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Biomedical subjects

F Galland

Publications and source records attributed to F Galland.

At least 37 records · Page 2Linked to original sources

Chromosomal localization of FLT4, a novel receptor-type tyrosine kinase gene.

A new human gene encoding a putative receptor-type tyrosine kinase (RTK) was isolated by screening a placenta cDNA library with a mouse Flt3 probe. The deduced amino acid sequence of the intracellular region of the molecule showed that it was strongly related to the FLT1 and KDR/FLK1 gene products and to a lesser degree to members of the class III RTKs: FMS/CSF1R, PDGFRA/B, KIT, and FLT3. The gene was named FLT4. Cosmid clones of the mouse Flt4 gene were isolated. The human gene was localized to bands q34-q35 of chromosome 5, i.e., slightly telomeric to the CSF1R/PDGRFB tandem of genes, and the mouse homolog to chromosome 11, region A5-B1.

Amino Acid Sequence↗

Localization of the 5' end of the MCF2 oncogene to human chromosome 15q15----q23.

Oncogenic activation of the MCF.2 cell line-derived transforming sequence gene (MCF2) occurs through substitution of part of its 5' coding region by unrelated nonsyntenic sequences. Analysis of the MCF2 oncogene locus revealed complex recombination events involving four discontinuous human DNA segments. The upstream replacing sequence, named URS, represents the farthest 5' portion of the locus. The URS sequence maps to the D15S93 locus on human chromosome 15q15----q23.

Base Sequence↗

Restriction and complexity of Mcf2 proto-oncogene expression.

MCF2/DBL is an X-linked proto-oncogene encoding a protein with a yet undetermined function. It can be activated in vitro by loss of 5' sequences in NIH3T3 bioassays; in vivo, deletion of the gene has been found in some hemophilia B patients. PCR analysis of its expression in mouse tissues shows a restriction to the gonads and tissues of neuroectodermal origin. It also identifies an exon encoding 42 amino acids that is alternatively spliced in murine, but not human testis.

Amino Acid Sequence↗

Localization of the mouse Mcf-2 (Dbl) protooncogene within a conserved linkage group on the mouse X chromosome.

A mouse cDNA probe homologous to the human MCF2 transforming sequence has been identified and partially cloned, and is used here to localize the gene on the mouse X chromosome. The human gene has been physically mapped to within 60 kb of the gene for coagulation factor IX, within a large conserved linkage group between the mouse and human genomes which extends from HPRT to G6PD on the X chromosomes of both mammalian species. In situ hybridization of the mouse Mcf-2 probe onto mouse metaphase chromosomes indicates that this gene lies in the same region of the X chromosome as Cf-9, the mouse gene for coagulation factor IX. Moreover, segregation of species-specific genomic DNA polymorphisms for Mcf-2 and Cf-9 in a total of 203 individuals derived from two large interspecific mouse backcross populations (which are also segregating for 17 other X-linked molecular markers) demonstrates that the mouse genes are separated by only 0.5 +/- 0.5 cM. Despite this short distance we were able to order Mcf-2 and Cf-9 relative to one another and other genes in this region. The mouse gene order Hprt-Cf-9-Mcf-2-G6pd predicts a similar ordering of genes on the human X chromosome, a gene order which has only recently been demonstrated by physical mapping. Thus, the map location and linkage relationships of the Mcf-2 gene are similar in man and mouse, and this unique protooncogenic locus is part of a conserved linkage group on the mammalian X chromosome.

Animals↗

Effect of the circulating renin-angiotensin system on prolactin release in humans.

We recently reported that renin, angiotensinogen, and angiotensin-converting enzyme were present in normal human pituitary lactotroph cells and PRL-secreting adenomas. Angiotensin-II and -III have also been shown to modulate PRL release in vitro. The present study was designed to determine whether angiotensin modulates PRL secretion in vivo. In 36 hypertensive patients with widely varying renin levels, active renin and basal PRL levels did not correlate. In 10 normal volunteers, both a sustained infusion of angiotensin-II and a graded infusion of angiotensin-III induced a 2- to 3-fold increase in aldosterone levels, but had no effect on PRL secretion. Administration of the angiotensin-converting enzyme inhibitor captopril had no effect on PRL circadian rhythm in 10 normal subjects or on PRL concentrations in 11 patients with PRL-secreting adenomas. Cross-over administration of placebo and captopril did not affect the peak PRL level measured after TRH treatment in 10 hypertensive men (placebo, 43.1 +/- 5.4; captopril, 40.0 +/- 6.2 micrograms/L; P = NS) or the rise in PRL induced by doperidone in 6 normal women (placebo, 129.5 +/- 16.2; captopril, 150.0 +/- 35.7 micrograms/L; P = NS). Further, administration of enalapril for 30 days to 6 hypertensive patients did not alter basal PRL concentrations or the peak concentrations induced by TRH. These data indicate that in humans the circulating renin-angiotensin system does not interact with diurnal PRL release or with the response to TRH or domperidone.

Adenoma↗

Structure, chromosome mapping and expression of the murine Fgf-6 gene.

The sixth member of the fibroblast growth factor gene family was cloned and analysed in the mouse. It is composed of three coding exons and encodes a putative growth protein of 198 amino acids, possessing a potential signal peptide, and presenting 79% and 93.5% sequence similarity with the mouse Hst/K-fgf and human FGF-6 genes products, respectively. The murine Fgf-6 gene is located in a region distinct from the Int-41 locus and belongs to a linkage group conserved between chromosome 12 in man and chromosome 6 in mouse. It presents an intrinsic oncogenic capacity since it is able to transform cultured fibroblasts. Fgf-6 mRNA levels are developmentally regulated with a peak of expression in the developing fetus at day 15.5 of gestation, moderate levels during late gestation and in the neonate. In the adult, Fgf-6 mRNA can be detected in testis, heart and skeletal muscle.

Animals↗

Immunocytochemical and biochemical evidence of renin in human lactotrophic cell cultures.

Primary cell cultures from human prolactin (PRL)-secreting adenomas were used to test the ability of human lactotrophs to synthesize renin in vitro. The renin content of the culture medium and of cellular extracts was measured by enzyme-linked immunosorbent assay. The level of PRL release in the culture medium and the amount of PRL in a cellular extract were determined by radioimmunoassay. Morphologic studies included indirect immunofluorescence, pre-embedding immunoelectron microscopy using a three-layer peroxidase-antiperoxidase method and postembedding immunoelectron microscopy using protein A-gold complexes. Renin was detected in cellular extracts and was found to be absent in the culture medium, whereas PRL was extracellularly secreted. PRL and renin immunoreactivity was observed in all the cultures studied by immunofluorescence. The subcellular localization of renin was found to be similar to that of PRL and was observed in the rough endoplasmic reticulum, the Golgi apparatus, and cytoplasmic secretory granules. The results suggest that, in vitro, renin may be synthesized and intracellularly metabolized in human adenomatous lactotrophic cells rather than secreted. Cell cultures may be a useful model to further the understanding of the role of a local renin-angiotensin system in PRL secretion.

Female↗

Activation of a mcf.2 oncogene by deletion of amino-terminal coding sequences.

The mcf.2 transforming sequence was previously identified by tumorigenicity-assay of the mammary carcinoma cell line MCF-7, molecularly cloned and localized to Xq27 by in situ hybridization. cDNA clones representing both the activated gene and the corresponding portion of its normal counterpart were isolated and their nucleotide sequence determined. Sequence analysis showed that the mcf.2 gene was activated by rearrangement and loss of 5' sequences and no other alteration. Comparison of the mcf.2 nucleotide sequence with the recently published dbl sequence (Eva, A., G. Vecchio, D. Rao, S. Tronick & S. Aaronson (1988) Proc. Natl. Acad. Sci. USA, 85, 2061-2065) revealed that mcf.2 and dbl represent two different activated versions of the same proto-oncogene.

Amino Acid Sequence↗

[Prevention of thromboembolic complications during total hip arthroplasty by pre- and postoperative heparinotherapy with adapted doses. Apropos of 356 cases].

From January 1980 to July 1987, a continuous series of 356 total hip replacement underwent preventive treatment of subcutaneous Heparin, prescribed in adapted doses, both before and after surgery, and relayed at the 7th postoperative day by Ethyl Biscoumacetate. This medication was continued for 45 days. Modern methods of detection were used to detect thromboembolic complications: up to the 7th day radioactive labeled Fibrinogen and, at the slightest hint of problem, phlebocavography of the lower limbs. The established procedure made it possible to lower significantly the rate of phlebothromboses to 14 cases (3.9%) of which 3 (0.8%) developed non lethal pulmonary embolisms. The surgical site revealed an hematoma in 5% of the case, of which 1.4% had to be subjected to a surgical relief. Of the 4 deaths observed in this series, two resulted from the anticoagulant preventive method. The biological monitoring disclosed a lasting fall in the Antithrombin III in the three days following the operation and significant drop in the coagulation tests between the 4th and 6th day in the case of the patients who were to develop a thromboembolism.

Adolescent↗

[Non-tumor-related hirsutism in the adult woman: ovarian dystrophy or disorders of adrenal gland hormonogenesis?].

As Yen admits, polycystic ovarian disease (POD) probably has several causes, one of which involves an adrenal origin. In 20 out of a group of 45 hirsute women, the authors detected a biologic pattern suggesting ovarian dystrophy. Kinetic investigation of the adrenal function in these subjects during a synacthen retard test detected abnormal adrenal hormone production due to partial enzymatic block: in 3 cases of 21-hydroxylase, in 1 case of 11-hydroxylase and in 3 cases of 3 beta-hydroxydehydrogenase. The existence of the first two types of blockade is well established, but that of the third type remains subject to doubt. Systematic screening for disorders of this type during ovarian dystrophy would appear to be of clinical interest. The frequently empirical prescription of dexamethasone in dysovulation in POD cases may find its justification in this phenomenon; the same is also true for the use of bromocriptine in 3 beta-hydroxydehydrogenase.

Adrenal Gland Diseases↗

[Bone densitometry by monochromatic photon absorption. Study of a normal population and values obtained in various pathological conditions].

Monophotonic absorption densitometry of the forearm is an exact method for the evaluation of the bone mineralisation, provided the positioning of the forearm is strictly controlled. It is also able to demonstrate progressive enlargement of the bones with age, up until the ages of about 60 to 70 years. The measurements should be performed in two sites: diaphyseal (cortical bone) and epiphyseal (cortical and trabecular bone). The curves obtained from 1,011 controls are in agreement with the current state of knowledge concerning the variations in bone mass during life in both sexes. In women, the number of pregnancies has no influence on the mineralisation index (MI). The values obtained in 156 osteoporotic patients and in 53 subjects with idiopathic hypercalciuria were appreciably lower than those obtained in age-matched controls. In individual subjects, this method appears to be much more discrimination than the measurement of the trabecular bone volume (TBV) for the diagnosis of osteoporosis and no statistically significant correlation was observed between the MI and the TBV. In male controls, there was a depression of the mean curves around the age of 45 years in all four sites of measurement. This depression was also observed in male subjects with hypercalciuria. They correspond to the generations born between 1930 and 1940. The responsibility of a relative nutritional deficiency affecting growing boys during the 1939-45 war is proposed.

Adolescent↗

[Seasonal variations of vitamin D metabolites in man].

Studies concerning the influence of seasons and ultraviolet radiations on the metabolism of 1,25-dihydrocholecalciferol (1,25 (OH)2D), the active form of vitamin D, have given conflicting results. In the present study serum concentrations of the 3 main vitamin D metabolites--25-hydroxyvitamin D, 24,25-dihydroxyvitamin D and 1,25-dihydroxyvitamin D--were measured by radiocompetitive assay (a) monthly during one year in 7 normal subjects, and (b) before, during and after 4 weeks of "whole body" exposure to ultraviolet radiations in 11 other subjects. In study (a) parallel changes in 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D concentrations were observed during the year, with a rise in the summer; there were no significant monthly or quarterly changes in 1,25-dihydroxyvitamin D concentrations. In study (b), 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D concentrations rose by 150% and 200% respectively after 4 weeks' exposure to ultraviolet radiations and again, there were no significant changes in 1,25-dihydroxyvitamin D concentrations. These results confirm that when synthesis of the substrate (25-hydroxyvitamin D) increases, synthesis of 1,25-dihydroxyvitamin D is inhibited by a regulatory process which does not apply to 24,25-dihydroxyvitamin D synthesis.

Adult↗

[Assay of the free fraction of thyroxine. Its role in the study of thyroid function].

In a prospective study of 467 subjects with normal, increased or decreased thyroid function the results of free thyroxine (FT4) assays by 2 radioimmunological methods were compared with the free thyroxine index (FT1) and the T4/TBG ratio. It appeared from this study that FT4 assays were at least as good as the FT1 to confirm the diagnosis of euthyroidism and were distinctly superior to measurements of FT1, T4 adn T3 in patients with abnormal thyroid function. In view of the close correlation observed between clinical findings and the results of FT4 assays, a new strategy may be proposed to investigate thyroid function. However, further studies are required to evaluate the reliability of FT4 assays in some severe pathological conditions or in patients taking drugs interfering with thyroid hormone metabolism.

Humans↗

[Fruste form of hyperthyroidism manifested by auricular arrhythmia. Importance of the assay of the free fraction of thyroxine (FT4) and the role of the TRH test].

The TRH test was used to detect hyperthyroidism in 87 patients aged from 38 to 85 years who presented with atrial arrhythmia with or without heart disease. The patients had no clinical evidence of thyrotoxicosis, and total thyroxine (T4), free thyroxine index (FTI) and triiodothyronine (T3) values were normal. Hyperthyroidism was diagnosed in the 18 patients (21%) with negative TRH test; 15 of them had high free thyroxine (FT4) levels. The most common causes of hyperthyroidism were "warm" nodules in 7 and iodine overload in 10. Adding an anti-thyroid treatment to the hitherto unsuccessful anti-arrhythmic treatment resulted in a return to sustained sinus rhythm in 50% of cases. FT4 levels became normal in all. This study indicates that all patients with atrial arrhythmia, with or without heart disease, should be investigated for occult hyperthyroidism. It also demonstrates the value of FT4 assays to detect the disease. The TRH test is only required as a second-line exploratory method in some patients, notably those with iodine overload.

Adult↗

[Relation between serum levels and inotropic effect of digoxin in advanced cardiac failure during long-term treatment].

The aim of this study was to determine the relationship of digoxin serum levels to their inotropic effects in advanced cardiac failure during long-term therapy with different dosages. The study was based on the analysis of left ventricular systolic time intervals (STI) measured at 97 follow-up appointments of 20 patients in advanced, stable cardiac failure over an average period of 37 days. The dosage of digoxin was varied at successive consultations so that the serum digoxin levels reached 0.50 ng/ml on at least one occasion. The serum digoxin levels (SD) varied between 0 and 4 ng/ml. Four levels of SD were individualised: A) "control" SD less than 0.25 ng/ml (22 consultations); B) SD: 0.25 to 1 ng/ml (n = 25); C) SD: 1.0 to 2.0 ng/ml (n = 29); D) SD greater than 2 ng/ml (n = 21) including 6 cases with clinical and/or ECG signs of digoxin toxicity. A progressive significant shortening of the electromechanical systolic index (Q-S2 I) was observed up to levels of 2 ng/ml (B and C, -18 ms and -28 ms respectively). The same phenomenon was observed with the ejection time index (ETi) and pre-ejection time index (PETi) (-7 ms and -14 ms; -11 ms and -15 ms respectively) compared to the basal values. At SD greater than 2 ng/ml the reduction remained stable and then started to decrease (positive difference between C and D). These changes were observed in the absence of significant variations of the heart rate. There was a significant linear relationship between the variations of the STI and SD in 15 out of 18 patients (in whom the regression could be calculated, these patients having attended at least 3 appointments). These linear relationships were observed for the Q-S2 i (11-18), the ETi (9-18) and/or PETi (10-18). An unexpected increase in the pre-ejection period was observed in 2 patients. In conclusion, a linear relationship has been shown between SD and inotropic effect which is particularly noticeable at SD levels less than 2 ng/ml. When SD is greater than 2 ng/ml, further increases in SD are associated with smaller variations of the STI. On the other hand, a significant inotropic effect is observed with small doses and SD levels less than 1 ng/ml. This inotropic effect persists unchanged at long-term.

Aged↗