Biomedical subjects

R L Modlin

Publications and source records attributed to R L Modlin.

82 records · Page 5Linked to original sources

PubMed1983

Kaposi's sarcoma in homosexual men: an immunohistochemical study.

A recent outbreak of disseminated Kaposi's sarcoma has been recognized in homosexual men in New York, San Francisco, and Los Angeles. Biopsy specimens of skin lesions were obtained from nine of these homosexual men in Los Angeles and San Francisco. T lymphocyte subset antigens, factor VIII-related antigen, and HLA-Dr antigen were evaluated in situ in frozen sections using immunoperoxidase technics. Factor VIII-related antigen and HLA-Dr antigen were present on tumor cells, supporting a vascular endothelial origin of this neoplasm. Langerhans cells and T lymphocytes were present in numbers similar to that of normal skin in skin specimens from seven patients with Kaposi's sarcoma with visceral dissemination, but were increased in specimens from two patients with only cutaneous involvement.

Antigens↗

PubMed1983

Demonstration of a subpopulation of Ia+ T-helper cells in mycosis fungoides and the Sézary syndrome.

This is a report of the finding of a T-cell subpopulation bearing T-helper cells and Ia antigens in specimens of skin from patients with mycosis fungoides and the Sézary syndrome. Frozen sections of skin tissue from eight patients examined with monoclonal antibodies against mature T-cells, helper T-cells, suppressor T-cells, and Ia antigens exhibited similar staining patterns by a modified immunoperoxidase method. Antibodies against mature T-cells and helper T-cells stained 70-80% of the lymphocytes in the dermis. The antibody defining the phenotype of suppressor T-cells labelled 5-10% of the lymphocytes scattered throughout the lesions. Eighty to 90% of the lymphocytes took the stain for Ia antigen. Anti-thymocyte antibody (OKT6) stained cells in both the epidermis and dermis of the specimens. Of nonmalignant conditions examined, lesions from five cases of lichen planus exhibited a quantitatively different staining pattern than that of mycosis fungoides in that the number of T-helper cells was about equal to the number of T-suppressor cells. The findings reported are evidence for a homogeneous population of T-helper, Ia-positive lymphocytes in the cutaneous lesions of mycosis fungoides and the Sézary syndrome.

Adult↗

PubMed1983

Kaposi's sarcoma.

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Acquired Immunodeficiency Syndrome↗

PubMed1983

Immunoperoxidase techniques applied to dermatopathology.

Immunoperoxidase techniques provide the pathologist with the capability for staining a wide range of antigens in tissue sections. More than 100 different antigens have been successfully demonstrated in fixed paraffin sections; other antigens can only be visualized in frozen sections. This latter group particularly includes lymphocyte surface antigens detectable by monoclonal antibodies. This review describes the current state of the art and provides several illustrations of the use of monoclonal antibodies for the identification of T-lymphocyte phenotypes in frozen section from cases of leprosy, mycosis fungoides, halo nevus, Kaposi's sarcoma, lichen planus and atopic dermatitis. Technical details and potential applications are discussed. The growing availability of commercial immunostaining kits makes these techniques more accessible to the surgical pathologist; indeed a whole new range of truly specific, special stains are available, as pathologists we must simply learn to use them.

Antibodies, Monoclonal↗

PubMed1983

In situ demonstration of T lymphocyte subsets in granulomatous inflammation: leprosy, rhinoscleroma and sarcoidosis.

T lymphocyte subpopulations in frozen tissue sections of four granulomatous conditions (five patients with tuberculoid leprosy, five with lepromatous leprosy, seven with sarcoidosis and four with rhinoscleroma) were studied using monoclonal antibodies and a modified immunoperoxidase technique. Two immunohistological patterns were observed. In tuberculoid leprosy and sarcoidosis, lymphocytes expressing the helper/inducer phenotype were present within the aggregates of mononuclear phagocytes (epithelioid cells); however, cells with the suppressor/cytotoxic phenotype were predominantly in the lymphocytic mantle surrounding each granuloma. In lepromatous leprosy and rhinoscleroma the helper/inducer T cells and suppressor/cytotoxic T cells were both diffusely distributed among the mononuclear phagocytes (histiocytes) without any discernible mantle. The segregation of the helper/inducer and suppressor/cytotoxic phenotypic subsets was associated with an epithelioid cell differentiation of mononuclear phagocytic cells, bacterial elimination and a delayed type hypersensitivity response. The intimate admixture of helper/inducer and suppressor/cytotoxic subsets was associated with undifferentiated mononuclear phagocytes, bacterial proliferation and the absence of a delayed type hypersensitivity response. Thus the different distributions of T cell subpopulations in granulomas may be associated with differences in the host's immune response in several forms of granulomatous reactions.

Granuloma↗

PubMed1983

In situ characterization of T lymphocyte subsets in the reactional states of leprosy.

Using monoclonal antibodies and the immunoperoxidase technique, the numbers and distribution of T lymphocyte subsets in the tissues of reactional states of leprosy (six reversal reaction, nine erythema nodosum leprosum (ENL) and two Lucio's reaction) were determined and compared with those found in stable, non-reactional patients (six tuberculoid, two borderline lepromatous and seven lepromatous). The pattern of segregation of the suppressor/cytotoxic phenotype at the periphery of the granuloma was found in both non-reactional tuberculoid lesions and reversal reactions, but was better developed in the former. In ENL and Lucio's reaction, as well as in non-reactional lepromatous tissue, the helper/inducer and suppressor/cytotoxic phenotypes were both admixed with the aggregated histiocytes. However, the helper/suppressor ratio in ENL (2.1 +/- 0.4) was significantly larger than that in non-reactional lepromatous tissue (0.7 +/- 0.4, P less than 0.001). The immature thymocyte antigen OKT6 was found on scattered large non-lymphoid cells, most commonly in tuberculoid and reversal reaction tissues, less commonly in ENL, but only irregularly in non-reactional lepromatous tissue. The peripheral pattern of the suppressor/cytotoxic phenotype may be an immunohistological reflection of a cell-mediated immune response common to both non-reactional tuberculoid and reversal reaction patients. The reversal of the helper/suppressor ratio in ENL as compared to non-reactional lepromatous disease suggests some role for cell-mediated immunity in the pathogenesis of ENL. The OKT6 positive cell is of unknown origin and function.

Antibodies, Monoclonal↗

PubMed1975

Analysis of fluorescence decay curves by means of the Laplace transformation.

A computational procedure is described for the analysis of fluorescence decay data convolved with a lamp flash of finite width. The computer program calculates the ratio of the Laplace transforms of the decay and the lamp flash for different values of s to give the transforms of the impulse response for each value of s. These are set equal to the analytical Laplace transforms of the decay law involved. Solution of the nonlinear simultaneous equations yields the desired decay parameters. The method can be modified to analyze data that contains a component due to scattered light and can also provide essential information regarding transit time changes of the photomultiplier with changes in emission wavelength. The method was tested by the analysis of real and simulated data. The accuracy of the analysis depends on the degree of correlation among the parameters.

Fluorescence↗

PubMedDate not supplied

An immunopathologic evaluation of lymph nodes from monkey and man with acquired immune deficiency syndrome and related conditions.

Morphology and immunostaining of lymph nodes taken from rhesus monkeys and man are compared. The monkeys were inoculated with biologic materials known to transmit simian acquired immune deficiency syndrome (SAIDS) and the human biopsies were obtained from homosexual men with persistent generalized lymphadenopathy syndrome or acquired immune deficiency syndrome (AIDS). The lymph nodes from monkey and man share common immunohistochemical features, ranging from exhuberant follicular hyperplasia to lymphocyte depletion stage. The follicular hyperplasia differed from reactive controls by the larger follicular size and disorganization within the follicular centers as well as an increase in the number of cells with the T suppressor/cytotoxic phenotype. The lymphocyte depletion stage showed a loss of reactive follicles and small T lymphocytes with a predominance of mature monocytes/macrophages. Most monkeys and humans with the lymphocyte depletion morphology fulfilled the case definitions for AIDS and SAIDS while those with follicular hyperplasia usually had 'prodromal' findings. The simian agent is associated with alterations in lymph node morphology and immunostaining which parallel the changes seen in spontaneous human cases supporting a similar pathogenesis for AIDS and SAIDS.

Acquired Immunodeficiency Syndrome↗

PubMedDate not supplied

Genetically restricted suppressor T-cell clones derived from lepromatous leprosy lesions.

Leprosy is a spectral disease in which immune responses to Mycobacterium leprae correlate with the clinical, bacteriological and histopathological manifestations of disease, so study of its pathology provides insights into immunoregulatory mechanisms in man. At the tuberculoid pole, patients have few lesions in the skin which contain rare organisms and are able to mount strong cell-mediated immune responses to M. leprae antigens. In contrast, at the lepromatous pole, patients have disseminated skin lesions containing large numbers of acid-fast bacilli and are selectively unresponsive to antigens of M. leprae. M. leprae-induced suppressor cells derived from peripheral blood have been reported to be active in vitro, yet their in vivo significance has remained unclear. Because the focal point of the immune response to M. leprae is the skin lesion consisting of lymphocytes and macrophages, we have recently developed methods for isolating lymphocytes from skin biopsies of leprosy patients. We report here that two T8 clones derived from lepromatous leprosy skin biopsies, in the presence of lepromin, suppress concanavalin A (Con-A) responses both of peripheral blood mononuclear cells and of T4 clones in an HLA-D (HLA, histocompatibility locus antigen)-restricted manner. Moreover, these T8 clones suppressed responses of HLA-D-matched, but not HLA-D-mismatched antigen-responsive T4 clones to M. leprae antigens, indicating that T-cell suppression is major histocompatibility complex (MHC)-restricted at some level in man.

Antigens, Bacterial↗

PubMedDate not supplied

T-cell receptors of human suppressor cells.

Cells which can suppress the immune response to an antigen (TS cells) appear to be essential for regulation of the immune system. But the characterization of the TS lineage has not been extensive and many are sceptical of studies using uncloned or hybrid T-cell lines. The nature of the antigen receptor on these cells is unclear. T cells of the helper or cytotoxic lineages appear to recognize their targets using the T-cell receptor (TCR) alpha beta-CD3 complex. TCR beta-gene rearrangements are also found in some murine and human suppressor cell lines but others have been shown not to rearrange or express the beta-chain or alpha-chain genes. We previously established TS clones derived from lepromatous leprosy patients which carry the CD8 antigen and recognize antigen in the context of the major histocompatibility complex (MHC) class II molecules in vitro. We here report the characterization of additional MHC-restricted TS clones which rearrange TCR beta genes, express messenger RNA for the alpha and beta chains of the TCR and express clonally unique CD3-associated TCR alpha beta structures on their cell surface but do not express the gamma chain of the gamma delta TCR on the cell surface. We conclude that antigen recognition by at least some human CD8+ suppressor cells is likely to be mediated by TCR alpha beta heterodimers.

Antibodies, Monoclonal↗