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1.
Regnier V; Meddeb M; Lecointre G; Richard F; Duverger A; Nguyen VC; Dutrillaux B; Bernheim A; Danglot G 《Human molecular genetics》1997,6(1):9-16
Type 1 neurofibromatosis (NF1) gene encodes for a member of the GTPase
activating protein family and is considered to be a tumor suppressor gene.
Its very high rate of de novo mutation in humans led us to study a specific
feature of this gene: the presence of numerous NF1-related sequences.
According to our results, the human genome contains at least 11 NF1-related
sequences, nine of which are scattered near centromeric sequences of seven
different chromosomes. These NF1-related sequences, whose extent is quite
varied according to loci, are unprocessed copies of the NF1 gene, and bear
numerous mutations. A phylogenetic analysis of the six largest sequences
indicates that they are all derived from a common ancestor, which would
have appeared 22-33 million years ago, and was subsequently duplicated
several times during hominoid evolution. The most recent duplication and
interchromosomal transposition occurred in the last million years
suggesting that the process could still be ongoing. Intriguing similarities
between the evolution of alpha- satellite DNA and NF1-related sequences
suggest the involvement of a common genetic mechanism for the generation
and pericentric spreading of these NF1 partial copies.
相似文献
2.
3.
Herbert Thurston 《Clinical and experimental pharmacology & physiology》1992,19(S19):67-71
1. Perindopril (4 mg) was compared with atenolol (50 mg), captopril (25 mg b. d.) or a diuretic (hydrochlorothiazide 50 mg and amiloride 5 mg) in three studies involving a total of 503 hypertensive patients with a diastolic blood pressure (DBP) of 95–125 mmHg.
2. A 4 week single-blind placebo period preceded 12 weeks of active treatment. Dose titration was at weeks 4 and 8 if supine DBP >90 mmHg. The dose was doubled and if necessary a diuretic was added in the atenolol or captopril comparisons, and atenolol was added in the diuretic study.
3. The fall in supine blood pressure (BP) was 27/17 mmHg with perindopril and 21/16 mmHg for atenolol. Monotherapy controlled 55% of patients on perindopril and 48% on atenolol, increasing to 78% and 58% with the addition of hydrochlorothiazide, respectively. Captopril caused a BP fall of 19/12 mmHg compared with 27/18 mmHg for perindopril, with 49% of both groups being controlled on monotherapy.
4. Diuretic addition produced a greater antihypertensive effect with perindopril (75%) compared with 57% for captopril in achieving control. Perindopril caused a comparable fall in supine BP to the diuretic combination 27/19 mmHg and 31/18 mmHg, but the fall in erect systolic BP was significantly greater for the diuretic. At 3 months, 85% of the diuretic group and 78% of the perindopril group achieved the target BP.
5. A multicentre trial of 856 patients treated with perindopril (690 patients treated for 1 year or more) has shown that BP control is maintained in the long term with a low incidence of side-effects (7.9%) causing withdrawal from treatment. These studies demonstrate that perindopril compares favourably with standard first-line therapy for mild to moderate hypertension. 相似文献
2. A 4 week single-blind placebo period preceded 12 weeks of active treatment. Dose titration was at weeks 4 and 8 if supine DBP >90 mmHg. The dose was doubled and if necessary a diuretic was added in the atenolol or captopril comparisons, and atenolol was added in the diuretic study.
3. The fall in supine blood pressure (BP) was 27/17 mmHg with perindopril and 21/16 mmHg for atenolol. Monotherapy controlled 55% of patients on perindopril and 48% on atenolol, increasing to 78% and 58% with the addition of hydrochlorothiazide, respectively. Captopril caused a BP fall of 19/12 mmHg compared with 27/18 mmHg for perindopril, with 49% of both groups being controlled on monotherapy.
4. Diuretic addition produced a greater antihypertensive effect with perindopril (75%) compared with 57% for captopril in achieving control. Perindopril caused a comparable fall in supine BP to the diuretic combination 27/19 mmHg and 31/18 mmHg, but the fall in erect systolic BP was significantly greater for the diuretic. At 3 months, 85% of the diuretic group and 78% of the perindopril group achieved the target BP.
5. A multicentre trial of 856 patients treated with perindopril (690 patients treated for 1 year or more) has shown that BP control is maintained in the long term with a low incidence of side-effects (7.9%) causing withdrawal from treatment. These studies demonstrate that perindopril compares favourably with standard first-line therapy for mild to moderate hypertension. 相似文献
4.
Background : Many recent reports of the results of decompression of the median nerve in the carpal tunnel have concentrated on only one aspect of recovery (numbness, grip etc.), and there are no reports of a comprehensive study of outcome. The aim of the present study was to review comprehensively the results of the direct visualization method of decompression of the carpal tunnel and to compare them with the published results of endoscopic release. Methods : Patients' perceptions of the severity of pain, numbness and paraesthesiae due to carpal tunnel syndrome (CTS), before and after open carpal tunnel release (CTR) in 188 hands were reviewed retrospectively at a minimum time of follow-up of 18 months. Motor and sensory testing, provocation testing and measurement of scar tenderness in 135 hands were performed at a clinical review. Results : Subjective results showed that 70% experienced a reduction in the severity of pain after CTR, 78% of hands experienced a reduction in the severity of paraesthesiae and 77% experienced a reduction in the severity of numbness. A total of 49% had improvements in all three symptoms after CTR. At the clinical review, sensory testing revealed that 59% of hands had normal or slightly diminished light touch, 35% had normal static two-point discrimination and 61% had normal dynamic two-point discrimination. Results for Tinel's test, Phalen's test and pressure provocation testing were positive in 10% of hands. There was no scar tenderness in 38%, no persisting thenar atrophy in 90%. Normal grip strength was found in 93% and 91% had normal pinch strength. Conclusions : It was concluded that open carpal tunnel release remains a safe and reliable treatment for carpal tunnel syndrome. The very low incidence of serious complications from the open technique of CTR, when compared with endoscopic CTR as published by different authors in the literature, and the comparable clinical results, appears to make the open technique a safer and preferable option. However, a properly controlled trial of both techniques is necessary to compare them. 相似文献
5.
Idia B. Thurston Jessica Curley Sherecce Fields Dimitra Kamboukos Ariz Rojas Vicky Phares 《Journal of community psychology》2008,36(4):411-420
Mental health services are underutilized in our society by both adults and children. This finding presents a potential problem for researchers conducting community‐based research. Previous studies have demonstrated that community‐based researchers frequently do not screen participants for the presence of psychopathology nor do they ascertain whether therapeutic services are currently utilized. The present study explored the prevalence of psychopathology and treatment involvement in a sample of families recruited from the community. Results indicated that a fifth of the participants in this community‐based sample met diagnostic criteria for a psychiatric disorder or were in treatment for psychological difficulties at the time of recruitment for this study. Furthermore, mothers, fathers, and adolescents who met the criteria according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM‐IV; American Psychiatric Association, 1994 ) for a psychological disorder had higher symptomatology than those who did not meet criteria. Methodological suggestions are provided. © 2008 Wiley Periodicals, Inc. 相似文献
6.
Arbour NC; Zlotogora J; Knowlton RG; Merin S; Rosenmann A; Kanis AB; Rokhlina T; Stone EM; Sheffield VC 《Human molecular genetics》1997,6(5):689-694
Achromatopsia is an autosomal recessive disease of the retina,
characterized clinically by an inability to distinguish colors, impaired
visual acuity, nystagmus and photophobia. A genome-wide search for linkage
was performed using an inbred Jewish kindred from Iran. To facilitate the
genome-wide search, we utilized a DNA pooling strategy which takes
advantage of the likelihood that the disease in this inbred kindred is
inherited by all affected individuals from a common founder. Equal molar
amounts of DNA from all affected individuals were pooled and used as the
PCR template for short tandem repeat polymorphic markers (STRPs). Pooled
DNA from unaffected members of the kindred was used as a control. A
reduction in the number of alleles in the affected versus control pool was
observed at several loci. Upon genotyping of individual family members,
significant linkage was established between the disease phenotype and
markers localized on chromosome 2. The highest LOD score observed was 5.4
(theta = 0). When four additional small unrelated families were genotyped,
the combined peak LOD score was 8.2. Analysis of recombinant chromosomes
revealed that the disease gene lies within a 30 cM interval which spans the
centromere. Additional fine-mapping studies identified a region of
homozygosity in all affected individuals, narrowing the region to 14 cM. A
candidate gene for achromatopsia was excluded from this disease interval by
radiation hybrid mapping. Linkage of achromatopsia to chromosome 2 is an
essential first step in the identification of the disease-causing gene.
相似文献
7.
M L Figueroa B E Rosenbloom A C Kay P Garver D W Thurston J A Koziol T Gelbart E Beutler 《The New England journal of medicine》1992,327(23):1632-1636
BACKGROUND. Alglucerase (Ceredase) provides effective enzyme-replacement treatment for patients with Gaucher's disease, but at the usually recommended dose of 60 U per kilogram of body weight every two weeks (130 U per kilogram per month), it costs $382,200 per year for a 70-kg patient. Theoretical considerations suggest that more frequent administration would be more efficient. METHODS. Fourteen patients with type 1 Gaucher's disease that was moderately severe to severe were given 30 U of alglucerase per kilogram per month, in divided doses given either daily or three times weekly, or 120 U given three times weekly. The effect of the treatment on the size of the liver and spleen and on blood counts was compared with published data on patients who received a total dose four to five times as large as the lower dose we used and who received treatment every two weeks. RESULTS. The response to 30 U of alglucerase per kilogram per month, fractionated into three or seven doses weekly, was approximately the same as that reported after the administration every two weeks of a dose four or five times as large, given in the large infusions usually recommended. A fourfold increase in the dose given three times weekly, from 2.3 to 9.2 U per kilogram, did not substantially increase the rate of improvement. CONCLUSIONS. The treatment of Gaucher's disease with smaller total doses of alglucerase given more frequently yields satisfactory results. A dose of 2.3 U per kilogram three times weekly yields major financial benefits with no sacrifice of therapeutic effect. Even taking into account the increased ancillary costs of more frequent administration, this method of administering alglucerase reduces the annual cost of the drug for a 70-kg patient to about $100,000. 相似文献
8.
Hyperactive vestibulo-ocular reflex in cerebellar degeneration: pathogenesis and treatment 总被引:2,自引:0,他引:2
We studied a patient with a cerebellar degeneration and hyperactive vestibulo-ocular reflex (VOR). He complained of oscillopsia and blurred vision with head movement. A twofold increase in VOR gain (peak eye velocity/peak head velocity) at high frequencies was associated with a VOR time constant of 6 seconds (low normal). Visual cancellation ("suppression") of the VOR and smooth pursuit were also abnormal. We hypothesized that his high VOR gain was due to dysfunction of olivocerebellar projections. Physostigmine reduced his VOR gain, consistent with the hypothesis that these projections are cholinergic. 相似文献
9.
Frederick Thurston Drake Melanie L. Lyden Jennifer H. Kuo Wen T. Shen Lilah F. Morris-Wiseman Sally E. Carty Tracy S. Wang 《Surgery》2021,169(3):488-495
BackgroundApproximately 80% of general surgery residents undertake some form of fellowship training. Our objective was to characterize goals and burdens of the interview process among applicants to Comprehensive Endocrine Surgery Fellowship programs.MethodsParticipants included trainees from 2013 to 2019. Results for ranking questions are presented as a mean rank reported out of the total number of selections.ResultsResponse rate was 54% (n = 75). The most important goal for interviews was meeting the faculty (mean rank 2.4/9), followed by “behind the scenes information” and “make a good impression” (mean rank 3.6 and 3.7, respectively). The most substantial burden for the applicant was expense (mean rank 2.1/7), followed by time away from residency (mean rank 3.1/7). The economic burden of 51% of the applicants was $2,500 to $7,500. Geographic location and expense were the top 2 reasons applicants declined offers of interviews. Despite the process, 76% of respondents indicated that no improvements to the interview process are necessary. Alternative strategies such as videoconferencing or centralized interviews received little support (<10%).ConclusionDespite identifying several burdens, survey respondents believed that in-person interviews are an integral component of the fellowship application process. Indeed, 70% of applicants do not have a first-choice program before interviews, and meeting the faculty is ranked as the greatest priority goal. Our data illustrate the importance of individual specialties evaluating and optimizing their own processes for fellowship interviews. 相似文献
10.
The purpose of this study was to determine the importance of inhibition of beta-adrenergic function in thiopentone-induced
myocardial depression. Using an isolated, electrically stimulated rat left atria model, contractile dose-response curves to
thiopentone (200 μM, 400 μM, 600 μM, 800 μM) were shifted to the right in preparations treated with 10− 3 M dibutyryl cyclic adenosine monophosphate (cAMP) compared with atria stimulated with 10− 6 M isoprenaline, demonstrating that inhibition of beta-adrenergic mechanisms by thiopentone is physiologically important.
Depression by thiopentone was similar in atria treated with 10− 5 M forskolin compared with preparations stimulated with 10− 6 M isoprenaline, indicating that thiopentone does not block beta-adrenergic receptors. It is concluded that thiopentone depresses
myocardial function by several mechanisms, one of which involves inhibition of the adenyl cyclase cascade. The adenyl cyclase
enzyme is a likely site where thiopentone inhibits the system; however, other components of the cascade may also be involved.
L’objectif de cette étude consiste à déterminer l’influence de l’inhibition de l’activité β-adrenergique sur la dépression
myocardique induite par le thiopentone. A l’aide d’un modèle constitué d’une oreillette gauche de rat stimulée électriquement,
la relation dose-effet du thiopentone sur la contractilité (200 μM, 400 μM, 600 μM, 800 μM) se déplace vers la droite dans
des préparations traitées avec de l’adénosine monophosphorique cyclique (cAMP) 10− 3 M comparativement à des oreillettes stimulées avec de l’isoprénaline 10− 6 M, ce qui démontre que l’inhibition β-adrénergique provoquée par le thiopentone est physiologiquement importante. La dépression
de l’oreillette provoquée par le thiopentone est identique à celle que produit la forskoline 10− 5 M comparativement à celle de l’isoprénaline 10− 6 M, ce qui indique que le thiopentone n’inhibe pas les récepteurs β-adrénergiques. Les auteurs concluent que le thiopentone
déprime la fonction myocardique par plusieurs mécanismes qui impliquent l’inhibition de la cascade de l’adényl cyclase. L’inhibition
du système se produit vraisemblablement au niveau de l’enzyme adényl cyclase; cependant, il est possible que d’autres éléments
de la cascade de l’adényl cyclase soient impliqués. 相似文献