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Biomedical subjects

D R Katz

Publications and source records attributed to D R Katz.

At least 91 records · Page 5Linked to original sources

Regulation of human tonsillar T-cell proliferation by the active metabolite of vitamin D3.

We have examined the effects of 1,25(OH)2D3 on T-cell populations isolated by buoyant density and E rosetting from human tonsils. Cell proliferation was assessed by measuring the incorporation of 125iododeoxyuridine; interleukin-2 (IL-2) production was measured using an IL-2-dependent cell line, and the number of 1,25(OH)2D3 receptors was measured by whole-cell nuclear association assay. At a concentration of 10(-7) M, 1,25(OH)2D3 inhibited mitogen-induced T-cell proliferation in all E+ T-cell populations. This effect was more pronounced in the cells from the intermediate and high density layers and was reflected both in cell proliferative responses and in relative IL-2 synthesis. By adding the 1,25(OH)2D3 during the course of the mitogen assay, we demonstrated that activation of the T cell precedes the 1,25(OH)2D3-mediated inhibition. Cells that had been preincubated with mitogen in the presence of the 1,25(OH)2D3 were refractory to further stimulation by mitogens. Receptors for 1,25(OH)2D3 could not be detected in unstimulated T cells. However, activation led to the expression of high-affinity receptors for 1,25(OH)2D3. Co-incubation of the cells with mitogen and 1,25(OH)2D3 increased the number of receptors compared with mitogen alone. The effects provide further evidence for the hypothesis that 1,25(OH)2D3 is an important potential modulator of the immune system through its action on T cells. Taking our observations in conjunction with the known capacity of monocytes to hydroxylate the precursor metabolite (and thus synthesize the active form of cholecalciferol), the results support the suggestion that 1,25(OH)2D3 plays a role as a local mediator of mononuclear phagocyte-T cell interaction in human lymphomedullary tissues.

Calcitriol↗

Comparative accessory cell function of Langerhans cells isolated from mouse skin.

We have isolated Fc receptor bearing cells from murine epidermis and examined these cells using both structural and functional methods. From 60 to 70% of these cells are Ia positive, phagocytic and express Mac 1 and F4.80 markers. They do not have Birkbeck granules in their cytoplasm. In functional studies these cells are not active as inducer cells in allogeneic and mitogen responses. The results do not support direct homology between these Langerhans cells and the interdigitating dendritic cell. Thus within the epidermis these cells may be more closely related to a macrophage, possibly involved in antigen uptake.

Animals↗

Differing role of dendritic cells and macrophages in the induction of delayed-type hypersensitivity responses to PPD.

In order to study the antigen-presenting cell (APC) requirements for the priming of delayed-type hypersensitivity (DTH), murine spleen cells were fractionated on bovine serum albumin gradients, pulsed in vitro with tuberculin, and then injected subcutaneously into normal mice. The other footpad was challenged with tuberculin between 24 hr and 7 days later and swelling was measured 2 hr and 18-24 hr after challenge. Optimum priming for 2-hr and 24-hr responses at 7 days was achieved by an injection of 5 X 10(5) tuberculin-pulsed intermediate-density Fc + ve cells. Time-course studies revealed that the 2-hr component could be elicited as early as 24 hr after injection of pulsed APC, while the 24-hr component became significant at 3 days. Elimination of T cells or B cells did not affect the response. Injection of pulsed APC into allogeneic mice primed the 2-hr but not the 24-hr component. Neither pulsed high-density cells (mostly T cells) nor pulsed dendritic cells (DC) primed mice for these responses. Failure to elicit DTH after injection of tuberculin-pulsed DC was due to their failure to prime the 2-hr component, which other authors have shown to be a prerequisite for the appearance of the later components. That DC did prime the MHC-restricted 24-hr component was demonstrated by protocols involving the use of both macrophages and DC as APC.

Animals↗

Differential expression of class II MHC antigens on cells derived from human tissue.

Human lymphomedullary tissue cells, separated on the basis of density, Fc and E receptors, show characteristic and consistent differences in their expression of class II MHC antigens. A low density, FcR-ve cell type displays high expression of HLA-DR and acts as the most efficient accessory cell in the induction of a Con A driven proliferative response. Exposure of cells to Con A inhibits subsequent binding of anti-HLA-DR antibodies. Addition of -methyl-D-mannoside reverses both the proliferative response to Con A and returns binding of anti-class II MHC antibodies to normal levels. This experimental system can be used to study: the nature of the association between cell bound molecules and class II MHC products, both spatially and functionally; and the relative functional importance of these products in antigen presentation.

Antibodies, Monoclonal↗

Characterization of stimulator cells for alloreactive cytotoxic-T-lymphocyte responses in vivo.

Mouse spleen cells were fractionated and tested for their ability to induce alloreactive cytotoxic-T-lymphocyte responses in vivo. The cells with allostimulatory potential are enriched maximally in a population of low density, Ig-negative, Thy 1-negative cells. This fraction has the cytochemical and ultrastructural characteristics of cells of the early myeloid series and not those of typical dendritic cells or macrophages. These myeloid cells represent a new subset of accessory cells which could be a potential source of allostimulation in organ grafts. They should be considered along with other accessory cell types as potential elements which induce transplantation responses.

Acid Phosphatase↗

[Histopathological study of the cubital epineurium in patients with undifferentiated forms of Hansen's disease].

Twelve hanseniasis patients, undifferentiated group, with negative bacilloscopy and having undergone no prior treatment, were submitted to a biopsy of the cubial epineurium for histopathological study. All subjects were clinically observed after one month, and six of them were examined 4 to 5 years afterwards. Histopathology of the epineurium presented acid-fast bacilli in one patient and tuberculoid granuloma formation tendency in another. Epineural thickening was observed in nine patients and perivascular lymphomonocuclear inflammatory infiltration in six. The clinical examination after 1 month in the 12 patients as well as after 4 to 5 years in 6 of them, demonstrated innocuousness of the performed biopsy. Four to five years after the initial observation, the clinical examination showed that two patients who remained Mitsuda negative did not present histopathologically thickened epineurium at the beginning, while in four patients who then presented positive Mitsuda, the initial histopathological examination showed epineural thickening. Among the nine patients having a histopathologically thickened epineurium, six did not present initial lesions in the upper limbs. Therefore, the study of the cubital epineurium early thickening deserves special mention, and should be performed in a larger number of patients, as well as in control groups, since the follow-up of four among six patients showed epineural thickening and reversal of the Mitsuda reactions to positivity.

Adolescent↗

Heterogeneity of stimulator cells in the murine mixed leukocyte response.

Mouse spleen cells were fractionated and tested for their ability to stimulate a primary mixed leukocyte response (MLR). Several nonlymphoid populations were stimulatory, purified dendritic cells and 18-h adherent macrophages being the most effective. B and T lymphocytes and peritoneal washout cells were almost ineffective by comparison. This hierarchy of stimulator potential was observed whether the genetic difference between stimulator and responder was whole H-2 or H-2 subregion (K, D, I, I-J). Allostimulatory populations contained a high proportion of cells expressing I region determinants. The functional importance of these antigens was confirmed using specific anti-I region antisera. Thus, it appears that stimulator cells in the MLR are heterogeneous, Ia-bearing, and of "accessory" rather than lymphoid type.

Animals↗

Alloreactive cytotoxic T lymphocyte responses to H-2 products on purified accessory cells.

Several purified accessory cell populations were examined for their capacity to stimulate allospecific cytotoxic T lymphocytes (CTL). A number of non-lymphoid accessory cells stimulated CTL directed against the whole H-2 region and to isolated Class I or Class II products of the major histocompatibility complex (MHC). The accessory cells which stimulated CTL expressed surface Ia. The generation of CTL to Class I MHC products could be inhibited by antisera directed at Class II molecules on the same accessory stimulator cell surface. These findings demonstrate the importance of Class II MHC products on heterogeneous accessory cells capable of stimulating alloreactive CTL.

Animals↗

The macrophage in Hodgkin's disease.

Methods used to separate macrophages from human lympho-medullary tissue samples have been applied to involved and uninvolved spleens and lymph nodes from 44 patients with Hodgkin's disease. The tumour samples yielded a population of ultrastructurally atypical cells with the anatomical and functional attributes of macrophages. The findings suggest that the macrophage was the neoplastic element in the cases of Hodgkin's disease studied. A feature of samples of uninvolved tissue from Hodgkin's disease patients was that there were fewer macrophages identifiable in the samples than in the normal control tissues. These findings suggest that they may be a deficiency of normal macrophages as well as macrophage neoplasia in this disease. Both abnormalities would contribute to the defective cell-mediated immunity which is a characteristic of Hodgkin's disease.

Adolescent↗

Macrophages in non-Hodgkin lymphomas and hairy cell leukaemia.

Methods used in the study of human mononuclear phagocytes in vitro were applied to surgical specimens from 49 patients with non-Hodgkin lymphomas and eight patients with hairy cell leukaemia. Two of the tumours (both classified as "true histiocytic" neoplasms by the Kiel criteria) were distinguished by the presence of atypical macrophages in the in vitro system. In one the atypical cells were adherent; in the others they were non-adherent. These tumours were the only examples of mononuclear phagocyte neoplasia identified in this series. All the remaining 47 cases of non-Hodgkin lymphoma were judged to be of lymphoid origin. While initial observations on hairy cell leukaemia-derived spleen cells suggested macrophage neoplasia, this impression does not stand up to more detailed analysis. The findings are more in keeping with a B lymphoid cell lineage. In hairy cell leukaemias and low grade lymphoma the proportion of macrophages per gram weight of tissue is diminished. This suggests a deficiency of macrophage functional activity compared with normal; the nature of this defect is not clear.

Cell Adhesion↗

Macrophages from malignant effusions.

Cells from 11 malignant effusions have been examined for macrophage functional attributes and for evidence of macrophage malignancy. Three patients with Hodgkin's disease and one patient with histiocytic medullary reticulosis had atypical macrophages in their serous fluids. This adds further evidence to support the theory that the macrophage is the malignant cell in these tumour types. Two other patients with LRMPS tumours had atypical non-adherent cells in their effusions; these were probably lymphoid in origin. Samples from patients with benign disease and with epithelial tumours did not have atypical LRMPS cells. One patient with Hodgkin's disease lacked the atypical macrophage. In this patient the ascites was not due primarily to tumour involvement. There was no evidence to suggest a Hodgkin's disease-related macrophage deficit as has been reported in tissue samples. It is concluded that cells from malignant effusions are a particularly valuable source of information about the histogenesis of tumours which may be of macrophage origin.

Adult↗

Dendritic cells induce T cell proliferation to synthetic antigens under Ir gene control.

Dendritic cells prepared by a modification of the method of Steinman and Cohn are I-A+ and FcR-. They are extremely potent at activating not only allogeneic T cell proliferation but also antigen-specific syngeneic T cell proliferation. Dendritic cells from nonresponder strains are unable to present antigens to responder X nonresponder T cells, suggesting that they may be a site of Ir gene product expression.

Animals↗

Children's pure-tone detection.

A three-alternative, forced-choice adaptive procedure, with suitable reinforcement, is appropriate for testing auditory sensitivity in young children. Data obtained using this rigidly specified test protocol support previous findings of reduced auditory sensitivity in young children.

Audiometry↗

Giant condyloma of the rectum: report of a case.

The case of a woman who had a giant condyloma arising in the rectum and manifesting with a rectovaginal fistula is described. Radical surgical excision was performed. The clinical and pathologic features of this locally malignant condition are described and a plea is made for early radical surgical excision.

Abscess↗