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M D'Souza

Publications and source records attributed to M D'Souza.

At least 19 recordsLinked to original sources
PubMed1996

In vitro comparison of cytokine release from antithymocyte serum and OKT3. Inhibition with soluble and microencapsulated neutralizing antibodies.

Antilymphocyte antibodies are widely used to prevent and treat rejection after organ transplantation. Induction of cytokine release is implicated in the side effects produced by these antibodies. In this study, cytokine release induced by OKT3 was compared with antithymocyte serum (ATS) using an in vitro whole blood model. The efficacy of the microsphere form of cytokine-neutralizing antibodies to attenuate OKT3 and ATS-induced cytokine release was compared with the soluble form of cytokine-neutralizing antibodies. OKT3-induced significantly higher amounts of tumor necrosis factor-alpha and interleukin 1 beta levels compared with ATS. The microsphere form of tumor necrosis factor-alpha and interleukin 1 beta neutralizing antibodies attenuated OKT3 and ATS-induced cytokine release much more efficiently compared with the soluble form. The results suggest that the severity of the side effects is related to the amount of cytokine release. Microencapsulated cytokine-neutralizing antibodies might be a better therapeutic agent than the soluble form of cytokine-neutralizing antibodies in the treatment of side effects induced by antilymphocyte antibodies.

Antilymphocyte Serum↗
PubMed1995

Immunoprinting reveals different genetic bases for (auto)immuno diseases.

The genetic basis of complex (auto)immune diseases has been studied for an ovine nematode infection, human rheumatoid arthritis (RA), early onset pauciarticular arthritis (EOPA) and multiple sclerosis (MS). Immunoprinting combines the powerful simplicity of polymerase chain reaction (PCR)-based amplification of discrete, highly informative microsatellite loci with the principle of genetic associations. This approach has allowed us to define novel genetic risk factors in adult RA patient categories whereas EOPA forms in juveniles display other prominent genetic contributions. Differentially regulated tumor necrosis factor (TNF) expression may lead to a better understanding of the causal pathogenesis of EOPA while T cell receptor (TCR) gene polymorphisms appear crucial for RA manifestations in certain patient groups. Statistically significant marker associations have still to be defined for MS in larger panels of patient and control cohorts. The clinical course of the disease will probably have to be taken into account when associations with lymphokine levels are evaluated. In essence a convoluted myriad of negative and a few positive disease association data have been generated efficiently by immunoprinting. As expected, the interrelationships are truly complicated between the polymorphic genetic instances predisposing to autoimmune disease. Nevertheless, risk factors may be defined on an individualized basis by indirect gene diagnosis revealing predispositions and providing a more solid basis for differential diagnosis and treatment.

Adult↗
PubMed1995

Prolongation of murine cardiac allograft survival by microspheres containing TNF alpha and IL1-beta neutralizing antibodies.

Efficient delivery of therapeutic agents to a critical microenvironment may increase the efficacy of drugs used to modulate the allograft rejection response. This study demonstrates the ability of the combination of microspheres containing neutralizing anti-TNF alpha and anti-IL1-beta antibodies to significantly prolong murine cardiac allograft survival. These results suggest that the microsphere technique is an efficacious method to target antibody delivery to prolong allograft survival.

Animals↗
PubMed1994

Multiple trichoepitheliomas with rare features.

A case of multiple trichoepitheliomas associated with epidermal cysts is reported. The trichoepithelioma lesions were florid and extensive with large nodulo-cystic lesions on the face and a new variant simulating hidradenitis suppurativa near the gluteal cleft.

Epidermal Cyst↗
PubMed1991

Synthesis and utilization of a nonhydrolyzable phosphoadenosine phosphosulfate analog.

3'-Phosphoadenosine 5'-phosphosulfate (PAPS) functions as the high-energy sulfate donor for sulfate ester synthesis in all higher organisms. This activated sulfate, like its adenosine 5'-phosphosulfate precursor, is both chemically labile and vulnerable to sulfohydrolase degradation. These obstacles have limited the utility of the native PAPS in the purification and mechanistic description of the numerous PAPS-utilizing enzymes. This paper describes the synthesis of the 2'- and 3'-isomers of a nonhydrolysable, and thus stable, PAPS analog, beta-methylene-PAPS, from the previously described beta-methylene-APS (L. Callahan et al., Anal. Biochem. 177, 67-71, 1989). The method involves phosphorylation of beta-methylene-APS with trimetaphosphate and separation of the resulting mixed 2'(3')-isomers by ion-pair reverse-phase HPLC. The utilization of this analog as an inhibitor of APS kinase and PAPS translocase, two of the numerous PAPS-utilizing activities, as well as an affinity ligand for purification of APS kinase, is described.

Animals↗
PubMed1990

Polymorphism of HLA-DR2,DQw1 haplotypes in Asian Indians.

We examined the polymorphism of DR2,DQw1 haplotypes in Epstein-Barr virus-transformed B-lymphoblastoid cell lines (HTCs) and unrelated (32 Canadian Caucasians and 24 Asian Indians) individuals by restriction fragment length polymorphism (RFLP) and oligonucleotide typing. The data demonstrate that three subtypes of DR2,DQw1 haplotypes, DRw15(B1.1501).DQw6a(A1.0102,B1.0602),DRw15(B1.1502). DQw6b(A1.0103,B1.0601), DRw16(B1.1601).DQw5(A1.0102,B1.0502) are present in HTCs and Canadian Caucasians. Of these, DRw15(B1.1501).DQw6a (A1.0102,B1.0602) haplotype was present in majority (81.3%) of Caucasians. Among Asian Indians, this haplotype was present only in one DR2,DQw1-positive individual. In addition, three new haplotypes representing different combinations of DRB1, DQA1 and DQB1 genes were demonstrable in Asian Indians. These new haplotypes are DRw15(B1.1501).DQw6b(A1.0103,B1.0601),DRw15(B1.1501). DQw5(A1.0102,B1.0502), and DRw15(B1.1501).DQw6c(A1.0102, B1.0601). The most frequent haplotypes among Asian Indians were DRw15(B1.1502).DQw6b(A1.0103,B1.0601) and DRw15(B1.1501). DQw6b(A1.0103,B1.0601). The distribution of subtypes of DR2,DQw1 haplotypes in Asian Indians was significantly different from that in Canadian Caucasians. The results in the present study have important implications for HLA and for HLA-disease associations.

Asia↗
PubMed1990

DNA restriction fragment length polymorphism of HLA-DR2 haplotypes in normal individuals and in patients with rheumatoid arthritis.

A strong association between HLA-DR4 and rheumatoid arthritis (RA) has been found in a number of populations. In contrast, the incidence of DR2 is decreased in patients with RA, suggesting that this specificity may confer some protection against the disease. A number of subtypes of DR2 have been defined by serology, by responses in mixed lymphocyte culture reaction, and, more recently, by restriction fragment length polymorphism. These subtypes of DR2 are in linkage disequilibrium with different subspecificities of DQw1. It is thus likely that the distribution of these subtypic DR,DQ haplotypes in DR2 positive patients with RA may be important in understanding the genetic basis of susceptibility/resistance to RA. In this paper a study of the subtypes of DR2,DQw1 haplotypes in 18 patients with RA, who required sodium aurothiomalate as a disease remitting drug, and unrelated healthy individuals is reported. Three subtypes of DR2 haplotypes, DRw15 (Dw2),DQw1.2(DQw6), DRw15(Dw12),DQw1.12(DQw6), and DRw16(Dw21),DQw1, AZH (DQw5), were analysed with a cDNA probe for the DQ beta gene. The data show that DR2 positive patients with RA carried either the DRw15(Dw2),DQw6 or DRw15(Dw12),DQw6 haplotype. No patient with RA was positive for the DRw16(Dw21),DQw5 subspecificity. In contrast, six of 29 (21%) normal healthy DR2,DQw1 positive individuals carried the DRw16(Dw21),DQw5 haplotype. These data together with earlier results on the distribution of the DR4,DQw7 haplotype in patients with RA support the hypothesis that DQB1 chain polymorphism may be important in determining susceptibility to severe RA.

Arthritis, Rheumatoid↗
PubMed1990

Polymorphism of major histocompatibility complex extended haplotypes bearing HLA-DR3 in patients with rheumatoid arthritis with gold induced thrombocytopenia or proteinuria.

The distribution of DR3 and of extended haplotypes bearing DR3 was studied in three groups of subjects: 35 patients with rheumatoid arthritis (RA) with gold induced thrombocytopenia or proteinuria, 185 patients with RA without these side effects, and 300 normal healthy controls. The extended haplotypes bearing DR3 were analysed with cDNA probes for DR alpha, DR beta, DQ alpha, and DQ beta genes. The data showed that the prevalence of DR3 was significantly higher in patients who developed gold induced thrombocytopenia or proteinuria than in normal controls or patients with RA without these side effects. Distribution of three extended haplotypes bearing DR3 (B8, DR3; B18,DR3; non-B8,non-B18,DR3) in patients with RA with thrombocytopenia or proteinuria was significantly different from that in normal controls, but not from that in patients with RA without these toxic reactions. Southern blot analysis of DR, DQ genes with cDNA probes showed that the extended haplotype bearing B8,DR3, which carries DQA2.1 and DQB2.1 genes, was present in a significantly higher proportion of patients with RA with gold induced thrombocytopenia or proteinuria (22/24, 92%) than in patients with RA without these side effects (32/45, 71%) or normal subjects (40/61, 66%). The data suggest that the genomic region on chromosome 6 involved in susceptibility to gold induced thrombocytopenia or proteinuria should be extended to the DQA2, DQB2 gene loci.

Arthritis, Rheumatoid↗
PubMed1990

Is the prevalence of atopy increasing?

There is controversy about whether allergic disease has increased in recent decades. This study compared the prevalence of atopy, as shown by allergy skin prick testing among adults in 1988 (n = 74) with a similar study carried out in 1974 (n = 1359). Both study groups were drawn from the general population in south west London, but the 1988 sample specifically excluded people with rhinitis. The proportion of subjects with at least one positive reaction to a panel of three common allergens increased significantly from 23% in 1974 to 46% in 1988 (P less than 0.01). If allowance was made for the exclusion of rhinitis subjects from the 1988 sample, the current prevalence of atopy may be higher still. The increase in prevalence was significant in older subjects (aged 55-59 years) and women but not in other age groups or in men. This small study raises the possibility that atopy has increased in prevalence in the UK over recent decades and additional studies are needed to evaluate the validity of this hypothesis.

Adult↗