33 results on '"Dewitt, C. W."'
Search Results
2. IMMUNOGENETIC CONTROL OF EXPERIMENTAL COLLAGEN-INDUCED ARTHRITIS IN RATS. II. ECIA SUSCEPTIBILITY AND IMMUNE RESPONSE TO TYPE II COLLAGEN (CALF) ARE LINKED TO RT1.
- Author
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Griffiths, Marie M. and DeWitt, C. W.
- Published
- 1981
- Full Text
- View/download PDF
3. Outcome of cardiac transplant recipients with a positive donor-specific crossmatch--preliminary results with plasmapheresis.
- Author
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Ratkovec RM, Hammond EH, O'Connell JB, Bristow MR, DeWitt CW, Richenbacher WE, Millar RC, and Renlund DG
- Subjects
- B-Lymphocytes immunology, Graft Survival, Histocompatibility Testing, Humans, Immunoglobulin G analysis, T-Lymphocytes immunology, Heart Transplantation immunology, Plasmapheresis, Tissue Donors
- Abstract
To assess the influence of a positive T or B cell IgG crossmatch on the development of rejection and mortality following cardiac transplantation, we reviewed all cardiac transplants performed in Utah between March 1985 and October 1990. Of the 328 cardiac allograft recipients, 11 (3.4%) had an IgG positive crossmatch. Actuarial survival at 24 months in the positive crossmatch group was 57.3% +/- 0.02 while that of the controls was 86.1% +/- 2.1 (P < 0.05). Allograft rejection occurred earlier in recipients with a positive crossmatch (10.0 +/- 5.8 days versus 34.0 +/- 2.3 days, P < 0.001). The first allograft rejection episode in patients with a positive crossmatch was characterized by immunoglobulin and complement deposition in small blood vessels and interstitial edema and endothelial cell activation in the absence of a lymphocytic infiltrate. Furthermore, the allograft rejection in the positive crossmatch group was accompanied by hemodynamic compromise in a large proportion of the patients (73%). In addition to augmentation of immunosuppression, plasma exchange therapy was performed within the first week following transplantation in 8 of the 11 positive crossmatch patients. Survival in the patients treated with plasma exchange (75%) appears to be better than in those not receiving plasma exchange (33%) within one week of transplantation. While immunosuppressive therapy aimed at the humoral arm of the immune system and plasma exchange therapy may improve survival in recipients with a positive donor-specific crossmatch, survival is worse in patients with a positive crossmatch than in patients with a negative crossmatch. Thus, it would appear prudent to prospectively crossmatch cardiac transplant candidates with a greater risk of developing a positive crossmatch, such as those potential recipients with an elevated level of panel-reactive antibodies.
- Published
- 1992
- Full Text
- View/download PDF
4. Possible association of the extended MHC haplotype B44-SC30-DR4 with autism.
- Author
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Warren RP, Singh VK, Cole P, Odell JD, Pingree CB, Warren WL, DeWitt CW, and McCullough M
- Subjects
- Adolescent, Adult, Alleles, Child, Child, Preschool, Female, Histocompatibility Testing, Humans, Male, Autistic Disorder genetics, Haplotypes, Major Histocompatibility Complex genetics
- Abstract
We previously reported that the complement C4B null allele appears to be associated with infantile autism. Since the C4B null allele is known to be part of the extended or ancestral haplotype [B44-SC30-DR4], we investigated the incidence of [B44-SC30-DR4] in 21 autistic children and their parents. This extended haplotype was increased by almost six-fold in the autistic subjects as compared with healthy controls. Moreover, the total number of extended haplotypes expressed on chromosomes of autistic subjects was significantly increased as compared with those expressed on chromosomes of healthy subjects. We conclude that a gene related to, or included in, the extended major histocompatibility complex may be associated with autism.
- Published
- 1992
- Full Text
- View/download PDF
5. Sensitization to OKT3 monoclonal antibody in heart transplantation: correlation with early allograft loss.
- Author
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O'Connell JB, Renlund DG, Hammond EH, Wittwer CT, Yowell RL, DeWitt CW, Jones KW, Gay WA Jr, Menlove RL, and Bristow MR
- Subjects
- Animals, Antibodies analysis, Antibodies, Monoclonal therapeutic use, Enzyme-Linked Immunosorbent Assay, Female, Humans, Immunization, Incidence, Male, Mice immunology, Middle Aged, Muromonab-CD3, Time Factors, Antibodies immunology, Antibodies, Monoclonal immunology, Graft Rejection immunology, Heart Transplantation immunology, Immunosuppression Therapy
- Abstract
Because administration of murine monoclonal anti-CD3 antibody (OKT3) may result in the formation of human antimouse antibody, which complexes with OKT3, we conducted this study to assess the incidence and effect of human antimouse antibody formation during prophylactic administration of OKT3 in heart transplantation. Human antimouse antibody developed in eight of 55 (14%) cardiac allograft recipients receiving OKT3 prophylaxis as measured by enzyme-linked immunosorbent assay. Additionally, two recipients had an inexplicable rise in CD3+ lymphocytes during therapy without detectable antibody. The outcome of these 10 sensitized recipients was compared with that of 45 nonsensitized recipients. Age, preoperative diagnosis, hemodynamics, and the need for intravenous inotropes or mechanical assistance before transplantation were similar in both groups. No female patients were in the sensitized group, whereas 33% of the nonsensitized group were female patients. A trend toward greater sensitization when prophylaxis was extended to 21 days (28%) compared with the more conventional 14-day administration (10%) was not statistically significant. Retransplantation because of rejection was required in a single patient in each group. Allograft survival was significantly lower by 3 months in the sensitized group, and allograft loss caused by rejection selectively accounted for that difference. In survivors, rejection frequency and infectious complications were similar. These findings suggest that sensitization to OKT3 occurs at low frequency after prophylactic administration in heart transplantation but is associated with an increased frequency of graft loss because of rejection.
- Published
- 1991
6. Clinical manifestations of vascular rejection in cardiac transplantation.
- Author
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Ensley RD, Hammond EH, Renlund DG, Yowell RL, Bristow MR, DeWitt CW, Menlove RL, Ratkovec RM, and O'Connell JB
- Subjects
- Adult, Antibody Formation, Blood Vessels immunology, Heart Transplantation pathology, Histocompatibility, Humans, Immunity, Cellular, Middle Aged, Survival Analysis, Graft Rejection, Heart Transplantation immunology
- Published
- 1991
7. Relationship of OKT3 sensitization and vascular rejection in cardiac transplant patients receiving OKT3 rejection prophylaxis.
- Author
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Hammond EH, Wittwer CT, Greenwood J, Knape WA, Yowell RL, Menlove RL, Craven C, Renlund DG, Bristow MR, and DeWitt CW
- Subjects
- Antibodies, Anti-Idiotypic analysis, Antibodies, Monoclonal blood, Antibodies, Monoclonal immunology, Antigen-Antibody Complex analysis, Graft Occlusion, Vascular, Humans, Muromonab-CD3, Antibodies, Monoclonal therapeutic use, Graft Rejection immunology, Heart Transplantation mortality
- Abstract
We prospectively and serially monitored plasma levels of OKT3 in 20 patients who were receiving 14- or 21-day rejection prophylaxis with OKT3. We retrospectively compared plasma OKT3 levels with biopsy scores assessed by light microscopy and immunofluorescence, clinical findings, human antimouse antibody (HAMA) production assessed by a blocking assay and by ELISA, and circulating immune complex levels assessed by a flow cytometric Raji cell assay. Using these methods, we evaluated the relationship of OKT3 sensitization, a humorally mediated immune response, to the development of vascular rejection in these patients. We found that 6 of 20 patients had declines in plasma OKT3 levels to less than 50% of their steady-state value before the conclusion of therapy (OKT3 consumption). This fall in plasma OKT3 preceded a significant rise in the CD 3 lymphocyte level by up to 3 days. All 6 patients showed HAMA production by either blocking or ELISA assay (P = less than 0.02) and developed vascular rather than cellular rejection (P = less than 0.01). OKT3 sensitization was significantly more common in patients treated with 21-day rejection prophylaxis (4 of 6 patients, P = less than 0.01). Only 4 of 14 other patients showed vascular rejection; 2 of these 4 also developed HAMA without OKT3 consumption and both had been treated with 21-day rejection prophylaxis with OKT3. None of the 20 patients showed significant levels of circulating immune complexes. This study demonstrates that OKT3 sensitization is strongly associated with vascular rejection. Vascular rejection was usually demonstrated 7 days after OKT3 consumption was seen and was coincident with HAMA production. By contrast, 4 patients without OKT3 sensitization had vascular rejection demonstrable in the early posttransplant period; in such patients, prospective immunofluorescence of biopsies was the only reliable indicator of this rejection type. The higher incidence of vascular rejection in these 20 patients was definitely related to the use of 21-day OKT3 rejection prophylaxis. Overall, 7 of the 12 patients treated with this regimen developed vascular rejection. Allograft and patient survival among patients with vascular rejection was significantly worse than in patients with cellular rejection (P = less than 0.01). Prospective monitoring of patients treated with OKT3 by serial plasma levels and by biopsy immunofluorescence will identify patients at risk for these types of humoral rejection.
- Published
- 1990
- Full Text
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8. Use of Orthoclone OKT3 monoclonal antibody in cardiac transplantation: early experience with rejection prophylaxis and treatment of refractory rejection.
- Author
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Gilbert EM, Eiswirth CC, Renlund DG, Menlove RL, DeWitt CW, Freedman LA, Herrick CM, Gay WA, and Bristow MR
- Subjects
- Adolescent, Adult, Antibodies, Monoclonal adverse effects, Heart Diseases pathology, Heart Diseases surgery, Humans, Immunosuppression Therapy, Male, Middle Aged, Muromonab-CD3, Myocardium pathology, Time Factors, Antibodies, Monoclonal therapeutic use, Graft Rejection, Heart Transplantation
- Published
- 1987
9. Immunogenetic control of experimental type II collagen-induced arthritis. I. Susceptibility and resistance among inbred strains of rats.
- Author
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Griffiths MM, Eichwald EJ, Martin JH, Smith CB, and DeWitt CW
- Subjects
- Animals, Arthritis chemically induced, Arthritis genetics, Disease Models, Animal, Hypersensitivity diagnosis, Otitis pathology, Rats, Skin Tests, Arthritis immunology, Collagen pharmacology, Immunity, Innate, Rats, Inbred BUF immunology, Rats, Inbred Lew immunology, Rats, Inbred Strains immunology, Rats, Inbred WF immunology
- Abstract
Seven inbred rat strains were tested for susceptibility to experimental type II collagen-induced arthritis and for development of cellular immunity to type II collagen by delayed hypersensitivity skin testing. WF (RT1u), LEW (RT1l), and DA (RT1a) were the most susceptible of the strains tested with respect to incidence (greater than 95%) and severity of disease. LEW and DA were strongly skin test reactive to calf type II collagen. BUF (RT1b) developed moderate skin test responses to calf type II collagen and showed low susceptibility to collagen arthritis (1/8). MAXX (RT1n), LEW.B3 (RT1nvl), and AUG (RT1c) were not susceptible to collagen arthritis and showed negative to very weak skin test responses to type II collagen. Disease susceptibility was inherited as a dominant trait in the F1 progeny of (WF X LEW.B3) matings. These data suggest that clinical expression of experimental collagen-induced arthritis and immune responsiveness to type II collagen are controlled in part by genes within or closely linked to the rat major histocompatibility complex--RT1.
- Published
- 1981
- Full Text
- View/download PDF
10. Treatment of refractory cardiac allograft rejection with OKT3 monoclonal antibody.
- Author
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Gilbert EM, Dewitt CW, Eiswirth CC, Renlund DG, Menlove RL, Freedman LA, Herrick CM, Gay WA, and Bristow MR
- Subjects
- Adult, Female, Humans, Leukocyte Count, Male, Middle Aged, Myocardium immunology, Myocardium pathology, T-Lymphocytes classification, T-Lymphocytes immunology, Antibodies, Monoclonal therapeutic use, Graft Rejection, Heart Transplantation
- Abstract
OKT3 monoclonal antibody is a murine monoclonal antibody specific for the T lymphocyte T3 cell surface receptor that mediates antigen recognition. The use of OKT3 monoclonal antibody for the treatment of cardiac allograft rejection refractory to conventional therapy with high-dose steroids and antithymocyte globulin is described. Seven patients received 5 mg of OKT3 monoclonal antibody intravenously per day for 10 to 14 days. Diagnosis of moderate or severe rejection was made in all seven from right ventricular endomyocardial biopsy. Biopsy was repeated 48 to 72 hours and seven to 10 days after OKT3 monoclonal antibody was begun. With treatment, four patients had a complete response, with improvement on both early and late biopsy. Two patients had partial responses, with improvement on early biopsy followed by worsening rejection on late biopsy. One patient died of graft failure six hours after receiving OKT3 monoclonal antibody. Adverse events were common in the first two days of therapy but were well tolerated. It is concluded that OKT3 monoclonal antibody is useful in the treatment of refractory cardiac allograft rejection.
- Published
- 1987
- Full Text
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11. Ultraviolet light induces tumors with both unique and host-associated antigenic specificities.
- Author
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DeWitt CW
- Subjects
- Absorption, Animals, Antigens, Neoplasm, Cattle, Cross Reactions, Female, Fibroblasts immunology, Immune Sera pharmacology, Mice, Mice, Inbred BALB C, Mice, Inbred C3H, Mice, Inbred C57BL, Ultraviolet Rays, Epitopes, Neoplasms, Radiation-Induced immunology
- Abstract
Murine tumors induced by ultraviolet light (UV) are immunogenic in syngeneic and semi-syngeneic hosts, evoking antibody of several different specificities. Cytotoxic antibody specific for the immunizing syngeneic tumor (tumor-specific antigen) comprises the early response and a minor portion of the later response of C3H and C3H.SW mice. It is the primary specificity to which C57BL/6 and C57BL/10 hosts respond. The major portion of the antibody produced by C3H and C3H.SW against syngeneic tumors cross-reacts strongly with other tumors, both UV and chemically induced, arising in C3H and C3H.SW but not in B6.H2k, C57BL/6, C57BL/10, or (C3H X B6)F1. Normal adult cells or embryonic fibroblasts do not cross-react with the antisera. These results are interpreted as evidence for the involvement of a host component (non-MHC) in this tumor-associated antigen (TAA). (C3H X B6)F1 and (C3H X BALB/c)F1 hosts respond to C3H tumors with antibody with cross-reactive specificities identical to those of the C3H and C3H.SW hosts. thus detecting the TAA(C3H) specificity. (C3H X B6)F1 hosts respond to syngeneic F1 tumors, however, with a totally cross-reactive antibody that is interpreted as evidence for the existence of a common antigen in addition to the evident immune response control. An undetected TAA (B6) specificity in the (C3H X B6)F1 tumors is speculatively proposed.
- Published
- 1981
12. Age-associated decline in cardiac allograft rejection.
- Author
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Renlund DG, Gilbert EM, O'Connell JB, Gay WA Jr, Jones KW, Burton NA, Doty DB, Karwande SV, Dewitt CW, Menlove RL, Herrick CM, and Bristow MR
- Subjects
- Actuarial Analysis, Adolescent, Adult, Female, Follow-Up Studies, Humans, Immunosuppressive Agents therapeutic use, Male, Middle Aged, Statistics as Topic, Time Factors, Aging immunology, Graft Rejection, Heart Transplantation
- Abstract
The influence of age on cardiac allograft rejection was studied in 57 consecutive recipients. Twenty-one subjects were 54 years of age or older (mean, 57.7 +/- 0.6 years [+/- SEM]; range, 54 to 63 years) and 36 subjects were 52 years of age or younger (mean, 39.9 +/- 1.8 years; range, 16 to 52 years; p less than 0.001). The older recipients had fewer rejection episodes during the first four months following cardiac transplantation (0.24 +/- 0.05 episodes per month versus 0.72 +/- 0.09 episodes per month; p less than 0.001) and during the total duration of follow-up (0.20 +/- 0.03 episodes per month versus 0.40 +/- 0.07 episodes per month; p = 0.045), and experienced their first rejection episode later (50.4 +/- 4.0 days versus 27.7 +/- 8.5 days; p = 0.008). Younger age was found to add significantly as a predictor of rejection in a multivariate analysis that controlled for sex, immunosuppressive agents, cause of heart failure, and pretransplantation lymphocyte cross-match status (r = 0.64, p less than 0.05). Decreased rejection frequency occurred without a concomitant increase in the serious infection rate (67 percent in both groups). The 12-month actuarial survival was 100 percent in the older group and 94 percent in the younger group (p = NS). Decreased rejection in the older recipients is likely a manifestation of an age-associated decline in immune function and might represent an advantage in transplantation for carefully selected older patients.
- Published
- 1987
- Full Text
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13. The LEW.BN(2R) strain: a recombinant in the rat MHC.
- Author
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Lynch DH and DeWitt CW
- Subjects
- Alleles, Animals, Cross Reactions, Crosses, Genetic, Cytotoxicity, Immunologic, Epitopes, Genetic Linkage, Lymphocyte Culture Test, Mixed, Protein Biosynthesis, Rats, Rats, Inbred F344, Major Histocompatibility Complex, Rats, Inbred BN genetics, Rats, Inbred Lew genetics, Rats, Inbred Strains genetics, Recombination, Genetic
- Abstract
Cell-mediated cytolytic (CMC) responses resulting from immunizations between rat strains considered to be RT1 (Ag-B) identical (LEW.B3:BN) are capable of detecting a membrane determinant(s) controlled by a locus linked to RT1, which has been designated Ag-L. The Ag-L gene region has been isolated in a recombinant line, tentatively designated as LEW.BN(2R), and has been assigned the RT1r5 haplotype. The data presented demonstrate that the genes responsible for MLR stimulation in the 2R strain are of LEW origin. In addition, LEW.B3 anti-BN CTL appear to recognize multiple specificities, only one of which is in the 2R strain. Some of the remaining specificities in BN may be the result of interactions between undetected genes that have been separated in the LEW.B3 and 2R strains.
- Published
- 1980
14. HLA A, B and DR typing in idiopathic dilated cardiomyopathy: a search for immune response factors.
- Author
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Anderson JL, Carlquist JF, Lutz JR, DeWitt CW, and Hammond EH
- Subjects
- ABO Blood-Group System immunology, Adult, Aged, Female, HLA-A Antigens, HLA-B Antigens, HLA-DR Antigens, Haploidy, Humans, Male, Middle Aged, Cardiomyopathy, Dilated immunology, HLA Antigens immunology, Heart Failure immunology, Histocompatibility Antigens Class II immunology, Histocompatibility Testing methods
- Abstract
Several autoimmune diseases have been associated with increased frequencies of various histocompatibility antigen (HLA) types that may be linked to immune response genes. Idiopathic dilated cardiomyopathy (IDC) has been proposed as a disease with autoimmune features, but HLA associations have not been evaluated. We performed HLA typing in 37 consecutive patients with IDC. Patients with habitual alcoholism were excluded. Results showed that no single HLA type could account for most cases; IDC is a genetically heterogeneous disease. However, uneven distributions were noted for certain types. Haplotype frequency of B27 was 0.145 in patients vs 0.033 in 5,726 local control subjects (p less than 0.001). Other A and B frequencies (except A2) were evenly distributed. HLA DR typing also revealed differences. The DR4 locus was present in 54% (19 of 35) of patients, vs 32% (26 of 82) of blood bank control subjects (p less than 0.02). The associated relative risk of DR4 was 2.2 and the etiologic fraction 0.29. Sex, disease chronicity, functional class, ejection fraction and biopsy evidence of myocarditis did not distinguish DR4-positive from DR4-negative patients, but they were older (54 +/- 12 vs 42 +/- 14 years, p less than 0.02). Of note, 68% were positive for DR4 or B27, or both. HLA DR6Y was underrepresented; it was present in 9% (3 of 35) of patients, vs 26% (21 of 82) of control subjects (p less than 0.04). The relative risk of DR6Y was 0.27 and the preventive fraction 0.19. These associations will require independent confirmation. However, they suggest that genetically determined immune response factors associated with HLA loci may play a role in pathogenesis in certain patients with IDC.
- Published
- 1984
- Full Text
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15. Efficacy of OKT3 retreatment for refractory cardiac allograft rejection.
- Author
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O'Connell JB, Renlund DG, Gay WA Jr, DeWitt CW, Hammond EH, Yowell RL, Jones KW, Karwande SV, Doty DB, and Bristow MR
- Subjects
- Adult, Antibodies, Monoclonal adverse effects, Female, Humans, Male, Middle Aged, T-Lymphocytes immunology, Transplantation, Homologous, Antibodies, Monoclonal therapeutic use, Graft Rejection, Heart Transplantation
- Abstract
Although OKT3 monoclonal antibody is a useful therapy for refractory cardiac allograft rejection, the use of OKT3 for prophylaxis may be limited by the potential of sensitization and subsequent loss of efficacy on retreatment. OKT3 was required for refractory rejection in 21 of 165 recipients transplanted between March 1985 and August 1988. Twelve of these patients had previously been exposed to OKT3, and the retreatment efficacy was evaluated. The study population averaged 42.1 +/- 15.3 years of age (mean +/- SEM) and had experienced 2 +/- 1 previous episodes of rejection. The prior episodes of rejection had been treated with pulse methylprednisolone and antithymocyte globulin, and in addition 3 patients (25%) also required a course of antilymphoblast globulin. Retreatment OKT3 for refractory rejection was required 120 +/- 94 days following transplantation. CD3+ lymphocytes were eliminated from the circulation within 24-48 hr in 11 of 12 patients, all of whom showed histologic improvement within the first week. Total resolution on the initial follow-up biopsy was noted in 9 (75%) during the course of therapy. Subsequent rejection episodes occurred in 9 (82%) of the survivors at 71 +/- 64 days. One-year survival was 83% in this vigorously rejecting patient population. Serious infections occurred within 3 months of therapy in 4 (36%). The side effects of OKT3 retreatment were similar to those seen with first exposure and did not require OKT3 discontinuation. Thus OKT3 may be administered with success in most patients who have previously been exposed to it.
- Published
- 1989
- Full Text
- View/download PDF
16. HLA and recurrent episodic arthropathy associated with rubella vaccination.
- Author
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Griffiths MM, Spruance SL, Ogra PL, Thompson GR, and DeWitt CW
- Subjects
- Adolescent, Adult, Child, Child, Preschool, Chromosome Mapping, Humans, Infant, Joint Diseases genetics, Joint Diseases immunology, Recurrence, Rubella prevention & control, HLA Antigens, Histocompatibility Antigens, Joint Diseases etiology, Rubella Vaccine adverse effects
- Abstract
The frequencies of 21 HLA antigens in 33 patients who developed recurrent, episodic arthropathy after receiving the HPV-77 DK-12 rubella vaccine have been determined and compared with those of a control population. Trends toward increased frequencies of HLA antigens B12 (P = 0.02) and B14 (P = 0.04) and of the haplotype A2, B12 (P = 0.01) did not reach significance when corrections for the number of antigen determinations were included in the statistical analysis. These data show that the syndrome of recurrent arthropathy following rubella vaccination is genetically distinct from the connective tissue diseases associated with HLA-B27.
- Published
- 1977
- Full Text
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17. Immunogenetic control of experimental collagen-induced arthritis in rats. II. ECIA susceptibility and immune response to type II collagen (CALF) are linked to RT1.
- Author
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Griffiths MM and DeWitt CW
- Subjects
- Animals, Antibody Formation, Arthritis chemically induced, Cattle, Collagen adverse effects, Collagen immunology, Phenotype, Rats, Arthritis genetics, Arthritis immunology, Major Histocompatibility Complex, Rats, Inbred Strains genetics
- Abstract
The segregation of genes controlling ECIA susceptibility and the level of immune response to native calf type II collagen were determined in the F2 progeny of matings between WF (RT1u/u; ECIA-susceptible; high responders) and LEW.B3 (RT1n/n; ECIA-resistant; low to intermediate responders). RT1n/n F2 progeny showed resistance to ECIA, low skin test reactivity to type II collagen and intermediate levels of IgG anti-collagen antibodies (-log2 of 6.2 +/- 2.6; mean +/- SD, n = 10). RT1u/u and RT1u/n F2 progeny were susceptible to ECIA and were high responders to type II collagen by skin testing and IgG antibody titres (-log2 of 12.1 +/- 1.3, mean +/- SD, n = 26). Although all rats that developed arthritis were also high responders to type II collagen one group of immature F2 progeny, RT1u/u and RT1u/n, showed high anti-collagen immune responses in the absence of detectable arthritis. The data indicate that genes linked to RT1.A control susceptibility to ECIA and at least part of the immune response to native calf type II collagen in WF and LEW.B3 rats.
- Published
- 1981
- Full Text
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18. Rat cell surface antigens. I. Isolation and partial characterization of an Ag-B antigen.
- Author
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Callahan GN and Dewitt CW
- Subjects
- Amino Acids analysis, Animals, Cell Membrane immunology, Chromatography, Affinity, Electrophoresis, Polyacrylamide Gel, Epitopes, Iodine Radioisotopes, Molecular Weight, Rats, Histocompatibility Antigens isolation & purification, Lymphocytes immunology, Rats, Inbred Strains immunology
- Abstract
Rat major histocompatibility or Ag-B antigen was isolated from soluble extracts of lymphoid cells by affinity chromatography. The purified antigen was shown in SDS gel electrophoresis to have a molecular weight of 30,000 to 35,000 daltons. In addition, amino acid composition was found to resemble, generally, that of HL-A and H-2 antigens. It thus appears that the demonstrated homology between H-2 and HL-A extends also to Ag-B.
- Published
- 1975
19. Analysis of cytotoxic effector cell populations by kinetic and monolayer adsorption techniques.
- Author
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Lynch DH and DeWitt CW
- Subjects
- Animals, Binding Sites, Cell Adhesion, Cells, Cultured, Clone Cells immunology, Immunosorbent Techniques, Kinetics, Lymphocytes immunology, Rats, Rats, Inbred BN, Rats, Inbred Lew, Time Factors, Cytotoxicity, Immunologic
- Abstract
Cytolytically active lymphocytes were generated by immunizations between rat strains and evaluated by both kinetic and monolayer adsorption techniques. Kinetic analysis yields two values (Ka and Vmax), which are characteristic of interactions between individual effector and target cell populations. The Ka values this obtained correlate with the quantitative level of adsorption of CTL onto cellular monolayers, and we conclude that Ka is a measure of the binding avidity of effector and target cells.
- Published
- 1980
20. Ag-F: serological and genetic identification of a new locus in the rat governing lymphocyte membrane antigens.
- Author
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DeWitt CW and MCCullough M
- Subjects
- Absorption, Animals, Antibody Formation, Antibody Specificity, Cross Reactions, Cytotoxicity Tests, Immunologic, Female, Genetic Linkage, Humans, Immune Sera, Lymph Nodes cytology, Male, Polymorphism, Genetic, Rats, Rats, Inbred BN, Rats, Inbred F344, Rats, Inbred Lew, Rats, Inbred Strains, Recombination, Genetic, Cell Membrane immunology, Histocompatibility Antigens isolation & purification, Lymphocytes immunology
- Abstract
A new genetic locus in the rat (Ag-F) is described. It controls expression of lymphocyte membrane antigens as determined by allospecific cytotoxic antibody. It is linked by approximately two recombination units to the gene for albinism and is therefore in linkage group I. It is suggested that Ag-F is the homologue in the rat of mouse H-1. It appears to be highly polymorphic and yields antigens which are highly cross reactive serologically. Disparity at Af-F is the probable cause of alloantibody responses attributable to reciprocal immunization between the Lewis and Fischer strains.
- Published
- 1975
21. Lymphocyte membrane antigens in the rat: two serologically determined loci at the MHC and three new minor histocompatibility loci.
- Author
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DeWitt CW and McCullough M
- Subjects
- Animals, Cell Membrane immunology, Chromosome Mapping, Cross Reactions, Immune Sera analysis, Rats, Rats, Inbred ACI, Rats, Inbred BN, Rats, Inbred BUF, Rats, Inbred F344, Rats, Inbred Lew, Rats, Inbred WF, Histocompatibility Antigens, Lymphocytes immunology
- Published
- 1977
22. The effect of neonatal thymectomy on antibody responses to histocompatibility antigens in the rat.
- Author
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Miller CL and DeWitt CW
- Subjects
- Animals, Animals, Newborn, Antibodies analysis, Antigens, Centrifugation, Density Gradient, Chromium Radioisotopes, Cytotoxicity Tests, Immunologic, Female, Fibroblasts immunology, Immunoglobulin M analysis, Lymph Nodes cytology, Lymphocytes immunology, Male, Rats, Rats, Inbred Strains, Spleen cytology, Sucrose, Thymectomy, Thymus Gland cytology, Antibody Formation, Histocompatibility Antigens, Thymus Gland immunology
- Published
- 1974
- Full Text
- View/download PDF
23. Further studies on the use of mouse epidermal cells for the in vitro induction and detection of cell-mediated cytotoxicity.
- Author
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Esplin DG, Steinmuller D, and DeWitt CW
- Subjects
- Animals, Cell Count, Cells, Cultured, Cytotoxicity Tests, Immunologic, H-2 Antigens, Immunity, Cellular drug effects, In Vitro Techniques, Lymphocytes immunology, Male, Mice, Mice, Inbred Strains, Species Specificity, Trypsin pharmacology, Cytotoxicity, Immunologic drug effects, Skin immunology
- Published
- 1979
- Full Text
- View/download PDF
24. Rat cell surface antigens. II. Isolation of a minor histocompatibility antigen.
- Author
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Callahan GN and Dewitt CW
- Subjects
- Animals, Cell Membrane immunology, Electrophoresis, Polyacrylamide Gel, Iodine Radioisotopes, Molecular Weight, Histocompatibility Antigens isolation & purification, Lymphocytes immunology, Rats immunology
- Abstract
A cell surface antigen was isolated from soluble extracts of rat lymphoid cells. Molecular weight of the purified antigen was estimated by SDS gel electrophoresis to be 10 to 20,000 daltons. Physical as well as immunologic properties of this antigen do not resemble those of any known antigenic product of the major histocompatibility locus of the rat. It is therefore proposed that it is a rat minor histocompatibility antigen.
- Published
- 1975
25. False-positive antibody tests for human immunodeficiency virus in transplant patients with antilymphocyte antibodies.
- Author
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Wittwer CT, Smith AM, Ash KO, and DeWitt CW
- Subjects
- Cross Reactions, False Positive Reactions, HIV Antibodies, Humans, Lymphocytes immunology, Reagent Kits, Diagnostic, Antibodies, Viral analysis, HIV immunology, Immunoenzyme Techniques, Kidney Diseases immunology, Kidney Transplantation
- Published
- 1987
26. Isolation and partial characterization of AgF-1:a rat lymphocyte membrane antigen.
- Author
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Williams PB and DeWitt CW
- Subjects
- Animals, Antigens analysis, Cell Membrane immunology, Detergents, Electrophoresis, Polyacrylamide Gel, Polyethylene Glycols pharmacology, Rats, Rats, Inbred Lew, Sodium Dodecyl Sulfate, Tissue Extracts immunology, Antigens isolation & purification, Lymphocytes immunology
- Abstract
A genetically defined, serologically identified antigen of the rat lymphocyte membrane (AgF-1) has been isolated. Viable spleen and lymph node cells, prepared by Ficoll-Hypaque density centrifugation from Fischer rats, were radioiodinated with soluble lactoperoxidase. Extracts obtained with Nonidet P-40 were shown to contain numerous radiolabeled proteins including cell-surface globulin. AgF-1 was isolated from these extracts by precipitation with a highly specific alloantibody in conjunction with xenospecific anti-globulin antibody and polyethylene glycol (PEG). The use of PEG greatly increased the efficiency of the double antibody technique. The putative antigenic peak was eluted from sodium dodecyl sulfate polyacrylamide gels (SDS-PAGE) and specific antigenic activity was recovered. Removal of the SDS from these eluates was achieved by equilibration with urea and passage over an anion exchange resin. Renaturation, as evidenced by specific inhibition of complement-mediated cytotoxicity, occurred upon the removal of urea by dialysis. The m.w. of the purified antigen was estimated to be 35 to 40,000 daltons by SDS-PAGE and was unaffected by reduction with 2-mercaptoethanol. Amino acid composition was roughly similar to those reported for the major histocompatibility antigens of the rat and other species.
- Published
- 1976
27. The quantitative flow cytometric plasma OKT3 assay. Its potential application in cardiac transplantation.
- Author
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Wittwer CT, Knape WA, Bristow MR, Gilbert EM, Renlund DG, O'Connell JB, and DeWitt CW
- Subjects
- Antibodies, Monoclonal therapeutic use, Antigens, Differentiation, T-Lymphocyte analysis, CD3 Complex, Humans, Receptors, Antigen, T-Cell analysis, Antibodies, Monoclonal analysis, Heart Transplantation, Immunosuppression Therapy methods
- Published
- 1989
28. OKT3 therapy as a cause of high panel-reactive antibodies in serum using standard microcytotoxicity techniques.
- Author
-
Wittwer CT, Bristow MR, Gilbert EM, Renlund DG, O'Connell JB, and DeWitt CW
- Subjects
- Animals, Antigen-Antibody Reactions, Graft Rejection, Humans, Immunosuppressive Agents therapeutic use, Mice, Antibodies, Monoclonal therapeutic use, Cytotoxicity Tests, Immunologic methods, Heart Transplantation, T-Lymphocytes immunology
- Published
- 1988
- Full Text
- View/download PDF
29. The immunobiology of ultraviolet-radiation carcinogenesis.
- Author
-
Daynes RA, Burnham DK, Dewitt CW, Roberts LK, and Krueger GG
- Subjects
- Animals, Humans, Immunity, Cellular, Inflammation, Lymphocytes immunology, Lymphocytes radiation effects, Skin Neoplasms etiology, Skin Neoplasms immunology, Neoplasms, Experimental immunology, Neoplasms, Radiation-Induced immunology, Ultraviolet Rays
- Published
- 1985
30. Genetic control of collagen-induced arthritis in rats: the immune response to type II collagen among susceptible and resistant strains and evidence for multiple gene control.
- Author
-
Griffiths MM and DeWitt CW
- Subjects
- Animals, Arthritis immunology, Crosses, Genetic, Epitopes genetics, Female, Histocompatibility Antigens immunology, Hypersensitivity, Delayed genetics, Hypersensitivity, Delayed immunology, Immunity, Innate, Immunoglobulin G biosynthesis, Male, Rats, Rats, Inbred ACI, Rats, Inbred BN, Rats, Inbred BUF, Rats, Inbred F344, Rats, Inbred Lew, Rats, Inbred WF, Species Specificity, Arthritis genetics, Collagen immunology, Genes, MHC Class II, Histocompatibility Antigens genetics
- Abstract
We evaluated the cellular and humoral immune response to type II collagen and the relative susceptibility to type II collagen-induced arthritis (CIA) in 14 inbred rat strains representing six RT1 specificities and including four congenic strain pairs differing only at RT1, by using a standard protocol with native calf type II collagen as the immunogen: WF(RT1u) was a high responder and susceptible; RT1c , RT1a , and RT1l strains were intermediate responders and, on a strain basis, were variably susceptible or resistant; RT1b and RT1n strains were low responders and resistant to CIA. An intermediate to high immune response to type II collagen, although associated with CIA, was not sufficient for the induction of clinical arthritis. A high degree of cross-reactivity between calf and rat type II collagen was found. No selective, antigen-specific decrease in immune response to rat type II collagen as compared to calf type II collagen was found in the resistant strains. In six strains, resistance correlated with the expression of public Ia antigens cross-reactive with the public Ia antigens of BN. The non-MHC-linked BN genome also exerted a suppressive effect on the incidence and severity of CIA in strains carrying collagen-responder and CIA-susceptible RT1 alleles. Together, the data show that CIA in rats is under the control of multiple genes, both RT1-linked and nonlinked .
- Published
- 1984
31. Strong and weak immune responses across the same major histocompatibility barrier in rats.
- Author
-
Goodnight JE, Coleman DA, and Dewitt CW
- Abstract
Inbred rat strains, Fischer 344 (F-344) and Lewis (LEW), share the serologicalAg-Bl allele and react very weakly in mixed lymphocyte culture (MLC). Despite this apparent identity atAg-B, these strains differ markedly in their immune responses to anAg-B disparate third strain Marshall 520 (M-520) (Ag-B6). F-344 recipients allowed M-520 heart grafts an extended survival, whereas LEW recipients rejected them rapidly. F-344 and M-520 showed a weak response in MLC in contrast to a strong response for LEW and M-520. F-344 produced antisera in response to injection of M-520 cells that had a relatively high antibody titer but low cytotoxic activity. F-344 responded to another strain, Buffalo (BUF) (alsoAg-B6), in a similar fashion. F-344 apparently can produce a strong allogeneic response, as it was able to rapidly reject heart grafts from (LEW x Brown-Norway) F(1) donors (LBN) (Ag-B 1/3). The low response of F-344 to M-520 probably was not due to shared antigens between the two strains because M-520 heart grafts underwent rapid rejection in LEW hosts highly tolerant to F-344. To explain the contrasting response of F-344 and LEW to theAg-B6 disparity, we propose that it is controlled by an immune-response gene(s); that F-344 has a low-responding allele and LEW has a high-responding allele. The data do not reveal a location for this proposed gene. The high-responding allele appears to be dominant, as M-520 hearts were rejected rapidly by (F-344 x LEW) F(1) recipients.
- Published
- 1978
- Full Text
- View/download PDF
32. Genetic identification of a locus linked to the rat MHC that codes for a membrane antigen detectable with cytotoxic lymphocytes.
- Author
-
Lynch DH and Dewitt CW
- Subjects
- Animals, Binding, Competitive, Histocompatibility Antigens genetics, Immune Sera pharmacology, Lymphocyte Culture Test, Mixed, Rats, Rats, Inbred ACI, Rats, Inbred BN, Rats, Inbred BUF, Rats, Inbred F344, Rats, Inbred Lew, Recombination, Genetic, Skin Transplantation, Antigens, Surface genetics, Chromosome Mapping, Cytotoxicity, Immunologic, Lymphocytes immunology, Major Histocompatibility Complex
- Abstract
Cell-mediated cytolytic (CMC) responses resulted from immunizations between rat strains purported to be identical at Ag-B, the major histocompatibility complex (MHC), but differing at other loci not linked to Ag-B. In vivo-priming followed by secondary in vitro stimulation was required to generate a measurable CMC response as determined by a 51Cr-release assay. Neither in vivo nor in vitro stimulation alone was adequate. The CMC responses generated in a strain combination considered Ag-B identical (LEW . B3:BN) were specific for a determinant controlled by a gene linked to Ag-B, which has been designated Ag-L. The CMC response appears not to be restricted to sygeneity at Ag-B. In addition, the data presented demonstrate a recombinant between Ag-B and Ag-L, and suggest that the gene has failed to transfer with the MHC during the isolation of the LEW . B3 and F-344 . B3 congenic strains.
- Published
- 1978
33. Modulation of collagen-induced arthritis in rats by non-RT1-linked genes.
- Author
-
Griffiths MM and DeWitt CW
- Subjects
- Animals, Arthritis, Experimental genetics, Crosses, Genetic, Female, Genetic Linkage, Hypersensitivity, Delayed genetics, Hypersensitivity, Delayed immunology, Immunity, Innate, Male, Rats, Rats, Inbred BN, Sex Characteristics, Arthritis immunology, Arthritis, Experimental immunology, Collagen immunology, Genes, MHC Class II, Histocompatibility Antigens genetics
- Abstract
An immunogenetic analysis of the progeny of F1, F2, and (F1 x parental strain) test cross-matings between the CIA-susceptible DA(RT1av1) and the CIA-resistant BN(RT1n) rat strains was performed. Hybrid progeny were tested for susceptibility to CIA as induced by native calf type II collagen, and for immune response to native rat and calf type II collagens. The results show a minimum of one non-RT1-linked gene which modifies susceptibility to CIA in RT1a/a hybrid progeny. These hybrids have anti-collagen immune responses equivalent to those of the parental DA strain as measured by skin testing and IgG antibody titers. An affect of sex hormones on susceptibility to CIA is indicated, because hybrid females were more susceptible than were hybrid males of equivalent RT1 allotypes.
- Published
- 1984
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