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41.
Mutation spectrum and genotype-phenotype analyses in Cowden disease and Bannayan-Zonana syndrome, two hamartoma syndromes with germline PTEN mutation 总被引:22,自引:1,他引:22
Marsh DJ; Coulon V; Lunetta KL; Rocca-Serra P; Dahia PL; Zheng Z; Liaw D; Caron S; Duboue B; Lin AY; Richardson AL; Bonnetblanc JM; Bressieux JM; Cabarrot-Moreau A; Chompret A; Demange L; Eeles RA; Yahanda AM; Fearon ER; Fricker JP; Gorlin RJ; Hodgson SV; Huson S; Lacombe D; Eng C 《Human molecular genetics》1998,7(3):507-515
The tumour suppressor gene PTEN , which maps to 10q23.3 and encodes a 403
amino acid dual specificity phosphatase (protein tyrosine phosphatase;
PTPase), was shown recently to play a broad role in human malignancy.
Somatic PTEN deletions and mutations were observed in sporadic breast,
brain, prostate and kidney cancer cell lines and in several primary tumours
such as endometrial carcinomas, malignant melanoma and thyroid tumours. In
addition, PTEN was identified as the susceptibility gene for two hamartoma
syndromes: Cowden disease (CD; MIM 158350) and Bannayan-Zonana (BZS) or
Ruvalcaba-Riley-Smith syndrome (MIM 153480). Constitutive DNA from 37 CD
families and seven BZS families was screened for germline PTEN mutations.
PTEN mutations were identified in 30 of 37 (81%) CD families, including
missense and nonsense point mutations, deletions, insertions, a
deletion/insertion and splice site mutations. These mutations were
scattered over the entire length of PTEN , with the exception of the first,
fourth and last exons. A 'hot spot' for PTEN mutation in CD was identified
in exon 5 that contains the PTPase core motif, with 13 of 30 (43%) CD
mutations identified in this exon. Seven of 30 (23%) were within the core
motif, the majority (five of seven) of which were missense mutations,
possibly pointing to the functional significance of this region. Germline
PTEN mutations were identified in four of seven (57%) BZS families studied.
Interestingly, none of these mutations was observed in the PTPase core
motif. It is also worthy of note that a single nonsense point mutation,
R233X, was observed in the germline DNA from two unrelated CD families and
one BZS family. Genotype-phenotype studies were not performed on this small
group of BZS families. However, genotype-phenotype analysis inthe group of
CD families revealed two possible associations worthy of follow-up in
independent analyses. The first was an association noted in the group of CD
families with breast disease. A correlation was observed between the
presence/absence of a PTEN mutation and the type of breast involvement
(unaffected versus benign versus malignant). Specifically and more
directly, an association was also observed between the presence of a PTEN
mutation and malignant breast disease. Secondly, there appeared to be an
interdependent association between mutations upstream and within the PTPase
core motif, the core motif containing the majority of missense mutations,
and the involvement of all major organ systems (central nervous system,
thyroid, breast, skin and gastrointestinal tract). However, these
observations would need to be confirmed by studying a larger number of CD
families.
相似文献
42.
GABA-level increasing and anticonvulsant effects of three different GABA uptake inhibitors 总被引:12,自引:0,他引:12
Dalby NO 《Neuropharmacology》2000,39(12):2399-2407
The present study examines the effect of tiagabine (a selective inhibitor of GABA transporter 1, GAT-1), SNAP-5114 (a semi-selective inhibitor of rat GAT-3/mouse GAT4) and NNC 05-2045 (a non-selective GABA uptake inhibitor) in modulating GABA levels in the hippocampus and thalamus. Anticonvulsant effects of the same compounds were assessed (after intranigral administration) after maximal electroshock (MES) in juvenile rats. Anticonvulsant effects were also tested after intraperitoneal (i.p.) administration against audiogenic seizures in DBA/2 mice and against pentylentetrazole (PTZ)-induced tonic convulsions or MES in NMRI mice. Tiagabine (30 microM, perfused through the microdialysis probe in halothane anaesthetized rats) increased GABA levels to (% basal+/-SEM) 645+/-69 in the hippocampus and 409+/-61 in the thalamus. SNAP-5114 (100 microM) increased GABA levels in the thalamus (% basal+/-SEM) to 247+/-27 but had no effect on hippocampal GABA-levels. NNC 05-2045 (100 microM) increased GABA levels both in the hippocampus (% basal+/-SEM, 251+/-51) and in the thalamus (298+/-27). All compounds protected against tonic hindlimb extension (THE) in juvenile male rats after intranigral administration. Sound induced convulsions in DBA/2 mice were dose-dependently inhibited by all compounds (administered intraperitoneal, i.p.) with ED(50) values of 1, 6 and 110 micromol/kg, for tiagabine, NNC 05-2045 and SNAP-5114, respectively. Tiagabine and NNC 05-2045 but not SNAP-5114 protected against PTZ-induced tonic convulsions whereas only NNC 05-2045 protected against MES-induced tonic convulsions in NMRI mice. However, tiagabine and NNC 05-2045 exerted a synergistic effect in the MES model. These findings substantiate and extend previous findings of different effects of selective versus non-selective GABA uptake inhibitors in animal models of epilepsy. 相似文献
43.
M Z Siodlak J E Dalby P J Bradley J B Campbell P Strickland J G Fraser D J Willatt L M Flood P M Stell 《Clinical otolaryngology and allied sciences》1989,14(1):17-22
Between 1978 and 1981, 85 patients with advanced squamous cell carcinoma of the head and neck were randomized to receive induction VBM followed by radiotherapy, or radiotherapy alone. The shortest follow-up is thus 6 years. The median survival of patients receiving induction chemotherapy was 46 weeks, that of the radiotherapy group alone was 75 weeks. As the two groups were not balanced despite randomization, multivariate methods (GLIM) were used to identify significant prognostic factors. These were: response to radiotherapy (P less than 0.001), nodal status (P less than 0.001), age (P less than 0.01), and histological grade (P less than 0.01). Neither treatment with, nor response to, chemotherapy had a significant effect on survival. 相似文献
44.
Posteroanterior (PA) and caudally angulated PA views were obtained in 20 patients undergoing routine coronary arteriography. Although the left main coronary artery (LMCA) was seen well on both views in all patients, the PA-caudal view improved depiction of the LMCA bifurcation in 15 (75%). In addition, the PA-caudal view markedly improved depiction of the circumflex artery, affording optimal depiction of this artery and its branches in 78%-89% of patients. Neither the PA nor the PA-caudal view allowed adequate depiction of the left anterior descending artery. Thus, the PA-caudal view should supplant the PA view in routine coronary arteriography. 相似文献
45.
Recurrence after radiotherapy for glottic carcinoma 总被引:2,自引:0,他引:2
A series of 478 patients with T1-3N0 glottic carcinoma treated by irradiation is presented. Of these patients, 320 were previously untreated, whereas 158 patients were referred for treatment of a recurrence after receiving radiotherapy elsewhere. The primary recurrence rate in the previously untreated patients was 10%. The rate was higher in T2 and T3 tumors, poorly differentiated tumors, and in patients who were in poor general condition. Over 80% of the recurrent tumors were Stage pT3 or pT4, whereas 12% of total laryngectomy specimens showed necrosis only with no evidence of tumor. The necrosis rate in previously untreated patients was 1% for T1 tumors, 4% for T2 tumors, and 3% for T3 tumors. Of all tumors, 60% were transglottic when they recurred, whereas only 29% were confined to the glottis at recurrence. Histologic diagnosis had a high sensitivity but a low specificity, indicating that a negative histologic report is unreliable. Of patients with a recurrent primary tumor, 13% were untreatable. The 5-year survival after a primary recurrence was 39%, and the main prognostic factors were sex, T stage at recurrence, and time to recurrence. Of patients available for follow-up at 5 years 49% were alive with a larynx, 5% were alive without a larynx, 13% were dead of the original cancer, and 33% had died of other causes. In those suffering a primary recurrence, the commonest cause of death was a subsequent lymph node metastasis, followed in order of frequency by stomal recurrence and recurrence in the pharyngeal remnant. The hospital mortality rate after laryngectomy was 3%, and 30% of patients undergoing laryngectomy developed a pharyngocutaneous fistula. The recurrence rate in lymph nodes was 14% at 5 years, general condition and T stage being the only significant predictors of recurrence. Only 17% of patients had small (N1) nodes by the time the diagnosis of cervical lymph node recurrence was made, and 27% of all patients were unsuitable for treatment. Host, tumor factors, and time to recurrence were not significant predictors of survival after node recurrence. The survival rate 5 years after node recurrence was 16%, and the main cause of death in those who died was uncontrolled disease in the neck. The hospital mortality after salvage neck dissection was 4.7%. 相似文献
46.
PL.RM. Palaniappan Selvi Sabhanayakam N. Krishnakumar M. Vadivelu 《Food and chemical toxicology》2008,46(7):2440-2444
Catla catla fingerlings were reared in freshwater and exposed to 15.5 ppm concentration of lead for 60 days. The morphological changes on the gill of the C. catla fingerlings due to lead intoxication and the effect of DMSA (meso 2,3-dimercaptosuccinic acid) on the affected tissues were observed using Scanning Electron Microscope. It has been found that the lead treated gill tissues showed certain marked changes, such as cell hypertrophy, alteration in the lamellar surfaces, epithelial hyperplasia and the fusion of adjacent lamellae. The antidote DMSA treatment reduces the toxic effects and helps the recovery of gill tissue and its return to the level of the control/normal. 相似文献
47.
48.
J S Durham J Nash G Rothery J E Dalby P M Stell 《Clinical otolaryngology and allied sciences》1990,15(6):529-534
We describe 50 patients with anaplastic carcinoma presenting with a mass in the neck. The diagnosis of anaplastic carcinoma was confirmed by immunocytochemistry to exclude very poorly differentiated squamous carcinomas, amelanotic melanoma, and non-Hodgkin's lymphoma. The primary site was established immediately in 26 patients (25 in the head and neck; 1 in the lung); a further 4 had radiological evidence of a primary tumour in the lung. The primary site was established later in 1 patient, in the ethmoid sinuses. In 20 patients the primary site was never established. The commonest primary site was the nasopharynx. The basic treatment policy was radiotherapy, although 20% of patients with a known primary tumour, and 50% of those without, were untreated. The 2-year survival was about 30% in both groups, and did not differ significantly. Prognostic factors for survival were age, performance status, and T status of the primary tumour. Sex, node status, node level, and laterality of nodes, were not. 相似文献
49.
John W Sellors Robert Hayward Graham Swanson Anita Ali R Brian Haynes Ronald Bourque Karen-Ann Moore Lynne Lohfeld Dawn Dalby Michelle Howard 《BMC public health》2002,2(1):14-9
Background
Self-administered computer-assisted blood donor screening strategies may elicit more accurate responses and improve the screening process. 相似文献50.
M Perry I Drašković T van Achterberg GF Borm MIJ van Eijken PL Lucassen MJFJ Vernooij-Dassen MGM Olde Rikkert 《BMC health services research》2008,8(1):71