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61.
G Zaidi RP Sahu L Zhang G George N Bhavani N Shah V Bhatia A Bhansali G Jevalikar RV Jayakumar GS Eisenbarth E Bhatia 《Clinical genetics》2009,76(5):441-448
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare recessive disorder resulting from mutations in the autoimmune regulator ( AIRE ) gene. There is no information on AIRE mutations in Indians. In a cross-sectional study, nine patients (eight families), from four referral hospitals in India, were studied for AIRE mutations by direct sequencing. We screened for new mutations in 150 controls by allele-specific PCR. The patients had 1–7 known components of APECED. Three patients had unusual manifestations: presentation with type 1 diabetes; chronic sinusitis and otitis media; and facial dysmorphism. All patients carried homozygous, probably recessive, AIRE mutations. Two unrelated patients from a small in-bred community (Vanika Vaisya) in south India carried an unreported missense mutation, p.V80G, in the N-terminal caspase recruitment domain. Another unique mutation, p.C302X, resulting in a truncated protein with deletion of both zinc-finger domains, was detected in a patient from Gujarat. Neither mutation was detected in controls. Other mutations, previously described in Caucasians, were: 13 base pair deletion (p.C322fsX372) in 4 (38%), and Finn-major (p.R257X) and p.R139X (Sardinian) mutation in one subject each. In conclusion, in this first series of APECED in Indians, we detected AIRE mutations previously reported in Caucasians, as well as unique mutations. Of these, p.V80G is possibly an ancestral mutation in an in-bred community. 相似文献
62.
Protein tyrosine phosphorylation is an important early event in the signal transduction of numerous cell receptors involved in the immune response. The implication of protein tyrosine kinases in allergic asthma is well recognized, but the role of protein tyrosine phosphatases (PTPs) remains poorly understood. However, we recently reported that global inhibition of PTPs during either the allergen-sensitization phase or the allergen-challenge phase reduced the development of asthma and that this correlated with an increased T helper 1 (Th1) response in both lung and spleen tissues. Therefore, in this study we investigated individual roles of PTPs involved in regulating the immune response. We observed that genetic deficiency for PTP-1B resulted in increased recruitment of lung inflammatory cells, while protein tyrosine phosphatase-phosphatase and tensin homologue deleted (PTP-PEST)-deficient mice exhibited a phenotype similar to that of wild-type mice. Importantly, we found that a heterozygous mutation of T cell PTP (TC-PTP) dramatically abrogates immunoglobulin E production and reduces the recruitment of inflammatory cells to the lung, conferring an important role for TC-PTP in the development of allergic asthma. As opposed to other studies on Src homology phosphatase-1 (SHP-1) deficiency, specific acute SHP-1 inhibition during allergen challenge did not affect disease outcome. Collectively, our results underscore the importance of PTPs in the development of allergic asthma. 相似文献
63.
K.D. Statler P. Scheerlinck W. Pouliot M. Hamilton H.S. White F.E. Dudek 《Epilepsy research》2009,86(2-3):221-223
Preclinical models of pediatric posttraumatic epilepsy (PTE) are lacking. We hypothesized that traumatic brain injury (TBI), induced by controlled cortical impact, in immature rats would cause electroencephalographic (EEG) epileptiform activity and behavioral seizures. TBI or sham craniotomy was performed on postnatal day 17. Using video-EEG monitoring 4–11 months post-TBI, most TBI rats (87.5%) showed EEG spiking and one had spontaneous, recurrent seizures. Controls showed neither EEG spikes nor electrographic/behavioral seizures. Late seizures were rare after TBI, but EEG spiking was common and may represent a surrogate for PTE. 相似文献
64.
Sandra Pouliot Fanny Bourgeat Samy Barkat Catherine Rouby Moustafa Bensafi 《Chemosensory perception》2008,1(1):43-47
During menopause, some women suffer from anhedonia. Anhedonia is an inability to experience pleasure from normally pleasurable life events, such as eating a favorite meal or smelling agreeable flowers. In this study, we explored whether degree of anhedonia in menopausal women was associated with performance on the European Test of Olfactory Capabilities (Thomas-Danguin et al., Rhinology, 41:142–151 2003). Also, we investigated whether degree of anhedonia predicted how menopausal women would appreciate pleasant, neutral or unpleasant odors. We found that women who were more anhedonic had a worst olfactory function than women who were less anhedonic. Also, we found that only the women in the less anhedonic group rated less odors as unpleasant than as neutral or pleasant. Anhedonia was correlated negatively with percentage of odors categorized as being pleasant but was not with percentage of odors perceived as neutral or unpleasant. Our results are consistent with studies showing that not all menopausal women exhibit disrupted affect, such as anhedonia. However, we suggest that when anhedonia occurs, it does so together with a decreased olfactory function and a shift in olfactory hedonism. 相似文献
65.
Martin AG Roy J Beaulieu L Pouliot J Harel F Vigneault E 《International journal of radiation oncology, biology, physics》2007,67(2):334-341
PURPOSE: To report outcomes and toxicity of the first Canadian permanent prostate implant program. METHODS AND MATERIALS: 396 consecutive patients (Gleason < or =6, initial prostate specific antigen (PSA) < or =10 and stage T1-T2a disease) were implanted between June 1994 and December 2001. The median follow-up is of 60 months (maximum, 136 months). All patients were planned with fast-simulated annealing inverse planning algorithm with high activity seeds ([gt] 0.76 U). Acute and late toxicity is reported for the first 213 patients using a modified RTOG toxicity scale. The Kaplan-Meier biochemical failure-free survival (bFFS) is reported according to the ASTRO and Houston definitions. RESULTS: The bFFS at 60 months was of 88.5% (90.5%) according to the ASTRO (Houston) definition and, of 91.4% (94.6%) in the low risk group (initial PSA < or =10 and Gleason < or =6 and Stage < or =T2a). Risk factors statistically associated with bFFS were: initial PSA >10, a Gleason score of 7-8, and stage T2b-T3. The mean D90 was of 151 +/- 36.1 Gy. The mean V100 was of 85.4 +/- 8.5% with a mean V150 of 60.1 +/- 12.3%. Overall, the implants were well tolerated. In the first 6 months, 31.5% of the patients were free of genitourinary symptoms (GUs), 12.7% had Grade 3 GUs; 91.6% were free of gastrointestinal symptoms (GIs). After 6 months, 54.0% were GUs free, 1.4% had Grade 3 GUs; 95.8% were GIs free. CONCLUSION: The inverse planning with fast simulated annealing and high activity seeds gives a 5-year bFFS, which is comparable with the best published series with a low toxicity profile. 相似文献
66.
Chen AM Chang S Pouliot J Sneed PK Prados MD Lamborn KR Malec MK McDermott MW Berger MS Larson DA 《International journal of radiation oncology, biology, physics》2007,69(3):825-830
PURPOSE: To evaluate the feasibility of gross total resection and permanent I-125 brachytherapy followed by hyperfractionated radiotherapy for patients with newly diagnosed glioblastoma. METHODS AND MATERIALS: From April 1999 to May 2002, 21 patients with glioblastoma multiforme were enrolled on a Phase I protocol investigating planned gross total resection and immediate placement of permanent I-125 seeds, followed by postoperative hyperfractionated radiotherapy to a dose of 60 Gy at 100 cGy b.i.d., 5 days per week. Median age and Karnofsky performance status were 50 years (range, 32-65 years) and 90 (range, 70-100), respectively. Toxicity was assessed according to Radiation Therapy Oncology Group criteria. RESULTS: Eighteen patients completed treatment according to protocol. The median preoperative tumor volume on magnetic resonance imaging was 18.6 cm(3) (range, 4.4-41.2 cm(3)). The median brachytherapy dose measured 5 mm radially outward from the resection cavity was 400 Gy (range, 200-600 Gy). Ten patients underwent 12 reoperations, with 11 of 12 reoperations demonstrating necrosis without evidence of tumor. Because of high toxicity, the study was terminated early. Median progression-free survival and overall survival were 57 and 114 weeks, respectively, but not significantly improved compared with historical patients treated at University of California, San Francisco, with gross total resection and radiotherapy without brachytherapy. CONCLUSIONS: Treatment with gross total resection and permanent I-125 brachytherapy followed by hyperfractionated radiotherapy as performed in this study results in high toxicity and reoperation rates, without demonstrated improvement in survival. 相似文献
67.
David S Finley Frederic Pouliot Arnold I Chin Brian Shuch Alan J Pantuck Arie S Belldegrun Jean B Dekernion 《International journal of urology》2011,18(2):94-101
At present, immunotherapy in urological malignancy is experiencing a renaissance, particularly with the emergence of a host of innovative cancer vaccines. Herein, we will review promising immunotherapeutic approaches and evaluate the data supporting their inclusion in novel combination strategies. 相似文献
68.
Association of the steroid synthesis gene CYP11a with polycystic ovary syndrome and hyperandrogenism 总被引:12,自引:0,他引:12
Gharani N; Waterworth DM; Batty S; White D; Gilling-Smith C; Conway GS; McCarthy M; Franks S; Williamson R 《Human molecular genetics》1997,6(3):397-402
Biochemical data implicate an underlying disorder of androgen biosynthesis
and/or metabolism in the aetiology of polycystic ovary syndrome (PCOS). We
have examined the segregation of the genes coding for two key enzymes in
the synthesis and metabolism of androgens, cholesterol side chain cleavage
(CYP11a) and aromatase (CYP19), with PCOS in 20 multiply-affected families.
All analyses excluded CYP19 cosegregation with PCOS, demonstrating that
this locus is not a major determinant of risk for the syndrome. However,
our results provide evidence for linkage to the CYP11a locus (NPL score =
3.03, p = 0.003). Parametric analysis using a dominant model suggests
genetic heterogeneity, generating a maximum HLOD score of 2.7 (alpha =
0.63). An association study of 97 consecutively identified Europids with
PCOS and matched controls demonstrates significant allelic association of a
CYP11a 5' UTR pentanucleotide repeat polymorphism with hirsute PCOS
subjects (p = 0.03). A strong association was also found between alleles of
this polymorphism and total serum testosterone levels in both affected and
unaffected individuals (p = 0.002). Our data demonstrate that variation in
CYP11a may play an important role in the aetiology of hyperandrogenaemia
which is a common characteristic of polycystic ovary syndrome.
相似文献
69.
J Pouliot O Morin M Aubin J-F Aubry J Chen J Speight M Roach 《Cancer radiothérapie》2006,10(5):258-268
The Megavoltage cone-beam (MV CBCT) system consists of a new a-Si flat panel adapted for MV imaging and an integrated workflow application allowing the automatic acquisition of projection images, cone-beam CT image reconstruction, CT to CBCT image registration and couch position adjustment. This provides a 3D patient anatomy volume in the actual treatment position, relative to the treatment isocenter, moments before the dose delivery, that can be tightly aligned to the planning CT, allowing verification and correction of the patient position, detection of anatomical changes and dose calculation. In this paper, we present the main advantages and performance of this MV CBCT system and summarize the different clinical applications. Examples of the image-guided treatment process from the acquisition of the MV CBCT scan to the correction of the couch position and dose delivery will be presented for spinal and lung lesions and for head and neck, and prostate cancers. 相似文献
70.