properties including maternal transmission, the ability to replicate in post-mitotic cells, a high mutation rate and an extremely compact molecular architecture with no introns and no large non-coding sequences.
2. Point mutations, deletions and duplications of mitochondrial DNA may occur. Mitochondrial DNA defects may co-exist with wild-type sequence within a cell (heteroplasmy). The level of heteroplasmy may vary in different tissues within the same individual (segregative replication).
3. A number of neurological disorders are characterized by morphological and biochemical mitochondrial defects. It is now clear that mitochondrial DNA mutations underlie these conditions although there is not always a clear correlation between a particular mutation and clinical presentation.
4. Mitochondrial DNA defects, particularly deletions, accumulate in senescent tissue and studies have been performed with the aim of linking such somatic mutations with degenerative disorders.
5. Recently mitochondrial DNA mutations have been implicated in a wider range of clinical disorders including diabetes and nerve deafness.
6. Nuclear gene defects may result in mitochondrial disorders by predisposing to multiple mitochondrial DNA deletions or quantitative depletions of mitochondrial DNA content.
Sodium—Lithium Countertransport, Sodium—Hydrogen Exchange and Membrane Microviscosity in Patients with Hyperlipidaemia
Authors: MacLeod M. J. , Lee W. K. , Devlin A. M. , Caslake M. , Anderson N. H. , Packard C. J. , Dominiczak M. H. , Reid J. L. , Dominiczak A. F. 
Published: August 2015

1. We measured sodium-lithium countertransport, sodium-hydrogen exchange and membrane microviscosity in 48 individuals with familial hypercholesterolaemia, 33 subjects with hypertriglyceridaemia and 54 normolipaemic controls. Full lipid profile, blood pressure, body mass index, fasting glucose and insulin levels were also measured.
2. Subjects with hypertriglyceridaemia had higher blood pressure, body mass index, fasting glucose and insulin levels than normal controls.
3. Vmax of the sodium-lithium countertransport was elevated in the hypertriglyceridaemic group compared with controls. Across the whole group loge triacylglycerols correlated with Vmax of the sodium-lithium countertransport. There was no difference in sodium-lithium countertransport Km between the groups.
4. Sodium-hydrogen maximal proton efflux rate (Vmax) and Km were not different between the three groups. There were no correlations between sodium—hydrogen exchange and sodium—lithium countertransport parameters.
5. Microviscosity as measured by diphenylhexatriene was reduced at the core of the membrane in subjects with hypertriglyceridaemia compared with those with familial hypercholesterolaemia or normolipaemic controls, suggesting an alteration in membrane structure.
6. Changes in sodium transport in hyperlipidaemia may be mediated by changes in membrane structure resulting in altered protein conformation or turnover.
Na+,K+-ATPase Expression in Maleic-Acid-Induced Fanconi Syndrome in Rats
Authors: Castaño Esther , Marzabal PAU , Casado F. Javier , Felipe Antonio , Pastor-Anglada Marçal 
Published: August 2015

1. Na+,K+-ATPase activity and its α1 subunit protein and mRNA in kidney cortex were monitored in rats developing Fanconi syndrome after the administration of maleate. Na+,K+-ATPase activity was significantly lower than in saline-injected controls, although this was partially mediated by a general, non-specific decrease in the cortex protein content.
2. The low activity of the sodium pump correlated with low abundance of α1 subunit mRNA and protein levels. Hsp60 protein levels were also decreased in kidney cortex from maleate-treated rats.
3. Kidney cortex brush-border membrane vesicles from maleate-treated rats showed a marked decrease in Na+-dependent alanine and glucose transport, which was not dependent on the Na+-transmembrane gradient itself, a finding which is consistent with a more stable effect at the plasma membrane level.
4. The effect of maleate may be partially nonspecific and involve a great variety of proteins, but seems to be restricted to selected tissues because α1 subunit Na+,K+-ATPase and hsp60 protein amounts were not significantly modified in livers from rats developing Fanconi syndrome.
5. These results show that maleate administration induces a low activity of selected concentrative transport systems and a decrease in Na+,K+-ATPase activity and expression. The combination of both effects may explain the increased excretion of most organic solutes present in rats developing Fanconi syndrome.
Low-Dose Brain Natriuretic Peptide Infusion in Normal Men and the Influence of Endopeptidase Inhibition
Authors: Florkowski C. M. , Richards A. M. , Espiner E. A. , Yandle T. G. , Sybertz E. , Frampton C. M. 
Published: August 2015

1. To assess the threshold dose for bioactivity of brain natriuretic peptide and the role of endopeptidase 24.11 in metabolism of brain natriuretic peptide at physiological plasma levels, we studied eight normal men receiving 2 h infusions of low-dose brain natriuretic peptide [0.25 and 0.5 pmol min−1 kg−1 with and without pretreatment with an endopeptidase inhibitor (SCH 32615, 250 mg intravenously)] in placebo-controlled studies.
2. Plasma brain natriuretic peptide increased 2-fold during the infusion of 0.25 pmol min−1 kg−1 (mean increment above control 3.9 pmol/l, P &lt; 0.001), and tripled (P &lt; 0.001) with 0.5 pmol min−1 kg−1. Plasma renin activity was inhibited by both doses (14.8%, P &lt; 0.01, and 20%, P &lt; 0.001, respectively). A significant natriuresis (56% increase in urine sodium/creatinine ratio, P &lt; 0.02) occurred with the higher dose. Blood pressure, haematocrit, plasma cGMP, atrial natriuretic peptide and aldosterone were unaffected by either dose.
3. Compared with brain natriuretic peptide (0.5 pmol min−1 kg−1) alone, SCH 32615 pretreatment increased peak plasma brain natriuretic peptide (13.4±0.78 versus 12.4±0.86 pmol/l, P &lt; 0.05), ANP (7.5±0.96 versus 5.9±0.4 pmol/l, P &lt; 0.01) and cGMP (4.8 ± 1.7 versus 3.9 ± 1.4 nmol/l, P &lt; 0.001). Plasma renin activity was further suppressed with SCH 32615 pretreatment (29% compared with 20%, P &lt; 0.001).
4. Small acute increments in plasma brain natriuretic peptide (4 pmol/l) have significant biological effects in normal men without altering plasma atrial natriuretic peptide or cGMP.
Differential Excretion of Leucocyte Granule Components in Inflammatory Bowel Disease: Implications for Pathogenesis
Authors: Dwarakanath A. D. , Finnie I. A. , Beesley C. M. , O'Dowd G. M. , Nash J. , Tsai H. H. , Parker N. , Rhodes Jonathan M. 
Published: August 2015

1. Faecal excretion of the leucocyte primary granule component, myeloperoxidase, and of the secondary granule component, lactoferrín, were compared in inflammatory bowel disease and infective diarrhoea.
2. Faecal lactoferrín correlated with faecal myeloperoxidase in both inflammatory bowel disease (P = 0.0018; n = 32) and infective diarrhoea (P = 0.00013; n = 37), but inflammatory bowel disease was associated with a much higher faecal excretion of lactoferrín but lower excretion of myeloperoxidase than infective diarrhoea. As a consequence, the median ratio of lactoferrin/myeloperoxidase excretion (both expressed as ng/mg of protein) for inflammatory bowel disease was 7.5 (range 3.5–21.3) with similar values for ulcerative colitis (n = 18) and Crohn's disease (n = 14) compared with only 0.9 (range 0.4–2.3; P &lt; 0.0001) for infective diarrhoea. In inflammatory bowel disease faecal lactoferrín and myeloperoxidase excretion remained increased even in clinical remission.
3. In subsequent immunohistochemical studies to assess the possible explanation for these findings, lactoferrín and myeloperoxidase were demonstrated within crypt abscesses and surface mucus, both in inflammatory bowel and in infective diarrhoea mucosal samples. There was a slight increase in the number of lactoferrin-containing cells in the mucosal samples from ulcerative colitis and in the submucosa of samples from Crohn's disease compared with infective diarrhoea, but these changes were not sufficient to account for the marked increase in faecal lactoferrín excretion in inflammatory bowel disease.
4. In all mucosal samples, including those from normal mucosa, lactoferrín was also shown to be contained within mast cells.
5. These results could best be explained by a different mechanism for leucocyte activation in inflammatory bowel disease compared with infective diarrhoea, and are compatible with selective secretion of secondary granule components, which include lactoferrín but not myeloperoxidase, as a result of leucocyte activation by N-formylated bacterial peptides in inflammatory bowel disease.