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W Digel

Publications and source records attributed to W Digel.

25 records · Page 2Linked to original sources

Strategy for the treatment of hairy cell leukemia.

Both splenectomy and alpha-interferon are efficient treatments for hairy cell leukemia. Since interferon therapy seems to induce remissions of the disease, avoids the risks of surgery, and sustains the spleen, it should be discussed if this therapy may replace splenectomy as primary treatment for this disease. In order to make this decision the biologic relevance of complete remissions in hairy cell leukemia, the reliability of methods to confirm remission, the benefits and risks of both splenectomy and interferon therapy, and some aspects of the pathogenesis of the disease have to be considered. Based on our experimental and clinical results and data from other groups, we conclude that splenectomy should still be recommended as primary therapy in hairy cell leukemia provided that treatment is indicated and the patient is eligible for surgery.

Combined Modality Therapy↗

Induction of interferon gamma in leucocyte cultures of the peripheral blood of mice.

The present report summarizes a number of approaches to elicit the production of interferon gamma (IFN-gamma) in leucocytes derived from the peripheral blood of mice. Only moderate titers were observed when the blood cells were obtained from untreated mice. Significantly higher IFN production in response to phytohemagglutinin (PHA) or Concanavalin A (Con A) was observed when mice were tested after pretreatment with B. pertussis organisms, which caused a marked lymphocytosis. Additionally, two restimulation approaches are presented which are based on preactivation of peripheral leucocytes with Con A (plus in one case with T cell growth factor) and subsequent restimulation with different mitogens. These techniques allow to obtain high yields of IFN-gamma in lymphocyte cultures derived from the peripheral blood of mice.

Animals↗

Interferons and bacterial infections.

Viruses have been established initially as interferon inducers and interferons have been considered to be antiviral proteins only. By our article we wish to draw attention to two observations: a) bacteria and derivatives thereof also are inducing the production of interferon b) interferons activate a number of defense mechanisms that are of potential relevance in antibacterial resistance. These two observations are not new. However, we believe, they deserve renewed attention within the framework of the pleiotropism of interferon effects and of the complexity of antibacterial defense mechanisms.

Animals↗

A whole-blood technique for testing production of human interferon by leukocytes.

Interferon production was studied in mixtures of whole blood of healthy adults with tissue culture medium. There was no need to supplement the system with additional foreign serum and even the autologous serum and even the autologous serum could be removed by washing in serum-free medium with-out impairment of interferon production. Heparinized blood samples could be stored in the refrigerator overnight before performing the assay. In this test, production of interferon gamma was observed in response to phytohemagglutinin, concanavalin A, pokeweed mitogen, staphylococcal enterotoxin A, and to OKT-3, a monoclonal anti-T cell antibody. Production of interferon alpha was observed when viruses were used as inducers. Our experiments show that in the whole-blood assay the responses to several inducers of different types of interferons may be readily monitored under serum-free conditions. We believe that this test will be of value for testing large numbers of normal individuals (for investigations of the genetics of interferon production) or of patients with a variety of diseases.

Antilymphocyte Serum↗

Spontaneous interferon-alpha antibodies in a patient with pure red cell aplasia and recurrent cutaneous carcinomas.

High-titered spontaneous interferon (IFN) antibodies were detected in a patient with pure red cell aplasia (PRCA), a benign mediastinal tumor, and recurrent cutaneous carcinomas. The circulating IFN antibodies reacted broadly with various human IFN-alpha subtypes (20-140 x 10(3) neutralizing units/ml serum) but not with IFN-beta or IFN-gamma, and they neutralized the antiviral activity of the patient's endogenous IFN-alpha. The IFN-alpha-binding activity was restricted to the IgG1 subclass in a nonmonoclonal manner. Whereas the PRCA repeatedly responded to immunosuppression with high-dose cyclosporin A (CSA) and CSA plus plasmapheresis, IFN antibody production continued during treatment with cyclophosphamide and CSA. Serological analysis revealed past infection with parvovirus B19 and persistent B19 IgM titers. Antibody-mediated impairment of the IFN-alpha system might have favored the development of both PRCA and the various cutaneous carcinomas in this patient.

Aged↗

Elevated plasma cortisol levels during interferon-gamma treatment.

We investigated plasma levels of cortisol and ACTH in 9 patients with advanced metastatic tumors before and during treatment with interferon-gamma (IFN-gamma), 2-4 h after administration of IFN-gamma there was a sharp rise in plasma cortisol levels. The rise coincided with the onset of fever. Highest cortisol levels were reached 4-6 h after IFN-gamma injections, whereas IFN-gamma serum levels peaked 6-10 h after the IFN-gamma injections. Elevated cortisol levels during IFN-gamma treatment may be part of a homeostatic response of the neuroendocrine system to the immunological stimulus induced by IFN-gamma. On the other hand, the increased plasma levels of cortisol in response to pharmacological doses of IFN-gamma may dampen the in vivo effectiveness of IFN-gamma.

Adrenocorticotropic Hormone↗

Antiviral effects of recombinant tumour necrosis factor in vitro.

Tumour necrosis factor (TNF) was first described as a factor in the serum of mice injected with tubercle bacilli (BCG) and several days later with lipopolysaccharide (LPS). The gene encoding TNF has recently been cloned and pure recombinant human TNF is now available. TNF is known for its in vivo antitumour effect and in vitro cytotoxicity on certain transformed cell lines. Similarities in amino acid sequence and biological activity to lymphotoxin and cachectin have been reported, and very recently a growth-factor-like activity on diploid fibroblasts was observed. There is no similarity between these proteins and interferons (IFNs), which are also induced during in vivo induction of TNF. Here we describe the antiviral activity of pure recombinant human TNF in a typical in vitro antiviral assay which we discovered while investigating the possible role of TNF as an inducer of IFN.

2',5'-Oligoadenylate Synthetase↗