PubMed Health⌕ Search

Biomedical subjects

F Guillemot

Publications and source records attributed to F Guillemot.

At least 73 records · Page 4Linked to original sources
PubMed1995

Analysis of the role of basic-helix-loop-helix transcription factors in the development of neural lineages in the mouse.

The development of neural lineages is a complex process which is being actively investigated in both vertebrate and invertebrate models. A detailed genetic analysis of sensory organ development in Drosophila has revealed the contribution of numerous genes which function to progressively to specify the fate of neural precursor cells. Many of these genes have mammalian homologs which are also expressed in the developing nervous system, among which two families of genes encoding transcription factors of the helix-loop-helix class. The two mouse Mash genes are homologs of the Drosophila achaete-scute genes, which are positive regulators of neural precursor development. The five mouse HES genes are homologs of the Drosophila hairy and Enhancer of split genes, which act as negative regulators in this process. We have generated a null mutation in the mouse Mash1 gene by homologous recombination in embryonic stem cells. Animals homozygous for this mutation die at birth, and show severe losses in olfactory and autonomic neurons. In both lineages, the mutation appears to affect the development of neuronal precursors. We have also started a genetic analysis of the mouse HES genes to study their function during neurogenesis and the possibility that they regulate the activity of Mash1 and other positive regulators.

Animals↗
PubMed1995

Genomic imprinting of Mash2, a mouse gene required for trophoblast development.

The mouse gene Mash2 encodes a transcription factor required for development of trophoblast progenitors. Mash2-homozygous mutant embryos die at 10 days postcoitum from placental failure. Here we show that Mash2 is genomically imprinted. First, Mash2+/- embryos inheriting a wild-type allele from their father die at the same stage as -/- embryos, with a similar placental phenotype. Second, the Mash2 paternal allele is initially expressed by groups of trophoblast cells at 6.5 and 7.5 days post-coitum, but appears almost completely repressed by 8.5 days post-coitum. Finally, we have genetically and physically mapped Mash2 to the distal region of chromosome 7, within a cluster of imprinted genes, including insulin-2, insulin-like growth factor-2 and H19.

Alleles↗
PubMed1995

A large-scale gene-trap screen for insertional mutations in developmentally regulated genes in mice.

We have used a gene-trap vector and mouse embryonic stem (ES) cells to screen for insertional mutations in genes developmentally regulated at 8.5 days of embryogenesis (dpc). From 38,730 cell lines with vector insertions, 393 clonal integrations had disrupted active transcription units, as assayed by beta-galactosidase reporter gene expression. From these lines, 290 clones were recovered and injected into blastocysts to assay for reporter gene expression in 8.5-dpc chimeric mouse embryos. Of these, 279 clones provided a sufficient number of chimeric embryos for analysis. Thirty-six (13%) showed restricted patterns of reporter-gene expression, 88 (32%) showed widespread expression and 155 (55%) failed to show detectable levels of expression. Further analysis showed that approximately one-third of the clones that did not express detectable levels of the reporter gene at 8.5 dpc displayed reporter gene activity at 12.5 dpc. Thus, a large proportion of the genes that are expressed in ES cells are either temporally or spatially regulated during embryogenesis. These results indicate that gene-trap mutageneses in embryonic stem cells provide an effective approach for isolating mutations in a large number of developmentally regulated genes.

Animals↗
PubMed1995

[Results of the celioscopic modification of Hill's operation (HMC). Apropos of an experience of 50 cases].

The objective of this study was to evaluate the clinical, endoscopic and manometric results of modified Hill's operation performed by laparoscopy. Between may 1991 and december 1992, 50 symptomatic patients (27 males and 23 females, mean age: 47 +/- 15.3 years, mean weight: 74.5 +/- 12.6 kg) were operated by laparoscopic modified Hill's operation. Gastro-oesophageal endoscopy and oesophageal manometry (25 cases) were performed preoperatively and postoperatively. The patients were interviewed by an independent observer with a mean follow-up of 8 +/- 4.9 months after the operation. Preoperatively, the mucosal cardia was situated 36 cm from the dental arch (range: 30-43), 29 patients presented with ulcerated oesophagitis refractory to treatment (58%), while the mean resting pressure of the lower oesophageal sphincter was 7.24 +/- 4.93 mmHg. After introduction of the laparoscope and insertion of the various trocars, the operation consisted of dissecting the hiatal orifice, posterior myorrhaphy of the diaphragmatic crura, suture of the right border of the oesophagus to the diaphragmatic crura and closure of the angle of His. This antireflux device was completed by an anterior hemivalve, fixed to the left and right crura. Postoperatively, the mucosal cardia was situated 39.8 cm from the dental arch (range: 35-45) and only one case of oesophagitis persisted (3.4%). The mean resting pressure of the lower oesophageal sphincter was significantly increased to 18.5 +/- 6.86 mmHg (p < 0.001). The mean duration of anaesthesia and the mean operating time were 116 +/- 45 min and 92 +/- 40 min, respectively. The mean hospital stay was 6 +/- 2.3 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

[Treatment of diversion colitis with short-chain fatty acids. Bacteriological study].

OBJECTIVES: Bacterial imbalance may be involved in the pathogenesis of diversion colitis, via diminished production of short chain fatty acids. The aim of the study was to evaluate the effectiveness of short chain fatty acids on microbial flora of patients with diversion colitis and to compare this flora to the microbial flora of controls. METHODS: We prospectively evaluated the effectiveness of short chain fatty acids irrigation on bacterial flora of the excluded colon in 13 patients (8 males, 5 females; mean age: 43.7 years). The causes of diversion were inflammatory bowel disease (n = 4) colonic cancer (n = 2) sigmoid diverticulitis with perforation (n = 3) ischio-rectal abscess (n = 2) and miscellaneous (n = 2). Patients were given, twice a day for 14 days in a double blind manner, a 60 mL enema containing either short chain fatty acids (acetate: 60 mmol/L; propionate: 30 mmol/L; and n-butyrate: 40 mmol/L) (group 1; n = 7) or isotonic NaCl (group 2; n = 6). Bacteriological studies were carried on before starting the trial (D1) and 14 days later (D14). RESULTS: Before and after treatment, there was no difference between group 1 and group 2 concerning bacterial counts and species. Bacterial flora of patients with diversion colitis was characterized by: a) an increase of the count of aerobic bacteria; b) an increase of aerobic and aeroanaerobic species; c) the presence of black pigmented Gram negative anaerobic rods such as Prevotella intermedia and Porphyromonas asaccharolytica which were not found in rectal flora of the control group (16 volunteers, mean age: 27 years). CONCLUSIONS: These data suggest that: a) enema with short chain fatty acids does not induce significant changes in the composition of the microbial flora in patients with diversion colitis; b) bacterial dysbiosis may be involved in pathogenesis of diversion colitis without involving the action of short chain fatty acids.

Adult↗
PubMed1994

Essential role of Mash-2 in extraembryonic development.

The outer layer of the blastocyst, or trophectoderm, is the first cell lineage to differentiate in the mouse embryo, but little is known about the genetic control of its development. Lineage-specific transcription factors may be important in lineage specification, and the product of the Mash-2 gene fulfils the criteria for such a factor. Mash-2 is a mammalian member of the achaete-scute family which encodes basic-helix-loop-helix transcription factors and is strongly expressed in the extraembryonic trophoblast lineage. Mash-2 transcripts are found in the female germ line and in the embryo throughout preimplantation development, but are highly expressed later only in the ectoplacental cone, the chorion and their derivatives in the placenta. Mash-2 transcripts are not found in primary and secondary giant cells, yolk sac or allantois at any post-implantation stage, and are present only transiently and at low levels in the embryo during gastrulation. To analyse the role of Mash-2 in development, we have used gene targeting to generate mice having no Mash-2 function. We report here that Mash-2-/- embryos die from placental failure at 10 days postcoitum. In mutant placentas, spongiotrophoblast cells and their precursors are absent and chorionic ectoderm is reduced. We have rescued this placental mutant phenotype by constructing chimaeras with tetraploid wild-type embryos which contribute almost exclusively to extraembryonic tissues. Mash-2-/- embryos developed normally and adult Mash-2-/- mice were viable, demonstrating that Mash-2 has no major role in the embryo itself. Mash-2 is the first transcription factor shown to play a critical part in the development of the mammalian trophoblast lineage.

Animals↗
PubMed1994

Gene targeting and development of the nervous system.

Gene targeting provides a means of directly assaying the function of specific genes during mouse nervous system development. Generation of targeted mutant mice has provided the first evidence of developmental roles for genes whose function was suggested based on their expression, but for which appropriate assay systems were lacking. In other cases, where gene function was known, targeted mutations have revealed in which cell population, and at what developmental stage, particular genes are first indispensable. The existing targeted mutants suggest that an early mechanism of pattern formation in mammals involves regional control of proliferation or survival of neural precursors, and that later general functions, such as the control of differentiation of precursors, may be performed by different genes in distinct neural lineages. As many genes display complex temporal and spatial patterns of expression, analysis of the full range of functions of such genes will require the generation of a series of alleles, including stage- and tissue-specific mutations.

Animals↗
PubMed1994

MASH-1: a marker and a mutation for mammalian neural crest development.

The ability to generate mice containing null mutations in any cloned gene promises new insights into the molecular control of mammalian neural crest development. This approach has recently been applied to MASH-1, a transcription factor in the bHLH family that is a mammalian homologue of the Drosophila proneural genes achaete-scute. In wild-type embryos, this gene is expressed early in the development of the autonomic nervous system, in apparent precursors of sympathetic, parasympathetic, and enteric neurons (as well as in restricted regions of the central nervous system). A null mutation in the MASH-1 gene eliminates sympathetic and parasympathetic neurons and enteric neurons of the foregut (esophagus); however, enteric neurons of the stomach and hindgut are only partially affected. Analysis with other markers indicates that the mutation acts after neural crest cells have localized in the anlagen of the autonomic nervous system to prevent neuronal differentiation. The differentiation of autonomic glia appears unaffected. Thus, MASH-1 provides one of the most specific mutations affecting neural development in mammals, as well as a valuable marker to study the early segregation of neural crest cell lineages.

Adrenal Glands↗
PubMed1994

Comparison of omeprazole and famotidine on esophageal pH in patients with moderate to severe esophagitis: a cross-over study.

OBJECTIVES: This open cross-over study compared the effects on esophageal pH of omeprazole (O) (20 mg once a day) and famotidine (F) (40 mg b.i.d.) in 19 patients with proven acid gastroesophageal reflux (GER) complicated by erosive or ulcerated esophagitis. METHODS: Each drug was taken for 7 days. A wash-out interval of at least 3 days separated the two treatment periods in each subject. Twenty-four-hour pH measurements were performed in similar standardized conditions at 7 +/- 2 days, at the end of each period of treatment. RESULTS: Compared with the pretreatment results, both O and F reduced the following pH parameters: percent of time with esophageal pH < 4, total number of GER episodes, number of nocturnal GER episodes, and duration of the longest GER episodes. O was more effective than F except for the percent of time esophageal pH < 4 and the number of nocturnal GER episodes, not different between the two treatments. With O, GER was reduced to physiological value in 19 of the 19 patients and abolished in 13. With F, GER was normalized in 13 and abolished in four. The effects of both drugs and grading of esophagitis were not correlated. Both treatments were well-tolerated. CONCLUSIONS: In patients with acid GER complicated by ulcerative esophagitis, O, 20 mg daily, and F, 40 mg b.i.d. significantly reduced acid exposure. O was superior to F, but the latter drug improved significantly two important prognostic variables: the total percent of time pH < 4 and the nocturnal GER.

Adult↗
PubMed1993

Mammalian achaete-scute homolog 1 is required for the early development of olfactory and autonomic neurons.

The mouse Mash-1 gene, like its Drosophila homologs of the achaete-scute complex (AS-C), encodes a transcription factor expressed in neural precursors. We created a null allele of this gene by homologous recombination in embryonic stem cells. Mice homozygous for the mutation die at birth with apparent breathing and feeding defects. The brain and spinal cord of the mutants appear normal, but their olfactory epithelium and sympathetic, parasympathetic, and enteric ganglia are severely affected. In the olfactory epithelium, neuronal progenitors die at an early stage, whereas the nonneuronal supporting cells are present. In sympathetic ganglia, the mutation arrests the development of neuronal precursors, preventing the generation of sympathetic neurons, but does not affect glial precursor cells. These observations suggest that Mash-1, like its Drosophila homologs of the AS-C, controls a basic operation in development of neuronal progenitors in distinct neural lineages.

Adrenal Medulla↗
PubMed1993

Action of in situ nitroglycerin on upper anal canal pressure of patients with terminal constipation. A pilot study.

Nitroglycerin (NTG) in situ reduces the pressure of the upper anal sphincter (UAS). We have tested the effects of NTG on the UAS of patients with terminal constipation. We studied two groups of constipated patients. Group 1 consisted of 11 patients (nine females and two males) with hypertonicity of the UAS (> 70 mm Hg); age was 49.5 +/- 15.6 years. Group 2 consisted of 10 patients (nine females and one male) without hypertonicity; age was 40.1 +/- 14.1 years. Group 3 consisted of eight asymptomatic controls (four females and four males); age was 51.7 +/- 6.9 years. After a 10-minute resting pressure recording of the UAS with a water-filled balloon, the probe was pulled through the outside and the UAS was assessed after spreading 5 mg of placebo and then 5 mg of NTG on the balloon. Resting pressure (RP), delay of the pressure decrease (DP), pressure after five minutes either during the NTG (PN5) or placebo (PP5) period, and mean duration of the pressure decrease (MD) were measured. None of the subjects experienced a decrease of PP5 vs. RP. All patients in Group 1 (106.2 vs. 38.4 mm Hg), Group 2 (57.9 vs. 31.4 mm Hg), and controls (62.2 vs. 33.7 mm Hg) experienced a significant decrease of pressure of the UAS (P < 0.005). Delay of the pressure decrease was less than two minutes, with wide interindividual variability of duration of the pressure decrease. Mild side effects--anal pain and transient headache--were reported in five patients. In situ NTG significantly reduced UAS Pressure in all groups. NTG has to be evaluated in anal pathology, especially in patients with hypertonic sphincter terminal constipation or acute hypertonicity of the sphincter due to a fissure.

Administration, Rectal↗
PubMed1993

Dynamic expression of the murine Achaete-Scute homologue Mash-1 in the developing nervous system.

The Drosophila Achaete-Scute Complex genes encode transcriptional regulators belonging to the basic-helix-loop-helix family which control early steps of development of the central and peripheral nervous systems. We have isolated two mouse homologues of Achaete-Scute Complex genes, Mash-1 and Mash-2, by using the conservation of the basic-helix-loop-helix domain in this family. In this article, we analyse the expression of Mash-1 from its onset during neurulation to adult stages by RNA in situ hybridization on whole mounts and sections. As was observed for the rat Mash-1 protein, mouse Mash-1 RNA expression is restricted to cells of the developing central and peripheral nervous systems. We have observed three successive phases in the distribution of Mash-1 transcripts in the developing central nervous system. Initially, between embryonic day 8.5 and 10.5, Mash-1 transcripts are found in restricted domains in the neuroepithelium of the midbrain and ventral forebrain, as well as in the spinal cord. Between embryonic day 10.5 and 12.5, Mash-1 expression pattern changes from a restricted to a widespread one. Mash-1 transcripts are then found at variable levels in the ventricular zone in all regions of the brain. From embryonic day 12.5 to post-natal stages, Mash-1 is also expressed in cells outside of the ventricular zone throughout the brain. In addition, Mash-1 is expressed during development of the olfactory epithelium and neural retina. Overall, its expression pattern suggest that Mash-1 plays a role at early stages of development of specific neural lineages in most regions of the central nervous system and of several lineages in the peripheral nervous system. We have also compared the expression of Mash-1 and mouse Notch because their Drosophila homologues have been shown to interact genetically. The two genes show very similar expression patterns, both spatially and temporally, in the early developing brain and in the retina, suggesting that both genes may participate in the development of the same neural lineages.

Amino Acid Sequence↗
PubMed1992

Influence of the timing of administration of 300 mg ranitidine on 24-hour gastric pH in patients acute duodenal ulcer.

The 24-hour intragastric pH of 12 patients with an acute duodenal ulcer was recorded with the aim of comparing the effects of two different times of administration of 300 mg ranitidine: post evening meal, or bedtime. This double-blind crossover trial involved 3 centres. Twenty-four-hour gastric pH was measured under standard conditions (meals, time schedule) at the middle of each 14-day treatment period. The analysis was performed on the percentage of times spent at pH levels below 1.5, 2, 3 and 4 for different periods and for the total 24 hours. During the whole day and night combined, as well as during the afternoon (12.00 hours-19.00 hours), there was no difference between the 2 regimens regardless of the pH profile studied. During the morning (07.30 hours-12.00 hours), the time spent below pH 1.5 and 2 was less when the drug was taken at bedtime (P less than 0.05). In contrast, during the whole night (19.00 hours-07.30 hours) the percentage of time spent below pH 1.5, 2 and 3 was significantly less when the drug was taken at post evening meal (P less than 0.05). These results show that in patients with acute duodenal ulcer, 300 mg ranitidine administered at the end of the evening meal provides better control of nocturnal acidity than administration at bedtime and hence is suggested for optimization of therapeutic efficacy.

Acute Disease↗