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I Khalil

Publications and source records attributed to I Khalil.

51 records · Page 3Linked to original sources

A combination of HLA-DQ beta Asp57-negative and HLA DQ alpha Arg52 confers susceptibility to insulin-dependent diabetes mellitus.

Family and population studies indicate that predisposition to insulin-dependent (type I) diabetes mellitus (IDDM) is polygenic. It has been shown that the absence of the aspartic acid in position 57 (Asp57) of the DQ beta chain is positively correlated to IDDM. However, Asp57-negative haplotypes do not always confer susceptibility and conversely, some Asp57-positive haplotypes seem to be disease associated. It has been suggested that other HLA class II sequences, probably belonging to the HLA DQA1 gene, confer susceptibility to IDDM. This report, based on extensive oligonucleotide dot blot hybridization of PCR-amplified DQA1 and DQB1 genes, reinforces the importance of the Asp57-negative DQ beta chain, but also introduces the possibility that a DQ alpha chain bearing an arginine in position 52 (Arg52) confers susceptibility to IDDM. A molecular model of susceptibility to IDDM is proposed. This model strongly suggests that the disease susceptibility correlates quantitatively with the expression at the cell surface of a heterodimer, composed of a DQ alpha-chain bearing an Arg52 and a DQ beta chain lacking an Asp57. In view of the respective positions of the two residues and their charge, we might anticipate that both residues DQ beta Asp57 and DQ alpha Arg52 are critical for modulation of susceptibility, presumably via viral-antigenic peptide and/or autoantigen presentation.

Base Sequence↗

HLA DQ alpha/beta molecule associated with the susceptibility to insulin-dependent diabetes mellitus. A model for HLA/autoimmune disease association.

We have proposed a molecular model of susceptibility to Insulin-Dependent Diabetes Mellitus (IDDM) based on the proportional expression at the cell surface of the following susceptible (S-S) HLA-DQ heterodimere composed of a chain DQ alpha Arg 52 positive (S) and a chain HLA-DQ beta Asp 57 negative (S). All other DQ alpha/beta chains associations are considered as protective molecules. This model allows a predictive scale of risk for the disease.

Alleles↗

Typing for HLA DQ using oligonucleotidic probes.

We have typed 25 homozygous B lymphoblastoid cell lines, defined as reference panel during the Xth International Histocompatibility Workshop, using PCR (Polymerase Chain Reaction) and oligonucleotidic probes recognizing sequences of DQA and DQB genes. The polymorphism of 8 HLA-DQA1, and 12 DQB1 alleles is reported and the advantages of this technique are compared to that of other typing methods, currently used.

Cell Line↗

Autonomic nervous stimulation affects left ventricular relaxation more than left ventricular contraction.

We studied the effects of stimulation of the vagal and also the sympathetic efferent cardiac nerves on left ventricular (LV) relaxation and contraction in 11 anesthetized, open-chest dogs. In each dog, we paced the ventricles at a fixed rate of 120 beats.min-1 and kept the systemic arterial pressure constant. The maximum rate of LV pressure decline, (dP/dt)min, and the time constant of LV isovolumic pressure decline, tau, were used as our indexes of LV relaxation. The maximum rate of LV pressure rise, (dP/dt)max, was used as our measure of LV contractility. Vagal stimulation decreased (dP/dt)min more than (dP/dt)max (P less than 0.01) when examined at frequencies that ranged from 2 to 12 Hz. Vagal stimulation at 12 Hz reduced (dP/dt)min by 26% (P less than 0.001) and increased tau by 57% (P less than 0.0001) but decreased (dP/dt)max by only 20%. Sympathetic stimulation, at frequencies that ranged from 2 to 12 Hz, increased (dP/dt)min more than (dP/dt)max (P less than 0.001). Sympathetic stimulation at 12 Hz increased (dP/dt)min by 130% (P less than 0.0001) whereas it increased (dP/dt)max by 60% (P less than 0.0001). Sympathetic stimulation at 12 Hz decreased tau by 74% (P less than 0.0001). Our studies suggest that cardiac autonomic nerve stimulation affects left ventricular relaxation more than left ventricular contraction.

Animals↗

Surgical treatment for aneurysm of aberrant subclavian artery based on a case report and a review of the literature.

Experiences with the recent successful treatment of a patient with an aneurysm arising from an aberrant subclavian artery are described. The reported experiences with surgical treatment by others were reviewed in detail: Only 16 such patients were found, with a surprising frequency of serious complications. These data led to the conclusion that a two-stage approach, through right cervical and left thoracotomy incisions, seems to offer the ideal method of treatment for this unusual problem.

Aneurysm↗

Late axillary artery thrombosis in patients with occluded axillary-femoral bypass grafts.

The axillary-femoral bypass graft is an alternative to direct anatomic procedures for patients with aortoiliac occlusive disease. Touted for its low morbidity and mortality rates, with corresponding improved patency rates, this extra-anatomic procedure has been considered safe and effective. Noncompromising upper extremity ischemia and one case of upper extremity loss, associated with early graft thrombosis, have been reported previously. This article describes two cases of late axillary artery thrombosis, occurring 4 and 6 months after graft thrombosis, which severely jeopardized the viability of the ipsilateral upper extremity. Experience with these patients has shown that a thrombosed axillary-femoral bypass graft may jeopardize the viability of the ipsilateral upper extremity many months after its failure. The absence of information in the literature regarding this complication suggests this is a rare complication of thrombosed axillary-femoral grafts.

Aged↗

HLA DQA1 and DQB1 study in Algerian type 1 diabetes families.

The distribution of HLA class II alleles associated with insulin-dependent diabetes mellitus (Type 1) in the Algerian population is poorly known. We have typed 36 Algerian Type 1 diabetic probands and their families using DQA1 and DQB1 oligonucleotide probes. Fifty-nine parental haplotypes non transmitted to diabetic offspring served as controls. The frequencies of DQA1 and DQB1 alleles and haplotypes and their associations with Type 1 diabetes were, except minor differences, similar to those reported in French. Susceptibility DQA1 (Arg52+) and DQB1 (Asp57-) alleles were significantly increased among patients versus controls (90% vs 53%, RR = 8.4, p < 10(-6), and 94% vs 64%, RR = 9.4, p < 10(-5), respectively). 85% of Type 1 diabetics versus 34% of control haplotypes were either DR3DQw2 or DR4DQw8 susceptibility haplotypes (DQA1 Arg52+, DQB1 Asp57-) (RR = 10.8, p < 10(-7). 75% of the probands vs 14% of the controls (RR = 18, p < 10(-5)) and 73% of affected siblings versus 24% of unaffected siblings (RR = 8.4, p < 0.02) possessed a genotype composed of these two susceptibility haplotypes in the homozygous or heterozygous state. 42% of the probands were DR3DQw2/DR4DQw8, corresponding to Hardy-Weinberg expectations. The lack of excess of heterozygotes could be due to the consanguine families in this sample, as among the patients with consanguine parents the frequency of DR3, 4 heterozygotes was lower (27% vs 48% in non-consanguine patients, NS) and that of DR3 homozygotes increased (45% vs 12%, respectively, p < 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Algeria↗

Role of surgery in the prevention and correction of hip subluxation and dislocation in cerebral palsy.

Forty-three patients (80 hips) were available for clinical and radiological follow-up. These patients underwent adductor tenotomies separately or in combination with other procedures on the hip, with or without proximal femural correction. The range of abduction in all hips before surgery was 40 degrees or less, and in 54 hips combined with flexion-contracture (10 degrees-50 degrees).

Adolescent↗

[The role of the HLA system in the genetics of Type I diabetes mellitus].

Major determinants of susceptibility to Type 1 (insulin-dependent) diabetes (IDDM) have been mapped to the HLA complex, near to or identical with genes encoding class II molecules. The association of IDDM with HLA-DR3 and/or DR4 antigens and the highest risk for DR3/4 heterozygotes suggest a synergistic effect of the two haplotypes. The characterization at the molecular level of the class II region has provided evidence that DQ rather than DR determinants may primarily influence the disease. In caucasians the susceptibility strongly correlates with the absence of aspartic acid at position 57 on the DQ beta chain and/or the presence of arginine at position 52 on the DQ alpha chain. The formation of a putative DQ susceptibility molecule (DQ alpha Arg52+, DQ beta Asp57-) accounts best for the disease associations when trans-complementation between alpha and beta chains encoded by different haplotypes is postulated to explain the excess of heterozygotes. Observations in other populations and in animal models indicate, however, that other residues on DQ alpha and beta chains, other class II (DR beta) molecules and non-HLA linked genes also contribute to the susceptibility. The mechanism(s) by which susceptibility determinants influence IDDM is not known. It is probably in relation with the role of class II molecules in the antigen presentation to T lymphocytes.

Diabetes Mellitus, Type 1↗