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F Guillemot

Publications and source records attributed to F Guillemot.

At least 55 records · Page 3Linked to original sources
PubMed1998

The bHLH protein NEUROGENIN 2 is a determination factor for epibranchial placode-derived sensory neurons.

neurogenin2 encodes a neural-specific basic helix-loop-helix (bHLH) transcription factor related to the Drosophila proneural factor atonal. We show here that the murine ngn2 gene is essential for development of the epibranchial placode-derived cranial sensory ganglia. An ngn2 null mutation blocks the delamination of neuronal precursors from the placodes, the first morphological sign of differentiation in these lineages. Mutant placodal cells fail to express downstream bHLH differentiation factors and the Notch ligand Delta-like 1. These data suggest that ngn2 functions like the Drosophila proneural genes in the determination of neuronal fate in distal cranial ganglia. Interestingly, the homeobox gene Phox2a is activated independently of ngn2 in epibranchial placodes, suggesting that neuronal fate and neuronal subtype identity may be specified independently in cranial sensory ganglia.

Animals↗
PubMed1998

Mash2 is expressed in oogenesis and preimplantation development but is not required for blastocyst formation.

The basic helix-loop-helix transcription factor, Mash2, has been shown to be necessary for the development of the spongiotrophoblast of the mature chorioallantoic placenta of the mouse. Here we show that Mash2 is transcribed during oogenesis and expressed throughout preimplantation development, only becoming restricted to the diploid trophoblast around the time of implantation. This expression raised the possibility that Mash2 has earlier functions in the trophoblast lineage that were not detectable in mutant embryos because of the persistence of oogenetically derived protein. This was tested by generating viable Mash2-/- females by tetraploid rescue of the extraembryonic defect. Mutant embryos derived from such females showed no enhanced phenotype over embryos produced from heterozygous females, demonstrating unequivocally that neither maternal nor zygotic Mash2 is required for early trophoblast development. If Mash2 functions in other aspects of trophoblast development, it must act cooperatively with other factors.

Animals↗
PubMed1998

Control of noradrenergic differentiation and Phox2a expression by MASH1 in the central and peripheral nervous system.

Mash1, a mammalian homologue of the Drosophila proneural genes of the achaete-scute complex, is transiently expressed throughout the developing peripheral autonomic nervous system and in subsets of cells in the neural tube. In the mouse, targeted mutation of Mash1 has revealed a role in the development of parts of the autonomic nervous system and of olfactory neurons, but no discernible phenotype in the brain has been reported. Here, we show that the adrenergic and noradrenergic centres of the brain are missing in Mash1 mutant embryos, whereas most other brainstem nuclei are preserved. Indeed, the present data together with the previous results show that, except in cranial sensory ganglia, Mash1 function is essential for the development of all central and peripheral neurons that express noradrenergic traits transiently or permanently. In particular, we show that, in the absence of MASH1, these neurons fail to initiate expression of the noradrenaline biosynthetic enzyme dopamine beta-hydroxylase. We had previously shown that all these neurons normally express the homeodomain transcription factor Phox2a, a positive regulator of the dopamine beta-hydroxylase gene and that a subset of them depend on it for their survival. We now report that expression of Phox2a is abolished or massively altered in the Mash1-/- mutants, both in the noradrenergic centres of the brain and in peripheral autonomic ganglia. These results suggest that MASH1 controls noradrenergic differentiation at least in part by controlling expression of Phox2a and point to fundamental homologies in the genetic circuits that determine the noradrenergic phenotype in the central and peripheral nervous system.

Animals↗
PubMed1998

Cell-free whey from milk fermented with Bifidobacterium breve C50 used to modify the colonic microflora of healthy subjects.

The ingestion of viable bacteria is thought to be required to modify intestinal microflora. In the present study, the effects on fecal flora of consumption of cell-free concentrated whey from milk that had been fermented with Bifidobacterium breve C50 was tested using 10 healthy human volunteers. Results were compared with effects of a commercial milk formula that had been fermented with Streptococcus thermophilus and B. breve C50 and given to 10 control subjects. Nitroreductase and beta-glucuronidase activities were assessed as risk indexes for colon carcinogenesis, and beta-galactosidase was measured as an indicator of the fermentation capacity of the colonic flora. Fecal excretion of Bacteroides fragilis, Clostridium perfringens, and clostridial spores decreased after 7 d of consumption of either preparation; however, counts of bifidobacteria only increased after intake of B. breve whey. Fecal pH was reduced from 7.1 +/- 0.2 to 6.6 +/- 0.3 after intake of whey that had been fermented with Bif. breve. Fecal nitroreductase and beta-glucuronidase significantly decreased, and beta-galactosidase activity increased, after consumption of either preparation. The results indicate that ingestion of viable bifidobacteria was not required to modify intestinal flora of humans. Repression of B. fragilis and clostridia seems to be independent of colonic bifidobacterial overgrowth in humans.

Adult↗
PubMed1997

Nitrate-reducing bacteria in diversion colitis: a clue to inflammation?

A pathogenic role of nitric oxide has been suggested in acute and chronic intestinal inflammation. We took the opportunity offered by studies in patients with excluded colon, which represents a model of chronic intestinal inflammation with no exogenous nitrite or nitrate supply, to evaluate the quantity and the quality of nitrate reducers in diversion colitis. Thirty patients (17 men, 13 women, mean age 45 years) having an excluded colon for various reasons were sampled by rectal swabs and compared to 30 healthy controls (11 men, 19 women, mean age 28 years). The percentage of nitrate-reducers among the total count of subcultured bacteria was 46 +/- 41% (mean +/- SD) in patients with diversion colitis as compared to 19 +/- 24% in healthy controls. This difference was significant (P < 0.05) despite great heterogeneity in individual values. In patients with diversion colitis, 75/254 (29.5%) different isolated bacterial strains were nitrate-reducers as compared to 61/294 (21%) (P < 0.05) in controls. Among the 75 nitrate-reducing strains isolated from patients with diversion colitis, 55 were aerobes. Pseudomonas species were only encountered in this population. The predominant group was enterobacteria with a high isolation rate of species belonging to the genera Proteus, Providencia, and Morganella. In healthy controls nitrate-reducing anaerobes were nearly as frequent as aerobes. The most frequent species was Eubacterium lentum, followed by Clostridium perfringens. It could be suggested that nitric oxide synthase might produce a bacterial substrate increasing the growth of bacteria with a high pathogenic potential, creating conditions for chronic inflammation and infection in patients with excluded colon.

Adult↗
PubMed1997

The human Achaete-Scute homologue 2 (ASCL2,HASH2) maps to chromosome 11p15.5, close to IGF2 and is expressed in extravillus trophoblasts.

Here we describe the cloning of the human Achaete Scute Homologue 2 (HASH2) gene, officially designated ASCL2 (Achaete Scute complex like 2), a homologue of the Drosophila Achaete and Scute genes. In mouse, this gene is imprinted and maps to chromosome 7. We mapped the human homologue close to IGF2 and H19 at 11p15.5, the human region syntenic with mouse chromosome 7, indicating that this imprinted region is highly conserved in mouse and man. HASH2 is expressed in the extravillus trophoblasts of the developing placenta only. The lack of HASH2 expression in non-malignant hydatidiform (androgenetic) moles indicates that HASH2 is also imprinted in man.

Amino Acid Sequence↗
PubMed1997

Achalasia: outcome of patients treated with intrasphincteric injection of botulinum toxin.

BACKGROUND: To evaluate the safety and clinical efficacy of botulinum toxin (BT) in patients with achalasia followed up for six months. METHODS: Fifty five symptomatic patients with manometrically proven achalasia were included in a multicentre prospective trial. Before and two weeks and two months after intrasphincteric injection of BT, symptoms of dysphagia, regurgitation, and chest pain were scored on a 0-3 scale, and lower oesophageal sphincter pressure (LOSP) was assessed. The symptom score was determined again at six months, clinical improvement being defined by < or = 3, relapse by > 3, and failure as a relapse after two injections or loss to follow up. RESULTS: Except for transient chest or epigastric pain (22%), no side effects were observed. There was a significant decrease in LOSP after treatment. Symptom scores were significantly improved at two weeks (2.0 (SD 1.6)), two months (1.7 (1.8)), and six months (1.9 (2.0)) compared with pretreatment values (5.1 (1.8), p < 0.001). At six months, 33 patients had clinical improvement (27 after one injection), 17 were considered failures, and five had just relapsed. Although there was a trend for age (older patients being more responsive), age, sex, prior duration of symptoms, initial symptom score, weight loss, LOSP, magnitude of oesophageal contractions, vigorous or non-vigorous achalasia, previous dilatations, and radiological features were not predictive of results. CONCLUSIONS: This multicentre series confirms that intrasphincteric injection of BT is a safe procedure, resulting in clinical improvement in 60% of patients with achalasia at six months. The therapeutic role of BT in achalasia needs further evaluation with regard to other alternatives.

Adult↗
PubMed1997

The activity of neurogenin1 is controlled by local cues in the zebrafish embryo.

Zebrafish neurogenin1 encodes a basic helix-loop-helix protein which shares structural and functional characteristics with proneural genes of Drosophila melanogaster. neurogenin1 is expressed in the early neural plate in domains comprising more cells than the primary neurons known to develop from these regions and its expression is modulated by Delta/Notch signalling, suggesting that it is a target of lateral inhibition. Misexpression of neurogenin1 in the embryo results in development of ectopic neurons. Markers for different neuronal subtypes are not ectopically expressed in the same patterns in neurogenin1-injected embryos suggesting that the final identity of the ectopically induced neurons is modulated by local cues. Induction of ectopic motor neurons by neurogeninl requires coexpression of a dominant negative regulatory subunit of protein kinase A, an intracellular transducer of hedgehog signals. Moreover, the pattern of endogenous neurogenin1 expression in the neural plate is expanded in response to elevated levels of Hedgehog (Hh) signalling or abolished as a result of inhibition of Hh signalling. Together these data suggest that Hh signals regulate neurogenin1 expression and subsequently modulate the type of neurons produced by Neurogenin1 activity.

Amino Acid Sequence↗
PubMed1997

Mash1 activates a cascade of bHLH regulators in olfactory neuron progenitors.

The lineage of olfactory neurons has been relatively well characterized at the cellular level, but the genes that regulate the proliferation and differentiation of their progenitors are currently unknown. In this study, we report the isolation of a novel murine gene, Math4C/neurogenin1, which is distantly related to the Drosophila proneural gene atonal. We show that Math4C/neurogenin1 and the basic helix-loop-helix gene Mash1 are expressed in the olfactory epithelium by different dividing progenitor populations, while another basic helix-loop-helix gene, NeuroD, is expressed at the onset of neuronal differentiation. These expression patterns suggest that each gene marks a distinct stage of olfactory neuron progenitor development, in the following sequence: Mash1>Math4C/neurogenin1>NeuroD. We have previously reported that inactivation of Mash1 function leads to a severe reduction in the number of olfactory neurons. We show here that most cells in the olfactory epithelium of Mash1 mutant embryos fail to express Math4C/neurogenin1 or NeuroD. Strikingly, a subset of progenitor cells in a ventrocaudal domain of Mash1 mutant olfactory epithelium still express Math4C/neurogenin1 and NeuroD and differentiate into neurons. Cells in this domain also express Math4A/neurogenin2, another member of the Math4/neurogenin gene family, and not Mash1. Our results demonstrate that Mash1 is required at an early stage in the olfactory neuron lineage to initiate a differentiation program involving Math4C/neurogenin1 and NeuroD. Another gene activates a similar program in a separate population of olfactory neuron progenitors.

Amino Acid Sequence↗
PubMed1996

Restricted expression of a novel murine atonal-related bHLH protein in undifferentiated neural precursors.

Tissue-specific bHLH proteins play important roles in the specification and differentiation of neural cell lineages in invertebrate and vertebrate organisms. Two groups of bHLH proteins, atonal and achaete-scute, have proneural activities in Drosophila, and the mouse achaete-scute homolog MASH1 is required for the differentiation of several neural lineages. In a screen for proteins interacting with MASH1, we have isolated a novel bHLH protein related to atonal, named MATH4A, which is broadly expressed in neural precursor cells in the mouse embryonic CNS and PNS. Interaction assays in yeast and in vitro demonstrate that MATH4A interacts efficiently with both MASH1 and the ubiquitous bHLH protein E12. MATH4A-E12 heterodimers, but not MATH4A-MASH1, bind to a consensus E-box sequence. Math4A expression is restricted to undifferentiated neural precursors and is complementary to that of Mash1 in most regions of the nervous system. In particular, Math4A is transcribed at high levels in the cerebral cortex, dorsal thalamus, and epibranchial placodes, which present little or no Mash1 expression. However, expression of the two genes shows limited overlap in certain CNS regions (retina, preoptic area of the hypothalamus, midbrain, hindbrain). Its structure and expression pattern suggest that MATH4A may regulate an early step of neural development, either as a partner of ubiquitous bHLH proteins or associated with other neural-specific bHLH proteins.

Amino Acid Sequence↗
PubMed1996

Integrated physical, genetic, and genic map covering 3 Mb around the human NGF gene (NGFB) at 1p13.

We have characterized 11 overlapping yeast artificial chromosomes (YACs) in the 1p13 region, 8 of them containing the human nerve growth factor (NGF) gene (HGMW-approved symbol NGFB). Sequence-tagged sites (STSs) corresponding to YAC extremities have been designed and used for chromosome assignment on a panel of monochromosomic somatic cell hybrids to check for YAC chimerism, in parallel with analyses by fluorescence in situ hybridization. Determination of end STS content and restriction mapping of the YACs led to the construction of a 3-Mb YAC contig. Four microsatellite markers from the Généthon collection and seven genes known to map to the 1p13 region have been ordered on the contig around the NGF gene. A new gene transcript from the Genexpress catalog has been localized on the contig. This work provides an integrated physical, genetic, and genic map of this chromosome 1 region. It constitutes a basis for determining the structure of the NGF gene and for further characterizing its genic environment.

Animals↗
PubMed1996

Mammalian hairy and Enhancer of split homolog 1 regulates differentiation of retinal neurons and is essential for eye morphogenesis.

Mammalian hairy and Enhancer of split homolog 1 (HES1), a basic helix-loop-helix factor gene, is expressed in retinal progenitor cells, and its expression decreases as differentiation proceeds. Retinal progenitor cells infected with HES1-transducing retrovirus did not differentiate into mature retinal cells, suggesting that persistent expression of HES1 blocks retinal development. In contrast, in the retina of HES1-null mutant mice, differentiation was accelerated, and rod and horizontal cells appeared prematurely and formed abnormal rosette-like structures. Lens and cornea development was also severely disturbed. Furthermore, in the mutant retina, bipolar cells extensively died, and finally disappeared. These studies provide evidence that HES1 regulates differentiation of retinal neurons and is essential for eye morphogenesis.

Animals↗
PubMed1996

Mash1 promotes neuronal differentiation in the retina.

BACKGROUND: Mash1, a mammalian homologue of Drosophila achaete-scute proneural gene complex, plays an essential role in differentiation of subsets of peripheral neurones. Whereas Mash1 is expressed during retinal development, no apparent abnormalities were found during embryogenesis as well as at birth in Mash1-null retina, suggesting that early differentiating cells such as ganglion, amacrine and cone cells develop normally. Because Mash1-null mice die soon after birth, their postnatal development cannot be examined in vivo. Thus, it remains to be determined whether or not Mash1 functions in postnatal development of retina. RESULTS: Here, Mash1 roles in postnatal development of retina was examined by using retinal explant that develops like in vivo retina. Without Mash1, differentiation of late appearing cells such as rod, horizontal, and bipolar cells was delayed and the final number of bipolar cells was significantly reduced. In contrast, vimentin-positive cells (probably Muller glial cells) were increased in Mash1-null retina. CONCLUSIONS: These results provide evidence that Mash1 promotes neuronal differentiation during retinal development and is essential for proper ratios of retinal cell types.

Animals↗
PubMed1995

Targeted disruption of mammalian hairy and Enhancer of split homolog-1 (HES-1) leads to up-regulation of neural helix-loop-helix factors, premature neurogenesis, and severe neural tube defects.

Mammalian hairy and Enhancer of split homolog-1 (HES-1) encodes a helix-loop-helix (HLH) factor that is thought to act as a negative regulator of neurogenesis. To directly investigate the functions of HES-1 in mammalian embryogenesis, we performed a targeted disruption of the HES-1 locus. Mice homozygous for the mutation exhibited severe neurulation defects and died during gestation or just after birth. In the developing brain of HES-1-null embryos, expression of the neural differentiation factor Mash-1 and other neural HLH factors was up-regulated and postmitotic neurons appeared prematurely. These results suggest that HES-1 normally controls the proper timing of neurogenesis and regulates neural tube morphogenesis.

Animals↗
PubMed1995

Biofeedback for the treatment of fecal incontinence. Long-term clinical results.

UNLABELLED: Biofeedback therapy has been proposed as a treatment for fecal incontinence with good, short-term results. PURPOSE: This study was designed to assess long-term clinical results of biofeedback therapy compared with medical therapy alone and to assess manometric results in patients treated with biofeedback. METHODS: Two groups of incontinent patients were studied. Group 1 consisted of 16 patients (3 males and 13 females; mean age, 59.9 years). Etiologies treated by biofeedback included descending perineum syndrome (7), postfistula or hemorroidectomy (4), and miscellaneous (5). Group 2 consisted of eight patients (two males, six females; mean age, 62.2 years). Etiologies treated with medical treatment alone (including enema and antidiarrheal therapy) included descending perineum syndrome (3), postfistula or hemorroidectomy (2), and miscellaneous (3). The incontinence score was initially 17.81 +/- 3.27 (standard deviation) in Group 1 and 17.0 +/- 2.77 in Group 2. Resting pressure of the upper and lower anal sphincter, maximum squeezing pressure, and duration of contraction were not initially different in Groups 1 and 2 but were significantly lower than in the control group of patients without incontinence (n = 12; 8 males, 4 females; mean age, 66.4 years) (P < 0.05). Follow-up duration was 30 months, with intermediate clinical score at 6 months for Group 1. RESULTS: After biofeedback therapy, the incontinence score at 30 months was lower in Group 1 (14.43 +/- 6.35 vs. 17.81 +/- 3.27; P < 0.035) and unchanged in Group 2 (18.0 +/- 2.72 vs. 17.0 +/- 2.77). However, in Group 1 the score at 6 months was much lower than at 30 months (6.31 +/- 7.81 vs. 14.43 +/- 6.35; P < 0.001). Only the amplitude of voluntary contraction and upper anal pressure (51.1 (range, 27-90) vs 36.7 (range, 20-80) mmHg) were significantly increased (81.5 (range, 55-120) vs. 62.1 (range, 30-90) mmHg; P < 0.05). CONCLUSION: Biofeedback improved continence at 6 months and at 30 months. However, the score at 6 months was much better, suggesting that the initial good results may deteriorate over a long time. These data suggest that it could be useful to reinitiate biofeedback therapy in some patients.

Adult↗