Shuttling components of nuclear import machinery involved in nuclear translocation of steroid receptors exit nucleus via exportin-1/CRM-1* independent pathway.

The nucleocytoplasmic transport processes are mediated by soluble transport factors constantly navigating between nuclear and cytoplasmic compartments. Our understanding about nuclear export of general 'nuclear import factors' that deliver the cargo to the nucleus is still fragmentary. Utilizing green fluorescent protein tagged glucocorticoid receptor (GR) and relA as our working model and with judicious use of LMB, we show in living cells that all the soluble components of the nuclear import machinery exit nucleus via exportin1/CRM1 independent pathway(s).

Risk factors for non-fatal myocardial infarction in young South Asian adults.

Objective: To determine the risk factors for premature myocardial infarction among young South Asians.

Design And Setting: Case-control study in a hospital admitting unselected patients with non-fatal acute myocardial infarction.

Methods And Subjects: Risk factor assessment was done in 193 subjects aged 15-45 years with a first acute myocardial infarct, and in 193 age, sex, and neighbourhood matched population based controls.

Risk factors for coronary heart disease in type 1 diabetic patients in Europe: the EURODIAB Prospective Complications Study.

Objective: The goal of the study was to examine risk factors in the prediction of coronary heart disease (CHD) and differences in men and women in the EURODIAB Prospective Complications Study.

Research Design And Methods: Baseline risk factors and CHD at follow-up were assessed in 2,329 type 1 diabetic patients without prior CHD. CHD was defined as physician-diagnosed myocardial infarction, angina pectoris, coronary artery bypass graft surgery, and/or Minnesota-coded ischemic electrocardiograms or fatal CHD.

Pulse pressure is associated with age and cardiovascular disease in type 1 diabetes: the Eurodiab Prospective Complications Study.

Objective: Type 1 diabetic individuals are thought to have increased arterial stiffness, and are at high risk for cardiovascular disease. However, it is not known whether increased arterial stiffness in type 1 diabetes causes cardiovascular disease. To explore this issue, the present study investigated the association, in type 1 diabetes, of age and pulse pressure, an estimate of arterial stiffness, and the influence of the presence of microvascular complications on this association.

Ethnic differences and determinants of proteinuria among South Asian subgroups in Pakistan.

Background: Hypertension, diabetes, increasing age, and smoking are known risk factors for proteinuria. Prevalence of proteinuria is high in South Asians. However, ethnic subgroup differences and determinants of proteinuria within the South Asian population have not been explored.

The prevalence of hepatitis C virus antibodies among the voluntary blood donors of New Delhi, India.

Infection with hepatitis C virus (HCV) is a major cause of transfusion-associated hepatitis, cirrhosis and hepatocellular carcinoma. The present study was conducted with an objective to evaluate the prevalence of anti-HCV antibody in New Delhi, India using a large number of healthy voluntary blood donors. A total of 15,898 healthy voluntary blood donors were subjected to anti-HCV testing (using a commercially available third generation anti-HCV ELISA kit) and 249 were found to be reactive for anti-HCV antibody, yielding an overall prevalence of 1.

Ethnicity, socio-economic position and gender--do they affect reported health-care seeking behaviour?

While the pursuit of equity of access to health care is a central objective of many health care systems, there is evidence that patients of ethnic minority descent, in lower socio-economic position (SEP) or of female gender are less likely than Whites, more affluent groups or men, respectively, to access secondary and tertiary medical care. However, it is unclear at which point in the chain of events leading from perception of need through attendance at primary/emergency care, to referral and receipt of secondary care, this inequality occurs. This study examined the influence of ethnicity, socio-economic position and gender on an individual's perception of the need and urgency for seeking health care.

Vascular risk factors and markers of endothelial function as determinants of inflammatory markers in type 1 diabetes: the EURODIAB Prospective Complications Study.

Objective: Inflammatory activity is increased in type 1 diabetes and may predispose to vascular disease. Its origin is not clear. We therefore investigated determinants of inflammation in type 1 diabetes.

Ethnic subgroup differences in hypertension in Pakistan.

Objective: Cardiovascular risks are globally elevated in South Asians, but this masks important ethnic subgroup differences in risk factors, such as hypertension, which have not been fully explored. We conducted this study to explore the variations in hypertension within ethnic subgroups among South Asians.

Design: Cross-sectional survey [National Health Survey of Pakistan (NHSP) (1990-1994)].

Differing aspects of insulin resistance in diabetes complications: the shape of things to come. RD Lawrence Lecture 2000.

The anticipated global epidemic of diabetes, largely as a consequence of increased rates of obesity, will particularly impact on people of South Asian and African Caribbean descent, two populations at elevated risk of insulin resistance. This article contrasts the consequent heightened risk of heart disease on the one hand in South Asians, and the paradoxical protection from heart disease in African Caribbeans on the other. Protection from the hypertriglyceridaemic effects of insulin resistance is likely to account for much of the African Caribbean paradox, although the mechanisms remain unclear.

The DIabetic Retinopathy Candesartan Trials (DIRECT) Programme, rationale and study design.

The DIabetic Retinopathy Candesartan Trials (DIRECT) Programme consists of three randomised, double-masked, parallel, placebo-controlled studies to determine the impact of treatment with candesartan on diabetic retinopathy. In Type 1 diabetes, 1,700 patients without retinopathy will be randomised into a primary prevention study, and 1,200 with non-proliferative retinopathy into a secondary prevention study. In Type 2 diabetes, 1,600 patients with non-proliferative retinopathy will be randomised.

The renin-angiotensin-aldosterone system and the eye in diabetes.

Diabetic retinopathy is the leading cause of blindness in the under 65s, and with the burden of disease case load expected to exceed 200 million worldwide within 10 years, much effort is being spent on prophylactic interventions. Early work focused on improving glycaemic control; however, with the publication of EURODIAB Controlled trial of Lisinopril in Insulin-dependent Diabetes (EUCLID) and United Kingdom Prospective Diabetes Study (UKPDS), the focus has recently moved to control of blood pressure and specifically the renin-angiotensin system (RAS). There is a large body of evidence for a local RAS within the eye that is activated in diabetes.

Circulating and urinary transforming growth factor beta1, Amadori albumin, and complications of type 1 diabetes: the EURODIAB prospective complications study.

Objective: Transforming growth factor (TGF)-beta1 is overexpressed in diabetes as a consequence of hyperglycemia and the creation of early glycated end products and may be responsible for the characteristic structural renal changes associated with diabetes. We sought to examine the role of both urinary and circulating TGF-beta1 and its promoter Amadori albumin in the vascular complications of type 1 diabetes.

Research Design And Methods: The present article reports on a nested case-control study from the EURODIAB Prospective Complications Study of Europeans with type 1 diabetes.

Autonomic neuropathy is associated with increased cardiovascular risk factors: the EURODIAB IDDM Complications Study.

Aims: To assess the prevalence of and risk factors for autonomic neuropathy in the EURODIAB IDDM Complications Study.

Methods: The study involved the examination of randomly selected Type I (insulin-dependent) diabetic patients from 31 centres in 16 European countries. Neuropathic symptoms and two tests of autonomic function (changes in heart rate and blood pressure from lying to standing) were assessed and data from 3007 patients were available for the present analysis.

Mechanism of magnesium activation of calcium-activated potassium channels.

Large-conductance (BK type) Ca(2+)-dependent K(+) channels are essential for modulating muscle contraction and neuronal activities such as synaptic transmission and hearing. BK channels are activated by membrane depolarization and intracellular Ca(2+) and Mg(2+) (refs 6-10). The energy provided by voltage, Ca(2+) and Mg(2+) binding are additive in activating the channel, suggesting that these signals open the activation gate through independent pathways.

Amadori-albumin correlates with microvascular complications and precedes nephropathy in type 1 diabetic patients.

Background: Amadori-albumin, a major glycated protein, is involved in experimental hyperglycaemia-induced microvascular complications, and is associated with advanced nephropathy in Type I diabetic patients in humans. Our aim was to assess the association of Amadori-albumin with early nephropathy and with retinopathy in Type I diabetic patients and the involvement of chronic low-degree inflammation therein.

Design And Methods: Amadori-albumin, the Amadori product of haemoglobin (HbA1c), C-reactive protein, and fibrinogen levels were measured in the EUCLID study, a 2-year randomised, double-blind, placebo-controlled trial of lisinopril in 447 Type I diabetic patients.

The retinal renin-angiotensin system: implications for therapy in diabetic retinopathy.

Retinopathy is the most common complication of diabetes, and a leading cause of blindness in people of working age. Optimal blood pressure and metabolic control can reduce the risk of diabetic retinopathy, but are difficult to achieve in clinical practice. In the EUCLID Study, the angiotensin converting enzyme (ACE) inhibitor lisinopril reduced the risk of progression of retinopathy by approximately 50%, and also significantly reduced the risk of progression to proliferative retinopathy.

Blood pressure response to standing in the diagnosis of autonomic neuropathy: the EURODIAB IDDM Complications Study.

Autonomic neuropathy is associated with poor prognosis. Cardiovascular reflexes are essential for the diagnosis of autonomic nerve dysfunction. Blood pressure response to standing is the most simple test for the evaluation of sympathetic integrity, however it is still discussed which diagnostic criteria of abnormal response should be considered as optimal.

Risk of diabetes-related amputation in South Asians vs. Europeans in the UK.

Aims: To compare the risk of and risk factors for diabetes-related amputation in South Asians and Europeans.

Methods: This was a population-based case control study based in the health districts of Bolton, Oldham and Central Manchester in the UK. Cases with diabetes-related amputation performed between 1992 and 1997 (n = 172) and controls with diabetes and no amputation (n = 376) were selected from the primary care-based North-west Diabetes Foot Study database.

Ethnicity and risk of diabetes-related lower extremity amputation: a population-based, case-control study of African Caribbeans and Europeans in the United kingdom.

Background: In the United States, people of black African descent with diabetes have 2 to 3 times the amputation risk of whites. This may be due to differences in care or pathophysiological characteristics. We therefore determined diabetes-related amputation rates in African Caribbeans vs Europeans in the United Kingdom, where care delivery is more equitable.

Risk factors for progression to proliferative diabetic retinopathy in the EURODIAB Prospective Complications Study.

Aims/hypothesis: Proliferative diabetic retinopathy (PDR), a leading cause of blindness, cannot be totally prevented by optimizing metabolic and blood pressure control and responds to no specific treatment other than partially destructive retinal photocoagulation. Recognizing risk factors using large-scale epidemiological studies could help identify targets for treatment. The EURODIAB Prospective Complications Study (PCS) includes the largest cohort so far of patients with Type I (insulin-dependent) diabetes mellitus.

Birth weight, childhood growth and abdominal obesity in adult life.

Objective: To examine the relationship of adult abdominal obesity to birth weight, childhood growth and lifetime socioeconomic circumstances.

Methods: A cohort of 3200 men and women with measured waist and hip circumference, height and weight at age 43 who have been followed since their birth in March 1946 in England, Scotland and Wales. Regression models were used to examine mean waist-hip ratio and waist circumference in relation to prospective measures of birth weight, weight relative to height in childhood at ages 4, 7, 11 and 15 and adult body mass index, and to test the independent and interactive nature of the associations and adjust for childhood and adult social class.