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Biomedical subjects

C Gattringer

Publications and source records attributed to C Gattringer.

At least 55 records · Page 3Linked to original sources

[Infiltration pattern of immunocompetent lymphocytes in the tissue of malignant non-Hodgkin's lymphoma: relationship to histological and clinical parameters].

The number and distribution of reactive cells in more than 100 non-Hodgkin lymphomas (NHL) were evaluated in situ in cryostat sections. The results were compared with histological and clinical findings. 40% of the T cell content of normal lymphatic tissues was found in tissues of B-cell NHL. This corresponds to a mean of 2 X 10(4) reactive T-cells/microliter tumour tissue. The numerical density of natural killer (NK) cells within tumours was similar to that of normal lymphatic tissues (0.5 X 10(4) cells/microliter). The distribution of the reactive cells within the tumours was diffuse except in the case of centroblastic/centrocytic lymphomas. On evaluation of the different histological entities a significant correlation was obtained between number of helper/inducer (TH) cells, TH:T-suppressor (Ts) ratio and prognostically favourable histological subgroups. Furthermore, independent of histological criteria, a close correlation was found between a high number of TH-cells, a high TH:Ts ratio and a favourable clinical course (p less than 0.04). NK-cell infiltration was present to a markedly higher extent in tissues of patients with generalized disease as compared with localized disease (p less than 0.03). Low-grade malignant NHL contained significantly more NK cells than high-grade malignant NHL, as was the case also in treated, as opposed to untreated patients. These findings together suggest that reactive cells influence tumour growth via local interactions. However, tissue distribution and infiltration density of T-cell subpopulations and NK cells were clearly different. Thus, in tumour tissues different and independent immunoregulatory mechanisms seem to be associated with these two lymphocyte subsets.

Antibodies, Monoclonal↗

[Host reaction in non-Hodgkin's lymphomas: tumor infiltration with monocytes/macrophages].

The number and distribution of macrophages in deep frozen sections of various non-Hodgkin lymphomas (NHL) were evaluated in situ by immunomorphometry using stereological methods. The density of infiltration was correlated with clinical parameters. Several monoclonal antibodies reactive with antigens present on cells of the monocyte-macrophage series were tested in parallel. The density of macrophages within NHL of high malignancy with 11.3 X 10(3) +/- 1739 positive cells/microliter tumour tissue was higher than in those of low malignancy (4.7 X 10(3) +/- 628). The highest value of positive cells was found in immunoblastic lymphoma (17.3 X 10(3) +/- 2773), differing significantly from other histological subtypes of NHL and normal tissue (normal tissue: 6.5 X 10(3) +/- 1027, p less than 0.005). With regard to clinical parameters, localized NHL displayed lower infiltration numbers than generalized NHL. Possible mechanisms of influencing tumour growth are discussed in view of the large infiltration density of the monocyte macrophage series in NHL of unfavourable histology and advanced clinical stage.

Antibodies, Monoclonal↗

Surface glycoproteins (S-GP) on normal and malignant human leukocytes.

This study aimed to investigate high molecular weight surface glycoprotein (S-GP) patterns on various types of human leukocytes. S-GP were externally labelled by the Galactose-oxidase-NaB3H4 technique. Results based on the analysis of 120 samples derived from different types of normal and malignant leukocytes indicate that the relative expression of high molecular weight S-GPs changes during haemopoietic cell differentiation and to some extent these changes enable the classification of human leukocytes.

Antigens, Surface↗

Follow-up studies on proliferative T cell responses in cadaveric kidney graft recipients under combined immunosuppressive treatment with cyclosporine and prednisone.

In 5 recipients of cadaveric renal allografts, we tested the influence of prophylactic immunosuppression with cyclosporine (Cy A) and low dose prednisone on in vitro proliferative T cell responses, T-helper/T-suppressor cell ratios and spontaneous- or lectin-induced unspecific suppressor cell activity and on serum mediated inhibition of proliferative T cell responses. Results revealed a reduction of the overall proliferative T cell responsiveness, which was particularly seen in cultures supplemented with autologous serum and was maximally expressed after approximately 30 days of treatment. This impaired proliferative capacity was neither accompanied by shifts of the T-helper/T-suppressor ratios nor by alterations of spontaneous- or lectin-induced suppressor activity. The capacity of patients' plasma to inhibit lymphocyte proliferation was also tested. Results indicated that almost every plasma of Cy A patients was capable of inhibiting mixed lymphocyte culture (MLC) responses. The inhibitory capacities of these plasma, however, were not directly correlated with their Cy A content.

Adult↗

Infiltration density of HNK 1 positive cells in non-Hodgkin's lymphomas depends on histologic subtype: an in situ morphometric analysis.

Numbers and distribution of HNK-1 (Leu 7) positive cells within 115 malignant Non-Hodgkin's lymphomas (NHL) were evaluated in situ by immunomorphometry. Results on the infiltration were related to histological and clinical parameters. A mean of 4.099 +/- 350 HNK 1+ cells/microliter tumor tissue was found, which was comparable to normal (reactive) lymphatic tissues (4.441 +/- 1.235) and was about a quarter of the population density of T helper/inducer (TH) and T cytotoxic/suppressor (TS) lymphocytes together. The distribution of HNK 1+ cells within the tumors was diffuse except in nodular lymphomas of follicular center cell origin (centroblastic/centrocytic = cb/cc NHL). When evaluating the different histological subgroups, the highest number of HNK 1+ cells was found within the tumor areas of cb/cc, which contained about three times as many positive cells as the other NHL. High numbers were also found in the diffuse variant of cb/cc but not in centrocytic NHL. Different degrees of HNK 1+ cell densities were observed in lymphocytic lymphomas (4.426 +/- 754), with high numbers in about 30% of the patients. Splenic tissues of 6 hairy cell leukemias displayed lower numbers of HNK 1+ cells as compared with other low grade malignant NHL. In "large cell" NHL, the lymphoblastic subtype showed only sparse HNK 1+ cells (1.345 +/- 386). The number was significantly reduced in comparison to all other NHL (p less than 0.01) and markedly lower than in the other NHL of high malignancy (immunoblastic and centroblastic NHL, p less than 0.02). The diminuation was not due to a simple dilution phenomenon in a rapidly proliferating tumor, as TH and TS infiltrates were comparable to other NHL. Correlating results with the clinical course (available in 58 patients), significantly higher numbers of HNK 1+ cells were found in NHL of low malignancy (p less than 0.02), but patients with a favourable course did not differ from those with progressive disease (p less than 0.5). Patients treated by cytotoxic drugs showed higher numbers of HNK 1+ cells than those before or without treatment (p less than 0.02). Results on TH and TS cell numbers in comparison to HNK 1+ cells showed completely different patterns of infiltration.

Antibodies, Monoclonal↗

[Immunocytologic diagnosis of leukemia and lymphoma: monoclonal antibodies in the differential diagnosis of hematologic neoplasms].

Malignant lymphomas and leukemias are related to maturation stages of distinct subpopulations of hematopoietic or lymphoid cells as defined by immunocytological methods. We first describe various monoclonal antibodies, and the methodology employed in our investigations and report on recent developments in the standardization of these reagents (part 1). The maturation sequence of normal lymphoid cells and their precursors in the bone marrow, thymus and the peripheral lymphoid organs are discussed in part 2. Typical immunomorphological findings in Non Hodgkin Lymphomas (NHL) are summarized in respect to lymphocytic NHL (CLL, lymphoplasmocytoid NHL, hairy cell and prolymphocytic leukemia, some lymphomas of peripheral T-lymphocytes), to NHL of follicular center cells (centroblastic-centrocytic, centrocytic NHL), to "large cell" NHL (centroblastic, immunoblastic NHL, large cell NHL derived from T-lymphocytes or "lymphomas" of macrophage origin) and to lymphoblastic NHL (derived from T-lymphocytes, pre-B lymphocytes and Burkitt-type). Findings in multiple myeloma are also summarized in part 3. Immunocytological features of the normal Myelo-, Mono-, Erythro- and Thrombopoieses are discussed in part 4. The reactivity of some monoclonal antibodies with precursor cells of these cells (CFU-GM, BFU-e and CFU-e, CFU-M) are also described. Finally we summarized the immune phenotype of acute leukemias (part 5) in respect to acute lymphoid leukemias (cALL, T-ALL, O-ALL, B-ALL), to acute non lymphoid leukemias (M1-M6 type according to the FAB-Classification) and to blastic stages of chronic leukemias.

Antibodies, Monoclonal↗

Effects of human recombinant alpha 2 arg-interferon and gamma-interferon on human breast cancer cell lines: dissociation of antiproliferative activity and induction of HLA-DR antigen expression.

Human recombinant gamma-interferon (rhu-IFN-gamma) and human recombinant alpha-interferon (rhu-IFN-alpha 2 arg) with a chemical purity of over 95% were compared for their antiproliferative and HLA-DR-inducing activity in five human breast cancer cell lines (BT 20, ZR 75.1, MCF 7, 734B, Hs578T). Cytostatic effects on tumor cells were evaluated in monolayer cultures. HLA-DR antigen expression was examined by an indirect immunofluorescence technique using two different anti-HLA-DR monoclonal antibodies (anti-HLA-DR, VID-1) against framework determinants. rhu-IFN-gamma and rhu-IFN-alpha 2 arg differed in their antiproliferative efficiency in terms of both dose dependency and the spectrum of sensitive target cells. Combinations of rhu-IFN-gamma and rhu-IFN-alpha 2 always resulted in higher cytostatic effects. HLA-DR expression was exclusively inducible by rhu-IFN-gamma and did not correspond to its antiproliferative activity. Furthermore, HLA-DR expression did not depend on proliferation but did require intact RNA and protein syntheses as shown by inhibition with cycloheximide and actinomycin D. HLA-DR antigen expression in mammary cancer lines was dependent on time, dose, and the continued presence of rhu-IFN-gamma. Thus, our data suggest that in particular combinations type I and type II interferons might be useful in the treatment of breast cancer because they provide effective cytostatic and cell membrane-modulating properties.

Antibodies, Monoclonal↗

Immunopathology of non-Hodgkin lymphomas.

The immunopathological features of lymphocytic non-Hodgkin lymphomas (NHL), follicular centre cell tumours and "large-cell" NHL are described with particular emphasis on in situ evaluation of cryostat sections using monoclonal antibodies. The immunological phenotypes of tumour cells and the pattern of "reactive" cellular infiltrates with characteristic differences for the various subtypes are summarized. Immunological membrane features of the following lymphocytic NHL of B lymphocyte origin are discussed in detail: B-CLL (most common phenotype of the lymphoma cells: VIB-C5, To-15, Ia, Leu-1), lymphoplasmocytoid NHL (To-15, Ia), B-prolymphocytic leukaemia (VIB-C5, To15, Ia, Leu (+/-), FMC-7(+/-] and hairy-cell leukaemia (HCL: To-15, Ia, FMC-7). NHL of T-lymphocytes detailed in respect of mycosis fungoides and Sézary syndrome (OKT-3, OKT-4, OKT-11), to subtypes of T-CLL with particular emphasis on the "azurophilic" type, to T-zone NHL, and to adult T-cell leukaemia/lymphoma (OKT-3, OKT-4, OKT-11, anti-tac), all of them with the usual immunological phenotype of T-helper (TH) lymphocytes. NHL with a predominance of T-suppressor (TS) lymphocytes include the immunoblastic lymphadenopathy like T-cell lymphoma (OKT-3, OKT-8, OKT-11) and some lymphoepitheloid (Lennert) lymphomas. Immunological features of follicular centre cell tumours are discussed with emphasis on similarities and differences with the normal germinal centre. Tumour cells usually show the following membrane phenotype: centroblastic/centrocytic (cb/cc: To-15, VIL-Al, Ia; meshwork of non-neoplastic R4/23+, To-5 + DRC), centrocytic (VIB-C5, To-15, Leu-1, Ia; R4/23 and To-5 meshwork), centroblastic (cb, To-5, To-15, Ia, VIL-Al +/-). "Large-cell" NHL include the last entity (cb), immunoblastic (B-ib, T-ib) and lymphoblastic (lb) NHL and are discussed in respect to B-ib (Ia, To-15 +/-, VIL-Al +/-), T-lb (WT-1, OKT-6 +/-, OKT-11 +/-), pre-B-lb (VIB-C5, Ia, TdT, VIL-Al +/-) and Burkitt-type NHL (VIB-C5, VIL-Al, Ia, sIg). "Reactive" cellular infiltrates may account for a large fraction of the cellular content of NHL (e.g. the mean TH and TS content amount to about 40% of that seen in normal lymph nodes). In comparison to other NHL B-CLL and cb/cc showed the highest, HCL the lowest number of TH X TS exhibited less typical alterations.(ABSTRACT TRUNCATED AT 400 WORDS)

Antibodies, Monoclonal↗

Subpopulations of colony-forming B lymphocytes exhibit distinct in vitro growth characteristics.

Human peripheral blood cells enriched for B lymphocytes were stimulated to focal proliferation in semisolid cultures with lymphocyte-conditioned media, Protein A (Prot A), lipopolysaccharide (LPS) and 2-mercaptoethanol (2-ME). After 6-8 days of incubation, two morphologically distinct colony types were observed. Type I colonies were diffusely proliferating aggregates within the agar layer, whereas another subset of B-cell-colony-forming cells (CFU-BL) formed round compact type II colonies which appeared to leave the agar layer and continued to proliferate in the liquid overlayer of our culture system. They reached maximum proliferation 2 days earlier than type I colonies. Cells derived from both colony types were positively identified as B lymphocytes by monoclonal antibodies using immunoperoxidase staining. In addition to this distinct growth pattern, both colony types exhibited different proliferative responses which were dependent on the kind of conditioned media used and the mitogen concentration. In secondary cultures both type I and type II colony-derived cells showed recloning capacity. However, after replating, both colony types gave rise to round compact type II colonies. These results demonstrate that there exist at least two subpopulations of colony-forming B lymphocytes, possibly one more primitive than the other, which can be distinguished by in vitro growth characteristics.

B-Lymphocytes↗

Imbalance of helper and suppressor T lymphocytes in malignant non-Hodgkin lymphomas: an in situ morphometric analysis.

The number and distribution of reactive T cells within 100 malignant B-cell lymphomas were evaluated in situ by immunomorphometry using stereological methods. Findings were related to histological and clinical parameters. A mean of 2 X 10(4) reactive T cells/microliter tumour tissue was found. This corresponds to 40% of the T-cell content of normal lymphatic tissues. The distribution of reactive T cells within the tumours was diffuse except for centroblastic/centrocytic lymphomas. When evaluating the different histological entities a correlation between number of helper T cells, T helper:T suppressor (TH:TS) ratio and histological subgroups emerged, particularly in non-Hodgkin lymphomas of low-grade malignancy. The highest ratio was found in prognostically favourable subgroups, CLL (2.7 +/- 0.3) and tumour areas of centroblastic/centrocytic lymphomas (2.9 +/- 0.4). In contrast, a significantly lower ratio was found in centrocytic lymphomas (1.4 +/- 0.3) corresponding well to the worst prognosis of this subgroup. The relationship between the number of helper T cells in tumour tissues, TH:TS ratio and prognosis was confirmed and extended by the evaluation of clinical data. It could be shown that, independently of histological criteria, a close correlation exists between the number of T cells, particularly T helper cells within the tumour, TH:TS ratio and clinical course. Patients with a favourable course had 1.4 X 10(4) T helper cells/microliter tumour tissue compared to only 0.8 X 10(4) for patients with an unfavourable clinical course (p less than 0.01); the TH:TS ratio was 2.8 for the favourable and 1.8 for the unfavourable group, respectively (p less than 0.04). In contrast, neither treatment nor tumour stage had a clear-cut influence on the extent of T-cell infiltration.

B-Lymphocytes↗

[The first case of AIDS in the Tyrol].

This case report deals with a description of the first case of AIDS in Tirol. Our patient was an intravenous drug abuser and presented with both opportunistic infections (candidiasis, interstitial pneumonia due to Pneumocystis carinii) and with Kaposi's sarcoma. He died within 4 weeks as a result of staphylococcal septicaemia refractory to intensive chemotherapy.

Acquired Immunodeficiency Syndrome↗

[Long-term osteoporosis with multiple fractures as the early monosymptomatic stage of multiple myeloma].

A 44 year old man with kappa-light plasmacytoma is presented who had been treated for osteoporosis and multiple bone fractures since 12 years. On admittance he had a rapidly progressive myeloma kidney and an extensive extramedullary tumor within the pelvis. Remission was induced using combination chemotherapy according to the VMCP-protocol. It is discussed that the long-lasting osteoporosis of the present case represents an unusually long, monosymptomatic early stage of a multiple myeloma rather than an independent primary disease.

Adult↗

[Immunopathology of lymphatic systemic diseases].

Immunopathological findings in the various non-Hodgkin lymphomas are summarized in this report, with special emphasis on recent results with monoclonal antibodies. Results are presented in different types of lymphocytic lymphoma, in those derived from the germinal centre, from T-lymphocytes of "central" and "peripheral" origin and in some disorders involving early precursors of B-lymphocytes. These diseases very probably represent maturation defects ("frozen states") of defined subpopulations of lymphoid cells. The possible diagnostic role of immunoperoxidase and immunofluorescence techniques in cell suspensions and, particularly, in frozen sections of diseased tissues obtained from patients with lymphomas and leukaemias is discussed.

Adult↗

[Immunologic detection and in vitro activity of suppressor cells].

Suppressor cells can be identified in vitro either by specific antibodies or by functional test assays. On investigation of the latter, a close relationship was demonstrated between spontaneously active and in vitro induced (ConA) suppressor cells. The activity of these cells, however, showed a wide day to day variation. Hence, no clinically relevant conclusions could be drawn from a comparison of patients and controls. This was shown both for SLE and myeloma. However, in multiple myeloma indirect evidence of increased activity of short-lived suppressor cells emerged from a different methodological approach. Helper and suppressor cells were evaluated using monoclonal antibodies. Patients with Hodgkin's disease in long-term remission had decreased proportions of T-lymphocytes. Helper T-cells but not suppressor T-cells were strongly diminished. The helper-suppressor ratio was changed from 2.1 in controls to 1.2 in patients. The stimulation (PHA-stimulation) index of the patients was half of the control value. The interactions of suppressor and tumour cells were investigated in non-Hodgkin's lymphoma. In general, a marked reactive infiltration of neoplastic lymph nodes was found. The pattern of suppressor cell distribution argued in favour of a functional role of these cells in tumour growth.

Adult↗

[In vitro studies of clonable human B lymphocytes].

A recently developed micro agar culture system has been optimized for the in vitro growth of human B-lymphocytes. Enriched B-lymphocytes from the peripheral blood of normal individuals were suspended in an agar layer, above which a liquid overlayer containing 20% PHA-LCM, 2-ME and Prot A or LPS as stimulants was added. Two morphologically distinguishable colony types were observed using this culture technique: diffusely proliferating colonies (Type I) were found within the agar layer, and round, compact colonies (Type II) appeared to leave the agar layer and continue growth in the liquid overlayer. For both colony types a linear relationship was demonstrated between the number of seeded cells and the number of formed colonies. The appearance of the two colony types in vitro was not concurrent, and they exhibited differing sensitivity to mitogen concentration and to the type of serum used as additive to the culture medium. The implications of clonal in vitro cultivation of lymphocytes, both normal and pathological, are discussed.

Adult↗

[Therapy of malignant lymphomas].

Prognostic factors in patients with Hodgkin's disease and the non-Hodgkin lymphomas are reviewed and discussed since they form the basis of the therapeutic approach to these conditions. Hodgkin's disease is treated according to stage, histology and other prognostic criteria and the appropriate management is presented in tabular form. In the non-Hodgkin lymphomas, prospective studies using the Kiel classification indicated that these lymphomas could be subdivided into types of low-, intermediate- and high-grade malignancy, each requiring different treatment modalities. An expectative approach is often, but not always, recommended in lymphomas of low malignancy. The natural history of lymphomas of high-grade malignancy is unfavourable and, usually, prolonged survival is observed only in those cases in which a complete remission is achieved. Our therapeutic approach to the various forms of these lymphomas is based on the stage of the disease and the respective schedules are summarized for lymphomas of low- and high-grade malignancy. Finally, the chances of cure in Hodgkin's disease and in the non-Hodgkin lymphomas are discussed and recent developments are mentioned.

Adolescent↗

Large granular lymphocytes: morphological and functional properties. I. Results in normals.

Large granular lymphocytes (LGL) represent a morphologically distinct mononuclear cell type. In healthy individuals an average of 12.5 +/- 5.2% of peripheral mononuclear cells exhibit this morphology. Structurally they are characterized by azurophilic granules, light cell density, low surface adherence and expression of Fc-IgG receptors. Functional analyses on LGL suspensions enriched by means of density gradient fractionation and adherence procedures included testing of T-cell and monocyte-specific in vitro reactions as well as evaluation of their natural cytotoxicity (NC). Results indicated a close correlation between the percentages of LGL and the capacity to bind and to lyse NC-susceptible tumor targets. In agreement with others we would thus conclude that LGL embrace the majority of NK-effector cells. The morphological definition of LGL provides an additional tool for the clinical evaluation of this cell mediated immune reactivity.

Antigens, Surface↗

Human autologous mixed lymphocyte reactivity is primarily specific for xenoprotein determinants adsorbed to antigen-presenting cells during rosette formation with sheep erythrocytes.

We present evidence that most T cells proliferating in response to autologous sheep erythrocyte (SRBC)-separated non-T cells (NT) cells are not specific for autoantigens but for antigens derived from xenogeneic sources. The conclusion was based on the following three observations. First, we found that NT cells isolated in the absence of xenoproteins by means of density gradient centrifugation on Percoll only weakly stimulated autologous T cells. Because this weak proliferation could not be expanded in restimulation experiments, its significance as an immune recognitive event remains questionable. NT cells isolated by the above method in the absence of xenogeneic determinants readily acquired stimulatory capacity after brief exposure to either SRBC or fetal calf serum. Second, restimulation of T memory cells generated in 1 degree autologous mixed lymphocyte reaction (AMLR) against SRBC-separated autologous NT cells was exclusively seen when NT cells exposed to or separated with xenoproteins were used for restimulation. Third, T memory cells generated against SRBC-separated autologous NT cells were specifically restimulated by autologous Percoll-separated NT cells that had been pulsed with a variety of xenogeneic mammalian sera. These xenogeneic determinants were preferentially recognized in context with autologous HLA-DR+ cells. From these findings and from our previous results that indicated an absolute requirement of HLA-DR+-adherent NT cells (8), we conclude that human AMLR primarily does not represent an autoantigen but a xenoantigen response that is genetically restricted by the HLA-DR type of the antigen-presenting cell.

Animals↗