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Biomedical subjects

J Bonnet

Publications and source records attributed to J Bonnet.

At least 199 records · Page 11Linked to original sources
PubMed1981

Chemoimmunotherapy for multiple myeloma.

The effect of chemoimmunotherapy consolidation treatment using alternating courses of alkylating agents and BCG was studied in 105 responding patients with multiple myeloma. The survival time of these patients was similar to that of responding patients treated on previous maintenance programs, indicating no apparent value from BCG for myeloma. The duration of unmaintained remission was longest in those with low numbers of residual plasma cells, and relapse usually developed within one year in patients with persistent serum myeloma peaks. Disease recontrol was achieved in 50% of relapsing patients whose median survival from retreatment was 20 months. Patient follow-up without chemotherapy until relapse was justified mainly for those responding patients with disappearance of myeloma proteins.

Adult↗
PubMed1981

Cloning of the yeast methionyl-tRNA synthetase gene.

A pool of random wild type yeast DNA fragments obtained by partial Sau IIIA restriction enzyme digestion and inserted in the Bam HI site of the hybrid yeast Escherichia coli plasmid ((pFL1) has been used to transform to prototrophy a methionyl-tRNA synthetase-impaired mutant requiring methionine. In the numerous prototroph strains recovered at least two independent clones have been obtained which show nonchromosomic inheritance character and an approximately 30-fold increase in methionyl-tRNA synthetase activity as compared to the wild type. Measurement of the Km for methionine in the transformed yeast cells indicates that the activity has been restored by decreasing the Km for methionine to the same level as found for the wild type methionyl-tRNA synthetase. Southern blotting experiments show that the yeast DNA's fragments inserted in the two independent plasmids share a common sequence which must correspond at least partly to the structural gene for methionyl-tRNA synthetase. They also suggest that the methionyl-tRNA synthetase gene is differently orientated in the two plasmids

Amino Acyl-tRNA Synthetases↗
PubMed1981

Platelet-activating factor acether (PAF-acether) involvement in acute inflammatory and pain processes.

PAF-acether is a potent aggregating agent released by various cells involved in acute inflammatory process. In this paper, exogenous PAF-acether has been investigated for its ability to generate signs of inflammation (edema measured by plethysmometry) and hyperalgesia (Randall-Sellito test) by standard subplantar injection in the rat paw. From 0.005 microgram. PAF-acether induced significant edema of the paw, maximal 1 hour after injection; it was dose-dependent from 0.1 to 5 microgram. Significant dose-dependent hyperalgesia occurred from 1.25 microgram; it reached a plateau from 2 to 4 hours after injection. Both phenomena were long-lasting (greater than 6 h). PAF-acether was 1.5 to 10 times stronger than PGI2 and PGE2 in inducing edema, pain, and in increasing vascular permeability. We investigated the interaction of miscellaneous drugs with the edema and the hyperalgesia caused by 2.5 microgram of PAF-acether. Non-steroidal anti-inflammatory (NSAI) drugs exerted only moderate effects on the edema without affecting hyperalgesia. Edema was highly reduced by various agents: prednisolone, L-cysteine, anti-calcic drugs, theophylline, PGI2, salbutamol, clonidine. All of them, except clonidine, and in contrast to NSAI drugs, were more potent on PAF-acether edema than on kaolin edema; a possible link between these agents is their ability to increase cyclic AMP levels in the cells and consequently to reduce lysosomal enzyme release. PAF-acether itself, injected intra-peritoneally, inhibited PAF-acether edema without preventing pain, at doses inactive on arterial pressure and hematocrit, but inducing marked gastric mucosal damage. Among the drugs tested, including analgesics, only PGI2 and imidazole improved PAF-induced hyperalgesia, showing a dissociation between edema and hyperalgesia not only in their induction (doses of PAF required, time course of the phenomena), but in the drugs able to antagonize their development too.

Analgesics↗
PubMed1979

5 FU infusion with mitomycin-C vs. 5 FU infusion with methyl-CCNU in the treatment of advanced upper gastrointestinal cancer: a Southwest Oncology Group Study.

A randomized trial was conducted by the Southwest Oncology Group (SWOG) in advanced carcinoma of the stomach and pancreas. Patients were assigned to receive monthly 5-fluorouracil 96-hour continuous infusions with either bolus mitomycin-C or oral methyl-CCNU. Mitomycin-C and methyl-CCNU were administered every eight weeks. The 5 FU-mitomycin combination produced a 14% and 22% response rate in disseminated stomach and pancreatic carcinoma, respectively. The combination of infusion 5 FU and methyl-CCNU achieved responses in 9% and 5% of stomach and pancreatic tumors, respectively. There was no significant difference in survival between limbs for either tumor. Median survival in gastric carcinoma on the 5 FU-mitomycin regimen was 25 weeks vs. 18 weeks on the 5 FU-METHYL-CCNU arm. In pancreatic carcinoma median survival on the mitomycin limb was 19 weeks as compared to 17 weeks on the methyl-CCNU program. Leukopenia was greater for the first course on the mitomycin limb. Regression analysis demonstrated that performance status was the most important pretreatment characteristic for predicting survival in both tumors. Neither 5 FU infusion combination appears to significantly alter the dismal prognosis of advanced upper gastrointestinal neoplasms.

Antineoplastic Agents↗
PubMed1979

Lack of correlation between affinity of the tRNA for the aminoacyl-tRNA synthetase and aminoacylation capacity as studied with modified tRNAPhe.

The interactions of several modified yeast tRNAPhe [tRNAPhe lacking 7-methylguanine; a fragment comprising about 3/4 of the whole molecule: tRNAPhe (18--76); tRNAPhe (18--76) lacking 7-methylguanine] with yeast phenylalanyl-tRNA synthetase were studied. Upon excision of the 5'-quarter of the tRNAPhe molecule, the residual fragment still tightly binds to the synthetase, but can no longer by aminoacylated. Surprisingly, upon removal of the 7-methylguanine base at position 46 in this fragment, althought the affinity drops by a factor 10, a significant aminoacylation is restored. These results are discussed in terms of molecular flexibility and a model is proposed for tRNA-enzyme interaction, involving multisite recognition.

Amino Acyl-tRNA Synthetases↗
PubMed1979

An automated microscope for quantitative cytology combining television image analysis and stage scanning microphotometry.

This paper describes an automated microscope developed for operation in conjunction with the Leyden Television Analysis System. It features automated control of magnification, illumination, movement of scanning stages, and fine focus. These functions are controlled by means of a microcomputer. This enables a flexible design and relieves the supervising computer of simple but time consuming tasks. The combination of an automated microscope and Leyden Television Analysis System provides a powerful tool in quantitative cytological research. The flexible design permits other microscopic functions to be added with relatively little effort.

Computers↗
PubMed1978

5FU infusion with mitomycin-C versus 5 FU infusion with methyl-CCNU in the treatment of advanced colon cancer: a Southwest Oncology Group Study.

The Southwest Oncology Group (SWOG) in a randomized trial evaluated 5FU infusions in combination with either Mitomycin-C or Methyl-CCNU in patients with disseminated large bowel cancer. A response rate of 18% was noted on the 5FU-Mitomycin limb as compared to 16% on the Methyl-CCNU arm (p = .39). Median survival for all treated patients was 43 weeks on both arms. Myelosuppression was found to be more significant on the Mitomycin-C arm. Regression analysis demonstrated that performance status, sex, and primary site were significant pretreatment characteristics for predicting survival. The response rates associated with this burdensome method of 5FU administration in combination with either Mitomycin-C or Methyl-CCNU appear to offer little advantage over bolus 5FU alone.

Adenocarcinoma↗
PubMed1978

[Effects of small doses of gamma rays on gestation in mice].

Female mice were irradiated with 10 rads of 60Co gamma ray, 7 hours after mating. This low dose induces a decrease in implantation number, and alive foetus number and is followed by a lower number of corpora lutea. These results to seem to show an effect of gamma irradiation on ovary and embryonic development.

Animals↗
PubMed1977

A new type of cytocentrifuge, the valve-centrifuge.

A new type of cytocentrifuge has been developed in which the sedimentation process of the cells onto the slides is separated from the draining of the sedimentation fluid. This is realised by electrically controlled valves which can be closed and opened while the centrifuge is running. Sedimentation is carried out with closed valves, draining of adhering medium with open valves. The preparations, freed of adhering medium by the centrifugal force can be taken out and the cells can be fixed. Alternatively the valves can be closed again and fixative can be introduced through a central well, the cells still being under the influence of the centrifugal force. With subsequent draining of the fixative and introduction of washing and staining solutions through the central well, the whole process from sedimentation to staining can be carried out in the running centrifuge. The process seems well suited for complete automation. Using dilution series from a suspension of human buffy coat cells counted in a Buerker chamber, the cell counts in the centrifuge preparations showed virtually total recovery of cells, with no apparent selection or specific distribution of cell types. Draining of the sedimentation and fixative fluids at a slow rate was found to be vital for optimal recovery of cells. The morphology of different cell types sedimented on the slide was excellent. The flattening of nuclei thorugh gravity was studied by cytophotometry of Feulgen-stained leucocytes. The nuclear area of these cells was found to be approximately double that from cells in identically stained classical smears. With this type of valve-centrifuge a quantitative and unbiased recovery of uniformly spread and flattened cells on coverslips or slides may be obtained, thus making the procedure well suited to automated analysis based on cytophotometric principles and morphometric pattern recognition.

Animals↗
PubMed1977

Combination therapy for multiple myeloma.

The effect of six different chemotherapy regimens were evaluated in 462 previously untreated patients with multiple myeloma. In comparison with other treatments, drug combinations that included vincristine and were given at 3-week intervals were associated with higher response rates and longer survival times. No gain was noted from the use of Adriamycin or from combinations of alkylating agents unless vincristine was given and the treatment intervals were short. Seventy-one responding patients were allocated at random to maintenance treatment with intermittent courses of either azathioprine--prednisone or a combination of melphalan--cyclophosphamide--carmustine (BCNU)--prednisone. The survival time was not prolonged with either maintenance treatment in comparison with that for responding patients continued on other therapies or on no therapy in previous studies. Attempts to reduce tumor was maximally with a change in the therapeutic modality, such as with immunotherapy or radiotherapy, remain to be evaluated.

Antineoplastic Agents↗
PubMed1976

Interpretation of tRNA-mischarging kinetics.

Incorrect tRNA aminoacylation reactions are characterized by very slow reaction rates and by the fact that in most cases they are incomplete. In a previous study some of us explained the incompleteness of the correct aminoacylation reactions of tRNA, which can be encountered under certain experimental conditions (for instance low enzyme concentration or high ionic strength) by an equilibrium between the aminoacylation and the deacylation reactions [J. Bonnet and J.P. Ebel (1972) Eur. J.Biochem. 31, 335-344]. In the present report we bring evidence that the incorrect valylation of yeast tRNAfMet by yeast valyl-tRNA synthetase studied under standard experimental conditions, can also be described by a kinetic rate law including the rate equations of the aminoacylation and of the various deacylation reactions. In particular we show that the incomplete mischarging plateaus reflect the existence of an equilibrium between the valylation reaction on the one hand and the spontaneous and enzymic deacylation of valyl-tRNAfMet and the reverse of the valylation reaction on the other hand. However, when the valyl-tRNA synthetase concentration is not very high the reverse reaction of the amino-acylation does not play a predominant part in the establishment of the plateau. These interpretations have been extended to other mischarging systems: valylation of yeast tRNAPhE by yeast valyl-tRNA synthetase and mischarging of tRNAfMet and tRNA2Val from yeast by yeast phenylalanyl-tRNA synthetase. Unusual mischarging kinetics have been discussed. Furthermore, and as in correct systems, we found that during the mischarging of tRNAfMet one ATP is hydrolyzed per tRNA charged with valine. We conclude that the correct and the incorrect amino-acylation of tRNA behave kinetically in a similar way.

Amino Acyl-tRNA Synthetases↗
PubMed1975

Influence of various factors on the recognition specificity of tRNAs by yeast valyl-tRNA synthetase.

Using filtration through nitrocellulose membranes we found that complexes between yeast valyl-tRNA synthetase can easily be detected at low pH and ionic strength with the cognate tRNAVal, but also with several non-cognate tRNAs (tRNAPhe, tRNATyr, tRNAMet and tRNAAsp). We show here that the amino acid linked to the tRNA has no detectable effect on these interactions. The influence of various factors on the discrimination by the enzyme between the cognate and the non-cognate tRNAs has been studied. An increase in pH or ionic strength leads to a decrease in the same ratio of the affinity constants between the enzyme and the cognate as well as the noncognate tRNA. The addition of organic solvents has little effect on these constant either in the cognate or in the non-cognate systems; the addition of substrates of the aminoacylation reaction has not effect on the ratio between the constants. This similar behaviour suggests that at least part of the specific of non-specific interactions must be identical. On the contrary, magnesium between 1 mM and 50 mM increases the specificity of recognition, showing the importance of slight conformational changes in the tRNA molecule to the specificity of interaction.

Amino Acyl-tRNA Synthetases↗