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Biomedical subjects

H Kirchner

Publications and source records attributed to H Kirchner.

At least 343 records · Page 19Linked to original sources
PubMed1985

Proliferation and interferon production in whole blood samples and isolated lymphocyte preparations.

To establish a method for the evaluation of immunological parameters in small blood samples, a whole blood technique was developed for the estimation of mitogen induced cell proliferation and interferon (IFN) production. The results obtained were compared with data using isolated peripheral blood lymphocytes (PBL). Mixtures of heparinized whole blood and culture medium or equal numbers of PBL of healthy volunteers or of patients were cultured with the mitogens concanavalin A, phytohemagglutinin, pokeweed mitogen or the monoclonal antibodies OKT3 and anti-Leu-4. Cell proliferation as measured by 3H-thymidine incorporation and interferon production were found to be of higher magnitude in the whole blood assay. The only situation in which results were similar was pokeweed mitogen induced cell proliferation. Since in the whole blood assay the cell populations are present in their natural distribution, this test system may reflect the in vivo situation better than the test using isolated lymphocytes. Furthermore, our data indicate that whole blood samples may be used clinically for the evaluation of different immune parameters, as data on a limited number of patients with Hodgkin's disease have shown.

Antibodies, Monoclonal↗
PubMed1985

Inhibition of replication of herpes simplex virus in mouse macrophages by interferons.

The replication of herpes simplex virus (HSV) type 1 in macrophages grown from spleen cells of mouse strains susceptible to HSV infection in vivo was very sensitive to interferon (IFN). Different types of mouse IFN (alpha, beta, gamma) exhibited similar antiviral activities. However, treatment of cells with IFN-gamma in combination with IFN-alpha or IFN-beta resulted in a synergistic inhibition of virus growth. As shown by assaying HSV DNA polymerase, IFN inhibited expression of the beta-genes. Inhibition of enzyme induction correlated well with the reduction of viral yield. Induction of HSV DNA polymerase was delayed by IFN in a dose-dependent manner. These results show that IFN inhibits HSV replication at an early step prior to or during the synthesis of beta-proteins.

Animals↗
PubMed1985

Injection of anti-thy-1.2 serum breaks genetic resistance of mice against herpes simplex virus.

Nude mice have been shown to be as resistant to intraperitoneal infection with herpes simplex virus type 1 (HSV) as their heterozygous littermates. Here we document that both activation of natural killer (NK) cells and interferon induction were normal in nu/nu mice after injection of HSV. Injection of silica caused increased mortality by HSV in C57BL/6 mice. Silica, in addition, led to a significant reduction of NK cell activity but had no effect on the interferon response. Treatment of C57BL/6 mice with anti-asialo GM1 (an antiserum with a predominant effect on NK cells) caused complete abolition of the NK cell response, but had no effect on interferon induction or virus-induced mortality. In further studies a monoclonal anti-thy-1.2 antibody was utilized which possessed high activity in vivo in depleting T cell responses in mice. Injection of anti-thy-1.2 decreased NK cell activation but was without effect on the interferon response. Unexpectedly, in view of the data in nu/nu mice, this antibody increased HSV-induced mortality in C57BL/6 mice. Similar data were obtained when anti-thy-1.2 was injected into nu/nu mice. Our results are compatible with the hypothesis that T cell precursors sensitive to anti-thy-1.2 present in homozygous nude mice play a role in resistance against HSV. Furthermore, the data in the euthymic mice may indicate a role of T cells in the primary resistance of mice against HSV.

Animals↗
PubMed1985

Decreased production of interferon alpha and interferon gamma in leucocyte cultures of schizophrenic patients.

In a first approach to measure the activity of the interferon system in schizophrenic patients, leucocyte cultures of schizophrenic patients and normal control individuals were set up using a whole blood assay. In this system both lymphoproliferation and the induction of interferon was tested. The lymphoproliferation (LP) test was performed with one bacterial recall antigen (PPD) and four different mitogens (phytohemagglutinin (PHA), concanavalin A (Con A), pokeweed mitogen (PWM) and a novel mitogen derived from mycoplasma arthritidis - MAS). For induction of interferon two inducers of interferon alpha (Corynebacterium parvum and Newcastle disease virus (NDV] and two inducers of interferon gamma (PHA and Con A) were tested. Leucocytes of the patients responded to C. parvum, NDV and Con A with significantly lower titers of interferon, whereas the responses to PHA were lower than those of normals, but this difference was not significant. Regarding the LP test, significantly lower responses of the patients were obtained with PHA and Con A, whereas there were no significant differences when the responses to MAS, PWM or PPD were compared. Although our data cannot rule out a role of the medications in the defects observed, they may be indicative of a defect in the interferon system of schizophrenic patients.

Adult↗
PubMed1985

[Interferon production and lymphoproliferation in whole blood of schizophrenia patients].

Using a whole blood assay the activity of the interferon system and mitogen-induced lymphoproliferation were tested in schizophrenic patients and normal individuals. Leucocytes of the patients produced significantly less interferon than controls after stimulation with the alpha interferon inducers Corynebacterium parvum (CP) or Newcastle disease virus (NDV) and with the gamma interferon inducers PHA and Con A. Differences in the lymphoproliferation test were also measured. Significantly lower responses of the patients were observed when using PHA and Con A as mitogens.

Humans↗
PubMed1985

Identification of herpes simplex virus type 1 (HSV-1) glycoprotein gC as the immunodominant antigen for HSV-1-specific memory cytotoxic T lymphocytes.

The frequency and fine specificity of herpes simplex virus (HSV)-reactive cytotoxic T lymphocytes (CTL) of C57BL/6 mice was investigated in limiting dilution culture. The reactivity patterns of virus-specific CTL were assayed on target cells infected with HSV type 1, strain KOS, HSV type 2, strain Mueller, and mutants of HSV-1 (KOS) antigenically deficient or altered in glycoproteins gC or gB, two of the four major HSV-1-encoded cell surface glycoprotein antigens. Most CTL clones recognized type-specific determinants on target cells infected with the immunizing HSV serotype. In addition, the majority of HSV-1-specific CTL did not cross-react with cells infected with syn LD70, a mutant of HSV-1 (KOS) deficient for the presentation of cell surface glycoprotein gC. These data are the first demonstration of the clonal specificity of HSV-1-reactive CTL, and they identify gC as the immunodominant antigen. The fine specificity of gC-specific CTL clones was analyzed on target cells infected with mutant viruses altered in the antigenic structure of gC. These mutants were selected by resistance to neutralization with monoclonal antibodies, referred to as monoclonal antibody-resistant (mar) mutants. Most mar mutations in gC did not affect recognition by the majority of CTL clones. This indicated that most epitopes recognized by CTL are distinct from those defined by antibodies. The finding, however, that one mar mutation in gC affected both CTL and antibody recognition of this antigen may help to define antigenic sites important to both humoral and cell-mediated immunity to herpesvirus infection.

Animals↗
PubMed1985

Proliferative responses to human cytomegalovirus in lymphocyte cultures of male homosexuals.

29 healthy adults and 32 male homosexuals were investigated for their humoral and cellular immunity against human cytomegalovirus (HCMV). In contrast to 30% of the controls, all homosexuals had HCMV serum antibodies. In addition, 84% of the homosexuals reacted positively in HCMV induced in vitro lymphocyte proliferation as compared to 66% of the controls. The study group also showed significantly higher mean reactivities in the lymphoproliferative response towards HCMV. In the group of homosexuals, a correlation could be established between the humoral and cellular immune reactivity to HCMV.

Adult↗
PubMed1985

[Effect of anastomosis technic on wound healing in the gastrointestinal tract. Animal experiment study of the dog colon with special reference to manual suture technics].

Three manual suture techniques (double-layer inverting, single-layer end-to-end, and continuous suture of the submucosa) were compared with anastomoses performed by stapling instruments (EEA, KZ 28) on the canine colon. The two manual techniques with exact end-to-end apposition led to primary wound-healing during the early postoperative period (3-20 days). There was no significant stenosis at the site of anastomosis five and ten months postoperatively. Inverting sutures as well as stapled anastomoses, however, showed delayed healing with considerable inflammatory reaction, resulting in marked stenosis after five to ten months.

Animals↗
PubMed1985

[Manometry studies in the evaluation of anal continence].

In a complex measuring program performing anorectal perfusion manometry a great number of parameters were determined in incontinent patients, patients after continence improving operations and in healthy persons. In this way, we were able to select 20 parameters in which healthy persons differ from incontinent patients, the difference occurring with a security of 99.0 to 99.9%. Our investigations were carried out with test persons at rest, after distension of the rectal ampulla, during abdominal straining and coughing. Rectoanal resting profiles and stress profiles were recorded and the measuring values obtained compared with an anamnestic score.

Adolescent↗
PubMed1985

[Manometry studies of continence performance in patients following gracilisplasty].

Out of a total of 10 patients who had undergone a Pickrell-procedure of the gracilis muscle from 1970-1980, 6 were now followed-up by clinical examination and perfusion manometry of the anal canal. The manometric parameters were compared with an anamnestic score. For anal continence the degree of resting activity of the transposed gracilis muscle is in our opinion not decisive. For that reason, there is no necessity for a permanent contraction.

Adolescent↗
PubMed1984

Interferon induction in human mixed leukocyte-tumor-cell reactions: evidence for restriction to a certain lineage expressing glycophorin A.

This study reports the induction of interferon (IFN) in human mononuclear cells (MNC) by hematopoietic tumor cells. Only 3 out of 15 cell lines were capable of inducing IFN in the mixed leukocyte/tumor-cell reaction (MLTR). K562, a pluripotent stem cell line and DUTKO-I, a hybrid between K562 and Daudi (Burkitt lymphoma) induced high levels of antiviral activity (ranging from 50-440 units IFN/ml). PUTKO-I, a hybrid between K562 and P3HR-I (Burkitt lymphoma) induced very low levels of IFN (10 units/ml). This antiviral activity was produced by HLA-DR + adherent cells as revealed by different cell separation techniques, and shared well-known properties of IFN gamma (isoelectric point, inactivation by anti-human IFN gamma antibodies; species-restricted protection). MLTR-induced IFN induction could be blocked by enzyme treatment of tumor cells, but was still present when glutaraldehyde-fixed cells were used for induction. Analysis of the cells by flow cytometry for expression of glycophorin A (GpA) revealed that expression of GpA correlated with the ability to induce antiviral activity in MLTR. Furthermore, isolated GpA could be used as a stimulant as well and the response to either K562 cells or soluble GpA was enhanced up to ten-fold by the addition of a GpA-specific monoclonal antibody.

Cell Communication↗
PubMed1984

Experimental infection of inbred mice with herpes simplex virus. VI. Effect of interferon on in vitro virus replication in macrophages.

Peritoneal exudate cells (PEC) of DBA/2 mice, after 7 days of in vitro preculture and consisting of virtually 100 per cent macrophages, were able to support the replication of Herpes Simplex Virus type 1 strain WAL (HSV). Using a standard medium based on Dulbecco's Modified Eagle Medium (D-MEM), no virus replication was observed in freshly isolated PEC. However a medium based on RPMI 1640 consistently yielded higher virus titres in precultured PEC than the D-MEM medium, and also allowed virus replication in freshly isolated PEC. Macrophages derived from the spleens or the bone marrow, and precultured in the same way as PEC represented a highly pure population and were permissive for infection with HSV. Titres of about 10(6) PFU HSV were observed in PEC 48 hours after infection with 10(3) or 10(6) PFU. However, whereas a complete destruction of the cell monolayer was observed 24 hours after infection with 10(6) PFU, complete cytopathogenicity in PEC infected with 10(3) PFU required at least twice this time. In the latter situation, plaque formation was observed 24 hours after infection. PEC of different strains of mice were compared. Of these, PEC of all mice that are susceptible to HSV infection in vivo replicated HSV to the same degree as PEC of DBA/2 mice, whereas PEC of resistant C57BL/6 and C3H/HeJ mice produced 1000 fold lower titres of viral progeny. Whereas the number of infectious centres were equal in PEC of DBA/2 and C57BL/6 mice, the plaques observed after infection of confluent PEC with a low MOI were considerable smaller in cells from C57BL/6 mice. Furthermore, significantly higher titres of interferon were measured in the supernatants of HSV-infected C57BL/6 macrophages than in those of DBA/2 macrophages, and the former were made fully susceptible by the in vitro addition of an anti-interferon serum.

Animals↗
PubMed1984

la-positive T lymphocytes are the producer cells of interferon gamma.

The production of gamma-interferon (IFN gamma) in human peripheral blood T lymphocytes was induced by stimulation with PHA. For identification of the producer cell of IFN gamma, double fluorescence studies were undertaken and titers of interferon were determined in preparatively separated T-cell subpopulations reactive with one of the monoclonal antibodies OKT3, OKT4, OKT8, and OKIal . Production of IFN gamma was found in OKT3+, OKT4+, and OKT8+ cells. However, IFN gamma production occurred only in T cells also reactive with the monoclonal antibody OKIal . Addition of macrophages had no substantial effect on interferon titers in these subpopulations. It is suggested that the T cell subset producing IFN gamma is characterized by its reactivity with the monoclonal antibodies OKT3, OKT4 or OKT8, and OKIal .

Antibodies, Monoclonal↗
PubMed1984

Mitogen-induced gamma interferon production in peripheral blood lymphocytes from patients with colorectal tumors.

Mitogen-induced interferon production in peripheral blood lymphocytes from patients with colorectal tumors was not significantly different from that observed in patients with Crohn's disease and sex- and age-matched controls. In the group of patients with colorectal carcinomas, no correlation was obtained with regard to the interferon titer, the in vivo lymphocyte proliferation and the clinical stage of the disease or tumor staging and grading respectively. Most importantly, the data show that despite an obvious defect in T-lymphocyte proliferation, measurement of lymphokine production in mitogen-stimulated cell cultures was not impaired.

Colonic Neoplasms↗