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H Kirchner

Publications and source records attributed to H Kirchner.

At least 271 records · Page 15Linked to original sources
PubMed1989

Enhanced interferon-gamma production by lymphocytes induced by a mitogen from mycoplasma arthritidis in patients with ankylosing spondylitis.

We have examined proliferation of and interferon-gamma (IFN-gamma) production by peripheral blood lymphocytes induced by a purified mitogen derived from mycoplasma arthritidis (MAS) in patients with seronegative spondylo-arthropathies and healthy individuals. In all patients and healthy controls MAS exerted a potent nonspecific lymphoproliferation. In contrast, only patients with ankylosing spondylitis (ASp) showed a strong IFN-gamma production after stimulation with MAS. The maximal IFN-gamma response was observed in HLA-B27+/HLA-DQw3+ patients. However, healthy controls with the HLA-DQw3 haplotype with or without the presence of HLA-B27 exhibited also a slight but statistically not significant increase of IFN-gamma production. Moreover, in this study we have found an enhanced frequency of HLA-DQw3 in patients with ASp and reactive arthritis. This immunogenetic association explains the enhanced lymphocyte reactivity in these inflammatory rheumatic disorders to mycoplasmal antigens.

Antigens, Bacterial↗
PubMed1989

Chemotherapy of Hodgkin's lymphoma with alternating cycles of COPP (cyclophosphamide, vincristin, procarbazine, prednisone) and ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine). Results of the HD1 and HD3 trials of the German Hodgkin Study Group.

Untreated patients with Hodgkin's lymphoma in stages I-IIIA with risk factors (large mediastinal mass, massive splenic involvement, extranodal disease) were entered into the HD1 protocol and received a combined chemo-radiotherapy [2 X (COPP + ABVD) + 40 Gy extended field irradiation (EF) vs 2 X (COPP + ABVD) + 20 Gy EF]. Patients in stages IIIB/IV (HD3 protocol) received induction chemotherapy [3 X (COPP + ABVD)] and were randomized into consolidation by radiotherapy [20 Gy involved field irradiation (IF)] vs chemotherapy [1 X (COPP + ABVD)]. Seventy-three of 89 evaluable patients (82%) treated according to the HD1 protocol achieved a complete remission. Freedom from progression and survival of patients in stages I-IIIA with risk factors treated according to HD1 were no worse than those of patients in stages I and II without risk factors who received only radiotherapy. Eighty-six of 137 patients (63%) treated according to the HD3 protocol achieved complete remission after induction chemotherapy with COPP + ABVD. This is significantly better than the 31% complete remission rate observed in a previous pilot study with COPP alone (P less than 0.01). Including salvage therapy (radiotherapy in case of persisting nodal disease; chemotherapy with 4 X CEVD in case of persisting disseminated disease), a total of 76% complete remissions in stages IIIB/IVAB were achieved. A high erythrocyte sedimentation rate (greater than 80 mm h-1) was the most significant risk factor for achieving freedom from progression.

Adolescent↗
PubMed1989

Resistance of human blood monocytes to infection with herpes simplex virus.

Human blood monocytes isolated by centrifugal elutriation were resistant to infection with herpes simplex virus type 1 (HSV). In vitro cultivation for several days resulted in a stepwise increase of virus yield. Similar amounts of virus absorbed to fresh and cultured monocytes. No viral DNA was associated with the nuclear fraction of freshly isolated monocytes early after infection indicating that early steps of virus infection were already inhibited in resistant cells. This argues against HSV induced interferon (IFN) being a major mediator of resistance. Culturing the cells for some hours was sufficient to overcome the early block. However, as revealed by virus yield assays, monocytes after 1 day of cultivation were not as susceptible as cells after 6 days of cultivation. Viral sequences could be demonstrated in the nuclei of freshly isolated monocytes after treatment with the fusion-promoting agent polyethylene glycol. Under these conditions no DNA replication occurred, indicating that overcoming the block of viral DNA entry into the nucleus was not sufficient to break resistance of the cells. Thus, the results show that several mechanisms are involved in the primary resistance of human blood monocytes to HSV.

DNA, Viral↗
PubMed1989

Role of interleukin 1 in mycoplasma mitogen-induced proliferation of human T cells.

Recently, a mitogenic effect of the supernatant of cultured mycoplasma arthritidis (MAS) on human and murine lymphocytes has been described. Here, we studied the role of accessory cells (AC) in MAS-induced T cell proliferation in a system of human leukocytes. Nylon-wool purified T cells were non-responsive to MAS with regard to both proliferation and IFN-gamma production. The capacity of T lymphocytes to respond to MAS could be restored when viable AC were added. Treatment of AC with UV light resulted in a cell population which was incapable of reconstituting T cells. Addition of human recombinant interleukin 1 alpha (IL 1 alpha) or IL 1 beta again showed a reconstituting effect. However, only a partial reconstitution of the T cell response could be achieved by addition of recombinant IL 1 alpha or IL 1 beta. The optimal restoration was achieved by adding IL 1 at a concentration of 100 U/ml IL 1 alpha or 100 U/ml IL 1 beta. The results indicate that metabolically active AC were required for MAS-induced T cell proliferation to occur and that IL 1 was able to substitute for the role of AC. Since this restoration was only partial, it remains to be determined whether factors others than IL 1 are required to fully substitute the role of accessory cells.

Antigen-Presenting Cells↗
PubMed1989

Tumour necrosis factor production and natural killer cell activity in peripheral blood during treatment with recombinant tumour necrosis factor.

Tumour necrosis factor (TNF) has been found to be an important immunomodulator. Among other functions TNF activates natural killer (NK) cells and stimulates monocytes/macrophages in an autocrine fashion. TNF production and NK activity in peripheral blood mononuclear cells were determined in a clinical phase I study in which recombinant human (rh) TNF was administered as a continuous infusion weekly for a period of 8 weeks. Even though TNF production and NK activity were significantly reduced directly after rhTNF infusion the effect proved to be transient and most pronounced at the first rhTNF administration. One day after completion of the rhTNF infusion the peripheral cells released more TNF into the supernatant compared to TNF activity immediately before the rhTNF infusion. This effect was conspicuous in non-stimulated cultures. After repeated rhTNF infusions both stimulated and non-stimulated TNF production of the peripheral blood mononuclear cells was increased. NK cell activity was also enhanced after repeated cycles of rhTNF administration as compared to early rhTNF treatment. Thus, repeated rhTNF infusions lead to a stimulatory effect on TNF production and NK activity of peripheral blood cells.

Adult↗
PubMed1989

Persistent replication of herpes simplex virus type 1 in JOK-1 cells.

Infection of the human B cell line JOK-1 with herpes simplex virus type 1 persisted over a period of more than 12 months (to date). Although limited cytopathic effects were seen, viral infection did not lead to extinction of the culture. Infectious centre assays, performed at various times after infection, revealed that only a small proportion of cells (1 to 10%) produced infectious virus particles. However, immunofluorescence studies showed that at any given time considerably more cells than calculated by infectious centre assays contained the immediate early viral protein ICP4 and expressed viral glycoproteins. These observations were confirmed by in situ hybridization analyses which revealed the presence of viral DNA even in cells not producing infectious particles. Since no evidence for the involvement of interferon could be found, some other so far unknown intrinsic property of the cells must be responsible for the restriction of virus replication and/or maturation.

Antigens, Viral↗
PubMed1989

In vitro development of bone-marrow-derived macrophages. Influence of mouse genotype on response to colony-stimulating factors and autocrine interferon induction.

Responsiveness to granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage CSF (M-CSF) of bone marrow cells derived from different mouse strains was investigated. There were great variations in proliferation between different strains of inbred mice. Bone marrow cells from mouse strains with a high rate of proliferation in response to GM-CSF also had a high proliferating capacity to M-CSF. The response to either CSF did not correlate with a certain H-2 haplotype. GM-CSF induced consistently higher proliferation than M-CSF. Proliferation in response to M-CSF, but not to GM-CSF, could be enhanced by the addition of antibodies against interferon (IFN). IFN is the only known inducer of (2'-5') oligoadenylate (oligo (A] synthetase. This enzyme was induced in macrophages grown in the presence of M-CSF, but not in GM-CSF promoted cells. Enzyme induction was completely abrogated by simultaneous treatment with anti-IFN alpha/beta. Infection of macrophages with herpes simplex virus type 1 (HSV) and vesicular stomatitis virus (VSV) revealed that GM-CSF-promoted cells were highly susceptible to lytic infection by these viruses. In contrast, virus titres in M-CSF-cultured cells were 100-fold lower. We conclude that, contrary to M-CSF, GM-CSF does not induce autocrine IFN during haematopoiesis. As judged from data with BALB/c mice, the sensitivity to the anti-proliferative effect of the autocrine IFN may be a factor which influences M-CSF-promoted proliferation.

2',5'-Oligoadenylate Synthetase↗
PubMed1989

Immunophenotypic demonstration of two natural killer surface markers, H25 and H366, on fresh human leukemic cells.

Using a modified alkaline-phosphatase/antialkaline-phosphatase method for phenotyping fresh human leukemias, we could demonstrate peripheral blood and bone marrow-derived blast cells to specifically react with two monoclonal antibodies (MoAbs), H25 and H366, previously shown to recognize natural killer cells, activated T lymphocytes and a proportion of normal hematopoietic precursor cells. MoAbs H25 and H366 were found to identify the majority of leukemic cells in patients presenting with T-ALL, LGL leukemia, pre-B-ALL, CML, and AML, respectively.

Animals↗
PubMed1989

[Mechanism of resistance to tumor necrosis factor].

To find clues as to the possible mechanisms of resistance against the cytotoxic activity of tumor necrosis factor (TNF), we developed TNF-resistant and TNF-sensitive subclones of the human cervic carcinoma cell line ME 180 and the mammary carcinoma cell line BT-20. Resistant subclones were selected by gradually increasing the TNF concentration in the culture medium over 4 months or 20 passages. Resistance to TNF was conserved in the absence of TNF after nearly 3 years and less than 100 passages. There were no differences in the number and affinity of TNF receptors between the sensitive and resistant clones. Similarly, SDS-PAGE of cell lysates showed identical bands. Sensitivity to actinomycin D, mitomycin C, and interferon-gamma was the same. No TNF message could be demonstrated in either subclone. As tumors grown in nude mice derived from the sensitive and resistant clones responded equally well to an intratumoral injection of TNF, we conclude that different mechanisms are responsible for sensitivity and resistance to the cytotoxic effect of TNF in vitro and in vivo.

Animals↗
PubMed1989

[Surgical therapy of anorectal abscesses and fistulas].

Retrospective analyses were made of 171 of 200 patients on whom operations had been performed for anorectal abscesses and fistulas, between 1981 and 1985. For abscess exposure and deroofing, we tried to perform simultaneous fistulotomy, with no recurrence being recorded from 37 patients treated that way. The major courses of anorectal fistulas proved to be predictible in most cases. Surgical approach and postoperative management are described in some detail. Clinical records were evaluated together with a questionnaire, with particular reference being made to the type of fistula, susceptibility to recurrence, faecal continence as well as length of hospitalisation and certified absence from work.

Abscess↗
PubMed1989

Lymphokines.

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Animals↗
PubMed1988

Different antitumor mechanisms of interferon-alpha in the treatment of hairy cell leukemia and renal cell cancer.

There is increasing evidence for the therapeutic effectiveness of Interferon-alpha (IFN-alpha) in malignant diseases. However, the antitumor mechanisms of IFN-alpha are not known. Using two examples, hairy Cell leukemia (HCL) and renal cell cancer (RCC), it is shown that the requirements for successful IFN-alpha therapy of HCL and RCC are different. In HCL low doses of IFN-alpha are sufficient to treat the disease. The reduction of hairy cells in peripheral blood is detectable within the first week of treatment. The endogenous IFN-alpha production in these patients is impaired as demonstrated by the lack of IFN-alpha induction and by low levels of 2-5 oligoadenylate synthetase in peripheral blood mononuclear cells. A possible reason for deficient endogenous IFN-alpha production is the lack of monocytes in HCL patients. It is likely that therapy with low doses of IFN-alpha substitutes for the endogenous IFN-alpha deficiency. In RCC comparatively high doses of IFN-alpha are necessary for a clinical response. There may be differences between the effectiveness of natural and recombinant alpha interferons. High doses given within a week seem to be more important than high single doses, which therefore suggests the need of daily treatment. Responses of RCC to IFN-alpha therapy are usually seen several months after the beginning of therapy. These differences in the effectiveness of IFN-alpha therapy for HCL and RCC suggest that IFN-alpha acts differently in the treatment of each disease.

2',5'-Oligoadenylate Synthetase↗
PubMed1988

Clonal analysis of human T cell activation by the Mycoplasma arthritidis mitogen (MAS).

Mycoplasma arthritidis produces an as yet undefined soluble molecule (MAS) that has a potent mitogenic effect on T cells of several species. We have used cloned human cytotoxic and proliferative T lymphocytes to dissect the molecular mechanism of T cell activation by this mitogen. Reactivity to MAS is clonally expressed among T cell receptor (TcR) alpha/beta chain-expressing T cell clones of CD4+ or CD8+ phenotype, as well as CD4-8- TcR alpha/beta chain-negative T lymphocyte clones expressing the CD3-associated TcR gamma chain. MAS is able to induce cytotoxicity and/or proliferation in these T cell clones. For triggering of these T cells, regardless of their phenotype of specificity, the presence of autologous, allogeneic or xenogeneic major histocompatibility complex (MHC) class II molecules on accessory cells or target cells is necessary. However, T cells do not immunologically recognize MAS on class II molecules, since a direct action of MAS on the T cells themselves can be demonstrated. Triggering of T cells by MAS can be blocked by monoclonal antibodies against CD2, CD3 and the TcR alpha/beta chain dimer. We discuss as a possible explanation that MAS is a functionally bivalent molecule cross-linking TcR and MHC class II molecules. Thus, the mechanism of T cell activation by MAS has striking similarities to the mechanisms by which Staphylococcal enterotoxins activate T cells. It is intriguing that a similar mitogenic principle has been developed by two evolutionary distinct pathogenic microorganisms.

Antigen-Antibody Reactions↗
PubMed1988

Processing requirements for T cell activation by Mycoplasma arthritidis-derived mitogen.

Mycoplasma arthritidis produces in culture a polyclonal mitogen which is active for murine and human T lymphocytes in the presence of accessory cells (AC). We studied the requirements for processing and presentation by AC of Mycoplasma arthritidis supernatant (MAS) mitogen to human T cells. As inhibitors of AC processing, several agents were used which inhibit lysosomal function: the weak bases chloroquine and NH4Cl, the cationic ionophore monensin and the competitive protease inhibitor leupeptin. When these agents were used to inhibit processing by presenting cells and washed out before T cells were added to culture, they inhibited lymphocyte activation and, therefore, we assume that they interfered with the presentation of the mitogen. Thus, if MAS requires a processing step, it appears to involve lysosomal proteolysis which can be blocked in vitro.

Ammonium Chloride↗
PubMed1988

Depressed PPD and tetanus toxoid presentation by monocytes to T lymphocytes in patients with rheumatoid arthritis: restoration by interferon gamma.

A diminished antigen presentation of blood monocytes to autologous T cells has been recently described in patients with rheumatoid arthritis (RA). In this study the defective presentation of common recall antigens by blood monocytes revealed it to be a monocyte dysfunction specific for RA which could not be found in other chronic inflammatory rheumatic or non-rheumatic diseases and which could be restored by recombinant human interferon gamma. In addition, RA monocytes in blood exhibited a strongly reduced expression of HLA-DR determinants on the cell surface. T cells from RA patients produced almost normal interleukin-2 (IL-2) levels and showed a normal IL-2 sensitivity after phytohemagglutinin (PHA) stimulation. Several reasons may be responsible for this altered monocyte function in RA. Among these an in vivo "preactivation" of monocytes associated with a reduced antigen-presenting capacity or an impaired regulation of monocyte/macrophage differentiation are discussed.

Adult↗
PubMed1988

Interferon treatment inhibits onset of herpes simplex virus immediate-early transcription.

Pretreatment of primary cultures of splenic mouse macrophages with murine IFN-alpha/beta leads to a stable inhibition of herpes simplex virus type 1. Analysis of viral DNA, RNA, and protein synthesis identifies expression of "immediate-early" genes as a major target of IFN-mediated inhibition. Determination of viral DNA in the nuclei early after infection, i.e., before onset of DNA replication, suggests that virus uptake, transport to the nucleus, and DNA stability are not decreased in IFN-pretreated macrophages. Nuclear runoff transcription analysis shows a significant reduction of immediate-early transcription rates following IFN treatment. End-specific probes for the ICP4 gene locate the inhibition to the onset of transcription. Northern blot analysis reveals a decrease in ICP4 transcripts in accordance with the observed inhibition of transcription. The observed inhibition of early gene transcription may be a consequence of decreased immediate-early gene expression.

Animals↗
PubMed1988

Blocking of interferon synthesis in murine macrophages by pretreatment with interferon.

The influence of pretreatment with interferon (IFN) on subsequent IFN synthesis was investigated in macrophage cultures of DBA/2 and C57BL/6 mice. The doses of IFN alpha/beta for pretreatment ranged from 10,000 U/ml to 100 U/ml and the incubation time was between 18 and 2 h. No blocking effect was observed for chemical induction with poly I:poly C or CMA. However, for viral infection with NDV, blocking was observed. This inhibition of IFN synthesis was dependent on the dose and time of IFN pretreatment and of the titer of the inducing virus. Similarly in mouse fibroblast cultures no blocking activity was observed for induction with poly I:poly C/DEAE-dextran. Again, with NDV as inducer, pretreatment with IFN resulted in inhibition of interferon synthesis. Thus, our data show that blocking occurs only with a viral inducer and suggest that it is caused by an antiviral effect.

Animals↗