bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigation into thiol conjugation of transthyretin in hereditary transthyretin amyloidosis
Authors: Suhr  , Ando  , Ohlsson  , Olofsson  , Andersson  , Lundgren  , Ando  , Holmgren  
Published: March 2003

BackgroundFor all forms of amyloidosis, the amyloid‐generating mechanism is unknown. Familial amyloidotic polyneuropathy type I is caused by a variant transthyretin (TTR Met‐30). As electrospray ionization mass spectrometry (ESI‐MS) discloses both thiol‐conjugated and ‐unconjugated forms of wild‐type and variant TTR, we wanted to investigate the relationship between TTR conjugation and clinically overt amyloid disease.MethodsPlasma from 35 individuals (12 symptomatic TTR Met‐30 carriers, nine asymptomatic and 14 healthy control subjects) were analysed using ESI‐MS.ResultsThe total TTR concentration was significantly lower in symptomatic TTR Met‐30 carriers than in control subjects. An increased percentage of conjugated TTR Met‐30 was found in symptomatic carriers compared with asymptomatic, whereas the percentage conjugated wild‐type TTR was similar for control subjects, asymptomatic and symptomatic TTR Met‐30 carriers.ConclusionThe finding of a decreased ratio of unconjugated to conjugated TTR Met‐30 in plasma samples from symptomatic TTR Met‐30 carriers indicates that thiol conjugation of TTR could be involved in amyloid formation.
Cardiovascular risk factors associated with clinically isolated and diffuse atherosclerosis in Spanish patients with coronary artery disease
Authors: Meco  , Pintó  , Escribà  , Vela  , Jara  , Pallarés  , Castiñeiras  , Pujol  
Published: March 2003

BackgroundPatients with coronary artery disease (CAD) associated with peripheral (PAD) or cerebrovascular disease (CVD), a condition called diffuse atherosclerosis, have a higher risk of death than patients with isolated CAD. The prevalence of diffuse atherosclerosis and the atherogenic risk factors associated with this condition in our geographic area have not been described previously.MethodsA cohort of 2597 patients (62 ± 10.8 years, 665 women) consecutively admitted at Bellvitge Hospital because of acute coronary syndromes were studied. CAD patients were divided in two groups with diffuse and located atherosclerosis according to whether they had or they had not an associated PAD or CVD. Baseline history, physical data and lipid profile were recorded in each patient according to a standardized questionnaire.ResultsA total of 370 patients (14.2%) had diffuse atherosclerosis. Among them, there were more men and women older than 55 years than among those with isolated CAD. Patients with diffuse atherosclerosis were more frequently hypertensive, diabetic and former smokers than those with isolated CAD (60.5% vs. 49.4%, P < 0.01; 37.4% vs. 24.5%, P < 0.01; and 47% vs. 35.7%, P < 0.01, respectively). There were no significant differences in the mean values of total cholesterol (TC), low‐density cholesterol (LDL‐C), high‐density cholesterol (HDL‐C) and triglycerides between both groups of patients, but patients with diffuse atherosclerosis had a lower HDL‐C/TC ratio, with borderline statistical significance (0.18 ± 0.06 vs. 0.19 ± 0.06, P = 0.06). Using multiple logistic regression analysis, the variables associated with diffuse atherosclerosis in men were age greater than 55 years (OR 1.97, CI 1.33–2.93), hypertension (OR 1.50, CI 1.14–2.20), diabetes (OR 1.78, CI 1.20–2.70), smoking (former smokers) (OR 2.09, CI 1.36–3.24) and HDL‐C/TC < 0.20 (OR 1.60, CI 1.18–2.17); and in women hypertension (OR 3.43, CI 1.48–7.94) and diabetes (OR 2.58, CI 1.55–4.80).ConclusionsClinically overt diffuse atherosclerosis is a relatively common disease. Older patients and those with hypertension, diabetes or low HDL‐C/TC ratio are more likely to have diffuse atherosclerosis than those without these conditions.
Carbohydrate‐deficient transferrin and gamma‐glutamyltransferase are inversely associated with lipid markers of cardiovascular risk
Authors: Nikkari  , Koivu  , Anttila  , Raunio  , Sillanaukee  
Published: March 2003

BackgroundA variety of epidemiological studies have suggested a U‐shaped association between alcohol consumption and atherosclerosis progression and incidence events. Moderate intake of alcohol is considered beneficial, whereas heavy drinking increases cardiovascular disease risk.MethodsAlcohol and cardiovascular risk‐related laboratory tests were carried out in 70 consecutive male employees in connection with an occupational health survey in 1996. Carbohydrate‐deficient transferrin (CDT) and gamma‐glutamyltransferase (GGT) were used as markers for alcohol consumption. The subjects were divided into quartiles on the basis of CDT or GGT value.ResultsThe highest CDT quartile had significantly higher serum high‐density lipoprotein (HDL)‐cholesterol (P < 0.05) than the lowest quartile. The highest GGT quartile had significantly higher serum total cholesterol (P < 0.01), lower serum HDL‐cholesterol (P < 0.05), higher serum low‐density lipoprotein (LDL)‐cholesterol (P < 0.01) and higher serum triglyceride (P < 0.01) than the lowest quartile.ConclusionsAn explanation for the findings is that high alcohol consumption without significant liver induction increases the level of HDL‐cholesterol, whereas high alcohol consumption with induction of liver may have adverse effects on lipoprotein metabolism. The results were interpreted to indicate that CDT and GGT detect different populations of drinkers in regard to cardiovascular lipid risk factors.
Scopolamine model of dementia: electroencephalogram findings and cognitive performance
Authors: Ebert  , Kirch  
Published: March 2003

BackgroundMemory and cognitive functions are known to decline with advancing age. Studies have suggested that this may be due to a decrease in cholinergic function in the brains of elderly people. This review aims to assess studies documented in the literature dealing with the ‘scopolamine model’ of dementia.MethodsSources included MedLine searches from the last 10 years (search for ‘scopolamine model’, ‘dementia’, ‘electroencephalogram’, ‘cognition’) and references from original and review articles. The aim was to include human and animal studies occupying the cholinergic hypothesis in cognitive dysfunction. Electroencephalographic (EEG) and cognition findings were considered.ResultsScopolamine influences delta, theta, alpha and beta activity in EEG and partially mimics the EEG changes found in patients with senile dementia or dementia of the Alzheimer type. Effects on different cognitive functions have been extensively documented.ConclusionScopolamine produces similar memory deficits seen in the elderly, but the drug cannot induce the full range of deficits seen in patients with Alzheimer's disease. Various aspects of memory were unaffected by scopolamine administration. Memory improvements in elderly subjects can be achieved after cholinergic stimulation.
Growth factor receptor expression in human gastroenteropancreatic neuroendocrine tumours
Authors: Wulbrand  , Wied  , Zöfel  , Göke  , Arnold  , Fehmann  
Published: March 2003

BackgroundHuman gastroenteropancreatic neuroendocrine tumours are functionally and biologically heterogeneous, but their exact growth factor receptor expression pattern, important for onco‐ and carcinogenesis, remains unknown.MethodsThis study searched for the mRNA expression pattern of six tyrosine‐ and serine/threonine kinase receptors [hepatocyte growth factor (HGFR), fibroblast growth factor (FGFR), epidermal growth factor (EGFR), insulin‐like growth factor (IGF)‐1R, transforming growth factor (TGF)‐βR1, TGF‐βR2] together with the five somatostatin receptors in human gastroenteropancreatic neuroendocrine tumours (gastrinomas, insulinomas, tumours with carcinoid syndrome, functionally inactive neuroendocrine tumours) using reverse transcriptase‐polymerase chain reaction (RT‐PCR).ResultsEGF receptor was expressed almost exclusively in gastrinomas. Among the four tumour subtypes, expression frequencies of the somatostatin receptors 1 and 5, HGF‐, IGF‐1‐, TGF‐βR1, TGF‐βR2 and the EGF‐receptor varied significantly.ConclusionsIn spite of the common cellular origin of these tumours, differences in growth factor receptor expression suggest the existence of different pathways during tumour subtype development.
T‐cell receptor gene usage in patients with fibrosing alveolitis and control subjects
Authors: Lympany P. A. , Southcott A. M. , Welsh K. I. , Black C. M. , Boylston A. W. , Du Bois R. M. 
Published: March 2003

BackgroundFibrosing alveolitis is characterized by inflammation, fibrosis and increased numbers of activated CD4+ T‐cells in the lower respiratory tract. The aims of this study were to compare the T‐cell antigen receptor repertoire in the lungs of subjects with fibrosing alveolitis systemic sclerosis (FASSc) with cryptogenic fibrosing alveolitis (CFA) and normal control subjects, to determine whether FASSc is driven by a specific T‐cell trigger and is determined by a T‐cell driven immune response, and to assess the clonality of CD4+ and CD8+ TcR usage in subjects with FASSc.Materials and methodsWe used reverse transcription polymerase chain reaction with specific Vα‐ and Vβ‐chain primers to identify the TcR gene usage in biopsy material, bronchoalveolar lavage fluid or peripheral blood from our subjects.ResultsWe found individual‐specific restriction of Vα‐ and Vβ‐chain usage in lung biopsies from patients and control subjects. To establish whether this was due to expression bias in the CD4+ or CD8+ T‐cells and was restricted to the lung, the αβ‐T‐cell receptor chain usage was assessed in T‐cell subsets separated from the lungs of patients with fibrosing alveolitis and was compared with that of the peripheral blood. There was no consistent difference in the expression of any variable family chain among the population studied, although there was a significant difference between lung and peripheral blood lymphocyte Vβ‐families in CD8+ T‐cells (P = 0.0007).ConclusionWe conclude that there is individual TcR Vα‐ and Vβ‐expression bias in subjects with fibrosing alveolitis.
Physicochemical and functional modifications induced by obesity on human erythrocyte membranes
Authors: Faloia  , Garrapa  , Martarelli  , Camilloni  , Lucarelli  , Staffolani  , Mantero  , Curatola  , Mazzanti  
Published: March 2003

BackgroundNa+,K+‐ATPase activity was evaluated in relation to membrane composition and molecular organization in erythrocyte membranes from obese patients by the amphyphylic molecule 6‐dodecanoyl‐2‐dimethylamino‐naphthalene (Laurdan). Its possible relationship with fat distribution and hyperinsulinaemia was also investigated.DesignSubjects were 10 obese men (OM), 12 women with subcutaneous obesity (FSO), 10 women with abdominal obesity (FAO) and 41 healthy lean subjects, 26 women (FC) and 15 men (MC). An oral glucose tolerance test was administered to all subjects to evaluate insulin secretion and glucose tolerance.ResultsNa+,K+‐ATPase activity was increased in all obese patients. Values were higher in FSO and FAO than in FC (with FAO greater than FSO) and in OM than in MC. The erythrocyte membrane cholesterol‐to‐phospholipid ratio was increased in obese patients and was significantly different in FSO patients compared with FC. The erythrocyte membrane protein‐to‐phospholipid ratio was also increased in all obese subjects, reaching statistical significance only in FSO vs. FC. The liquid crystalline phase, as tested by Laurdan generalized polarization (GP), was decreased in obese patients, indicating the presence of greater molecular environmental order; all patients groups showed lower GP values than control subjects, but only FAO reached statistical significance compared with FC. There was no evident correlation between membrane Na+,K+‐ATPase activity and insulin levels, nor did membrane composition and properties show any evident relationship with insulin levels.ConclusionBoth increased Na+,K+‐ATPase activity and altered fluidity and lipid composition were observed in the erythrocyte membrane of all obese patients. These findings are in line with previous observations by our group and indicate that the changes in Na+,K+‐ATPase activity observed in obese patients could be related to changes in plasma membrane organization and composition.
Endothelial activation and response in patients with hand arm vibration syndrome
Authors: Kennedy  , Khan  , McLaren  , Belch  
Published: March 2003

BackgroundHand–arm vibration syndrome (HAVS) is a form of secondary Raynaud's phenomenon (RP) of occupational origin. In other forms of RP, blood and blood vessel wall interaction is one factor in the pathophysiology. Cytokines and cell adhesion molecules both play an important role in this interaction, and basal vascular tone and vasodilatation are regulated by nitric oxide.MethodsBlood flow responses to acetylcholine (ACh) and sodium nitroprusside (SNP) and levels of soluble intercellular adhesion molecule‐1 (sICAM‐1) and the inflammatory cytokine interleukin 8 (IL‐8) were measured in eight male patients with vibration white finger disease, which is part of HAVS, and in eight healthy matched male control subjects.ResultssICAM‐1 levels were statistically higher (P = 0.02, Mann–Whitney U‐test) and IL‐8 levels (P < 0.01, Mann–Whitney) were significantly lower in the patient group. The patients with HAVS had significantly reduced vascular responses to SNP (P < 0.05,
anova).ConclusionsIn this study, we reveal differences in vascular responses to SNP that suggest there may be an impairment of the smooth muscle response to nitric oxide in patients with HAVS. The increase in sICAM‐1 that occurs in patients with HAVS suggests that leucocyte adhesion is increased and that adherent neutrophils may contribute to the microvascular damage seen in this disease. The impeded flow of blood cells through the microcirculation may result in the low levels of circulating IL‐8 due to the cytokine binding to erythrocytes. The possible role of NO activity in HAVS warrants further investigation.
Skin perfusion in patients with erythromelalgia
Authors: Littleford  , Khan  , Belch  
Published: March 2003

BackgroundErythromelalgia (EM) is a chronic disorder characterized by intermittent pain, warmth and erythema of the extremities. Symptoms can be precipitated by increasing the temperature of the affected limb and can be partially relieved by direct cooling.Materials and methodsMicrovascular assessment was conducted under ‘hot’ (28°C) environmental conditions in 61 EM (EMI) patients and 30 control subjects. Twenty patients with many of the symptoms of EM were enrolled as an active control group (EMII). Using laser Doppler flowmetry, basal skin erythrocyte flux (SkEF) and the hyperaemic response to local heating (44°C) were measured.ResultsCompared with control subjects, basal SkEF was reduced at the toe (P < 0.001), index finger (P < 0.05), dorsal and plantar aspects of the foot (P < 0.01) in both patient groups and at the medial mid‐calf (P < 0.05) in EMI patients. Both EM groups also had a significantly reduced maximum SkEF at the dorsum of foot and medial mid‐calf (all P < 0.001) compared with control values. In a subset of patients and control subjects, transcutaneous carbon dioxide levels were raised in EMI patients (P < 0.02) compared with levels in control subjects. Toe temperature was significantly reduced in both EM groups compared with control subjects (both P < 0.001).ConclusionOur study indicates for the first time that there is a vasoconstrictor tendency in patients with EM, which may be related to functional or structural changes in skin microvessels. Thus, the previous hypothesis that the pathophysiology of EM relates to vasodilatation is not supported in our patients. We believe that, in EM, vasoconstriction precedes reactive hyperaemia, similar to that seen in Raynaud's phenomenon.
[13C]‐Galactose breath test: correlation with liver fibrosis in chronic hepatitis C
Authors: Mion  , Rousseau  , Scoazec  , Berger  , Minaire  
Published: March 2003

BackgroundThe galactose elimination capacity test is a quantitative liver function test that has been shown to be a potential surrogate marker for death in advanced chronic liver diseases. However, this test lacks sensitivity in early liver disease. The goal of this study was to evaluate a [13C]‐galactose breath test (GBT) in a population of patients with chronic hepatitis C.DesignThe GBT was performed in 10 control subjects and 50 patients with chronic hepatitis C; the results were compared with the METAVIR pathological scoring of liver biopsy specimens and with standard biochemical liver function tests.ResultsIn 10 patients, oral vs. intravenous administration of galactose yielded similar results for the GBT (3.01% ± 0.12% dose h−1 for oral galactose vs. 2.98 ± 0.21 for intravenous). The GBT was then performed orally in the remaining 40 patients and 10 control subjects. A significant difference was observed between control subjects and patients (4.51% ± 0.18% vs. 2.97% ± 0.14% dose h−1, P < 0.0001). A significant difference for GBT results was observed between each fibrosis stage, but not with regard to the activity score.ConclusionsThe GBT results are dependent on the severity of liver fibrosis in chronic hepatitis C. Further studies are needed to evaluate the usefulness of the GBT for the follow‐up of chronic hepatitis C.
Plasma acylation stimulating protein, adipsin and lipids in non‐obese and obese populations
Authors: Maslowska  , Vu  , Phelis  , Sniderman  , Rhode  , Blank  , Cianflone  
Published: March 2003

BackgroundAcylation stimulating protein (ASP) is a potent stimulator of TG synthesis in human adipocytes.DesignIn the present study, we have analysed plasma ASP and adipsin levels and their relationships to plasma lipids in non‐obese and obese groups.ResultsThe results show that the frequency distribution of ASP is skewed but that of adipsin is normal in both groups. In the non‐obese population, the mean levels of plasma ASP and adipsin were 20.2 nmol L−1 (median) and 66.6 ± 19 nmol L−1 (mean) respectively. No difference was observed between men and women for each of the parameters. In the obese population, the median plasma ASP was increased by 246% (69.9 nmol L−1) and adipsin by 31% (87.0 ± 22.7 nmol L−1) above that of the control group. Although the levels for men and women were not statistically different for adipsin, the median ASP plasma concentration was 1.9‐fold higher in obese women than in obese men (71.8 nmol L−1 vs. 37.6 nmol L−1, P < 0.05). Best subset regression analysis provided a model with variables that best predict plasma ASP [r2 = 0.160, P < 0.008 for body mass index (BMI), P < 0.05 for triacylglycerol (TG), P < 0.03 for free fatty acid (FFA)] and plasma adipsin (r2 = 0.057, P < 0.017 for BMI) in a non‐obese population. In obese subjects, the model was different for plasma ASP (P = NS for any of the variables) and plasma adipsin (r2 = 0.356, P < 0.008 for FFA, P < 0.0002 for BMI, P < 0.02 for age). There was no correlation between ASP and adipsin in either the non‐obese or the obese group.ConclusionThe present data suggest involvement of the ASP/adipsin pathway in the pathogenesis of obesity.
Angiotensin II increases erythropoietin production in healthy human volunteers
Authors: Freudenthaler  , Schreeb  , Körner  , Gleiter  
Published: March 2003

BackgroundA number of animal studies and our own clinical trials point towards a possible influence of the renin‐angiotensin‐system (RAS) on erythropoietin (EPO) production. In this study we investigated the role of angiotensin II in the regulation of EPO production in humans.MethodsAfter a hemorrhage of 750 ml as a basic physiological stimulus 72 healthy male volunteers received in a parallel design either placebo (physiologic electrolyte solution) for 6 h, angiotensin II i.v. for 6 h (1–3 μg min−1, sufficient to increase systolic blood pressure by 20 mmHg), the selective AT1‐receptor antagonist losartan, the ACE‐inhibitor captopril, angiotensin II + losartan, or angiotensin II + captopril.ResultsAdministration of angiotensin II alone and in combination with captopril resulted in a significantly higher CmaxEPO (67% higher vs. placebo, P < 0.05) and AUCEPO (0–24h) (40% higher vs. placebo, P < 0.05). In the groups receiving losartan or captopril alone or the combination of angiotensin II + losartan no significant difference of CmaxEPO and AUCEPO(0–24h) compared to placebo could be detected.ConclusionsThis study shows in a model of controlled, basic physiological stimulation of renal EPO production that angiotensin II is able to increase EPO levels in humans. This effect of angiotensin II can be blocked by the specific AT1‐receptor antagonist losartan but not by the ACE‐inhibitor captopril. The result may be interpreted as a hint that one signal for the control of EPO production in humans may be mediated by angiotensin II (AT1)‐receptors.
The type and time of menopause as decisive factors for bone mass changes
Authors: Hadjidakis  , Kokkinakis  , Sfakianakis  , Raptis  
Published: March 2003

BackgroundEarly menopause, whether it be natural or surgical, is one of the established risk factors for osteoporosis. Surgical menopause, however, differs from natural menopause owing to the abrupt cessation of estrogen secretion. This study attempts to investigate the influence of menopause type on bone mineral density (BMD) changes.MethodsFour groups, each consisting of 30 women, were compared: early menopause (EMP), surgical menopause (SUMP) and two groups of natural menopause. The two groups share a similar number of years since menopause (YSM) but have a different chronological age (NMPO), or share a similar age but different YSM (NMPY) to the EMP and SUMP. BMD was measured by the DXA method at L2–L4 vertebrae and proximal femur.ResultsMean vertebral BMD of EMP was lower than that of SUMP (P < 0.05) and of NMPY (P < 0.001) women. Femoral neck BMD did not differ between SUMP and EMP women but both exhibited significantly lower BMD than either natural menopause groups. BMD of SUMP and vertebral BMD of NMPY women was inversely correlated to chronological age and to number of YSM. Pertaining to T‐score values according to the osteoporotic range, NMPO, EMP and SUMP women being homogeneous exhibited significantly lower values than NMPY in the vertebrae (F‐ratio = 7.84, P < 0.001). Whereas, in the femoral neck and the trochanter major, EMP and SUMP categories presented significantly lower T‐score values than the NMPO and NMPY (F = 3.61, P < 0.01 and 2.8, P < 0.05 respectively).ConclusionWomen with early menopause exhibit lower vertebral BMD than women of similar age after either surgical or natural menopause. In women of similar age, surgical menopause results in lower vertebral and femoral neck densities compared to natural menopause. Chronological age and the interval after menopause negatively affects bone density in women with similar age whether in surgical or natural menopause.