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51.
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
52.
53.
Aim: Although obesity and weight gain generally are anticipated to be caused by an imbalance between energy intake and energy expenditure, the significance of thyroid hormones (TH) remains unclear. Examination of mitochondrial function may reflect intracellular thyroid hormone effect and elucidate whether a lower metabolic rate is present. Methods: In a group of 34 obese adolescents (age <16 years and body mass index above the age‐related 95th percentile), and an age‐ and gender‐matched group of 32 lean adolescent, thyroid stimulating hormone (TSH) and basal oxygen consumption were measured and mitochondrial function in peripheral blood monocytes was determined by flow cytometry. Results: Significant increase in TSH (3.06 ± 1.56 mU/L vs. 2.33 ± 0.91 mU/L, p < 0.05) and a decrease in VO2 (129 ± 16 mL O2/m2*min vs. 146 ± 15 mL O2/m2*min, p < 0.05) were observed in obese adolescents compared with lean adolescents. Flow cytometry analysis demonstrated a lower mitochondrial mass (6385 ± 1962 a.u. vs. 7608 ± 2328 a.u., p < 0.05) and mitochondrial membrane potential (11426 ± 3861 a.u. vs. 14017 ± 5536 a.u., p < 0.05) in obese adolescents compared with lean adolescents. These results are even more pronounced in adolescents with obese mothers. Conclusion: In obese adolescents, the increased TSH and lowered VO2 propose a lowered basal metabolic rate and the impaired mitochondrial function suggests a decreased thyroid hormone stimulation of mitochondrial energy production. The maternal in‐heritage is suggestive of a basal metabolic defect or mitochondrial resistance for TH. 相似文献
54.
55.
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
56.
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
57.
R Foa M T Fierro P Lusso M Bonferroni D Raspadori M Buzzi P L Zinzani L Resegotti F Lauria 《Leukemia》1987,1(4):377-379
The role of in vivo administration of lymphoblastoid alpha-interferon (IFN-alpha) on the immune status of 12 patients with hairy cell leukemia (HCL) was studied. In most cases an increase in T3(CD3), T4(CD4), and T8(CD8) lymphocyte subsets was documented at the same time as hairy cells disappeared from the circulation. This led in most cases to an improved T4/T8 ratio. The effect of treatment with IFN-alpha was particularly evident on the natural killer cell compartment, which is often functionally depressed in HCL at diagnosis. After therapy, a progressive increase in the cytotoxic activity was observed in most patients. This was more evident 6-9 months after commencing treatment. These findings suggest that, in addition to the known clinicohematological effects, IFN-alpha can improve both the T and natural killer compartments in patients with HCL. 相似文献
58.
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
Background
Early diagnosis of dementia benefits both patient and caregiver. Nevertheless, dementia in primary care is currently under-diagnosed. Some educational interventions developed to improve dementia diagnosis and management were successful in increasing the number of dementia diagnoses and in changing attitudes and knowledge of health care staff. However, none of these interventions focussed on collaboration between GPs and nurses in dementia care. We developed an EASYcare-based Dementia Training Program (DTP) aimed at stimulating collaboration in dementia primary care. We expect this program to increase the number of cognitive assessments and dementia diagnoses and to improve attitudes and knowledge of GPs and nurses. 相似文献59.
When inferior vena caval obstruction complicates the Budd-Chiari syndrome, conventional portosystemic shunts are not possible. The mesoatrial shunt has been devised to enable portal and sinusoidal decompression in these patients. Findings in 12 patients with Budd-Chiari syndrome and inferior vena caval obstruction in whom a mesoatrial shunt was performed are reported. Preoperative inferior vena cavography with pressure measurements is essential to determine the appropriate shunt procedure. Postoperatively, shunt patency is assessed with superior mesenteric arterial portography. Where possible, transvenous catheterization of the shunt is performed to confirm patency and assess hemodynamic function. 相似文献
60.
Conventional computer-based medical expert systems deliver advice to physicians as written text. While such advice is useful, it has distinct limitations in a visually oriented discipline such as diagnostic radiology, in which decisions often depend on pattern recognition and appreciation of subtle morphologic features. The authors developed a prototype expert computer system, IMAGE/ICON, which displays groups of images sorted into a series of axes based on different ways in which they may be similar. They may share a common feature, group of features, causes, or clinical setting. IMAGE/ICON may display examples of morphologic variations of a dominant finding or a spectrum of abnormalities seen in an specific disease or group of diseases. The system also assembles a written analysis of key features of a case. Such a tool may be useful as a diagnostic aid or for continuing medical education. It is likely to have particular impact in the form of an intelligent radiologic workstation, as picture archiving and communication systems become available. 相似文献