Biomedical subjects
A A Jabbar
Publications and source records attributed to A A Jabbar.
Atherosclerotic aortic gangliosides enhance integrin-mediated platelet adhesion to collagen.
Gangliosides, sialic acid-containing glycosphingolipids, accumulate in atherosclerotic vessels. Their role in the pathogenesis of atherosclerosis is unknown. Gangliosides isolated from tumor cells promote collagen-stimulated platelet aggregation and ATP secretion and enhance platelet adhesion to immobilized collagen. These activities are all mediated by ganglioside effects on the platelet integrin collagen receptor alpha2beta1. Therefore, we hypothesized that gangliosides isolated from atherosclerotic plaques would enhance platelet adhesion to immobilized collagen, a major component of the subendothelial matrix of blood vessels. Furthermore, we questioned whether this effect of atherosclerotic gangliosides might play a role in the pathogenesis of atherosclerosis. To test this hypothesis, we isolated the gangliosides from postmortem aortas of patients with extensive atherosclerotic disease and examined their effects on platelet adhesion. Samples of aortic tissue taken from areas involved with atherosclerotic plaque demonstrated accumulation of gangliosides (64.9+/-6.5 nmol/g wet weight) compared with gangliosides isolated from control normal aortic tissue taken from children who died of noncardiac causes (NAGs; 21.1+/-6.4 nmol/g wet weight). Interestingly, samples of tissue taken from diseased aortas but from areas not involved with gross plaque formation also demonstrated ganglioside accumulation (47.6+/-12.8 nmol/g wet weight). Next, the activity of each of these gangliosides on platelet adhesion to immobilized type I collagen was studied. Atherosclerotic aortic gangliosides (AAGs) as well as those isolated from grossly unaffected areas of the same aorta (UAGs) both increased platelet adhesion compared with control NAGs (OD570, 0. 37+/-0.11 and 0.29+/-0.14 versus 0.16+/-0.07, respectively; P<0.01 and P<0.05, respectively). These OD570 values corresponded to 9x10(5), 8x10(4), and 6x10(3) platelets per well after preincubation with 5 micromol/L AAG, UAG, and NAG, respectively. Increased adhesion was observed after preincubation with as little as 0.5 micromol/L AAG, and maximal adhesion was seen at 2.5 micromol/L, with a plateau extending to the highest concentration tested, 10 micromol/L. The effect of AAGs on platelet adhesion to collagen was abrogated by incubation of treated platelets with F-17 anti-alpha2 monoclonal antibody (OD570, 0.13+/-0.02). Finally, the effects of the major individual gangliosides isolated from atherosclerotic tissues, GM3 and GD3, were tested. GM3 increased adhesion to collagen (OD570, 0.415+/-0.06) as did GD3 (0.31+/-0.08). Similar to that of AAGs, the effect of both molecules was blocked by F-17 (0. 09+/-0.04 and 0.13+/-0.06, respectively). These experiments demonstrate that accumulated atherosclerotic gangliosides promote platelet adhesion to collagen, the major component of the subendothelial matrix. Furthermore, this activity is mediated by an effect of the gangliosides on the collagen-binding integrin alpha2beta1. This activity may provide a mechanism for the development of platelet thrombi at sites where atherosclerotic gangliosides accumulate and help to explain the role of platelets in the process of atherosclerotic disease progression.
HLA and disease associations in Iraq.
The HLA system is deeply involved in susceptibility to a variety of diseases. Relationships between HLA and diseases are of considerable interest and importance, as they provide new tools for studying the inheritance, classification, and pathogenesis of these diseases. Studies on the distribution of HLA antigens in different populations have revealed the existence of racial variation and are therefore a prerequisite for studying HLA and disease associations in different racial groups. This study reviews six articles concerning HLA and disease in the Iraqi population. A comparison of these associations and an analysis of overall antigen frequencies among other Arab population and different ethnic groups are included. Some of our HLA-disease associations confirm other studies reported in these racial groups, while other diseases showed different HLA antigen associations from those recorded in other racial groups.
Association of HLA antigens with coeliac disease among Iraqi children.
Forty children with coeliac disease were subjected to HLA-A and B antigens typing using the two-way lymphocytotoxicity technique. An increase in the frequency of HLA-B8 and B12 was found in patients as compared to the control group. Family studies conducted in 4 selected families have indicated that four out of five siblings who inherited the HLA-B8 antigen from their parents have contracted coeliac disease. In one of the families both siblings had HLA-B8 but only one of them contracted coeliac disease. It is suggested that the association of coeliac disease with HLA-antigen could be multifactorial, i.e. the disease could be attributed to the presence of more than one antigen.
HLA-antigen frequency in an Iraqi population.
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HLA antigens associated with susceptibility to herpes simplex virus infection.
HLA antigen frequencies in 150 patients with recurrent herpes simplex virus infection and 176 normal Iraqi controls were studied. Highly significant increased frequencies of HLA-A1, -B5 and -DR1 were found in patients as compared to control individuals. The frequencies of HLA-A3 and -A23 were also significantly increased in patients. When we subdivide the patients into groups according to rate of recurrence of symptomatic infection or ELISA reading of antibody titre no preferential association of HLA antigens with any particular subgroup is apparent. These results were compared with published findings for other ethnic populations and found to be compatible with them.
Association of HLA antigens with diabetes mellitus in an Iraqi population.
HLA antigen frequencies in 50 patients with IDDM, 56 patients with NIDDM, and 109 normal Iraqi controls were studied. Three families with one patient suffering from IDDM were also studied. No significant HLA antigens associated with NIDDM were found. Highly significant association of HLA, A1, B8, DR3, and DR4 were found in patients with IDDM as compared to normal individuals. The frequency of HLA-B5 and DR2 were significantly decreased in patients with IDDM. In contrast to previously reported findings in Caucasoids there was no significant association with B15 and a negative association with HLA-B5, not with B7. These results were compared with published findings for Arabs and other ethnic populations.