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Biomedical subjects

J Awad

Publications and source records attributed to J Awad.

At least 37 records · Page 2Linked to original sources
PubMed1990

Cardiopulmonary dynamics during pumpless arteriovenous bypass for respiratory assistance.

The effect of a pumpless arteriovenous bypass with a microporous membrane oxygenator (MO) on the cardiopulmonary dynamics of dogs revealed an increase in cardiac output and cardiac work proportional to the increase in extracorporeal blood flow. Several current MOs offer so little resistance to blood flow that shunt flows exceeding a third of the normal cardiac output can easily be obtained. This should be enough for CO2 extraction covering metabolic production, and would add a non negligible amount of O2 to the blood.

Animals↗
PubMed1989

2'-5' oligoadenylate synthetase and its relationship to HLA and genetic markers of insulin-dependent diabetes mellitus.

Cytokines and their related enzyme pathways may play a part in the development of insulin-dependent diabetes mellitus (IDDM). We have therefore studied the activity of the enzyme 2'-5' oligoadenylate synthetase (which is induced by both interferon and the tumour necrosis factors) in circulating mononuclear cells from 40 subjects with IDDM and 32 healthy control subjects. There was no difference in mean basal enzyme activity between the two groups. A polymorphism of the 2'-5' oligoadenylate synthetase gene, not previously described, was found using the restriction enzyme Bam HI. There was no association of 2'-5' oligoadenylate synthetase genotypes with IDDM, but there was a significant correlation between basal 2'-5' oligoadenylate synthetase activity and 2'-5' oligoadenylate synthetase genotypes. Significantly higher mean basal levels of 2'-5' oligoadenylate synthetase activity were associated with HLA-DQA 4.6 phenotype (determined using the restriction enzyme Taq 1 and a DQA probe) and HLA-DR3 (determined serologically), whereas significantly lower mean levels of enzyme activity were associated with HLA-DQA 5.5 and HLA-DR7, in both IDDM and control subjects. An analysis of variance confirmed that these associations were independent 2'-5' oligoadenylate synthetase genotype. Likewise, a significantly higher mean level of enzyme activity was associated with the heterozygous 1/3 insulin-related genotype in the IDDM subjects only. This study therefore suggests that the possession of certain HLA haplotypes might be associated with differing levels of basal 2'-5' oligoadenylate synthetase activity.

2',5'-Oligoadenylate Synthetase↗
PubMed1989

HLA class III haplotypes in multicase rheumatoid arthritis families.

The class III complement proteins (C2, BF, C4A, and C4B) were studied in 57 multicase rheumatoid arthritis (RA) families. When the gene frequencies for RA probands were compared to a normal control panel (162 haplotypes), a significantly higher frequency of the rare variant C4B*3 was observed (p less than 0.05). No significant differences were seen for the other C2, BF, C4A, or C4B alleles. The most common haplotype found in the probands was HLA-Cw5,B44,C2*C,BF*S,C4A*3,C4B*3,DR4, occurring with a frequency of 0.088. Haplotypes containing HLA-DR4 and Bw62 were found to carry either C4A*3,C4B*3; C4A*3,C4B*1; or C4A*4,C4B*2. When only haplotypes containing DR4 were compared between probands and controls, the frequency of the C4B*3-bearing haplotype remained higher in the probands. It is concluded that Bw62,C4A*3,C4B*3DR4 is a haplotype which is especially associated with RA. The low frequency in the RA population of this haplotype indicates that C4B*3 has a minor role in overall RA susceptibility.

Alleles↗
PubMed1989

HLA-DR4 associated Dw types in rheumatoid arthritis.

Frequencies of HLA-DR4 and its related Dw types were compared between randomly selected normal controls and the index cases of multiplex rheumatoid arthritis (RA) families. A DR4 frequency of 68.3% was observed in index cases (n = 57) compared to 31.2% in normal controls (n = 96). Cellular typing with homozygous typing cells (HTCs) revealed significant increases of Dw4 (49.1% vs 22.9% RR = 3.2 p less than 0.001) and Dw14 (22.8% vs 2.1% RR = 13.9 p less than 0.001) in the index cases. A non-significant increase was seen for Dw13 (8.8% vs 4.1%). When DR4 positive patients and controls were compared, a significant increase was seen only for Dw14 (34.2% vs 6.6% RR = 7.3 p less than 0.01). Data from HLA genotyped RA and normal families allowed an examination of haplotype combinations of HLA-B antigens and DR4/Dw types to be made. HLA-Dw4 was predominantly found with B44 and Bw62 with nearly all DR4/Bw62 haplotypes being Dw4 positive. HLA-Dw13 was associated with B44 and Dw14 with Bw60, B44 and B27. Based on HTC and normal family data. Dw10 was found to be strongly associated with B38 containing haplotypes. Analysis of 69 C4A, C4B complement typed DR4 haplotypes failed to show any statistically significant association between Dw type and "complotype". However, there was a suggestion of C4A3. BQO being associated with Dw4 (34.2% vs 16.1% X2 = 2.9 p = ns) and C4A3, B1 with Dw14 (45.5% vs 27.6% X2 = 2.1 p = ns).(ABSTRACT TRUNCATED AT 250 WORDS)

Arthritis, Rheumatoid↗
PubMed1989

HLA-D region heterogeneity in a Nigerian population.

HLA class II antigens were studied in a panel of 130 Nigerians. Complex patterns of associations were seen between HLA-Dw, -DR and -DQ specificities, differing widely from those reported for other populations. A number of Dw types were associated with the same DR antigen: Dw'1N' and Dw'BERN' with DR1, Dw2 and Dw'2N' with DR2, Dw5 and Dw'5N' (Dw5 + Dw'F5') with DRw11. It was also observed that a Dw type associated with more than one DR antigen: HLA-Dw3 was assigned to individuals who were DR3 negative and similarly Dw10, Dw13 and Dw14 to individuals negative for DR4. HLA-DRw8 and Dw8 were completely dissociated in Nigerians, and Dw8 did not show a preferential DR association. These results demonstrate that DR and DQ identity between HTC stimulator and responder cell is not necessarily a prerequisite for Dw to be assigned. Preliminary studies show that subtypes of HLA-Dw1 and Dw8 detected by HTC typing correlate with restriction fragment length polymorphisms (RFLPs) detected with a combination of Bgl II enzyme and DRA/DRB cDNA probes. HLA-DP antigen frequencies differed between Nigerians and British Caucasoids. The most common DP antigen in Nigerians was DPw1, compared with DPw4 in Caucasoids. HLA-DPw6 appeared to be absent or rare in both Nigerians and British Caucasoids. Only five out of 68 Nigerians tested were assigned two DP specificities. The association between HLA-DR3 and DPw1 reported in Caucasoid panels was absent in Nigerians.

Black People↗
PubMed1988

A comparative serological and molecular study of linear IgA disease and dermatitis herpetiformis.

The class I and class II HLA serologically defined antigens and DQ alpha and DX alpha restriction fragment length polymorphism (RFLP) in 23 patients with linear IgA disease (LAD) were determined and their frequencies compared with those in a group of patients with dermatitis herpetiformis (DH) and healthy controls. In LAD there was a significant increase in HLA-B8 and DR3 and a larger increase in the DQw1-DR2/DRw6 related DQ alpha 6.2 kb and 6.8 kb RFLP. In DH there was a significantly increased frequency of HLA-A1, B8, DR3, and DQw2 with a concomitant increase in the DR3-DQw2 related DQ alpha 4.6 kb RFLP. The difference in DR3 frequencies and the increased frequency of DQw1 rather than DQw2 in LAD indicates that different susceptibility genes operate in the two diseases.

Dermatitis Herpetiformis↗
PubMed1987

HLA-DR alpha, -DX alpha, and DR beta III gene association studies in DR3 individuals.

In this study we have examined the results of probing with synthetic oligomers at the DR beta III locus, together with restriction fragment length polymorphisms defined by BglII digestion and a cDNA DR alpha probe, and Taq 1 digestion and a genomic DQ alpha probe. We have demonstrated heterogeneity of the human leukocyte antigen DR3 and close association of the DR alpha, DR beta III, and DX alpha genes. Two DR3-related preferential allelic associations have been identified, which may prove useful in family analysis as well as for investigations of DR3-related diseases.

Alleles↗
PubMed1987

Frequency and associations of HLA-DR and HLA-DQ antigens in a British Caucasoid panel.

The frequencies of the HLA-DR and -DQ antigens, including those of the new specificities "DRBr" and TA10, were established in a random panel of 286 British Caucasoids. The most frequent DR antigens were DR2, DR4 and DR7. The DR-DQ antigen associations were examined and the only heterogeneity found was with DR7 which was found to be associated predominantly with DQw2 but also with DQw3. The DR4's were subdivided into those positive and those negative for TA10 and DR4-TA10 was found to be associated with HLA-B44.

Gene Frequency↗
PubMed1987

HLA class II alpha chain gene polymorphisms in patients with insulin-dependent diabetes mellitus, dermatitis herpetiformis, and celiac disease.

We have investigated DNA polymorphism of the class II alpha chain genes in HLA typed patients with insulin dependent diabetes mellitus (IDDM; n = 79), celiac disease (CD; n = 46), dermatitis herpetiformis (DH; n = 53), and controls (n = 86). Preferential allelic associations of HLA genes and gene products have thus been constructed for susceptibility to these diseases. DR alpha and DQ alpha gene polymorphisms indicated heterogeneity of HLA DR3, DRw6, and DR7, and HLA DR2 and DRw6, respectively. In DR7 positive CD patients a 3.8-kilobase (kb) DR alpha fragment, which correlated with DQw3, was found in only 11% of patients compared with 45% of corresponding controls (P less than 0.05). An increased frequency of a DX alpha genotype UU in all three diseases was found (IDDM 59%, DH 45%, CD 48%, compared to 21% in controls, P less than 0.001), which is not explained solely by the increased frequencies of DR3-DX alpha U. We therefore conclude part of the genetic susceptibility for these three conditions is encoded by genes within the DQ-DX subregion.

Celiac Disease↗
PubMed1987

DQ beta restriction fragment length polymorphism and its relationship to insulin dependent diabetes mellitus.

HLA Class II serological and DQ beta restriction fragment length polymorphisms (RFLPs) were compared in 69 patients with insulin-dependent diabetes mellitus (IDDM) and 81 healthy British Caucasoid controls. The backbone of the analysis was formed by two Taq 1 RFLPs of the DQ beta region designated T2 omega and T6. The two are not allelic and can be inherited individually, together on one, or separately on both, parental haplotypes, the latter almost invariably in association with DR4. In our study the frequency in IDDM patients of both T2 omega and T6 together (relative risk for IDDM = 6.4) is similar to that of DR3/DR4 (relative risk for IDDM = 5.4) with an even higher relative risk for IDDM when they are combined, (relative risk = 18 with 95 per cent confidence limits between 14 and 22). We have thus defined DQ beta RFLPs which tightly associate with IDDM individuals with DR4.

DNA Probes, HLA↗
PubMed1987

HLA associations with multiple sclerosis in Sicily and Malta.

The islands of Sicily and Malta have very different prevalence rates for multiple sclerosis (MS): at least 44 per 100,000 in Sicily and only 4 per 100,000 in Malta. In Northern Europe, MS is associated with HLA-DR2/Dw2. The other components of the commonest DR2-containing haplotype of this region, HLA-A3-B7-DR2-Dw2, also tend to be present at higher frequency in MS patients. HLA Class I and II antigen frequencies and associations in controls and MS patients from Sicily and Malta were studied to discover whether they might account for the difference in MS prevalence. In Sicilian MS patients, DR2 is increased in frequency compared with controls and four out of five DR2-positive patients also type as Dw2. In the Maltese population, DR2 is present at high frequency but approximately half of the DR2 positive individuals do not type as Dw2 so that DR2 is probably most commonly present as part of Class II haplotypes other than those commonly associated with MS. Additional differences in HLA profile of the Sicilian and Maltese populations were found when HLA-A, -B, and B-DR antigen associations were examined. Therefore, some of the difference in MS prevalence might be explained by genetic factors.

Cross-Sectional Studies↗
PubMed1986

A DR3-related DX alpha gene polymorphism strongly associates with insulin-dependent diabetes mellitus.

HLA-DQ alpha and HLA-DX alpha gene polymorphisms were analyzed by Southern blot techniques in 78 Caucasoid insulin-dependent diabetes mellitus (IDDM) subjects and 55 control subjects. Five restriction fragment length polymorphisms of the HLA-DQ alpha gene correlated with HLA-DR typing. Two allelic DX alpha-related gene fragments, of 2.1 kb (U) and 1.9 kb (L) in size were identified. Genotype frequencies in the IDDM group for UU, UL, and LL were 54%, 38.5%, and 7.5%, respectively, whereas the corresponding frequencies in the control group were 24%, 40%, and 36% (P less than 0.00005 for differences in genotype frequencies). The U allele was associated particularly with IDDM patients who were DR3, with healthy controls who were DR3, as well as with IDDM patients who were not DR3. Thus, if this DX alpha U allele is not the DR3-associated IDDM susceptibility gene, it is the closest marker hitherto studied.

Chromosome Mapping↗
PubMed1986

HLA-Dw specificity assignments are independent of HLA-DQ, HLA-DR, and other class II specificities and define a biologically important segregant series which strongly activates a functionally distinct T cell subset.

Several lines of evidence indicate that HLA-Dw, as defined by HTC typing, is not the result of the combined stimulatory effect of HLA-DR and DQ. Therefore, responder cells do not have to share HLA-DQ antigens with the stimulator HTCs to give a typing response. The common HLA-DR-DQ associations observed in HTCs correspond to different patterns of linkage disequilibrium in different populations. HLA-DQ and HLA-Dw are functionally heterogeneous. Although HLA-DQ molecules may play a role in primary stimulation, this role is distinct from that of Dw determinants which have strong lymphocyte activating properties. The role of the HLA-DQ determinants on the other hand, is one of modulating the total T cell response by controlling the proliferation of suppressor and cytotoxic cells. The primary MLC response is the result of the proliferative effect of HLA-Dw, DR, DP, and other associated determinants, in conjunction with a modulatory effect of DQ molecules. However, HLA-Dw (as detected by HTC typing) are DR associated determinants which are immunodominant in primary MLR. The genes of the HLA-DR subregion have been named DR by the WHO nomenclature committee. This subregion encodes the HLA-DR specificities and the DRw52 and DRw53 determinants. Unfortunately this nomenclature does not take into account the need to define the genetic basis of the HLA-Dw determinants--whether they are encoded by separate genes within the HLA-DR subregion or whether they are encoded by as yet unspecified genes in the HLA class II region in linkage disequilibrium with HLA-DR DRw52/53. There are at least three and possibly four beta chain genes in the HLA-DR subregion, all in strong linkage disequilibrium with each other. Some of these are expressed in most haplotypes while others are not; some behave as pseudogenes in some haplotypes and in others, all the genes are expressed. All the genes of the class II region have not been fully characterized. HLA-Dw determinants may be specified by one or more of these genes. When more information becomes available, the genetic and molecular basis of the HLA-Dw series as well as the functional heterogeneity and antigenic strength of the various class II determinants will be better understood.

Epitopes↗
PubMed1986

HLA antigens in palindromic rheumatism and palindromic onset rheumatoid arthritis.

Fifty patients who presented with typical palindromic rheumatism of at least 6 months' duration were tissue-typed for HLA A, B, C antigens. DR typing was also performed but was not possible for technical reasons in three patients. Twenty-three patients who had progressed to definite or classical rheumatoid arthritis (RA) after a mean interval of 5 years were compared with 20 patients whose palindromic attacks had persisted over a similar period. Both groups showed a significantly higher frequency of DR4 antigen than a control population. The RA group also showed an increased frequency of DR1. There was no significant difference in the frequency of DR4 or any other DR antigen between the two patient groups. The frequency of B27 antigen was significantly higher in the palindromic group compared with the controls. It is suggested that although DR4 may be associated with a tendency to inflammatory joint problems, environmental or other unrelated genetic factors may be more important in determining the progression of palindromic rheumatism to RA.

Arthritis, Rheumatoid↗