Use of immunoblotting to detect idiotypic determinants on monoclonal antibodies.
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Biomedical subjects
Publications and source records attributed to C Petit.
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A retrospective study was carried out on 386 patients with advanced cervical carcinomas treated with radiation therapy between 1973 and 1983. The influence of hemoglobin concentrations and blood transfusions before and/or during treatment on the occurrence of distant and/or local regional failures were examined in a univariate and multivariate analyses. In the multivariate analysis hemoglobin concentrations were prognostic only during treatment and patients with at least one value below the threshold of 10 gm% had a significantly higher risk of local regional failure than the patients with all their values above the threshold. Moreover 70% of these high risk patients had less than half of their values below the threshold. It is possible that blood transfusions might be beneficial when given before treatment. However, although it was not significant, blood transfusions given during treatment tended to be an adverse prognostic factor suggesting that blood transfusions might not have completely offset acute anemia prior to transfusion. Our study suggests that anemia during treatment, even of short duration might be detrimental to patients.
Human Y(+) XX maleness has been shown to result from an abnormal terminal Xp-Yp interchange that can occur during paternal meiosis. To test whether human XY females are produced by the same mechanism, we followed the inheritance of paternal pseudoautosomal loci and Xp22.3-specific loci in two XY female patients. Y-specific sequences and the whole pseudoautosomal region of the Y chromosome of their fathers were absent in these patients. However, the entire pseudoautosomal region and the X-specific part of Xp22.3 distal to the STS locus had been inherited from the X chromosome of the respective father. This Xp transfer to Yp was established by in situ hybridization experiments showing an Xp22.3-specific locus on Yp in both cases. Such results demonstrate that an abnormal and terminal X-Y interchange generated the rearranged Y chromosome of these two XY females; they appear to be the true countertype of Y(+) XX males. In these patients, who also display some Turner stigmata, the Y gene(s) involved in this phenotype is (are) localized to interval 1 or 2. If the loss of such gene(s) affects fetal viability, their proximity to TDF would account for the underrepresentation of interchange 46,XY females compared with Y(+) XX males.
The activity of various inhibitors on several subcellular enzymes was studied. First we determined the inhibitory concentration required to reduce maximum enzymatic activity by 50%, then the effect of various hahnemannian dilutions of the same inhibitory agent was tested. Seven inhibitory agents were tested in this way on seven different enzymatic systems. No effects of these hahnemannian dilutions were shown.
A cytogenetic prenatal diagnosis due to maternal age led us to find a male fetus with a (X;Y) translocation. This translocation is found in the mother, who presents no phenotypic abnormalities or mental retardation. The 22 cases described in the literature indicate that among male carriers of an (X;Y) translocation, half the cases present mental retardation and 2/3 phenotypic anomalies. These findings led us to give a genetic counselling of therapeutic abortion. Post mortem histological examination revealed no morphodysplasia.
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A long-range restriction map of the pseudo-autosomal or exchange pairing region (corresponding to the terminal parts of the short arms of the human sex chromosomes) has been established using pulsed field gel electrophoresis. A total of seven loci have been located on this physical map based essentially on the analysis of 45,X Turner genomes. The region spans a total of 2600 kb. The 5' end of the MIC2 gene maps at less than 80 kb from the proximal pseudo-autosomal boundary. Since the total pseudo-autosomal linkage interval represents approximately 50% of recombination at male meiosis, 1 cM corresponds to 50-60 kb. This is consistent with the almost 20-fold increase in recombination frequency observed in male versus female meiosis in this region. The present data show no distortion between both physical and linkage maps. The distribution of the CpG-rich restriction sites is notably disequilibrated. A large subset of these sites is concentrated within the 500 kb closest to the telomere whereas others appear in clusters (probably HTF islands) scattered in the rest of the pseudo-autosomal region.
A microscale colorimetric assay for neutral sugars, in which neutral sugars react with resorcinol in the presence of 75% sulfuric acid solution is described. This assay, based on the use of microtiter plates with 96 U-shaped wells is simple and easy to handle; it allows accurate determinations with small samples (20 microliters) containing 1 to 100 nmol of neutral sugars and is quite convenient for detection of glycoconjugates in chromatographic column effluents.
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To determine if human XX maleness results from an abnormal chromosomal X-Y interchange, we studied the inheritance of the paternal pseudoautosomal region in nine patients. Those six patients in whom Y-specific DNA was found (Y(+)) inherited the entire pseudoautosomal region from the paternal Y chromosome and lost that of the paternal X chromosome. Moreover, in three Y(+) cases, we observed the deletion of a paternal Xp locus tightly linked to the pseudoautosomal region. These results definitively show that an abnormal and terminal X-Y interchange during paternal meiosis causes Y(+)XX maleness. In contrast, no abnormal X-Y interchange was observed in any of the three Y(-) cases analyzed, suggesting that maleness can occur in the absence of any Y-specific DNA.
Two pseudoautosomal loci DXYS15 and DXYS17 from the pairing region of the human sex chromosomes display a high variability with at least eight alleles each. The structural elements responsible for the polymorphisms have been isolated and sequenced. In both cases the variations result from DNA rearrangements occurring in tandemly repeated sequences (minisatellites) of 21-29 nucleotides for DXYS15 and 28-33 nucleotides for DXYS17. At reduced stringency, the DXYS15 minisatellite detects other hypervariable sequences located in other parts of the genome and hence represents a new family of minisatellites. In contrast to most other known hypervariable families, the DXYS15 hypervariable sequence displays a very high AT content.
During the last 4 years we collected 27 specimens of calcium oxalate nephrolithiasis in patients receiving long-term treatment with piridoxilate, a drug composed of an equimolar combination of glyoxylate and pyridoxine. The mean duration of treatment was 3.6 years (range 4 months to 10 years) and the mean daily dose was 580 mg. piridoxilate, which contained 160 mg. glyoxylate. Calculi often recurred, with an average number of 9.9 per patient, and an open operation, shock wave lithotripsy or percutaneous nephrolithotomy was required in 22 patients (81 per cent). Oxalate excretion was 727 +/- 246 mumol. per day while on the drug and 382 +/- 201 mumol. per day after the drug was withdrawn. Whewellite was the major component of calculi in all cases but the stones exhibited a peculiar morphological arrangement, with multiple small indentations and a fine mamillary structure. Freshly voided urine specimens contained unusual crystals, which on infrared spectroscopy were composed of calcium oxalate trihydrate, a variety of crystal never observed previously in human urine. Piridoxilate-induced calcium oxalate nephrolithiasis is a new variety of metabolic drug-induced nephrolithiasis. Our observations suggest that even large doses of pyridoxine may be unable to prevent the excessive production of oxalate from glyoxylate.
A single obligatory recombination event takes place at male meiosis in the tips of the X- and Y-chromosome short arms (i.e. the pseudoautosomal region). The crossover point is at variable locations and thus allows recombination mapping of the pseudoautosomal loci along a gradient of sex linkage. Recombination at male meiosis in the terminal regions of the short arms of the X and Y chromosomes is 10- to 20-fold higher than between the same regions of the X chromosomes during female meiosis. The human pseudoautosomal region is rich in highly polymorphic loci associated with minisatellites. However, these minisatellites are unrelated to those resembling the bacterial Chi sequence and which possibly represent recombination hotspots. The high recombination activity of the pseudoautosomal region at male meiosis sometimes results in unequal crossover which can generate various sex-reversal syndromes.
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Numerous studies of cell hybrids have indicated that somatic cells produce negative regulators (extinguishers) that prevent the expression of functions foreign to their own differentiation. Here, we report genetic evidence of such control. In microcell hybrids between well-differentiated rat hepatoma cells and microcells of mouse fibroblast L cells, the extinction of albumin synthesis is directly related to the presence of a single specific chromosome of the mouse fibroblast parent. The expression of several other hepatic functions is not affected. Transfection of these hybrids with a recombinant plasmid, containing a tissue-specific control element of the upstream region of the rat albumin gene linked to coding sequences of the chloramphenicol acetyltransferase gene, reveals that extinction acts on or via this cis-control element.
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The rapid loss of alloreactivity within populations of antigen-primed, in vitro propagated T cells cannot be explained by the appearance of suppressor cells nor by the dilution effect of the proliferative antigen-specific T cells alone. The involvement of trans-stimulation in loss of alloreactivity, i.e. the recruitment of non-antigen-specific T cells into proliferation in an antigen-dependent and specific fashion, was assessed. Susceptibility to trans-stimulation was found to correlate directly with state of activation at the outset of assay. Large T cells (low buoyant density) but not small T cells (high buoyant density) are susceptible to trans-stimulation. Moreover, in vitro pre-activation of small T cells by mitogen confers susceptibility to trans-stimulation. Analysis of the alloreactivity in Percoll fractions of antigen-primed lymph node T cells revealed activity in both large- and small-T-cell fractions with some enrichment in the latter. The small T cells, refractive to trans-stimulation, are diluted out of the population within the early weeks of antigen-mediated in vitro propagation, accounting for a rapid loss of considerable alloreactivity. The loss of all detectable alloreactivity within antigen-selected populations suggests that the state of activation conferring sensitivity to trans-stimulation must be maintained, and that neither the antigen nor the culture conditions employed met this requirement.
Usually calcium nephrolithiasis is due to "idiopathic" hypercalciuria associated with failure of the compensatory mechanisms (dissolving substances and crystallisation inhibitors. Classically a sufficient diuresis, a low calcium diet, the phosphate ion or (and) the thiazidic diuretics manage to reduce the hypercalciuria and to decrease the chances of relapse. This aim may be differently reached when hyperuricosuria is associated with hypercalciuria. The use of uric acid synthesis inhibitors (allopurinol, thiopurinol) brings the frequency of the recurring stone formation down and... the calciuria often. Series dealing with 141 calcium lithiasis with hyperuricosuria.