bluuebunny/crossref_metadata_2025_split huggingface dataset:
The assessment of hookworm calreticulin as a potential vaccine for necatoriasis
Authors: Winter J. A. , Davies O. R. , Brown A. P. , Garnett M. C. , Stolnik S. , Pritchard D. I. 
Published: May 2005

SUMMARY A vaccine against the human hookworm Necator americanus is urgently required to reduce hookworm‐induced morbidity in endemic areas. In the present study, recombinant hookworm calreticulin, a nominated vaccine candidate, has been tested in mice. Mice given calreticulin had 43–49% fewer worms in their lungs, compared to non‐vaccinated controls, following challenge infection with infective hookworm larvae. These levels of protection were achieved in the absence of adjuvant following intraperitoneal administration of three doses of 15 µg antigen. Antigen was also encapsulated in PLG microparticles. Encapsulated calreticulin elicited higher levels of anti‐calreticulin IgG1 than free antigen but failed to induce protective immunity. The protection induced by free calreticulin was associated with low levels of serum IgE and moderate lung eosinophilia whilst administration of calreticulin‐loaded microparticles was associated with high levels of serum IgE and higher lung eosinophil activity, suggesting that the classical Th2 phenotype may not always be associated with protective immunity, albeit in experimental necatoriasis.
Elevated blood concentrations of calcineurin inhibitors during diarrheal episode in pediatric liver transplant recipients: Involvement of the suppression of intestinal cytochrome P450 3A and P‐glycoprotein
Authors: Maezono Sachiko , Sugimoto Koh‐ichi , Sakamoto Koh‐ichi , Ohmori Masami , Hishikawa Shuji , Mizuta Koichi , Kawarasaki Hideo , Watanabe Yoshiteru , Fujimura Akio 
Published: May 2005

Abstract:  We encountered two cases of pediatric living‐related liver transplant recipients who showed increases in blood concentration of cyclosporine or tacrolimus, a dual substrate for cytochrome P450 (CYP) 3A and P‐glycoprotein (P‐gp), during a diarrheal episode. To investigate the effect of intestinal inflammation on the metabolic and efflux pump activities, we conducted the experiments using the lipopolysaccharide (LPS)‐induced intestinal damage model.Intestinal epithelial CYP3A activity was assessed by nifedipine oxidation using intestinal epithelial microsomes in rat. Drug efflux by P‐gp was tested using digoxin flux with the excised intestine perfusion system in rats. Intraperitoneal injection of LPS (0.3 mg/kg) significantly reduced the intestinal epithelial CYP3A activity by 41% (p < 0.01). In the proximal jejunal segment of the rats treated with LPS, mucosal to serosal flux of digoxin was significantly enhanced compared to that of control (p < 0.05). Efflux of digoxin, which was taken up by intestinal epithelium, to mucosal perfusate was significantly blunted in the jejunum treated with LPS (p < 0.05), which indicates that the LPS treatment reduced the P‐gp activity in rat small intestine.These findings suggest that the suppression of CYP3A and P‐gp activities may be involved in the mechanism of elevated blood concentrations of cyclosporine and tacrolimus during enteritis‐induced diarrhea. To prevent a drug‐induced adverse effect, dose of a drug, which is a substrate of CYP3A or P‐gp, should be reduced during such an episode.
Chronic alcohol exposure reduces hippocampal neurogenesis and dendritic growth of newborn neurons
Authors: He Jun , Nixon Kimberly , Shetty Ashok K. , Crews Fulton T. 
Published: May 2005

AbstractHippocampal neurogenesis is known as the formation of new neurons from the proliferating neural progenitor cells (NPC) at the dentate gyrus. Cell proliferation, survival, differentiation and maturation are critical stages leading to the generation of healthy neurons. As all of these stages can be influenced by alcohol exposure, we studied the effects of chronic alcohol on each process by immunocytochemistry for stage‐specific antigens and prelabelling newborn cells with bromodeoxyuridine (BrdU). Rats were administered alcohol liquid diet or control diet for one, two or four weeks. We found that cell proliferation was inhibited as proliferating cell nuclear antigen (PCNA) expression was reduced by approximately 50% in alcohol‐treated animals at all time points. Doublecortin (DCX), a microtubule protein expressed early in differentiating neurons, was progressively decreased over the duration of exposure and significantly reduced after two and four weeks of drinking. Morphological analyses of DCX‐positive cells revealed that four weeks of alcohol treatment reduced the size of the dendritic tree including the total length of apical dendrites, number of nodes and endings. Furthermore, BrdU labelling demonstrated a dramatic decrease in cell survival after four weeks of drinking, while cell death was increased by such treatment. Confocal analysis indicated that over 80% of BrdU+ cells colabelled with NeuN suggesting that alcohol reduced neurogenesis. In conclusion, chronic alcohol exposure disrupts neurogenesis by decreasing NPC proliferation, inhibiting cell survival and altering morphological maturation of newborn neurons. These data implicate impaired hippocampal neurogenesis with the cognitive and affective dysfunction associated with chronic alcoholism.
Decreased firing frequency of midbrain dopamine neurons in mice lacking mu opioid receptors
Authors: Mathon Daniel S. , Ramakers Geert M. J. , Pintar John E. , Marinelli Michela 
Published: May 2005

AbstractDopamine neurons originating in the midbrain and projecting to cortico‐limbic and motor structures are one of the major neuronal substrates implicated in the reinforcing properties of drugs of abuse. The output of this system is largely determined by its impulse activity (amount and pattern of firing activity). Several intrinsic and synaptic factors can influence dopamine neuronal activity and, consequently, addiction liability. Pharmacological studies indicate that µ‐opioid receptors and their activation by endogenous opioids may play an important role. In the present study, we use a genetic approach to better understand the role of µ‐opioid receptors in modulating dopamine neuronal activity in vivo. Using in vivo extracellular single‐unit recordings, we show that mice lacking µ‐opioid receptors exhibit lower firing rates of dopamine neurons compared with their wild‐type littermates. Although we observed no overall changes in bursting activity compared with wild‐type mice, animals lacking µ‐opioid receptors exhibited a higher proportion of regular‐spiking cells that lacked bursting activity. These findings are the first to emphasize the critical role of µ‐opioid receptors in modulating action potential output of dopamine neurons in vivo using a genetic approach. They also provide a possible underlying mechanism for the decreased reinforcing properties of drugs of abuse that was previously observed in mice lacking µ‐opioid receptors.
Risk of specific congenital abnormalities in offspring of women with diabetes
Authors: Nielsen G. L. , Nørgard B. , Puho E. , Rothman K. J. , Sørensen H. T. , Czeizel A. E. 
Published: May 2005

AbstractAims  To assess the extent to which the increased risk of congenital abnormalities seen in women with pre‐gestational insulin‐treated diabetes mellitus is unspecific or related to the embryology of specific organs.Methods  Cases with congenital abnormalities were identified in the population‐based Hungarian Congenital Abnormality Registry from 1980 to 1996 with two newborn children without congenital abnormality selected from the National Birth Registry as controls. We adjusted for parity, maternal age, and use of antipsychotic drugs.Results  Among cases we found 63/22 843 babies with maternal diabetes compared with 50/38 151 in the control group [adjusted prevalence odds ratio (POR) 2.1; 95% CI 1.5–3.1]. The association was strongest for the following congenital abnormalities: renal agenesis (POR: 14.8; 95% CI, 3.5–62.1), obstructive congenital abnormalities of the urinary tract (POR: 4.3; 95% CI, 1.3–13.9), cardiovascular congenital abnormalities (POR: 3.4; 95% CI, 2.0–5.7), and multiple congenital abnormalities (POR: 5.0; 95% CI, 2.4–10.2).Conclusions  These data indicate that pre‐gestational maternal diabetes is associated with strong teratogenic effects on the kidney, urinary tract, and heart, and strongly associated with multiple congenital abnormalities. We found no material association between diabetes and spinal congenital abnormalities and limb deficiencies.
Association analysis of the variant in the regulatory subunit of phosphoinositide 3‐kinase (p85α) with Type 2 diabetes mellitus and hypertension in the Chinese Han population
Authors: Chen S. , Yan W. , Huang J. , Ge D. , Yao Z. , Gu D. 
Published: May 2005

AbstractAims  To determine whether variants in the gene for the regulatory subunit of phosphoinositide 3‐kinase (p85α) are associated with Type 2 diabetes mellitus (Type 2 DM) and hypertension in a Chinese population.Methods  We performed a case‐control study genotyping the Met326Ile and IVS4+82A>G polymorphisms in 494 patients with Type 2 DM and hypertension and 557 normal controls from the north of China. Individual genotypes were identified by the polymerase chain reaction—restriction fragment length polymorphism (PCR–RFLP) method. The IVS4+82A>G polymorphism was further confirmed by direct sequencing in 20 randomly selected cases.Results  The IVS4+82A>G polymorphism that is common in Caucasians was not detected in our population. Frequencies of genotypes and alleles of Met326Ile polymorphism were not significantly different between cases and controls in whole samples by univariate analysis. Logistic regression analysis demonstrated that Ile326Ile genotype was associated with a 2.085‐fold (95% CI, 1.043–4.168, P = 0.0377) relative risk of diabetes and hypertension. After stratification by obesity, the frequency of Ile326Ile genotype in cases was higher than that in controls (18/304 vs. 13/510, P = 0.015) among non‐obese individuals (BMI < 28 kg/m2). We did not find that this missense mutation was associated with blood pressure, glucose and blood lipids in the control group.Conclusion  Our data indicate that the Met326Ile variation in the gene encoding the p85α protein might contribute to the increased risk of Type 2 DM and hypertension in Chinese.
Pre‐gestational maternal body mass index predicts an increased risk of congenital malformations in infants of mothers with gestational diabetes
Authors: Martínez‐Frías M. L. , Frías J. P. , Bermejo E. , Rodríguez‐Pinilla E. , Prieto L. , Frías J. L. 
Published: May 2005

AbstractAims  The aim of the present study was to identify characteristics in women diagnosed with gestational diabetes mellitus (GDM) that could be predictive of congenital malformations in their infants.Methods  Using data from the Spanish Collaborative Study of Congenital Malformations (ECEMC), a hospital‐based case‐control study and surveillance system, we assessed the relationship between a number of maternal variables, including pre‐gestational body mass index (BMI), and specific congenital malformations in their infants.Results  The overall risk for a selected group of congenital malformations in an infant of an obese mother with GDM compared with an obese mother with normal glucose tolerance (NGT) was 2.78 (1.38–5.55, P < 0.001). Within the group of mothers with GDM, obesity (BMI ≥ 30 kg/m2) was associated with a significantly increased risk of cardiovascular defects compared with non‐obese women [OR = 2.82 (1.31–7.04), P < 0.01]. In mothers with NGT, pre‐gestational BMI was not associated with congenital malformations.Conclusion  Pre‐gestational obesity is a predictive variable for congenital malformations in infants of mothers with GDM. The greater their BMI, the higher the risk for congenital malformations in their offspring. Given the blastogenic origin of the congenital defects identified, and the relationship between obesity and Type 2 diabetes, it is probable that this increased risk is as a result of previously unidentified pre‐gestational diabetes mellitus (PGD). It is important that overweight and obese women planning a pregnancy be evaluated for the presence of diabetes.
Setting and negotiating targets in people with Type 2 diabetes in primary care J. Stewart & D. Kendrick
Authors: Stewart J. , Kendrick D. ,   the Nottingham Diabetes Blood Pressure Study Group
Published: May 2005

AbstractAims  To investigate the provision of diabetes care, the frequency of practices setting targets for their diabetic population, the targets set and the frequency of targets being negotiated with people with diabetes.Methods  Cross‐sectional study using a survey of 123 general practices within four Primary Care Trusts in Nottingham UK.Results  Eighty per‐cent (99) of practices responded. Of these, 88 and 89%, respectively, had set glycosolated haemoglobin (HbA1c) and blood pressure targets for people with Type 2 diabetes. Twenty‐five per‐cent (24) of practices reported negotiating targets with almost all people with Type 2 diabetes for HbA1c and 31% (30) for blood pressure. In 46% (45) of practices, the annual diabetic review for some or all of the people with Type 2 diabetes was carried out by the practice nurse alone. In these practices, targets were negotiated with a smaller proportion of people than those where the doctor was involved in the annual review for both blood pressure [43 vs. 64% negotiated blood pressure targets with almost all or many people odds ratio (OR) 0.42 (95% CI 0.19, 0.96), P = 0.04] and HbA1c[39 vs. 60% negotiated HbA1c targets with almost all or many people, OR 0.41 (95% CI 0.18, 0.94), P = 0.03].Conclusions  Negotiating targets with people with Type 2 diabetes does not routinely occur in primary care. Targets are negotiated less often in practices where nurses undertake reviews alone and further work is needed to explore the reasons for this.
Left ventricular diastolic dysfunction in patients with chronic renal failure: impact of diabetes mellitus
Authors: Miyazato J. , Horio T. , Takiuchi S. , Kamide K. , Sasaki O. , Nakamura S. , Nakahama H. , Inenaga T. , Takishita S. , Kawano Y. 
Published: May 2005

AbstractAims  Left ventricular (LV) hypertrophy and LV diastolic dysfunction are cardiac changes commonly observed in patients with chronic renal failure (CRF) as well as hypertension. Although the impairment of LV diastolic function in patients with diabetes mellitus has been shown, little is known about the specific effect of diabetes on LV diastolic function in patients with CRF. The present study was designed to investigate the impact of diabetic nephropathy on LV diastolic dysfunction, independent of LV hypertrophy, in CRF patients.Methods  In 67 patients with non‐dialysis CRF as a result of chronic glomerulonephritis (n = 33) or diabetic nephropathy (n = 34), and 134 hypertensive patients with normal renal function, two‐dimensional and Doppler echocardiographic examinations were performed, and LV dimension, mass, systolic function, and diastolic function were evaluated.Results  LV mass was increased and LV diastolic dysfunction was advanced in subjects with CRF compared with hypertensive controls. In the comparison of echocardiographic parameters between the two groups of CRF patients, i.e. chronic glomerulonephritis and diabetic nephropathy groups, all indices of LV diastolic function were more deteriorated in the diabetic nephropathy group than in the chronic glomerulonephritis group, although LV structure including hypertrophy and systolic function did not differ between the groups. In a multiple regression analysis, the presence of diabetes (i.e. diabetic nephropathy group) was a significant predictor of LV diastolic dysfunction in CRF subjects, independent of other influencing factors such as age, blood pressure, renal function, anaemia and LV hypertrophy.Conclusion  The present findings suggest that LV diastolic dysfunction, independent of LV hypertrophy, is specifically and markedly progressed in patients with CRF as a result of diabetic nephropathy.
Quality assurance for diabetic retinopathy telescreening
Authors: Schneider S. , Aldington S. J. , Kohner E. M. , Luzio S. , Owens D. R. , Schmidt V. , Schuell H. , Zahlmann G. 
Published: May 2005

AbstractAims  TOSCA was an EU‐Commission supported international research project designed to develop telescreening services in diabetic retinopathy and glaucoma. This paper describes the quality assurance methods developed for the diabetic retinopathy telescreening service within the TOSCA project.Setting  The study was performed in 1895 patients with diabetes between 2000 and 2002 at diabetic retinopathy screening sites in five European countries. Data were analysed centrally.Methods  Patients attending each clinic's diabetic retinopathy screening service received standardized retinal photography. The images and associated data were transferred electronically to a remote location for grading. Each photographer uploading images and each grader downloading images for assessment was controlled by a systematic quality management approach. The quality assurance measures defined were image quality, intragrader reliability. A cockpit chart was developed for the management and presentation of relevant results and quality measures. For the intragrader reliability tests, 10% of the images were processed for a second grading. An algorithm for calculating differences between repeated gradings was developed.Results  The assessment of image quality for the different sites showed that only 0–0.7% were unassessable. One hundred per cent agreement for both gradings was achieved in 50–85% of graded cases, depending on site and grader, and an agreement better than 95% in 71–100% of cases.Conclusions  A telemedicine‐supported quality assurance process is practical and advantageous. The cockpit charts have proven to be useful tools when monitoring the performance of a telescreening service. Grader feedback showed high satisfaction with the quality assurance process.
The SPINK1 N34S mutation is not associated with Type 2 diabetes mellitus in a population of the USA
Authors: Schneider A. , Lawrence E. C. , Barmada M. M. , Norris J. M. , Hamman R. F. , Marshall J. A. , Ferrell R. E. , Whitcomb D. C. 
Published: May 2005

AbstractAims  Mutations in the serine protease inhibitor (SPINK1) gene have been associated with all forms of chronic pancreatitis. Recently, an association of SPINK1 mutations with early‐onset Type 2 diabetes mellitus has been reported in patients from Bangladesh. Therefore, we determined the frequency of SPINK1 N34S mutations in patients with Type 2 diabetes mellitus from the USA.Methods  The study population of Hispanic and non‐Hispanic white people consisted of 387 patients with Type 2 diabetes and familial clustering of the disease, 232 family members without diabetes, 259 patients with Type 2 diabetes without a family history, and 302 ethnically matched healthy controls as part of the San Luis Valley Diabetes Study. We performed linkage‐ and association‐analysis in 82 multiplex families with Type 2 diabetes mellitus.Results  No significant linkage or allele sharing was detected between Type 2 diabetes mellitus and the SPINK1 locus. The frequency of the N34S mutation was determined by fluorescence polarization and was similar between patients (n = 14/387 patients with familial clustering; n = 2/259 patients without family history) and controls (n = 5/232 family members without diabetes; n = 10/302 individuals). Variables such as ethnicity, age of diabetes onset and percentage of individuals with impaired glucose tolerance did not differ significantly between carriers and homozygous normal individuals.Conclusion  The SPINK1 N34S mutation appears not to predispose Hispanic or non‐Hispanic white people from the USA to the development of Type 2 diabetes mellitus.
Association between MspI polymorphism of the APO AI gene and Type 2 diabetes mellitus
Authors: Morcillo S. , Cardona F. , Rojo‐Martínez G. , Esteva I. , Ruíz‐de‐Adana M. S. , Tinahones F. , Gómez‐Zumaquero J. M. , Soriguer F. 
Published: May 2005

AbstractAims  Genes of the Apo AI/CIII/AIV cluster on chromosome 11 have been related to plasma lipid patterns. The close relationship between carbohydrate metabolism and lipid metabolism warrants investigation of the association between this cluster and Type 2 diabetes mellitus. We therefore examined the possible association between polymorphisms of this cluster and Type 2 diabetes mellitus as part of a study of the prevalence of diabetes and the metabolic syndrome in southern Spain.Methods  A total of 1224 persons were selected randomly from the town of Pizarra in the province of Malaga, southern Spain. The sample errors for the prevalence of Type 2 diabetes mellitus and the three polymorphisms studied were all ≤ 4%. All subjects underwent phenotyping after an oral glucose tolerance test (75 g) (WHO 1998 criteria) and the XmnI and MspI polymorphisms of Apo AI and the SstI polymorphism of Apo CIII were genotyped.Results  Those subjects with the mutated AA genotype of the MspI polymorphism (−75 G→A) of Apo AI had a greater risk of impaired glucose tolerance [odds ratio (OR) = 1.95, CI = 1.02–3.8, P = 0.05], Type 2 diabetes mellitus, both known (OR = 7.38, CI = 1.3–39.7, P = 0.02) and unknown (OR = 3.7, CI = 1.4–9.9, P = 0.009). This risk was independent of age, sex, obesity, triglyceride level, HDL cholesterol and pattern of insulin resistance.Conclusions  Pending confirmation in prospective studies, the AA genotype of the MspI polymorphism of the Apo AI gene, within the Apo A‐I/C‐III/A‐IV cluster, seems to be a risk factor for Type 2 diabetes mellitus.
Prevalence of undiagnosed Type 2 diabetes and impaired fasting glucose in older B ritish men and women
Authors: Thomas M. C. , Walker M. K. , Emberson J. R. , Thomson A. G. , Lawlor D. A. , Ebrahim S. , Whincup P. H. 
Published: May 2005

AbstractAim  To estimate the prevalence of undiagnosed diabetes and impaired fasting glucose in older British men and women, using the 1999 World Health Organization (WHO) thresholds based on fasting glucose measurements.Methods  Participants in the British Regional Heart Study and the British Women's Heart and Health Study were selected from one socially representative general practice in 24 British towns. Included in this analysis were 3736 men and 3642 women aged 60–79 years (predominantly white), who provided a single fasting blood sample at a clinical examination between 1998 and 2001, and who had no previous diagnosis of diabetes.Results  Two hundred and eleven men (5.7%) and 190 women (5.2%) had a fasting blood glucose level consistent with the WHO threshold for a diagnosis of diabetes (≥ 7.0 mmol/l), whilst a further 667 men (17.9%) and 642 women (17.6%) had impaired fasting glucose levels (6.1 ≤ 7 mmol/l). When analyses were restricted to subjects who had fasted for at least 8 h, and whose blood sample was taken before 12.00 h, the predicted prevalence of undiagnosed diabetes (based on two separate measurements) was 6.7% in men and 6.0% in women. The predicted prevalence of impaired fasting glucose (based on two separate measurements) was approximately 20% in both sexes.Conclusions  More than one‐fifth of older white British men and women have either undiagnosed diabetes or impaired fasting glucose according to new WHO criteria. Strategies for the primary and secondary prevention of Type 2 diabetes among older individuals are urgently needed.