Erythema multiforme: report of two cases and speculation on immune mechanisms involved in the pathogenesis.
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Adult↗
Biomedical subjects
R A Good
Publications and source records attributed to R A Good.
Thymic activity in severe combined immunodeficiency diseases.
Thymic function was evaluated by quantitation of circulating thymic factor in patients with several forms of severe infantile immunodeficiency diseases. Direct quantitation of thymic factor in serum of patients with severe combined immunodeficiency revealed heterogeneity of this syndrome by this parameter, as was also shown by study of susceptibility of the marrow cells to differentiation in vitro. Thymic factor was not detectable in one patient with severe combined immunodeficiency, but was present in normal or near-normal concentrations in three others. Circulating levels of this hormonal activity were also not detectable in a patient with DiGeorge athymic syndrome. Following marrow or fetal liver transplantation, which corrected the severe combined immunodeficiency thymic factor levels either increased slightly or did not change appreciably. Fetal thymic transplantation, which together with fetal liver transplantation corrected the immunodeficiency in one patient with severe combined immunodeficiency, was associated with increase of thymic factor to normal levels. Fetal thymus transplantation alone, which was employed to correct the immunodeficiency of DiGeorge athymic syndrome, caused an increase in thymic factor activity to normal or near normal levels in this patient.
Bone Marrow Cells↗
Suppression of immunoglobulin synthesis and secretion by peripheral blood lymphocytes from normal donors.
Concanavalin A (Con A)-treated peripheral blood lymphocytes from healthy volunteer donors have been shown to suppress proliferative responses associated with thymus-derived lymphocytes (T-cells). The present investigations demonstrate that peripheral blood lymphocytes incubated with Con A for 48 hr can abrogate pokeweed mitogen-stimulated differentiation of bone-marrow-derived (B) lymphocytes to immunoglobulin-synthesizing and -secreting plasma cells. This effect was manifested when washed Con A-treated peripheral blood lymphocytes were added to pokeweed mitogen-stimulated cocultures containing fresh autologous or allogeneic mononuclear cells, and it did not appear to involve cytotoxicity. Parallel control cultures consisting of mononuclear leukocytes incubated for 48 hr in the absence of Con A also had immunoglobulin suppressor activity in mixing experiments. This effect, however, was most pronounced when preincubated cells were added to fresh autologous pokeweed mitogen-stimulated peripheral blood lymphocytes. Cell mixtures containing peripheral blood lymphocytes demonstrated a spectrum of immunoregulatory effects ranging from suppression to enhancement of pokeweed mitogen-stimulated immunoglobulin synthesis and secretion. Several functional subclasses of suppressor cells that reflect varying levels of specific activity have thus been demonstrated in human beings. Moreover, a degree of genetic identity appears to be required for the expression of "weak" immunoregulatory influences.
Concanavalin A↗
Bioassay determinations of thymopoietin and thymic hormone levels in human plasma.
Thymopoietin is a thymic hormone that induces differentiation of thymocytes from precursor cells which arise in hemopoietic tissues. This paper describes a sensitive in vitro assay for the induction of Thy 1.2 antigen on null lymphocytes from germ-free athymic (nu/nu) mice. The sensitivity and specificity of the bioassay were increased by adding high concentrations of ubiquitin (a nonspecific inducer) to the induction incubations. The bioassay was sufficiently sensitive to detect thymopoietin at less than 0.25 ng/ml. A dose-response relationship was shown between thymopoietin concentration and the percentage of cells induced to express Thy 1.2 antigen. When normal human plasma was assayed, induction was registered with activity corresponding to thymopoietin at greater than 1 ng/ml in plasma from infants or young adults. Activities in the thymopoietin range of 0.25 ng/ml were registered with plasma from healthy subjects over 50 years of age. Thymectomy was followed by loss of this inductive activity from the plasma. This bioassay permits clinical studies on T (thymus-derived) cell inducers released by the human thymus into the circulation.
Adult↗
Rationale for combined use of fetal liver and thymus for immunological reconstitution in patients with variants of severe combined immunodeficiency.
Bone marrow cells from a patient with severe combined immunodeficiency were studied in vitro for thymus-dependent lymphocyte (T cell) differentiation by using, at varying times, thymic epithelial monolayers and culture supernatants, thymopoietin, ubiquitin, and thymic extract as inducing agents. On initial evaluation, with thymopoietin or human thymic extract, only a partial differentiation of marrow cells was achieved into cells bearing the human T cell antigenicity without the capacity to form rosettes with sheep erythrocytes, suggesting that the stem cells were defective. Two fetal liver transplantations aimed at reconstitution were unsuccessful, despite evidence of chimerism. Induction studies at that time demonstrated rosetting capacity (with sheep erythrocytes) of the patient's bone marrow cells after coculture with thymic epithelial monolayers but not with their supernatants. An 18-week fetal thymus (irradiated) was then transplanted, but the transplantation was unsuccessful and no clear evidence of chimerism was demonstrated. Subsequently, transplantation of another fetal liver resulted in chimerism and immunologic reconstitution. Serum thymic factor activity rose from 1:2 before transplantation to 1:16 after reconstitution. The combined use of fetal thymus and liver may provide effective immunological reconstitution in some variants of severe combined immunodeficiency.
Bone Marrow↗
Sequential stages of human T lymphocyte differentiation.
Induction of thymus-dependent lymphocyte (T cell) differentiation was performed in vitro with thymic factors as inducers. T cell precursors from human bone marrow first expressed surface differentiation antigens and then acquired the capacity to form rosettes with sheep erythrocytes. The latter marker could not be induced when cells with differentiation antigens had been eliminated. The proliferative responses to phytomitogens or to allogeneic stimuli appeared to be characteristics of later stages in differentiation that also can be induced or amplified by in vitro incubation of marrow cells or thymocytes with thymic factors. When phytomitogen-responsive cells from peripheral blood were inactivated in vitro, the allogeneic response was enhanced. Although these responses are acquired almost concomitantly, they are therefore envisioned to be characteristics of separate T cell subsets. After immunological reconstitution of patients, the T cell development in vivo involves a succession of differentiation events similar to that described above. Our experiments with mice, using similar methods, have also shown that graft-versus-host inducing capacity is a function of a cell population distinct from that which yields a proliferative response to in vitro stimulation by phytohemagglutinin. These results support our model of sequential differentiation of human prothymocytes into various subsets of mature T cells.
Antigens↗
Diabetes: relentless progress against a relentless disease.
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Diabetes Mellitus↗
HLA-D compatibility between parent and child: increased occurrence in severe combined immunodeficiency and other hematopoietic diseases.
Weak or weak intermediate reactions in one-way mixed lymphocyte culture (MLC) were seen between a patient and at least one parent in the families of 6 of 15 patients with severe combined immunodeficiency disease, 3 of 4 patients with Fanconi's anemia, and 3 of 7 patients with congenital neutropenia (CN). In control family material, weak MLC reactions were seen in 1.4 per cent (4 of 285) of individual parent-child and child-parent combinations or in 2.1 per cent (3 of 143) of the total number of parent-child pairs. The increase in frequency of weak MLC reactions seen in the familes of patients with severe combined immunodeficiency disease and Fanconi's anemia occurred most frequently between mother and patient. This finding could be relevant to the pathogenesis of these diseases. In children with CN, the disease seems to be associated with the HLA antigen B12; in addition, two of the patients with CN appear to be homozygous for HLA-D. Because of the relatively frequent compatibility seen in MLC reactions between parents and children with severe combined immunodeficiency disease, Fanconi's anemia, and CN, it is suggested that those parents could be potential donors for bone marrow transplantation.
Adult↗
Exacerbation of GVHD following repeated infusion of immunocompetent donor cells.
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Anemia, Aplastic↗
The significance of retroperitoneal lymph node morphology in testicular tumours.
The role of the regional lymph nodes in cancer is controversial. Non-neoplastic changes in lymph node histology can be correlated with prognosis for some tumour types and reactivity has been interpreted as evidence of an immune response to the tumour. Attempts to correlate the patterns of retroperitoneal lymph node activity with prognosis in patients with seminoma and non-seminoma germinal testicular tumours have not been successful. The implications of these findings are discussed.
Dysgerminoma↗
Defective recognitive immunity in family aggregates of colon carcinoma.
Cancer-free individuals from family agregates of seemingly hereditary colon carcinoma were studied to determine the nature of their cell-mediated immune capacities in miexed leukocyte culture. Members of families who demonstrated no evidence of a precancerous condition such as polyposis coli did demonstrate substantial cellular immunopathology. Of these, 44% showed a decreased responsiveness of their peripheral mononuclear cells to allogeneic stimuli, and in a number of these individuals this deficiency clearly manifested itself as an inappropriate suppression of potentially normal lymphocyte blastogenic capacities by an adherent population of mononuclear leukocytes. This in vitro defect of recognitive immunity appears to be the same type of defect that has already been described for individuals with established maligancies. The pattern of phenotypic expression of this immunopathology within these families is not inconsistent with an hereditary disorder. Individuals from families with a known hereditary somatic precancerous condition usually did not demonstrate this immunopathology. It is appropriate to speculate that the defect of recognitive immunity in the former families could be contributory to the genesis of the colon carcinoma.
Adolescent↗
Modulatory effects on immunoglobulin synthesis and secretion by lymphocytes from immunodeficient patients.
Incubation of peripheral lymphocytes (PBL) from normal donors with pokeweek mitogen (PWM) induced terminal differentiation by B lymphocytes to immunoglobulin (Ig) synthesizing and secreting plasma cells. B cells from hypogammaglobulinemic patients with different primary immunodeficiencies failed to undergo functional differentiation after similar treatment with PWM. Co-cultures of BL from normal donors and hypogammaglobulinemic patients often resulted in deviations, both positive and negative, from expected levels of PWM-stimulated intracellular Ig biosynthesis. Suppression of B-cell differentiation was manifested by PBL from patients with several different primary immunodeficiencies, including infantile sex-linked agammaglobulinemia. Immunoregulatory activities were noted to vary with the normal donor used in co-culture experiments and with time. Cell populations that were active in influencing B-cell differentiation to functional plasma cells did not have an appreciable modulatory effect on T-lymphocyte responses to mitogens. These observations may provide a functional subclassifications for immunoregulatory cells in man.
Adolescent↗
Human immunodeficiency disease: impairment of cellular interactions leading to abnormal mediator production in mixed lymphocyte culture reaction.
Leukocyte migration inhibitory factor (LMIF) production in mixed lymphocyte culture (MLC) reactions is the result of cellular interactions based on two separate phenomena: the capacity of lymphocytes to stimulate in MLC, and the capacity of lymphocytes to respond in MLC. Puromycin-treated lymphocytes are capable of stimulating allogeneic cells for LMIF production, but are unable to respond with synthesis of LMIF (one-way MLC-LMIF test). We have studied the stimulating and responding capacity of lymphocytes from patients with different immunodeficiency syndromes in a one-way MLC-LMIF assay. Lymphocytes from patients known to have qualitative and quantitative defects of T cell or B cell functions (Hodgkin's disease, mycosis fungoides, thymoma, chronic lymphatic leukemia) were found to respond poorly as measured by mediator production although their stimulating fuction was frequently retained. Patients with advanced solid tumors often had both MLC-stimulating and responding functions depressed. There was no apparent correlation between mitogen response and MLC-induced LMIF responses or between MLC proliferative response (as measured by thymidine incorporation) and mediator production. Studying of stimulatory and responding capacity of lymphocytes in the MLC-LMIF assay provides a new tool for assessing immunocompetence and allows for in vitro evaluation of cellular interactions that may play an important role in vivo.
Candidiasis, Cutaneous↗
HLA and MLC typing in patients with Hodgkin's disease.
HLA typing for 27 A and B locus antigens was performed in 137 Caucasian patients with Hodgkin's disease. A and B locus antigen frequencies were compared for the entire group of patients, for 51 patients studied in a prospective manner and for 62 patients surviving with Hodgkin's disease for more than 5 years. MLC typing (HLA-D) was performed in 51 unselected Caucasian patients using 6 differend HLA-D homozygous test cells which define 3 HLA-D specificity groups (DW2, DW3, and DW4). HLA-AW33 was found in 0.0% of patients and in 5.9% of random Caucasian blood donors at the Sloan--Kettering Institute (X2 equals 7.04, p less than 0.01). HLA-A1 was found to be increased to 35.8% in the entire patient group (N = 137) as compared to 25.4% in 855 random North American Caucasians (X2 = 5.97, p less than 0.02). There was no significant deviation of any A or B locus antigen in relation to sex, histology, age of patient, or duration of survival (newly diagnosed vs 5-year survivors). No significant deviation for either of the 3 common HLA-D determinants (DW2, DW3, or DW4) was observed.
Adult↗
In vitro lymphocyte transformation of MS patients to paramyxovirus antigens.
The immune response of 21 MS patients and 21 healthy volunteers was tested in vitro lymphocyte transformation assay. The stimulating antigens were measles, mumps, parainfluenza, E. coli, S. aureus and C. albicans. MS patients were found to respond similarly to the normal controls to all antigens tested with the exception of mumps antigen. The maximum responses of the MS patients to this antigen were significantly lower than those observed for the normals. However, since 95 per cent of the MS lower maximum responses were still within the positive range, the immunological significance of this phenomenon will require further clarification.
Antigens, Viral↗
Induction of human granulocyte differentiation in vitro by ubiquitin and thymopoietin.
Human bone marrow cells were separated according to density by centrifugation on Ficoll-Hypaque gradients and then according to size by velocity sedimentation. This procedure resulted in fractions enriched for immature granulocytes, mature granulocytes, and lymphocytes. Cells in these fractions were analyzed for their expression of certain surface and functional differentiation markers and for their ability to respond to thymopoietin and ubiquitin with the expression of additional differentiation markers. A higher percentage of band form and segmented granulocytes than of more immature granulocytes expressed complement receptors on their surfaces. Thymopoietin and ubiquitin induced a significant percentage of the cells in the immature granulocyte fraction to express this marker. These data suggested that the complement receptor may be viewed as a differentiation marker on human granulocytes, the expression of which can be induced in vitro by thymopoietin and ubiquitin. Furthermore, fractions containing predominantly band form granulocytes were induced by ubiquitin (but not thymopoietin) to develop the capacity to respond to chemotactic agents, and cell fractions containing predominantly myelocytes and metamyelocytes were induced by thymopoietin and ubiquitin to develop the capacity to phagocytose latex particles. These findings indicated that thymopoietin and ubiquitin, two agents known to induce a number of stages of human and mouse lymphocyte differentiation, are also capable of inducing some stages of human granulocyte differentiation in vitro.
Binding Sites, Antibody↗
Use of a radioimmune assay in detection of measles antibodies in cerebrospinal fluid and serum.
Evidence that different structural components of the measles virus may act as antigens has been demonstrated by the serologic methods of hemagglutination inhibition, hemolysin inhibition and nucleocapsid complement fixation. Using radioiodinated measles viral antigens, an immune precipitation assay has been designed which is capable of discriminating varying reactivities to measles viral structural components in serum or CSF and of differentiating whether IgG and IgM antibody is involved. This technic has been applied to the study of measles antibodies in CSF and sera of patients with multiple sclerosis (MS) and other neurologic diseases. From data presented here, it is found that both groups of patients have individual reactivity to measles proteins, present in CSF and serum, while three normal CSF sample were not found to have such antibodies.
Antibodies, Viral↗
Ecotaxis: the principle and its application to the study of Hodgkin's disease.
A study of the function, characterization and distribution of T and B lymphocytes in five children with Hodgkin's disease is presented. The results, indicating that lymphocyte depletion in the peripheral blood does not necessarily reflect an overall lack of circulating lymphocytes, are presented to demonstrate that failure of ecotaxis (normal lymphocyte migration and distribution) can occur in man. The underlying reasons for such failure and their relevance to the pathogenesis of Hodgkin's disease are discussed.
Adolescent↗