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Biomedical subjects

J Ara

Publications and source records attributed to J Ara.

32 records · Page 2Linked to original sources
PubMed1995

Pakistan national diabetes survey: prevalence of glucose intolerance and associated factors in Shikarpur, Sindh Province.

The prevalence of diabetes mellitus and impaired glucose tolerance (IGT) and their relationship to age and obesity was estimated in the rural town of Shikarpur in Sindh Province, Pakistan by a population-based survey in 1994. Oral glucose tolerance tests were performed in a stratified random sample of 967 adults (387 men, 580 women) aged 25 years and above. The diagnoses of diabetes and IGT were made on the basis of WHO criteria. The response rate was 71% for men and 80% for women. The prevalence of diabetes was 16.2% (9.0% known, 7.2% newly diagnosed) in men, and 11.7% (6.3% known, 5.3% newly diagnosed) in women. The prevalence rose with age to a peak of 30% and 21% in 65-74 year-old men and women respectively. IGT was detected in 8.2% of men and 14.3% of women. Thus, total glucose intolerance (diabetes and IGT combined) was present in 25% of subjects examined. These results indicate that glucose intolerance in South Asians can no longer be regarded as a problem confined to migrant communities. Of the 72 subjects previously known to have diabetes, none was using insulin treatment, but 57 (79%) took oral hypoglycaemic agents. Central obesity and positive family history were strongly associated with diabetes, as was prevalence of hypertension. The association with central obesity was greater for women than for men, and suggests important, modifiable risk factor(s) related to lifestyle.

Adult↗
PubMed1995

Antigenic specificity of anti-ROS DNA antibodies: involvement of lysyl residues in antigen binding.

The antigenicity of native DNA modified with reactive oxygen species was examined. Goats were immunized with the modified polymer and the antibody response was estimated by direct binding and competition ELISA. The induced antibodies bound ROS-DNA and showed considerable binding to native DNA as well. Specificity analysis of the purified antibodies revealed the recognition of native B-, A- and allied conformations presented by various synthetic polynucleotides. The contribution of lysine residues to the immunochemical binding of purified IgG was investigated by modifying the free amino groups of lysine residues. The modification of lysine residues paralleled loss in IgG binding to ROS-DNA to the extent of 50%, suggesting that such residues might be involved in the antigen binding site of immunoglobulin molecule.

Acylation↗
PubMed1993

Polynucleotide specificity of anti-reactive oxygen species (ROS) DNA antibodies.

Hydrogen peroxide in the presence of short wavelength UV light was able to induce alterations in native DNA fragments of 300 bp (ROS-DNA), thereby rendering it immunogenic in experimental animals. The specificity of induced antibodies was investigated by direct binding and competition ELISA. Inhibition studies revealed nearly 89% inhibition in the antibody binding by the immunogen and recognition of native B-, A- and allied conformations presented by various synthetic polynucleotides. Gel retardation assay reiterated the formation of immune complexes between induced antibodies and native and ROS-DNA fragments. It was observed that naturally occurring anti-DNA autoantibodies from systemic lupus erythematosus (SLE) sera recognize ROS-DNA. The comparison of the specificities of anti-DNA autoantibodies from 10 SLE patients showed a 20-50-fold preference for ROS-DNA over native DNA. These results demonstrate that anti-DNA antibodies can be induced by ROS-DNA, and that some of the autoimmune DNA binding antibodies found in SLE may result from response to reactive oxygen species.

Animals↗
PubMed1993

Assay of antinuclear antibodies by ELISA using nuclei as antigen.

An enzyme-linked immunosorbent assay to detect antinuclear antibodies in the sera of patients with autoimmune diseases is described. Goat liver nuclei were immobilized on polystyrene plates and antinuclear antibodies were used to standardize the assay. The effects of variables, such as the nuclei concentration, conditions of nuclei storage, and the length of the incubation period were investigated on the assay. Prototype sera with known antibody specificity were used to evaluate the assay. The method described is highly sensitive, autoantibodies being detectable at serum dilutions of 1:1000 or higher. According to the intra- and inter-assay coefficient of variation, the results were highly reproducible.

Animals↗
PubMed1992

Reactive oxygen species modified DNA fragments of varying size are the preferred antigen for human anti-DNA autoantibodies.

In vitro studies were carried out to determine if reactive oxygen species modified DNA molecules are the preferred antigen for anti-DNA antibodies found in SLE sera. Reactive oxygen species were generated by 254 nm irradiation of hydrogen peroxide. Single stranded breaks, decrease in Tm and modification of adenine (21.7%) and thymine (48%) were the major effects observed on native DNA fragments of 300 bp in length. The ROS-modified DNA showed increased binding with naturally occurring anti-DNA autoantibodies as compared to unmodified DNA fragments. These results were substantiated by competition ELISA. Measurement of binding with DNA fragments of varying size revealed considerably increased binding as the fragment size increased from 50 bp to 800 bp. The relative affinity of anti-DNA IgG for ROS-modified and native DNA fragments of 300 bp were in the order of 6.26 x 10(-8) M and 4.07 x 10(-8) M, respectively.

Animals↗
PubMed1992

Antibodies against free radical modified native DNA recognize B-conformation.

Hydroxyl radical, a prominent entity of reactive oxygen species, is known to modify cellular DNA and has been implicated in several human diseases. In the present studies, the radical was generated by exposure of hydrogen peroxide to 254 nm light in the presence of native calf thymus DNA. Single strand breaks, decrease in Tm and modification of adenine and thymine were some of the modifications observed in nDNA. Antibodies induced in experimental animals against the modified DNA were immunogen specific. These antibodies also recognize native B-conformation. It was observed that naturally occurring anti-native DNA autoantibodies from SLE sera recognize modified DNA in direct binding and competition ELISA. Gel retardation assay reiterated the formation of immune complexes between induced antibodies and DNA fragments of around 300 bp (B-conformation). The possible significance of these findings in the etiology of SLE has been discussed.

Animals↗
PubMed1991

Cholinergic blockade with pirenzepine induces dose-related reduction in glucose and insulin responses to a mixed meal in normal subjects and non-insulin dependent diabetics.

OBJECTIVE: The aim of the study was to assess the effects of cholinergic blockade with pirenzepine on glucose and insulin responses to a mixed meal in normal subjects and patients with non-insulin dependent diabetes (NIDDM). Further, to assess in normal subjects the relative importance of nocturnal GH suppression by pirenzepine. DESIGN: Placebo, 100 or 200 mg pirenzepine were given to the normal subjects 1 hour before a standard mixed meal. The effects of placebo or 200 mg pirenzepine at night on nocturnal GH secretion and subsequent breakfast carbohydrate tolerance were also studied. NIDDMs were given placebo or 200 mg pirenzepine before the meal. SUBJECTS: We studied six healthy male volunteers (ages 20-22, body mass indices 20.3-23.3) and ten NIDDMs (eight men, ages 42-74); five obese (BMI 25.5-31.8) and five non-obese (BMI 21.2-24.8). MEASUREMENTS: Serial plasma glucose and insulin concentrations were measured for 3 hours after a standard mixed meal. RESULTS: Acute pretreatment of normal male volunteers with pirenzepine produced a dose-related improvement in carbohydrate tolerance. Peak post-prandial plasma glucose levels were delayed and significantly reduced following 200 mg orally (6.5 +/- 0.1 mmol/l), but not following 100 mg (7.3 +/- 0.3), compared with placebo (7.6 +/- 0.3). Peak insulin levels were similarly delayed and reduced by the 200 mg dose only (36.5 +/- 6.1 mU/l, compared with 49.8 +/- 8.7). Suppression of nocturnal GH by 200 mg pirenzepine at night produced a small reduction in fasting plasma glucose (5.0 +/- 0.1 mmol/l, compared with 5.3 +/- 0.1, P less than 0.02) but did not improve subsequent breakfast carbohydrate tolerance. Peak plasma glucose in NIDDMs was reduced following pirenzepine (12.4 +/- 0.9 mmol/l) compared with placebo (14.3 +/- 1.0, P less than 0.01). This reduction was equally significant in obese and non-obese groups. Peak plasma insulin was also reduced by pirenzepine (22.4 +/- 3.9 mU/l) compared with placebo (42.4 +/- 5.3, P less than 0.01). Insulin suppression was quantitatively greater in obese than in non-obese patients. CONCLUSIONS: Improvement in carbohydrate tolerance after pirenzepine in normal subjects is dose related and largely independent of GH suppression. Cholinergic blockade can also improve meal carbohydrate tolerance with simultaneous reduction in plasma insulin concentrations in non-insulin dependent diabetics, particularly those with obesity.

Adult↗
PubMedDate not supplied

Modulation of glucose and growth hormone responses to meals and exercise in type 1 diabetes by cholinergic muscarinic blockade.

Anticholinergic drugs suppress nocturnal and exercise-related growth hormone (GH) secretion in Type 1 diabetes; nocturnal GH suppression is associated with a fall in fasting plasma glucose levels. The aim of this study was to assess the effect of GH suppression on glucose levels following a period of meals and exercise in physiological pattern. Six Type 1 diabetic men recruited from the outpatient clinic were studied in random order at least 1 week apart. After an overnight fast subjects received two-thirds of their usual subcutaneous insulin and either 200 mg oral pirenzepine or placebo at time 0 min. Between 90 and 120 min subjects exercised continuously on an ergometric cycle. Standard meals or snacks were eaten at 30, 150, 270, and 390 min. Venous blood was collected from an indwelling cannula between 0 and 570 min. The mean incremental rise in plasma glucose after breakfast (delta peak/90 min) was 2.6 +/- 0.5 (mean +/- SEM mmol l-1 (pirenzepine) vs 4.5 +/- 0.8 (placebo)), p < 0.05. Following exercise the fall in plasma glucose (delta gluc90-240 min) was 6.4 +/- 1.9 (pirenzepine) vs 2.0 +/- 1.3 (placebo), p < 0.005. The exercise-related peak rise in GH was 12.6 +/- 3.3 (pirenzepine) vs 28.5 +/- 6.0 mU l-1 (placebo), p = 0.08. Excluding one outlying result there was an inverse correlation between the integrated exercise-related increase in GH between 90 and 240 min and the fall in glucose over the corresponding time period (n = 11, r = -0.75, p = 0.008).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Serum levels of soluble interleukin-2 receptor in patients with ANCA-associated vasculitis.

Serum soluble interleukin-2 receptor (sIL-2R) concentrations were determined using the ELISA method in 19 cases of ANCA-associated vasculitis. These patients were classified as 7 cases of Wegener's granulomatosis (WG) and 12 cases of microscopic polyangiitis (MPA). Elevated levels of sIL-2R were present in the sera of these patients. Levels of serum sIL-2R were not significantly different in patients with WG and MPA either in the active or inactive phase, so the results were expressed as a unified ANCA associated vasculitis group. Concentrations of serum sIL-2R were significantly higher in ANCA-associated vasculitis during the active phase than during the inactive phase (p<0.05), and serum sIL-2R levels were significantly increased in these patients, in the active or inactive stage, compared with a group of healthy subjects (p<0.05). In patients with vasculitis, serum sIL-2R levels correlated with serum levels of C-reactive protein (p<0.05). In the active phase, concentrations of serum sIL-2R correlated to creatinine concentrations. No correlation was found between sIL-2R and ANCA levels in any of the stages of the disease. These findings suggest cellular immune activation in ANCA associated vasculitis.

Adult↗
PubMedDate not supplied

High prevalence of antithyroid antibodies in anti-glomerular basement membrane antibody-mediated disease.

Anti-glomerular basement membrane antibody (anti-GBM Ab)-mediated disease and autoimmune thyroiditis are characterized by the presence of organ-specific antibodies. The diagnosis of autoimmune thyroiditis is usually based on the presence of serum antithyroid antibodies. Few studies have addressed the relationship between anti GBM-Ab mediated disease and autoimmune thyroid pathology. Given that this disorder is often asymptomatic, associations of the two pathologies may be under-diagnosed. This study investigated the prevalence of serum antithyroid antibodies (antithyroglobulin (anti-TG) and anti-thyroid peroxidase (anti-TPO)) in patients with anti-GBM Ab-mediated disease. Antithyroid antibodies presence was investigated in sera from 35 patients in whom anti-GBM Ab-mediated disease had been diagnosed. Anti-glomerular basement membrane antibodies and anti-thyroid antibodies (anti-TG and anti-TPO) were assayed using an enzyme-linked immunosorbent assay. Forty-five percent of patients with anti-GBM Ab-mediated disease (16/35) had positive antithyroid antibody titers. Eighteen percent (3/16) suffered from subclinical hypothyroidism. In conclusion, the high prevalence of antithyroid antibodies in these patients suggests a possible pathogenic link between autoimmune thyroiditis and anti GBM Ab-mediated disease.

Adult↗
PubMedDate not supplied

[Anti-glomerular basement membrane disease: a new disease causing fever of unknown origin?].

Antiglomerular basement membrane disease is an autoimmune disorder characterized by the presence of antibodies directed against glomerular basement membrane. Pyrexia of unknown origin (PUO) is defined as temperatures higher than 38.3 degrees C on several occasions, with a duration of more than 3 weeks, and failure to reach a diagnosis despite 1 week of in-patient investigation. There is a large list of causes of PUO including infections, malignancies and autoimmune diseases, but antiglomerular basement disease has not been described as a cause. We present the first case of antiglomerular basement disease which presented with PUO.

Anti-Glomerular Basement Membrane Disease↗
PubMedDate not supplied

[Rapid-detection GBM-ANCA ELISA. An emergency tool for the early diagnosis of type I and II rapidly progressive glomerulonephritis].

Rapidly progressive glomerulonephritides (RPGN) are forms of necrotizing glomerulonephritis associated with anti-glomerular basement membrane (anti-GBM) and anti-neutrophil cytoplasmic antibodies (ANCA) against the antigens proteinase-3 (anti-PR3) and myeloperoxidase (anti-MPO). RPGN have a course of rapid progression to renal failure. We compared the results from the semiquantitative ELISAs for anti-GMB antibodies, PR3-ANCA and MPO-ANCA and the indirect immunofluorescence technique (IIF) against a new rapid assay (30 minutes) for the same antibodies in patients with clinically suspected RPGN. The semiquantitative ELISAs for anti-GBM antibodies and PR3-ANCA and MPO-ANCA have a proven diagnostic significance in patients with RPGN I and III. There were no significant differences between the ANCA-GBM screening test and the results from the semiquantitative ELISAs (p > 0.05). We did not find significant differences between the results for PR3-ANCA and MPO-ANCA from the ANCA-GBM screening test with C-ANCA and P-ANCA IIF values (p > 0.05). We also corroborated that the ANCA-GBM screening test is a diagnostic tool for RPGN I and III as useful as the semiquantitative ELISAs and the IFF technique. The ANCA-GBM ELISA screening test is a tool as useful as the semiquantitative ELISA against anti-GBM antibodies for diagnosis of RPGN I. The comparison of the screening ELISA with the IIF technique and the semiquantitative ELISAs against PR3-ANCA and MPO-ANCA showed similar utility for diagnosis of RPGN III. The advantages of the new screening assay are that three antibodies are tested at the same time, yielding results in only 30 minutes.

Adolescent↗