Search PubMed⌕ Search

Biomedical subjects

I Khalil

Publications and source records attributed to I Khalil.

At least 19 recordsLinked to original sources

Hughes syndrome associated with varicella infection.

We report a case of Hughes syndrome 1 week after the occurrence of chickenpox. The patient presented with the clinical picture of acute right iliofemoropopliteal deep vein thrombosis. IgM and IgG anticardiolipin (aCL) were both positive upon admission. The IgM aCL antibodies were still positive 6 weeks later, which suggests their role as a predisposing factor of deep vein thrombosis.

Adolescent↗

Inferior vena cava obstruction in Budd-Chiari syndrome: successful treatment by radiological stenting followed by a portosystemic shunt.

Surgical decompression by a portosystemic shunt in Budd-Chiari syndrome depends on the caval state. Obstruction of the inferior vena cava (IVC) precludes such an operation due to the risk of reduced blood flow across the shunt and subsequent thrombosis. Similar risks are encountered in more complicated operations such as mesoatrial shunt. We report a patient with Budd-Chiari syndrome in whom obstruction of the intrahepatic IVC by a hypertrophied caudate lobe of the liver precluded the construction of a standard portocaval shunt. A two-step procedure with preoperative radiological stenting of the narrowed IVC followed by a portocaval shunt was successfully performed. This is the fifth case reported in the literature of such an approach.

Adult↗

Minimally invasive axillary-LAD saphenous vein bypass.

The left internal mammary artery (LIMA) is the arterial conduit of choice for minimally invasive coronary bypass to the left anterior descending (LAD). However, in redo cases when the LIMA is not available, the use of a saphenous vein graft as an extra-anatomic bypass from the axillary artery to the LAD offers a lower risk alternative than conventional reoperative trans-sternal surgery [Knight 1997]. We report on 3 patients who underwent axillary-LAD saphenous vein bypass. At six months, follow-up by Duplex ultrasound showed patent grafts in all three patients.

Aged↗

Altered intrathymic T-cell repertoire in human myasthenia gravis.

In myasthenia gravis, the thymus is thought to be the primary site of autosensitization. We investigated the V beta T-cell repertoire at different intrathymic differentiation stages in 17 patients with myasthenia gravis and 8 age-matched control subjects by tricolor immunofluorescence, using a panel of six anti-V beta antibodies. We observed an increased expression of V beta 5.1 and V beta 8 subfamilies in the patients compared to the control subjects. These increases were observed not only in mature cells but also in the latest thymic precursors of mature cells (double-positive CD3 high), while there was no change in intermediate precursors (double-positive CD3 low), pointing to biased selection during intrathymic differentiation. In addition, there was a strong correlation between the percentage of V beta 5.1+ and V beta 8+ cells among both the CD4 and CD8 subsets in the patients, but not in control subjects, suggesting that thymic events relevant to the disease lead to these selected populations. Finally, location studies of V beta 5.1+ cells on thymic sections indicated that these cells were overrepresented both in the core of germinal centers and in perifollicular areas of hyperplastic thymuses, suggesting a role in the autoimmune response. Taken together, these findings are compatible with the hypothesis of a biased intrathymic selection in myasthenia gravis.

Adolescent↗

Association of the AChRalpha-subunit gene (CHRNA), DQA1*0101, and the DR3 haplotype in myasthenia gravis. Evidence for a three-gene disease model in a subgroup of patients.

Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction having multigene control. HLA-linked loci and the HB*14 micro-satellite marker located within the CHRNA gene which encodes the muscular acetylcholine receptor (AChR) alpha-subunit, the target self-antigen, were previously associated with MG. Combined analysis of these loci revealed a significant increase of DQA1*0101 alleles in HB*14+ vs. HB*14- patients and of DQA1*0501 alleles in HB*14/DQA1*0101 patients. Importantly, the effect of DQA1*0101 was independent of allelically associated DQB1 and DRB1 genes. In contrast, the effect of DQA1*0501 could not be dissociated from that of DRB1*03 and DQB1*0201 on the extended DR3 haplotype. These results indicate that a combination of three genes, of which two are linked to HLA, contributes to disease susceptibility in a subgroup of MG patients.

Adult↗

Differences in endogenous peptides presented by HLA-B*2705 and B*2703 allelic variants. Implications for susceptibility to spondylarthropathies.

The association between HLA-B27 and spondylarthropathies is currently being reinvestigated in the light of HLA-B27 subtyping. At least 11 different subtypes have been described among which B*2703, B*2706, and B*2709 could be less closely associated with disease at the population level. Differences in the presentation of antigenic peptides by these subtypes could be related to differences in disease susceptibility. We focused our work on the comparison of B*2705 and B*2703 which differ at a single position at residue 59 in pocket A of the peptide binding groove. Endogenous peptides from the human C1R line transfected by B*2705 or B*2703 were acid-eluted and separated by HPLC. Major individual fractions were sequenced by Edman NH2-terminal degradation. Differences observed between B*2705 versus B*2703 individual ligands were confirmed in an in vitro stabilization assay with T2-B*2705 or B*2703 transfected cells in the presence of synthetic peptides. One B*2705 associated peptide is derived from the sequence 169-179 in the second extracellular domain of several HLA class I molecules including HLA-B27. This sequence (RRYLENGKETL) is highly homologous to a previously reported sequence (LRRYLENGK) sharing similarities with proteins from enteric bacteria. We show here that it is naturally presented as a major endogenous peptide by B*2705 and B*2702 disease-associated subtypes and not by B*2703.

Amino Acid Sequence↗

Definition of the HLA-A29 peptide ligand motif allows prediction of potential T-cell epitopes from the retinal soluble antigen, a candidate autoantigen in birdshot retinopathy.

The peptide-binding motif of HLA-A29, the predisposing allele for birdshot retinopathy, was determined after acid-elution of endogenous peptides from purified HLA-A29 molecules. Individual and pooled HPLC fractions were sequenced by Edman degradation. Major anchor residues could be defined as glutamate at the second position of the peptide and as tyrosine at the carboxyl terminus. In vitro binding of polyglycine synthetic peptides to purified HLA-A29 molecules also revealed the need for an auxiliary anchor residue at the third position, preferably phenylalanine. By using this motif, we synthesized six peptides from the retinal soluble antigen, a candidate autoantigen in autoimmune uveoretinitis. Their in vitro binding was tested on HLA-A29 and also on HLA-B44 and HLA-B61, two alleles sharing close peptide-binding motifs. Two peptides derived from the carboxyl-terminal sequence of the human retinal soluble antigen bound efficiently to HLA-A29. This study could contribute to the prediction of T-cell epitopes from retinal autoantigens implicated in birdshot retinopathy.

Alleles↗

Carotid artery disease practice guidelines for the general practitioner.

Carotid artery disease is a major public health concern. Cost-effective screening can be effected in a certain cohort of patients, especially if the referring physician uses vascular laboratories with expert technologists. Once the grade of stenosis, plaque morphology, and the patient's life expectancy and co-morbid conditions are known, the physician can offer the patient the safest therapeutic option. If the patient is a surgical candidate, it is important for the general practitioner to remember that the efficacy of carotid surgery is a balance between the risk of the surgeon versus the risk of the plaque Patient selection for low risk and surgeon selection for good track record should be secured before subjecting the patient to surgical intervention.

Arteriosclerosis↗

[Human major histocompatibility complex: the HLA system].

The HLA (human leukocyte antigens) system, or human major histocompatibility complex, is the most polymorphic functional genetic entity known at present. It consists of HLA class I genes and molecules (A, B and C) which control CD8+ cell-mediated antiviral responses, and class II genes and molecules (DR, DQ and DP) which control CD4+ cell responses (anti-bacterial and anti-toxin). HLA molecules function by presenting antigenic peptides to CD8+ cells (class I) and CD4+ cells (class II). Antigen presentation depends on the intracellular location of the antigen. Antigens present in the exocytosis pathway are presented by class I molecules, while class II molecules present antigens associated with the endocytosis pathway. More than 200 alleles have been detected by means of serological testing (microlymphocytotoxicity) and biochemical methods (IEF) in the HLA class I system, and now by means of molecular biology techniques for class II molecules (PCR-SSO and PCR-RFLP). This molecular typing has revealed the amino acids in HLA molecules that confer genetic susceptibility or resistance to numerous HLA-associated diseases. This is the case for example of ankylosing spondylitis (region 45-46 of HLA-B27 molecules), juvenile diabetes (aa 57 of D beta Q) and rheumatoid arthritis (aa 65-71 of DR beta). Thus, the HLA system is a genetic tool for diagnostic and therapeutic decision-making.

Animals↗

Nebulizer therapy with antibiotics in chronic suppurative lung disease.

Aerosolized antibiotics have been shown to be a useful modality of treatment in patients with cystic fibrosis. In this investigation we examined the utility of this treatment in patients with other chronic suppurative lung disorders. These included forty patients, thirty men and ten women with chronic airway infection (27 with bronchiectasis, 6 with chronic abscess and 7 with chronic suppurative bronchitis). Pathogenic organisms were isolated from the affected part of the lung by a fiberoptic bronchoscopy using a sterile disposable bronchial microbiology brush. Cultures from these specimens were used to determine the appropriate antibiotic. A second control group of 20 patients was treated with systemic antibiotics alone. Both systemic and aerosolized antibiotics were administered in 20 patients. A statistically significant improvement in clinical, and ventilatory functions was recorded in the first group compared to the second. Nebulized antibiotics used as adjunctive therapy in association with systemic antibiotics may offer a therapeutic advantage in chronic suppurative lung diseases.

Adult↗

HLA-DRB1, DQA1 and DQB1 DNA polymorphisms in healthy Algerian and genetic relationships with other populations.

This study presents the results of HLA-DRB1, -DQA1, and -DQB1 sequence-specific oligonucleotide probe (SSOP) typings for a population sample of 47 individuals originating from Western Algeria. Allele and haplotype frequencies, as well as linkage disequilibria are computed by the standard methods used for the XIth International Histocompatibility Workshop data. A total of 24 alleles are detected at the DRB1 locus, where a very high heterozygosity level (0.914) is found. The highest DRB1 frequencies are 0.160, DRB1*1101, and 0.138, for DRB1*0301 and DRB1*0701. The DQA1 and DQB1 loci are less polymorphic. Among the 8 DQA1 alleles detected, DQA1*0501 is highly predominant with a frequency of 0.383. Thirteen DQB1 alleles are observed among which DQB1*0301 and DQB1*0201 are the most frequent (0.351 and 0.245, respectively). Three haplotypes predominate clearly: DRB1*1101-DQA1*0501-DQB1*0301 (0.138), DRB1*0701-DQA1*0201-DQB1*0201 (0.128) and DRB1*0301-DQA1*0501-DQB1*0201 (0.117). The two latter are among the most frequent haplotypes found in European and North American Caucasoid populations, but the DQA1*0501-DQB1*0201 association is not significant in Algerians. The genetic distances computed for each locus among a set of populations from different continents are significantly correlated to geography. They indicate that the Algerians are very close to South European populations, particularly to Sardinians, Italians, Romanians and French, with some intermediate characteristics between Europeans and sub-Saharan Africans. These results may serve as reference for future studies of HLA and disease in the Algerian population.

Adult↗

Determination of DRB alleles using PCR amplification and allele-specific primers.

HLA class-II allelic diversity is commonly defined using polymerase chain reaction (PCR) in combination with sequence-specific oligotyping (PCR-SSO) or the combination of PCR and restriction fragment length polymorphism methods (PCR-RFLP). Nevertheless, the identification of the DRB polymorphism by PCR-SSO is a time-consuming procedure and the PCR-RFLP is cumbersome. A rapid technique which allows a precise and extensive HLA-DRB typing is required, particularly in order to study the role of class-II matching in organ transplantation. A DRB typing method based on the detection and length of PCR products amplified using combination of allele specific primers has been developed. Thirty-four DRB alleles (29 DRB1, 4DRB3, 1DRB4) can be detected using 29 primers distributed into 19 amplification mixtures.

Alleles↗