Papers by Robert Winchester
AIDS Research and Human Retroviruses, 1996
and Participants in the LONG-TERM SURVIVOR PROJECT* INTRODUCTION: STUDY BACKGROUND A substantial ... more and Participants in the LONG-TERM SURVIVOR PROJECT* INTRODUCTION: STUDY BACKGROUND A substantial number of children who were infected perinatally with human immunodeficiency virus type 1 (HIV-1) have survived early childhood and are now approaching or have entered adolescence. These children fall into two broad categories: those who remain asymptomatic, and those who survive despite the development of significant HIV-1-related symptoms. As the population of perinatally infected children has matured, the initial assumption that perinatal HIV-1 infection inevitably followed a rapid course to mortality has given way to clearer understanding of the course of disease progression. More recent studies have extended our knowledge of the survival of perinatally infected children,1-3 one of which2 indicated that over 49.5% of these children survive for more than 9 years. In addition, it was reported by Mary Glen Fowler at a previous Pédiatrie AIDS Foundation-sponsored workshop (Miami, 1993) that of 422 perinatally infected children in an AIDS Clinical Trial Group (ACTG) cohort, 156 (37%) were more than 9 years old. In an attempt to determine what factors might contribute to long-term survival in perinatally infected children the Pédiatrie AIDS Foundation sponsored a collaborative cross-sectional study among five university-affiliated medical centers (Drs.
The Journal of Immunology
Whether homotypic neutrophil aggregation depends on the quantitative increase of gp165/95 molecul... more Whether homotypic neutrophil aggregation depends on the quantitative increase of gp165/95 molecules (Mac 1, CR3) recruited to the cell surface during activation was studied using mAb of the CD11b group that recognize distinct epitopes encoded by the alpha-subunit of this glycoprotein. After the addition of antibody MN41, neutrophils did not aggregate in response to a chemoattractant, FMLP. Blockade of preexisting surface gp165/95 by mAb MN41, followed by removal of the excess antibody from the mixture, was used to show that the molecules of gp165/95 newly expressed in response to stimulation by a chemoattractant were incapable of effectively mediating the induced cell-cell interactions of aggregation. Flow cytometry studies confirmed that binding of unlabeled antibody MN41 did not block further increases in surface expression of gp165/95 after stimulation with FMLP. These data suggest that molecules of gp165/95 exhibit two functionally distinct forms, one, present on the surface of ...
Advances in Experimental Medicine and Biology, 1982
Cell surface antigenic analysis using 10 different monoclonal antibodies indicates the following.... more Cell surface antigenic analysis using 10 different monoclonal antibodies indicates the following. (a) The membrane antigenic phenotype of various members of the mononuclear phagocyte lineage is characterized by the co-expression of multiple but distinct antigenic determinants. (b) The maturational evolution of the cells is associated with qualitative and/or quantitative modifications of cell surface antigens resulting in the definition of different phenotypic entities. (c) In vitro culture of blood monocytes is accompanied by significant modulation of these antigens. In particular, the expression of MoP-15 appears to be modulated following in vitro activation. (d) The occurrence of these antigens on various normal and leukemic cell populations provides a basis for the establishment of defined patterns of antigenic expression corresponding to successive maturational states of the human mononuclear phagocyte cell lineage. (e) The reactivity of AML cells with various antibodies defines patterns of antigen expression related to the degree of leukemic cell maturity. These patterns change during culture.
Springer Seminars in Immunopathology, 1981
Studies on the population of patients with rheumatoid arthritis and families with multiple cases ... more Studies on the population of patients with rheumatoid arthritis and families with multiple cases of rheumatoid arthritis have provided definite evidence that susceptibility to the disease is determined both by genetic factors associated with alleles of the major histocompatibility complex as well as environmental factors. The development of seropositive, but not seronegative rheumatoid arthritis is associated with the presence in an individual of the Ia alloantigen HLA-DR4. This association is common to all major ethnic groups. Some evidence exists that this association is stronger in patients that have more severe disease but this fact requires further study. The fraction of the seropositive patients with rheumatoid arthritis that lack HLA-DR4 has not been well characterized. The occurrence of certain untoward side effects of therapy is influenced by the presence of HLA-DR2 or HLA-DR3. Family studies emphasize the association with HLA-DR4, and indicate that the disease has a dominant mode of inheritance with partial penetrance. The inheritance of susceptibility appeared, at least in some families, to be primarily associated with the inheritance of HLA-DR4 itself and not well explained by a hypothetical disease susceptibility gene present at low frequency and associated in linkage disequilibrium with a HLA-DR4 marker. However, in others different mechanisms appeared more likely. A model of two MHC genes involved in influencing disease susceptibility is postulated. Speculations concerning the primary disease mechanism are presented involving abnormalities of IR genes, general immune regulation, and factors outside of the immune system.
Annals of Internal Medicine, 1979
... David N. Romond, and Henry Drink-er for doing the synovectomies and Dr. Nicholas H. Bartenhag... more ... David N. Romond, and Henry Drink-er for doing the synovectomies and Dr. Nicholas H. Bartenhagen for helping with patient care; Dr. Marilena Fotino for identifying HLA antigens in certain patients; Ms. Stella Cretella for expert laboratory assistance; and Ms. Elise DeSanna for ...
The Journal of experimental medicine, 1975
A group of alloantibodies are found in pregnancy sera which react with antigens present on B lymp... more A group of alloantibodies are found in pregnancy sera which react with antigens present on B lymphocytes and monocytes but are not detectable on the vast majority of unstimulated T cells. This specificity distinguishes them from HL-A antibodies which react with both cell types. They were readily recognized through indirect fluorescent antibody analysis by employing the combination of B-cell lymphoid lines and normal peripheral blood T cells. Different sera gave a variety of patterns of reactivity with a panel of 11 lymphoid lines. Similar differential patterns were also observed with normal B cells from different individuals particularly after concentrating the B cells. The antibodies were also cytotoxic to B cells and this procedure gave parallel results to the fluorescence method. The pattern of reactions obtained indicated a very heterogeneous system similar to that for HL-A. Special study of certain of the sera provided evidence that the lymphocyte-defined determinants of the mi...
The Journal of experimental medicine, 1980
Two distinct types of Ia-positive T cells have been described. One type represents a blastoid T c... more Two distinct types of Ia-positive T cells have been described. One type represents a blastoid T cell responding from stimulation by mitogens, antigens, and in allogeneic and autologous mixed lymphocyte culture reactions. This is a large cell that is strongly positive for Ia antigens as measured by a variety of different antisera. The other general type is a smaller cell with a lower expression of Ia antigens that is found at low levels in normal peripheral blood and is markedly elevated in various pathological states. It also rises rapidly after inoculation with tetanus toxoid and PPD in sensitized individuals. This cell does not incorporate thymidine and is enriched in the Tgamma fraction; it can be markedly concentrated from normal lymphocytes, and current evidence indicates that it is a T cell. The marked elevation of this cell in the blood of patients with rheumatoid arthritis is of special interest. Considerable evidence indicates that, at least in certain instances, the Ia ant...
The Journal of Experimental Medicine, 1974
A marked homogeneity of the light chains was observed in an analysis of 17 IgM proteins with anti... more A marked homogeneity of the light chains was observed in an analysis of 17 IgM proteins with anti-γ-globulin activity. The V region subgroups of the light chains were determined by both sequence and antigenic analysis. The latter procedure permitted large scale screening for comparisons with control proteins. The two methods showed general agreement in the determination of Kappa III proteins; all proteins positive by antigenic analysis were also positive by sequence but exceptions were noted in the opposite direction. The anti-γ-globulins showed by antigenic analysis a 92% incidence of VK III light chains as compared to an incidence of 27% among 81 control proteins without this activity. A similar selection was observed for an antigen (VK III b) which subdivided the kappa III proteins. The major Wa group of anti-γ-globulins which had been delineated previously on the basis of cross-idiotypic specificity was primarily responsible for the special light-chain selection. All the protein...
Immunobiology of HLA, 1989
Previous studies by Amar et al (1) indicated that the risk for pemphigus vulgaris (PV) is prefere... more Previous studies by Amar et al (1) indicated that the risk for pemphigus vulgaris (PV) is preferentially associated with the Dw10 subtype of DR4, as well as with DRw6 in the Israeli population. This raised the possibility that third hypervariable (HVIII) region sequences, which are identical in DR4, Dw10 (2), and DRw6a (3) DRβ1 chains, might constitute a disease susceptibility epitope.
The Journal of Immunology
Summary Certain cases of chronic lymphocytic leukemia possess monoclonal bands in the serum. Idio... more Summary Certain cases of chronic lymphocytic leukemia possess monoclonal bands in the serum. Idiotypic antibodies to the isolated IgM protein of one such case demonstrated that the leukemic lymphocytes carried the identical specificity on their lymphocytes. Both the lymphocyte IgM and the IgD possessed this same specificity. This was demonstrated best through the use of rhodamine-conjugated Fab fragments of IgM- and IgD-specific antisera which were both capped by the idiotypic antiserum.
Current Topics in Developmental Biology
Publisher Summary This chapter focuses on the evidence for the presence of Ia antigens on normal ... more Publisher Summary This chapter focuses on the evidence for the presence of Ia antigens on normal and malignant hematopoietic cells and their role as a surface marker related to differentiation events. It also discusses the occurrence of Ia antigens on certain solid tumors such as malignant melanoma. Ia antigens are selectively distributed as dominant glycoproteins on a limited number of cells. They are restricted both to certain cell lineages and to particular stages of differentiation within the cell series. Yet, at least in the T and B lymphocytes, Ia antigens can be induced with appropriate stimulation and their expression appears to be under flexible control. The period in the differentiation sequence in marrow cells when the Ia antigens are a dominant membrane component is the time when the maximal control of proliferation would be anticipated to occur, suggesting a role for the Ia antigens in this process. This raises the question of interesting parallels between the aspects of the immune response and events in the early stages of hematopoiesis.
Clinics in Rheumatic Diseases, 1985
Since the first description of human leukocyte agglutination antibodies, knowledge of the MHC, pa... more Since the first description of human leukocyte agglutination antibodies, knowledge of the MHC, particularly the Ia region, has grown immensely and it is now recognized as a major polymorphic multigene family involved in the regulation of immune response and disease susceptibility. This review examined the hypothesis that there is another level of complexity within the Ia system, beyond multiple loci and allelic series, that involves specific epitopes as the functionally important components of the Ia molecule. Certain of these epitopes are likely to be responsible for the regulation of immune responses and susceptibility to certain autoimmune diseases such as rheumatoid arthritis (RA). Evidence was presented that certain monoclonal antibodies recognize epitopes found in a significantly more positive association with susceptibility to RA than available markers such as DR4. Biochemical characterization of the Ia molecules bearing this epitope revealed that the same epitope was present on two different molecules. The possibility was considered that such epitopes are closely related but not identical to Ia determinants that are primarily involved in producing the abnormal immune state characterizing those with RA.
Advances in Immunology, 1980
Publisher Summary This chapter discusses conceptual and technical developments in the field of hu... more Publisher Summary This chapter discusses conceptual and technical developments in the field of human Ia antigens by describing the chemical structure and immunologic relationship to their murine counterparts. The distribution of human Ia antigens is limited primarily to the B lymphocyte series, stimulated T cells, and stem and precursor hematopoietic cells, suggestive of both cell type and differentiation specificity. The association of certain Ia antigens with susceptibility or resistance to a variety of diseases, including rheumatoid arthritis, systemic lupus erythematosus, idiopathic thrombocytopenic purpura, rheumatic fever, multiple sclerosis, and diabetes, provides both a valuable clinical predictive measure and a lead for the future study of pathogenetic factors possibly related to the particular Ia genes involved. The chapter examines the Ia antigens from two principal perspectives: (1) as membrane components related to differentiation, and (2) as part of a genetically intricate system of molecules bearing alloantigens that have relevance to susceptibility to certain diseases. Three types of antisera are used to detect Ia antigens: alloantisera, heteroantisera raised in rabbits or similar species, and monoclonal hybridoma reagents. It is apparent that the relationship of diseases to the Ia alloantigens is an intricate one and is likely to involve several distinct factors.
The Journal of Experimental Medicine, 1971
γG globulin complexed in an unusual form has been demonstrated in the serum of many patients with... more γG globulin complexed in an unusual form has been demonstrated in the serum of many patients with rheumatoid arthritis. Such complexes have been detected and isolated principally through precipitation reactions with monoclonal γM rheumatoid factors. These monoclonal rheumatoid factors exhibited a greater sensitivity to react with small complexes or aggregates of γ-globulin than polyclonal rheumatoid factor from rheumatoid arthritis sera or isolated C1q. The serum complexes consisted in large part of high molecular weight but acid-dissociable 7S γG globulin molecules They however differed from the complexes in the joint fluid by not yielding precipitates with C1q and were not found in association with evidence of marked serum complement fixation or activation. A small number of systemic lupus erythematosus sera, primarily those forming cryoprecipitates, also gave reactions with monoclonal rheumatoid factor. Sera from patients with a variety of nonrheumatic diseases gave a low inciden...
Journal of Experimental Medicine, 1971
Precipitin reactions of C1q in gel diffusion proved useful in detecting unknown complexes contain... more Precipitin reactions of C1q in gel diffusion proved useful in detecting unknown complexes containing γ-globulin in the sera of patients with SLE. Using this method low molecular weight C1q reactants also have been detected in a number of sera from patients with SLE as well as other diseases. Both the circulating complexes and the unidentified low molecular weight reactants are associated with disease activity and in vivo complement depression. In some sera from patients with SLE, circulating complexes as detectable by C1q precipitation were closely associated with cryoprecipitins and an active nephritic process. Evidence is presented that both rheumatoid factors and C1q interact with circulating complexes in these patients and that the interaction is related to cryoprecipitation. The demonstration of the same rheumatoid factors in the cryoprecipitates and in the renal glomerular deposits suggests that rheumatoid factors have a special significance in the presence of circulating comp...
Immunobiology of HLA, 1989
Five human monoclonal antibodies (MAbs) were derived from a single polytransfused patient awaitin... more Five human monoclonal antibodies (MAbs) were derived from a single polytransfused patient awaiting renal transplantation. In microcytotoxicity assays, the patient’s serum displayed strong positive reactions against >90% of a panel of cells representing the known human leukocyte antigen (HLA) specificities. The donor’s (RR, HLA phenotype: Al, A9; B35, B37; DR3, DR4; DRw52, DRw53; DQw2, DQw3) peripheral blood lymphocytes (PBLs) were infected with Epstein-Barr (EBV), cloned, and supernatants of the virustransformed cultures were screened for the presence of IgG antilymphocyte reactivity utilizing an ELISA method. Positive cultures were recloned and fused with the human/mouse heteromyeloma SHM.
Bulletin on the rheumatic diseases, 1994
The Journal of experimental medicine, 1971
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Papers by Robert Winchester