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Biomedical subjects

D Niethammer

Publications and source records attributed to D Niethammer.

At least 235 records · Page 13Linked to original sources
PubMed1983

Patterns of cross-resistance to the antifolate drugs trimetrexate, metoprine, homofolate, and CB3717 in human lymphoma and osteosarcoma cells resistant to methotrexate.

Methotrexate (MTX)-resistant sublines of malignant human cells were selected in vitro by stepwise increase in drug concentration in the medium. By this procedure a subline of Burkitt's lymphoma cells (RAJI) was made 290-fold resistant (RAJI/MTX-R), T-cell leukemia cells (CCRF-CEM) were obtained 210-fold resistant (CEM/MTX-R), and 3 MTX-resistant human osteosarcoma lines were selected: TE-85/MTX-R (19-fold resistant; relative to wild-type); MG-63/MTX-R (8-fold resistant); and SAOS-2/MTX-R (200-fold resistant). We also studied a B-cell lymphoblastoid line, WI-L2/m4, that was 13,000-fold resistant. Assay of cellular dihydrofolate reductase (DHFR) showed the following pattern of activity in resistant cell lines, relative to parental cell activity: RAJI/MTX-R, 550-fold increased; CEM/MTX-R, unchanged; TE-85/MTX-R, 4-fold increased; MG-63/MTX-R, 6-fold increased; SAOS-2/MTX-R, unchanged; and WI-L2/m4, 110-fold increased. Measurement of MTX membrane transport showed decreased uptake in CEM/MTX-R and SAOS-2/MTX-R, relative to parental cell lines. The other DHFR-overproducing cells all gave normal initial MTX uptake rates but increased total uptake. The DHFR-overproducing lines all had significant cross-resistance to both metoprine and trimetrexate; the two lines with defective MTX transport were not cross-resistant, and the CEM/MTX-R cells showed collateral sensitivity to these agents. Only minor cross-resistance to homofolic acid was found in all MTX-resistant lines. The highly MTX-resistant RAJI/MTX-R and WI-L2/m4 cells showed minor cross-resistance to the dual inhibitor of thymidylate synthetase and DHFR, CB3717 (5- and 15-fold, respectively). These studies demonstrated that, depending upon the mechanism of resistance, MTX-resistant human tumor cells may be effectively killed by antifolates with different routes of uptake into cells, or with a different enzyme target. Thus, there are at least three functionally distinct classes of folate antagonist with antitumor activity.

Antineoplastic Agents↗
PubMed1983

Malignant ovarian tumours during childhood.

Malignant ovarian tumours in childhood are rare. Germinal cell tumours are the most common tumours and are extremely malignant, with the exception of dysgerminomas. The possibilities of therapy have improved considerably in the last 3 to 4 years, thanks to combined chemo- and radiotherapy following surgical resection of the tumour. Exact staging at the beginning of therapy is very important. A second operation, primary or as a second look procedure, is recommended after emergency operations. Therapy should be carried out in pediatric oncology centres. Because of the invasive measures, medical and psychological care are necessary after the conclusion of therapy. The rarity of these tumours should prevail upon us to organize national and international therapeutic studies.

Adenocarcinoma↗
PubMed1983

[Combination of a Shwachman syndrome and a complex granulocyte function disorder in a girl].

We report the case of a 1-year-old girl with the typical symptoms of Shwachman syndrome: neutropenia, insufficiency of the exocrine pancreas, and metaphyseal dysostosis. The clinical course is complicated by recurrent infections caused by the neutropenia and an additional defect of granulocyte function. We demonstrate a severe defect of chemotactic activity as well as a disturbance of the intracellular oxidative metabolism leading to defective killing of Staphylococcus aureus and Candida albicans.

Bone Marrow Diseases↗
PubMed1982

[Bone marrow transplantation in patients with leukemia].

Between October 1979 and March 1982, bone marrow transplantations were performed by the Tübingen Group for BMT on 19 patients with acute leukemia in remission and on one patient with chronic myelocytic leukemia in chronic phase. The conditioning regimen consisted of 2 x 60 mg cyclophosphamide/kg and 10 Gy whole-body irradiation with the linear accelerator. The lung dose was limited by shielding to 8 Gy. In 15 patients, the bone marrow cell suspension of the donor was preincubated with antihuman T-cell globulin (AHTCG) for prophylaxis of graft-versus-host disease (GVHD). All patients showed prompt engraftment of donor cells with good hemopoietic function and complete chimerism. Under reverse isolation in sterile units, no severe bacterial or fungal infections were seen in the phase of bone marrow aplasia. Twelve in twenty patients survived between 25 and 900 days. A severe GVHD was seen only in two patients - one after preincubation with AHTCG. One patient died from relapse of his leukemia, another patient had a testicular relapse which was treated with local radiotherapy. Major problems were seen with chronic GVHD (six patients) and infectious complications, most importantly interstitial pneumonia, in the late post-transplant period.

Acute Disease↗
PubMed1982

Effect of human fibroblast interferon on natural killer cell activity: stimulation in vitro and inhibition in vivo.

This paper describes the influence of human fibroblast interferon (IFN-beta) on the cytotoxic activity of natural killer cells (NK) in vitro and in vivo using the blood of healthy donors and myeloma patients. IFN-beta stimulates NK activity against all target cells tested in vitro in a dose-dependent way up to 250% of pretreatment values. At higher IFN concentrations, stimulation returned to baseline values. Stimulation was most pronounced in the lowest lymphocyte to target cell ratio. 1- to 2-h preincubation of effector cells with IFN was enough to achieve maximal stimulation. The effector cells of IFN-treated myeloma-patients, or patients with herpes zoster, showed a clear reduction of toxicity against all cells tested during the first infusion, as compared to the pretreatment values.

Cytotoxicity, Immunologic↗
PubMed1982

Autoantibodies against human beta interferon following treatment with interferon.

Recently we reported the appearance of human beta interferon (HuIFN-beta) neutralizing antibodies in a patient with a nasopharyngeal carcinoma treated successfully with a preparation of HuIFN-beta. This was the first report presenting evidence for antigenicity of IFN in an homologous system. In the present report we asked whether the unusual appearance of antibodies was due to a genetic defect of the patient's cells to produce HuIFN-beta or whether the patient's cells produce an antigenically different variant of HuIFN-beta. We demonstrate that a fibroblast cell strain established from this patient produces HuIFN-beta which does not from a serological standpoint react differently from the HuIFN-beta preparation administered. The conclusion is drawn that the antibodies against therapeutic HuIFN-beta are reacting like autoantibodies with the patient's own HuIFN-beta.

Autoantibodies↗
PubMed1982

[Fatal granulocyte function defect in a male infant. Results of in vitro and in vivo stimulation with ascorbic acid as well as in vitro stimulation with levamisol and lithium chloride].

We report about a boy who suffered from repeated bacterial infections starting at the age of 4 weeks. A severe defect of chemotactic activity of the neutrophils, and an additional deficient phagocytosis were discovered. The child died at the age of 3 months from septicemia. Chemotactic activity could be stimulated in vitro by ascorbic acid and levamisole but not by lithium chloride. In vivo, however, the effect of ascorbic acid was minimal and treatment with this vitamin could not prevent the lethal end.

Ascorbic Acid↗
PubMed1981

Interferon-neutralizing antibodies in a patient treated with human fibroblast interferon.

During recent years clinical trials have shown that human leukocyte interferon (HuIFN-alpha) may be useful in the treatment of cancer, but very little has been done concerning the possible use of human fibroblast interferon (HuIFN-beta). Treuner et al. recently reported the successful treatment of a nasopharyngeal carcinoma with HuIFN-beta: in the course of IFN-therapy a HuIFN-beta neutralizing activity appeared in the serum of this patient. We report here that such activity is due to IgG antibodies--this study is the first to present evidence for antigenicity of IFN in a homologous system.

Antibody Formation↗