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Biomedical subjects

C R Stiller

Publications and source records attributed to C R Stiller.

At least 127 records · Page 7Linked to original sources

HLA in multiple sclerosis. Relationship to measles antibody, mitogen responsiveness and clinical course.

In our study of multiple sclerosis (MS) patients we have found significant increases in the A3, B7, and DW2 antigens. We have also studied immune responses in these same patients. There was elevation of measles antibodies in MS patients positive for A3, B7, and B18 as compared to MS patients without those antigens. The first study of mitogen responsiveness (31 patients) showed a decreased response in A3, and B7 positive patients. Study of a second and a larger group (62 patients), at a different time, failed to confirm this deficiency. We propose that there is a genetically linked (HLA) T cell deficiency in some MS patients and that this deficiency results in high humoral responses to measles antigens and an evanescent (or cyclical) reduced T cell response to mitogen.

Antibodies, Viral↗

HLA-D typing with an association of Dw2 and absent immune responses towards herpes simplex (type i) antigen in multiple sclerosis.

We have confirmed that HLA-Dw2 is increased in MS patients to 47% (normals 20%). Lymphocyte transformation and antibody studies with herpes simplex antigen show that many of the DW2-positive MS patients have low or absent responses. The association of low responses to HSV and the presence of Dw2 is statistically significant at a p value less than 0.01.

Antibody Formation↗

HLA antigens and mitogen responsiveness in multiple sclerosis.

Thirty-one MS patients were studied for their in vitro response to lymphocyte mitogens. Patients with HLA antigens A3 and/or B7 had lower mean peak responses to all three mitogens compared to A3, B7-negative patients. The difference in the mean peak responses to Con A were significantly different at a level of p less than 0.05. This supports the concept of a histocompatibility-linked T-cell deficiency in many patients with MS.

HLA Antigens↗

Effects of a gold salt on lymphocyte responses.

The effects of sodium aurothiomalate (SATM) on certain lymphocyte functions in vitro were tested. Lymphocytes were obtained from both healthy donors and patients with rheumatoid arthritis (RA). SATM depressed tritiated thymidine uptake in lymphocyte cultures stimulated by phytohaemagglutinin, and in a mixed lymphocyte response assay. Cytotoxic effector cell generation assayed by percentage specific 51Cr release was also depressed by SATM using lymphocytes from healthy donors, and from patients with RA. These effects imply that SATM inhibits both exogenous thymidine uptake, and blastogenesis, and suggest that gold salts may act in RA by interference with T-cell dependent functions.

Arthritis, Rheumatoid↗

Anti-donor immune responses in prediction of transplant rejection.

We assessed various immune responses against donor tissue to determine their value in the diagnosis and prediction of clinical rejection episodes. Twenty-six consecutive clinical renal-transplant recipients were examined. Cell-mediated lymphocytotoxicity preceded and accompanied 41 of 45 rejection episodes (P less than 0.001). Complement-dependent antibody was present in 12 of 15 rejections (P less than 0.002)--four not accompanied by, and eight in association with, cell-mediated lymphocytotoxicity. Mixed lymphocyte reactivity or nonreactivity and inhibition by autologous serum occurred equally often in rejection and quiescence. Lymphocyte-dependent antibody occurred during both rejection episodes and quiescent phases, with a greater frequency during quiescence (P = 0.05). Cell-mediated lymphocytotoxicity was the best predictor of rejection (P less than 0.05). Cell-mediated lymphocytotoxicity was the best predictor of rejection (P less than 0.001), and was more easily suppressed by standard immunosuppressive therapy, than complement-dependent antibody. If specific cell-mediated lymphocytotoxicity, with or without antibody, recurred after rejection therapy, the graft underwent further rejection.

Antigen-Antibody Reactions↗

Spontaneous rupture of the renal pelvis: complication of renal homotransplantation.

The first reported case of rupture of the renal pelvis associated with transplantation is presented. The obstruction was in the ureteral tunnel of the hypertrophic bladder. The cause of the weakness in the pelvic wall could not be determined. Differential diagnosis was acute rejection and lymphocele. Excretory urography was diagnostic. Treatment included revision of the ureteroneocystostomy with repair of the defect and internal stenting. Postoperative morbidity was minimal and satisfactory graft function was maintained.

Adult↗

Measles antibodies as related to HL-A types in multiple sclerosis.

One hundred thirty-six patients with multiple sclerosis and several control groups were studied for measles antibodies using several different antigens. Measles antibodies were higher in the multiple sclerosis population, but siblings also had higher titers than matched and random controls. The elevation in antibody titers (complement fixation) was found in female multiple sclerosis patients and male patients with HL-A types 3, 7, and W-18. Male patients not carrying these HL-A antigens had, as a group, relatively normal antibody levels. These data confirm a familial factor in elevated measles antibody titers. We suggest that HL-A antigens are linked to one of the factors that determines measles antibody titers in multiple sclerosis patients.

Age Factors↗

Transplant monitoring: patterns of the immune response.

Immune responses, specific to the stored donor tissue, were measured in 26 recipients over 4,000 days. CML positive crossmatches were associated with accelerated rejections (three cases). LDA positive crossmatches resulted in primary non-functioning kidneys (three cases). Post-transplantation. CML (16 hour inculation) was associated with rejection (p equals 0.001), highly predictive of rejection (p equals 0.001), and when positive after rejection treatment, was associated with a failure to respond (p equals 0.005 - 0.01). 51Cr-CDA was also associated with rejection (p equals 0.002). Recovery of these immunologic participants from the explanted kidney substantiated that they were important effector mechanisms in vivo.

Antibodies↗

Lymphocyte-dependent antibody and renal graft rejection.

A patient with preformed cytotoxic lymphocyte-dependent antibody (L.D.A.) against the specific renal transplant donor rapidly rejected the grafted kidney. The characteristics of rejection were not those of hyperacute rejection due to cytotoxic complement-dependent antibody or of acute rejection is attributed to the cytotoxic activity of L.D.A. The avoidance of transplants based on positive crossmatches by the L.D.A. test or at least the carrying out of the L.D.A. crossmatch is advised.

Adult↗

Autoimmunity: present concepts.

Autoimmune disease may be effected by humoral mechanisms (direct antibody effect or pathogenic antigen-antibody complexes), cell-mediated mechanisms, and possibly complement in the absence of antibody. In view of recent work, self-tolerance can no longer be explained by the clonal selection theory; cells that are capable of recognizing self-antigens and effecting an autoimmune response seem to be present in the normal individual but actively regulated by a process involving antigen-antibody complexes or suppressor T cells. The determination that a clinical state is an autoimmune disease cannot, therefore, be made only on the basis of the presence of autoantibody as this may be part of the normal and active state of immunoregulation of autoimmunity. Indeed, the absence of autoantibody may be the immunodeficient state that allows a full-blown autoimmune disease to occur. In view of this knowledge, the basis for the diagnosis of autoimmune disease and the rationale for treatment based on the objective of inhibiting all immune responses to the autoantigen require re-examination.

Animals↗

HL-A frequencies in patients with multiple sclerosis.

The histocompatibility antigens (HL-A) have been determined in 100 multiple sclerosis (M.S.) patients and 140 randomly selected controls. In the M.S. group there was a statistically significant increase in the frequency of HL-A 7 and W 18 with an insignificant increase in HL-A 3. The variance from normal HL-A patterns in the M.S. population may play some role in establishing the substrate for this disease. Studies in experimental animals have shown that susceptibility to autoimmune disease and to virus infection is linked to the major histocompatibility locus. This has interesting implications for both the "slow virus" and the "autoimmune" theories of the etiology of multiple sclerosis.

Autoimmune Diseases↗