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G Gastl

Publications and source records attributed to G Gastl.

At least 109 records · Page 6Linked to original sources
PubMed1986

Abnormal expansions of granular lymphocytes: reactive lymphocytosis or chronic leukemia? Case report and literature review.

A case of chronic lymphoproliferative disorder is presented, wherein a morphologically homogeneous population of lymphoid cells displayed properties similar to those described for large granular lymphocytes (LGL). Besides their LGL-like phenotype (VEP 13+, OKM 1+, OKT 10+ Fc-IgG-receptor+, OKT 3-), the proliferating cells were cytotoxic to NK targets as well as to antibody-coated target cells. Clinically, our patient presented low-grade lymphocytosis, splenomegaly, neutropenia, hyperimmunoglobulinemia and recurrent infections. Based upon this and 32 similar cases reported in the literature, we conclude that lympho-proliferative disorders involving GL encompass a variety of clinical entities, ranging from reactive GL lymphocytoses to overt lymphocytic malignancies.

Adult↗
PubMed1986

Treatment of hairy-cell leukemia with recombinant alpha 2-interferon.

Eleven patients with hairy-cell leukemia (eight with progressive and three with non-progressive disease) were treated with low dose recombinant human alpha 2-interferon. After a 3-month treatment period, nine patients showed an improvement and one patient a partial remission. By then, transfusions were not required any more and serious infections were no longer encountered. Four patients were further treated: three for a total period of 9 months and one for 6 months; all of them reached a partial or complete remission. The treatment was equally effective in patients with both progressive and non-progressive disease. Previous absence of response to splenectomy did not preclude a positive effect of IFN therapy. In two patients, IFN dose reduction was necessary due to unremitting flu-like symptoms.

Humans↗
PubMed1986

Macrophage infiltration in non-Hodgkin's lymphomas: a quantitative in situ study.

The frequency and distribution pattern of macrophages within 93 non-Hodgkin's lymphomas (NHL) were evaluated in situ by immunomorphometry using stereological methods. For the identification of macrophages (M phi), several antibodies (Mono 1, Mono 2, OKM 1) reactive with surface antigens on cells of the monocyte-macrophage series and cytochemical staining for acid phosphatase were applied. The average number of macrophages within lymph node tissue of NHL was 6,299 +/- 760 cells/microliter (similar to reactive lymphatic tissue: 6,559 +/- 1,027). The highest number of infiltrating macrophages was detected in immunoblastic NHL (17,306 +/- 2,773), differing significantly from other histological subtypes and reactive lymphatic tissue (p less than 0.005). The possible impact of tumor-infiltrating macrophages on lymphoma cell proliferation and differentiation is discussed.

Antibodies, Monoclonal↗
PubMed1986

A biological approach to optimize interferon treatment in hairy cell leukemia.

Progress with the clinical application of interferons to neoplastic diseases has been slow and complicated by the need for attention to a new spectrum of therapeutic and toxic effects manifested by the interferons. In this report, we present a new approach to define clinically effective but atoxic doses of interferon-alpha for treatment of hairy cell leukemia. In order to find in vivo biologically active interferon doses, the biochemical marker neopterin was selected as a means to assess a cellular interferon response in vivo. Subcutaneous administration of minimal doses of recombinant interferon-alpha-2 (5-8 X 10(5) U/day), which induced maximum neopterin release in serum and urine, proved to be clinically effective: Eight of nine patients responded to this dose regimen. This response rate was comparable to that of a conventional dose schedule (3 X 10(6) U/sqm/day) which was also applied to nine patients (eight responders). Whereas no difference in the clinical efficacy between the two therapeutic strategies could be established, toxicity was clearly confined to the conventional dose regimen. These preliminary results suggest that at least in hairy cell leukemia the therapeutic dose range of interferon can be separated from the toxic.

Biopterins↗
PubMed1985

Effect of human recombinant alpha-2- and gamma-interferon on the growth of human cell lines from solid tumors and hematologic malignancies.

We studied the growth effects of human recombinant interferon (IFN)-alpha-2 and -gamma on various human cell lines. Four cell lines from solid tumors (WiDr, CCL 185, BT 20, KB) and three cell lines from hematologic malignancies (U 937, U 266, MOLT 4) were chosen. The study was performed using two different assays: (1) a soft agar cloning assay, and (2) a monolayer and suspension culture. In the soft agar assay alpha-IFN inhibited colony growth of 6/6 lines tested (the line MOLT 4 could not be plated); in the monolayer assay it inhibited proliferation of 6/7 lines tested. Gamma-IFN showed inhibitory effects on 5/6 cell lines tested in the soft agar assay, but on one line (CCL 185) low concentrations of gamma-IFN led to a significant increase in the number of colonies. Using the monolayer assay, gamma-IFN showed inhibition of 6/7 lines tested, whereas a stimulation of growth could not be observed. With a combination of alpha- and gamma-IFN, synergistic effects were seen on a histiocytic cell line (U 937) in both assays and a marginal synergism on the T-cell line MOLT 4 in the monolayer assay.

Cell Division↗
PubMed1985

Treatment with low dose human recombinant interferon-alpha-2-ARG induces complete remission in patients with hairy cell leukemia.

Five cases with advanced hairy cell leukemia refractory to treatment with splenectomy and chemotherapy as well as one patient presenting with a stage-A response to splenectomy were treated with rhu-IFN-alpha 2-arg. 5 X 10(6) were administered intramuscularly every day. Both patients, with advanced disease resistant to conventional therapy and treated for six or more months with rhu-IFN-alpha 2-arg, achieved complete clinical remissions. Three further cases treated for less than half a year and also with advanced disease achieved partial remission states with marked reduction of circulating hairy cells and with recovery of normal hemopoiesis. Minimal residual disease in the remaining patient during a three-month period of treatment did not respond. Side effects of rhu-IFN-alpha 2 low dose therapy were minimal in 5 cases and comprised a severe leukopenia reversible after dose reduction in one patient.

Adult↗
PubMed1985

Interferon-alpha-2C in the treatment of advanced hairy cell leukaemia. Results of a phase II trial.

The efficacy of recombinant interferon-alpha 2 in the treatment of advanced hairy cell leukaemia is investigated in 31 patients. Preliminary results show a complete and partial response rate of 69%. An optimal dose study utilizing maximal stimulation of an interferon-dependent pathway was carried out in 5 patients. The optimal dose of the order of 5 X 10(5) IU/day is effective and without side-effects. Interferon treatment did not enhance natural killer cell activity and therefore a direct mode of action upon tumour cells is proposed.

Dose-Response Relationship, Drug↗
PubMed1985

[Results of a phase II study on the treatment of hairy cell leukemias with various doses of alpha-2-recombinant interferon].

Hairy-cell leukemia has been shown to be extraordinary sensitive to treatment with alpha-interferon. In order to define clinically effective interferon doses associated with minimal toxicity two different dose regimens were applied in this clinical trial: firstly, a conventional dose schedule, and secondly, a biologically defined dose regimen. For dose finding in the latter group, neopterin, a GTP degradation product produced by macrophages under control of interferon, was chosen. Six patients (Group A) received conventional doses of recombinant interferon--alpha-2 (rIFN-alpha-2) 3 X 10(6) U/sqm/daily by the subcutaneous route. Five patients (Group B) were treated with the minimal dose of rIFN-alpha-2 which had previously been shown to induce maximum neopterin levels in urine. Already interferon doses in the range of 3 to 5 X 10(5) U/sqm2/daily administered subcutaneously proved to be sufficient for triggering maximum neopterin excretion in the urine. After six months of interferon treatment all patients were evaluable. At this time both doses regimens proved to be effective in terms of their anti-leukemic activity, but differed significantly in toxicity, which was only seen in Group A patients.

Adult↗
PubMed1985

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↗
PubMed1984

[Löffler's parietal fibroplastic endocarditis--a case report].

A 62-year-old patient showed blood eosinophilia for 10 years. In-patient treatment was necessary several times on account of cardiac decompensation. The cardiac damage progressed irreversibly and the patient died from acute cardiac failure. Post-mortem examination revealed massive parietal fibrous formation in the left ventricle (endocarditis parietalis fibroplastica "Löffler"). Aetiology and pathogenesis remain unsolved. It is possible in the present case to postulate a causal connection with an incident of polytrauma many years ago.

Cardiac Catheterization↗
PubMed1984

[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↗
PubMed1984

Human large granular lymphocytes and their relationship to natural killer cell activity in various disease states.

This study investigated the numbers of large granular lymphocytes (LGL) and their relationship to natural killer (NK) function, as assessed by their capacity to lyse the human tumor target, K562. Peripheral blood mononuclear cells from 42 normal controls and from 171 patients suffering from various nonmalignant or malignant diseases were evaluated. Also studied were samples from a patient undergoing autologous bone marrow reconstitution following total body irradiation. Results suggested the existence of a close relationship between the numbers of LGL and the capacity to lyse K562 targets, further supporting the view that LGL are crucial effector cells mediating NK lysis. In certain diseases, such as malignant states, functional capacity was not simply determined by the numbers of LGL. Here preferential reduction of the capacity to lyse K562 targets was observed, indicating that additional limiting factors are involved in the determination of the cytotoxic potential. Based on the relationship between LGL and natural immune functions, as well as on the identification of leukemias affecting this cell type, we would recommend their evaluation on a large scale clinical basis.

Adolescent↗
PubMed1984

The relationship of HNK-1 (Leu 7) and VEP13 antigens on human cells mediating natural killing.

The NK cell associated antigens defined by the two monoclonal antibodies, HNK-1 (anti-Leu 7) and VEP13, were investigated for their mutual expression on peripheral blood lymphocytes of healthy donors. In double labelling experiments only 6 +/- 3.9% of peripheral blood lymphocytes (PBL) were found to carry both markers. When VEP13+ cells were enriched by rosette formation using VEP13 coated ox red blood cells all the NK activity was recovered in the VEP13+ cell preparation, whereas the VEP13- subset was devoid of it, despite of the fact that there was a remainder (7-13%) of HNK-1+ cells. These VEP13- HNK-1+ cells were found to also bear the T3 antigen but lack the M1 antigen. Thirty-eight to sixty-eight per cent of VEP13+ enriched cell population expressed the HNK-1 antigen too. When these cells were further separated into HNK-1+ and HNK-1- cells by means of the FACS thus yielding the VEP13+ HNK-1+ and VEP13+HNK-1- subsets, it could be demonstrated that both populations were able to mediate natural killing against K-562 target cells thus indicating existence of an HNK-1- natural killer cell population. Investigating lymphocytes from a patient suffering from a leukaemia in which 75% of cells were of LGL morphology, 32% of cells were found to be HNK-1+ while 76% of cells were shown to bear the VEP13 antigen, thus revealing a similar phenotype as observed in normal individuals. Our results indicate the existence of a HNK-1- VEP13+ natural killer cell population.

Antibodies, Monoclonal↗
PubMed1983

[Large, granular lymphocytes, a new population of mononuclear blood cells].

Large granular lymphocytes (LGL) represent a morphologically distinct and new population of mononuclear blood cells. In normals on average 12% of their peripheral blood mononuclear cells exhibit morphological features of LGL. In this article we summarize experimental evidence suggesting that LGL represent the effectors of spontaneous cell mediated cytotoxicity responses in normal as well as in diseased states. This conclusion is based on two main findings: 1. the frequency of LGL correlates with the capacity to mediated spontaneous cell mediated cytotoxicity when pooled data of normal controls were analyzed, as well as when different density fractions or organs from one and the same individual were compared. 2. disease associated reduction in the numbers of LGL is invariably accompanied by an impaired spontaneous cytotoxicity. It thus appears that evaluation of LGL by morphological means represents a new way to assess spontaneous cell mediated cytotoxicity responses.

Anemia, Aplastic↗
PubMed1983

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↗
PubMed1982

Large granular lymphocytes: morphological studies.

Large granular lymphocytes from normal human blood were enriched by centrifugation on discontinuous Percoll density gradients. Their capacity for natural killing, but not for phagocytosis of yeast cells, was demonstrated. Large granular lymphocytes are characterized in electron microscopy by their fine structure, especially by typical granules and by inclusions of tubular structures in a parallel array. Their lymphocyte nature is supported by activity of acid-alpha-naphthyl acetate esterase and by the absence of myelo-peroxidase (POX) and of macrophage POX. The Fc gamma receptor of their cell membrane is marked by soluble POX-anti-POX-complexes; labeled parts of their membrane are not incorporated into the cytoplasm as in monocytes.

Humans↗