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41.
42.
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
43.
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44.
45.
Nicholas M. Barbaro MD Mark Quigg MD MSc Donna K. Broshek PhD Mariann M. Ward RN NP Kathleen R. Lamborn PhD Kenneth D. Laxer MD David A. Larson PhD MD William Dillon MD Lynn Verhey PhD Paul Garcia MD Ladislau Steiner MD PhD Christine Heck MD Douglas Kondziolka MD MSc Robert Beach MD William Olivero MD Thomas C. Witt MD Vicenta Salanova MD Robert Goodman MD 《Annals of neurology》2009,65(2):167-175
46.
Effect of femoral component designs on the contact and tracking characteristics of the unresurfaced patella in total knee arthroplasty. 总被引:6,自引:0,他引:6
OBJECTIVES: To determine the effect of 5 different femoral components used in total knee arthroplasty (TKA) on the contact area and tracking characteristics of the nonresurfaced patella and to identify any design features that might adversely affect these characteristics. DESIGN: An in-vitro study. SETTING: The biomechanics laboratory, Department of Mechanical Engineering, McGill University, Montreal. SPECIMENS: Six fresh-frozen cadaveric knee-joint specimens. INTERVENTIONS: An unconstrained quadriceps simulator was used to apply the conditions of static lifting to the specimens first in their normal state and then sequentially implanted with femoral and tibial components of various designs (Miller/Galante II, Anatomic Modular Knee [AMK] System, Whiteside Ortholoc Modular, press-fit condylar and Insall-Burstein II). OUTCOME MEASURES: Patellar 3-dimensional tracking characteristics, determined by using a 6 degrees-of-freedom electromechanical goniometer attached directly to the patella, and patellar contact pressure measurements, obtained using low-range Fuji Prescale film. RESULTS: Articulation of the normal patella on a prosthetic femoral component resulted in alterations in the normal patellofemoral contact and tracking characteristics. The exact departure depended on the design of the prosthetic trochlea. Although all of the selected prostheses demonstrated satisfactory contact characteristics near extension, marked alterations occurred at higher flexion angles. With 90 degrees or more of flexion, there was incompatibility between the geometries of the prosthetic notch of 2 femoral designs (AMK and PFC) and the normal knee. CONCLUSION: The design of the prosthetic femoral component must be taken into account when determining whether or not to resurface the patella at the time of TKA. 相似文献
47.
High-field surface coil magnetic resonance (MR) images were obtained of 12 ankles: two from healthy volunteers, seven from patients, and three from fresh cadavers. The cadaver ankles were sectioned in the coronal, sagittal, and axial planes for direct comparison with the MR images. Plain film confirmation of pathologic conditions was obtained in all patients, and five underwent arthroscopy or surgery, or both. MR imaging provided excellent delineation of ligaments and cartilaginous structures in all cases. 相似文献
48.
49.
This study evaluated the cytotoxicity of commonly used topical agents to human dermal fibroblasts and epidermal keratinocytes, which play a prominent role in wound healing. The effects of these topical agents were assessed using two separate assays for the fibroblasts--tritiated thymidine incorporation and the uptake of a vital dye (neutral red). Keratinocytes were evaluated with the neutral red assay. Serial dilutions of each of 10 commonly used topical agents produced decreases in both the uptake of neutral red and the incorporation of thymidine at clinically relevant doses. Only Neosporin G.U. irrigant showed no significant difference compared with controls in the assays for both the fibroblasts and the keratinocytes. Careful attention must be paid to which agent is used in the clinical setting, since many of these can have profound effects on cells that influence wound healing. 相似文献
50.
Among 55 patients undergoing temporal lobectomy for refractory epilepsy, patients with seizures in the week following surgery had a poor long-term, seizure-free outcome compared with patients without seizures. Outcome for patients with single seizures or seizures restricted to the first postoperative day seemed favorable compared with patients with multiple or later seizures. Seizure type and similarity to preoperative events did not predict outcome. 相似文献