PubMed Health⌕ Search

Biomedical subjects

W Falk

Publications and source records attributed to W Falk.

At least 91 records · Page 5Linked to original sources
PubMed1990

[Long-term results in the treatment of 100 metastatic hypernephroid carcinomas].

The success of renal cell carcinoma (RCC)-nephrectomy with radical lymph node dissection in stage I and II disease is undisputed. Through these measures 23% of metastases are controlled. The five-year survival time in stage III disease, however, stagnates at 35% +/- 14% despite radical surgery. Also, the additional tumor-vaccine-therapy of the Mainz-Joint-Study-Group was successful only in stage I and II disease, whereas stage III disease did not benefit from this therapy. As 50% of all radically operated patients developed metastases within three years after surgery, the call by radio-oncologists for supplementary radiotherapy beginning with stage III disease must be put foreward. The problems of therapy and chances of survival in generalized disease are demonstrated in 100 of our cases treated by surgery, radiotherapy and with MPA (medroxyprogesteroneacetate). Whereas Schmiedt et al. show a total survival time of 10,3 months after diagnosis of metastatic disease, the Offenbach patients achieved 16,5 months with a median survival time of 11,75 months. The necessity of therapeutic intervention is confirmed by the fact that the most favorable median survival time, 15,75 months, was achieved in metastatic disease involving three organs. We present here the special features of the individual organ manifestations and point out that not only the mean and median survival time, but also the very widely varying survival times in individual cases, make conscientious oncological post-treatment follow up and management a requirement.

Antineoplastic Agents↗
PubMed1989

Monoclonal antibody-mediated tumor regression by induction of apoptosis.

To characterize cell surface molecules involved in control of growth of malignant lymphocytes, monoclonal antibodies were raised against the human B lymphoblast cell line SKW6.4. One monoclonal antibody, anti-APO-1, reacted with a 52-kilodalton antigen (APO-1) on a set of activated human lymphocytes, on malignant human lymphocyte lines, and on some patient-derived leukemic cells. Nanogram quantities of anti-APO-1 completely blocked proliferation of cells bearing APO-1 in vitro in a manner characteristic of a process called programmed cell death or apoptosis. Cell death was preceded by changes in cell morphology and fragmentation of DNA. This process was distinct from antibody- and complement-dependent cell lysis and was mediated by the antibody alone. A single intravenous injection of anti-APO-1 into nu/nu mice carrying a xenotransplant of a human B cell tumor induced regression of this tumor within a few days. Histological thin sections of the regressing tumor showed that anti-APO-1 was able to induce apoptosis in vivo. Thus, induction of apoptosis as a consequence of a signal mediated through cell surface molecules like APO-1 may be a useful therapeutic approach in treatment of malignancy.

Animals↗
PubMed1989

IL-1 induces high affinity IL-2 receptor expression of CD4-8- thymocytes.

We investigated the role of cytokines for the growth of CD4-8-thymocytes (double negative thymocytes) (DNT) in vitro and found that IL-1-induced IL-2-dependent proliferation of only the IL-2R-positive DNT subpopulation. The presence of IL-1 during the first 18 h of culture was sufficient for an optimal response and suggested that IL-1 induced DNT differentiation. We could indeed show by RNA dot blot analysis that IL-1 stimulated de novo expression of the p55 chain of the IL-2R thus initiating high affinity IL-2 binding and a proliferative response. Because macrophages and epithelial cells in the thymus produce IL-1 we propose that IL-1 is involved in early events during maturation of immature thymocytes.

Animals↗
PubMed1989

Internalization of interleukin 1 (IL 1) correlates with IL 1-induced IL 2 receptor expression and IL 2 secretion of EL4 thymoma cells.

The cytokine interleukin 1 (IL 1) plays an important role in the induction of IL 2 secretion and high-affinity IL 2 receptor (IL 2R) expression by T cells. The events that follow binding of IL 1 to IL 1R, however, are still unknown. In this study we describe two variants of the murine thymoma EL4 (5D3 and D6/76) that express comparable numbers of cell surface IL 1 receptors and bind IL 1 with the same affinity, but show distinct IL 1-dependent IL 2 secretion and IL 2R expression. In the presence of the tumor promoter phorbol 12-myristate 13-acetate IL 1 augments IL 2 secretion and IL 2R expression of EL4 5D3 but not of EL4 D6/76 cells. Comparison of the internalization of IL 1 by both clones revealed that EL4 D6/76 was unable to transport cell surface-bound IL 1 to the cytoplasm. These findings suggest that internalization of receptor-bound IL 1 is required for the action of this cytokine.

Animals↗
PubMed1989

Optimal induction of tumor necrosis factor production in human monocytes requires complete S-form lipopolysaccharide.

Optimal activation of human monocytes in vitro for the biosynthesis of tumor necrosis factor was achieved only with complete S-form lipopolysaccharide. Endotoxin preparations with shorter carbohydrate chains or the lipid A component of lipopolysaccharide were not able to induce release of comparable amounts of tumor necrosis factor by monocytes under the conditions described. The same differences in the level of tumor necrosis factor mRNA were observed. Moreover, addition of these agents to appropriate monocyte-activating substances inhibited the production of tumor necrosis factor. The regulatory implications of this phenomenon are discussed.

Cell Line↗
PubMed1989

[Patient education and counseling responsibilities of an organization for handicapped patients in the field of rehabilitation].

Organizations of the disabled do not see their information and counselling activities as competing against those of the financially responsible administrations but as complementary ones. Crucial to their work are the provision of guidance through the structured social protection system, familiarization of disabled persons with rehabilitation as well as their motivation and support, with the aim of rendering the disabled individual an equal partner in the process of rehabilitation. The area of social rehabilitation is a major focus in the counselling of disabled people. As specific institutional responsibilities for social rehabilitation do not exist, information and counselling activities in these matters are also directed at administrations and industry.

Combined Modality Therapy↗
PubMed1989

Lack of interleukin-2 (IL-2) dependent growth of TAC positive T-ALL/NHL cells is due to the expression of only low affinity receptors for IL-2.

Binding of interleukin-2 (IL-2) to high affinity receptors on activated normal T cells was shown to be the essential step in induction of proliferation of such cells. The finding of abundant IL-2 receptors on malignant T cells in adult T cell leukemia suggested a deregulation of the IL-2/IL-2 receptor system and was assumed to account for aberrant growth in malignant disorders of T cells. In this study we use malignant T cells from nine patients with the clinical diagnosis of T-ALL or T-NHL and did not detect IL-2 dependent growth under conditions in which normal T cells responded to IL-2. IL-2 receptors comparable in numbers to activated T cells were found on T-ALL/T-NHL cells stimulated with PHA and PMA. However, binding studies using radiolabeled IL-2 indicated that the receptors present on malignant T cells were not able to bind to IL-2 with high affinity. Therefore, if IL-2 is involved in the proliferation of malignant T cells, its mechanism of growth regulation may be different from the one for normal T cells. Alternatively, IL-2 may not play a role in the regulation of growth of malignant T cells in vitro.

Adolescent↗
PubMed1989

Activation of T cells by interleukin 1 involves internalization of interleukin 1.

The cytokine interleukin-1 plays an important role in the induction of IL-2 secretion and IL-2 receptor expression. The events that follow binding of IL-1 to its receptor are not known. We found that in a purified T cell population (comprising the Lyt2- and L3T4- T cells) IL-1 in the absence of antigen or mitogen induced strong proliferation and de novo expression of IL-2R light chain mRNA. This was accompanied by high affinity IL-2 binding. Production of IL-2 or IL-2 mRNA was not detected under these conditions. As a model system for IL-1 action two EL4 subclones were isolated. EL4 5D3 responded to IL-1 by augmentation of PMA induced IL-2 secretion and IL-2R expression. EL4D6/76 bound IL-1 with the same affinity but did not respond. We found that this line was unable to internalize surface bound IL-1. The finding suggests that in T cells internalization of IL-1 is required for its activity.

Animals↗
PubMed1987

Interferon gamma and lymphotoxin or tumor necrosis factor act synergistically to induce macrophage killing of tumor cells and schistosomula of Schistosoma mansoni.

Macrophages play a crucial role in the defense against tumors and parasites. Activation of tumoricidal and microbicidal effector mechanisms requires stimulation of macrophages with macrophage-activating factors (MAF). One such MAF is interferon gamma (IFN-gamma). In some assays, substantial activity of IFN-gamma on murine macrophages, however, is only observed in synergy with lipopolysaccharide (LPS) or other cytokines (1). In addition, certain cytokines have been shown to induce monocyte or macrophage activation in the absence of IFN-gamma (2-5). We previously described lymphokines in the supernatant of a murine T cell clone that synergized with IFN-gamma in the induction of tumoricidal and schistosomulicidal murine macrophages (1). We called this lymphokine(s) macrophage cytotoxicityinducing factor 2 (MCIF2)(1). A candidate for MCIF2 was lymphotoxin (LT), because the T cell clone supernatant contained high amounts of LT. LT is functionally homologous and structurally related to the macrophage product tumor necrosis factor (TNF). Therefore, we tested whether recombinant (r) LT or rTNF can function as MAF. We report here that rLT or rTNF synergize with rIFN-gamma in the induction of tumoricidal and schistosomulicidal murine macrophages.

Cells, Cultured↗
PubMed1987

A new assay for interleukin-1 in the presence of interleukin-2.

A simple and reliable assay for interleukin-1 (IL-1) is described which has the advantage over other assays that it is independent of interleukin-2 (IL-2) production by the test cells. The assay makes possible the detection of IL-1 in the supernatants of T cell populations. The ability of IL-1 to induce IL-2 receptor expression in the absence of T cell mitogen is the basis of this assay. Thus, proliferation of mouse thymocytes incubated in the presence of saturating concentrations of IL-2 (10 U/ml) was directly dependent on the concentration of IL-1. The sensitivity of the assay is comparable to the sensitivity of the classical thymocyte co-stimulator assay. Natural and recombinant human and murine IL-1 were measured in this test system with comparable sensitivity.

Animals↗
PubMed1987

Endotoxic activities of tumor necrosis factor independent of IL1 secretion by macrophages/monocytes.

Recombinant tumor necrosis factor (TNF) had hypothermic activity in vivo. Intravenous injection of TNF resulted in a hypothermic reaction of mice within 3 to 6 hours. This reaction was not the result of interleukin 1 (IL1) release from macrophages/monocytes. Peritoneal exudate cell cultures from endotoxin low responder mice or human peripheral mononuclear leukocyte cultures did not generate IL1 activity in the supernatant after exposure to TNF. The addition of interferon-gamma (IFN-gamma) or preexposure to IFN-gamma and then stimulation with TNF did also not result in IL1 secretion. No IL1 inhibitor was generated and TNF did not interfere with the IL1 test systems. Therefore, we conclude that the hypothermic activity of TNF is not mediated via the induction of IL1 production by mononuclear phagocytes.

Animals↗
PubMed1986

[Immunologic findings in oral pertussis vaccination].

Whooping cough specific surface IgA antibodies, agglutinating serum IgG antibodies and the in vitro lymphocyte reactivity to Bordetella pertussis germs were investigated in newborns and infants both unvaccinated and parenterally and orally immunized against whooping cough. Furthermore the E-rosette formation and the lymphocyte reactivity to phytohaemagglutinin, pokeweed mitogen and concanavalin A were studied. Only oral pertussis immunisation effected a local immune reaction with formation of secretory surface IgA antibodies in the saliva and prevented the postnatal disappearance of the Bordetella pertussis specific IgG antibodies seen in unvaccinated infants. From the third month of life the lymphocyte reactivity to a Bordetella pertussis germ suspension resulted in measurable stimulation following oral whooping cough vaccination. After the third month of life the pertussis stimulation indices of the orally immunized infants remained above the values for adults with a history of whooping cough and were equivalent to those for the parenterally immunized infants.

Administration, Oral↗
PubMed1985

Inhibition of interleukin 2 production by prostaglandin E2 is not absolute but depends on the strength of the stimulating signal.

In view of the eminently important role of interleukin-2 (IL-2) in T-cell responses, and in view of reports about immune stimulatory effects of PGE2, we reinvestigated the question whether PGE2 inhibits IL-2 production. It was found that PGE2 does not inhibit IL-2 production in murine spleen cell cultures after optimal stimulation (5 micrograms/ml concanavalin A) but does inhibit at suboptimal stimulation conditions. The failure of PGE2 to inhibit IL-2 production at optimal concanavalin A concentration was demonstrated by two independent IL-2 assays namely by the co-stimulator assay and by the proliferation of IL-2-dependent T-cell clone W-2. Our observations indicated that the inhibitory effect of PGE2 depends on the strength of the stimulating signal. IL-2 production in cultures with 5 micrograms/ml concanavalin A was also not suppressed by PGE1, by prostaglandin D2, thromboxane B2 (T X B2), and prostaglandin F2.

Animals↗
PubMed1985

A combination of soluble helper factors bypasses the requirement for stimulator cells and induces nonspecific cytotoxic T cell responses.

The specificity of cytotoxic T lymphocyte (CTL) responses generated in the presence of lymphokines was studied. Thymic responder cells were activated in the presence of stimulator cells that differed in their metabolic activity. After 5 days of culture, the cytotoxic response was estimated in a 4-h 51Cr-release test. Coculture of thymic responders with irradiated splenic stimulator cells in the presence of interleukin 2(IL 2) led to preferential cytolysis of target cells that expressed the same histocompatibility antigens as the cells used for sensitization. Addition of T cell cytotoxicity-inducing factor 1 (TCF1), however, to those cultures made the presence of stimulator cells unnecessary and induced cytotoxic responses against all target cells tested, including target cells syngeneic to the responder cells. This activation was neither due to contaminating mitogen nor to the effect of heterologous serum in the assay system. The conclusion of these findings was that either polyclonal activation of CTL was induced by TCF1 or that some specific CTL clones differentiated into unrestricted killer cells under the influence of TCF1.

Animals↗
PubMed1985

Development and clinical use of an oral heat-inactivated whole cell pertussis vaccine.

An orally administered, killed whole cell pertussis vaccine was developed which proved to be safe and potent in animal experiments. This vaccine was studied in limited field trials in Austria. In these field trials 1 X 10(12) bacterial cells were given orally on days 2, 3, 4, and 5 after birth with an oral booster of 1 X 10(12) cells given at six weeks. This vaccine was tolerated without side effects in more than 20,000 newborns, did induce a specific immune response including anti-pertussis IgG in serum, anti-pertussis IgA in saliva and specific pertussis mitogen stimulation. This immune response occurred significantly earlier in the orally but not in the parenterally vaccinated group. In addition, anti-pertussis antibodies in saliva were not induced in the parenterally vaccinated group. Pertussis morbidity in 11,192 orally vaccinated infants was compared to 3496 infants who did not receive oral vaccination and was found to be significantly lower for up to one year. There was no overall difference between orally and non-orally vaccinated infants as far as pertussis hospitalization and verified pertussis infection after one year was concerned.

Administration, Oral↗