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Biomedical subjects

B Persson

Publications and source records attributed to B Persson.

At least 145 records · Page 8Linked to original sources
PubMed1996

Diabetes mellitus and raised serum triglyceride concentration in treated hypertension--are they of prognostic importance? Observational study.

OBJECTIVE: To analyse whether metabolic changes during long term treatment with antihypertensive drugs are associated with an increased risk of coronary heart disease. DESIGN: Observational study. SETTING: Gothenburg, Sweden. SUBJECTS: 686 middle aged hypertensive men, recruited after screening of a random population sample, and followed for 15 years during treatment with predominantly beta adrenoceptor blockers or thiazide diuretics, or both. Coronary heart disease and diabetes mellitus were registered at yearly patient examinations. Entry characteristics, as well as within study serum concentrations of cholesterol and triglycerides and the development of diabetes mellitus, were related to the incidence of coronary heart disease in a time dependent Cox's regression analysis. MAIN OUTCOME VARIABLE: Coronary heart disease morbidity. RESULTS: Diabetes mellitus, raised serum cholesterol and triglyceride concentrations present at the beginning of the study were all significantly predictive of coronary heart disease in univariate analysis. The relative risk of diabetes mellitus and of a 1 mmol/l increase in the cholesterol and triglyceride concentrations was 2.12 (95% confidence interval 1.11 to 4.07), 1.21 (1.05 to 1.39), and 1.21 (1.03 to 1.43) respectively. However, when the within study metabolic variables were analysed, only the serum cholesterol concentration was significantly and independently associated with coronary heart disease (relative risk 1.07 (1.02 to 1.13)). Although the triglyceride concentrations increased slightly during the follow up, the within study serum triglyceride concentrations were not associated with the incidence of coronary heart disease (1.04 (0.96 to 1.10)). New diabetes mellitus-that is, onset during follow up-was not significantly associated with an increased risk for coronary heart disease (1.48 (0.37 to 6.00)). CONCLUSIONS: Metabolic disturbances such as diabetes mellitus and hyperlipidaemia presenting before the start of antihypertensive treatment have a prognostic impact in middle aged, treated hypertensive men. Moreover, while within study cholesterol concentration was an independent predictor of coronary heart disease, drug related diabetes mellitus and raised serum triglyceride concentrations that are associated with treatment do not seem to have any major impact on the coronary heart disease prognosis in this category of patients.

Adrenergic beta-Agonists↗
PubMed1996

Repeated immunotherapy using intratumoural injection with recombinant interleukin-2 and tumour-infiltrating lymphocytes inhibits growth of breast cancer and induces apoptosis of tumour cells.

This study tested the effect of repeated intratumoural injection with recombinant interleukin-2 (rIL-2) and tumour-infiltrating lymphocytes (TILs) on inhibition of growth of breast cancer and on induction of apoptosis of tumour cells. The tumour cell line LDLX43 was used to induce breast cancer in Wistar rats. Group I (10 rats) was the control. Group II (12 rats) received repeated intratumoural injection with rIL-2 and TILs. rIL-2 at the dose of 5 x 10(5) IU/day was given for 7 days, and 1 x 10(7) TILs were injected on the second day of each rIL-2 therapy, for a treatment session. Overall, two treatment sessions of immunotherapy with rIL-2 and TILs were given in all treated animals. Rapid increased tumour volume was found in the control group. In the treated group the total response rate was 42%, of which 25% tumours showed partial regression and 17% tumours reached complete remission where infiltration of plenty of T lymphocytes was detected, indicating that T cell-mediated antitumour immunity is primarily responsible for tumour rejection. Further investigation showed the repeated immunotherapy using intratumoural injection with rIL-2 and TILs could induce the development of apoptosis of breast cancer cells.

Animals↗
PubMed1996

Pea formaldehyde-active class III alcohol dehydrogenase: common derivation of the plant and animal forms but not of the corresponding ethanol-active forms (classes I and P).

A plant class III alcohol dehydrogenase (or glutathione-dependent formaldehyde dehydrogenase) has been characterized. The enzyme is a typical class III member with enzymatic parameters and substrate specificity closely related to those of already established animal forms. Km values with the pea enzyme are 6.5 microM for NAD+, 2 microM for S-hydroxymethylglutathione, and 840 microM for octanol versus 9, 4, and 1200 microM, respectively, with the human enzyme. Structurally, the pea/human class III enzymes are closely related, exhibiting a residue identity of 69% and with only 3 of 23 residues differing among those often considered in substrate and coenzyme binding. In contrast, the corresponding ethanol-active enzymes, the long-known human liver and pea alcohol dehydrogenases, differ more (47% residue identities) and are also in functionally important active site segments, with 12 of the 23 positions exchanged, including no less than 7 at the usually much conserved coenzyme-binding segment. These differences affect functionally important residues that are often class-distinguishing, such as those at positions 48, 51, and 115, where the plant ethanol-active forms resemble class III (Thr, Tyr, and Arg, respectively) rather than the animal ethanol-active class I forms (typically Ser, His, and Asp, respectively). Calculations of phylogenetic trees support the conclusions from functional residues in subgrouping plant ethanol-active dehydrogenases and the animal ethanol-active enzymes (class I) as separate descendants from the class III line. It appears that the classical plant alcohol dehydrogenases (now called class P) have a duplicatory origin separate from that of the animal class I enzymes and therefore a paralogous relationship with functional convergence of their alcohol substrate specificity. Combined, the results establish the conserved nature of class III also in plants, and contribute to the molecular and functional understanding of alcohol dehydrogenases by defining two branches of plant enzymes into the system.

Alcohol Dehydrogenase↗
PubMed1996

Health effects of working in pulp and paper mills: malignant diseases.

This paper reviews the available literature regarding the work environment in pulp and paper mills and the risk for malignant diseases. An increased risk for lung cancer among pulp and paper mill workers has been reported. Most studies are inconclusive with regard to considerations of etiologic agents. However, maintenance workers seem to be at an increased risk for lung cancer, as well as for malignant mesothelioma, indicating that this occupational group was (is) exposed to asbestos. Workers exposed to chlorine compounds also seem to run an increased risk for lung cancer. An increased risk for malignant lymphomas among pulp mill workers is a constant finding. The increased risk is observed both among sulfite and sulfate workers, indicating a common exposure. Such an exposure could be wood dust, terpenes, or preservatives present in the wood. An increased risk for leukemias has been found in many studies carried out on pulp and paper workers, but the studies do not permit any conclusions about etiologic factors. In some studies an increased risk for stomach cancer has been found. However, the socioeconomic status of the workers is strongly related to stomach cancer, and factors, such as dietary habits, have not been taken into account in any of the reviewed studies. Hence, no further conclusions can be drawn regarding etiologic agents.

Air Pollutants, Occupational↗
PubMed1996

Topology prediction of membrane proteins.

A new method is described for prediction of protein membrane topology (intra- and extracellular sidedness) from multiply aligned amino acid sequences after determination of the membrane-spanning segments. The prediction technique relies on residue compositional differences in the protein segments exposed at each side of the membrane. Intra/extracellular ratios are calculated for the residue types Asn, Asp, Gly, Phe, Pro, Trp, Tyr, and Val, preferably found on the extracellular side, and for Ala, Arg, Cys, and Lys, mostly occurring on the intracellular side. The consensus over these 12 residue distributions is used for sidedness prediction. The method was developed with a test set of 42 protein families, for which all but one were correctly predicted with the new algorithm. This represents an improvement over predictions based on the widely used "positive-inside rule" and other techniques, where at least six mispredictions were observed for the same data set. Further, application of this and other methods to 12 protein families not in the test set still showed the better performance of the present technique, which was subsequently applied to another set of membrane protein families where the topology has yet to be determined.

Algorithms↗
PubMed1996

Diagnostic sensitivity of immunodominant epitopes of glutamic acid decarboxylase (GAD65) autoantibodies in childhood IDDM.

The prevalence and titre of epitope-specific autoantibodies to glutamic acid decarboxylase (GAD65) in 155 insulin-dependent diabetic (IDDM) and 9 GAD65 antibody (Ab)-positive healthy children were determined using four GAD65/67 chimaeric molecules which discriminate among the N-terminal (N), middle (M) and C-terminal (C) epitopes of GAD65. Radioligand binding assays for IgGAb used immunoprecipitation of in vitro translated 35S-GAD. We found autoantibodies to GAD65 in 116 of 155 (75%), to GAD67 in 19 of 155 (12%) (p < 0.0001) and to the GAD65-N-67 chimaera in 25 of 155 (16%) (p < 0.0001) IDDM sera. GAD67Ab were found almost exclusively (17 of 19, 89%) in GAD65Ab-positive sera and the levels of GAD67Ab correlated with those of GAD65Ab (r2 = 0.5913; p = 0.009). GAD65Ab directed to GAD65-M were found in 104 of 155 (67%), to GAD65-C in 104 of 155 (67%) and to GAD65-M + C in 116 of 155 (75%) of IDDM sera, and indicated reactivity to at least two distinct epitopes. Among the nine GAD65Ab-positive healthy children, two (22%) were also positive with GAD67, nine (100%) with GAD65-M + C, seven (78%) with GAD65-M, eight (89%) with GAD65-C and two (22%) with GAD65-N-67. Titres of GAD65Ab (p = 0.007), GAD65-C-Ab (p = 0.002) and GAD65-C + M-Ab (p = 0.003), but not of GAD65-M-Ab (p = 0.101) were significantly higher in IDDM than in healthy children. We conclude that GAD65Ab in IDDM and healthy children are directed to middle and C-terminal epitopes, and propose that levels of antibodies specifically directed to the carboxy-terminal end of GAD65 may distinguish IDDM from healthy children.

Adolescent↗
PubMed1996

Troglitazone, an insulin action enhancer, improves metabolic control in NIDDM patients. Troglitazone Study Group.

The effects of troglitazone, a novel thiazolidinedione, in non-insulin-dependent diabetic (NIDDM) patients were studied in a double-blind, parallel-group, placebo-controlled, dose-ranging trial. A total of 330 patients (63% male), mean age 57 years (range 39-72), with two fasting capillary blood glucose values > or = 7 and < or = 15 mmol/l (within 2.5 mmol/l of each other) were randomised to treatment with placebo or troglitazone at doses of 200, 400, 600 or 800 mg once daily, or 200 or 400 mg twice daily, for 12 weeks. Prior to the study, treatment had been with diet alone (38% patients) or with oral hypoglycaemic agents which were stopped 3-4 weeks before study treatment started. During treatment, HbA1c tended to rise in patients taking placebo (7.2-8.0%), but remained unchanged with all doses of troglitazone. After 12 weeks of treatment, HbA1c was significantly lower in the troglitazone-treated (mean 7.0-7.4%) compared to the placebo-treated (8.0%) patients (p = 0.055 to < 0.001), as was fasting serum glucose concentration (troglitazone, 9.3-11.0 mmol/l vs placebo, 12.9 mmol/l, p < 0.001). All doses of troglitazone were equally effective. Troglitazone also lowered fasting plasma insulin concentration, by 12-26% compared to placebo (p = 0.074 to < 0.001). Insulin sensitivity assessed by homeostasis model assessment (HOMA) was greater after 12 weeks of treatment in troglitazone-treated patients (troglitazone, 34.3-42.8% vs placebo, 29.9%, p < 0.05). In addition, serum triglyceride and non-esterified fatty acid concentrations were significantly lower and HDL cholesterol higher at troglitazone doses of 600 and 800 mg/day. LDL cholesterol increased at 400 and 600 mg doses only (from 4.3 and 3.9 mmol/l at baseline to 4.8 and 4.5 mmol/l, respectively at 12 weeks, p < 0.05), but not at doses of 800 mg once daily or 400 mg twice daily. LDL/HDL ratio did not change during treatment. All doses were well tolerated; incidence of adverse events in troglitazone-treated patients was no higher than in those treated with placebo. However, a tendency to reduced neutrophil counts was observed in patients taking the highest doses of troglitazone. We conclude that troglitazone is effective and well-tolerated and shows potential as a new therapeutic agent for the treatment of NIDDM.

Adult↗
PubMed1996

Evaluation of the antihypertensive efficacy and tolerability of moexipril, a new ACE inhibitor, compared to hydrochlorothiazide in elderly patients.

OBJECTIVE: To compare the antihypertensive efficacy of moexipril, a new angiotensin-converting enzyme (ACE) inhibitor, to treatment with hydrochlorothiazide (HCTZ). PATIENTS: Two hundred and one non-hospitalized male and female patients between 65 and 80 years of age with essential hypertension. METHODS: This was a multicentre, placebo-controlled, double-blind study with a parallel group design. Subjects with a sitting diastolic blood pressure (DBP) > or = 95 mmHg were randomized to monotherapy with placebo, moexipiril 7.5 mg o.d., moexipril 15 mg o.d. or HCTZ 25 mg o.d. for 8 weeks. RESULTS: Throughout the study period treatment with moexipril and HCTZ resulted in significant reductions of DBP compared with placebo, but there were no significant differences between the active treatment groups. At end point the adjusted mean reductions were 10.5, 8.7 and 10.1 mmHg in the HCTZ, moexipril 7.5 mg and moexipril 15 mg groups, respectively, compared to 3.9 mmHg in the placebo group. Treatment with moexipril was associated with two cases of first dose hypotension and two cases of moderate and reversible increases in serum creatinine levels. Otherwise, both dosages of moexipril were well tolerated and the overall percentages of patients who had adverse experiences were smaller than in the placebo group. CONCLUSION: Moexipril is well tolerated and is at least as effective as HCTZ in elderly patients with essential hypertension.

Aged↗
PubMed1996

Polyelectrolyte/amphiphile interaction studied by surface tension measurements.

The interaction of kappa-carrageenan with three positively charged drug molecules with amphiphile character has been examined using surface tension measurements. The surface tension was measured by the pendant drop method which makes possible the determination at an apparent steady state which is important for polymeric systems. The results are compared with adsorption isotherms from dialysis equilibrium. The surface tension data, show that the presence of kappa-carrageenan in the amphiphile solutions leads to an increased and pronounced lowering of the surface tension in a low concentration range of amphiphile. It is also shown that not only the hydrophobicity of the amphiphile but also the structure of the polyelectrolyte (charge density and helix-coil structure) largely determine the extent of interaction.

Adsorption↗
PubMed1996

Fetal size at birth in relation to quality of blood glucose control in pregnancies complicated by pregestational diabetes mellitus.

OBJECTIVE: To determine the relation between maternal levels of blood glucose and glycated haemoglobin (HbA1c) and infant size at birth in pregestational diabetes. DESIGN: Longitudinal study from 6 to 14 weeks gestation. Women were treated intensively with insulin, aiming at normoglycaemia but avoiding hypoglycaemia. Blood glucose was determined six times daily, HbA1c every four weeks. Individual mean fasting and postprandial glucose levels were calculated for three-week periods of gestation. Birthweight > 2 SD or within +/- 2 SD for gestational age and gender was classified as large (LGA) or appropriate (AGA), respectively. Birthweight ratio was calculated as the ratio of birthweight to normal mean birthweight after correction for gestational age and gender. PARTICIPANTS: One hundred and thirteen consecutive pregnant women with pregestational diabetes and their newborn infants. RESULTS: Perinatal mortality was nil, the rates of spontaneous preterm delivery (8.9%) and severe maternal hypoglycaemia (4.4%) were low. Mothers with LGA infants (26%) had a significantly higher fasting glucose between weeks 27 and 32 than mothers of AGA infants (P < 0.01). Relative birthweight was significantly and independently associated with pre-pregnancy bodyweight (r = 0.24, P < 0.05) and fasting glucose at weeks 27 to 29 (r = 0.27, P < 0.01) but together could only explain 12.3% of the variation in birthweight (mult. r = 0.35, P < 0.01). HbA1c correlated with glucose levels but was unrelated to birthweight ratio. The fasting glucose level between weeks 30 and 32 was significantly interrelated with the fasting glucose level from each of the six preceding three-week periods. CONCLUSION: Near normoglycaemia cannot be obtained in all patients, presumably due to intrinsic differences in glucoregulatory ability between individuals. The incidence of LGA infants was unexpectedly high. The modest abnormality in glycaemic control in mothers with LGA infants could only partly explain fetal oversize, suggesting that other factors must be implicated to explain fetal growth acceleration.

Adolescent↗
PubMed1996

Hemorheologic effects of vasodilation in essential hypertension.

Arterial hypertension is often associated with plasma volume contraction and hemoconcentration, which negatively affect the vascular flow resistance and microcirculation. Since some antihypertensive drugs can affect blood rheology, the purpose of this study was to evaluate whether acute and long-term arterial vasodilation with cadralazine influences rheologic parameters in essential hypertension. Twelve patients with unsatisfactorily controlled essential hypertension were studied. In the acute double-blind phase of the study the patients were allocated to treatment with either cadralazine or placebo. Intraarterial blood pressure, cardiac output (dye dilution), and blood rheology (viscosity, hematocrit) were registered before and after the first dose of cadralazine. Then 9 patients (3 dropouts) were treated with cadralazine and placebo during two four-week crossover periods and continued with cadralazine medication during the eight-week open phase of the study. Blood pressure and blood hemoglobin were followed during long-term treatment. A single oral dose of cadralazine caused vasodilation (total peripheral resistance index decreased from 45 to 33 U x m2, P < 0.05), which was accompanied by hemodilution (hematocrit declined from 46.9% to 42.5%, P < 0.05) and a blood viscosity reduction of more than 10%. Viscosity of 45% suspension of erythrocytes in plasma was also reduced, suggesting a possible modification of the microrheologic factors. The changes in total peripheral resistance correlated negatively with the changes in hematocrit. An antihypertensive effect of cadralazine was still observed during the chronic phase of the study, which was not accompanied by hemodilution. It is concluded that arterial vasodilation with cadralazine reduces flow resistance in the circulatory system in hypertension and has acute rheologic effects that disappear during chronic medication.

Antihypertensive Agents↗
PubMed1996

Three cases of dental technician's pneumoconiosis related to cobalt-chromium-molybdenum dust exposure.

Dental technician's pneumoconiosis (DTP) is a rather recent finding in subjects exposed to the dust generated in dental laboratories producing metal-framed removable partial dentures from alloys based on cobalt, chromium, and molybdenum. This study presents details of the first three Swedish cases of DTP with some emphasis on the diagnostic procedures and the dust exposure. A follow-up of at least 5 years from diagnosis is included.

Adult↗
PubMed1996

Increased molar proinsulin-to-insulin ratio in women with previous gestational diabetes does not predict later impairment of glucose tolerance.

OBJECTIVE: To evaluate if an increased proinsulin-to-insulin ratio (PI/I) in former gestational diabetes mellitus (GDM) subjects could be a marker for later impairment of glucose tolerance. RESEARCH DESIGN AND METHODS: This study is a prospective follow-up. In a previous follow-up study of former GDM subjects 3-4 years after an index pregnancy, an increased PI/I was found also in normoglycemic nonobese former GDM subjects compared with control subjects. A 75-g oral glucose tolerance test (OGTT) was performed 3 years after the first follow-up, i.e., 6-7 years after the index pregnancy in 97 of the former GDM subjects and in 23 control subjects. A 75-g OGTT according to the World Health Organization was performed. Glucose, insulin, proinsulin, and C-peptide were determined at 0, 30, 60, 90, 120, 150, and 180 min after the glucose intake. RESULTS: Since the first follow-up, an additional 3 in 97 (3.1%) and 15 in 97 (15.5%) of the former GDM subjects had NIDDM or impaired glucose tolerance (IGT), respectively. All control subjects still had a normal OGTT. The fasting PI/I at follow-ups 1 and 2 was significantly correlated in the former GDM subjects (r = 0.41, P < 0.001) and in the control group (r = 0.46, P < 0.05). There was no significant correlation between the PI/I in follow-up 1 and the fasting or 2-h glucose values at follow-up 2. If GDM subjects with a PI/I in the upper quartile in the first follow-up were compared with those with a lower PI/I, there were no significant differences in outcome of OGTT in the second follow-up. CONCLUSIONS: The hypothesis that an increased fasting PI/I is a marker for later development of NIDDM or IGT in former GDM subjects could not be supported.

Adult↗
PubMed1996

Twenty years' colonoscopic surveillance of patients with ulcerative colitis. Detection of dysplastic and malignant transformation.

BACKGROUND: Endoscopic cancer surveillance in patients with ulcerative colitis has been performed for almost 3 decades. There is still no consensus on its clinical value. METHODS: This study evaluates a 20-year prospective study of 143 patients with extensive ulcerative colitis and a disease duration exceeding 10 years. Colonoscopy with double biopsy specimens from nine locations of the colon was performed every 2nd year. Biopsy specimens showing dysplasia were reviewed at the end of the study. RESULTS: Through the surveillance dysplasia/cancer was detected in 55 patients; 7 of these patients had carcinomas, and 2 were in a possibly curable stage (Dukes A). The predictive value of low-grade dysplasia for either high-grade dysplasia or cancer was 41%. CONCLUSIONS: Although impaired by limiting factors, colonoscopic surveillance of chronic extensive colitis may identify patients with dysplasia and thereby prevent malignant transformation.

Adult↗
PubMed1996

Stimulatory effect of insulin on tubular sodium reabsorption in normotensive subjects with a positive family history of hypertension.

BACKGROUND: Insulin resistance and hyperinsulinaemia has been suggested as a pathogenetic mechanism in hypertension. METHODS: In this investigation the renal response to insulin was studied in normotensive subjects with a positive family history of hypertension in two generations (n = 14), in one weight-matched (n = 11) and one lean (n = 13) control group. During hyperinsulinaemia (euglycaemic hyperinsulinaemic clamp technique) we determined renal haemodynamics (clearances of 51Cr-EDTA and PAH) and urinary sodium excretion. Lithium clearance was used to estimate the segmental tubular reabsorption of sodium. RESULTS: In subjects with a positive family history of hypertension, hyperinsulinaemia did not influence renal plasma flow (RPF) or glomerular filtration rate (GFR) but urinary sodium excretion decreased by 50%. Estimated proximal tubular sodium reabsorption was unaffected by insulin while estimated distal fractional sodium reabsorption increased, P < 0.01. At the end of the clamp a low-dose infusion of angiotensin II (0.1 ng/kg per min) was superimposed. GFR and RPF then decreased significantly concomitant with urinary excretion of sodium. In control subjects hyperinsulinaemia caused an unchanged GFR in both groups, increased RPF in the lean control group and 15-25% reduction in sodium excretion. No alteration was seen in estimated proximal tubular sodium reabsorption, but estimated distal tubular sodium reabsorption increased (P < 0.05) in the lean control group. Angiotensin II elicited a further increase in distal fractional tubular sodium reabsorption in both groups (P < 0.05). CONCLUSION: In normotensive subjects with a positive family history of hypertension, in contrast to control subjects without such history, hyperinsulinaemia caused a marked decrease in urinary sodium excretion in presence of unchanged RPF and GFR indicating a renal tubular effect of insulin located at distal site of the renal tubules. Angiotensin II caused further sodium retention, probably due to an effect on renal haemodynamics.

Adult↗
PubMed1996

Occupational exposure and malignant lymphoma.

The incidence of malignant lymphoma, especially non-Hodgkin's lymphoma has increased over the last few decades. This statement is true despite the fact that methods for diagnosing malignant lymphoma have changed and misclassification has become a problem. The present review is mainly concerned with occupational aspects of malignant lymphoma. Several subsequent studies have dealt with malignant lymphoma among woodworkers and pulp and paper mill workers pointing to increased risks. Exposure to phenoxy herbicides have provided reasonable evidence to be connected with an increased risk of non-Hodgkin's lymphoma, whereas there is limited information regarding Hodgkin's disease. The relationship between solvent exposure and malignant lymphoma has been observed in a great number of studies. It is, however, still hard to identify specific solvent compounds responsible for the increased risk. Other occupational exposures i.e. wood preservatives, welding, asbestos, hair dyes and exposure to animal viruses among meatworkers and veterinarians have also been studied in relation to malignant lymphoma. This review shows that occupational factors, especially exposure to solvents and phenoxy herbicides and also to wood, play a role in the epidemiology of malignant lymphoma.

Abattoirs↗
PubMed1995

Radioimmunoassays for glutamic acid decarboxylase (GAD65) and GAD65 autoantibodies using 35S or 3H recombinant human ligands.

Autoantibodies are an important marker of human autoimmune diseases and the development of simple, precise and reproducible immunoassays to detect autoantibodies is important to our understanding of human autoimmunity. GAD65 autoantibodies occur frequently in insulin-dependent diabetic patients and is a useful marker for IDDM. A RIA to detect immunoreactive GAD65 has not been described. In the present study we describe a semi-automated fluid-phase immunoassay for the rapid detection of GAD65 autoantibodies in human serum. We also developed a sensitive RIA to determine immunoreactive human GAD65 in biological fluids and in vitro cell systems. Using in vitro translated recombinant human GAD65 in a multiwell-adapted procedure, our GAD65Ab RIA combines high specificity and sensitivity with a high capacity to analyze a large number of samples. In this report the three critical steps in the GAD65Ab RIA, DNA preparation, in vitro translation and immunoprecipitation, have been optimized. In our RIA, GAD65Ab were detected in 116/155 (75%) new onset Swedish IDDM children and in 1/85 (1.2%) healthy controls. In an immunoassay to detect autoantibodies against the proinsulin converting enzyme 2 (PC-2) no such antibodies were detected in IDDM patients. In the GAD65 RIA the lower detection limit was 2 ng/ml (31 fmol/ml). Our data demonstrate that autoantigen radioligands produced by in vitro translation are useful in RIA for autoantibodies and autoantigens in studies of human autoimmunity.

Adolescent↗