[Recurrent paralysis induced by vincristine during the treatment of Hodgkin's disease].
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Biomedical subjects
Publications and source records attributed to F Martin.
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Sucralfate suspension 1 g/10 ml four times per day was found to be significantly better than placebo for the healing of active duodenal ulcer. An eight-week, double-blind, randomized, placebo-controlled, parallel-group multicenter study was conducted. A total of 292 patients were evaluated. Ulcer healing was evaluated by endoscopy and symptom assessment occurred at baseline and at two, four, and eight weeks, or upon symptom worsening as determined by the investigator. Healing was defined as complete re-epithelialization of the crater, without residual erosion. Patients completed eight weeks of treatment regardless of whether or not they were healed at two or four weeks. Treatment groups were comparable with regard to age, sex, ulcer history, cigarette smoking, alcohol and caffeine consumption, ulcer size, and ulcer symptoms. Analysis of procedurally correct cases demonstrated that sucralfate suspension was significantly more effective in healing duodenal ulcers than placebo at two, four, and eight weeks. Ulcer-healing rates efficacy analysis are as follows. At two weeks, the healing rate of sucralfate suspension was 22 of 125 patients (18 percent) and the healing rate of placebo suspension was eight of 130 patients (6 percent; p = 0.006). At four weeks, 58 of 114 patients (51 percent) for sucralfate and 38 of 112 patients (34 percent) for placebo (p = 0.011) were healed. At eight weeks, 80 of 105 (76 percent) for sucralfate and 53 of 100 (53 percent) for placebo (p = 0.001) were healed. Sucralfate-treated patients experienced significantly greater reductions in both daytime and nighttime pain scores at two weeks. A significant difference between treatment groups was also found for daytime symptoms at four weeks. At four and eight weeks, patients who smoked cigarettes had significantly lower healing rates than those who did not, regardless of treatment group. Sucralfate suspension was found to be effective for the treatment of active duodenal ulcer.
From one colonic carcinoma chemically induced in the rat, 2 sublines of tumor cells have been cloned, one (PROb) inducing progressive tumors, the other (REGb) generating tumors that regress a few weeks after s.c. injection into syngeneic hosts. Our study was aimed at comparing cellular immunity between animals bearing PROb or REGb tumors. Spleen cells were first tested for in vitro proliferation in response to mitomycin-treated PROb or REGb cells. Only spleen cells from rats injected with REGb cells proliferated significantly when mixed with PROb or REGb cells. The proliferative response induced by REGb cells was considerably higher than the response to PROb cells. When spleen cells from rats bearing REGb tumors were cultured with a mixture of REGb and PROb cells at various PROb/REGb cell ratios, PROb cells significantly suppressed the strong proliferative response generated by the same number of REGb cells alone. REGb-immune spleen cells, after in vitro stimulation by PROb or REGb cells, were not cytotoxic for either cell variant. REGb-immune spleen cells did not differ in their content of T lymphocytes expressing CD4 or CD8 markers when they were stimulated by PROb or REGb cells in vitro, but REGb cells induced a larger number of activated lymphocytes expressing the IL-2 receptor. Our results indicate that, compared to REGb cells, PROb cells are poorer stimulators of proliferation of tumor-immune spleen cells, and that they are able to suppress the proliferative response induced by REGb cells.
Difficulties associated with in vitro manipulation and culture of the early chicken embryo have restricted generation of transgenic chickens to approaches that use replication-competent retroviruses. The need to produce transgenic chickens in the absence of replicating virus prompted development of a new method of gene transfer into the chicken. Microinjection of the replication-defective reticuloendotheliosis virus (REV) vector ME111 beneath unincubated chicken embryo blastoderms results in infection of germline stem cells. This vector contains genetic information exogenous to the chicken genome, including both the herpes simplex virus type 1 thymidine kinase gene and the Tn5 neomycin phosphotransferase gene. About 8 percent of male birds hatched from injected embryos contained vector DNA in their semen. All four positive males tested passed vector sequences onto their progeny. Analysis of G1 offspring showed that gonads of G0 male birds were mosaic with respect to insertion of vector provirus. Thus, primordial germ cells present in the unincubated chicken embryo blastoderm are susceptible to infection by defective REV vectors.
From 1978 to 1985, 297 patients were entered in a double-blind randomized trial comparing levamisole to placebo as adjuvant therapy of Dukes' C carcinoma of the colon. Therapy consisted of from two to five tablets of 50 mg levamisole (or placebo) twice a week, depending on bodyweight for 1 year. Levamisole was generally well tolerated, with only four reversible cases of agranulocytosis reported among 129 patients. The trial failed to show a benefit of levamisole on disease-free survival (P = 0.53) or on survival (P = 0.35). There was no difference between the two treatment groups in terms of number of disease relapses, sites of relapse, or time to relapse. The proportion of patients still alive at 5 years was 51 per cent (standard error, 5.5 per cent) in the levamisole group versus 39 per cent (standard error, 5.4 per cent) in the placebo group.
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Four levels of regulation of glucocorticoid receptor (GR) activity have been investigated. (1) Phosphorylation of the GR was studied in NIH 3T3 cells metabolically labeled with [32P]orthophosphate. A highly specific antiserum against the GR was used to immunoprecipitate 32P-labeled GR, and protein blotting was used to determine the GR concentration. Comparison of the relative specific activities of non-activated and activated receptor revealed a 3-4-fold increase in GR phosphorylation within 60 min upon hormone activation. (2) The affinity of the GR for its hormone response element (GRE) was quantitated in in vitro binding and gel shift experiments. The comparison of monomers, dimers and trimers of the GRE showed that GR binding affinity to multimers is much higher than the affinity for a GRE monomer. (3) The concentration of the GR was determined in quantitative protein blot assays as a function of time after hormone treatment of NIH 3T3 cells. A down-regulation of GR was observed. Only 30% of the maximal GR concentration observed in the absence of hormone remained after 24 h of hormone treatment. (4) The effect of the presence of hormone on the subcellular location of the GR was studied. Hormone treatment and withdrawal experiments indicated that the presence of hormone is not only required to initiate the cascade of events resulting in transcriptional trans-activation. GR translocated to the nucleus upon hormone addition returns rapidly to the cytoplasm upon hormone withdrawal. This indicated an active role for the hormone in the tight nuclear binding of GR.
Proteins, including lens proteins, were incubated in the presence of 3-hydroxyanthranilic acid (30 HA) under oxidizing conditions. Samples were monitored for alterations in color, fluorescence, sulfhydryl content, lysine availability, methionine content, tryptophan content and protein size. Incubation of proteins with 30 HA produced rapid brown coloration and a correspondingly rapid decrease in sulfhydryl content. Alpha-, beta- and gamma-crystallins were all found to react with 30 HA. An increase in protein fluorescence (excitation 340/emission 425 nm) accompanied the color development. No significant decrease in the content of tryptophan or any other amino acid was detected by amino acid analysis. The levels of available lysine were not affected significantly by treatment with 30 HA. Oxidation of methionine to methionine sulfoxide and the covalent cross-linking of polypeptides was obtained by subsequent treatment of the tanned proteins with H2O2. The modifications observed are very similar to those found in the senile nuclear cataract lens.
The effects of cyclosporin-induced immunosuppression were assessed in a rat model of progressive and regressive colonic tumors. Two cloned cell variants, obtained from the same chemically induced colonic carcinoma, differ in their capacity to grow when injected into the syngeneic rat. PROb cells yield progressive tumors and often metastases; in contrast, REGb cells produce tumors which regress in 3 to 6 weeks. Cyclosporin A (CsA) administered daily, 20 mg/kg subcutaneously (s.c.) for 30 days after tumor cell inoculation, drastically enhanced the local growth of PROb tumors and increased the number of metastases. It increased the local growth and prevented the regression of REGb tumors which persisted even as long as 8 weeks after the termination of CsA administration and occasionally yielded metastases. CsA prevented the accumulation of inflammatory cells with the T lymphocyte phenotype at the periphery of both PROb and REGb tumors but did not alter the tumor infiltration by macrophages and NK cells. CsA did not modify the natural cytotoxicity of peripheral blood mononuclear cells against PROb and REGb target cells. These results suggest that CsA-induced suppression of T lymphocyte activity may enhance tumor progression and suppress tumor regression in this model.
The course of atrophy of type I and type II muscle fibers of the posterior cricoarytenoid muscle, the lateral cricoarytenoid muscle and the medial thyroarytenoid muscle of 9 dogs have been investigated after resection of the ipsilateral recurrent laryngeal nerve after 2, 4 and 10 months. Using ATP-ase staining the histochemical results revealed a predominant atrophy of type II fibers, a reactive hypertrophy of type I fibers after a period of 4 months and a pattern of type-grouping with signs of a complete reinnervation in all laryngeal muscles within 10 months. The existence of a supplementary innervation of the intrinsic laryngeal muscles in dogs and its implication on experiments in laryngeal reinnervation are discussed.
Haematoporphyrine-derivative (hpd) selectively photosensitises malignant tumours following intravenous application. 48 hours after injection of hpd an integral laser-light application of the tumour and the surrounding normal tissue was performed. We report on the successful administration of this photodynamic therapy in a patient with a spinocellular carcinoma of the auricle. 16 days after therapy the tumour showed a complete response without damage of the also irradiated surrounding normal tissue. Apart from a temporary sensitivity to light no side effects of the therapy were seen.
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Replication-defective vectors derived from reticuloendotheliosis virus were used to transduce exogenous genes into early somatic stem cells of the chicken embryo. One of these vectors transduced and expressed the chicken growth hormone coding sequence. The helper cell line, C3, was used to generate stocks of vector containing about 10(4) transducing units per ml. Injection of 5- to 20-microliters volumes of vector directly beneath the blastoderm of unincubated chicken embryos led to infection of somatic stem cells. Infected embryos and adults contained unrearranged integrated proviral DNAs. Embryos expressed the transduced chicken growth hormone gene and contained high levels of serum growth hormone. Blood, brain, muscle, testis, and semen contained from individuals injected as embryos contained vector DNA. Replication-defective vectors of the reticuloendotheliosis virus transduced exogenous genes into chicken embryonic stem cells in vivo.
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Cyclic monkeys were deprived of FSH for specific periods on different days of the follicular phase by injecting them with minimal doses of an FSH antiserum characterized for specificity and bioneutralizing ability. The effect of the antiserum on follicular maturation was assessed by determining (a) serum oestrogen concentrations through the midcycle period, (b) serum progesterone concentrations as an index of ovulation and luteal function, (c) laparoscopic examination of the surface of the ovary when necessary, and (d) overall cycle length. While antiserum injection on Day 5 of the cycle caused delay in the oestrogen surge from Days 9 to 11, injection on Day 6 led to the occurrence of two oestrogen surges, on Days 9 and 14. Laparoscopic examination showed that the earlier follicle had disappeared and a new follicle had appeared by Day 14. Antiserum injection on Day 7 of the cycle arrested further growth of the maturing follicle, but a new follicle appeared 9 days later, as indicated by a surge of oestrogen on Day 16. Injection of antiserum beyond Day 7 had no effect on follicular development, ovulation and luteal function. These observations suggest that the mature follicle becomes relatively independent of FSH support about 48 h before ovulation and this event could be a marker for follicular dominance.
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