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Biomedical subjects

T H Rea

Publications and source records attributed to T H Rea.

At least 91 records · Page 5Linked to original sources
PubMed1984

Identification of cells lining pseudovascular spaces of benign pigmented nevi.

So-called pseudovascular spaces, said to occur in 10% of benign pigmented nevi, are presumed to be shrinkage artifacts of tissue processing. In an attempt to characterize the cells lining these spaces, three benign pigmented nevi were studied with immunoperoxidase techniques. It was found that they stained positively with an anti-melanoma antibody, P97a (gamma-2a), but negatively with an antibody against an antigen-related factor VIII, which is a marker for vascular endothelium. We conclude that these spaces are lined by melanocytes of nevi and that the spaces are not truly vascular. In one specimen, the spaces were filled with erythrocytes, which suggest that the spaces were present before fixation. It has been suggested, though, that altered collagen and elastic tissue and the nevi themselves may diminish the resistance of the dermis to the mechanical stress of the biopsy procedure, which results in the formation of these spaces.

Antibodies, Neoplasm↗
PubMed1984

In situ identification of cells in human leprosy granulomas with monoclonal antibodies to interleukin 2 and its receptor.

Leprosy is a chronic granulomatous disease with an immunologic spectrum in which lepromatous leprosy patients have defective cell-mediated immune responses, in comparison to tuberculoid leprosy patients. Immunoregulatory aspects of this spectrum were investigated by using monoclonal antibodies to interleukin 2 (IL 2), IL 2 receptors (Tac), and T lymphocyte subpopulations with immunoperoxidase techniques on frozen sections of skin biopsy specimens from 10 tuberculoid and 10 lepromatous patients. A comparison of IL 2+ cells revealed markedly fewer IL 2+ cells in lepromatous specimens (lep. 0.028% +/- 0.02 vs tub. 0.46% +/- 0.28, p less than 0.001). These IL 2+ cells were large, exhibited cytoplasmic staining, and on double immunostaining were Leu-4+, Leu-3a+, Leu-2a-, Tac-, and OKT6-, consistent with the fact they are IL 2 producers. Equivalent numbers of Tac+ cells were observed in both lepromatous and tuberculoid granulomas (lep. 1.5% +/- 0.5 vs tub. 2.1% +/- 0.7, p, NS), suggesting that the responder cells are present in both conditions. The tuberculoid granuloma was highly organized, composed of a central core of mature macrophages, Leu-3a+ and Tac+ cells with a surrounding mantle of Leu-2a+, Leu-3a+, IL 2+, Tac+, and OKT6+ cells. In lepromatous granulomas, Leu-2a+, Leu-3a+, Tac+, and rare IL 2+ cells were randomly admixed with bacilli-laden macrophages. The defective cell-mediated immune responses in lepromatous leprosy appears to be associated with diminished IL 2 production and disorganization of the granuloma.

Antibodies, Monoclonal↗
PubMed1984

Peripheral blood T lymphocyte subsets in leprosy.

Peripheral blood T lymphocyte subsets were measured by flow cytometry in 122 patients with leprosy, in 23 normal controls, and in 27 patients with systemic lupus erythematosus (SLE). Active lepromatous patients not in reaction showed a significant lymphopenia and a significant proportionate reduction in the number of OKT3-positive (pan T), OKT4-positive (helper/inducer), and OKT8-positive (suppressor/cytotoxic) cells, but no alteration in distribution as judged by percentage and no abnormality in the helper: suppressor ratio. Borderline lepromatous subjects not in reaction had a significant selective deficiency in the number of cells of the OKT4-positive subset, with a significant but secondary lymphopenia and OKT3-positive cytopenia, a pattern similar to that found in SLE patients. Patients undergoing reversal reactions had a selective deficiency in the OKT4-positive subset in both absolute numbers and as a percentage of total lymphocytes, and a secondary deficiency in the percentage of OKT3-positive cells. No abnormalities were demonstrated in patients with active erythema nodosum leprosum, lepromatous patients with long-term treatment, and untreated or treated borderline tuberculoid patients.

Humans↗
PubMed1984

Granuloma annulare. Identification of cells in the cutaneous infiltrate by immunoperoxidase techniques.

To characterize the immunopathologic process of granuloma annulare, frozen sections of eight specimens were evaluated with monoclonal antibodies directed against T lymphocytes and the monocyte-macrophage series, in conjunction with immunoperoxidase techniques and with histochemical staining. The predominant lymphocyte was an activated T lymphocyte (Leu 1+, HLA-Dr+) with an excess of helper-inducer phenotype (Leu 3a+), as compared with suppressor-cytotoxic phenotype (Leu 2a+). OKT-6+ Langerhans' cells were observed in the epidermis, and numerous OKT-6+ cells were observed in the perivascular and granulomatous infiltrate. The use of four monoclonal antibodies, having specificity against peripheral blood monocyte antigens, revealed three different staining patterns in the granulomas. Finally, mast cells were present in perivascular and granulomatous infiltrates. Our results demonstrate that the cutaneous infiltrate of granuloma annulare contains all of the principal cell types that characterize cell-mediated immune responses.

Antibodies, Monoclonal↗
PubMed1984

Dermal ultrastructure in leprosy.

We studied the ultrastructure of the dermal inflammatory response in 18 patients with leprosy. Biopsy specimens from 14 lepromatous patients, including four with Lucio's phenomenon and four with erythema nodosum leprosum, were compared with biopsy specimens from one borderline lepromatous and three borderline tuberculoid patients. In all, the dermal infiltrate consisted of macrophages, lymphocytes, and mast cells. This infiltrate was predominantly perivascular, and chronic reactive changes were found in the small dermal vessels. The macrophages contained phagocytized organisms within membrane-bound vacuoles and a wide variety of lysosomal residual dense bodies. Intraendothelial organisms were occasionally seen, especially in biopsy specimens from the patients with Lucio's phenomenon. The greatest number of mast cells were also seen in the infiltrate in those cases. The frequent close association of macrophages with lymphocytes and mast cells suggests an interrelationship between these cells that appears typical of the host response to leprosy.

Adolescent↗
PubMed1983

T-lymphocyte subsets in lymph nodes from homosexual men.

To evaluate further the immunodeficiency of homosexual men, blood and lymph node specimens were obtained from five homosexual men with lymphadenopathy and from seven homosexual men with Kaposi's sarcoma. Monoclonal antibodies were used to identify T-lymphocyte subsets in blood by cytofluorometry and in frozen sections of nodes by immunoperoxidase techniques. The homosexuals with Kaposi's sarcoma had a T-helper/suppressor ratio in blood of 0.7; the homosexuals with lymphadenopathy had a ratio of 0.6, compared with controls of 2.1. Control lymphoid tissue had a ratio of 3.0 in the interfollicular areas compared with the reactive lymph nodes in the homosexuals with lymphadenopathy, which was 0.7, and nodes from patients with Kaposi's sarcoma, 0.9. The nodes from homosexual men had evident numerous suppressor cells in the follicular center and mantle regions, locations in normal lymphoid tissue where suppressor cells were uncommon.

Flow Cytometry↗
PubMed1983

T lymphocyte subsets in the skin lesions of patients with leprosy.

Lymphocyte subsets in the tissues of fourteen patients with leprosy were studied using monoclonal antibodies and a modified immunoperoxidase technic. Two immunohistologic patterns were observed. In tuberculoid leprosy, helper-inducer cells were present among the aggregates of mononuclear phagocytes (epithelioid cells), but the suppressor-cytotoxic cells were predominantly in the lymphocytic mantle surrounding the epithelioid cell aggregates. In reversal reaction and lepromatous tissues, the helper-inducer and the suppressor-cytotoxic cells were both distributed among the mononuclear phagocytes (histiocytes). In tuberculoid specimens the Langerhans cells of the epidermis were increased in number as compared to lepromatous and normal tissues. The technic used appears to be of value in studying some of the cellular components of the immune response in situ.

Antibodies, Monoclonal↗
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.

Explore the source record for details and available documents.

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↗
PubMed1983

Suppressor cell activity and phenotypes in the blood or tissues of patients with leprosy.

Suppressor cell activity has been demonstrated in the peripheral blood of patients with leprosy. Cells bearing the suppressor/cytotoxic phenotype have been enumerated in both peripheral blood and tissues, and microanatomical differences in tissue distribution have been observed. This first generation of studies has been characterized by considerable disagreement, a not unusual circumstance in the study of leprosy. In the case of blood suppressor cell activity, there appears to be no doubt as to its existence, but much uncertainty regarding its distribution. Concerning peripheral blood phenotypic suppressor cells, the observed differences in lepromatous and ENL patients may well reflect differences in methods used. Concerning phenotypic suppressor cells in tissue, there is no agreement as to their numbers or microanatomical distribution across the spectrum of leprosy or in its reaction states. Although these observational differences make firm conclusions impossible, this first generation of studies has provided new ways of considering old problems. For example, lepromin unresponsiveness might be a consequence of active cellular suppression. Differences in the numbers (or percentages) of the suppressor phenotype in blood or tissues of lepromatous patients with or without ENL reopens the door to the possibility of cell-mediated immune mechanisms in the pathogenesis of ENL. The identification of defective suppressor cells as important in the pathogenesis of hypergammaglobulinaemia is of interest in and of itself, but also gives rise to the possibility that other kinds of phenomena may be a consequence of defective or effete suppressor mechanisms. The observation of microanatomical differences in the distribution of the suppressor phenotype in tuberculoid and lepromatous leprosy indicates that effective or ineffective immunity might be a sequela of particular interactions between the suppressor/cytotoxic and helper/inducer phenotypes, and that these interactions merit further study. These new perspectives may be subject to experimental testing by the next generation of studies, which will surely include the techniques of clonal expansion and limiting dilution, as well as the study of interleukins 1 and 2.

Humans↗
PubMed1983

Lysozyme and angiotensin converting enzyme levels in experimental mycobacterial granulomas.

A study has been made on mycobacterial-induced granulomas in guinea-pig lymph nodes. Lysozyme and angiotensin-converting enzyme (ACE) were measured in the auricular lymph nodes and serum of guinea-pigs which had received live BCG (Pasteur) or Cobalt (Co)-irradiated armadillo-derived Mycobacterium leprae intradermally into the ear or dinitrofluorobenzene (DNFB) painted epicutaneously upon the ears. In the lymph nodes with granulomas induced by either live BCG or killed M. leprae, the mean concentrations of lysozyme and ACE varied directly with the mean weight of the lymph nodes but the temporal pattern of weight change differed with the two agents. In M. leprae recipients at the time of peak lymph node weight, serum lysozyme and ACE values were significantly greater than those observed in controls; in animals receiving live BCG (Pasteur), serum lysozyme but not ACE values were elevated significantly at the time of peak lymph node weight. Four days following the epicutaneous application of DNFB, where there was no granuloma, there was a similar increase in the concentration of lysozyme and ACE in the lymph nodes. At the same time, there was also significant elevation in the serum lysozyme and ACE concentrations. Thus, in the granulomatous responses, the parallel tissue and serum changes in lysozyme and ACE concentrations were consistent with increased production and secretion of each enzyme by cells of the mononuclear phagocyte series. The increased lysozyme and ACE concentrations found in the lymph nodes of DNFB sensitised animals gives further evidence that such changes are not unique to granulomas. Finally, the intradermal administration of dead M. leprae in guinea pigs also produced increased lysozyme and ACE levels similar to that found in leprosy in man.

Animals↗