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H Kirchner

Publications and source records attributed to H Kirchner.

At least 181 records · Page 10Linked to original sources
PubMed1994

[Sex and age-dependent gaps in tetanus immunization].

To test tetanus immunity, tetanus antitoxin titres were measured in the serum of 692 subjects (354 males, 338 females), aged one day (newborns) to 92 years (mean age 29 years). Those aged 18 to 65 years were first-time blood donors, the remainder were healthy newborns, while the children and those over 65 years were patients without immune-compromising disease. An inadequate protection (titre < 0.1 IU/ml) was found in 107 (15.5%), of whom 75 (70%) were females. Women aged 20 years and above also had significantly lower average antitoxin titres than men (1.7 vs. 3.5 IU/ml); P < 0.0001). The inadequate immunization protection of many young women is reflected in the lack of protective antibodies in 10 of the 49 examined newborns. In addition, 18% of children aged between 1 and 15 years had inadequate immunity against tetanus. In the whole group the titre level decreased with age, while the proportion of unprotected persons increased. Apart from the obvious age and sex dependency of the demonstrated inadequacy of immunological protection against tetanus, attention should also be paid to the lack of protective antibodies in newborns and the marked gaps of immunity among children.

Adolescent↗
PubMed1994

Cytokine-based biotherapy of gastrointestinal tumors.

Over the past 20 years the administration of cytokines has emerged as an important fourth modality for the treatment of human cancer. Advances in the field of therapy of gastrointestinal tumors have become a major focus of current research, given the lack of progress of conventional antineoplastic therapy in most of these tumors. Among the heterogeneous group of gastrointestinal malignancies, novel therapeutic strategies have been employed for each individual tumor type, and cytokines (interferon-alpha) have gained an established role in the treatment of advanced carcinoid tumors. Although our understanding of the mechanisms of biological response modification is still limited, further improvement in the management of gastrointestinal malignancies can be expected from multimodality therapy regimens employing cytokines in combination with other biological response modifiers, chemotherapeutic agents, active-specific immunotherapy, and immunotoxin- and radionuclide-conjugated monoclonal antibodies. A wide range of clinical and preclinical studies have been conducted in colorectal carcinoma; however, potential therapeutic benefit of cytokine-based biotherapy has not been fully defined. Therefore, largescale, i.e., multicenter, studies are required to quantify the potential therapeutic effects of cytokines in gastrointestinal tumors.

Clinical Trials as Topic↗
PubMed1994

Antiproliferative effects of interferon gamma in combination with alpha-difluoromethylornithine on human carcinoma cell cultures.

The antiproliferative effects of human recombinant interferon gamma (IFN gamma) in combination with alpha-difluoromethylornithine (DFMO) or as single agents were assessed on human cell cultures derived from carcinomas of the breast (MCF-7), the ovary (EFO-27) or the kidneys (EGI-4). Results were obtained in proliferation assays by direct cell counting. The cell lines differed considerably in their sensitivities to the antiproliferative effect of IFN gamma as compared by the 50% inhibition doses of the growth (ID50). In contrast to the findings with IFN gamma, similar antiproliferative effects resulted from the application of comparable doses of DFMO. While IFN gamma induced cytotoxic effects in EGI-4 cells, DFMO produced only cytostatic actions in the cell lines analyzed. Synergistic growth inhibition resulted from the combined application of IFN gamma and DFMO in EFO-27 cell cultures. This finding was most pronounced after treatment with IFN gamma or DFMO doses below the respective ID50 values. However, antagonistic effects occurred in cells of the line EGI-4 after DFMO had been combined with IFN gamma at concentrations below the cytotoxic dose range. Within the sensitivity of our proliferation assay, no synergistic interactions were found in MCF-7 cell cultures. In the cell lines tested, no relation between the sensitivity for the single agents and the effectivity of the drug combination was identified. Despite promising synergistic effects in the moderately IFN gamma-sensitive ovarian carcinoma cell line EFO-27, the efficacy of the IFN gamma/DFMO combination was restrained by possible antagonistic effects as demonstrated in the highly IFN gamma-sensitive EGI-4 renal carcinoma cell cultures. We conclude that the differential interaction patterns in the cell cultures analyzed preclude general suggestions for clinical studies using IFN gamma and DFMO.

Breast Neoplasms↗
PubMed1994

Semiautomated HLA-DQB1 typing by fluorescent dye photometry of amplified DNA on microtiter plates.

We report a simple semiautomated HLA class II typing method that suits the demands of a 24-hour-duty transplantation service for preorgan retrieval donor typing. The procedure consists of sequence-specific amplification of HLA alleles by the polymerase chain reaction (nested PCR-SSP) followed by fluorescent dye photometry of the resulting PCR products on microtiter plates. The entire typing procedure is semiautomated and completed in less than 90 minutes after DNA isolation. The test was evaluated for the definition of the specificities DQ1-DQ9 (generic HLA-DQB1 typing). Sensitivity and specificity as judged by DNA reference typing in a different laboratory was 99.5% (n = 202 alleles).

Alleles↗
PubMed1994

Soluble interleukin 2 receptors abrogate IL-2 induced activation of peripheral mononuclear cells.

Soluble interleukin 2 receptors (sIL-2R) exert a potential role in immunoregulation. We investigated the in vitro effects of sIL-2R on several interleukin 2 (IL-2)-dependent cellular events. Cytotoxicity of human rIL-2-stimulated PBMC against K562 and Daudi was correlated inversely to the concentration of sIL-2R in the culture medium during rIL-2 stimulation. sIL-2R concentrations higher than 4.0 pM produced a significant loss of cytotoxicity (P < 0.01). The effect of different sIL-2R concentrations added to cultured human PBMC on secondary sIL-2R production was tested by ELISA. Secondary sIL-2R production was abrogated by high initial sIL-2R dosages whereas low initial dosages were followed by a continuing production of secondary sIL-2R after five days of culture. Proliferation of the IL-2-dependent mouse cell line CTLL-2-was suppressed by sIL-2R added to the culture medium in a dose-dependent way. The neutralizing capacity of sIL-2R strongly depended on the initial number of CTLL set in per proliferation assay. In contrast, variation of rIL-2-concentration had no significant effect on reduction of proliferation by sIL-2R. Furthermore, preincubation of sIL-2R with rIL-2 did not enhance growth suppression. These last findings indicate that there is at least no functional interaction between sIL-2R and free IL-2, whereas an interaction of sIL-2R with the membrane-bound receptor for IL-2 seems possible.

Animals↗
PubMed1994

Sex difference in the serostatus of adults to the Epstein-Barr virus.

A total of 1047 adults, aged between 18 and 90 years, including blood donors and surgical patients of the Medical University of Lübeck in Germany, were screened for IgG antibodies to the Epstein-Barr Virus, either by standard indirect immunofluorescence or by a novel enzyme-linked immunosorbent assay (Enzygnost Anti-EBV/IgG, Behring, Marburg, Germany). There was a significant sex difference in the serostatus to the Epstein-Barr virus in adults. Male adults were more likely than females (p < 1%) to be EBV-seronegative. The same trend was seen in both a group of 713 blood donors and 334 surgical patients and when different test methods were used. However, this sex difference was not shown in the sera of 86 pediatric patients of the Medical University of Lübeck tested by indirect immunofluorescence for IgG antibodies to the Epstein-Barr virus. Furthermore, titers of IgG antibodies to Epstein-Barr virus specific antigens of female adults, obtained by the enzyme-linked immunosorbent assay (Enzygnost Anti-EBV/IgG), had significantly higher median values than male adults (p < 5%).

Adolescent↗
PubMed1994

Induction of cytokines and cytotoxicity against tumor cells by Newcastle disease virus.

The use of NDV as biological adjuvant in vaccines against human cancer is still actual in several clinical treatment protocols. In this study, we have investigated in vitro-effects of Newcastle disease virus (NDV) strain 73-T on isolated mononuclear blood cells and cultured tumor cells. Cellular cytotoxicity of PBMC freshly isolated from healthy donors against tumor cells was enhanced significantly (p < 0.01) after coincubation of NDV with effector cells. NDV failed to enhance cytotoxicity of effector cells when PBMC were stimulated three days with 500 IU recombinant interleukin-2 (rIL-2) per ml prior to coincubation with the virus. No significant enhancement of cellular lysis was seen when only target cells were coincubated with NDV. As shown by depletion of various lymphocyte subsets, NK cells were the predominant mediator of lysis. Enhancement of cytotoxicity correlated with the induction of interferon-alpha (IFN-alpha) in PBMC by NDV. NDV also induced high amounts of tumor necrosis factor-alpha (TNF-alpha) in PBMC. Induction of interferon-gamma (IFN-gamma) was weak. A direct cytopathic effect (CPE) of NDV on different target cells was detected by colorimetric measurement of metabolic cell activity. The human tumor cell lines A-498, A-704, Caki-1, Caki-2, and K-562 and the fibroblast line MRC-5 showed progressive cellular destruction 48 h after infection with NDV, whereas PBMC and Daudi cells remained unaffected during the observation period. The nontransformed monkey kidney cell line CV-1 and the transformed monkey kidney cell line COS-1 were both lysed by NDV with marginal difference in time course of CPE. Our results indicate a reasonable potential of pleiotropic modifications of the immune response against tumors by NDV.

Adjuvants, Immunologic↗
PubMed1994

Influence of various factors on interferon-alpha production in cultures of human leukocytes.

Inducer-specific gene loci and sex are known to play a role in the regulation of interferon-alpha (IFN-alpha) production in mice. Because little is known about the genetic control of the IFN-alpha system in man, we investigated the IFN-alpha production of 468 individuals by culturing peripheral blood with Newcastle disease virus (NDV) or Sendai virus (SDV). The IFN alpha release of different donors varied over a wide range. However, IFN-alpha production of 7 donors showed a donor-specific response over a period of 4 months, which led us to classify some donors as high and low responders. The amounts induced by NDV correlated positively to those induced by SDV. The donor's sex did not alter the IFN-alpha production significantly. The subjects were between 1 and 90 years in age. Highest IFN-alpha levels were obtained in children, followed by a gradual decline with age. Using a specific IFN-alpha-2 enzyme-linked immunosorbent assay (ELISA) and a bioassay, which detects all subtypes, our data showed that the net IFN-alpha production decreased with age. For further studies, we selected 17 low producers and 17 high producers. To analyze a possible influence of major histocompatibility complex (MHC) on IFN-alpha production, the HLA genotypes of 13 low producers and 12 high producers were determined. Here, no correlation between high or low production and HLA genotype was detectable.

Adolescent↗
PubMed1994

Hepatic and serologic toxicity of systemic interleukin-2 and/or interferon-alpha. Evidence of a risk-benefit advantage of subcutaneous therapy.

A total of 107 cancer patients were treated with 148 cycles of subcutaneous (SC) immunotherapy employing interleukin-2 (rIL-2) and/or interferon-alpha (rIFN-alpha). The systemic toxicities of SC cytokine therapy were retrospectively evaluated with regard to hepatic and metabolic adverse effects, and compared to adverse effects previously reported upon high- or intermediate-dose intravenous (IV) rIL-2 therapy. Our study cohorts consisted of 15 patients who received SC rIL-2 at doses of 4.8-14.4 million IU/m2/day on 5 days per week for a total of 8 weeks, 20 patients who received rIFN-alpha 2b at 3.0-6.0 million U/m2/day thrice weekly for a total of 6 weeks, and 72 patients who were given SC rIFN-alpha 2b at 6.0 million U/m2/day thrice weekly plus SC rIL-2 at 14.4-18.0 million IU/m2/day on days 1 and 2, followed by 4.8 million IU/m2/day, 5 days per week for 6 consecutive weeks. These treatment regimens were well tolerated in the outpatient setting; no toxic deaths occurred, and none of the patients developed life-threatening toxicity. Upon SC rIL-2/rIFN-alpha combination therapy, we observed mild decreases in plasma protein and albumin levels (mean nadir +/- standard deviation, 67 +/- 5 g/L and 38.8 +/- 3.9 g/L, respectively), minor albeit significant increases in serum total bilirubin levels (mean peak +/- standard deviation, 7.8 +/- 3.1 mumol/L), serum aspartate aminotransferase (25.9 +/- 9.9 U/L), alanine aminotransferase (42.0 +/- 45.9 U/L), alkaline phosphatase (301 +/- 255 U/L), lactate dehydrogenase (230 +/- 64 U/L), gamma-glutamyl transpeptidase (147 +/- 141 U/L) activities and triacylglyceride (2.6 +/- 0.9 mmol/L) concentrations. Cholinesterase activities (mean nadir +/- standard deviation, 42.6 +/- 13.7 kU/L), and serum cholesterol levels (4.4 +/- 0.9 mmol/L) decreased upon SC rIL-2/rIFN-alpha combination therapy. These mild clinical side effects and laboratory changes were in marked contrast to a multitude of dose-limiting and life-threatening adverse reactions described upon IV rIL-2 therapy. It is concluded that low-to intermediate-dose SC rIL-2/rIFN-alpha combination therapy as used in this study, can be given in the outpatient setting with good practicability and excellent safety.

Adult↗
PubMed1994

Expression of sCD23 in atopic and nonatopic blood donors: correlation with age, total serum IgE, and allergic symptoms.

Although structure, biologic activities, and expression of the low-affinity IgE receptor (FceRII, CD23) have been investigated, the diagnostic value for allergies of this molecule and its soluble circulating fragment (sCD23) remains unclear. Therefore, serum sCD23 levels were measured in 203 blood donors. They were divided into atopic and nonatopic subjects by allergy history, physical findings of allergic symptoms, and corresponding specific circulating IgE antibodies. The group consisting of nonatopic subjects was divided into four age categories in order to exclude age-dependent variations in the expression of the low-affinity IgE receptor. In our study population, sCD23 serum levels were not influenced by age. Furthermore, no significant differences, especially no decrease in serum sCD23 levels, between the four nonatopic age groups were detected. There was no significant increase of sCD23 serum levels in atopic subjects in comparison with nonatopic blood donors. In addition, no correlation between total IgE levels and sCD23 serum levels could be detected, in either the group of atopic donors or the group of nonatopics. Our data suggest that the circulating low-affinity IgE receptor does not appear to be an additional general marker for the diagnosis of allergies, as previously suggested.

Adult↗
PubMed1994

Differential induction of tumor necrosis factor alpha in murine and human leukocytes by Mycoplasma arthritidis-derived superantigen.

Mycoplasma arthritidis-derived superantigen (MAS) is exclusively produced by M. arthritidis, which is the only known mycoplasma to produce a superantigen. As a superantigen, MAS shows properties similar to those of the staphylococcal enterotoxins and related substances, such as binding to major histocompatibility complex (MHC) class II and V beta-specific stimulation of T cells. In this series of experiments, we demonstrate some differences between MAS and other superantigens. MAS induced the production of tumor necrosis factor alpha (TNF-alpha) mRNA in human as well as in murine leukocytes. However, only in murine leukocytes was the mRNA adequately translated into the protein. In human peripheral blood mononuclear cells, we found only small amounts of TNF, whereas in murine spleen cells we detected levels more than three times higher. The proliferative response to MAS has been shown to be restricted to I-E alpha in the murine MHC. Furthermore, TNF was induced in I-E alpha+ bone marrow-derived macrophages by MAS. In these cells, MAS rapidly induced very high levels of TNF and the amounts of mRNA detected correlated to the amount of protein produced. In comparison with other superantigens, including the staphylococcal enterotoxins, toxic shock syndrome toxin 1, and exfoliative toxin A, the failure of MAS to induce TNF-alpha in human peripheral blood mononuclear cells is specific for MAS and not common to all superantigens. The direct activation of bone marrow-derived macrophages also seems to be specific for MAS. These data suggest that the induction of TNF-alpha by MAS is dependent on the strength of binding to the MHC class II molecule.

Animals↗
PubMed1994

Dexa-BEAM in patients with Hodgkin's disease refractory to multidrug chemotherapy regimens: a trial of the German Hodgkin's Disease Study Group.

PURPOSE: A prospective phase II study was conducted to evaluate the efficacy of dexamethasone, carmustine, etoposide, cytarabine, and melphalan (Dexa-BEAM) as salvage chemotherapy for patients with Hodgkin's disease. PATIENTS AND METHODS: Fifty-five patients progressing on or relapsing after eight- or 10-drug chemotherapy (cyclophosphamide, vincristine, procarbazine, and prednisone plus doxorubicin, bleomycin, vinblastine, and dacarbazine [COPP+ABVD] or COPP+ABV+ifosfamide, methotrexate, etoposide, and prednisone [IMEP]) were treated with Dexa-BEAM. Patients who responded after two cycles of Dexa-BEAM either continued treatment for another two to three cycles or received high-dose chemotherapy/autologous bone marrow transplantation (HDCT/ABMT) with cyclophosphamide, etoposide, and carmustine (BCNU) (CVB) as conditioning regimen. RESULTS: Seventeen patients (31%) achieved a complete remission and 16 (29%) a partial remission, resulting in a response rate of 60% (95% confidence interval, 46% to 73%). Progressive disease developed in 18 patients. Toxicity of Dexa-BEAM was acceptable with pronounced, but temporary World Health Organization (WHO) grade III/IV granulocytopenia and thrombocytopenia occurring in more than 90% of all courses. Two patients died of sepsis during granulocytopenia. Three prognostic subgroups could be distinguished: (1) patients progressing on initial chemotherapy, (2) patients relapsing within 12 months, and (3) patients with late relapses. The response rates for these groups were 52%, 60%, and 83%, and the median survival duration 12, 29, and 40+ months, respectively. In a nonrandomized comparison, the survival of patients who responded to two cycles of Dexa-BEAM and had additional cycles of Dexa-BEAM (n = 14) was not different from those responding patients who underwent HDCT/ABMT (n = 19). However, the power to detect a 20% survival difference was only 33% in this comparison. CONCLUSION: Dexa-BEAM is an effective salvage treatment for patients with Hodgkin's disease who fail to respond to multidrug chemotherapy. Efficacy and toxicity are comparable to HDCT/ABMT and underline the need for prospective randomized trials to define better the role of HDCT with and without ABMT in these patients.

Adult↗
PubMed1994

Identification of HLA-DRB1 and HLA-DQB1 identical individuals by a cytokine-based mixed lymphocyte culture.

Cytokine determination in MLC is under discussion as providing more sensitive and specific information regarding host-graft compatibility, and is therefore suggested to represent a new method for transplantation medicine. Little is known, however, about the stimulatory influence of HLA class II antigens and minor lymphocyte-stimulating antigens (Mls). Our results demonstrate that cytokine determination in MLC is suitable to detect identical alleles of HLA-DRB1 and HLA-DQB1. Among more than 100 random MLC experiments, we observed one cytokine pattern similar to the cytokine release detected in a control MLC of HLA-identical siblings, which showed marginal or no secretion of IL-2, sIL-2R, IFN-gamma, TNF-alpha, and IL-6. HLA-typing of these two nonreactive individuals elevated identical HLA-DRB1 and HLA-DQB1 regions, while they differed in the HLA-DP locus. This suggests that HLA-DP has no stimulatory influence on cytokine release. Further investigation of the stimulatory capacity of HLA-DR and DQ showed that HLA-DR is more effective in inducing IFN-gamma release than HLA-DQ. To evaluate the stimulatory influence of human Mls, i.e., human endogenous retroviruses (HERV), we analyzed HERV sequences of nonreactive individuals. Both individuals showed identical HERV patterns. A third individual, who had shown distinct cytokine release in MLC with both nonreactive individuals, differed in the HERV fragments. In conclusion, cytokine determination in MLC is a new method of evaluating the biological relevance of stimulatory antigens after allogeneic stimulation detecting all individual diversities in one experiment.

Alleles↗
PubMed1994

[Cytokines, immunoglobulins, and IgG subclasses in patients with IgG plasmacytomas].

Cytokines play an essential role in normal and malignant B-cell proliferation and isotype-switching. Therefore we determined serum levels of different B-cell activating cytokines including IFN gamma, IL-4 and IL-10, IgG subclasses, further immunoglobulins and the soluble B-cell activation marker sCD23 in 68 patients with recently diagnosed and previously untreated IgG myelomas in comparison with age- and sex-matched healthy controls. Our results demonstrated that 16% of the myeloma patients had elevated IL-10 levels up to 1000 pg/ml and 8% showed increased IFN gamma serum concentrations. By contrast, only 7% of the controls showed detectable IL-10 levels and 3% had measurable IFN gamma levels. While in men 67% of the paraproteins were of the kappa light chain type, we found an equal occurrence of kappa and lambda light chains in women. In addition, the distribution of IgG subclasses differed in men and women. In comparison with the controls, no alteration of sCD23 was detected in myeloma patients. We found an apparent correlation of elevated IL-10 levels and the IgG1 subclass.

Aged↗
PubMed1994

Induction of cytokines by zinc ions in human peripheral blood mononuclear cells and separated monocytes.

Zinc plays an important role in the maintenance of immune functions. The immunological mechanisms triggered by zinc, however, are still poorly understood. In our experiments Zn2+ ions, added as ZnSO4, stimulated PBMC to produce IFN-gamma, IL-1 beta, IL-6, TNF-alpha, and sIL-2R in a concentration-dependent manner. CuSO4 and CaCl2 as cation and anion controls had no effect. The optimal concentration of zinc was 0.5 mM for monokine induction and 0.25 mM for induction of IFN-gamma and sIL-2R. The highest IL-1 beta and IL-6 levels were found on day 2 and maximum TNF-alpha after 16 h. IFN-gamma and sIL-2R production were optimum after 6 and 7 days, respectively. Monokines could be induced in autologous serum as well as in fetal calf serum and serum-free medium. Enriched monocytes and the human monocyte cell line Mono Mac 6 also released IL-1 beta after zinc challenge. Anti-IL-6 reduced IFN-gamma secretion whereas anti-IL-1 beta inhibited it. These data suggest that zinc acts primarily on monocytes by inducing monokine secretion and that T-cell activation represents a secondary effect in the cytokine cascade.

Cell Line↗
PubMed1994

Immediate-type hypersensitivity reactions after platelet transfusion.

Non-febrile non-haemolytic transfusion reactions (NHTR) after platelet substitution vary from severe (anaphylactic shock) to mild (urticaria) forms. Although the symptoms of these immediate-type hypersensitivity reactions are well documented, little is known about their pathophysiology. We therefore examined sera from patients suffering from different forms of NHTR regarding total serum IgE, specific IgE antibodies and complement activity. Our results show that specific IgE antibodies in the recipients' sera were clearly associated with immediate-type hypersensitivity NHTR and conclude that atopic patients have a higher risk of suffering from these forms of transfusion reactions than non-atopic patients. Allergy diagnostic for patients who require platelet transfusions should be considered in case of multiple platelet substitution.

Complement System Proteins↗