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T Meier

Publications and source records attributed to T Meier.

At least 73 records · Page 4Linked to original sources
PubMed1995

Differential effects of ifosfamide on the capacity of cytotoxic T lymphocytes and natural killer cells to lyse their target cells correlate with intracellular glutathione levels.

We established an in vitro model to study the influence of ifosfamide treatment on intracellular glutathione (GSH) levels in activated human effector cells with specific phenotypes and immunologic functions. Besides its role as the major intracellular reductant, GSH has been shown to affect the initiation and progression of lymphocyte activation after stimulation with lectins. An incubation of activated human peripheral blood lymphocytes (PBL) with 4-hydroxyifosfamide, the activated form of ifosfamide (4-OH-IF), resulted in a depletion of the intracellular GSH levels and a significant inhibition of the proliferative capacity in a dose-dependent manner. The cytotoxic activity of separated CD3- natural killer (NK) cells and CD3+ allospecific, cytotoxic T lymphocytes (CTL), either untreated or treated with 4-OH-IF at different concentrations, was compared in a standard 51chromium release assay (CML). There were three major findings. (1) The capacity of CD3+ major histocompatibility complex (MHC)-restricted CTL to lyse their specific allogeneic target cells was substantially reduced by preincubation of the effector cells with 4-OH-IF. This inhibition of the lytic activity in CD3+ CTL correlated with a substantial depletion of the intracellular GSH levels in this population. Rapid reconstitution of depleted GSH levels and restoration of cytotoxic activity of CTL was achieved by incubation of the effector cells with thiols, eg, glutathione ester (GSH-ester) or 2-mercaptoethanesulfonate (mesna). (2) In contrast, the lytic activity in CD3- NK cells was not substantially affected (up to 100 mumol/L 4-OH-IF). This result correlates with the capacity of NK cells to maintain their intracellular GSH levels after an ifosfamide treatment. (3) In comparison with CD3+ CTL, CD3- NK cells are more resistant to an ifosfamide treatment because they have higher initial GSH levels and a more than fourfold higher relative rate of GSH synthesis.

Antibodies, Monoclonal↗
PubMed1995

A stress-inducible 72-kDa heat-shock protein (HSP72) is expressed on the surface of human tumor cells, but not on normal cells.

It is suggested that members of the heat-shock protein (HSP) 70 and 90 families are involved in intracellular antigen processing and the presentation of cell-membrane-anchored antigens. We show that non-lethal heat shock (41.8 degrees C) causes comparable rates of HSP72 (about 20x) and HSP73 (about 3x) synthesis in both tumor (including human Ewing's sarcoma, ES and osteosarcoma cells, HOS58) and normal cells (including EBV-transformed B-LCL, PBL and fibroblasts derived from healthy human volunteers). However, following non-lethal heat stress and a recovery period at 37 degrees C, flow cytometric analysis with a specific MAb showed HSP72 to be expressed only on the cell surface of tumor cells. The cell-surface localization of HSP72 was confirmed by Western-blot analysis of separated membranes and by immunoprecipitation with the HSP72-specific MAb. In addition, co-incubation of untreated tumor cells with supernatants from lethally heat-shocked cells, which contain HSP72, did not lead to HSP72 cell-surface expression. Thus, non-specific association of HSP72 molecules with the outer plasma membrane is unlikely. In conclusion, despite comparable cytoplasmic HSP72 induction, human tumor cells differ from normal cells in their capacity to express HSP72 on their surface. This might imply clinical application as a means to target a stress-inducible, tumor-specific immune response.

Animals↗
PubMed1995

In vitro transcription close to the melting point of DNA: analysis of Thermotoga maritima RNA polymerase-promoter complexes at 75 degrees C using chemical probes.

The interaction of DNA dependent RNA polymerase of the extreme thermophile bacteria Thermotoga maritima with a promoter bearing DNA fragment was investigated in the temperature range from 20 to 85 degrees C. We show that the T. maritima RNA polymerase recognizes and utilizes the Escherichia coli T7 A1 promoter with an efficiency similar to that of the E. coli polymerase. We have investigated the interaction of both polymerases with the same promoter over a wide range of temperatures using hydroxyl radical foot-printing and osmium tetroxide probing. This study revealed that the T. maritima polymerase goes through a series of isomerisation events very similar to the E. coli polymerase, i.e. the closed, intermediate and open complexes, but the transitions themselves occur at radically different temperatures. This indicates that conformational changes in the DNA that accompany initiation of transcription such as promoter melting are determined by the polymerase rather than the DNA sequence.

2,2'-Dipyridyl↗
PubMed1995

Nitric oxide donor, linsidomine chlorhydrate (SIN-1), in the diagnosis and treatment of erectile dysfunction: critical appraisal and review of the literature.

Recent experimental work has demonstrated that nitric oxide (NO) is the neutrotransmitter responsible for cavernous smooth muscle relaxation. Different studies on the performance of the direct NO-donor linsidomine chlorhydrate (SIN-1) in patients with erectile dysfunction have come to conflicting results ranging from highest praise to complete dismissal. We reviewed all published studies on the use of SIN-1 for intracorporeal injection in erectile failure including our own. To this date, 3 groups published their data. Only the uncontrolled data from Hannover claim good results. The controlled data from Hamburg and Berlin on patients with erectile failure due to venous leakage, to a mixed aetiology in a double-blind fashion and to mixed aetiology with drug increase (1 mg versus 2 mg of SIN-1) showed a significantly worse performance of SIN-1 compared to the standard drug for penile injection, prostaglandin E1. We conclude that there is no place for linsidomine chlorhydrate in either the diagnosis or the treatment of erectile dysfunction.

Animals↗
PubMed1995

Immobilization of nicotinic acetylcholine receptors in mouse C2 myotubes by agrin-induced protein tyrosine phosphorylation.

Agrin induces the formation of highly localized specializations on myotubes at which nicotinic acetylcholine receptors (AChRs) and many other components of the postsynaptic apparatus at the vertebrate skeletal neuromuscular junction accumulate. Agrin also induces AChR tyrosine phosphorylation. Treatments that inhibit tyrosine phosphorylation prevent AChR aggregation. To examine further the relationship between tyrosine phosphorylation and receptor aggregation, we have used the technique of fluorescence recovery after photobleaching to assess the lateral mobility of AChRs and other surface proteins in mouse C2 myotubes treated with agrin or with pervanadate, a protein tyrosine phosphatase inhibitor. Agrin induced the formation of patches in C2 myotubes that stained intensely with anti-phosphotyrosine antibodies and within which AChRs were relatively immobile. Pervanadate, on the other hand, increased protein tyrosine phosphorylation throughout the myotube and caused a reduction in the mobility of diffusely distributed AChRs, without affecting the mobility of other membrane proteins. Pervanadate, like agrin, caused an increase in AChR tyrosine phosphorylation and a decrease in the rate at which AChRs could be extracted from intact myotubes by mild detergent treatment, suggesting that immobilized receptors were phosphorylated and therefore less extractable. Indeed, phosphorylated receptors were extracted from agrin-treated myotubes more slowly than nonphosphorylated receptors. AChR aggregates at developing neuromuscular junctions in embryonic rat muscles also labeled with anti-phosphotyrosine antibodies, suggesting that tyrosine phosphorylation could mediate AChR aggregation in vivo as well. Thus, agrin appears to induce AChR aggregation by creating circumscribed domains of increased protein tyrosine phosphorylation within which receptors become phosphorylated and immobilized.

Agrin↗
PubMed1995

Laparoscopic pelvic lymphadenectomy in prostatic cancer: an analysis of seventy consecutive cases.

From July 1992 to April 1994, 70 patients with prostatic cancer underwent laparoscopic pelvic lymph-node dissection (LPLD) before retropubic radical prostatectomy or afterloading therapy in our clinic. After an initial learning phase, the accuracy of LPLD was excellent, with only 3.0% residual nodes and no false-negative results due to LPLD. The rate of severe complications was 5.7% (4/70). No transfusions were required due to LPLD. If patients with positive nodes (D1) were excluded from local therapy, the benefits of LPLD were estimated as 12 patients with positive nodes avoiding open surgery (17.1%); 15 patients undergoing afterloading therapy and avoiding open surgery (21.4%); 1 patient with high preoperative prostate-specific antigen having a chance of surgical cure (1.4%) - a total of 28 of 70 patients (40.0%). We conclude that, depending on the therapeutic concept applied, LPLD is beneficial for patients with prostatic cancer, it opens the door for other curative procedures like after-loading therapy, and reappraisal of perineal prostatectomy.

Adult↗
PubMed1995

[Inflammatory pseudotumor the bladder wall after abdominal hysterectomy for uterine myoma].

We report on a 49-year-old woman who underwent an abdominal hysterectomy for uterine myoma. Six months after the primary surgery a 2 x 2 cm tumor was detected in the posterior wall of the urinary bladder. This tumor was associated with pain, dyspareunie and voiding disturbances. A repeat-laparotomy and partial resection of the urinary bladder were carried out. The histological and immunohistochemical examinations revealed an inflammatory pseudotumor of the urinary bladder. Similar lesions after surgery on the genito-urinary system were previously reported mainly in the urinary bladder. Difficulty may arise in differentiation of these lesions from low-grade leiomyosarcomas.

Diagnosis, Differential↗
PubMed1994

The 'helix clamp' in HIV-1 reverse transcriptase: a new nucleic acid binding motif common in nucleic acid polymerases.

Amino acid sequences homologous to 259KLVGKL (X)16KLLR284 of human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT) are conserved in several nucleotide polymerizing enzymes. This amino acid motif has been identified in the crystal structure model as an element of the enzyme's nucleic acid binding apparatus. It is part of the helix-turn-helix structure, alpha H-turn-alpha I, within the 'thumb' region of HIV-1 RT. The motif grasps the complexed nucleic acid at one side. Molecular modeling studies on HIV-1 RT in complex with a nucleic acid fragment suggest that the motif has binding function in the p66 subunit as well as in the p51 subunit, acting as a kind of 'helix clamp'. Given its wide distribution within the nucleic acid polymerases, the helix clamp motif is assumed to be a structure of general significance for nucleic acid binding.

Algorithms↗
PubMed1994

Ileal conduit urinary diversion 16 months before renal transplantation in a case of non-functioning lower urinary tract.

The case history of a cadaveric kidney graft recipient with complete non-functioning of the lower urinary tract is reported. An ileal conduit was formed 16 months prior to transplantation. The graft ureter was implanted into the conduit without any problems, graft functioning was excellent, and no surgical, metabolic, or infectious complications occurred during the 18-month follow-up period.

Adult↗
PubMed1994

Bladder cancer following prostate cancer--an analysis of risk factors.

Between 1969 and 1988, 1421 men had been treated for primary adenocarcinoma of the prostate. In 14 cases subsequent primary bladder cancer was observed, as compared to 5.98 cases to be expected, thus constituting a relative risk of 2.34. Seven of these cases developed synchronously (within 6 months), with a range of up to 10 years. Aetiologically, cigarette smoking was detected as the single most important denominator, whereas family history was positive for malignancy in only two cases.

Adenocarcinoma↗