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Biomedical subjects

G Simonin

Publications and source records attributed to G Simonin.

At least 37 records · Page 2Linked to original sources
PubMed1996

Expression of the multidrug resistance-associated protein (MRP) mRNA and protein in normal peripheral blood and bone marrow haemopoietic cells.

We studied the expression of multidrug resistance-associated protein (MRP) in normal haemopoietic cells from peripheral blood and bone marrow. The MRP mRNA levels were estimated by RT/PCR and in situ hybridization (ISH) assay, and the protein levels by flow cytometry. 21 samples of peripheral blood and 21 samples of bone marrow (11 normal bone marrow donors, 10 patients in complete remission after chemotherapy for large cell lymphoma or acute myeloid leukaemia) were analysed. In peripheral blood the mean MRP mRNA level in CD3+ cells was statistically higher than in the other cells (3-fold by the methods used). The levels of MRP in CD3+ varied from one individual to another (4.5-34.8 units by RT/PCR and 5-23 grains/cell by ISH); however, this was proportional to the variation in all the cell lineages of same individual (r = 0.84). In bone marrow the mean MRP levels of the various cell lineages (including CD34+) were similar to the basal level in HL60 cells. Individual expression levels were again variable; however, there was no difference between untreated normal bone marrow and post chemotherapy normal bone marrow. MRP protein expression was determined by flow cytometry with the monoclonal antibody MRPm6. The CD4+ lymphocytes exhibited a higher MRP protein expression than the other cell lineages, including CD8+ cells. There was a good correlation between the three methods used (RT/PCR and ISH, P = 0.0001, r = 0.87; RT/PCR and flow cytometry, P = 0.0001, r = 0.85; ISH and flow cytometry, P = 0.002, r = 0.67).

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Glutathione-S-transferases pi, alpha, mu and mdr1 mRNA expression in normal lymphocytes and chronic lymphocytic leukemia.

Chronic B cell lymphoproliferative disorders are frequently sensitive to alkylating agents. To assess the glutathione-S-transferases (GSTs) gene expression in B tumoral lymphocytes, possibly responsible for this sensitivity, we developed a sensitive RT-PCR assay for the three isoenzymes GST pi, GST mu and GST alpha mRNA. Normal B and T lymphocytes from 11 blood donors were separated by magnetic beads and tested with this assay. The GST pi was the most abundant transferase, and was detected in all B and T cell samples. GST mu was undetectable ('null' phenotype) in 6/11 normal donors, either in B or T cells. GST alpha was very stable from donor to donor, and was highly correlated between B and T cells of the same individual (P < 0.0001). There is no correlation between the three isoenzymes, and between each isoenzyme and mdr1 gene expression. Twenty-three B lymphoproliferative disorders (20 B-CLL, 3 CD5- chronic lymphoproliferative syndromes) were tested with the same technique. An average decrease of 57% of the GST pi expression was noted in the mononuclear cells of these patients (P < 0.02), with no differences between the untreated and treated cases. The GST alpha and mdr1 mRNA levels did not differ from normal B lymphocytes, but the proportion of patients with no detectable expression of GST mu is lower than in the control (13%). Interestingly, the low content of GST pi in B-CLL could explain the frequent sensitivity of this disease to alkylating agents.

Adult↗
PubMed1994

Cytoplasmic sequences of the growth hormone receptor necessary for signal transduction.

To study structure-function relationships of the growth hormone (GH) receptor (GHR), two functional systems have been developed. CHO cells were transiently cotransfected with the cDNA encoding the full-length rat GHR and with a construct consisting of the 5' flanking region of one of two GH-dependent genes encoding ovine beta-lactoglobulin or serine protease inhibitor 2.1 (Spi 2.1, formerly Spi.1; the corresponding rat gene has recently been redesignated Spin2a) coupled to the bacterial reporter gene encoding chloramphenicol acetyltransferase (CAT). Transfected cells were grown in the absence and presence of human GH and dexamethasone for the Spi 2.1 gene construct. GH was able to activate each promoter (with approximately 4-fold induction of CAT activity) in a dose-dependent manner. For both tests, the maximal effect was observed at 20 nM human GH. These tests have been used to identify functional domains of the GHR. Two truncated (T) GHRs, lacking most or part of the cytoplasmic domain [called T276 (ending at residue 276) and T436 (ending at residue 436)], were unable to stimulate CAT activity. The GHR contains a proline-rich region, called "Box I," conserved in the cytokine/GH/prolactin receptor family. Alanine substitutions for the four prolines of GHR Box I were introduced. Single proline-to-alanine mutations did not affect the functional activity of the GHR. However, modification of the four prolines together or deletion of the Box I (15 amino acids between positions 279 and 293) resulted in the complete absence of GH stimulation. Thus, the proline-rich region, shown to be important for other members of this receptor superfamily, is also critical for GH signal transduction.

Amino Acid Sequence↗
PubMed1994

Tolfenamic acid and mefenamic acid in the treatment of primary dysmenorrhoea.

The clinical efficacy of tolfenamic acid and mefenamic acid in the treatment of primary dysmenorrhoea was studied in a prospective, controlled, double-blind, cross-over study comprising 73 patients aged 13-39 with an average body weight of 56 kilos. The patients were randomized to receive either tolfenamic acid (200 mg t.i.d.) or mefenamic acid (500 mg t.i.d.) for 3 days, during 3 consecutive menstrual cycles each, in a sequential design A-B or B-A. At the beginning and at the end of each treatment period, 13 dysmenorrhoeic symptoms were evaluated on a visual analogue scale (lower back pain, interference with daily activities, nausea, vomiting, diarrhoea, headache, dizziness, fatigue, sweating, chills, hot flashes, depressant states, and mood swings). The data were analyzed by using two statistical models. The first one, for the 73 patients, by making paired comparisons regardless of treatment sequence. With respect to the initial values, the results showed that both drugs were statistically significant (P < 0.05) in reducing the intensity of the evaluated symptoms. When comparing both treatments, tolfenamic acid showed a significant difference as to interference with daily activities (P < 0.025) and hot flashes (P < 0.005). In the result analysis with the second model, the groups were divided according to the first assigned treatment and paired comparisons were made. It was observed that the group receiving tolfenamic acid in the last sequence reached a higher level of response and statistical significance was demonstrated in 8 of 13 evaluated symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Study of final height in Turner's syndrome: ethnic and genetic influences.

In understanding Turner's syndrome, spontaneous adult height is a prerequisite for an accurate assessment of the therapeutic efficiency of growth hormone treatment. The heights described in the literature reveal significant differences (136-147 cm). Our collaborative study pooled results from 16 pediatric endocrinology centers and obtained a large number of spontaneous adult heights (n = 216). The selective criteria were: chronological age (CA) > 18 years, bone age (BA) > 16 years, typical karyotype, no treatment with growth hormone or anabolic steroids. Mean CA was 23.3 +/- 5.6 years. Chromosomal anomalies were: monosomy X 56%; mosaicism 37.2%; structural aberration 10.6%. Mean final height in the whole group was 141.5 (129-160) cm. There was no significant difference in height between the three groups: monosomy X (n = 121: 141.1 +/- 6.4 cm); mosaicism (n = 72: 141.5 +/- 7.5 cm); X anomaly (n = 23: 141.4 +/- 5.0 cm). Mean parental height was 170.4 +/- 7.1 cm (father) and 160.1 +/- 6.2 cm (mother). Parental height and patients' heights correlated significantly, but more so with fathers' heights (r = 0.50) than with mothers' (r = 0.42). The correlation was still apparent with the target height (r = 0.55). The results of different series in the literature show the existence of significant variations as mean final heights are between 136 and 147 cm. These differences can be explained by the variations in normal female heights in each country. We have found in these different countries a very strong correlation (r = 0.91) between normal height and final height in Turner's syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Evidence for generation of the growth hormone-binding protein through proteolysis of the growth hormone membrane receptor.

The growth hormone-binding protein (GHBP) which circulates in plasma is a soluble short form of the membrane growth hormone receptor (GHR). In rats and mice, GHR and GHBP originate from two alternatively spliced mRNAs (4.5 and 1.2 kb). In human and rabbit tissues, a single predominant mRNA of 4.5 kb was detected and it was hypothesized that GHBP could be produced by proteolytic cleavage of the GHR. Using gel filtration and HPLC, we have detected a high level of GH binding activity in media of cells transfected with rabbit GHR cDNA. The [125I]hGH-GHBP complex eluted at the same time as the plasma complex and both the binding affinity and specificity of the BP were comparable to that of rabbit plasma. Immunoprecipitation experiments and Western blots confirmed that GHBP in the media of transfected cells was a 55 kDa protein related to the extracellular domain of the GHR. In contrast, no BP was detected in the media of cells transfected with the cDNA encoding the rat GHR. These results strongly suggest that, in rabbit and probably in man, the GHBP could, at least in part, be produced by proteolytic cleavage of the GHR.

Animals↗
PubMed1993

[Klinefelter syndrome in 1993. Results of a multicenter study on 58 cases and review of the literature].

A retrospective multicenter study found 58 cases of Klinefelter syndrome of which 23 (39%) were diagnosed before puberty. Although as common as Down syndrome, Klinefelter syndrome is underdiagnosed and often recognized only in adulthood. Suggestive manifestations in infants, children, and teenagers include facial dysmorphism, micropenis, and delayed speech and should lead to examination of the karyotype. Early recognition of Klinefelter syndrome could be achieved by routinely measuring the size of the testes in school-boys aged 11 to 15 years and performing a karyotype in boys with a volume of less than 2 ml. Early psychological and educational support and testosterone replacement therapy initiated at onset of puberty may lead to improved social and academic outcomes.

Adolescent↗
PubMed1992

[Serum human growth hormone assay. Comparison of six assay kits].

Measurements of human growth hormone (hGH) plasma levels using mono or polyclonal antibodies based on kits are often highly variable depending upon the kit used. We compared six kits commercially available: one based on polyclonal antiserum, five based on monoclonal antisera. We measured 695 sera obtained in short stature children (GH deficiency or normal GH secretory) and adults (normal, hypopituitarism or acromegaly). Our results confirm the variability between the assays. The maximal variation was obtained with SBhGH kit which showed mean results 1.7 fold higher than those obtained with hGH Coatria. Using the OMS 80.205 standard with the six kits, we found a good correlation between the six kits indicating that the standard used in each case was not responsible for the observed variations. This suggest that the different antibodies used in these kits may recognize different isoforms of circulating hGH. In addition variations in reagents used in the different kits may also explain these discrepancies. The variations observed using these six commercially available kits may have important clinical repercussion and especially may impede the diagnosis in hGH deficiency in children.

Adolescent↗
PubMed1992

[Vitamin D-resistant rickets type II: apropos of 2 cases].

We present two cases of vitamin D-dependent rickets type II, a rare disease caused by a hereditary disorder of the receptor for 1,25 dihydroxyvitamin D (1,25 (OH) 2 D). The first patient was seen for the first time at the age of 2 years with florid rickets, almost complete alopecia, and an elevated plasma level of 1,25 (OH) 2 D; there was no improvement following treatment with 1 alpha-hydroxy-vitamin D3). The second patient, a boy whose parents are first cousins, was seen at the age of 7 years with severe rickets, partial alopecia and an elevated serum level of 1,25 (OH) 2 D; the rickets disappeared after administering high doses of 1 alpha hydroxyvitamin D3 and vitamin D.

Alopecia↗
PubMed1991

The soluble receptor of interleukin 2 is not a serum marker of the autoimmune activity in type I diabetes mellitus.

In order to determine if soluble interleukin 2 receptor (IL2R) was useful as a marker in screening for early Type 1 diabetes and in monitoring immunological treatment, we assayed serum IL2R levels in 67 controls, 43 patients with newly diagnosed diabetes and 28 first degree relatives of diabetic patients (5 subjects were islet cell antibody positive). In 23 diabetes, specimens were analysed at 3 and 6 months after diagnosis whether or not cyclosporin A was administered. Seven patients were in a clinical trial using anti IL2R monoclonal antibody and cyclosporin A. Since IL2R level in the normal population is elevated in the first 5 years of life then decreases until adulthood (age:IL2R correlation between 0 and 15 years: r = -0.42, P less than 0.05), subjects were carefully matched in age. In recent onset diabetes, this negative correlation disappeared and IL2R levels tended to decrease particularly in younger subjects. In Type 1 prediabetic subjects presenting persistent islet-cell antibody serum IL2R was not elevated. During immunological treatment of recent onset diabetes, serum IL2R remained stable and was not modified by cyclosporin A. As expected IL2R became undetectable during treatment with anti IL2R MC Ab. But it rebounded when treatment was stopped with no effect on remission. We concluded that IL2R levels in Type 1 diabetic patients is not useful in screening autoimmune activity or in evaluating the effectiveness of immunosuppressors.

Adolescent↗
PubMed1988

[Syndrome of activation of the mononuclear phagocyte system. Initial manifestation of visceral leishmaniasis].

We report a case of mononuclear phagocyte system activation observed in a 12 month-old girl presenting with fever, hepatosplenomegaly, pancytopenia, histiocytic hyperplasia with hemophagocytosis in the bone marrow, high triglyceride and low fibrinogen blood levels. This syndrome was associated with visceral leishmaniasis. We conclude that systemic leishmaniasis is a curable cause of disorders characterized by an activation of the mononuclear phagocyte system.

Animals↗
PubMed1984

[Pharmacodynamic tests of the stimulation of hypophyseal function: simplification of the procedure without alteration of their diagnostic value].

The aim of this study was to examine if it was possible to simplify the procedure of some stimulation tests of pituitary function. This study was performed on 300 stimulation tests of TSH by TRH, PRL by TRH, LH by LHRH and FSH by LHRH, respectively. Simplified procedures may be proposed without altering the diagnostic value of the tests: assay of TSH and PRL 0 and 30 minutes after TRH injection and of LH and FSH 0, 30 and 60 minutes after LHRH injection.

Evaluation Studies as Topic↗
PubMed1983

Differential cytostatic effect of interferon on murine BALB/c B- and T-cell tumors.

The cytostatic effect of murine interferon (IFN) on several BALB/c-derived B- and T-cell tumor cells was examined. After incubation for 1 h in vitro with 1000 U of IFN, followed by intraperitoneal inoculation, tumor formation was not decreased in the case of B cell tumors or Lyt-1+2- or Lyt-1+2+3+ T cells tumors. Under the same conditions, the onset of tumor formation for Lyt-2+3+ T-cell tumors was delayed and the final incidence decreased. When the effect of IFN on cell multiplication in vitro was examined, Lyt-2+3+ T-tumor cells were found to be more sensitive to the cytostatic effect of IFN than Lyt-1+2+3+ T-tumor cells. This shows that the sensitivity of lymphocyte-derived tumor cells to the cytostatic effect of IFN is influenced by the type of differentiation of the cells.

Animals↗