bluuebunny/crossref_metadata_2025_split huggingface dataset:
Telomerase activity in needle biopsies from prostate cancer and benign prostates
Authors: Wymenga  , Wisman  , Veenstra  , Ruiters  , Mensink  
Published: March 2003

BackgroundTelomerase activation is thought to be essential for the immortality of cancer cells. It may be a prognostic factor in small volume well differentiated prostate cancers and hence a guide for the aggressiveness of the approach. The length of the chromosome tips (telomeres) are maintained by a specific enzyme (telomerase) independently of the normal cell division cycle. Although telomerase is not expressed in most normal human tissues, it is expressed in most human tumours. For the detection of telomerase in small prostate needle biopsy samples a recently developed telomeric repeat amplification protocol (TRAP) assay was used. The aim of the present study was: to measure telomerase activity in human prostate samples, and to evaluate the applicability of this assay on specimens from a prostate biopsy.Materials and methodsFrom 36 patients referred for lower urinary tract symptoms (LUTS) or suspicion of having prostate cancer a total of 288 prostate biopsy samples were obtained (8 in each patient). When the digital rectal examination was abnormal and/or when the PSA level was elevated in L.U.T.S., or asymptomatic patients' tissue samples were obtained by transrectal ultrasound (TRUS) guided biopsies. Samples were tested for telomerase activity by a modified TRAP and forwarded for histology.ResultsIn 19 out of 36 patients prostate cancer was diagnosed on histology. In 11 of these 19 tumours substantial telomerase activity was detected, whereas only very low telomerase activity existed in 2 of 17 samples from benign prostatic hypertrophy (BPH) patients. In this small series the relative telomerase activity in prostate cancer correlated with histopathological grade.ConclusionsOur results show the applicability of a TRAP assay to measure telomerase activity in small needle biopsied prostate samples. In poorly differentiated and metastatic cancer we observed that levels of telomerase activity were high. To establish accuracy and to distinguish the ‘relative good from the ugly’ further study is needed.
Serum concentration of 5‐S‐cysteinyldopa in patients with melanoma
Authors: Bánfalvi T. , Gilde K. , Boldizsár M. , Fejös Z. , Horváth B. , Liszkay G. , Beczássy E. , Kremmer T. 
Published: March 2003

Background5‐S‐cysteinyldopa (5‐S‐DC) is a precursor of melanin. Its serum and urinary level can reflect melanoma progression. In this study we examined the concentration changes of 5‐S‐CD in melanomas of different clinical stages and in patients with different symptoms of melanoma, during and after treatment.MethodSerum samples were taken from 252 melanoma patients on 765 occasions, from June 1996 to July 1998. Levels of 5‐S‐CD were determined by HPLC.ResultsThe value of 5‐S‐CD in patients with primary melanoma and in patients without symptoms ranged around the normal level. There was a significant difference between the values of patients with or without symptoms. There was also a significant difference between the 5‐S‐CD values at clinical Stage I and Stage III, as well as at clinical Stage II and Stage III, respectively. Analysing the values of patients with symptoms we found a significant difference between the mean values of primary tumour and stage III, between values in lymph node metastasis and stage III, between values in lung metastasis and stage III. The tumour burden was found to correlate with a rising marker level. In 7% of the symptomatic patients that had a marker level under the upper limit, amelanotic primary tumour was detected.ConclusionAccording to the high marker level in lung and liver metastases, the marker might be useful in monitoring both patients with disease free ocular melanomas, to detect liver metastasis and high‐risk patients after surgical removal of the primary tumour to reveal lung metastases.
Mutations and deletions in core promoter and precore stop codon in relation to viral replication and liver damage in Singaporean hepatitis B virus carriers
Authors: Chen  , Oon  
Published: March 2003

BackgroundThe core promoter of hepatitis B virus (HBV) is crucial for the viral replication and mutations may lead to the establishment of chronic infection and development of liver diseases. We analysed this region in Singaporean HBV carriers and assessed their association with viral replication and liver damage.Materials and MethodsThirty‐three Singaporean HBV carriers were selected. Serological markers for HBV infection and indicators for liver functions were analysed using commercial kits. Among these patients, 17 were chronic carriers, 10 had cirrhotic livers and 6 others had hepatocellular carcinoma (HCC). The region on the HBV genome covering the entire core promoter and core gene was amplified for each patient by polymerase chain reaction. The amplified DNA fragments were sequenced and analysed.ResultsThe incidence of mutations in the core promoter or the precore gene product (stop codon at amino acid 28) was not significantly higher compared with the wild type sequences in patients with liver damage. Most mutations in either the core promoter or precore gene significantly reduced the viral replication, as indicated by HBV DNA levels. High levels of HBV DNA were found in three mutants with deletion in the same region, presumably the binding site of liver enriched factor, within the core promoter.ConclusionOur findings revealed a different mutation pattern in the core promoter in Singaporean HBV carriers. While most mutations may not be directly associated with the development of liver diseases, deletions in the core promoter could contribute to enhanced viral replication and should be studied further.
Effects of comicronised fenofibrate on lipid and insulin sensitivity in patients with polymetabolic syndrome X
Authors: Idzior‐Walus B. , Sieradzki J. , Rostworowski W. , Zdzienicka A. , Kawalec E. , Wójcik J. , Żarnecki A. , Blane G. 
Published: March 2003

BackgroundThis study investigated the effects of comicronised fenofibrate in patients with dyslipidemia and polymetabolic syndrome X.DesignAfter a 6‐week dietary run‐in phase, 37 male patients eligible on lipid criteria entered a 12‐week treatment phase consisting of diet plus one capsule daily containing 200 mg of comicronised fenofibrate (Lipanthyl®).ResultsA significant reduction in plasma concentrations of total cholesterol, LDL cholesterol and triglyceride was observed after 4, 8 and 12 weeks of treatment with fenofibrate. The improvement in the atherogenic index LDL/HDL cholesterol from a pretreatment 3.8 to 3.0 after treatment was highly statistically significant and may be judged as satisfactory. Significant changes were also observed in haemostatic factors (fibrinogen reduced by 19%, factor VII activity reduced by 18%). Fasting serum insulin levels and insulin response (area under the curve) after oral glucose load were significantly reduced by 26.8% and 18.7%, respectively, indicating an improvement of insulin sensitivity. Systolic and diastolic blood pressure were significantly reduced. Uric acid was significantly reduced by 21.6%.ConclusionThese favourable effects of comicronised fenofibrate both on lipid and non lipid parameters, including insulin sensitivity, may confer to this product a particular interest in the treatment of patients with polymetabolic syndrome X.
Cytokine secretion is impaired in women with diabetes mellitus
Authors: Geerlings S. E. , Brouwer E. C. , Van Kessel K C. P. M. , Gaastra W. , Stolk R P. , Hoepelman A I. M. 
Published: March 2003

As women with diabetes mellitus (DM) have an increased prevalence of asymptomatic bacteriuria (ASB) and it is known that a correlation exists between the increased prevalence of genitourinary tract infection and impaired cytokine production in women infected with Human Immunodeficiency Virus (HIV), we studied urinary cytokine excretion in diabetic women and compared it with that of nondiabetic controls.To evaluate the cytokine secretion capacity of women with DM, both whole blood and isolated monocytes of women with and without DM were stimulated in vitro with lipopolysaccharide (LPS).Lower urinary interleukin‐8 (IL‐8) and interleukin‐6 (IL‐6) concentrations (P = 0·1 and P < 0·001, respectively) were found in diabetic women than in nondiabetic controls. A lower urinary leukocyte cell count correlated with lower urinary IL‐8 and IL‐6 concentrations (P < 0·05). Lower tumour necrosis factor‐alpha (TNF‐α) and IL‐6, but comparable interleukin‐10 (IL‐10) concentrations were found in whole blood (P < 0·04) and isolated monocytes (P = 0·03) of women with DM type 1 compared to women without DM.Diabetic women with ASB have lower urinary IL‐6 concentrations than nondiabetic bacteriuric controls. In addition, monocytes of women with DM type 1 secrete lower pro‐inflammatory cytokines after stimulation with LPS than monocytes of women without DM. This is not due to an inhibitory effect of the anti‐inflammatory cytokine IL‐10. This can have important consequences for both host defense, endothelial cell functioning and atherogenesis.
Serum tumour necrosis factor‐α levels in cancer patients are discontinuous and correlate with weight loss
Authors: Bossola M. , Muscaritoli M. , Bellantone R. , Pacelli F. , Cascino A. , Sgadari A. , Battaglia F. , Piccioni E. , Scambia G. , Doglietto G. B. , Fanelli F. Rossi 
Published: March 2003

Tumour necrosis factor‐α (TNF) has been regarded as a potential mediator of cancer cachexia. Assessment of TNF circulating levels in cancer patients and their correlation with weight loss has led to controversial results.We measured TNF circulating levels in 28 patients with gastrointestinal cancer and 29 controls with benign gastrointestinal diseases at different times (08.00 h, 14.00 h, 20.00 h) before operation.TNF activity was not detected in any of controls at any times. In cancer patients, TNF circulating levels were detectable in 18 cases (64·3%) and appeared to be discontinuous. TNF levels above the limit of detection were present in 15 patients (53·6%) at 08.00 h, in 14 (50%) at 014.00 h and in nine (32·1%) at 20.00 h. Mean TNF levels were 14·3 ± 4 pg mL−1 at 08.00 h, 16·7 ± 4·6 pg mL−1 at 14.00 h (P = 0·05) and 18·5 ± 10·2 pg mL−1 at 20.00 h (P < 0·05 vs. 08.00 h and 14.00 h). According to Spearman's analysis, the sum of TNF concentrations at the three times significantly correlated with the severity of weight loss (Spearman's correlation coefficient =− 0·420; P = 0·026). TNF concentrations were consistently and significantly higher in patients with severe weight loss than in those with moderate or light weight loss at 08.00 h (26·3 ± 8·3, 8·9 ± 4·2, 3·8 ± 2·1, respectively; P = 0·04 at one‐way anova). TNF levels were higher in anorectic than in nonanorectic patients at any hour, but the differences were not statistically significant.The present study demonstrates that TNF is intermittently or discontinuously detectable in patients with gastrointestinal cancer and that its levels correlate with the severity of weight loss.
Alterations of lipolytic enzymes and high‐density lipoprotein subfractions induced by physical activity in type 2 diabetes mellitus
Authors: Lehmann R. , Engler H. , Honegger R. , Riesen W. , Spinas G. A. 
Published: March 2003

ObjectiveThis study investigates the effects of regular moderate physical activity on lipolytic enzymes and plasma lipid concentration, particularly high‐density lipoprotein cholesterol (HDL‐C) subfractions, in patients with type 2 diabetes mellitus.Ten patients participated in a 3‐month exercise programme without any changes in current medical therapy. The control group consisted of six patients who were matched with regard to sex, age, diabetes duration and diabetes therapy.ResultsMean (± SE) physical activity in the intervention group increased from 70 ± 21 to 220 ± 28 min per week, which resulted in an increase in total HDL‐C from 1·04 ± 0·07 to 1·28 ± 0·12 (P < 0·001). The HDL3‐C subfraction increased from 0·71 ± 0·08 to 0·86 ± 0·08 mM (P = 0·01) with no significant changes in the HDL2‐C subfraction (0·33 ± 0·04 vs. 0·42 ± 0·05). These changes were paralleled by an 85% increase in hepatic lipase (HL) activity, from 25·7 ± 5·1 to 47·4 ± 4·9 µmol mL−1 h−1(P < 0·001) and a 45% increase in lipoprotein lipase (LPL) activity, from 16·8 ± 3·0–24·3 ± 2·7 µmol mL−1 h−1(P = 0·01). Lecithin‐cholesterol acyl‐transferase (LCAT) activity increased by 32%, from 156 ± 26 to 206 ± 32 nmol mL−1 h−1(P < 0·001). In the control group there were no significant changes in any of the variables assessed.ConclusionsRegular moderate physical activity in patients with type 2 diabetes led to an overall increase in HL, LPL, and LCAT. HL showed a more pronounced increase than LPL and LCAT. The changes in lipolytic and transferase enzyme pattern resulted in a significant increase of plasma HDL‐C, mainly of the HDL3‐C subfraction.
Increased levels of biochemical markers of bone turnover in relation to persistent immune activation in common variable immunodeficiency
Authors: Ueland T. , Frøland S S. , Bollerslev J. , Aukrust P. 
Published: March 2003

Background Based on the involvement of cytokines and growth factors in bone homeostasis, we hypothesised that patients with common variable immunodeficiency (CVI), characterised by persistent immune activation in vivo, may have disturbed bone metabolism as evaluated by biochemical markers of bone turnover. Materials and methods Serum levels of tumour necrosis factor α (TNFα), interleukin‐6 (IL‐6), bone‐specific alkaline phosphatase (B‐ALP), osteocalcin, carboxyterminal crosslinking telopeptide of type I collagen (CTX‐I), insulin‐like growth factor (IGF)‐I and IGF binding protein‐3 (IGFBP‐3) were measured in 25 patients with CVI and compared to 25 age‐ and sex‐matched healthy controls. Results Patients with CVI had significantly higher serum levels of CTX‐I and B‐ALP, and significantly lower serum levels of IGF‐I and IGFBP‐3 compared to controls as shown in cross‐sectional, and as for B‐ALP and CTX‐I, also during longitudinal testing. No differences were observed for osteocalcin between the two groups. The elevated B‐ALP and decreased IGF‐I and IGFBP‐3 levels were most pronounced in a subgroup of CVI patients characterised by persistent activation of proinflammatory cytokines in vivo. Raised B‐ALP and decreased IGF‐I and IGFBP‐3 were also significantly correlated with enhanced IL‐6 and TNF‐α levels in these patients. Conclusions The present study suggests that persistent immune activation in vivo, with raised levels of proinflammatory cytokines, may be related to disturbed bone homeostasis in CVI patients, further supporting an interaction between immune related mediators and bone metabolism in humans.
Type I collagen markers in cord serum of appropriate vs. small for gestational age infants born during the second half of pregnancy
Authors: Saarela T. , Risteli J. , Kauppila A. , Koivisto M. 
Published: March 2003

Background The serum concentration of the N‐terminal propeptide of type I procollagen (PINP) reflects the synthesis rate of type I collagen, whereas the corresponding C‐terminal telopeptide (ICTP) mirrors its degradation.Design PINP and ICTP were measured in a total of 690 cord serum samples from 592 appropriate‐for‐gestational‐age (AGA) infants and 98 smal‐for‐gestational‐age (SGA) infants. These markers were compared between AGA and SGA infants of different gestational ages, ranging from 23 to 41 weeks, and birth weights, from 620 to 4555 g.Results Both PINP and ICTP levels were very high in the preterm AGA infants and declined significantly with advancing gestational age, paralleling the shape of the fetal growth velocity curve. Regardless of the quite large interindividual variations observed in these markers, PINP was significantly lower in both the preterm and term AGA infants than in the SGA infants. This was also the case for ICTP in the preterm infants of gestational age less than 36 weeks. In stepwise multiple regression analyses, gestational age, being either AGA or SGA and head circumference were significant factors to explain the levels of PINP and ICTP. The levels of PINP and ICTP were correlated with each other highly significantly in both the AGA and SGA infants (rs = 0·700 and 0·692, respectively; P < 0·001 in both).Conclusions The levels of type I collagen markers seem to follow closely the shape of the fetal growth velocity curve during different stages of gestation. However, because of the large interindividual variations observed, further studies are needed before the significance of these markers for the assessment of normal and abnormal fetal growth can be established.
Association studies between haemochromatosis gene mutations and the risk of cardiovascular diseases
Authors: Hetet G. , Elbaz A. , Gariepy J. , Nicaud V. , Arveiler D. , Morrison C. , Kee F. , Evans A. , Simon A. , Amarenco P. , Cambien F. , Grandchamp B. 
Published: March 2003

Background Haemochromatosis is a common genetic disorder, inherited as an autosomal recessive trait that results in a progressive accumulation of iron in most tissues of the body. Positive association studies have been recently published between cardiovascular diseases and heterozygosity for the major mutation C282Y in the haemochromatosis gene HFE.Methods In the present work, we have determined the HFE genotypes for C282Y and H63D in subjects from two case‐control studies: the ECTIM and GENIC studies, designed to identify genetic variants associated with myocardial and brain infarction, respectively. In addition, we tested whether HFE mutations were associated with the degree of arteriosclerosis assessed non‐invasively by Doppler ultrasonography on the carotid and femoral arteries, in a group of apparently healthy individuals (the AXA Study).Results The prevalence of 282Y, and 63D allele carriers, did not differ between cases and controls in the ECTIM and in the GENIC studies, while 63D but not 282Y carriers were more numerous among subjects with atherosclerotic plaques in the AXA Study.Conclusions These three studies do not provide consistent evidence supporting the hypothesis that HFE mutations are associated with an increased risk of cardiovascular disease and with the development of arteriosclerosis.
Hepatic lipase gene variation is related to coronary reactivity in healthy young men
Authors: Fan Ym , Laaksonen R. , Janatuinen T. , Vesalainen R. , Nuutila P. , Koivula T. , Knuuti J. , Lehtimäki T. 
Published: March 2003

Background Impaired coronary flow reserve (CFR) can be used to indicate vascular dysfunction before the appearance of angiographic lesions. The hepatic lipase (HL) gene has a functional promoter polymorphism at position C‐480T, which affects transcription and leads to high activity (C/C) and low activity (C/T, T/T) genotypes. These genotypes modulate HL activity, but their role in coronary artery disease is controversial and the effect on coronary function has not been studied. We investigated whether HL genotypes are associated with coronary artery function in healthy young men.Materials and methods We studied 49 healthy, mildly hypercholesterolemic men (aged 35 ± 4 years). Myocardial blood flow was measured at rest and during adenosine induced hyperaemia with positron emission tomography using [15O] H2O. HL genotype was determined by PCR and Nla III enzyme digestion.Results Resting myocardial blood flow was not statistically different in subjects with high and low activity HL genotypes. However, CFR (the ratio of adenosine flow to resting flow) was 24% higher (4·62 ± 1·52 vs. 3·73 ± 1·08 mL g−1 min−1, P = 0·024) in men with the high activity genotype (n = 26) than in those with low activity (n = 23). In multivariate analysis, the HL genotype remained a significant predictor of CFR (P = 0·038) after adjusting for age, body mass index, serum lipids and smoking.Conclusions The findings of our preliminary study suggest that the C‐480T polymorphism of the HL gene may modify coronary reactivity and reflect differences in the early pathogenesis of coronary dysfunction in these healthy young men. If the association between HL polymorphism and impaired CFR is also present in subjects with other dyslipoproteinemias, the HL polymorphism could be a new risk factor for cardiovascular disease.
Analysis of exocrine pancreatic function in cystic fibrosis: one mild CFTR mutation does not exclude pancreatic insufficiency
Authors: Walkowiak J. , Herzig K.‐H. , Witt M. , Pogorzelski A. , Piotrowski R. , Barra E. , Sobczynska‐Tomaszewska A. , Trawinska‐Bartnicka M. , Strzykala K. , Cichy W. , Sands D. , Rutkiewicz E. , Krawczynski M. 
Published: March 2003

Background Cystic fibrosis (CF) is the most common cause of exocrine pancreatic insufficiency in childhood. The aim of the present study is to evaluate the correlation between genotype and exocrine pancreatic insufficiency in CF patients. The special emphasis was put on the analysis of mild CFTR mutations.Design The study comprised 394 CF patients and 105 healthy subjects (HS). Elastase‐1 concentrations were measured in all subjects.Results Severe pancreatic insufficiency was associated with the presence of two CFTR gene mutations (ΔF508, N1303K, CFTR dele 2,3 (21kb), G542X, 1717–1G‐A, R533X, W1282X, 621GT, 2183AAG, R560T, 2184insA and ΔI507, G551D, 895T) and mild insufficiency with the presence of at least one mutation (R117H, 3171insC, A155P2, 138insL, 296 + 1G‐A, E92GK, E217G, 2789 + 5G‐A. 3849 + 1kbC‐T/3849 + 1kbC‐T) genotype resulted in high elastase‐1‐values. However, in case of patients with genotype ΔF508/3849 + 10kbC‐T, 1717–1GA/3849 + 10kbC‐T as well as with ΔF508/R334W, both high and low elastase‐1 concentrations were found. Low E1 values were found in a patient with ΔF508/R347P genotype.Conclusion Patients who carry two ‘severe’ mutations develop pancreatic insufficiency, whereas those who carry at least one ‘mild’ usually remain pancreatic sufficient. However, the presence of one mild mutation does not exclude pancreatic insufficiency.
Ageing impairs insulin‐mediated vasodilatation but not forearm glucose uptake
Authors: Lind L. , Fugmann A. , Millgård J. , Berne C. , Lithell H. 
Published: March 2003

Background It is unclear if insulin‐mediated vasodilatation is altered by ageing and if this affects insulin‐mediated glucose uptake.Material and methods A 2‐h euglycaemic hyperinsulinaemic clamp (56 mU m−2 min−1) was performed in 10 healthy, nonobese elderly men (70–75 years) and 13 young men (23–28 years). Forearm blood flow (FBF) was measured by venous occlusion plethysmography and forearm glucose uptake was calculated by arterial and venous serum glucose determinations in the forearm.Results Insulin induced an increase in FBF in the younger men (from 3·9 ± 1·1 SD to 5·9 ± 2·2 mL min−1 100 −1mL tissue, P < 0·001), but this insulin‐mediated vasodilatation was completely blunted in the elderly subjects. Glucose extraction during the clamp was significantly higher in the elderly subjects (1·2 ± 0·76 vs. 0·82 ± 0·37 mmol L−1 at 120 min, P < 0·01), resulting in a similar forearm glucose uptake in the two groups. On the other hand, whole‐body glucose uptake was significantly decreased in the elderly subjects (5·3 ± 1·8 vs. 8·0 ± 1·1 mg kg−1 min−1, P < 0·001).Conclusion The present study showed that the ability of insulin to induce vasodilatation is blunted in the forearm in healthy, nonobese elderly subjects. However, the elderly compensate for this impairment with an increased glucose extraction from arterial blood to maintain an unaltered forearm glucose uptake.