Biomedical subjects

M Schmuth

Publications and source records attributed to M Schmuth.

28 records · Page 2Linked to original sources

PubMed1998

Extracorporeal photopheresis of cutaneous T-cell lymphoma is associated with reduction of peripheral CD4+ T lymphocytes.

BACKGROUND: Extracorporeal photopheresis (ECP) has been successfully introduced for the treatment of cutaneous T-cell lymphoma; however, the mechanism(s) of its action is (are) unknown. OBJECTIVE: To investigate the effects of ECP on the immune system of patients with cutaneous T-cell lymphoma. METHODS: Clinical response and changes of lymphocyte subpopulations in 20 patients with cutaneous T-cell lymphoma under ECP monotherapy or combined regimens were evaluated and compared after 3, 6 and 12 ECP cycles. RESULTS: Thirteen of 20 patients showed a > or = 50% reduction of skin lesions after 6-12 ECP cycles. An overall T-lymphocyte reduction was assessed with a balanced CD4+ T-helper and CD8+ T-suppressor cell decrease in responders. In contrast, there was a trend of CD4+ T-helper cell increase in nonresponders which could result from the failure of treatment to control the natural course of the disease. The CD4+/CD8+ ratios were 1.6 at baseline and 1.4 after 12 cycles in responders, while they increased from 1.7 to 4.1 in nonresponders, respectively (p = 0.47). In addition, there was an overall decrease in the CD57+/CD8+ T-cell subpopulation mostly due to a reduction in the responder group. CONCLUSION: The marked differences detected in certain T-cell subpopulations suggest an effect of ECP on peripheral T lymphocytes and, especially, on CD4+ cells.

Adult↗

PubMed1997

Cutaneous involvement in prelymphomatous angioimmunoblastic lymphadenopathy.

We describe prelymphomatous angioimmunoblastic lymphadenopathy with cutaneous involvement in a 73-year-old female patient. A maculopapular skin eruption was the first sign of the disease. Skin histology showed extensive perivascular and periadnexal mixed lymphoid infiltrates including centroblasts and immunoblasts with a high proliferative index and with focal erythrocyte extravasation. Lymph node histology confirmed the diagnosis, showing nearly complete effacement of the follicular architecture, a mixed lymphoid infiltrate, and numberous high endothelial venules in an expanded T-cell zone. Immunohistochemistry, however, demonstrated preservation of at least some follicular structures. T-cell receptor gene rearrangement analysis revealed oligoclonal patterns in both lymph node and skin specimens. In contrast, immunoglobulin heavy-chain gene rearrangement analysis revealed a polyclonal pattern. Accordingly, the disease was classified as a prelymphomatous stage of angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) with specific involvement of both lymph node and skin. The patient was treated with high-dose corticosteroids, and long-lasting remission was induced. In contrast to our case, most reported cases of AILD show a monoclonal T-cell pattern indicating AILD-type lymphoma. Therefore we discuss the concept of prelymphomatous AILD developing into AILD-type lymphoma. Persistence of some antigenic stimulus may induce the proliferation of a monoclonal population of lymphoid cells from a polyclonal background in a multistep fashion. Proper treatment of AILD at an early, prelymphomatous stage may protract or inhibit development of full-blown, fatal AILD-type lymphoma.

Aged↗

PubMed1997

UVB-induced alterations in permeability barrier function: roles for epidermal hyperproliferation and thymocyte-mediated response.

UV irradiation induces a variety of cutaneous responses, including disruption of epidermal permeability barrier function, the basis for which is not known. Herein, we investigated the separate roles of hyperproliferation and inflammation in the pathogenesis of UVB-induced barrier disruption. Adult hairless mice were exposed to increasing doses of UVB (1.5-7.5 MED), and transepidermal water loss (TEWL) was monitored daily for up to 7 d. The extent of TEWL increase was dependent on the UVB dose, but with all doses, the increase began after > or =48 h and peaked at 96 h, decreasing by 120 h. Epidermal [(3)H]thymidine incorporation increased at 24 h and peaked at 48 h (570%), preceding the maximal increase in TEWL. Cyclosporin A, methotrexate, 5-fluorouracil, or arabinosylcytosine significantly diminished the UVB-induced TEWL increase. Athymic nude mice also displayed a markedly diminished response to UVB, and DNA synthesis did not increased at 48 h. Transplantation of athymic mice with T-cell-enriched mixed immune cells significantly restored sensitivity to both the UVB-induced hyperproliferation and the barrier defect. Finally, although UVB exposure increased PGE2 levels in whole skin samples (2- to 3-fold within 1-3 h; p < 0.005), this increase was completely blocked by topical indomethacin, and neither topical indomethacin nor topical glucocorticoids blocked development of the barrier abnormality. These results show that (i) UVB produces delayed alteration in barrier function and (ii) both an epidermal proliferative response and thymocyte-mediated events (but not PGE2 production and nonspecific inflammation) appear to contribute to UVB-induced abrogation of the permeability barrier.

Adrenal Cortex Hormones↗

PubMed1996

Immunohistochemical identification of type II alternatively activated dendritic macrophages (RM 3/1+3, MS-1+/-, 25F9-) in psoriatic dermis.

Immunological mechanisms play an important role in the pathogenesis of psoriasis. Lesional psoriatic skin-derived T-cell clones have been shown to stimulate keratinocyte proliferation and to predominantly express a T-helper type 1 cytokine pattern. However, T-helper type 2-like cytokines have also been identified in some psoriatic T-cell clones. In parallel to the T-helper type 1/type 2 dichotomy, a distinction between interferon-gamma-induced (classically activated) macrophages and interleukin-4/glucocorticoid-induced (alternatively activated) macrophages has been put forward as a conceptual framework for a better understanding of immunopathological processes. In the present study, the phenotype of mononuclear phagocytes in psoriatic skin lesions (n = 21), allergic contact dermatitis (n = 4) and normal skin (n = 2) was investigated using a panel of monoclonal antibodies (mAb) against monocytes/macrophages and dendritic cells (mAb MS-1, RM 3/1, and 25F9 against subsets of in vitro alternatively activated macrophages, and mAb against myeloid antigens CD1a, CD11b, CD11c, CD34, CD36, and CD68). With regard to mononuclear phagocytes, psoriatic skin was found to be compartmentalized into epidermis, subepidermal space, and upper and lower dermis. RM 3/1++ +, MS-1+/-, 25F9- dendritic macrophages previously classified as type II alternatively activated macrophages were the dominant dermal macrophage population in psoriatic skin, while intraepidermal and epithelium-lining macrophages expressed a different, presumably classically activated, macrophage phenotype (RM 3/1-, MS-1-, 25F9-, CD68+2, CD11b+2). In allergic contact dermatitis, a classical T-helper type 1 disease, RM 3/1++ + macrophages were less prominent. Since MS-1 high molecular weight protein is much more sensitive to interferon-gamma-induced suppression than RM 3/1 antigen, a predominance of T-helper type 1 cytokines in psoriasis could explain why dermal dendritic macrophages do not express the fully induced MS-1++ +, RM 3/1++ +, 25F9+/- phenotype of type I alternatively activated macrophages.

Antibodies, Monoclonal↗

PubMed1996

[Rare variants of cutaneous T-cell lymphomas].

Besides the classical forms of cutaneous T-cell lymphoma (C-CTCL), such as mycosis fungoides and Sézary's syndrome, unique variants may be encountered. The classification of these rare cutaneous T cell lymphomas is problematic and controversial. Newer classifications of lymphoma in general, such as the Revised European-American Lymphoma (REAL) Classification, emphasize well-established clinico-pathological entities. It seems appropriate to attempt to bring greater clarity to the classification of cutaneous T-cell lymphomas using the same principles. In this review, we list and characterize the rare variants of cutaneous T-cell lymphoma, such as (1) clinical, histological and immunological variants of mycosis fungoides; (2) progressive cutaneous T-cell lymphoma (P-CTCL) including transformed classical cutaneous T-cell lymphoma (TC-CTCL) and primary progressive cutaneous T-cell lymphoma (PP-CTCL); (3) angiocentric and angioimmunoblastic cutaneous T-cell lymphomas; (4) large cell anaplastic, CD30+ cutaneous T-cell lymphoma; (5) HTLV-I-associated adult T-cell leukemia/lymphoma (ATLL); (6) cutaneous manifestations of primary extracutaneous T-cell neoplasias; (7) unclassifiable cutaneous T-cell lymphoma.

Antigens, CD↗

PubMed1996

Hereditary progressive mucinous histiocytosis.

We describe hereditary progressive mucinous histiocytosis, a rare autosomal dominant non-Langerhans cell histiocytosis, in a mother and daughter. Both had similar, progressive eruptions of skin-colored to red-brown papules on the nose, hands, forearms, and thighs. Light microscopy showed small collections of epithelioid histiocytes and telangiectatic vessels in the upper dermis of early lesions. In the mid dermis of early and well-developed lesions, nodular aggregates of tightly packed spindle-shaped cells were seen. Moderate to extensive mucin production was demonstrated in epithelioid histiocytes and spindle-shaped cells. Electron microscopy of spindle-shaped cells revealed many dendritic histiocytes with abundant lysosomal storage organelles such as myelin bodies and zebra bodies. Immunohistochemistry showed expression of macrophage antigens (CD68; MS-1 high-molecular-weight protein) in epithelioid histiocytes and in some of the spindle-shaped cells. The histologic and immunohistochemical features of hereditary progressive mucinous histiocytosis most closely resemble solitary histiocytoma/cellular-type dermatofibroma.

Adult↗

PubMed1996

The mononuclear phagocyte-dendritic cell dichotomy: myths, facts, and a revised concept.

Since Aschoff's reticuloendothelial system was abandoned a few decades ago, classification and characterization of the mononuclear phagocyte and dendritic cell systems have evolved separately or even in competition with one another. New information has now become available indicating that monocytes/macrophages and dendritic cells have a common origin in the bone marrow, and may even transdifferentiate. Morphological and functional distinctions-although valid under certain conditions-have been blurred by revelation of the versatility of monocytes/macrophages and dendritic cells in response to different contextual needs in inflammation and immunity. Monocytes/macrophages and dendritic cells share a sentinel, receptor/effector, and presentation mode, and may either activate or silence specific immune reactions. In keeping with the view of monocytes/macrophages and dendritic cells as interactive sentinels, we suggest that the mono-nuclear phagocyte and dendritic cell systems be replaced by the custocyte system (custos, Lat = sentinel, guard) as a unifying concept. Within the custocyte system, we recognize type I, type II, and type III custocytes. Type I and II custocytes exhibit predominance of presentation or effector/presenter interdependency, respectively, while type III custocytes are bipolar, passing through type I- and type II-like phases during their development and in inflammatory responses. The custocyte system brings into view monocytes/macrophages and dendritic cells as dynamic players in immunity and inflammation with a high degree of derivational, phenotypic, functional, and molecular plasticity.

Animals↗

PubMed1993

[Cytomegalovirus infection following lung transplantation].

The significance of cytomegalovirus (CMV) infection after lung transplantation was investigated in 20 patients (ten women and ten men; mean age 46 [21-67] years). Indications for transplantation were emphysema (n = 6), cystic fibrosis (n = 2), primary pulmonary hypertension (n = 2), pulmonary fibrosis (n = 5), obliterating bronchiolitis (n = 2), cystic lung (n = 2) and bronchiectasis (n = 1). Incidence, diagnostic parameters (serology, virus isolation and histology) and efficacy of prophylactic and therapeutic measures were recorded. 16 of the 20 patients developed a CMV infection, which in 12 was clinically significant. CMV pneumonia developed in two patients, proving fatal in one. The infection occurred a median of 47 (17-200) days after the transplantation. Administration of Ganciclovir (5 mg/kg twice daily intravenously) brought about remission of symptoms in all but one of the patients and improved the clinical parameters.--This experience demonstrates that regular monitoring of the patients for possible CMV infection and its early therapy can achieve a low death rate.

Adult↗

PubMedDate not supplied

Granulomatous slack skin: a distinct disorder or a variant of mycosis fungoides?

About 75% of cutaneous lymphomas belong to the group of T-cell lymphomas. Mycosis fungoides is the most common entity in this group. Granulomatous slack skin is a rare form of cutaneous T-cell lymphoma closely related to mycosis fungoides. We present here a patient with areas of lax skin for several years who developed a generalized erythroderma with associated immunoactivation and a deterioration in his general condition. This report discusses clinically and histologically the differential diagnoses, namely granulomatous slack skin and granulomatous mycosis fungoides, and suggests that these 2 disorders are only variants in the broad spectrum of a single disease.

Aged↗

PubMedDate not supplied

Clear cells in acral melanoma.

Acral melanoma may present clinically and histologically with atypical features causing a delay in proper diagnosis. The aim of the present study was to assess the frequency of a histological variant with clear cell changes. Clinical information, hematoxylin & eosin stained paraffin sections and immunohistochemical staining profiles were reviewed in 49 cases of acral melanoma. Twenty-one (43%) specimens contained tumor cells with clear cell changes in focal areas, whereas in 7 (14%) specimens clear cells were the major tumor constituting cells. The tumor thickness ranged from melanoma in situ to 14 mm. Immunohistochemistry demonstrated weak staining for S100 and HMB45 as well as strong positivity for Melan A and NK1C3. Recognition of clear cell features is important since differential diagnosis includes a variety of other clear cell malignancies, among them metastasis from renal cell carcinoma, clear cell sarcoma and hidradenocarcinoma.

Adolescent↗