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21.
22.
The GAP-related domain of tuberin, the product of the TSC2 gene, is a target for missense mutations in tuberous sclerosis 总被引:5,自引:0,他引:5
Maheshwar MM; Cheadle JP; Jones AC; Myring J; Fryer AE; Harris PC; Sampson JR 《Human molecular genetics》1997,6(11):1991-1996
Tuberous sclerosis is an autosomal dominant trait in which the
dysregulation of cellular proliferation and differentiation results in the
development of hamartomatous growths in many organs. The TSC2 gene is one
of two genes determining tuberous sclerosis. Inactivating germline
mutations of TSC2 in patients with tuberous sclerosis and somatic loss of
heterozygosity at the TSC2 locus in the associated hamartomas indicate that
TSC2 functions as a tumour suppressor gene and that loss of function is
critical to expression of the tuberous sclerosis phenotype. The TSC2
product, tuberin, has a region of homology with the GTPase activating
protein rap1GAP and stimulates the GTPase activity of rap1a and rab5a in
vitro. Here we show that the region of homology between tuberin and human
rap1GAP and the murine GAP mSpa1 is more extensive than previously reported
and spans approximately 160 amino acid residues encoded within exons 34-38
of the TSC2 gene. Single strand conformation polymorphism analysis of these
exons in 173 unrelated patients with tuberous sclerosis and direct
sequencing of variant conformers together with study of additional family
members enabled characterisation of disease associated mutations in 14
cases. Missense mutations, which occurred in exons 36, 37 and 38 were
identified in eight cases, four of whom shared the same recurrent change
P1675L. Each of the five different missense mutations identified was shown
to occur de novo in at least one sporadic case of tuberous sclerosis. The
high proportion of missense mutations detected in the region of the TSC2
gene encoding the GAP-related domain supports its key role in the
regulation of cellular growth.
相似文献
23.
Assisted reproductive technology and complex chromosomal rearrangements: the limits of ICSI 总被引:4,自引:0,他引:4
Siffroi JP; Benzacken B; Straub B; Le Bourhis C; North MO; Curotti G; Bellec V; Alvarez S; Dadoune JP 《Molecular human reproduction》1997,3(10):847-851
Complex chromosomal rearrangements are very rare events in the human
population. According to our knowledge on the consequences of simple
reciprocal translocations for male fertility, translocations involving
three or more chromosomes are thought to lead to severe reproductive
impairments in terms of meiotic disturbance or chromosomal imbalance of
gametes. We report the case of a 48 year old man whose sperm count revealed
either oligozoospermia (<10(3) spermatozoa/ml) or azoospermia. He was
referred to the laboratory for in-vitro fertilization after
intracytoplasmic sperm injection. Cytogenetic investigations showed a
complex chromosomal rearrangement involving firstly a translocation between
the short arm of chromosome 7 and the long arm of chromosome 13 and
secondly a translocation between the short arm of the same chromosome 13
and the short arm of chromosome 9. Diagnosis was ascertained by
fluorescence in-situ hybridization and staining of the nucleolar organizer
regions. Theoretical study of the translocated chromosomes predicted a
'chain' configuration of the hexavalent at the pachytene stage of meiosis.
In all, 32 modes of segregation were considered and only one resulted
either in a normal or a balanced gamete karyotype. Genetic counselling and
choice of appropriate artificial reproduction technique are discussed.
相似文献
24.
Conclusion The opening of the anal canal appears to be the factor which initiated the differentiation of the sphincter apparatus.The internal sphincter m. of the anus is entirely composed of smooth muscle as distinct from the striated fibers of the m. puborectalis, and the external sphincter which is a mixture of smooth and striated fibers (of skeletal type). It develops in the terminal part of the internal circular layer of the rectal m., outside which are longitudinal fibers which descend early to form the external sphincter (beginning around the third month).This study shows that the internal sphincter is scarcely evident before 12 SA. Thus continence between 10 and 12 SA (after the closure of the anal membrane) is closely related to the other components of the sphincter apparatus. On the other hand, the internal sphincter has become well formed after 28 to 30 SA and then plays a direct role in maintaining continence. 相似文献
25.
Melinda L. Higgs Tracey Wade Mark Cescato Michelle Atchison Anthony Slavotinek Bruce Higgins 《Journal of behavioral medicine》1997,20(4):391-405
This study examined two groups of people who were pursuing treatment for obesity: either medical intervention (a hospital group; N = 20) or support for dietary restriction (a community group; N = 18). This study addressed four questions: (1) Were there differences between the two groups in terms of their psychological distress (as measured by the Symptom Checklist)? (2) Does binge eating moderate psychological distress? (3) Do feelings of ineffectiveness moderate psychological distress? and (4) Which variables best accounted for group membership (i.e., type of treatment sought)? Results suggested that the hospital group was significantly more distressed than the community group. However, there were no differences between the two groups with respect to binge eating or feelings of ineffectiveness. These findings suggest that it is the effects of morbid obesity that are most likely to moderate psychological distress. 相似文献
26.
Gonadotrophin-releasing hormone agonist dose-dependency of pituitary desensitization during controlled ovarian hyperstimulation in IVF 总被引:2,自引:2,他引:2
Janssens RM; Vermeiden JP; Lambalk CB; Schats R; Schoemaker J 《Human reproduction (Oxford, England)》1998,13(9):2386-2391
The aim of this study was to find the minimal effective daily s.c. dose of
the gonadotrophin-releasing hormone (GnRH) agonist, triptorelin acetate,
that suppresses the GnRH-induced release of luteinizing hormone (LH) at
time of human chorionic gonadotrophin (HCG) injection and thereby prevents
spontaneous LH surges during in-vitro fertilization (IVF) stimulation
cycles. Therefore, a double-blind, prospective and randomized titration
study was performed. A total of 48 IVF patients were divided into four
groups of 12 patients. Each group received a different dose of triptorelin
acetate, namely 5, 15, 50 or 100 microg s.c. daily. Standard ovarian
stimulation was carried out using urinary follicle stimulating hormone
(FSH) preparations. A 500 microg GnRH test was performed 90 min before the
HCG injection in order to measure the degree of pituitary desensitization.
Spontaneous LH surges were not detected in any of the groups, although
three patients in the 5 microg group had ovulated at the time of ovum
retrieval. The pituitary LH response to the GnRH test at time of HCG,
expressed as area under the curve (AUC), appeared to be dose-dependent.
Thus, a daily s.c. dose of 100 microg triptorelin acetate appears to be too
high, since adequate desensitization of the pituitary (i.e. no spontaneous
LH surge) can be achieved with doses as low as 15 and 50 microg.
相似文献
27.
Bals-Pratsch M; De Geyter C; Muller T; Frieling U; Lerchl A; Pirke KM; Hanker JP; Becker-Carus C; Nieschlag E 《Human reproduction (Oxford, England)》1997,12(5):896-904
Preliminary data have suggested that female infertility due to corpus
luteum insufficiency may be caused by subclinical hypothyroidism
[exaggerated thyroid-stimulating hormone (TSH) response to thyrotrophin-
releasing hormone (TRH) stimulation]. L-Thyroxine supplementation has been
recommended to achieve pregnancies in subclinical hypothyroid women. This
controlled study was carried out in order to investigate the biochemical
diagnosis of subclinical hypothyroidism as a possible infertility factor.
Five infertile patients (aged 25-36 years) with subclinical hypothyroidism
(n = 4, stimulated TSH >20 microU/ml) or primary hypothyroidism (n = 1)
and five healthy controls (aged 22-39 years) with normal thyroid function
(stimulated TSH <15 microU/ml), regular cycles and no history of
infertility were studied in the early follicular phase. In the pre-study
evaluation, eight of 23 volunteers (34.8%) had to be excluded because of
subclinical hypothyroidism with stimulated TSH values (TSHs) >15
microU/ml. Cycle function of patients and controls was compared by the
method of LH pulse pattern analysis. Therefore blood samples were drawn
every 10 min during a 24 h period. Sleep was recorded from midnight to 7
a.m. Repetition of the TRH tests at the end of the 24 h blood sampling
period confirmed the difference in stimulated TSH values of the two study
groups. Pulse analysis for luteinizing hormone (LH), TSH and prolactin
showed no differences between patients and controls for pulse frequency,
amplitude, height, length, area under curve (AUC) and the 24 h mean. Even
the hypothyroid patient had a normal LH pulse pattern. Additional
measurement of melatonin in pooled sera every 30 min gave the
well-documented diurnal profiles during day and night for both groups.
Patients had significantly higher melatonin values at seven time points
during the night. Peaks for LH, TSH, prolactin and cortisol were correlated
with the sleep stages wake, rapid eye movement, 1 + 2 and 3 + 4. We
concluded that corpus luteum insufficiency in female infertility cannot be
explained by subclinical hypothyroidism and thus should not be treated with
L-thyroxine for fertility reasons.
相似文献
28.
Mercan R; Mayer JF; Walker D; Jones S; Oehninger S; Toner JP; Muasher SJ 《Human reproduction (Oxford, England)》1997,12(9):1886-1889
The aim of this study was to compare the efficacy of pure follicle
stimulating hormone (FSH) with that of FSH/human menopausal gonadotrophin
(HMG) combination in downregulated cycles. A total of 357 patients was
evaluated retrospectively. Sixty percent of patients in the FSH group and
55% in the FSH/HMG group were new; the others were repeat patients.
Ovulation was suppressed with leuprolide acetate in all patients, followed
by either FSH (n = 218) or FSH/HMG (n = 119). There was no difference in
patients' age, infertility factors, number of ampoules used, length of
stimulation, oestradiol levels on day of human chorionic gonadotrophin
(HCG) administration, number of oocytes recovered or the number of embryos
transferred. Also, nuclear maturity at aspiration and fertilization rates
were not different between the two groups. FSH stimulation resulted in a
significantly higher percentage of mature oocytes that showed the typical
'mature' morphological characteristics (P < 0.0001). The clinical
pregnancy rates per transfer were 40 and 28% in patients stimulated with
pure FSH and FSH/HMG respectively (P < 0.05). The significantly higher
number of immature oocytes matured in vitro in the FSH/HMG group (P =
0.001) suggests a possible effect on in-vitro maturation, due to
luteinizing hormone present in HMG. The difference in mature oocyte quality
may be an important determinant in the higher pregnancy rates for the FSH-
stimulated patients.
相似文献
29.
MR Sanguina R Perotta F Brunelli A Gilbert JP Lassau 《Surgical and radiologic anatomy : SRA》1994,16(1):111-112
Summary A cortico-cancellous flap from the anterolateral aspect of the upper third of the tibia was presented. Sixty lower limbs of fresh cadavers were dissected. The vascular bundle includes the anterior tibial artery and its recurrent collateral branches and recurrent and muscllo periostal arteries. The flap is harvested with the interosseous membrane and can be used either free or pedicled. We used this flap for two patients suffering from pseudarthrosis. Long range clinical and radiological results are good.
Le transfert osseux vascularisé tibial superieur
Résumé Les auteurs décrivent un transfert ostéo-periosté vascularisé, prélevé sur la face antéro-latérale de l'extremité supérieure du tibia. L'étude anatomique porte sur soixante membres inférieurs, conservés au froid. La vascularisation métaphysaire du transfert provient de la branche récurrente tibiale antérieure et de ses rameaux, la vascularisation diaphysaire étant issue des branches musculo-périostiées proximales. Le transfert vascularisé est prélevé avec la membrane interosseuse et peut être pediculé ou libre. L'expérience clinique porte sur deux cas de pseudarthroses multiopérées. Les résultats cliniques et radiologiques sont bons à long terme.相似文献
30.
MA Mayoux-Benhamou JP Barbet F Bargy C Vallée M Revel 《Surgical and radiologic anatomy : SRA》1990,12(3):181-185
Summary Biomechanical models of the cervical spine require knowledge of the position, size and orientation of the individual muscles that act on the cervical spine. We have developed a technique to stereometrically measure anatomical specimens. The apparatus is composed of three graduated metallic rods, which slide along a fixed support. This method is accurate to map the anatomy of individual muscles and provides quantitative data on their lines of action. Results are obtained from one specimen. The computer processing of the collected data allows formulation of a three-dimensional model of the neck muscles in man.
Méthode d'étude anatomique quantitative des muscles de la nuqueEtude préliminaire
Résumé Pour élaborer un modèle biomécanique de la colonne cervicale, il faut connaître la position, la taille et l'orientation des différents muscles du cou. Nous avons mis au point une méthode de mesure stéréométrique sur des sujets anatomiques. L'appareil est composé de 3 axes métalliques gradués qui coulissent sur un support fixe. Cette technique permet une étude anatomique précise de chacun des muscles de la nuque, fournissant des données quantitatives sur les différents faisceaux ou lignes d'action. Les résultats sont obtenus sur un sujet. Leur traitement informatique permettra l'élaboration d'un modèle mathématique tridimensionnel des muscles du cou chez l'homme.相似文献