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Biomedical subjects

R Assan

Publications and source records attributed to R Assan.

At least 55 records · Page 3Linked to original sources
PubMed1988

A simple strategy to amplify specifically the HLA-DQ beta gene region with genomic DNA as template.

The nature of codon 57 in the HLA-DQ beta gene was recently reported as a potential marker of genetic susceptibility to insulin-dependent diabetes mellitus. When exploring the relevance of this marker by using genomic DNA amplification, we encountered difficulties resulting from the coamplification of the homologous DX beta region. A simple strategy is proposed to amplify the DQ beta region exclusively. It involves the preliminary digestion of genomic DNA with a restriction enzyme which cleaves DX beta specifically, leaving intact the DQ beta sequence. The amplified material is suitable for dot blot analysis and restriction enzyme digestion. This strategy is of general interest when homologous sequences impair the specificity of enzymatic DNA amplification.

DNA↗
PubMed1988

MHC classes I, II, III antigens study in 70 insulin-dependent diabetics with associated auto-immune diseases.

Seventy IDDM patients (insulin-dependent diabetics), 48 females and 22 males, most of them adults at the onset of diabetes, and suffering from at least one other associated autoimmune manifestation (AAM) were studied for HLA A,B,C, DR markers and Bf, C4 complement components. Comparisons were made with 108 normal controls and a series of 287 IDDM patients with juvenile onset (under 25 years) and no patent other autoimmune disease. The increase in frequency of HLA-B8 among IDDM patients with AAM was confirmed (36% versus 20% in controls) (p less than 0.04). The frequency of DR4 among diabetics with AAM (33%) was not significantly different from the normal frequency (27%), and the allelic combination DR3/4 was found in only 13% of IDDM with AAM. Corresponding frequencies in patients with IDDM alone were 66% for DR4 and 34% for DR3/4 (p less than 10(-6) and 10(-3) respectively). These results confirm the heterogeneity of IDDM and support, by genetic arguments, the concept of overlapping entities. The hypothesis of a common background of autoimmunity associated with B8 DR3 can be postulated, while the organ specific target process should be associated with various DR alleles.

Adolescent↗
PubMed1988

Glucagon inhibits urinary acidification in the rat.

The effects on urinary acidification of an acute infusion of glucagon (GLU) were studied by paired experiments in plasma-replete rats whose endogenous GLU secretion was restrained by a 0.7 ng.min-1.g body wt-1 somatostatin infusion. GLU did not affect the glomerular filtration rate in any of the plasma-replete rats studied. In 10 thyroparathyroidectomized (TPTX) rats and five intact rats subjected to hypotonic volume expansion, a low-dose (0.02 ng.min-1.g body wt-1) GLU infusion that raised the plasma GLU concentration from 302 +/- 63 to 1,010 +/- 140 pg/ml significantly increased the urinary bicarbonate excretion and decreased the urinary net acid excretion; a high-dose (0.05 ng.min-1.g body wt-1) glucagon infusion in the intact rats, that increased the plasma GLU concentration to 1,609 +/- 307 pg/ml, further enhanced the urinary bicarbonate excretion rate. In intact plasma-replete rats that were not subjected to a hypotonic volume expansion, low- and high-dose GLU infusions failed to affect the urinary bicarbonate excretion rate. Finally, no change in urinary excretion rates was noted in TPTX volume-expanded time control rats. We conclude that 1) physiological increments in plasma GLU concentration decrease urinary acidification by affecting the tubular H+/bicarbonate transport; 2) the bicarbonaturic effect of GLU may be blunted by the renal effects of high circulating antidiuretic hormone levels, or may be facilitated in an undetermined manner by hypotonic volume expansion.

Animals↗
PubMed1987

Measurement of glycated albumin in diabetic patients by biospecific affinity chromatography.

The percentage of glycated plasma albumin was measured by a procedure involving ammonium sulphate precipitation and Affi-Gel-Blue and phenylboronate chromatographies. The value correlates well with the amount of ketoamine-bound sugars determined by colorimetric assay (r = 0.98, n = 39). The normal mean value is 3.9 +/- 0.3% (mean +/- S.D., coefficient of variation = 7.7%, n = 32) and varies from 3.9 to 21% in diabetics (n = 54). A good correlation is found with the mean blood glucose value of the preceding twenty days (r = 0.92, n = 57). Because of its relative ease of determination, glycated albumin constitutes a good short-term glycemic index and an alternative to glycated haemoglobin in some specific cases.

Blood Glucose↗
PubMed1987

Insulin-dependent diabetes: strategy for immune intervention.

Increasingly, experimental results are underlining the role played by autoimmune mechanisms in the pathogenesis of type I insulin-dependent diabetes mellitus (IDDM). It has appeared logical to attempt to preclude the onset of IDDM by suppressing immune responses, but trials using steroids or azathioprine were unequivocal. Subsequently, a Canadian and a French group performed pilot studies to assay a new immunosuppressive drug, cyclosporine A (CyA) in human diabetes (Stiller et al., 1984; Assan et al., 1985). However, further testing is required to evaluate and confirm its potential benefits and possible risks.

Cyclosporins↗
PubMed1987

Studies of gut and hepatic metabolism in conscious rabbits.

The present study was designed to develop the techniques for chronic catheterization of the hepatic and portal venous circulation in conscious rabbits and to apply these techniques to a study of hepatic metabolism in this species. Experiments were made after an 18-h fast and for 4 h after the initial feeding. Measurements of arteriovenous differences of substrates were combined with measurements of hepatic and gastrointestinal blood flow. Hepatic glucose production was suppressed by 60% at 1 h and had returned to control levels by 4 h. The hepatic uptake of lactate declined slightly at 1 h and had returned to control level 2 h after the meal. There was a marked and rapid fall in hepatic ketone body output after refeeding. Although amino acid concentrations displayed a transient increase 1 h after the meal, only the arterial concentration of branched-chain amino acids remained significantly elevated for 4 h. The total hepatic uptake of the gluconeogenic amino acids (alanine, serine, threonine) remained constant. Refeeding resulted in a doubling of arterial insulin concentrations at 1 h followed by a progressive decline over the next 3 h. It is concluded that in rabbits fed a mixed meal partial suppression of hepatic glucose output is mainly due to a decline in glycogenolysis rather than a decrease in gluconeogenesis, shortly after refeeding the liver is able to virtually shut off its ketone body production, the major gluconeogenic precursors (lactate, alanine, glycine, serine, and threonine) may contribute to approximately 40% of the glucose release.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1987

Effect of cyclosporin A treatment on the production of antibody in insulin-dependent (type I) diabetic patients.

Anti-islet cell and anti-insulin antibody production was studies over a 12-mo period in 82 recently diagnosed diabetics randomly receiving either cyclosporin or placebo. Cyclosporin had only minimal effects on the production of anti-islet cell antibodies whether directed to islet cytoplasmic (immunofluorescence) or membrane (cytotoxicity assay) antigens even in patients undergoing remission. These data suggest that these antibodies do not play a major role in the pathogenesis of the disease particularly since their (irregular) presence is not predictive of the clinical response to cyclosporin. Conversely, cyclosporin completely suppressed the synthesis of antibodies elicited by exogenous insulin irrespective of the insulin doses received, and decreased the autoantibody production against thyroid antigens, indicating that cyclosporin has variable effects on antibody production against various antigens.

Antibody Formation↗
PubMed1986

Cyclosporin increases the rate and length of remissions in insulin-dependent diabetes of recent onset. Results of a multicentre double-blind trial.

In a double-blind trial 122 patients aged 15-40 years with insulin-dependent diabetes of recent onset were randomly assigned to cyclosporin 7.5 mg/kg per day or placebo. At the sixth month 25.4% of the cyclosporin group and 18.6% of the placebo group were in complete remission (not a significant difference). Treatment was continued in those patients with complete or partial remission (insulin requirement less than 0.25 U/kg per day) and 106 patients were followed to nine months, at which stage 24.1% of the original cyclosporin group and 5.8% of the original placebo group were in complete remission (p less than 0.01). For those patients whose whole-blood trough cyclosporin levels in the first three months averaged 300 ng/ml or more, the rates of complete remission at six and nine months were 37.5% and 37%. The rates of partial remission were also higher in the cyclosporin group and at six months the rate of complete or partial remission was 46% in the whole cyclosporin group and 65.6% in those with an average blood level exceeding 300 ng/ml in the first three months, versus 28.8% in the placebo group. The principal side-effect of cyclosporin was a modest and reversible increase in plasma creatinine. These results indicate that cyclosporin promotes the remission of type I diabetes and suggest the need for new controlled protocols aimed at evaluating the length of the effect and selecting the best drug regimen.

Administration, Oral↗
PubMed1986

T-lymphopenia and T-cell imbalance in diabetic db/db mice.

The diabetic db/db mice of the C57 BL/KsJ strain display anti-islet immunity, thymic dysfunction, and lymphopenia. In the present work, lymphocytes, T-cells, and T-cell subsets were enumerated in thymus and spleen from diabetic db/db mice and their db/ + heterozygote littermates from the 10th day to the 10th month of life. A significant lymphopenia was detected in thymus and spleen from the second month on, involving specifically the T-cell compartment, as assessed by use of a monoclonal anti-Thy1 antibody in indirect fluorescence. The study of T-cell subsets by monoclonal anti-Lyt1 and anti-Lyt2 antibodies revealed a significant increase in Lyt1+ cells and a decrease in Lyt2+ cells, with a corresponding increase of the Lyt1+/Lyt2+ ratio. These anomalies appeared early in life, and were apparently linked neither with the degree of hyperglycemia nor with weight loss or infection. The T-cell depletion in thymus was more pronounced in young male (less than 3 mo) than in young female db/db mice. These alterations may correspond to an increase in the helper/suppressor-cytotoxic ratio and could be linked with the thymic anomalies present in these mice, contributing to the development of anti-islet autoimmunity.

Animals↗
PubMed1986

[Induction of remissions of insulin-dependent diabetes by cyclosporin].

The effect of cyclosporine was evaluated in a double blind placebo controlled trial in 122 recent onset insulin-dependent diabetics. A significantly higher incidence of complete remissions was observed in patients treated with cyclosporine than in those receiving placebo (respectively 24 and 5.8%). The effect was still more clear-cut in patients having presented the highest cyclosporine blood level (37%). These results which have been obtained with modest toxicity demonstrate that cyclosporine induces remission of insulin-dependent diabetes and prompt to set up new controlled trials to evaluate the duration of the effect obtained and the potential risks of the treatment.

Adolescent↗
PubMed1985

Metabolic and immunological effects of cyclosporin in recently diagnosed type 1 diabetes mellitus.

Cyclosporin 5-10 mg/kg daily was given for 2-8 months to twelve recently diagnosed type 1 diabetics from a mean of 49 +/- SE 14 days after the start of insulin therapy, which was regulated to give near-normal blood glucose and haemoglobin A1c values. Mean insulin dosage dropped from 46 +/- 5 U/day before cyclosporin treatment to 16 +/- 4 U/day by the 7th month. Four patients had a complete remission and the insulin needs of four more were cut by half. The remaining four did not have remissions. Initial basal and glucagon-stimulated C peptide concentrations were higher in those who went into remission than in those who did not; they rose during cyclosporin treatment in the former but not in the latter. OKT4+ lymphocyte functions were suppressed in all patients and OKT4/OKT8 ratios declined. Anti-beta-cell autoimmunity, as indicated by lymphocyte-induced inhibition of insulin release from mouse islet cells, declined in all patients who went into remission. No consistent trend was observed for anti-islet cell antibodies. In forty-four similar, but non-randomised, recently diagnosed diabetics treated with insulin alone, the incidence of remission was 6%.

Adult↗