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Biomedical subjects

G Hoffmann-Fezer

Publications and source records attributed to G Hoffmann-Fezer.

At least 55 records · Page 3Linked to original sources

Lymphoproliferative disorders in the bone marrow: histologic criteria for classification and staging.

Malignant lymphoproliferative disorders (LPD) were investigated in bone marrow biopsies of 1565 untreated patients. Marrow involvement was found in 90 per cent of multiple myeloma (MM), 70 per cent of non-Hodgkin lymphomas (NHL) and 10 per cent of Hodgkin disease (HD). In MM and NHL there were five major entities according to the predominant proliferative cell type: 1. plasmacytic, 2. lymphocytic, 3. hairy cell, 4. immunocytic and 5. centrocytic. On the basis of bone marrow histology they were classified into 3 distinct sub-types each of which had an independent prognostic significance. The mode of spread of all the LPD fell into one of six architectural patterns which together with the tumour cell burden (the quantity of infiltration in the biopsy) also had a significant predictive value. Consequently, bone marrow biopsy is a valuable diagnostic tool for histologic classification and clinical staging of any patient with LPD.

Biopsy↗

Bone marrow histology in Waldenström's macroglobulinaemia. Clinical relevance of subtype recognition.

Bone marrow biopsies of 137 patients with Waldenström's macroglobulinaemia (WM), 26 with non-secretory immunocytoma and 32 with benign monoclonal gammopathy were processed for histologic evaluation. Bone marrow involvement was found in 110 (80%) initially, and in 24 (18%) in sequential biopsies. 3 types were distinguished: lymphoplasmacytoid (47%), lymphoplasmacytic (42%) and polymorphous (11%) with median survivals of 74, 25 and 12 months, respectively. When grouped according to the tumour cell mass in the biopsies, the median survivals were 55, 21 and 8 months for less than 20 vol%, 20-50 vol% and greater than 50 vol% respectively; in each subtype, the tumour cell mass correlated with the disease progression. 6 clinical variables were also found prognostically significant. These results demonstrate that (i) 98% of patients with WM have bone marrow involvement; (ii) the lymph node sub-classification is applicable to the bone marrow and has both clinical and prognostic significance; (iii) patients may be staged according to the tumour cell burden in the bone marrow biopsy.

Adult↗

Distribution of IgM-, IgG-, and IgA-positive cells in lymphatic organs of normo- and dysgammaglobulinemic UM-B19 chickens.

Lymphatic organs of normo- and dysgammaglobulinemic chickens were studied by immunohistochemical methods concerning IgM-, IgG-, and IgA-positive cells. IgM- and IgA-positive lymphocytes and plasmacytic cells are similarly distributed in dys- and normogammaglobulinemic chickens. Follicles of the bursa of Fabricius contain cortical lymphocytes weakly and medullar lymphocytes distinctly stained by anti-IgM, as well as some larger irregularly shaped cells with intensely labeled cytoplasm. In spleen, periellipsoid lymphocytes, some red pulp lymphocytes, and varying numbers of plasmacytic cells are also distinctly labeled by anti-IgM. IgA-positive lymphocytes are not present in the bursa of Fabricius, but the bursal medulla is populated by some irregular, mostly longish cells with cytoplasmic IgA reaction. Spleen contains a few IgA-labeled lymphocytes and plasmacytic cells. The only difference between normo- and dysgammaglobulinemic chickens is found in IgG-positive cells, which are absent in permanently dysgammaglobulinemic chickens. The results from dysgammaglobulinemic chickens show that IgA can also be produced in untreated chickens lacking IgG synthesis and suggest that the theory of an IgM leads to IgG leads to IgA sequence is unlikely.

Agammaglobulinemia↗

Antilymphocytic antibodies and marrow transplantation. VI. Absence of immunosuppression in vivo after injection of monoclonal antibodies blocking graft-versus-host reactions and humoral antibody formation in vitro.

The in vivo and in vitro effectiveness of several monoclonal antimouse T and B cell antibodies, of anti-Th-1 and of Iak serum, as well as of ATG were compared. The parameters were prolongation of skin graft survival, prevention of graft-versus-host disease (GVHD), antibody and primary and secondary plaque formation against sheep redblood cells (RBCs), and T cell depletion of lymphoid tissues. In general, in vitro effectiveness of the monoclonal antibodies exceeded their in vivo effectiveness. Skin graft survival was prolonged by ATG, but not by monoclonal anti-T, or anti-T plus anti-B antibody. GVHD was prevented by in vitro incubation of donor bone marrow with monoclonal anti-Th-1, but in vivo treatment of marrow donors was ineffective. Treatment with ATG was successful. Anti Iak antibody blocked plaque formation by spleen cells incubated with sheep RBCs, but had no effect on secondary plaque formation when given in vivo. Neither was there any in vivo effect of anti-Iak or anti-Th-1 on antisheep RBC agglutinin formation. ATG was effective in both of these assays, although its cytotoxic and complement-fixing titer did not exceed that of anti-Th-1 or anti-Iak. Although anti-Th-1 was cleared more rapidly from the serum of mice expressing the corresponding Th-1 alloantigen, than from mice with the noncorresponding alloantigen and although anti-Th-1 was shown to bind to the T cell areas of the lymphoid tissue, it did not--unlike ATG--deplete these areas of T cells. Possible reasons for the difference in effectiveness of in vitro and in vivo application of these monoclonal antibodies are discussed.

Animals↗

Monoclonal antibodies against T-cell antigens studied by immunohistochemistry.

Fifteen monoclonal antibodies against different T-cell antigens were studied by immunohistochemistry in thymus, fetal thymus, fetal liver, palatine tonsils, and a few T-cell lymphomas. OKT 9 was identified as reacting with hemopoietic stem or precursor cells in fetal liver as well as with early B-determined lymphocytes in tonsillar germinal centres. OKT 10 labelled lymphocytes in thymus and surprisingly also the cytoplasm of some tonsillar cells with plasma-cell like appearance. OKT 6 and MAS 036 b reacted only with thymic cells. OKT 4, OKT 5, OKT 8,8-11, labelled thymic cells- and portions of interfollicular cells in tonsils. OKT 3, NEI 016, NEI 015, and T 28 stained a majority of thymic cells and of tonsillar interfollicular lymphocytes. IFH-M 203, NEI 012 and 4-11 were positive with the majority of T-lymphocytes in tonsils but labelled only a few thymic cells.

Animals↗

Cutaneous immunoblastic T-cell lymphoma.

The case of a 69-year-old male patient with an unusual type of malignant lymphoma is presented. Clinically, it was at first characterized by follicular papules and erythematous patches, later, by the development of cutaneous tumors and enlarged lymph nodes, and by a severe, finally excruciating pruritus. Treatment with PUVA (psoralen-ultraviolet-A) combined with 40--80 mg prednisolone and then with chemotherapy [COPP regimen (cyclophosphamide, vincristine, procarbacine, prednisone), high-dosage methotrexate followed by citrovorum factor rescue] was not successful. The patient died of pneumonia 2.5 years after the onset of the first clinical symptoms. An immunoblastic infiltrate was observed histologically and electromicroscopically in the initial lesions of the skin. Therefore, the diagnosis of a cutaneous immunoblastic T-cell lymphoma was tentatively made at the beginning, which was later confirmed in numerous biopsies and laboratory investigations. Immunocytologically and enzymecytochemically, the infiltrating cells were shown to be immature T cells; in the lymph nodes, numerous immunoblasts and large Sézary cells was observed in the peripheral blood, though there were no very large Sézary cells or blast cells. In the autopsy, a systemic involvement with an atypical lymphoid infiltration was found in numerous internal organs. The special nature of this case justifies its classification as high-grade malignant lymphoma and its differentiation from normal cases of mycosis fungoides. In contrast, mycosis fungoides generally fulfils criteria typical of low-grade malignant lymphomas.

Aged↗

Anatomical distribution of call antigen expressing cells in normal lymphatic tissue and in lymphomas.

Anatomical distribution of common acute lymphoblastic leukemia antigen (CALLA) was studied in lymphomas as well as in normal lymphatic organs using the monoclonal antibody VIL-A1. Twelve lymphomas were labelled by VIL-A1. Three of the 12 tumours also had T-cell marker, six lymphomas also showed immunoglobulin staining and only three tumours were pure CALLA lymphomas. Tonsils showed a distinct CALLA labelling of many germinal centre cells and of singular cells in interfollicular T-cell regions. Children's thymuses showed rare distinctly labelled cells in the cortex and medulla and slightly more cortical cells stained faintly by VIL-A1. Foetal thymuses of about the twelfth week of gestation contained many heavily labelled cells. The findings are discussed as evidence for the presence of CALLA on immature B as well as T lymphocytes. They favour the idea of CALLA as a common lymphocyte differentiation antigen although other possibilities of interpretation are also discussed.

Antigens, Neoplasm↗

Immunohistochemical identification of T- and B-lymphocytes delineated by the unlabelled antibody enzyme method. III. Topographical and quantitative distribution of T- and B-cells in human palatine tonsils.

T-lymphocytes and B-lymphocytes are identified in tissue sections of human tonsils by applying the unlabelled antibody enzyme method. The epithelium of the tonsils contains a majority of immunoglobulin-positive cells and fewer T-lymphocytes. In the subepithelial zones, areas composed of B-cells predominate, however, regions containing T-lymphocytes are also present. The latter are mainly arranged in the lamina propria around high-endothelial venules and often include plasma cells containing immunoglobulin. Follicles containing germinal centres display a complex structure which changes during development. The lymphocytic cap consists of densely packed lymphocytes, labelled heavily by anti-IgM and anti-IGD, and of individual T-lymphocytes. Germinal centres show a framework of immunoglobulin-positive dendritic reticular cells; they contain some heavily labelled lymphoid cells and several cells weakly labelled by anti-IgM and anti-IgA, as well as a small number of T-lymphocytes. Furthermore, the total areas of T- and B-lymphocytes measured by planimetry may differ considerably between different tonsils. Especially total areas of germinal centres vary to a great extent. The quantitative data on amounts of T- and B-cells achieved by planimetry are comparable to those reported in cellular suspensions of tonsils.

B-Lymphocytes↗

Lymphomatoid papulosis: a cutaneous T-cell pseudolymphoma.

It was the purpose of this study to further define the nature of the dermal infiltrates in lymphomatoid papulosis (LP) means of enzyme cytochemistry (acid phosphatase and esterase), immunology (rosetting techniques, immunoperoxidase technique on cryostat sections), and by semithin and ultrathin sections. The studies performed on biopsy samples with clinically and histologically typical LP indicated that most lymphoid cells display markers for T-lymphocytes, which were helper T-cells in the one case studied with monoclonal antibodies. Regarding the typical benign self-involutive clinical course, LP is considered to be a cutaneous pseudolymphoma of T-cell type.

Humans↗

Influence of the recipient thymus on the maturation of T-lymphocytes in H-2 different radiation chimeras.

Graft-versus-host reactions in mice can be suppressed by incubation of the donor cells with T-cell-specific antibodies prior to transplanting them into lethally irradiated recipients. Since reconstitution of the immune functions in these recipients requires the formation of a new T-lymphocyte population, we investigated whether H-2 differences between recipient thymus and donor stem cells as well as an age dependent thymic involution impaired the maturation of immunocompetent T-lymphocytes. For this purpose the immune response of different chimeric mice against SRBC and third party skin grafts as well as the repopulation of the lymphatic organs with T-lymphocytes was evaluated. Chimeras of the type CBL leads to CBL/CBA and CBL/CBA leads to CBA were used for the experiments. In addition chimeras which had been thymectomized, transplanted with the thymus of one parent strain, lethally irradiated and transfused with bone marrow from other parent strain were analyzed. In all chimeric combinations, even in the case of complete H-2 difference between donor cells and recipient thymus, a normal or almost normal reconstitution of the immune response against SRBC and incompatible skin grafts were detected. Furthermore age-involuted thymi returned to normal morphologically and functionally after bone marrow transplantation. The repopulation of the lymphatic organs in the investigated chimeric mice was remarkably similar to normal controls. This indicates that hemopoietic stem cells and/or lymphopoietic progenitors may differentiate in a thymus in spite of H-2 differences to functional T-lymphocytes able to respond against SRBC and incompatible skin grafts.

Animals↗

Bone marrow transplantation into recipients sensitized against donor-type T cells.

Immunization of prospective bone marrow recipients with thymocytes of the marrow donor strain prevented subsequent hemopoietic engraftment of the marrow. Immunization with thymocytes of a third party strain sharing the marrow donor's theta alloantigen but not his histocompatibility antigens permitted chimaerism and suppressed GVH in mice. Bone marrow of rat strains of the Th-1.1 group did not take in mice sensitized against mouse Th-1.1 thymocytes. This observation lead to the conclusion that hemopoietic stem cells of rats but not of mice express an early thymic and even prethymic antigen. This antigen is not restricted to the Th-1.1 specificity: rabbit anti-rat thymocyte globulin absorbed in a way which removed stem cell toxicity from a rabbit anti-mouse thymocyte globulin prevented hemopoietic engraftment when incubated with rat bone marrow before transfer to irradiated mice. Serologically this antiserum reacted with thymocytes as well as lymphocytes in the rat bone marrow but less with lymph node cells. An antiserum against rat lymph node cells was rendered T cell specific by absorption. It defined a postthymic T antigen lacking on stem cells, bone marrow lymphocytes and thymus. It labeled lymphocytes in the interfollicular T dependent area of lymph nodes by an immunohistochemical method. T cells in rats were thus found to express a prethymic and/or a postthymic antigen. Implications of theta alloantigens for the suppression of GVH in polytransfused bone marrow grafted patients are discussed.

Animals↗

Anatomical distribution of T- and B-lymphocytes in Marek's disease--an immunohistochemical study.

Neural lesions of Marek's disease, Marek's disease tumours in the ovary, liver, and kidney, as well as spleen and bursa of Fabricii of chickens bearing Marek's disease tumorous infiltrations, were examined by a new immunohistochemical technique basing upon Sternbergers unlabelled antibody enzyme method which allows the exact localization of lymphoid cells based on their surface antigens. Type C neural lesions contained T-lymphocytes almost exclusively. Type B neural lesions had relatively high proportions of T- and B-lymphocytes, and severe type A neural lesions possessed one part of heavily labelled T-lymphocytes and a number of cells stained weakly by rabbit-anti-chicken-T-cell-globulin. Tumorous infiltrations had similar characteristics as type A neural lesions. Spleen and interfollicular spaces of bursa of Fabricius were infiltrated by T-lymphocytes.

Animals↗

[Reticulosis of the skin - a heterogenic group of diseases].

In terms "reticulosis of the skin" has been used preferentially in the German dermatological literature to designate an autonomous, irreversible, atypical, systemic proliferation of elements of the reticulohistiocytic system in the skin, different from mycosis fungoides, reactive hyperplasias (pseudolymphoma), true neoplasias (reticulo sarcoma) and storage dermatosis (histiocytosis X). They provide about 1/4 of the lymphoreticular proliferations of the skin, a frequency which is comparable with that of cutaneous T-cell-lymphomas (mycosis fungoides and Sézary's syndrome). Enzymecytochemical demonstration of hydrolytic enzymes, immunological (surface-markers for B- and T-lymphocytes, quantitative determination of tissue immunoglobulins) and electron-microscopic studies in 266 patients with lymphoreticular proliferations in the skin (65 of these were "reticuloses") have lead to the following results: 1. Most of the "reticulosis of the skin" belong to the B-cell lymphomas of low grade malignancy. 2. In the skin they show a typical histomorphological feature (B-cell-pattern of infiltrate). 3. Following the Kiel Classification further differentiation into centrocytic (36%), "immunocytic" (32%), centroblastic/centrocytic (18%) and lymphocytic (14%) lymphoma can be made. 4. "Skin-reticuloses" may represent early changes of malignant lymphoma and may precede late manifestation of systemic involvement for many years.

Diagnosis, Differential↗