bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection of cytochrome P450 mRNA transcripts in prostate samples by RT‐PCR
Authors: Finnström N. , Bjelfman C. , Söderström T. G. , Smith G. , Egevad L. , Norlén B. J. , Wolf C. R. , Rane A. 
Published: March 2003

Background The expression of cytochrome P450 (CYP)‐dependent mono‐oxygenases in the prostate is important, as it will determine the rate of activation of potential carcinogens as well as the metabolism of hormones with implications in diseases of the prostate. In addition, the levels of cytochromes P450 in prostatic tumours may well be determinants of the outcome of therapy involving P450 substrates such as anti‐androgens.Methods The gene expression of 12 different CYP genes was measured by reverse transcription–polymerase chain reaction (RT‐PCR) in a total of 28 human prostatic tumour and nontumour samples.Results Intriguingly, a large number of CYP mRNAs were detected in the prostate samples, including CYP1A2, ‐1B1, ‐2C19, ‐2D6, ‐3A4, ‐3A5, ‐3A7 and ‐4B1. CYP1B1 was consistently expressed and CYP3A5 and CYP4B1 were expressed in a majority of the samples tested.Conclusions These data demonstrate a wide range of CYP genes being expressed in the prostate. The relative importance of these enzymes in the pathogenesis and treatment of prostatic disease remains an important theme for further study.
Oral nitric oxide during plaque deposition
Authors: Carossa S. , Pera P. , Doglio P. , Lombardo S. , Colagrande P. , Brussino L. , Rolla G. , Bucca C. 
Published: March 2003

Background Nitric oxide (NO) is one of the most powerful antibacterial compounds. We investigated if NO oral production increases during dental plaque deposition.Materials and methods Oral NO and salivary nitrite were measured in 31 healthy subjects – 11 smokers and 20 nonsmokers – with natural healthy teeth, in the morning after tooth cleaning (baseline), after withdrawal of oral hygiene for 24 h and again after tooth cleaning.Results NO and nitrite were significantly higher during plaque deposition than with clean teeth: mean NO values ± SEM were 44·3 ± 4·9 parts per billion (ppb) at baseline, 58·8 ± 3·7 ppb with plaque and 43·6 ± 3·7 ppb after tooth cleaning, P < 0·05; nitrite values were 32·9 ± 5·5 µm at baseline, 66·4 ± 8·2 with plaque and 37·5 ± 5·5 after tooth cleaning, P < 0·01. During plaque deposition, oral NO was significantly directly related to salivary nitrite (r = 0·497, P = 0·002) and so were their respective changes after tooth cleaning (r = 0·577, P < 0·001). Smokers had significantly lower oral NO than nonsmokers, with both clean and dirty teeth (P < 0·001), and higher bacteria counts in the plaque (38·6 ± 11·5 vs. 19·9 ± 2·3, P = 0·046).Conclusions Oral NO production increases during de novo deposition of dental plaque. NO might be an early host defence mechanism against bacterial proliferation in the plaque. Such a mechanism is inhibited by cigarette smoking.
Hyperhomocysteinaemia and folate deficiency in human immunodeficiency virus‐infected children
Authors: Vilaseca M. A. , Sierra C. , Colomé C. , Artuch R. , Valls C. , Muñoz‐Almagro C. , Vilches M‐A. , Fortuny C. 
Published: March 2003

Our aim was the detection of possible deficiencies of folate and cobalamin by the measurement of plasma total homocysteine (tHcy) in 69 human immunodeficiency virus (HIV) ‐infected children on antiretroviral treatment. We studied the relationship of these vitamins and methionine with tHcy values.Plasma tHcy was determined by high‐performance liquid chromatography with fluorescence detection, folate and cobalamin by competitive protein‐binding chemiluminescence, and methionine by ion exchange chromatography.Significant differences were observed between tHcy concentrations in the HIV‐infected patients and the reference values for children of similar ages (P < 0·0001). Folate values were significantly lower in HIV‐infected children compared with our reference paediatric population (P < 0·0001), but cobalamin concentrations were similar between patients and reference values. A significantly negative correlation was found between tHcy and folate (r = − 0·596; P < 0·0001), and a significantly positive correlation between folate and the methionine : tHcy ratio (r = 0·501; P < 0·0001). Plasma tHcy was significantly higher (P = 0·008), while folate values and methionine : tHcy ratios were significantly lower (P = 0·007 and P = 0·042), in patients on protease inhibitor treatment than in patients on other antiretroviral therapies.The hyperhomocysteinaemia and low methionine : tHcy ratios observed in our group of HIV‐infected children are probably a consequence of the low folate values, which interfere in the remethylation of homocysteine to methionine. Patients on protease inhibitor treatment showed significantly higher plasma tHcy concentrations, and lower folate values and methionine : tHcy ratios, compared with patients on other antiretroviral therapies. Hyperhomocysteinaemia is associated with the risk of premature stroke, which may have adverse consequences in the evolution of disease.
Increased cytokine release by leucocytes in survivors of stroke at young age
Authors: Grau A. J. , Aulmann M. , Lichy C. , Meiser H. , Buggle F. , Brandt T. , Grond‐Ginsbach C. 
Published: March 2003

Enhanced stimulus‐induced release of pro‐inflammatory cytokines by leucocytes may contribute to the pathogenesis of ischaemic stroke.We investigated the lipopolysaccharide‐induced release of interleukin‐1β (IL‐1β), IL‐6, IL‐8, and tumour necrosis factor‐α (TNF‐α) in whole blood from 20 patients with a history of ischaemic stroke under the age of 50, 20 patients with a history of cervical artery dissection (CAD) and 21 age‐ and sex‐matched healthy control subjects.Release of IL‐8 was higher (P = 0·006) and release of TNF‐α and IL‐6 tended to be higher (P < 0·1) in young stroke patients than in control subjects. No increased release existed in CAD patients. Vascular risk factors or history of infection before stroke did not modify IL‐8 production. A common T(250) → A polymorphism in the IL‐8 gene promotor was newly identified but did not correlate with the variability of IL‐8 release. The C(260) → T polymorphism in the gene of the monocytic LPS‐receptor CD14 – a risk factor for myocardial infarction – was not associated with increased cytokine release.We conclude that high inducible release of IL‐8 – and possibly of TNF‐α and IL‐6 – may contribute to the odds of ischaemic stroke in young adults.
Insulin resistance affects the regulation of lipoprotein lipase in the postprandial period and in an adipose tissue‐specific manner
Authors: Panarotto D. , Rémillard P. , Bouffard L. , Maheux P. 
Published: March 2003

AbstractAims Insulin is a potent stimulator of adipose tissue lipoprotein lipase (LPL). Logically, the postprandial period is therefore a privileged time of the day for the regulation of LPL by insulin in this tissue. It is not clear to what extent a defect such as insulin resistance could affect this regulation and contribute to postprandial, as well as fasting, hypertriglyceridaemia. The aim of the present protocol was to study the relationship between insulin resistance and LPL in adipose tissue and in plasma, in the particular context of the postprandial period.Methods For this study, 26 adult nondiabetic individuals (12 women and 14 men) with a wide range of whole‐body insulin‐mediated glucose uptake (as assessed with an insulin suppression test) were studied. An abdominal subcutaneous fat biopsy on one occasion, and post‐heparin plasma on another occasion, were obtained 4 h into a standardized meal profile administered in the fasting state.Results Postprandial triglyceride excursions (evaluated by the incremental area under the curve during the metabolic meal profile) were inversely correlated to adipose tissue LPL mRNA levels (ρ = −0·43, P < 0·03) as well as to adipose tissue LPL heparin‐releasable activity (ρ = −0·58, P < 0·01). Steady‐state plasma glucose (SSPG) concentrations during the insulin suppression test, a reflection of the degree of insulin resistance, were also negatively correlated to adipose tissue LPL mRNA (ρ = −0·50, P < 0·02) and activity (ρ = −0·56, P < 0·01). There was no correlation between plasma post‐heparin LPL activity/mass and postprandial triglycerides nor with insulin resistance.Conclusion Regulation of adipose tissue LPL is significantly affected in insulin‐resistant individuals in the postprandial period. This presumed impaired effect of insulin on LPL postprandially could be an important contributor to the atherogenic dyslipidaemia described in insulin resistance syndrome.
Matrix metalloproteinase‐9 is elevated in serum of alcohol abusers
Authors: Sillanaukee P. , Kalela A. , Seppä K. , Höyhtyä M. , Nikkari S. T. 
Published: March 2003

AbstractBackground Moderate alcohol consumption has been shown to protect against coronary heart disease. However, excessive alcohol use has been suggested to have detrimental effects on the cardiovascular system. We examined whether there is an association between alcohol abuse and circulating levels of matrix metalloproteinase‐9 (MMP‐9), which has been linked to unstable coronary heart disease and arterial inflammation.Design Serum MMP‐9 concentrations were compared between 40 male alcoholics (mean age 42 years) with ethanol consumption > 1000 g week−1 and 40 social drinker males with an ethanol consumption of < 200 g week−1 (mean age 45 years).Results The mean serum MMP‐9 concentration was significantly higher in sera of alcoholics compared to control subjects (70·9 ± 47·7 g L−1 and 43·1 ± 19·2 g L−1, respectively; P = 0·001). Within the alcoholic group, MMP‐9 concentration did not correlate with age, gamma glutamyl transferase, carbohydrate‐deficient transferrin, aspartate aminotransferase, alanine aminotransferase or alkaline phosphatase.Conclusion Our finding of elevated MMP‐9 concentrations in sera of chronic alcohol abusers helps understand the mechanisms of cardiovascular risk among these subjects.
Effects of high doses of glucocorticoids on free amino acids, ribosomes and protein turnover in human muscle
Authors: Löfberg E. , Gutierrez A. , Wernerman J. , Anderstam B. , Mitch W. E. , Price S. R. , Bergström J. , Alvestrand A. 
Published: March 2003

AbstractBackground  Treatment with glucocorticosteroids causes a negative nitrogen balance, but the kinetic mechanisms responsible for this catabolic effect are controversial. We investigated the effects of 60 mg day−1 prednisolone on protein synthesis and degradation in human skeletal muscle.Materials and methods Healthy adults (n = 9) were studied in the postabsorptive state, before and after 3 days of prednisolone treatment. The L‐[ring 2,6‐3H5]‐phenylalanine tracer technique, concentration and size distribution of the ribosomes, mRNA content of the ubiquitin‐proteasome pathway components in muscle, phenylalanine flux across the leg, and the free amino acid concentrations in skeletal muscle were used to study muscle protein metabolism.Results The concentrations of most amino acids in arterial blood increased after prednisolone. There were also increased effluxes of phenylalanine, asparagine, arginine, alanine, methionine and isoleucine from the leg. The rate of protein degradation, as measured by the appearance rate (Ra) of phenylalanine, increased by 67% (P = 0·023) which, together with a doubling of the net release of phenylalanine from the leg (P = 0·007), indicated accelerated protein degradation. The pathway was not identified but there was no significant increase in mRNAs’ encoding components of the ubiquitin‐proteasome pathway. There was a 6% reduction in polyribosomes (P = 0·007), suggesting a decrease in the capacity for protein synthesis, although there was no measured decrease in the rate of protein synthesis.Conclusions  These findings indicate that high doses of prednisolone lead to a sharp increase in net protein catabolism, which depends more on enhanced protein breakdown, and an uncertain effect on protein synthesis. The mechanisms stimulating proteolysis and the pathway stimulated to increase muscle protein degradation should be explored.
Cyclooxygenase‐2‐positive macrophages infiltrate the Alzheimer’s disease brain and damage the blood–brain barrier
Authors: Fiala M. , Liu Q. N. , Sayre J. , Pop V. , Brahmandam V. , Graves M. C. , Vinters H. V. 
Published: March 2003

AbstractBackground Monocyte/macrophages are known to infiltrate the brain of patients with HIV‐1 encephalitis (HIVE). In Alzheimer’s disease brain, the origin of activated microglia has not been determined.Materials and methods We employed the antigen retrieval technique, immunocytochemistry, immunofluorescense, and confocal microscopy to identify macrophages and microglia in relation to amyloid‐β plaques and the blood–brain barrier in autopsy brain tissues from patients with Alzheimer’s disease (AD) and HIVE.Results In both conditions, cyclooxygenase‐2 positive macrophages and, to a lesser degree, T and B cells infiltrate brain perivascular spaces and neuropil. The macrophages are distinguishable from ramified microglia, and decorate the vessels at the sites of apparent of endothelial tight junction protein ZO‐1 disruption. The macrophages also infiltrate amyloid‐β plaques, display intracellular amyloid‐β and are surrounded by amyloid‐β‐free lacunae. Furthermore, the macrophages partially encircle the walls of amyloid‐β‐containing vessels in amyloid angiopathy, and exhibit intracellular amyloid‐β but not paracellular lacunae. Significantly larger zones of fibrinogen leakage surround the microvessels in HIVE brain tissues compared with AD tissues (P = 0·034), and AD tissues have significantly greater leakage than control tissues (P = 0·0339). The AD group differs from a normal control age‐matched group with respect to both the area occupied by CD68 (P = 0·03) and cyclooxygenase‐2 immunoreactive cells (P = 0·004).Conclusion In both HIVE and AD, blood‐borne activated monocyte/macrophages and lymphocytes appear to migrate through a disrupted blood–brain barrier. The lacunae around macrophages in amyloid‐β plaques but not in vessel walls are consistent with the ability of macrophages to phagocytize and clear amyloid‐β deposits in vitro.
11b‐hydroxysteroid dehydrogenase activity in proteinuric patients and the effect of angiotensin‐II receptor blockade
Authors: Kerstens M. N. , Buter H. , Navis G. J. , Dullaart R. P. F. 
Published: March 2003

AbstractBackground It has been suggested that an altered setpoint of the 11βHSD‐mediated cortisol to cortisone interconversion towards cortisol contributes to sodium retention in nephrotic syndrome patients. We studied the parameters of 11βHSD activity in proteinuric patients, in particular its activity at the kidney level. We also studied the effect of angiotensin‐II receptor blockade on the parameters of 11βHSD activity.Materials and methods Serum cortisol/cortisone ratio and the urinary ratios of (tetrahydrocortisol + allo‐tetrahydrocortisol)/tetrahydrocortisone [(THF + allo‐THF)/THE] and of urinary free cortisol/free cortisone (UFF/UFE) were measured in eight proteinuric patients and compared with eight matched, healthy subjects. Patients were subsequently studied after 4 weeks’ treatment with losartan 50 mg day−1 and placebo, respectively.Results No significant differences between the proteinuric patients and the healthy subjects were observed in the serum cortisol, serum cortisone, serum cortisol to cortisone ratio, or in the urinary excretions of THF, allo‐THF, THE, sum of cortisol metabolites, or the (THF + allo‐THF)/THE ratio. Urinary free cortisol excretion and the UFF/UFE ratio were lower in the proteinuric patients than in the healthy subjects (56 ± 21 vs. 85 ± 24 pmol min−1, P < 0·05, and 0·39 ± 0·07 vs. 0·63 ± 0·28, P < 0·05, respectively). Mean arterial pressure and proteinuria were reduced significantly during losartan treatment, but without concomitant changes in peripheral cortisol metabolism.Conclusions Increased renal inactivation of cortisol in proteinuric patients does not support the contention that altered 11βHSD activity contributes to sodium retention in patients with nephrotic syndrome. Losartan 50 mg d.d. reduces mean arterial pressure and proteinuria, but does not exert a significant effect on the cortisol to cortisone interconversion.
Molecular study of electron transfer flavoprotein α‐subunit deficiency in two Japanese children with different phenotypes of glutaric acidemia type II
Authors: Purevjav E. , Kimura M. , Takusa Y. , Ohura T. , Tsuchiya M. , Hara N. , Fukao T. , Yamaguchi S. 
Published: March 2003

AbstractBackground Electron transfer flavoprotein is a mitochondrial matrix protein composed of alpha‐ and beta‐subunits (ETFα and ETFβ, respectively). This protein transfers electrons between several mitochondrial dehydrogenases and the main respiratory chain via ETF dehydrogenase (ETF‐DH). Defects in ETF or ETF‐DH cause glutaric acidemias type II (GAII).Materials and methods We investigated the molecular basis of ETFα deficiency in two Japanese children with different clinical phenotypes using expression study.Results Patient 1 had the severe form of GAII, a compound heterozygote of two mutations: 799G to A (αG267R) and nonsense 7C to T (αR3X). Patient 2 had the mild form and carried two heterozygous mutations: 764G to T (αG255V) and 478delG (frameshift). Both patients had one each of missense mutations in one allele; the others were either nonsense or truncated. Restriction enzyme digestion assay using genomic DNAs from 100 healthy Japanese revealed that these mutations were all novel. No signal for ETFα was detected by immunoblotting in cases of missense mutants, while wild‐type cDNA resulted in expression of ETFα protein. Transfection with wild‐type ETFα cDNA into cultured cells from both patients elevated incorporation of radioisotope‐labelled fatty acids.Conclusion These four mutations were pathogenic for GAII and missense mutations, αG255V and αG267R were considered anecdotal for mild and severe forms, respectively.
Polymorphisms of genes affecting thrombosis and risk of myocardial infarction
Authors: Kakko S. , Elo T. , Tapanainen J. M. , Huikuri H. V. , Savolainen M. J. 
Published: March 2003

AbstractBackground  As thrombosis is an essential factor in the pathogenesis of acute myocardial infarction (AMI), the genes of proteins affecting haemostasis are good candidate genes for AMI.Design  Associations of the known polymorphisms of the coagulation factor VII (FVII) gene (R353Q), the coagulation factor XIII (FXIII) gene (V34L) and the glycoprotein Ia (Gp1a) gene (C807T) with the occurrence of AMI were studied in 142 AMI survivors and 142 age‐ and sex‐matched control subjects.Results  Among those who smoked, the L34 allele of the amino acid FXIII polymorphism was less common in the AMI patients (16%) than in the controls (27%) (P = 0·06), suggesting a possible interaction of AMI risk between the FXIII genotype and smoking status. No differences in the allele or genotype frequencies of the studied polymorphisms were seen between the whole study groups. Logistic regression analysis showed the carriers of the L34 allele of the FXIII amino acid polymorphism to have a significantly (P = 0·03) lower AMI risk compared with those homozygous for the V34 allele (odds ratio = 0·54, 95% confidence interval 0·31‐0‐93).Conclusion  The L34 allele of the amino acid polymorphism of the FXIII gene is associated with a decreased risk of AMI, and this protecting association seems to be more pronounced in smokers.
Time‐dependent effect of statins on platelet function in hypercholesterolaemia
Authors: Puccetti L. , Pasqui A. L. , Pastorelli M. , Bova G. , Cercignani M. , Palazzuoli A. , Angori P. , Auteri A. , Bruni F. 
Published: March 2003

AbstractBackground Reduction of platelet activity induced by statins has been described as a positive effect exerted by such molecules on vascular thrombotic events. However, the relations among cholesterol (LDL‐C) reduction, the timing of the antiplatelet effect, the involved mechanisms and the doses of each statin able to reduce platelet function are not actually well known. The aim of our study was to evaluate the impact of simvastatin (20 mg day−1), atorvastatin (10 mg day−1), fluvastatin (40 mg day−1) and pravastatin (40 mg day−1) on platelet function in hypercholesterolaemic subjects with relation to (LDL‐C), oxidized‐LDL (ox‐LDL) and antiport mechanism modifications.Materials and methods Sixteen subjects were assigned to each treatment (40 males, 24 females, mean age 48·7 ± 13·4, LDL‐C 5·13 ± 0,23 mmol L−1) and evaluated for platelet surface P‐selectin (P‐sel), lipid profile, ox‐LDL, platelet‐associated ox‐LDL (Pox‐LDL), platelet cholesterol content, antiport mechanisms, and intracellular and systemic NO synthase every 7 days for one month.Results Our data show a strong relation between enhanced P‐sel and Pox‐LDL (r = 0·68, P < 0·01). Simvastatin, atorvastatin, fluvastatin and pravastatin reduce platelet activity after 1, 2, 3 and 4 weeks of treatment, respectively (P < 0·001, P < 0·001, P < 0·01, P < 0·05). Pox‐LDL are modulated early by simvastatin, atorvastatin and fluvastatin Pox‐LDL (r = 0·66, 0·65 and 0·52; P < 0·001, 0·001 and 0·01, respectively) whereas LDL‐C and ox‐LDL reductions associated to modifications of antiport activity act later. Moreouer, they are the most relevant finding in pravastatin‐related subjects.Conclusions  Our data suggest a different impact of several statins on platelet function, which is initially related to interference with Pox‐LDL rather than LDL‐C reduction.
Iron does not bind to the Apo‐B protein of low‐density lipoprotein
Authors: De Valk B. , Leus F. R. , Voorbij H. A. M. , Marx J. J. M. 
Published: March 2003

AbstractBackground Epidemiological and experimental evidence suggests that (nontransferrin‐bound) iron plays an important role in atherogenesis by catalysing peroxidation of low‐density lipoprotein (LDL). However, the mechanism of the interaction of iron and LDL is unclear. Iron has to be in the closest vicinity of LDL in order to catalyse the formation of the short‐lived hydroxyl. In this study we investigated whether iron can bind to LDL in order to facilitate LDL peroxidation.Methods LDL and [59Fe]ferric citrate were incubated at 37 °C and pH 7·4 for 30 min. Unbound [59Fe]ferric citrate was separated from LDL using a Sephadex G25‐M column. Activity of [59Fe]ferric citrate was measured in the collected fractions. A control experiment was performed using albumin instead of LDL.Results and conclusion No binding was observed between iron, as a low molecular weight Fe(III) complex, and LDL. As a control albumin was able to bind iron, it seems evident that interaction of iron with LDL will involve other iron complexes.