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H Wagner

Publications and source records attributed to H Wagner.

At least 469 records · Page 26Linked to original sources
PubMed1987

Human mumps virus-specific cytotoxic T lymphocytes: quantitative analysis of HLA restriction.

To obtain quantitative information about the use of HLA antigens as restriction element by antiviral cytotoxic T lymphocytes (CTL), we have analyzed precursors of human mumps virus-specific CTL by limiting dilution. CTL generated by restimulation of peripheral blood T lymphocytes with autologous mumps virus (MV)-infected stimulator cells were restricted by autologous HLA class I antigens, and derived from the T4-8+ population. They were specific for MV and did not lyse autologous target cells infected with other viruses. Frequencies of MV-specific CTL precursors ranged from 1/500 to 1/8000. HLA restriction was analyzed by split-well analysis of individual CTL colonies. CTL recognizing HLA-A or B antigens were unequally distributed: HLA-B7, -B13, and -B27 were found to function as predominant, in some cases as exclusive, restriction elements, whereas other antigens such as HLA-A24 were never or rarely used. In several combinations, there was no evidence for antigenic variants of HLA molecules as reason for the failure to be recognized. The proportion of CTL precursors recognizing HLA-A2 and -B8 seemed to be dependent on the presence or absence of "dominant" restriction elements. We conclude that CTL precursors recognizing certain virus-HLA combinations are preferentially expanded during an infection, but that low responsiveness to a given combination is not necessarily absolute.

Antigens, Viral↗
PubMed1987

Treatment toxicity reduction: breast cancer.

Since curative treatment of advanced breast cancer is still beyond our reach, the importance of reducing overall toxicity of systemic treatment must be stressed. This seems to be possible by adapting the form and intensity of therapy to the prognosis and stage of disease and by using drugs exhibiting high antitumoral efficacy combined with low systemic toxicity. In 475 patients with metastatic breast cancer, we initiated a prognosis-oriented therapeutic strategy. We developed a prognostic score so as to classify patients into 'high' and 'low' risk groups. In this way we were able to separate patients into two groups with statistically different survival times. In addition, we found that the impact of the first polychemotherapy on survival is different when comparing patient with favourable and unfavourable prognostic scores. Patients with favourable prognostic factors had exactly the same survival time independent of tumour progression, stable disease or even partial remission. Only patients achieving a complete remission survived longer. In contrast, patients with unfavourable prognostic factors apparently benefited from chemotherapy. Patients achieving stable disease or objective tumour remission had a significantly longer survival time than those patients with immediate tumour progression. Additionally, for most of the patients in this group, chemotherapy induced a transient stabilization or improvement of tumour induced symptoms. Therefore, we conclude that chemotherapy of advanced breast cancer is necessary. However, to reduce overall toxicity, it must be planned and administered according to the prognostic picture of the individual patient.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Clonal specificity analysis of mitogen-activated murine T lymphoblasts.

We have determined the frequencies and specificities of MHC-reactive and MHC-restricted cytotoxic T lymphocyte precursors (CTL-p) in mitogen (ConA)-activated splenocytes of normal unprimed mice. The limiting dilution (LD) system supported the growth of one out of three Lyt2+ T cell blasts. The generated CTL-populations lysed blast cell targets specifically as determined by split well analyses. MHC-gene product expression was necessary for lysis to occur, since MHC-negative F9 teratocarcinoma cells were not lysed. The frequency determinations and split well analyses revealed: 1) equally high numbers (approximately 1/100) of CTL-p that generated specific allo-MHC or self-MHC reactive CTL populations, 2) high frequencies of CTL-p which recognized hapten (TNP) or minor H (MH)-antigens in the context of self MHC or allo-MHC determinants. The results are discussed with respect to antigen, restriction and receptor specificities of mitogen-activated unprimed T cell blasts.

Animals↗
PubMed1987

Selective reduction of donor-specific cytotoxic T lymphocyte precursors in patients with a well-functioning kidney allograft.

We have recently developed a sensitive limiting dilution (LD) culture system to measure human alloreactive cytotoxic T lymphocyte precursors (CTL-p) in a given lymphoid cell population. We have now used this system to determine frequencies of donor HLA antigen-inducible CTL-p in the peripheral blood of human allograft recipients at various stages after transplantation. All patients (1 pancreas recipient and 9 kidney recipients) were on continuous cyclosporine treatment throughout the study. We report that, in patients with a well-functioning kidney graft (6/9), the number of donor-reactive CTL-p among peripheral blood lymphocytes decreased within 3-8 months after transplantation--in some cases (2/6) more than 10-fold. In contrast, frequencies of CTL-p with specificity for third-part HLA antigens remained largely unaltered in these patients. Furthermore, no decrease of donor-reactive CTL-p frequencies was seen in 3 of 4 patients showing clinical symptoms of graft rejection. These results indicate that functional clonal deletion of antigraft-reactive CTL-p may contribute to the state of graft tolerance in certain patients with a well-functioning kidney allograft.

Cells, Cultured↗
PubMed1987

The influence of plaque on reaction mechanism of MFP and NaF in vivo.

A modified Intra-oral Cariogenicity Test was used to study the influence of plaque on the reaction mechanism of sodium monofluorophosphate (MFP) or sodium fluoride (NaF) in either sound or demineralized enamel in vivo. Volunteer students, wearing mouth appliances holding enamel blocks, rinsed their mouths with MFP or NaF solution (1,000 ppm F-) three times a day. The amount of loosely-bound and acquired fluoride was determined after an experimental period of five days in plaque-covered, demineralized (PCD); clean, demineralized (CD); plaque-covered, sound (PCS); and clean sound enamel (CS). While no measurable loosely-bound fluoride could be found after MFP treatment, NaF caused deposition of a significant amount of alkali-soluble fluoride in all experimental groups. After MFP rinses, fluoride concentration in the enamel was increased in the following order: CS, PCS, CD, and PCD. After NaF treatment, demineralized enamel exhibited a higher fluoride acquisition when compared with sound enamel. Plaque had a minor effect on F- acquisition. It is concluded that demineralization of enamel enhances F- uptake from both NaF and MFP solutions. In the presence of plaque, F- acquisition was additionally increased only after MFP rinses in vivo.

Adult↗
PubMed1987

Human cytotoxic T lymphocytes. III. Large numbers of peripheral blood T cells clonally develop into allorestricted anti-viral cytotoxic T cell populations in vitro.

Cytotoxic T lymphocytes (CTL) recognize antigen in the context of syngeneic MHC class I gene products. The "learning" of MHC restriction is thought to take place during the early intrathymic development of cytotoxic lymphocyte precursors (CLP). This view does not allow for any significant number of "allorestricted" (as opposed to selfrestricted) T cells to occur among mature, peripheral T cells. Recent evidence indicates, however, that large numbers of antigen-specific, allorestricted CLP can be readily detected among splenic T cell populations from several strains of unprimed normal mice. The frequencies of allorestricted CLP as determined under limiting dilution (LD) culture conditions are in fact in the same order of magnitude as frequencies of selfrestricted CLP. These findings were at the origin of the present study, which was designed to investigate whether antigen-specific, allorestricted CTL populations could also be detected among human peripheral blood T lymphocytes. To address this issue we studied the CTL response to virus-infected allogeneic stimulator cells in two different LD systems. In the first system, peripheral T cells from normal donors were cocultured under precisely defined LD conditions with Epstein-Barr virus (EBV)-transformed allogeneic lymphoblastoid cell lines (LCL). Frequencies of CLP that lysed the stimulating LCL ranged from one in 70 to one in 200, while frequencies of CLP that lysed the respective allogeneic ConA blast targets were 3-40-fold lower. The split-well analysis suggested that a large fraction of developing CTL colonies specifically lysed the stimulating LCL targets but neither the respective ConA blasts nor HLA-mismatched third party LCL targets. CTL generated in this culture system thus displayed allorestricted specificity for LCL membrane antigens. Comparable results were obtained in a second LD system where T cells from normal donors were cocultured with mumps virus-infected allogeneic mononuclear cells (MNC) or ConA blasts. One of 600 to one of 2,800 T cells gave rise to a cytotoxic colony that lysed mumps virus-infected stimulator-derived ConA blast target cells. To assess the lytic specificity of the in vitro expanding CTL populations, individual microcultures were split into three aliquots and tested for cytolytic activity against mumps virus-infected and noninfected specific targets as well as mumps virus-infected, HLA-mismatched third party targets. Clonal CTL populations from four of seven donors lysed virus-infected stimulator targets but did not lyse either noninfected stimulator targets or mumps virus-infected third party targets, i.e., they again showed an antigen-specific allorestricted lytic r

Antibodies, Monoclonal↗
PubMed1987

Human cytotoxic T lymphocytes. II. Frequency analysis of cyclosporin A-sensitive alloreactive cytotoxic T-lymphocyte precursors.

A limiting dilution (LD) culture system was used to investigate the effect of cyclosporin A (CsA) on the activation and differentiation of human alloreactive cytotoxic T-lymphocyte precursors (CTL-p). CsA reduced in a dose-dependent fashion the frequency of alloantigen-inducible CTL-p. With most normal individuals tested there was a 20- to 50-fold reduction of alloreactive CTL-p frequencies in the presence of 500-1000 ng/ml CsA. Both unseparated T cells and CD8+ T cells were CsA-sensitive under LD culture conditions. Importantly, however, alloreactive CTL-p from two out of 21 normal individuals were found to be largely CsA-resistant. CsA did not affect the growth of MLR-primed CTL in secondary LD culture. Furthermore, CsA slightly inhibited the cytolytic activity of some alloantigen-specific CTL clones. These results are discussed with respect to the clinical use of CsA in transplantation medicine.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1987

Antiasthmatic effects of onions. Inhibition of platelet-activating factor-induced bronchial obstruction by onion oils.

Lyophilized onion extract and ether extracts of onions were separated by chromatographic methods into several subfractions and tested for their effects on asthmatic reactions of guinea pigs to allergen, histamine, acetylcholine and platelet-activating factor (PAF) inhalation as well as on thromboxane biosynthesis of human platelets and lung fibroblasts. Onion oils are counteracting the bronchial obstruction due to PAF inhalation.

Allium↗
PubMed1987

[Revision prosthesis for the hip joint in severe bone loss].

When total hip prostheses loosen after initial implantation and subsequent prosthesis replacement, increasing bone resorption occurs in the bed of the prosthesis. Finally, a very thin cortex remains in the bed of the prosthesis, which no longer provides sufficient mechanical stability. The replacement prosthesis described, which is anchored in the distal medullary canal without cement, provides a bridge over the damaged prosthesis bed and results in a condition of relative mechanical stability. After implantation of the replacement prosthesis, lively proliferation of the bone tissue occurs in the old prosthesis bed, which again replaces the bone loss that had taken place previously. The late results that would permit a final assessment of the procedure are not yet available.

Bone Regeneration↗
PubMed1987

Representation of interaural time difference in the central nucleus of the barn owl's inferior colliculus.

This paper investigates the role of the central nucleus of the barn owl's inferior colliculus in determination of the sound-source azimuth. The central nucleus contains many neurons that are sensitive to interaural time difference (ITD), the cue for azimuth in the barn owl. The response of these neurons varies in a cyclic manner with the ITD of a tone or noise burst. Response maxima recur at integer multiples of the period of the stimulating tone, or, if the stimulus is noise, at integer multiples of the period corresponding to the neuron's best frequency. Such neurons can signal, by means of their relative spike rate, the phase difference between the sounds reaching the left and right ears. Since an interaural phase difference corresponds to more than one ITD, these neurons represent ITD ambiguously. We call this phenomenon phase ambiguity. The central nucleus is tonotopically organized and its neurons are narrowly tuned to frequency. Neurons in an array perpendicular to isofrequency laminae form a physiological and anatomical unit; only one ITD, the array-specific ITD, activates all neurons in an array at the same relative level. We, therefore, may say that, in the central nucleus, an ITD is conserved in an array of neurons. Array-specific ITDs are mapped and encompass the entire auditory space of the barn owl. Individual space-specific neurons of the external nucleus, which receive inputs from a wide range of frequency channels (Knudsen and Konishi, 1978), are selective for a unique ITD. Space-specific neurons do not show phase ambiguity when stimulated with noise (Takahashi and Konishi, 1986). Space-specific neurons receive inputs from arrays that are selective for the same ITD. The collective response of the neurons in an array may be the basis for the absence of phase ambiguity in space-specific neurons.

Animals↗
PubMed1986

Splenic irradiation in the treatment of patients with chronic myelogenous leukemia or myelofibrosis with myeloid metaplasia. Results of daily and intermittent fractionation with and without concomitant hydroxyurea.

Seventeen patients with either chronic myelogenous leukemia (CML) or myelofibrosis with myeloid metaplasia (MMM) received 24 courses of splenic irradiation at this institution from 1973 to 1982. Eleven of the 17 patients had received prior chemotherapy. Patients were treated with 60Co gamma rays or 6 MV photons. The fraction size ranged from 15 to 100 rad and the total dose per treatment course from 15 to 650 rad, with the exception of one patient who received 1650 rad. Fourteen of 19 courses (71%) given for splenic pain yielded significant subjective relief while 17 of 26 courses given for splenomegaly obtained at least 50% regression of splenic size. Blood counts were carefully monitored before each treatment to limit hematologic toxicity. From this experience, the authors conclude that splenic irradiation effectively palliates splenic pain and reverses splenomegaly in the majority of patients with CML and MMM. Intermittent fractionation (twice or thrice weekly) is more convenient for the patient, appears to be as effective as daily treatment, and may be associated with less hematologic toxicity. Preliminary results of concurrent treatment with splenic irradiation and oral hydroxyurea show promise and warrant further study.

Adult↗
PubMed1986

Introduction of a selectable gene into murine T-lymphoblasts by a retroviral vector.

A recombinant retroviral vector with an inserted bacterial neomycin resistance (neo) gene was used to transfer in vitro neomycin resistance (neoR) into murine cytotoxic lymphocyte precursors (CLP). The infection protocol involved co-cultivation of mitogen-activated splenic T-blasts with irradiated cells that produced either the recombinant retrovirus plus a helper virus, or exclusively the recombinant retrovirus. Infected T-blasts were subsequently cultured under limiting dilution (LD) conditions that supported clonal in vitro development of a large fraction of murine CLP. In infected T-blast populations, frequency estimates were obtained for CLP that developed into functional cytotoxic T-lymphocyte (CTL) populations under G418-selected or non-selected conditions; from these frequency estimates, an efficiency of transduction of the neoR phenotype into murine CLP of 2-8% was calculated. Some conditions were defined that influenced transduction efficiency, i.e., the density of the infecting monolayer cells; the presence of interleukin 2-containing conditioned medium and mitogenic lectins during the co-culture period; a delayed onset of G418 selection after infection. It was demonstrated that the neoR phenotype of functional CTL populations derived from infected CLP resulted from expressed recombinant retrovirus.

Animals↗