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Biomedical subjects

H Kirchner

Publications and source records attributed to H Kirchner.

At least 415 records · Page 23Linked to original sources

Experimental infection of inbred mice with herpes simplex virus type 1. I. Investigation of humoral and cellular immunity and of interferon induction.

Considerable differences exist in the lethality of herpes simplex virus type 1 (HSV-1) after intraperitoneal (i.p.) infection in different inbred strains of mice. In this study humoral and cellular immunity and interferon production were compared in resistant and susceptible mice. The serum IgG response, as determined by an enzyme-linked immunosorbent assay (ELISA), was the same in different strains of mice. There was also no difference in neutralizing antibodies between resistant C57BL/6 and susceptible DBA/2 mice. The production of macrophage migration inhibitory factor, obtained from spleen cells of mice 7 days after infection with different doses of HSV-1, was the same in resistant and susceptible mice. Serum interferon could be detected 8 h after i.p. injection of 10(7) p.f.u. of HSV-1, but not at lower virus doses. At 8 h, high interferon titres [less than 1000 reference research units (iu)/ml] were observed in the serum of C57BL/6 mice but low titres (about 100 iu/ml) were found in the serum of DBA/2 mice. At 24 h, the titres were low in both strains of mice. Interferon production was also measured in vitro in spleen cell cultures exposed to inactivated HSV-1. These studies also showed high interferon production in spleen cell cultures of resistant mice, whereas low titres were produced by spleen cells of susceptible mice. Thus, our study has failed to reveal any differences in humoral or cellular immunity in mice resistant or susceptible to HSV but a difference in HSV-induced interferon production.

Animals↗

Experimental infection of inbred mice with herpes simplex virus. II. Interferon production and activation of natural killer cells in the peritoneal exudate.

The peritoneal exudate cells (PEC) represent the first line of defence against the virus in the mouse model of intraperitoneal (i.p.) infection with herpes simplex virus (HSV). We have therefore studied interferon production and activation of natural killer (NK) cells in vitro in PEC of HSV-injected mice. Injection of HSV caused a marked increase in NK cell activity, as reported by others. PEC from HSV-injected mice also produced high titres of interferon. This observation may be important since induction of interferon appears to be the primary event whereas activation of NK cells - as generally accepted - represents a secondary effect of the interferon produced. The HSV-induced NK cells shared the properties of NK cells in that they were sensitive to a monoclonal anti-theta antibody and to a monoclonal anti-Qa 5 antibody. In contrast, the cells producing interferon were not sensitive to either antibody. Irradiation (200 R) of the mice 24 h before injection of the virus decreased interferon production by more than 90%. The identity of the interferon-producing cells is unknown, but they may represent B cells.

Animals↗

Protection of mice against mouse hepatitis virus by Corynebacterium parvum.

C57BL/6 mice that are highly susceptible to infection with mouse hepatitis virus type 3 were protected against intraperitoneal viral infection by simultaneous intraperitoneal injection of Corynebacterium parvum. No protection was observed when C. parvum was given intravenously or when it was injected intraperitoneally 3 days before viral infection. Protective effects were, however, consistently found when C. parvum was given 2 h before or 2 h after viral infection. Activity was seen only against 10 50% lethal doses and not against 100 50% lethal doses. C. parvum also caused a significant decrease of virus type 3. These data suggest a direct effect of C. parvum on virus-susceptible cells. Injection of C. parvum in mice caused activation of natural killer (NK) cells and of interferon production. However, these two effects were equally demonstrable at high and low doses of C. parvum, whereas protection against mouse hepatitis virus type 3 was not demonstrable at low doses of C. parvum. Thus, antiviral protection may be dissociated from activation of NK cells and induction of interferon.

Animals↗

Immunogenetic studies on the resistance of mice to highly metastatic DBA/2 tumor cell variants. II. Influence of minor histocompatibility antigens on tumor resistance, gamma-interferon induction and cytotoxic response.

B10.D2 mice (H-2d) were found to be able to reject more than 10(6) cells of the DBA/2 (H-2d) tumor ESb, while DBA/2 mice could not reject even small (less than 10(1) cells) tumor cell inocula and died within a few weeks from the developing internal metastases. Chimaeric mice and F1 hybrids between DBA/2 and B10.D2 were susceptible to the tumor and its metastases, suggesting that tumor resistance was dependent on the ability of the host to recognize DBA/2 minor alloantigens. About two thirds of the (DBA/2 X B10.D2) F2 generation mice were ESb tumor-resistant. Also, the majority of C57B1/6 X DBA/2 recombinant inbred strains (BXD RI lines) of H-2d type were found to be able to reject ESb tumor cells. There was no apparent linkage of tumor resistance to coat color genes. Mls locus, or immunoglobulin heavy chain genes. It is suggested that tumor resistance in these mice was dependent on the recognition of several DBA/2 minor histocompatibility antigens such as H-1 and H-4. The most resistant of the BXD RI strains, BXD-6, was shown to react to minor DBA/2 antigens by the production in vitro of interferon and of cytotoxic cells. These cellular immune reactions were not observed in one of the less resistant strains, BXD-28, suggesting a close relationship between tumor rejection and the capability to produce interferon and cytotoxic lymphocytes.

Animals↗

Mycoplasma contamination in human tumor cell lines: effect on interferon induction and susceptibility to natural killing.

Cleaning of human tumor cell lines from arginine-dependent nonfermentative Mycoplasma orale 1 (MO1) by a recently developed technique profoundly altered several in vitro properties of the cell lines. Four melanoma lines (Mel I, Mel St, Mel K, IGR3) and 1 ovarian carcinoma line (Ro) induced human leukocyte interferon (IFN-alpha) only in the mycoplasma-infected state and not in the mycoplasma-free state. MO1-infected tumor lines were generally more susceptible to natural killer (NK) cell-mediated lysis than their mycoplasma-free counterparts. Reinfection of cleaned tumor lines with MO1 restored their interferonogenicity and the increased susceptibility to NK lysis. Thus, the amplifying role of MO1 infection on NK target lysis occurred in connection with an increased production IFN-alpha during the assay period. The human erythroleukemia cell line K562 was exceptional in that it also induced high levels of IFN in an apparently mycoplasma-free state and was unaffected in its susceptibility ot NK lysis by infection with MO1. Possible implications of these findings for the biologic significance of the NK reaction are discussed.

Cells, Cultured↗

[Studies into carcino-embryonic antigen (CEA) and enzyme activities of alkaline and acid phosphatase in patients with fibrocystic breast disease (author's transl)].

CEA as well as alkaline and acid phosphatase were measured in patients with fibrocystic breast disease. The values recorded from the punctured fluids were compared to those in peripheral blood. CEA concentrations in cyst fluid were elevated in patients with proliferative breast disease, whereas no correlations could be established between alkaline and acid phosphatase, on the one hand, and various histological forms of breast disease, on the other.

Acid Phosphatase↗

A possible correlation between the degree of karyotype aberrations and the rate of sister chromatid exchanges in lymphoma lines.

The sister chromatid exchange (SCE) frequencies of six freshly established and two old cell lines derived from patients with lymphatic tumors or leukemia were compared to the SCE rates of lymphoblastoid cell lines of normal controls. All cell lines from malignant tumors displayed significantly higher SCE values than the control lines. In general, the SCE rates seem to be correlated to the number of chromosomal markers and the degree of karyotypic instability of each line.

Cell Line↗

Dissociation between interferon production induced by phytohemagglutinin and concanavalin A in spleen cell cultures of nude mice.

Spleen cells of homozygous nude mice did not react with lymphoproliferation to both phytohemagglutinin (PHA) and concanavalin A (Con A), and there was no detectable interferon production in response to Con A. However, PHA-induced interferon production was equal in spleen cells of nu/nu mice and nu/+ mice. One possible explanation for these findings is that a subset of T cells responds to PHA with interferon production different from that responding to Con A with interferon production.

Animals↗

Human peripheral null lymphocytes. II. Producers of type-1 interferon upon stimulation with tumor cells, Herpes simplex virus and Corynebacterium parvum.

Human blood lymphocytes, exposed for 6 to 24 h in vitro to tumor cells (K 562, IGR3, L1210), Herpes simplex virus type 1 (HSV) or Corynebacterium parvum (CP), produced high levels of anti-viral activity which was identified as type-1 interferon (IF). In mixed lymphocyte tumor cell cultures (MLTC), the generated type-1 IF was definitely shown to originate from the lymphocytes and not from the tumor cells. Supplementation of leukocyte cultures with 10% fetal calf serum instead 10% human AB serum had little influence on tumor cell-induced IF production, but strongly reduced CP-induced IF production. Lymphocyte fractionation procedures involving iron/plastic treatment, nylon wool columns, Ig-anti-Ig columns and rosette (E, EA) separation led to the identification of null cells as highly efficient producers of type-1 IF. T cells obtained by different ways (E-rosette sedimentation, passage through 1 nylon and 2 Ig-anti-Ig columns, or thoracic duct lymphocytes) were poor IF producers in response to tumor cells, HSV and CP, but secreted anti-viral activity when stimulated with phytohemagglutinin. In MLTC, the level of generated type-1 IF roughly stimulated with phytohemagglutinin. In MLTC, the level of generated type-1 IF roughly paralleled nautral killer (NK) cell activity. Evidence is presented that type-1 IF can be produced by an Fc receptor-negative null cell subset, whereas NK activity requires Fc receptor-positive cells. It is suggested that production of type-1 IF represents one of the earliest functions in the differentiation process of mononuclear phagocytes and is likely to develop before the appearance of Fc receptors, diffuse esterase staining and latex phagocytosis.

Adult↗

Interferon production in cocultures between mouse spleen cells and tumor cells: possible role of mycoplasmas in interferon induction.

Interferon production was measured in the murine mixed lymphocyte tumor cell interaction (MLTI) using spleen cells of three inbred mouse strains and a number of in vitro grown lymphoma cells. No difference in interferon production was observed when syngeneic or allogeneic combinations were compared. Interferon was not detectable during the first 6 h of culture and reached its maximum after 12--24 h. In contrast, natural killer cell activity of spleen cells against one of these lymphoma lines (YAC-1) was already high after 4h. A cell line that was not susceptible to natural killing (MDAY-D2) induced the same amount of interferon as YAC-1. These findings suggest that natural killer cell activity and interferon induction in the MLTI are not correlated. Several lymphoma cell lines induced interferon in the MLTI whereas some others did not. All lines that were inductive were found to contain mycoplasmas. Furthermore, even the cell-free supernatants of inducing lines contained mycoplasmas and induced interferon. Purified mycoplasmas and membranes thereof were able to induce interferon production in mouse spleen cells. Our data strongly suggest that interferon production in the MLTI is caused by mycoplasmas. This artifact is the relevance for three reasons. First, cocultures between lymphoma cells and lymphocytes are widely studied in immunology. Secondly, contamination with mycoplasmas is extremely common and often goes unnoticed in immunological laboratories. Thirdly, interferon is known to affect profoundly a number of in vitro functions of immunocompetent cells.

Animals↗

Studies of the producer cell of herpes simplex virus-induced interferon in mouse spleen cell cultures.

The producer cell of type I interferon was studied in spleen cell cultures of C57BL/6 mice stimulated by inactivated Herpes Simplex Virus (HSV). Interferon production was not abolished by pretreatment of the spleen cells by anti-theta serum plus complement. The producer cell of interferon was not removed by plastic adherence and was not destroyed by the addition of silica. It was present in spleens of 3 day old C57BL/6 mice and in spleens of nu/nu mice. It was not inactivated by treatment of nu/nu spleen cells by anti-theta serum plus complement. HSV-induced interferon production was abolished by passage of the spleen cells through nylon wool columns and by irradiation (1000 R) of the spleen cells. Collectively these data suggest that in murine spleen cell cultures type I interferon is produced by B cells. However, our data do not allow to rule out that the interferon producing cell may be an immature macrophage or an immature T cell.

Animals↗

[Relevance of CEA in benign breast disease (author's transl)].

Serum CEA-concentrations were measured in patients with various benign breast tumors; in addition, CEA levels were determined in the fluid of mammary cysts present. Patients with proliferating mastopathia with and without atypia had CEA values exceeding 25 ng/ml in the cystic fluid (= 46). No significant correlation existed between serum and cystic fluid concentrations. CEA determination allows for a differentiation between simple and proliferating mastopathias.

Breast Diseases↗

Mitogen-induced interferon production by normal and steroid-resistant mouse thymocytes.

We have investigated the proliferative response and interferon production in cultures of mouse thymocytes stimulated with two different mitogens, PHA (phytohemagglutinin), or Con A (concanavalin A). Normal thymocytes proliferated weakly and did not produce detectable interferon levels in response to both mitogens. Supplementing this cell population with macrophages or adding 2-mercaptoethanol to the culture medium strongly enhanced the proliferative response to both mitogens, but only in response to PHA marginal levels of interferon could be detected. When the steroid-resistant population was tested, both PHA and Con A induced strong proliferative responses; in this case significant interferon levels could be obtained after stimulation with PHA, but only borderline levels with Con A. Peripheral lymphocytes from the spleen responded identically to both mitogens with respect to interferon production as well as proliferation. The data suggest that distinct differentiation pathways may exist for T lymphocytes producing interferon in response to different mitogens.

Animals↗

[Socio-psychological factors of "family-oriented obstetrics", including "rooming in" (author's transl)].

The introduction of the "rooming in" system to maternity wards of many hospitals has been accompanied by additional demands on the hospital made by parents together with their desire tor "natural birth". Therefore, additional factors have to be taken into due consideration in the context of "family-oriented obstetrics". Interviews were made with 1,000 mothers, just after delivery to find out what they thought about certain marginal conditions in maternity advisory centres, delivery rooms, and on maternity wards. Their replies were statistically evaluated.

Attitude↗