bluuebunny/crossref_metadata_2025_split huggingface dataset:
HPLC Glycosaminoglycan Analysis in Patients with Graves' Disease
Authors: Hansen CH , Fraiture B. , Rouhi R. , Otto E. , Förster G. , Kahaly G. 
Published: August 2015

1. Orbital accumulation of hydrophilic, interstitial glycosaminoglycans (GAGs) and subsequent expansion of retrobulbar tissue lead to the clinical manifestation of exophthalmos in patients with Graves' eye disease.
2. A highly specific method to determine the concentration and biochemical composition of different GAGs was developed in order to obtain a sensitive test system for the activity of the disease. By means of this method, GAG excretion in 24 h urine collections of 56 patients and 21 controls was analysed by precipitation with cetylpyridinium chloride and potassium acetate in ethanol, followed by sequential enzymic hydrolysis with chondroitin AC lyase, chondroitin ABC lyase and hyaluronate lyase, with HPLC analysis of the resulting α,β-unsaturated disaccharides by anion-exchange chromatography.
3. Concentrations of GAG, chondroitin sulphate A (CA), dermatan sulphate (DS) and hyaluronic acid (HA) were determined in patients and controls, with high recovery rates [72.2 ± 5.3%, mean ± SEM; detection limit, 4.2 μg/l (0.01 μmol/l)], revealing marked differences in urinary concentrations of total GAG and HA, as well as an elevation of CA in patients compared with controls.
4. Method sensitivity was 0.86 for patients with active Graves' eye disease, and 0.87 for patients with untreated ophthalmopathy, whereas specificity was 1.0 for patients with inactive disease. Patients with increased GAG concentration responded well to steroids and/or orbital irradiation (before therapy: GAG, 111.49 ± 40.32; CA, 59.58 ± 21.34; DS, 25.05 ± 8.12; HA, 26.88 ± 11.63 mg/24 h; during therapy: GAG, 54.22 ± 10.94; CA, 20.52 ± 4.58; DS, 17.65 ± 3.46; HA, 16.05 ± 3.69 mg/24 h), whereas GAG excretion increased markedly 2–3 months after stopping prednisone therapy in patients with still active eye disease (GAG, 109.9 ± 10.51; CA, 63.8 ± 7.34; DS, 24.1 ± 5.07; HA, 22.0 ± 6.28 mg/24 h).
5. This sensitive method determines the nature of renally excreted GAGs, reflecting the aberrant synthesis pattern of fibroblasts in patients with Graves' disease.
The Antibody Response in Human Autoimmune Thyroid Disease
Authors: McIntosh Richard S. , Asghar M. Suhail , Weetman Anthony P. 
Published: August 2015

1. The analysis of the antibody response in autoimmune thyroid disease has followed several historical trends. It was the investigation of thyroid-reactive antibody that allowed the initial characterization of the three principle thyroid autoantigens, thyroglobulin, thyroid peroxidase and the thyroid stimulating hormone receptor.
2. Analysis can be grouped under two broad areas: analysis of the physiological and pathological effects of the antibody, and analysis of the structure of the antibodies themselves. This review will focus on the latter.
3. Within recent years there has been a great increase in knowledge of thyroid-reactive antibody structure, principally through the adoption of phage display combinatorial library methodologies. While this latter technique has established some general principles for antibodies to thyroglobin and especially thyroid peroxidase, there is still a substantial gap in our knowledge of the antibody response to the thyroid stimulating hormone receptor.
4. Thyroid peroxidase antibodies have a relatively restricted V-region usage, and there is a correlation between the V-regions used and the epitope on thyroid peroxidase bound. In particular the Vκ light chain, Vκl(O12), is associated with reactivity to one epitope.
5. The purpose of this review is to bring together the latest results concerning the molecular analysis of the antibody response in autoimmune thyroid disease, to highlight areas of ignorance and conflict, and to discuss the methods adopted to circumvent the problems associated with analysis of the antibody response.
Elevated Plasma and Urinary Endothelin-I Levels in Human Salt-Sensitive Hypertension
Authors: Ferri Claudio , Bellini Cesare , Desideri Giovambattista , Mazzocchi Clarita , De Siati Luca , Santucci Anna 
Published: August 2015

1. The behaviour of the potent vasoconstrictive endothelium-derived peptide endothelin-1 was evaluated in salt-sensitive hypertension.
2. Circulating and urinary endothelin-1 levels were evaluated in 30 men (mean age 44.6 ± 3.1 years) with uncomplicated essential hypertension after three consecutive 2-week periods on an intermediate (120 mmol), low (20 mmol) and high (240 mmol) NaCl diet. On the same occasions, blood pressure was measured to identify salt-sensitive patients (n = 16), i.e. those patients showing a mean blood pressure increase &gt; 10 mmHg when switching from a low to a high NaCl diet, and salt-resistant patients (n = 14), i.e. those who did not show such mean blood-pressure variations.
3. Plasma endothelin-1 levels were higher (P &lt; 0.005) in salt-sensitive than in salt-resistant hypertensive patients after intermediate-, low- and high-NaCl diets. Urinary endothelin-1 excretion was similar in both groups after an intermediate-NaCl diet, whereas it was significantly higher in salt-sensitive than in salt-resistant hypertensive subjects after low (P &lt; 0.002) and high (P &lt; 0.007) NaCl diets. High NaCl intake induced a significant increase in plasma endothelin-1 levels (P &lt; 0.002) as compared with intermediate and low NaCl diet levels in salt-sensitive patients, but did not in salt-resistant subjects. No significant NaCl intake-related variations of urinary endothelin-1 excretion were observed in either group.
4. Salt-sensitive hypertensives are characterized by increased levels of endothelin-1 in both plasma and urine. This fact suggests that blood-pressure sensitivity to NaCl intake could be associated with an increased risk of developing both renal and cardiovascular damage.
Plasma Leptin, Energy Intake and Hunger following Total Hip Replacement Surgery
Authors: Stratton Rebecca J. , Dewit Odile , Crowe Elaine , Jennings Graham , Villar Richard N. , Elia Marinos 
Published: August 2015

1. This study aimed to investigate the possible role of leptin in post-traumatic anorexia by making pre- and post-operative (0–8 days) measurements of circulating leptin concentrations in six patients undergoing elective total hip replacement for osteoarthritis.
2. Mean daily hunger rating (four categories) and food intake (assessed by food record charts) were measured pre-operatively, as well as post-operatively for the first 5 days (days 0–5). Leptin concentrations, circulating metabolites [glucose, non-esterified fatty acids, glutamine and 3-hydroxy-butyrate] and insulin and cortisol concentrations were measured pre-operatively (day 0) and post-operatively (days 1, 2, 3, 5 and 8).
3. Mean leptin concentrations were significantly increased only on day 1 (56% increase compared with pre-operative values, P &lt; 0.009), whereas food intake (only 0.6 MJ on day 0) and hunger (5/6 patients ‘not hungry’ on day 0) only gradually improved over the next few days. (The energy intake over the first 5 days was 56% of the pre-operative value.)
4. Circulating insulin and cortisol concentrations were elevated on day 1 compared with pre-operative values on day 0 (P&lt;0.05). Of the measured metabolites implicated in the control of food intake, circulating non-esterified fatty acids and 3-hydroxybutyrate were not significantly altered in the post-operative period, but significant hyper-glycaemia was noted on day 1 compared with day 0 pre-operatively (8.8 compared with 6.4 mmol/l glucose; P &lt; 0.01).
5. It is concluded that circulating leptin is involved in the early (&lt;24 h) acute-phase response after moderately severe surgical trauma (characterized biochemically by a substantial acute-phase protein response, hypoalbuminaemia, hyperglycaemia and hypoglutaminaemia). Therefore, leptin may be implicated in post-traumatic anorexia, although other factors are likely to be involved, especially after the first 24 h when circulating leptin concentrations are no longer elevated.
Different Dietary Calcium Intake and Relative Supersaturation of Calcium Oxalate in the Urine of Patients Forming Renal Stones
Authors: Messa Piergiorgio , Marangella Martino , Paganin Luisa , Codardini Mara , Cruciatti Aldo , Turrin Daniela , Filiberto Zattoni , Mioni Giuseppe 
Published: August 2015

1. Dietary calcium restriction, an efficient practice in reducing urinary calcium excretion, has been reported to induce either an increase or no change in oxalate excretion, questioning its use in hypercalciuric stone-forming patients. In addition, calcium restriction has been previously demonstrated to induce other urinary changes which might influence the relative supersaturation of calcium oxalate. So the overall effect of calcium deprivation on the relative supersaturation of calcium oxalate is unpredictable.
2. The aim of the study was to evaluate the effect of dietary calcium restriction on the relative supersaturation of calcium oxalate in the urine of stone-forming patients utilizing a computer methodology which takes into account the main soluble complex species of oxalate.
3. We studied 34 stone-forming patients on both a free-choice diet, whose Ca and oxalate content (24 and 1.2 mmol respectively) was assessed by dietary inquiry, and after 30 days on a prescribed low-calcium and normal oxalate diet (11 and 1.1 mmol respectively). Under both conditions, the excretion of the main urinary parameters related to dietary composition, electrolytes, oxalate and daily citrate urinary excretion, were measured. The relative supersaturation of calcium oxalate was calculated by means of an iterative computer method which takes into account the main soluble complex species on which the solubility of calcium oxalate is dependent. In addition, intact parathyroid hormone and 1,25-dihydroxyvitamin D blood levels were also evaluated. In 13 of the patients intestinal calcium absorption was evaluated during both a free- and a low-calcium diet, utilizing kinetics methodology.
4. The low-calcium diet induced, together with an expected reduction of calcium excretion, a marked increase in oxalate urinary output. This finding was independent of the presence or otherwise of hypercalciuria and of the serum levels of parathyroid hormone and vitamin D. Intestinal calcium absorption was also stimulated by calcium deprivation and its levels were well correlated with oxalate excretion. Minor changes in magnesium and citrate excretion were also observed. The overall effect on the relative supersaturation of calcium oxalate consisted in a substantial increase in this parameter during the low-calcium diet.
5. In conclusion, our data reinforce the concept that dietary calcium restriction has potentially deleterious effects on lithogenesis, by increasing the relative supersaturation of calcium oxalate.
Angiotensin-Converting Enzyme Gene Polymorphism and Cardiovascular Disease
Authors: Butler R. , Morris A. D. , Struthers A. D. 
Published: August 2015

1. The crucial role played by the renin-angiotensin—aldosterone system in the cardiovascular system and the immense therapeutic potential of angiotensin-converting enzyme inhibitors and, more recently, angiotensin II receptor blocking agents, in both heart failure and post-myocardial infarction is becoming increasingly evident. Polymorphisms within the genes controlling this enzyme system are candidates for the elucidation of the pathogenesis of cardiovascular disease and this link is both intriguing and provocative. Recently, an association between a polymorphism of the angiotensin-converting enzyme gene and phenotypic expression of cardiovascular disease, namely myocardial infarction, was reported. Since then, several small case-controlled studies have confirmed an association with manifestations of ischaemic heart disease or various other cardiac end-points. However, in a large prospective study the angiotensin-converting enzyme gene conferred no appreciable risk.
2. Our aim was to review the evidence that links polymorphisms of the angiotensin-converting enzyme gene with cardiovascular disease. We searched the Medline database (1990–1997) using the key words myocardial infarction, ischaemic heart disease, angiotensin-converting enzyme and polymorphisms and performed a search of the reference citation of relevant articles. We selected clinical studies on cardiovascular disease related to the angiotensin-converting enzyme genotype
3. Taken together, the available evidence supports the notion that the DD-angiotensin-converting enzyme genotype adversely influences specific cardiovascular diseases but appears to do so in specific geographical areas and in particular patient subgroups. It is not yet known whether it does this through an interaction with other genes or by as yet unexplained biochemical mechanisms.
4. We should regard the current data with the angiotensin-converting enzyme genotype as an intriguing clue in the pathogenesis of cardiovascular disease. However, the main factor against this potential benefit is that the impact of the DD genotype appears to be small and its clinical manifestations rather heterogeneous.
Genetic Susceptibility to the Development of Autoimmune Disease
Authors: Heward Joanne , Gough Stephen C. L. 
Published: August 2015

1. Autoimmune diseases are common conditions which appear to develop in genetically susceptible individuals, with expression of disease being modified by permissive and protective environments. Familial clustering and data from twin studies provided the impetus for the search for putative loci. Both the candidate gene approach in population-based case-control studies and entire genome screening in families have helped identify susceptibility genes in a number of autoimmune diseases.
2. After the first genome screen in type 1 (insulin-dependent) diabetes mellitus it seems likely that most autoimmune diseases are polygenic with no single gene being either necessary or sufficient for disease development. Of the organ-specific autoimmune diseases, genome screens have now been completed in insulin-dependent diabetes mellitus and multiple sclerosis. Furthermore, the clustering of autoimmune diseases within the same individuals suggests that the same genes may be involved in the different diseases. This is supported by data showing that both HLA (human leucocyte antigen) and CTLA-4 (cytotoxic T-lymphocyte-associated-4) appear to be involved in the development of insulin-dependent diabetes mellitus and Graves' disease.
3. Genome screens have also been completed in some of the non-organ-specific autoimmune diseases including rheumatoid arthritis, inflammatory bowel disease and psoriasis. Many candidate genes have also been investigated although these are predominantly in population-based case-control studies.
4. Substantial progress has been made in recent years towards the identification of susceptibility loci in autoimmune diseases. The inconsistencies seen between case-control studies may largely be due to genetic mismatching between cases and controls in small datasets. Family-based association studies are being increasingly used to confirm genetic linkages and help with fine mapping strategies. It will, however, require a combination of biology and genetics, as has been necessary with the major histocompatibility complex in insulin-dependent diabetes mellitus, to identify primary aetiological mutations.
Increased l-arginine Transport in Human Erythrocytes in Chronic Heart Failure
Authors: Hanssen H. , Brunini T. M. C. , Conway M. , Banning A. P. , Roberts N. B. , Mann G. E. , Ellory J. C. , Ribeiro A. C. Mendes 
Published: August 2015

1. Transport of l-arginine was investigated under zero-trans conditions in human erythrocytes from healthy donors and patients with heart failure.
2. Saturable influx of l-arginine was mediated by the classical cationic amino acid transport systems y+ and y+L.
3. The Vmax for l-arginine transport via system y+ increased from 292 to 490 μmol h−-1 l−-1 of cells in heart failure.
4. With system y+ inhibited by N-ethylmaleimide (0.2 mmol/l), the Vmax for the transport of l-arginine via system y+L was unaffected in erythrocytes from patients with heart failure.
5. The inhibition of l-arginine and l-leucine influx by NG-monomethyl-l-arginine was similar in erythrocytes from control and heart failure patients.
6. Plasma l-arginine levels were reduced in patients with heart failure (59 μmol/l) compared with controls (125 μmol/l). Plasma from patients with heart failure also contained the endogenous l-arginine analogue NG-monomethyl-l-arginine, which was undetectable in plasma from controls.
7. Intracellular concentrations of l-arginine and NG-monomethyl-l-arginine were significantly elevated in erythrocytes from patients with heart failure compared with controls, consistent with an increased transport capacity for l-arginine and NG-monomethyl-l-arginine.
8. The present study provides the first evidence that system y+ mediates the increased transport of l-arginine in human erythrocytes from patients with chronic heart failure. These findings are similar to our previous results obtained in patients with chronic renal failure. Since both pathologies seem to present with an increased synthesis of nitric oxide, studies of l-arginine transport in erythrocytes may provide a valuable paradigm to study abnormalities of the l-arginine-nitric oxide signalling pathway.
Hypotensive and Regional Haemodynamic Effects of Exercise, Fasted and after Food, in Human Sympathetic Denervation
Authors: Puvi-Rajasingham Sharmini , Smith Gareth D. P. , Akinola Adeola , Mathias Christopher J. 
Published: August 2015

1. In human sympathetic denervation due to primary autonomic failure, food and exercise in combination may produce a cumulative blood pressure lowering effect due to simultaneous splanchnic and skeletal muscle dilatation unopposed by corrective cardiovascular reflexes. We studied 12 patients with autonomic failure during and after 9 min of supine exercise, when fasted and after a liquid meal. Standing blood pressure was also measured before and after exercise.
2. When fasted, blood pressure fell during exercise from 162 ± 7/92 ± 4 to 129 ± 9/70 ± 5 mmHg (mean arterial pressure by 22 ± 5%), P &lt; 0.0005. After the meal, blood pressure fell from 159 ± 8/88 ± 6 to 129 ± 6/70 ± 4 mmHg (mean arterial pressure by 22 ± 3%), P &lt; 0.0001, and further during exercise to 123 ± 6/61 ± 3 mmHg (mean arterial pressure by 9 ± 3%), P &lt; 0.01. The stroke distance—heart rate product, an index of cardiac output, did not change after the meal. During exercise, changes in the stroke distance—heart rate product were greater when fasted.
3. Resting forearm and calf vascular resistance were higher when fasted. Calf vascular resistance fell further after exercise when fasted. Resting superior mesenteric artery vascular resistance was lower when fed; 0.19 ± 0.02 compared with 032 ± 0.06, P &lt; 0.05. After exercise, superior mesenteric artery vascular resistance had risen by 82%, to 0.53 ± 0.12, P &lt; 0.05 (fasted) and by 47%, to 0.29 ± 0.05, P &lt; 0.05 (fed).
4. On standing, absolute levels of blood pressure were higher when fasted [83 ± 7/52 ± 7 compared with 71 ± 2/41 ± 3 (fed), each P &lt; 0.05]. Subjects were more symptomatic on standing post-exercise when fed.
5. In human sympathetic denervation, exercise in the fed state lowered blood pressure further than when fasted and worsened symptoms of postural hypotension.
Does Total Antioxidant Status Relate to Outcome in Very Preterm Infants?
Authors: Drury Josephine A. , Nycyk Julie A. , Baines Malcolm , Cooke Richard W. I. 
Published: August 2015

1. In healthy humans, a balance exists between oxygen-derived free-radical production and their removal by antioxidants. In preterm infants inadequate antioxidant defences may contribute to the pathogenesis of some of the complications of prematurity.
2. Plasma total antioxidant status and malondialdehyde concentration were measured during the first 11 days of life in 25 infants to determine whether increased lipid peroxidation is associated with low extracellular antioxidant status. In a second group of infants, total antioxidant status was quantified within 12 h of birth, and subsequently on days 4 and 10 to investigate the hypothesis that adverse neonatal outcome is associated with low antioxidant status.
3. There may be a weak negative correlation between the total antioxidant status of infants and the lipid peroxidation marker malondialdehyde in plasma (r = −0.24, P = 0.056, n = 89) during the first 11 days of life. In the second group of infants, total antioxidant status was found to be significantly related to plasma urate and bilirubin levels, but not to adverse neonatal outcomes such as chronic lung disease, intraventricular haemorrhage, retinopathy of prematurity or death.
4. If adverse neonatal outcomes are due to inadequate antioxidant defences, these are likely to be intracellular or localized rather than general extracellular deficiencies.
Bone Mineral Changes during Pregnancy and Lactation: A Longitudinal Cohort Study
Authors: Kolthoff Niels , Eiken PIA , Kristensen Bent , Nielsen Stig Pors 
Published: August 2015

1. The influence of pregnancy, lactation and weaning on bone mineral density in healthy women was investigated during a 2 year prospective study of 59 pregnant and lactating women from the 18th week of gestation.
2. Bone mineral density was measured by dual energy X-ray absorptiometry at the non-dominant radius ultra distally and more proximally in the 18th and 37th weeks of gestation, and 0, 3, 6, 12 and 18 months after delivery. Measurements of bone mineral density of the lumbar spine, the proximal femur and the whole body were performed at all dates after delivery.
3. Reappearance of menstruation after delivery averaged 6.1 months; mean lactating period was 8.7 months. During pregnancy and lactation bone mineral density tended to decrease, but different measuring sites showed different patterns of bone mineral density changes. The reduction in the ultra distal radius during pregnancy amounted to 2%, and no further changes were observed here during lactation. After delivery, reduction in mean bone mineral density was most pronounced in the spine (5.2% in 3 months), but the fall in bone mass tended to revert after resumption of menstruation. Bone mineral density was still reduced by 3.3% after 12 months in women with menstruation resumption later than 8 months after delivery. No significant reduction was observed 18 months after delivery. No association with calcium intake, weight changes or initial bone mineral density was observed. High calcium intake did not protect against bone mineral loss in the spine and the femur.
4. Thus it can be concluded that bone loss during pregnancy and lactation took place mainly from the trabecular skeleton. Resumption of menstruation tended to result in a regain of bone mass towards baseline.