bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of short‐term treatment with metformin on serum concentrations of homocysteine, folate and vitamin B12 in type 2 diabetes mellitus: a randomized, placebo‐controlled trial
Authors: Wulffelé M. G. , Kooy A. , Lehert P. , Bets D. , Ogterop J. C. , Borger van der Burg B. , Donker A. J. M. , Stehouwer C. D. A. 
Published: October 2003

Abstract.  Wulffelé MG, Kooy A, Lehert P, Bets D, Ogterop JC, Borger van der Burg B, Donker AJM, Stehouwer CDA (Bethesda General Hospital, Hoogeveen, The Netherlands; University of Mons, Mons, Belgium; Merck Nederland B.V., Amsterdam; Deaconesses’ Hospital, Meppel; Aleida Kramer Hospital, Coevorden; and Vrije Universiteit Medical Centre, Amsterdam; The Netherlands). Effects of short‐term treatment with metformin on serum concentrations of homocysteine, folate and vitamin B12 in type 2 diabetes mellitus: a randomized, placebo‐controlled trial. J Intern Med 2003; 254: 455–463.Objective. Metformin is a key treatment option in type 2 diabetes. However, metformin may decrease vitamin B12 levels and increase levels of homo‐cysteine, a cardiovascular risk factor. We investigated whether 16 weeks of treatment with metformin affects serum concentrations of homo‐cysteine, folate and vitamin B12 in subjects with type 2 diabetes treated with insulin.Design. Placebo‐controlled, randomized trial. Measurements: at baseline and 16 weeks later.Setting. This trial was conducted in the outpatient clinics of three general hospitals in The Netherlands.Subjects. A total of 745 patients with type 2 diabetes, treated with insulin and not known with a contraindication for the use of metformin, were approached; 390 gave informed consent and entered the study. Thirty‐seven subjects dropped out (12 placebo and 25 metformin users).Intervention. Addition of metformin or placebo to insulin therapy.Primary outcome parameters. Serum homocysteine, folate, vitamin B12, indices of glycaemic control and body weight.Results. Amongst those who completed 16 weeks of treatment, metformin use, as compared with placebo, was associated with an increase in homocysteine of 4% (0.2 to 8; P = 0.039) and with decreases in folate [−7% (−1.4 to −13); P = 0.024] and vitamin B12 [−14% (−4.2 to −24); P < 0.0001]. In addition, the increase in homocysteine could be explained by the decreases in folate and vitamin B12.Conclusion. In patients with type 2 diabetes, 16 weeks of treatment with metformin reduces levels of folate and vitamin B12, which results in a modest increase in homocysteine. The clinical significance of these findings remains to be investigated.
Effect of short‐term hyperglycaemia on haemodynamics in type 1 diabetic patients
Authors: Jacobsen P. , Rossing K. , Hansen B. V. , Bie P. , Vaag A. , Parving H.‐H. 
Published: October 2003

Abstract. Jacobsen P, Rossing K, Hansen BV, Bie P, Vaag A, Parving H‐H (Steno Diabetes Center, Gentofte; University of Aarhus, Aarhus; and University of Southern Denmark, Odense, Denmark). Effect of short‐term hyperglycaemia on haemodynamics in type 1 diabetic patients. J Intern Med 2003; 254: 464–471.Objectives. Mechanisms underlying glucose‐mediated development and progression of diabetic complications are incompletely understood. We tested the impact of short‐term hyperglycaemia on systemic blood pressure and regulatory hormones in type 1 diabetic patients.Design and methods. We included 18 patients [13 men, mean (SEM) diabetes duration 10 (1) years] without signs of autonomic neuropathy or renal complications in a randomized single‐blinded cross‐over trial using insulin–glucose clamp technique. Patients were clamped for 90 min to blood glucose of 5 mmol L−1 (euglycaemia) and 15 mmol L−1 (hyperglycaemia) in random order. Blood pressure was measured noninvasively every 5 min (Takeda TM2421 device). Regulatory hormones were determined at the end of each clamp period.Results. Systolic blood pressure increased [mean (95% CI)] 3 (1, 5) mmHg during hyperglycaemia from 123 (SEM 2) during euglycaemia, P = 0.01. Diastolic blood pressure remained unchanged at 78 (2) mmHg. Hyperglycaemia reduced plasma concentrations of: renin [14 (4, 23)%, P = 0.02], angiotensin II [17 (8, 25)%, P < 0.01] and adrenaline [20 (10, 29)%, P < 0.01]. Plasma concentration of atrial natriuretic peptide increased by 11 (6, 17) pg mL−1 (P < 0.01) from 43 (2) pg mL−1. We calculated a median (range) increase in extracellular volume and plasma volume (PV) of 2.6 (0.7–5.3)% and 5.0 (−4.7 to 8.6)%, respectively.Conclusions. In type 1 diabetic patients without signs of autonomic neuropathy short‐term hyperglycaemia induced a modest increase in systolic blood pressure and suppression of the renin–angiotensin system, possibly caused by PV expansion because of fluid shift from intra‐ to extracellular compartment.
Expansion of peripheral CD8+ T cells in patients with coronary artery disease: relation to cytomegalovirus infection
Authors: Jonasson L. , Tompa A. , Wikby A. 
Published: October 2003

Abstract. Jonasson L, Tompa A, Wikby A (Heart Center, University Hospital, Linköping; Ryhov Hospital, Jönköping; and School of Health Sciences, Jönköping University, Jönköping; Sweden). Expansion of peripheral CD8+ T cells in patients with coronary artery disease: relation to cytomegalovirus infection. J Intern Med 2003; 254: 472–478.Objectives. The nature of the immune response in coronary artery disease (CAD) is not fully defined. One pathogen that has been linked to atherogenesis, cytomegalovirus (CMV), is known to exert strong and long‐lasting effects on peripheral T cells. In the present study, we investigated the effect of prior CMV infection on the immune system in CAD patients.Subjects. Patients with stable angina and angiographically verified CAD (n = 43) and clinically healthy controls (n = 69) were included.Methods. The expression of CD57 and CD28 on peripheral CD4+ and CD8+ T cells was evaluated with three‐colour flow cytometry. The findings were related to serological markers of inflammation, T‐cell activation and CMV seropositivity.Results. An expansion of CD8+ T cells expressing CD57 but lacking CD28 was seen in the patient group. The numbers of CD8+ CD57+ and CD8+ CD28−T‐cell subsets were independently related to CMV seropositivity (P < 0.001) but also to CAD per se (P < 0.05). Serum concentrations of C‐reactive protein (CRP) and soluble interleukin‐2 receptor (sIL‐2R) were elevated in the patients but not related to CMV or CD8+ T‐cell subsets.Conclusion. A pronounced shift in peripheral T‐cell homeostasis was observed in CAD patients. Primarily CMV infection but also CAD per se contributed to the expansion of CD8+ T‐cell subsets. The T‐cell changes were not related to a systemic inflammatory response but should rather be considered as markers of a chronic antigen exposure and/or immunosenescence in CAD.
Basal glucometabolic status has an impact on long‐term prognosis following an acute myocardial infarction in non‐diabetic patients
Authors: Tenerz Å. , Nilsson G. , Forberg R. , Öhrvik J. , Malmberg K. , Berne C. , Leppert J. 
Published: October 2003

Abstract. Tenerz Å, Nilsson G, Forberg R, Öhrvik J, Malmberg K, Berne C, Leppert J (Central Hospital, Västerås; Karolinska Hospital, Stockholm; and University Hospital, Uppsala; Sweden) Basal glucometabolic status has an impact on long‐term prognosis following an acute myocardial infarction in non‐diabetic patients. J Intern Med 2003; 254: 494–503.Objectives. Patients with diabetes are known to have a worse prognosis after an acute myocardial infarction (AMI) compared with non‐diabetic patients. The primary aim of this study was to investigate the effect of glucometabolic status on long‐term prognosis in non‐diabetic patients with an AMI. The second aim was to evaluate the extent to which blood glucose levels at admission depended on acute stress, assessed as serum cortisol, previous glucometabolic status, measured as haemoglobin A1c (HbA1c), or both.Design. In a prospective study of patients with an AMI, blood glucose, HbA1c and cortisol were measured at admission. Fasting blood glucose was determined before discharge and also afterwards, if necessary, for classification. Patients were followed‐up for 5.5 years.Subjects. Of the 305 consecutive patients 24% were diagnosed as diabetic and 76% as non‐diabetic.Main outcome measures. Death or non‐fatal myocardial re‐infarction.Results. In non‐diabetic patients, a Cox regression model was used. With death or re‐infarction as endpoint, the following prognostic factors had an impact on event‐free survival: age (P < 0.001), HbA1c (P = 0.002), cortisol (P < 0.001) and thrombolytic treatment (P = 0.001). There was a correlation between cortisol and blood glucose at admission (r = 0.44, P < 0.001). Fasting blood glucose day 5 showed no association with event‐free survival.Conclusions. In non‐diabetic patients with AMI, admission HbA1c and cortisol were predictors for 5.5‐year survival without recurrent non‐fatal myocardial infarction. The glucometabolic status of importance for prognosis was detected by HbA1c but not by fasting blood glucose or admission blood glucose, of which the latter was influenced by cortisol.
Obesity – is it a genetic disorder?
Authors: Loos R. J. F. , Bouchard C. 
Published: October 2003

Abstract.  Loos RJF, Bouchard C (Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA, USA). Obesity – is it a genetic disorder? (Review). J Intern Med 2003; 254: 401–425.Obesity is one of the most pressing problems in the industrialized world. Twin, adoption and family studies have shown that genetic factors play a significant role in the pathogenesis of obesity. Rare mutations in humans and model organisms have provided insights into the pathways involved in body weight regulation. Studies of candidate genes indicate that some of the genes involved in pathways regulating energy expenditure and food intake may play a role in the predisposition to obesity. Amongst these genes, sequence variations in the adrenergic receptors, uncoupling proteins, peroxisome proliferator‐activated receptor, and the leptin receptor genes are of particular relevance. Results that have been replicated in at least three genome‐wide scans suggest that key genes are located on chromosomes 2p, 3q, 5p, 6p, 7q, 10p, 11q, 17p and 20q. We conclude that the currently available evidence suggests four levels of genetic determination of obesity: genetic obesity, strong genetic predisposition, slight genetic predisposition, and genetically resistant. This growing body of research may help in the development of anti‐obesity agents and perhaps genetic tests to predict the risk for obesity.
Cell damage and reactive oxygen species production induced by fluorescence microscopy: effect on mitosis and guidelines for non‐invasive fluorescence microscopy
Authors: Dixit Ram , Cyr Richard 
Published: October 2003

SummaryThe green fluorescent protein (GFP) and other intrinsically fluorescent proteins (IFPs) are popular reporters because they allow visualization of cellular constituents in living specimens. IFP technology makes it possible to view dynamic processes in living cells, but extended observation, using fluorescence microscopy (both wide‐field and confocal), can result in significant light energy exposure. Therefore, it is possible that cells experience light‐induced damage that alters cell physiology and confounds observations. To understand the impact that extended viewing has on cells, we obtained quantitative information about the effect of light energy dose and observation conditions on tobacco BY‐2 cell physiology. Our results show a non‐linear relationship between the excitation light intensity and mitotic arrest, and the frequency of mitotic arrest is dependent on the presence of an IFP that absorbs the excitation light. Moreover, fluorescence microscopy induces the production of reactive oxygen species (ROS), as assayed using BY‐2 cells loaded with oxidation‐sensitive dyes, and the level of ROS production increases if the cells express an IFP that absorbs the excitation light energy. The dye oxidation follows sigmoidal kinetics and is reversible if the cells are exposed to low irradiation levels. In addition, the dye oxidation rate shows a non‐linear relationship to the excitation light intensity, and a good correlation exists between photobleaching, mitotic arrest, and dye oxidation. The data highlight the importance of ROS scavenging for normal mitotic progression, and provide a reference for judiciously choosing conditions that avoid photobleaching that can lead to ROS accumulation and physiological damage.
Increased tryptophan decarboxylase and monoamine oxidase activities induce Sekiguchi lesion formation in rice infected with Magnaporthe grisea
Authors: Ueno Makoto , Shibata Hitoshi , Kihara Junichi , Honda Yuichi , Arase Sakae 
Published: October 2003

SummarySekiguchi lesion (sl)‐mutant rice infected with Magnaporthe grisea showed increased light‐dependent tryptophan decarboxylase (TDC) and monoamine oxidase (MAO) activities. TDC and MAO activities were observed before the penetration of M. grisea to rice cells and maintained high levels even after Sekiguchi lesion formation. Light‐dependent expression of TDC gene was observed in leaves inoculated with M. grisea before Sekiguchi lesion formation. Spore germination fluid (SGF) of M. grisea also induced Sekiguchi lesion formation accompanied by increased enzymes activities and tryptamine accumulation. Sekiguchi lesion was also induced by treatments with tryptamine and β‐phenylethylamine, which are substrates for MAO, but was not induced by non‐substrates such as indole‐3‐propionic acid, (±)‐phenylethylamine and tryptophan under light. Light‐dependent induction of Sekiguchi lesion by tryptamine was significantly inhibited in the presence of MAO inhibitors, metalaxyl and semicarbazide, and H2O2‐scavengers, ascorbic acid and catalase. H2O2 in M. grisea‐infected leaves with and without Sekiguchi lesions was demonstrated directly in situ by strong 3,3′‐diaminobenzidine (DAB) staining. On the other hand, H2O2 induced Sekiguchi lesions on leaves of cv. Sekiguchi‐asahi under light, but not in darkness. This difference was associated with the decrease of catalase activity in infected leaves under light and the absence of decrease in darkness. We hypothesize that the H2O2‐induced breakdown of cellular organelles such as chloroplasts and mitochondria in mesophyll cells may cause high TDC and MAO activities and the development of Sekiguchi lesion, and that the sl gene products in wild‐type rice may function as a suppressor of organelle breakdown caused by chemical or environmental stress.
Telomere looping in P. sativum (common garden pea)
Authors: Cesare Anthony J. , Quinney Nancy , Willcox Smaranda , Subramanian Deepa , Griffith Jack D. 
Published: October 2003

SummaryTelomeres vary greatly in size among plants and, in most higher plants, consist of a long array of 5′‐TTTAGGG‐3′/3′‐AAATCCC‐5′ (TTTAGGG) repeats. Recently, telomeric DNA in human, mouse, oxytricha, and trypanosome chromosomes have been found arranged into loops (t‐loops), proposed to sequester the telomere from unwanted repair events and prevent activation of DNA damage checkpoints. We have asked whether t‐loops exist in the higher order plant Pisum sativum (garden pea). DNA was isolated from the shoots and root tips of germinating seeds. Analysis of the telomeric restriction fragments showed that DNA hybridizing to a (TTTAGGG)n probe migrated as a smear centering around 25 kb, and direct sequencing verified the repeat to be (TTTAGGG)n. Total DNA in isolated nuclei was photo‐cross‐linked, and the telomeric restriction fragments were purified by gel filtration. Electron microscopic (EM) analysis revealed DNA molecules arranged as t‐loops with a size distribution consistent with that seen by gel electrophoresis. Some molecules had loops as large as 75 kb. These results show that the arrangement of telomeric DNA into loops occurs in higher plants.
Wyerone Acid Phytoalexin Synthesis and Peroxidase Activity as Markers for Resistance of Broad Beans to Chocolate Spot Disease
Authors: Nawar H. F. , Kuti J. O. 
Published: October 2003

AbstractInfection of broad bean (Vicia faba L.) leaves with Botrytis fabae (Sard.) resulted in wyerone acid phytoalexin accumulation and increase in peroxidase activities in resistant and susceptible broad bean cultivars. Rapid wyerone acid accumulation was observed in leaves of resistant cultivars that reached levels greater than twofold of the susceptible cultivars. Following infection of broad bean cultivars, either resistant or susceptible to B. fabae, wyerone acid synthesis in resistant cultivars peaked at 5 days then declined, whereas in susceptible cultivars synthesis gradually decreased. While the ethanol‐extract of wyerone acid significantly reduced B. fabae spore germination with increased concentrations, the phytoalexin had no effect on in vitro B. fabae germ‐tube growth. Peroxidase activity in infected leaves of resistant was 10 times higher than the susceptible cultivars and eight times higher in uninfected leaves of the resistant than the susceptible cultivars. Peroxidase activity in infected leaves was greater than twofold in resistant cultivars and less than twofold in susceptible cultivars, when compared with uninfected leaves. The ratio of peroxidase activity in infected to uninfected leaves increased over time in susceptible cultivars but remained unchanged in resistant cultivars. Peroxidase activity in uninfected and infected leaves and wyerone acid biosynthesis in infected broad bean plants were successfully used to ascertain the resistance and susceptibility of four broad bean cultivars to B. fabae. Using wyerone acid synthesis and peroxidase activity as preliminary markers for resistance of broad bean to chocolate spot disease, caused by B. fabae, is suggested in this study.
Fungal Endophytic Communities in Healthy and Declining Quercus robur L. and Q. cerris L. Trees in Northern Italy
Authors: Gennaro M. , Gonthier P. , Nicolotti G. 
Published: October 2003

AbstractHealthy and declining English oak (Quercus robur) and Turkey oak (Q. cerris) in north‐western Italy, in a plain oak forest showing decline for oak puzzle disease, were tested to assess possible variations in the composition of their fungal endophytic communities and their relation to the health status of trees. Samples collected in spring (buds) and in autumn (leaves, annual shoots and twigs) were surface‐sterilized, cut into fragments and placed on potato dextrose agar for a month; 26 fungal species were isolated, the most frequent being Tubakia dryina, Dendrodochium sp., Eutypella sp. and a sterile mycelium. Correspondence analysis showed significant qualitative differences between assemblages inhabiting twigs and herbaceous tissues that were due to the low frequency of Tubakia dryina in twigs and its higher frequency in buds, leaves and shoots. Tubakia dryina was isolated more frequently from leaves of declining oaks and from buds of healthy oaks; Monochaetia monochaeta showed a preference for healthy trees, especially leaves and buds. According to the Shannon–Wiener index, endophytic fungal communities of leaves, twigs and buds of declining English oak were poorer than those of declining Turkey oak, but there were no significant differences between healthy hosts.
The Effects of Oligosaccharide and Spores from Aspergillus niger on the Defence Responses of Taxus chinensis Leaves In vitro
Authors: Li M. Y. , Lan W. Z. , Chen C. , Yu L. J. 
Published: October 2003

AbstractSpores and oligosaccharide of a strain of Aspergillus niger, which had been isolated from the inner bark of Taxus chinensis, were used to treat T. chinensis leaves. The spores decreased the dry weight and chlorophyll content of the leaves, but increased their malondialdehyde content; oligosaccharide induced similar but more moderate changes. The changes in soluble protein, phenolic content, and peroxidase and phenylalanine ammonia‐lyase activity were also analysed. Oligosaccharide significantly increased all these, whereas the spores had contrary effects. Results indicate that oligosaccharide, but not the fungal spores, elicited a defence reaction in T. chinensis. Possible reasons for these different effects on T. chinensis leaves in vitro are discussed.
Effect of Crinipellis perniciosa Infection on Abscission of Cacao Cotyledons, Reserve Mobilization and Dry Matter Partitioning
Authors: Motilal L. A. , Sirju‐Charran G. , Sreenivasan T. N. 
Published: October 2003

AbstractInfection by Crinipellis perniciosa on cacao seedlings prevented the abscission of cotyledons which normally abscise within 32–61 days from seed sowing. The early growth and development of control and artificially inoculated seedlings was investigated for root dry mass (RDM), shoot dry mass (SDM), shoot‐to‐root ratio (SRR), total dry mass (TDM), cotyledonary dry mass (CDM) and cotyledonary water content (CWC). Cotyledonary reserve mobilization was estimated at 69 and 56% at 5 weeks and 79 and 64% at 8 weeks in control and infected seedlings, respectively. Infection induced the enlargement of tissues but was not accompanied by an increase in dry mass. Infection both delayed and reduced the utilization of cotyledonary food reserves resulting in slower accumulation of RDM, SDM and TDM culminating in a reduction of growth by a factor of 1.6 at 8 weeks. However, the SRR of inoculated plants was similar to that of control plants, suggesting that the balance between the root and shoot systems exists which is unchanged by the effect of the pathogen. CWC was decreased upon senescence to an average of 65% at abscission. The prevention of cotyledonary abscission in infected seedlings is suggested to be due in part to the CDM remaining above a critical level of 20% of the initial CDM. The implication of this response in relation to the infection biology of the pathogen is discussed.
Coexistence of focal nodular hyperplasia and pseudotumor caused by focal spared lesion in the liver of a young man
Authors: WU WEN‐CHIH , CHEN SHINN‐CHERNG , DIA CHIA‐YEN , YU MING‐LUNG , HSIEH MING‐YUH , LIN ZU‐YAU , WANG LIANG‐YEN , TSIA JUNG‐FA , CHANG WEN‐YU , CHUANG WAN‐LONG 
Published: October 2003

Abstract  We report a case of 19‐year‐old male with an underlying case of chronic hepatitis C infection who suffered from two types of benign liver tumor: focal nodular hyperplasia (FNH) and pseudotumor due to focal fatty spared area in a fatty liver. These two kinds of lesions rarely occur simultaneously. The spectral Doppler ultrasound (US) images of these lesions were also provided. We suggest that spectral Doppler US provides an alternative diagnostic tool for the differentiation of liver tumors regarding their vascular pattern, which might help ensure a correct diagnosis.© 2003 Blackwell Publishing Asia Pty Ltd
Is acupuncture a risk factor for hepatitis? Systematic review of epidemiological studies
Authors: ERNST E , SHERMAN Kj 
Published: October 2003

AbstractObjective:  Acupuncture has been repeatedly associated with infectious hepatitis. The aim of the present systematic review was therefore to critically evaluate such data from epidemiological investigations.Methods:  Four independent literature searches were carried out to identify all epidemiological evidence linking acupuncture with hepatitis. All studies were validated by the authors and data extracted according to predefined criteria.Results:  Fifteen investigations fulfilled our inclusion criteria. Most studies originated from Asia. One study included markers to hepatitis A virus, three to hepatitis B virus, and 13 to hepatitis C virus. Five investigations reported associations between acupuncture and seropositivity to hepatitis C virus. In those studies, acupuncture increased the risk only modestly.Conclusion:  A modest association between hepatitis C and acupuncture has been reported in some countries. This emphasizes the importance of exclusively using disposable acupuncture needles.