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I Khalil

Publications and source records attributed to I Khalil.

At least 19 recordsLinked to original sources
PubMed1992

The HLA-DRB1*0405 haplotype is most strongly associated with IDDM in Algerians.

Insulin-dependent diabetes mellitus (IDDM) in Caucasians is strongly associated with HLA-DR3-DQ2 and DR4-DQ8. In order to investigate the HLA class II associations with IDDM in Algerians, we have used polymerase chain reaction (PCR) and sequence specific oligonucleotide analysis (SSO) to identify DQA1, DQB1, and DRB1 alleles, haplotypes and genotypes in 50 unrelated IDDM patients and 46 controls from a homogeneous population in Western Algeria. Both DRB1*0301-DQA1*0501-DQB1*0201 (DR3-DQ2) and DRB1*04-DQA1*0301-DQB1*0302 (DR4-DQ8) haplotypes were found at increased frequencies among the patients compared to controls (45% vs. 13%, RR = 5.5, Pc < 10(-5) and 37% vs. 4%, RR = 12.9, Pc < 10(-4), respectively). Among the latter, in contrast to other Caucasian populations, only DRB1*0405-DQA1*0301-DQB1*0302 was significantly increased in the Algerian patients (25% vs. 1% in controls, RR = 30.3, Pc < 10(-3). Accordingly, the highest risk of disease was observed in DRB1*0301-DQA1*0501-DQB1*0201/DRB1*0405-DQA1+ ++*0301-DQB1*0302 heterozygotes (34% in patients vs. 0% in controls; RR = 49; Pc < 10(-3). This observation and its comparison with DR-DQ haplotypes in other ethnic groups suggest that the DRB1*0405 allele which encodes an Asp57-negative beta chain may contribute to IDDM susceptibility in a similar way as Asp57-negative DQ beta chains.

Algeria↗
PubMed1992

Dose effect of cis- and trans-encoded HLA-DQ alpha beta heterodimers in IDDM susceptibility.

Insulin-dependent diabetes mellitus (IDDM) in whites is strongly associated with particular HLA-DQ alpha beta heterodimers composed of a DQ alpha chain with an arginine at residue 52 (Arg52+) combined to a DQ beta chain lacking an aspartic acid at residue 57 (Asp57-). With the aim of confirming this association, clarifying which heterodimers account for the highest risk of IDDM and explaining the excess risk of DR3-DQw2/DR4-DQw8, 115 unrelated white IDDM patients and 108 unrelated healthy nondiabetic control subjects were studied. With polymerase chain reaction and sequence-specific oligonucleotide probes, both patients and control subjects were typed for their HLA-DQA1 and DQB1 alleles and their DQA1-DQB1 haplotype and genotype frequencies were compared. Four major findings emerged from our analysis. 1) Arg52+ DQ alpha/Asp57- DQ beta heterodimers, formed in cis and/or in trans, are strongly associated with susceptibility to IDDM; 97% of patients and 46% of control subjects had at least one such susceptibility heterodimer (relative risk [RR] 32, confidence interval [Cl] 14.25-71.86, P less than 10(-7). 2) The degree of disease susceptibility depends on the number of such DQ heterodimers that a subject can express according to his or her DQA1-DQB1 genotype. The highest RR was observed in patients with four susceptibility DQ heterodimers (RR 41, Cl 17.05-95.9). 3) Only part of the susceptibility DQ heterodimers were significantly increased in patients, conferring IDDM susceptibility of different strength. The strongest association was with the DQA1*0501-DQB1*0302 combination formed in trans position (RR 35.2, CI 12.88-96.78, P less than 10(-7).(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles↗
PubMed1991

Metoclopramide does not decrease the incidence of nausea and vomiting after alfentanil for outpatient anaesthesia.

Sixty patients were studied in a randomized, double-blind manner to determine whether metoclopramide added to droperidol decreased further the incidence of emetic symptoms (nausea, retching, vomiting) in outpatients receiving alfentanil anaesthesia for nasal surgery. Group 1 (n = 30) received metoclopramide 0.15 mg.kg-1 and Group 2 (n = 30) received placebo. In addition, both groups received droperidol 0.02 mg.kg-1 immediately before anaesthesia which was supplemented by alfentanil 20 micrograms.kg-1 at induction followed by an infusion of 0.25-1 micrograms.kg-1.min-1. Emetic symptoms were assessed 0-3 hr, 3-6 hr and 6-24 hr after surgery. Both groups received similar doses of alfentanil (mean +/- SD; Group 1 4641 +/- 1894 micrograms, Group 2 4714 +/- 1640 micrograms). The percentage of patients who had either nausea or vomiting at 0-3, 3-6 or 6-24 hr was 23%, 14% and 13% in Group 1; and 20%, 17% and 10% in Group 2. The overall incidence for each group was 8/30 (27%). There was no difference in the incidence of emetic symptoms between the groups at any time interval or throughout the study. Metoclopramide did not improve upon the antiemesis of droperidol during alfentanil anaesthesia for outpatient nasal surgery.

Adult↗
PubMed1991

HLA DQB1*0301 allele is involved in the susceptibility to erythema multiforme.

Erythema multiforme (EM) is an acute, episodic inflammatory disorder of the skin and mucous membranes of various etiology that could be related to immunologic hypersensitivity response. EM has been previously reported to be associated with serologically defined HLA-DRw53 and DQw3 antigens. In this report, we reevaluate the role of HLA class II alleles in EM manifestations. With use of the polymerase chain reaction, followed by sequence-specific oligonucleotide hybridization, 35 unrelated Caucasian EM patients and 80 randomly selected healthy subjects were studied, and the DRB3, DRB4, DQA1, and DQB1 alleles were analyzed. The comparison of frequencies of these alleles indicates that (i) susceptibility to EM disease is more associated with the HLA-DQ than the HLA-DR subregions and (ii) that the DQB1*0301 is the most frequent allele among EM patients. Sixty-six percent of the patients had the DQB1*0301 allele compared to 31% of the controls (RR = 4.1; p less than 0.001). An even stronger DQB1*0301 association was found in the patient group with herpes-associated EM (76%; RR = 6.5; p less than 0.001). Our data demonstrate a clear association between an HLA-DQB1 allele and susceptibility to EM.

Adolescent↗
PubMed1991

The role of genetic predisposition to type I (insulin-dependent) diabetes mellitus.

The aetiology of insulin-dependent diabetes (IDDM) involves genetic predisposition, a major component of which has been mapped in the HLA complex, near to or identical with genes encoding class II molecules. In Caucasian populations IDDM is strongly associated with the serologically defined HLA-DR3 and DR4 antigens, which are widely recognised as markers of susceptibility. The particularly high risk of DR3/DR4 heterozygotes suggests that susceptibility is determined by two genes acting synergistically. The development of recombinant DNA technology has allowed a finer description of the class II region and provided evidence that DQ rather than DR determinants may primarily influence IDDM susceptibility. The search for specific structural changes of the DQA and DQB genes has shown that susceptibility correlates with the absence of aspartic acid at position 57 on the DQ beta chain (DQ beta 57 Asp--) and/or the presence of arginine at position 52 on the DQ alpha chain (DQ alpha 52 Arg+). In Caucasians the formation of a putative DQ susceptibility molecule (DQ alpha 52 Arg+, DQ beta 57 Asp-) accounts best for the disease associations when transcomplementation molecules consisting of DQ alpha and beta chains encoded by different haplotypes are postulated to explain the excess risk of heterozygotes. The HLA-IDDM associations in the Japanese, however, are not explained by this model. These and other unresolved questions indicate that other residues of the DQ alpha and beta chains or other class II molecules (DR beta chains), as well as non-MHC genes, may also contribute to the susceptibility.

Diabetes Mellitus, Type 1↗
PubMed1991

[New data concerning the etiology of insulin-dependent diabetes].

The mechanism of pancreatic beta-cell destruction in type I (insulin-dependent) diabetes mellitus (IDDM) involves autoimmune events directed against these cells. Anti-beta-cell autoimmunity occurs in genetically predisposed individuals and may precede clinical manifestations of IDDM by several years. Markers for beta-cell autoimmunity, especially islet-cell antibodies, are being used with increasing reliability both for detection of IDDM and for evaluating the risk of development of the disease. HLA alleles associated with IDDM include DR3 and DR4, with the risk of IDDM being especially high in individuals with the heterozygous combination DR3/DR4. Recent advances in molecular biology have resulted in more accurate identification of genetic variants and even of amino acid sequences associated with IDDM. These markers can be used to identify patients with genetic susceptibility to the disease. The mechanism of action of genes associated with IDDM is as yet unknown but probably involves the receptor function of HLA molecules for antigens during immune responses.

Autoimmune Diseases↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1989

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↗
PubMed1988

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↗
PubMed1985

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↗