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31.
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
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33.
Yanjun Zhang Wei Huang Jiahuang Jiang Jing Xie Chunmin Xu Chunli Wang Lin Yin Li Yang Kevin Zhou Peter Chen KL Paul Sung 《Knee surgery, sports traumatology, arthroscopy》2014,22(9):1997-2006
Purpose
It was reported that not only ACL but also the synovium may be the major regulator of matrix metalloproteinases (MMPs) in synovial fluids after ACL injury. In order to further confirm whether synovium is capable of regulating the microenvironment in the process of ACL injury, the complicated microenvironment of joint cavity after ACL injury was mimicked and the combined effects of mechanical injury and inflammatory factor [tumour necrosis factor-α (TNF-α)] on expressions of lysyl oxidases (LOXs) and MMPs in synovial fibroblasts derived from normal human synovium were studied.Methods
Human normal knee joint synovial fibroblasts were stimulated for 1–6 h with mechanical stretch and inflammatory factor (TNF-α). Total RNA was harvested, reverse transcribed and assessed by real-time polymerase chain reaction for the expression of LOXs and MMP-1, 2, 3 messenger RNAs. MMP-2 activity was assayed from the collected culture media samples using zymography.Results
Compared to control group, our results showed that 6 % physiological stretch increased MMP-2 and LOXs (except LOXL-3), decreased MMP-1 and MMP-3; injurious stretch (12 %) decreased LOXs (except LOXL-2)and increased MMP-1, 2 and 3; the combination of injurious stretch and TNF-α decreased LOXs and increased MMP-1, 2 and 3 in synovial fibroblasts in a synergistical manner.Conclusion
This study demonstrated that combination of mechanical injury and inflammatory factors up-regulated the expressions of MMPs and down-regulated the expressions of LOXs in synovial fibroblasts, eventually alter the balance of tissue healing. Thus, synovium may be involved in regulating the microenvironment of joint cavity. Based on the mechanism, early interventions to inhibit the production of MMPs or promote the production of LOXs in the synovial fibroblasts should be performed to facilitate the healing of tissue. 相似文献34.
35.
克泻灵片中苦参碱类生物碱的HPLC分析 总被引:8,自引:0,他引:8
目的:对克泻灵片中主要有效生物碱定性、定量。完善产品的质量控制及评价手段。方法:采用HPLC,紫外测定波长:220nm。结果:片剂中有有效生物碱以苦参碱类生物碱为主,其中苦参碱和槐定碱含量高,分别占总生物碱的14.2%~31.6%和22.6%~62.7%,其次为槐颗碱和槐胺碱,氧化苦参碱的含量很低。结论:建立了HPLC测定克泻灵片中主要生物碱,方法简便快捷,精密度好,回收率高,可用于制剂及原料的质量控制。 相似文献
36.
Complementary medicine: use and attitudes among GPs 总被引:9,自引:0,他引:9
BACKGROUND: Information about use and attitudes of GPs towards
complementary medicine is required in order to inform the debate about its
place within mainstream medicine. There is evidence that public use of
complementary medicine is particularly high in the South-West of England.
OBJECTIVE: This study aimed to determine the use of, and attitudes towards,
complementary medicine among GPs. METHODS: A questionnaire survey was
performed of all primary care physicians working in the health service in
Devon and Cornwall. RESULTS: Replies were received from 461 GPs, a response
rate of 47%. A total of 314 GPs (68%, range 32-85%) had been involved in
complementary medicine in some way during the previous week. One or other
form of complementary medicine was practised by 74 of the respondents
(16%), the two most common being homoeopathy (5.9%) and acupuncture (4.3%).
In addition, 115 of the respondents (25%) had referred at least one patient
to a complementary therapist in the previous week, and 253 (55%) had
endorsed or recommended treatment with complementary medicine.
Chiropractic, acupuncture and osteopathy were rated as the three most
effective therapies, and the majority of respondents believed that these
three therapies should be funded by the health service. A total of 176
(38%) of respondents reported adverse effects, most commonly after
manipulation. CONCLUSION: Over two-thirds of the GPs in Devon and Cornwall
who responded to the survey had been involved with complementary medicine
in some way during the previous week. This figure is higher than the
national average. The majority of respondents believed that acupuncture,
chiropractic and osteopathy were effective and should be funded by the NHS.
相似文献
37.
BC SHARMA RP SINGH YK CHAWLA KL NARASIMHAN KLN RAO SK MITRA JB DILAWARI 《Journal of gastroenterology and hepatology》1997,12(8):582-584
Shunt surgery is considered to be the treatment of choice in patients with non-cirrhotic portal hypertension. There is little data on the effect of side-to-side lieno-renal (SSLR) shunt on oesophageal variceal size, splenic size and splenic pulp pressure (SPP) in patients with non-cirrhotic portal hypertension. We evaluated pre- and postoperatively endoscopic grading of varices, splenic size and SPP for predicting shunt patency in 86 patients with non-cirrhotic portal hypertension: 56 with extrahepatic portal venous obstruction (EHPVO) and 30 with non-cirrhotic portal fibrosis (NCPF). The EHPVO patients with patent shunts (n= 47) showed significant reduction in SPP (pre-operative 43.56±7.9 vs postoperative 29.96±7.7 cm of saline), splenic size (6.5±2.8 vs 4.00±2.6 cm below costal margin) and varices grades (2.96±0.5 vs 0.92±0.8). Patients with blocked shunt (n= 9) did not show significant reduction in SPP and varices grades. However, there was reduction in spleen size (8.6±3.0 vs 6.3±4.3). In the NCPF group, 28 had patent shunts and showed significant reduction in SPP (46.3±13.5 vs 33.8±7.6 cm of saline), splenic size (9.1±3.3 vs 6.8±4.6 cm below costal margin) and varices grades (2.8±0.7 vs 1.05±0.96). As only two patients with NCPF had blocked shunts, no statistical comparison between patients with patent and patients with blocked shunts could be done. In conclusion, following SSLR, there is a significant reduction in SPP and varices grades in patients with patent shunts. Endoscopic grading of varices can be used to predict shunt patency. However, spleen size is not a good criteria for predicting shunt patency. 相似文献
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