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Biomedical subjects

R Herrmann

Publications and source records attributed to R Herrmann.

At least 307 records · Page 17Linked to original sources

gamma-Aminobutyric acid-mediated inhibition at cholinergic synapses formed by cultured retinal neurons.

The purpose of this study was to investigate the effect of gamma-aminobutyric acid (GABA) on the function of synapses formed by cholinergic neurons derived from the chick retina. We used an experimental culture system in which striated muscle cells served as postsynaptic targets for cholinergic neurons of the retina. This cell culture system permitted the physiological monitoring of acetylcholine release at synapses formed by retinal neurons. By plating a low density of dissociated retinal cells with myotubes, it was possible to study relatively isolated, presynaptic cholinergic neurons. We found that GABA and its agonists, muscimol and isoguvacine, inhibited spontaneous transmission at retina-muscle synapses. These inhibitory effects were reversibly blocked by bicuculline, a GABA receptor antagonist. The benzodiazepine, flurazepam, potentiated GABA-mediated inhibition. Overall, our findings suggest a direct inhibitory action of GABA on the cholinergic retinal neurons studied in our cell culture system.

Animals↗

Sequential methotrexate (MTX) and 5-fluorouracil (FU) in human tumor xenografts.

Human and animal tumor-lines heterotransplanted in nude mice were treated with MTX and FU sequentially. In order to investigate the relationship between tumor response and drug toxicity sequence, time and dose of both MTX and FU were varied. Pretreatment with MTX followed by FU with intervals of 3 or 24 h produced superior therapeutic results when compared to single administration of MTX or FU, simultaneous treatment, or the reverse sequence. In the MTX followed by FU regimen, dose reduction of either MTX or FU tended to decrease the anti-tumor effect. To investigate the toxic effects of different regimens, tumor-free nude mice were treated with MTX and FU the same way as the tumor-bearing animals. In this case, toxicity (weight loss, leukopenia) was more pronounced in those schedules with the best therapeutic results. However, toxicity appears to be more clearly related to the applied FU-dose.

Animals↗

Aclarubicin (aclacinomycin A) in the treatment of relapsing acute leukaemias.

Forty patients with relapsing acute leukaemias were treated with aclacinomycin A (aclarubicin, ACM), 25 mg/m2 i.v. daily for 7 days. Twenty-nine patients with acute myeloid (AML) and five with acute lymphoblastic (ALL) leukaemia were evaluable. The overall response rate was 29.5%. Eight complete (CR) and one partial (PR) remissions were achieved in AML (31%). A high CR rate was induced in patients treated at first relapse without prior reinduction (6/12 patients). A small proportion of leukaemias resistant to daunorubicin or doxorubicin responded to ACM (3/17 patients). Median remission duration was 5.5 months (range: 2-9 months). The most common toxic effects were nausea, vomiting, stomatitis and diarrhoea. Acute cardiotoxic effects were documented in three patients. Congestive cardiomyopathy was not observed despite prior treatment with anthracyclines. We conclude that the present dose scheduling of ACM is effective in the treatment of relapsing AML and that it should be introduced in combined chemotherapy in phase III trials to compare its activity to that of daunorubicin or doxorubicin.

Aclarubicin↗

The effect of methotrexate pretreatment on 5-fluorouracil kinetics in sarcoma 180 in vivo.

Synergy of sequential MTX and 5-FU has been shown in several in vitro and in vivo systems. In the present study the influence of time interval between MTX and 5-FU and MTX dose on 5-FU accumulation in tumor cells has been examined in Sarcoma 180 in vivo. There was a clear relationship between MTX dose applied and amount of 5-FU detected in the acid-soluble fraction, the RNA fraction and the thymidylate synthase complex fraction. Also, the MTX-5-FU time interval affected clearly the amount of 5-FU detected in all three fractions, the optimum time interval being 8-12 hr. The results indicate that for sequential application of MTX and 5-FU selection of an adequate MTX dose and a sufficient time interval is crucial to achieve synergistic action.

Animals↗

Timing- and sequence-dependent synergism between etoposide and methotrexate or etoposide, methotrexate and 5-fluorouracil in advanced leukemia L1210.

The optimal synergism in combination therapy of leukemia L1210 depends on the sequence and the timing of the agents used. Etoposide (20 mg/kg applied intravenously) 3 h before methotrexate (50 mg/kg administered subcutaneously) results in significantly improved therapeutic action. Simultaneous application of these drugs, or an exceeding of that interval, do not entail synergism. Similar to the results obtained with other transplantable murine tumors, the optimal interval between methotrexate and 5-fluorouracil treatments of leukemia L1210 amounts to 6 h. Sequential treatment with etoposide (20 mg/kg given intravenously) significantly improves the efficacy of combined methotrexate (50 mg/kg applied subcutaneously) and 5-fluorouracil (80 mg/kg administered subcutaneously). The optimal synergism combining etoposide, methotrexate and 5-fluorouracil is achieved when the interval between etoposide and methotrexate amounts to 3 h followed 6 h later by 5-fluorouracil.

Animals↗

Surface proteins of Mycoplasma hyopneumoniae identified from an Escherichia coli expression plasmid library.

A genomic library of Mycoplasma hyopneumoniae was constructed by cloning random DNA fragments approximately 300 base pairs long in a fusion expression plasmid, pEx29, containing the N terminus of the phage MS2 polymerase under the control of the PL promoter of phage lambda. Clones that produced fusion proteins carrying surface-specific antigenic determinants were identified by using antiserum raised in a pig by intranasal inoculation of viable mycoplasmas. Rabbit antisera produced against gel-purified fusion proteins synthesized in Escherichia coli were analyzed by Western blotting to identify antigenically related mycoplasma components. Distinct mycoplasma proteins termed P90, P68, P50, P30, and P26 were identified. Evidence for the surface location of P90, P68, and P50 was provided by their sensitivity to trypsin and their comigration with lactoperoxidase-catalyzed iodinated proteins of intact mycoplasmas. Immune electron microscopy, performed with antiserum against the hybrid MS2-mycoplasma protein produced in E. coli and corresponding to P90, also showed that its antigenic determinant is associated with the mycoplasma surface.

Bacterial Proteins↗

[Prospective randomized study in advanced stomach cancer. Comparison between combinations of 5-fluorouracil and carmustine without and with adriamycin].

In a multi-center study of 77 patients with gastric carcinoma and metastases, the effects of combined 5-fluorouracil and carmustine with or without adriamycin (FB vs FAB) were compared. There was no significant difference between the two treatment groups as to rate of response or survival time, response to treatment was 20% (FB) and 24% (FAB), including "no change" 52% and 56%, respectively. But median survival time among the responders (partial remission and clinical improvement) and of the patients with unchanged findings was significantly longer (8.4 or 7.4 months, respectively) than that among patients with progression (4.5 months). Analysis of prognostic factors in terms of survival curves revealed no difference between patients with or without measurable tumor parameters, with or without local recurrences or liver metastases. However, there was a statistically significant worsening of prognosis for patients whose initial general state was reduced, who had lung metastases or increased WBC counts. Side effects were relatively mild with both therapy regimens, except for alopecia with FAB. After the second treatment cycle myelosuppression was more marked with FAB than FB.

Adult↗

Our experience with Solcoseryl Eye-Gel in the treatment of corneal lesions. A randomised double-blind study (with 1 color plate).

A comparative study of Solcoseryl Eye-Gel versus a 2.4% cysteine eye-gel was carried out under controlled conditions (randomised and double-blind) on a total of 61 patients with corneal lesions (52 foreign body injuries, 9 corneal erosions). The results showed a marked superiority of Solcoseryl Eye-Gel with respect to more rapid healing and also with respect to the possible subsequent development of a corneal macula.

Actihaemyl↗

Sequential methotrexate and 5-fluorouracil: improved response rate in metastatic colorectal cancer.

The efficacy of chemotherapy with sequential methotrexate (MTX) and 5-fluorouracil (5-FU) in metastatic colorectal cancer was studied in a multicenter phase II trial using a seven-hour time interval. Forty-two patients were evaluable for response and 16 achieved objective tumor regression (greater than 50%). Median survival of all patients was 12.5 months. The result of this study indicates that MTX and 5-FU are synergistic in human colorectal cancer if given sequentially with a seven-hour time interval. This is supported by a review of the literature that reveals a significantly higher response rate in patients treated with a four-hour or more MTX/5-FU interval as compared to a one-hour interval.

Adult↗