Genetic Analysis of a Kindred With X-linked Mental Handicap and Retinitis Pigmentosa

PubMed Central

Aldred, M. A.; Dry, K. L.; Knight-Jones, E. B.; Hardwick, L. J.; Teague, P. W.; Lester, D. H.; Brown, J.; Spowart, G.; Carothers, A. D.; Raeburn, J. A.; Bird, A. C.; Fielder, A. R.; Wright, A. F.

1994-01-01

A kindred is described in which X-linked nonspecific mental handicap segregates together with retinitis pigmentosa. Carrier females are mentally normal but may show signs of the X-linked retinitis pigmentosa carrier state and become symptomatic in their later years. Analysis of polymorphic DNA markers at nine loci on the short arm of the X chromosome shows that no crossing-over occurs between the disease and Xp11 markers DXS255, TIMP, DXS426, MAOA, and DXS228. The 90% confidence limits show that the locus is in the Xp21-q21 region. Haplotype analysis is consistent with the causal gene being located proximal to the Xp21 loci DXS538 and 5'-dystrophin on the short arm of the X chromosome. The posterior probability of linkage to the RP2 region of the X chromosome short arm (Xp11.4-p11.23) is .727, suggesting the possibility of a contiguous-gene-deletion syndrome. No cytogenetic abnormality has been identified. PMID:7977353

Clinicopathological features of Xp11.2 translocation renal cell carcinoma.

PubMed

Lim, Bumjin; You, Dalsan; Jeong, In Gab; Kwon, Taekmin; Hong, Sungwoo; Song, Cheryn; Cho, Yong Mee; Hong, Bumsik; Hong, Jun Hyuk; Ahn, Hanjong; Kim, Choung Soo

2015-03-01

Xp11.2 translocation renal cell carcinoma (RCC) is characterized by various translocations of the TFE3 transcription factor gene. These rare cancers occur predominantly in children and young adults. Here, we review the clinicopathological features of Xp11.2 translocation RCC. We identified 21 patients with Xp11.2 translocation RCC. We retrospectively analyzed patient characteristics, clinical manifestations, and specific pathological features to assess definitive diagnosis, surgical and systemic treatments, and clinical outcomes. The mean age at diagnosis was 43.4±20.0 years (range, 8-80 years; 8 males and 13 females). Eleven patients were incidentally diagnosed, nine patients presented with local symptoms, and one patient presented with systemic symptoms. The mean tumor size was 6.2±3.8 cm (range, 1.9-14 cm). At the time of diagnosis, 11, 1, and 5 patients showed stage I, II, and III, respectively. Four patients showed distant metastasis. At analysis, 15 patients were disease-free after a median follow-up period of 30.0 months. Four patients received target therapy but not effectively. Xp11 translocation RCC tends to develop in young patients with lymph node metastasis. Targeted therapy did not effectively treat our patients. Surgery is the only effective therapy for Xp11 translocation RCC, and further studies are needed to assess systemic therapy and long-term prognosis.

Clinicopathological features of Xp11.2 translocation renal cell carcinoma

PubMed Central

Lim, Bumjin; You, Dalsan; Jeong, In Gab; Kwon, Taekmin; Hong, Sungwoo; Song, Cheryn; Cho, Yong Mee; Hong, Bumsik; Hong, Jun Hyuk; Ahn, Hanjong

2015-01-01

Purpose Xp11.2 translocation renal cell carcinoma (RCC) is characterized by various translocations of the TFE3 transcription factor gene. These rare cancers occur predominantly in children and young adults. Here, we review the clinicopathological features of Xp11.2 translocation RCC. Materials and Methods We identified 21 patients with Xp11.2 translocation RCC. We retrospectively analyzed patient characteristics, clinical manifestations, and specific pathological features to assess definitive diagnosis, surgical and systemic treatments, and clinical outcomes. Results The mean age at diagnosis was 43.4±20.0 years (range, 8-80 years; 8 males and 13 females). Eleven patients were incidentally diagnosed, nine patients presented with local symptoms, and one patient presented with systemic symptoms. The mean tumor size was 6.2±3.8 cm (range, 1.9-14 cm). At the time of diagnosis, 11, 1, and 5 patients showed stage I, II, and III, respectively. Four patients showed distant metastasis. At analysis, 15 patients were disease-free after a median follow-up period of 30.0 months. Four patients received target therapy but not effectively. Conclusions Xp11 translocation RCC tends to develop in young patients with lymph node metastasis. Targeted therapy did not effectively treat our patients. Surgery is the only effective therapy for Xp11 translocation RCC, and further studies are needed to assess systemic therapy and long-term prognosis. PMID:25763125

MiT translocation renal cell carcinomas: two subgroups of tumours with translocations involving 6p21 [t (6; 11)] and Xp11.2 [t (X;1 or X or 17)].

PubMed

Hora, Milan; Urge, Tomáš; Trávníček, Ivan; Ferda, Jiří; Chudáček, Zdeněk; Vaněček, Tomáš; Michal, Michal; Petersson, Fredrik; Kuroda, Naoto; Hes, Ondřej

2014-01-01

MiT translocation renal cell carcinomas (TRCC) predominantly occur in younger patients with only 25% of patients being over 40 years. TRCC contains two main subgroups with translocations involving 6p21 or Xp11.2. Herein we present 10 cases. Eight cases were treated at main author's institution (identified among 1653 (0.48%) cases of kidney tumours in adults). Two cases were retrieved from the Pilsen (CZ) Tumour Registry. Six cases were type Xp11.2 and four 6p21; 7 female, 3 male patients; Xp11.2 4:2, 6p21 3:1. The mean age 49 years (range: 21-80), 5 patients (50%) over 40 years. The mean age of the group with Xp11.2 TRCCs was 55 (median 51) and 6p21 41 (32) years. One female with a 6p21 tumour (24 years) underwent nephrectomy at 4 months of pregnancy. Stage (UICC, 7th ed. 2009) was 5xI, 3xIII, 2xIV. The mean size of tumour was 80 (40-165) mm. The mean follow-up was 33.2 (1-92) months. In patients with 6p21 tumours, one (25%) died after 3 months due to widely metastatic disease. In patients with Xp11.2 tumours, 3 (50%) succumbed due to metastatic disease (range 1-8 months). Three patients with Xp11.2 are alive at 7, 52 and 92 months of follow-up, were diagnosed at early stage (T1a). TRCCs were more common in females. Patient with 6p21 tumours were younger than those with Xp11.2. Both types have definitive malignant potential Type Xp11.2 seems to be a more aggressive neoplasm than 6p21. The case with metastatic 6p21 tumour is the 4th case described in the English literature.

Renal Cell Carcinoma Associated with Xp11.2 Translocation/TFE3 Gene Fusions: Clinical Features, Treatments and Prognosis.

PubMed

Liu, Ning; Wang, Zhen; Gan, Weidong; Xiong, Lei; Miao, Baolei; Chen, Xiancheng; Guo, Hongqian; Li, Dongmei

2016-01-01

To investigate the clinical characteristics, treatments and prognosis of renal cell carcinoma associated with Xp11.2 translocation/TFE3 gene fusions (Xp11.2 tRCC), the epidemiological features and treatment results of 34 cases of Xp11.2 tRCC, which were diagnosed by immunohistochemistry staining of TFE3 and fluorescence in situ hybridization at our center, were retrospectively reviewed. The 34 patients included 21 females and 13 males aged 3 to 64 years (median age: 27 years). Four patients were children or adolescents (<18 years of age), and 26 patients were young or middle-aged adults (18-45 years). Radical nephrectomy was performed on 25 patients. Laparoscopic nephron-sparing surgery was performed on 9 patients who presented with an isolated mass with a small diameter (<7 cm) and well-defined boundary on computed tomography imaging. Postoperative staging showed that 25 cases (73.53%) were at stage I/II, while 9 cases (26.47%) were at stage III/IV. All stage I/II patients received a favorable prognosis with a three-year overall survival rate of 100%, including the patients who underwent laparoscopic nephron-sparing surgery. With the exception of 2 children, the other 7 stage III/IV patients died or developed recurrence with a median follow-up of 29 months. On univariate analysis, maximum diameter, adjuvant treatment, TNM stage, lymph node metastasis, inferior vena cava tumor thrombosis and tumor boundary were identified as statistically significant factors impacting survival (P<0.05). Multivariate analysis indicated that TNM stage and inferior vena cava tumor thrombosis were independent prognostic factors (P<0.05). In conclusion, Xp11.2 tRCC is a rare subtype of renal cell carcinoma that mainly occurs in young females. Nephron-sparing surgery was confirmed effective preliminarily in the treatment of small Xp11.2 tRCCs with clear rims. Advanced TNM stage and inferior vena cava tumor thrombosis were associated with poor prognosis.

Renal Cell Carcinoma Associated with Xp11.2 Translocation/TFE3 Gene Fusions: Clinical Features, Treatments and Prognosis

PubMed Central

Gan, Weidong; Xiong, Lei; Miao, Baolei; Chen, Xiancheng; Guo, Hongqian; Li, Dongmei

2016-01-01

To investigate the clinical characteristics, treatments and prognosis of renal cell carcinoma associated with Xp11.2 translocation/TFE3 gene fusions (Xp11.2 tRCC), the epidemiological features and treatment results of 34 cases of Xp11.2 tRCC, which were diagnosed by immunohistochemistry staining of TFE3 and fluorescence in situ hybridization at our center, were retrospectively reviewed. The 34 patients included 21 females and 13 males aged 3 to 64 years (median age: 27 years). Four patients were children or adolescents (<18 years of age), and 26 patients were young or middle-aged adults (18–45 years). Radical nephrectomy was performed on 25 patients. Laparoscopic nephron-sparing surgery was performed on 9 patients who presented with an isolated mass with a small diameter (<7 cm) and well-defined boundary on computed tomography imaging. Postoperative staging showed that 25 cases (73.53%) were at stage I/II, while 9 cases (26.47%) were at stage III/IV. All stage I/II patients received a favorable prognosis with a three-year overall survival rate of 100%, including the patients who underwent laparoscopic nephron-sparing surgery. With the exception of 2 children, the other 7 stage III/IV patients died or developed recurrence with a median follow-up of 29 months. On univariate analysis, maximum diameter, adjuvant treatment, TNM stage, lymph node metastasis, inferior vena cava tumor thrombosis and tumor boundary were identified as statistically significant factors impacting survival (P<0.05). Multivariate analysis indicated that TNM stage and inferior vena cava tumor thrombosis were independent prognostic factors (P<0.05). In conclusion, Xp11.2 tRCC is a rare subtype of renal cell carcinoma that mainly occurs in young females. Nephron-sparing surgery was confirmed effective preliminarily in the treatment of small Xp11.2 tRCCs with clear rims. Advanced TNM stage and inferior vena cava tumor thrombosis were associated with poor prognosis. PMID:27893792

Refinement of the NHS locus on chromosome Xp22.13 and analysis of five candidate genes.

PubMed

Toutain, Annick; Dessay, Benoît; Ronce, Nathalie; Ferrante, Maria-Immacolata; Tranchemontagne, Julie; Newbury-Ecob, Ruth; Wallgren-Pettersson, Carina; Burn, John; Kaplan, Josseline; Rossi, Annick; Russo, Silvia; Walpole, Ian; Hartsfield, James K; Oyen, Nina; Nemeth, Andrea; Bitoun, Pierre; Trump, Dorothy; Moraine, Claude; Franco, Brunella

2002-09-01

Nance-Horan syndrome (NHS) is an X-linked condition characterised by congenital cataracts, dental abnormalities, dysmorphic features, and mental retardation in some cases. Previous studies have mapped the disease gene to a 2 cM interval on Xp22.2 between DXS43 and DXS999. We report additional linkage data resulting from the analysis of eleven independent NHS families. A maximum lod score of 9.94 (theta=0.00) was obtained at the RS1 locus and a recombination with locus DXS1195 on the telomeric side was observed in two families, thus refining the location of the gene to an interval of around 1 Mb on Xp22.13. Direct sequencing or SSCP analysis of the coding exons of five genes (SCML1, SCML2, STK9, RS1 and PPEF1), considered as candidate genes on the basis of their location in the critical interval, failed to detect any mutation in 12 unrelated NHS patients, thus making it highly unlikely that these genes are implicated in NHS.

Postoperative recurrence of adult renal cell carcinoma associated with Xp11.2 translocation/TFE3 gene fusion.

PubMed

Wang, Zhen; Liu, Ning; Gan, Weidong; Li, Xiaogong; Zhang, Gutian; Li, Dongmei; Guo, Hongqian

2017-08-01

Objective To analyze the postoperative recurrence of renal cell carcinoma associated with Xp11.2 translocation/TFE3 gene fusion (Xp11.2 tRCC). Methods This retrospective study was approved by the institutional review board and performed in accordance with the ethical standards established by the institution. Demographic, clinical, pathological, and follow-up data were compiled for the study cohort. Results During a mean follow-up of 41.3 months (range, 3-104 months), 8 of 34 patients with Xp11.2 tRCC were confirmed to have recurrence. Three of these patients died with poor outcomes due to a vena cava tumor embolus, and one died of distant metastasis 48 months after the initial nephrectomy during which lymph node metastasis was found. Three patients survived after cytoreduction surgery. One patient was diagnosed with lung metastasis 11 months postoperatively. Conclusions The TNM classification provides significant prognostic information for Xp11.2 tRCC. A relatively active surveillance algorithm is recommended, and cytoreduction surgery is an effective approach for recurrent Xp11.2 tRCC. Larger studies are required to more extensively investigate the recurrence of these potentially aggressive tumors.

Postoperative recurrence of adult renal cell carcinoma associated with Xp11.2 translocation/TFE3 gene fusion

PubMed Central

Wang, Zhen; Liu, Ning; Li, Xiaogong; Zhang, Gutian; Li, Dongmei; Guo, Hongqian

2017-01-01

Objective To analyze the postoperative recurrence of renal cell carcinoma associated with Xp11.2 translocation/TFE3 gene fusion (Xp11.2 tRCC). Methods This retrospective study was approved by the institutional review board and performed in accordance with the ethical standards established by the institution. Demographic, clinical, pathological, and follow-up data were compiled for the study cohort. Results During a mean follow-up of 41.3 months (range, 3–104 months), 8 of 34 patients with Xp11.2 tRCC were confirmed to have recurrence. Three of these patients died with poor outcomes due to a vena cava tumor embolus, and one died of distant metastasis 48 months after the initial nephrectomy during which lymph node metastasis was found. Three patients survived after cytoreduction surgery. One patient was diagnosed with lung metastasis 11 months postoperatively. Conclusions The TNM classification provides significant prognostic information for Xp11.2 tRCC. A relatively active surveillance algorithm is recommended, and cytoreduction surgery is an effective approach for recurrent Xp11.2 tRCC. Larger studies are required to more extensively investigate the recurrence of these potentially aggressive tumors. PMID:28587544

Genetic analysis of a kindred with X-linked mental handicap and retinitis pigmentosa

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aldred, M.A.; Dry, K.L.; Hardwick, L.J.

1994-11-01

A kindred is described in which X-linked nonspecific mental handicap segregates together with retinitis pigmentosa. Carrier females are mentally normal but may show signs of the X-linked retinitis pigmentosa carrier state and become symptomatic in their later years. Analysis of polymorphic DNA markers at nine loci on the short arm of the X chromosome shows that no crossing-over occurs between the disease and Xp11 markers DXS255, TIMP, DXS426, MAOA, and DXS228. The 90% confidence limits show that the locus is in the Xp21-q21 region. Haplotype analysis is consistent with the causal gene being located proximal to the Xp21 loci DXS538more » and 5{prime}-dystrophin on the short arm of the X chromosome. The posterior probability of linkage to the RP2 region of the X chromosome short arm (Xp11.4-p11.23) is .727, suggesting the possibility of a contiguous-gene-deletion syndrome. No cytogenetic abnormality has been identified. 33 refs., 2 figs., 2 tabs.« less

Renal cell carcinoma associated with Xp11.2 translocation/TFE3 gene fusion: radiological findings mimicking papillary subtype.

PubMed

Kato, Hiroki; Kanematsu, Masayuki; Yokoi, Shigeaki; Miwa, Kousei; Horie, Kengo; Deguchi, Takashi; Hirose, Yoshinobu

2011-01-01

The authors describe the computed tomography (CT) and magnetic resonance imaging (MRI) findings of an 18-year-old man with renal cell carcinoma (RCC) associated with the Xp11.2 translocation/transcription factor E3 (TFE3) gene fusion (Xp11 translocation carcinoma). The lesion was hyperdense on unenhanced CT, hypovascular on contrast-enhanced studies, hypointense on T2-weighted MR images, and hemosiderin deposition was suspected on phase-shift gradient-echo MR images. Histopathological specimens revealed pathological findings resembling papillary RCC predominantly and exhibited immunoreactivity for TFE3. Because there is often considerable morphological overlap between this carcinoma and papillary RCC, the imaging findings of Xp11 translocation carcinoma may be similar to those of the papillary subtype. Therefore, Xp11 translocation carcinoma should be considered, particularly in young patients when radiologic images demonstrate a renal tumor mimicking the papillary subtype. Copyright © 2010 Wiley-Liss, Inc.

TFE3-Fusion Variant Analysis Defines Specific Clinicopathologic Associations Among Xp11 Translocation Cancers

PubMed Central

Argani, Pedram; Zhong, Minghao; Reuter, Victor E.; Fallon, John T.; Epstein, Jonathan I.; Netto, George J.; Antonescu, Cristina R.

2016-01-01

Xp11 translocation cancers include Xp11 translocation renal cell carcinoma (RCC), Xp11 translocation perivascular epithelioid cell tumor (PEComa), and melanotic Xp11 translocation renal cancer. In Xp11 translocation cancers, oncogenic activation of TFE3 is driven by the fusion of TFE3 with a number of different gene partners, however, the impact of individual fusion variant on specific clinicopathologic features of Xp11 translocation cancers has not been well defined. In this study, we analyze 60 Xp11 translocation cancers by fluorescence in situ hybridization (FISH) using custom BAC probes to establish their TFE3 fusion gene partner. In 5 cases RNA sequencing (RNA-seq) was also used to further characterize the fusion transcripts. The 60 Xp11 translocation cancers included 47 Xp11 translocation RCC, 8 Xp11 translocation PEComas, and 5 melanotic Xp11 translocation renal cancers. A fusion partner was identified in 53/60 (88%) cases, including 18 SFPQ (PSF), 16 PRCC, 12 ASPSCR1 (ASPL), 6 NONO, and 1 DVL2. We provide the first morphologic description of the NONO-TFE3 RCC, which frequently demonstrates sub-nuclear vacuoles leading to distinctive suprabasal nuclear palisading. Similar sub-nuclear vacuolization was also characteristic of SFPQ-TFE3 RCC, creating overlapping features with clear cell papillary RCC. We also describe the first RCC with a DVL2-TFE3 gene fusion, in addition to an extrarenal pigmented PEComa with a NONO-TFE3 gene fusion. Furthermore, among neoplasms with the SFPQ-TFE3, NONO-TFE3, DVL2-TFE3 and ASPL-TFE3 gene fusions, the RCC are almost always PAX8-positive, cathepsin K-negative by immunohistochemistry, whereas the mesenchymal counterparts (Xp11 translocation PEComas, melanotic Xp11 translocation renal cancers, and alveolar soft part sarcoma) are PAX8-negative, cathepsin K-positive. These findings support the concept that despite an identical gene fusion, the RCCs are distinct from the corresponding mesenchymal neoplasms, perhaps due to the

Familial Xp22.33-Xp22.12 deletion delineated by chromosomal microarray analysis causes proportionate short stature.

PubMed

Cho, Sung Yoon; Ki, Chang-Seok; Jang, Ja-Hyun; Sohn, Young Bae; Park, Sung Won; Kim, Se Hwa; Kim, Su Jin; Jin, Dong-Kyu

2012-06-01

Patients with Xp deletions have short stature and may have some somatic traits typical of Turner syndrome (TS), whereas gonadal function is generally preserved. In most studies of these patients, microsatellites have been used to determine the break point of the Xp deletion. In the present study, we describe the clinical, cytogenetic, and chromosomal microarray (CMA) analysis of a family with an Xp22.33-Xp22.12 deletion. Two female siblings, aged 8 years 9 months and 11 years 10 months, presented with short stature. The older sibling's height (index case) was 137.9 cm (-1.81 SDS) and the younger sibling's height was 118.6 cm (-2.13 SDS). The mother and both daughters had only a short stature; a skeletal survey showed normal findings except for mildly shortened 4th and 5th metacarpal bones. No features of TS were present. The deletion appeared terminal with a breakpoint within Xp22.2 located about 19.9 Mb from the Xp telomere. The deletion contained 102 protein-coding genes. A probe of the end breakage point was located at the 19,908,986th base of the X chromosome, and a probe of the marginal normal region near the breakage point was located at the 19,910,848th base of the X chromosome. Therefore, the breakage point was concluded to be located between these two probes. In summary, we report a familial case of an Xp deletion. The findings of our study may be helpful in further analyzing the phenotypes associated with Xp deletions. Copyright © 2012 Wiley Periodicals, Inc.

Renal cell carcinoma associated with Xp11.2 translocation/TFE3 gene fusions: clinical experience and literature review.

PubMed

He, Jian; Chen, Xiancheng; Gan, Weidong; Zhu, Bin; Fan, Xiangshan; Guo, Hongqian; Jia, Ruipeng

2015-01-01

To analyze the clinicopathological features of renal cell carcinoma (RCC) associated with Xp11.2 translocation/TFE3 gene fusions (Xp11.2 RCC) in our institution. We screened 983 RCC specimens. TFE3 immunohistochemical staining and FISH assay confirmed 22 Xp11.2 RCCs out of 65 suspicious cases. Clinicopathological and treatment outcomes of 22 patients were retrospectively analyzed. In total, 22 patients included 13 females and nine males with a mean age of 27 years. Ten patients showed gross hematuria. Treatments included surgeries, immunotherapy and molecular-targeted therapy. Seven cases were at stage III/IV and four cases had tumor thrombosis or distant metastasis. During a median follow-up of 34 months, 19 patients were alive while three died of distant metastasis. Xp11.2 RCC is rare and FISH proved a useful diagnostic tool. Surgical resection achieved favorable outcome for early disease. Adult patients at advanced stage had poorer outcomes even with postoperative adjuvant therapy.

A case of PSF-TFE3 gene fusion in Xp11.2 renal cell carcinoma with melanotic features.

PubMed

Zhan, He-Qin; Chen, Hong; Wang, Chao-Fu; Zhu, Xiong-Zeng

2015-03-01

Xp11.2 translocation renal cell carcinoma (Xp11.2 RCC) with PSF-TFE3 gene fusion is a rare neoplasm. Only 22 cases of Xp11.2 RCCs with PSF-TFE3 have been reported to date. We describe an additional case of Xp11.2 RCC with PSF-TFE3 showing melanotic features. Microscopically, the histologic features mimic clear cell renal cell carcinoma. However, the dark-brown pigments were identified and could be demonstrated as melanins. Immunohistochemically, the tumor cells were widely positive for CD10, human melanoma black 45, and TFE3 but negative for cytokeratins, vimentin, Melan-A, microphthalmia-associated transcription factor, smooth muscle actin, and S-100 protein. Genetically, we demonstrated PSF-TFE3 fusion between exon 9 of PSF and exon 5 of TFE3. The patient was free of disease with 50 months of follow-up. The prognosis of this type of tumor requires more cases because of limited number of cases and follow-up period. Xp11.2 RCC with PSF-TFE3 inevitably requires differentiation from other kidney neoplasms. Immunohistochemical and molecular genetic analyses are essential for accurate diagnosis. Copyright © 2015 Elsevier Inc. All rights reserved.

MDCT findings of renal cell carcinoma associated with Xp11.2 translocation and TFE3 gene fusion and papillary renal cell carcinoma.

PubMed

Woo, Sungmin; Kim, Sang Youn; Lee, Myoung Seok; Moon, Kyung Chul; Kim, See Hyung; Cho, Jeong Yeon; Kim, Seung Hyup

2015-03-01

OBJECTIVE. The purpose of this study was to compare the MDCT features of renal cell carcinoma (RCC) associated with Xp11.2 translocation and TFE3 gene fusion (Xp11 RCC) and papillary RCC. MATERIALS AND METHODS. The study included 19 and 39 patients with histologically proven Xp11 RCC and papillary RCC, respectively, who underwent multiphase renal MDCT before nephrectomy. CT findings were compared between Xp11 RCC and papillary RCC using the Student t test and chi-square test. Subgroup analyses of small (< 4 cm) renal masses for these features were performed. RESULTS. Patients with Xp11 RCC were younger (p < 0.001), and it was more prevalent in women (p = 0.007). Tumor size was greater in Xp11 RCC (p = 0.004) and more common in cystic change (p < 0.001). Calcification and unenhanced high-attenuating areas were more frequent in Xp11 RCC (p = 0.001 and 0.026, respectively). Xp11 RCCs were more prevalent in lymph node and distant metastasis (p < 0.001 and p = 0.031, respectively). Xp11 RCC and papillary RCC showed no significant difference in epicenter, margin, and venous and collecting duct invasion (p = 0.403-1.000). Although Xp11 RCC and papillary RCC had lower attenuation than the renal cortex on corticomedullary and early excretory phases (p < 0.001), only Xp11 RCCs were hyperattenuating to the cortex on the unenhanced phase (p < 0.001). Xp11 RCCs had significantly higher attenuation compared with papillary RCCs on all phases (p ≤ 0.02). Regarding small masses, cystic change, calcification, and lymph node metastasis were still more frequent in Xp11 RCCs (p ≤ 0.016). CONCLUSION. Greater size, more cystic change, calcification, high-attenuating areas on unenhanced imaging, and lymph node and distant metastasis were helpful for differentiating Xp11 RCC from papillary RCC.

Pseudocapsule of renal cell carcinoma associated with Xp11.2 translocation/TFE3 gene fusion: a clue for tumor enucleation?

PubMed

Cheng, Xiangming; He, Jian; Gan, Weidong; Fan, Xiangshan; Yang, Jun; Zhu, Bin; Guo, Hongqian

2015-01-01

To evaluate the feasibility and efficacy of tumor enucleation (TE) for patients with small renal cell carcinoma (RCC) associated with Xp11.2 translocation/TFE3 gene fusion (Xp11.2 RCC) by analyzing the pseudocapsule characteristics of Xp11.2 RCCs comparing with that of clear cell renal cell carcinoma (ccRCC). From June 2007 to February 2014, 22 patients with Xp11.2 RCC who were diagnosed by fluorescence in-situ hybridization polyclonal (FISH) assay and 32 patients with ccRCC treated in our institution were comparatively studied. 12 patients with ccRCC underwent radical nephrectomy (RN) and 20 received TE. Among 22 patients with Xp11.2 RCC, 19 were treated by RN and 3 by TE (1 by radiofrequency ablation assisted TE). Pseudocapsule and other clinicopathological characteristics of the two subtypes of RCC were compared. Survival of patients treated with different surgical methods was evaluated and compared. Pseudocapsule incidence of Xp11.2 RCC (14/22, 63.6%) was lower than that of ccRCC (32/32, 100%, P<0.001). However, pseudocapsule integrity rate of Xp11.2 RCC (10/14, 71.4%) was comparable with that of ccRCC (23/32, 71.9%, P=1.000). The 5-year overall survival of patients with ccRCC treated with RN and TE was 86% and 81%, respectively (P=0.845). Three patients with small Xp11.2 RCC performed well after TE. Over half Xp11.2 RCC had pseudocapsules, whose integrity rate was comparable to that of ccRCC. Treatment effectives of TE and RN were comparable in ccRCC. A preliminary attempt to treat small Xp11.2 RCC with intact pseudocapsule by using TE produced a favorable treatment outcome.

The multislice CT findings of renal carcinoma associated with XP11.2 translocation/TFE gene fusion and collecting duct carcinoma.

PubMed

Zhu, Qing-Qiang; Wang, Zhong-Qiu; Zhu, Wen-Rong; Chen, Wen-Xin; Wu, Jing-Tao

2013-04-01

Renal cell carcinoma associated with Xp11.2 translocation and TFE gene fusion (Xp11.2/TFE RCC), and collecting duct carcinoma (CDC) are uncommon subtypes of renal cell carcinomas. To investigate the multislice CT (MSCT) characteristics of these two tumor types. Nine patients with Xp11.2/TFE RCC and 10 patients with CDC were studied retrospectively. MSCT was undertaken to investigate differences in tumor characteristics and enhancement patterns. All patients had single tumors centered in the renal medulla. Two patients with each tumor type had lymph node involvement and there was a single case of hepatic metastasis (Xp11.2/TFE RCC). The mean tumor diameter of Xp11.2/TFE RCC tumors was significantly larger than for CDC tumors. Two patients with Xp11.2/TFE RCC had cystic components as did eight patients with CDC (P < 0.05). Calcifications were present in six patients, each with CDC. Clear tumor boundaries were visible in two patients with CDC and in nine with Xp11.2/TFE RCC (P < 0.05). The density of Xp11.2/TFE RCC tumors was greater than that of CDC tumors, normal renal cortex, or medulla on unenhanced CT. Enhancement was higher with Xp11.2/TFE RCC than with CDC tumors during all phases. Xp11.2/TFE RCC enhancement was higher than in the renal medulla during cortical and medullary phase but lower than in normal renal medulla during the delayed phase. CDC tumor enhancement was lower than that for normal renal medulla during all enhanced phases. Both tumor types originated from the renal medulla. Distinguishing features included density on unenhanced CT, enhancement patterns, and capsule signs. Identifying these differences may aid diagnosis.

Pseudocapsule of renal cell carcinoma associated with Xp11.2 translocation/TFE3 gene fusion: a clue for tumor enucleation?

PubMed Central

Cheng, Xiangming; He, Jian; Gan, Weidong; Fan, Xiangshan; Yang, Jun; Zhu, Bin; Guo, Hongqian

2015-01-01

Objectives: To evaluate the feasibility and efficacy of tumor enucleation (TE) for patients with small renal cell carcinoma (RCC) associated with Xp11.2 translocation/TFE3 gene fusion (Xp11.2 RCC) by analyzing the pseudocapsule characteristics of Xp11.2 RCCs comparing with that of clear cell renal cell carcinoma (ccRCC). Methods: From June 2007 to February 2014, 22 patients with Xp11.2 RCC who were diagnosed by fluorescence in-situ hybridization polyclonal (FISH) assay and 32 patients with ccRCC treated in our institution were comparatively studied. 12 patients with ccRCC underwent radical nephrectomy (RN) and 20 received TE. Among 22 patients with Xp11.2 RCC, 19 were treated by RN and 3 by TE (1 by radiofrequency ablation assisted TE). Pseudocapsule and other clinicopathological characteristics of the two subtypes of RCC were compared. Survival of patients treated with different surgical methods was evaluated and compared. Results: Pseudocapsule incidence of Xp11.2 RCC (14/22, 63.6%) was lower than that of ccRCC (32/32, 100%, P<0.001). However, pseudocapsule integrity rate of Xp11.2 RCC (10/14, 71.4%) was comparable with that of ccRCC (23/32, 71.9%, P=1.000). The 5-year overall survival of patients with ccRCC treated with RN and TE was 86% and 81%, respectively (P=0.845). Three patients with small Xp11.2 RCC performed well after TE. Conclusions: Over half Xp11.2 RCC had pseudocapsules, whose integrity rate was comparable to that of ccRCC. Treatment effectives of TE and RN were comparable in ccRCC. A preliminary attempt to treat small Xp11.2 RCC with intact pseudocapsule by using TE produced a favorable treatment outcome. PMID:26191243

Xp11.2 translocation renal cell carcinoma with PSF-TFE3 rearrangement.

PubMed

Zhong, Minghao; Weisman, Paul; Zhu, Bing; Brassesco, Maria; Yang, Youfeng; Linehan, W Marston; Merino, Maria J; Zhang, David; Rohan, Stephen; Cai, Dongming; Yang, Ximing

2013-06-01

Xp11.2 translocation renal cell carcinoma (Xp11.2 RCC) is a subtype of RCC characterized by translocations involving a breakpoint at the TFE3 gene (Xp11.2). Moderate to strong nuclear TFE3 immunoreactivity has been recognized as a specific diagnostic marker for this type of tumor. However, exclusive cytoplasmic localization of a TFE3 fusion protein was reported in UOK 145 cells, a cell line derived from an Xp11.2 RCC harboring the PSF-TFE3 translocation. If reproducible using immunohistochemistry (IHC), this finding would have important implications for pathologists in the diagnosis of Xp11.2 RCC, calling into question the specificity of nuclear immunoreactivity for TFE3 in these tumors. The purpose of this study was to determine whether the above-noted cytoplasmic localization of the TFE3 fusion protein could be reproduced using IHC. UOK 145 cells and fresh frozen tissue from 2 clinical cases of Xp11.2 RCC found to harbor the PSF-TFE3 gene rearrangement (by cytogenetic testing) were collected. All samples were subjected to histopathologic evaluation by board-certified pathologists, TFE3 IHC, reverse transcription polymerase chain reaction, and Sanger sequencing analysis. A strong nuclear TFE3 immunoreactivity was demonstrated in all samples including the UOK 145 cell line. No cytoplasmic immunoreactivity was seen. Reverse transcription polymerase chain reaction and Sanger sequencing confirmed the previously reported PSF-TFE3 gene fusion between exon 9 of PSF and exon 6 of TFE3 in the UOK 145 cell line and in one of 2 clinical cases of Xp11.2 RCC. A novel PSF-TFE3 gene fusion between exon 9 of PSF and exon 5 of TFE3 was detected in the second clinical case of Xp11.2 RCC.

Ultrasonographic Findings of Renal Cell Carcinomas Associated with Xp11.2 Translocation/TFE3 Gene Fusion.

PubMed

Ling, Wenwu; Ma, Xuelei; Luo, Yan; Chen, Linyan; Wang, Huiyao; Wang, Xiaoling; Chen, Ni; Zeng, Hao; Li, Yongzhong; Cai, Diming

2017-01-01

This study was to investigate the features of renal carcinomas associated with Xp11.2 translocations/TFE3 gene fusions (Xp11.2-RCC) on conventional ultrasound (US) and contrast-enhanced ultrasound (CEUS). US and CEUS features of twenty-two cases with histopathologically proven Xp11.2-RCC were retrospectively reviewed. 22 patients (11 males, 11 females) were included in this study, with a mean age of 28.3 ± 20.4 years. Eight tumors (36.3%, 8/22) were in left kidney, and 14 tumors (63.7%, 14/22) were in right kidney. All tumors (100%, 22/22) were mixed echogenicity type. 13 tumors (59.1%, 13/22) presented small dotted calcifications. The boundary of 14 tumors (63.6%, 14/22) was sharp and the other 8 tumors' (36.4%, 8/22) boundary was blurry. By CEUS, in early phase, the solid element of all tumors showed obvious enhancement. In delayed phase, 13 tumors showed hypoenhancement, seven tumors showed isoenhancement, and 2 tumors showed hyperenhancement. There were irregular nonenhancement areas in all tumors inside. By US and CEUS, when children and adolescents were found to have hyperechoic mixed tumor in kidney with sharp margin and calcification, and the tumors showed obvious enhancement and hypoenhancement with irregular nonenhancement areas in the tumor in early phase and delayed phase, respectively, Xp11.2-RCC should be suspected.

Ultrasonographic Findings of Renal Cell Carcinomas Associated with Xp11.2 Translocation/TFE3 Gene Fusion

PubMed Central

Zeng, Hao

2017-01-01

Objective This study was to investigate the features of renal carcinomas associated with Xp11.2 translocations/TFE3 gene fusions (Xp11.2-RCC) on conventional ultrasound (US) and contrast-enhanced ultrasound (CEUS). Methods US and CEUS features of twenty-two cases with histopathologically proven Xp11.2-RCC were retrospectively reviewed. Results 22 patients (11 males, 11 females) were included in this study, with a mean age of 28.3 ± 20.4 years. Eight tumors (36.3%, 8/22) were in left kidney, and 14 tumors (63.7%, 14/22) were in right kidney. All tumors (100%, 22/22) were mixed echogenicity type. 13 tumors (59.1%, 13/22) presented small dotted calcifications. The boundary of 14 tumors (63.6%, 14/22) was sharp and the other 8 tumors' (36.4%, 8/22) boundary was blurry. By CEUS, in early phase, the solid element of all tumors showed obvious enhancement. In delayed phase, 13 tumors showed hypoenhancement, seven tumors showed isoenhancement, and 2 tumors showed hyperenhancement. There were irregular nonenhancement areas in all tumors inside. Conclusions By US and CEUS, when children and adolescents were found to have hyperechoic mixed tumor in kidney with sharp margin and calcification, and the tumors showed obvious enhancement and hypoenhancement with irregular nonenhancement areas in the tumor in early phase and delayed phase, respectively, Xp11.2-RCC should be suspected. PMID:29333109

The influence of DNA repair on neurological degeneration, cachexia, skin cancer and internal neoplasms: autopsy report of four xeroderma pigmentosum patients (XP-A, XP-C and XP-D)

PubMed Central

2013-01-01

Background To investigate the association of DNA nucleotide excision repair (NER) defects with neurological degeneration, cachexia and cancer, we performed autopsies on 4 adult xeroderma pigmentosum (XP) patients with different clinical features and defects in NER complementation groups XP-A, XP-C or XP-D. Results The XP-A (XP12BE) and XP-D (XP18BE) patients exhibited progressive neurological deterioration with sensorineural hearing loss. The clinical spectrum encompassed severe cachexia in the XP-A (XP12BE) patient, numerous skin cancers in the XP-A and two XP-C (XP24BE and XP1BE) patients and only few skin cancers in the XP-D patient. Two XP-C patients developed internal neoplasms including glioblastoma in XP24BE and uterine adenocarcinoma in XP1BE. At autopsy, the brains of the 44 yr XP-A and the 45 yr XP-D patients were profoundly atrophic and characterized microscopically by diffuse neuronal loss, myelin pallor and gliosis. Unlike the XP-A patient, the XP-D patient had a thickened calvarium, and the brain showed vacuolization of the neuropil in the cerebrum, cerebellum and brainstem, and patchy Purkinje cell loss. Axonal neuropathy and chronic denervation atrophy of the skeletal muscles were observed in the XP-A patient, but not in the XP-D patient. Conclusions These clinical manifestations and autopsy findings indicate advanced involvement of the central and peripheral nervous system. Despite similar defects in DNA repair, different clinicopathological phenotypes are seen in the four cases, and therefore distinct patterns of neurodegeneration characterize XP-D, XP-A and XP-C patients. PMID:24252196

Zoom‐in comparative genomic hybridisation arrays for the characterisation of variable breakpoint contiguous gene syndromes

PubMed Central

Johnston, Jennifer J; Walker, Robert L; Davis, Sean; Facio, Flavia; Turner, Joyce T; Bick, David P; Daentl, Donna L; Ellison, Jay W; Meltzer, Paul S; Biesecker, Leslie G

2007-01-01

Contiguous gene syndromes cause disorders via haploinsufficiency for adjacent genes. Some contiguous gene syndromes (CGS) have stereotypical breakpoints, but others have variable breakpoints. In CGS that have variable breakpoints, the extent of the deletions may be correlated with severity. The Greig cephalopolysyndactyly contiguous gene syndrome (GCPS‐CGS) is a multiple malformation syndrome caused by haploinsufficiency of GLI3 and adjacent genes. In addition, non‐CGS GCPS can be caused by deletions or duplications in GLI3. Although fluorescence in situ hybridisation (FISH) can identify large deletion mutations in patients with GCPS or GCPS‐CGS, it is not practical for identification of small intragenic deletions or insertions, and it is difficult to accurately characterise the extent of the large deletions using this technique. We have designed a custom comparative genomic hybridisation (CGH) array that allows identification of deletions and duplications at kilobase resolution in the vicinity of GLI3. The array averages one probe every 730 bp for a total of about 14 000 probes over 10 Mb. We have analysed 16 individuals with known or suspected deletions or duplications. In 15 of 16 individuals (14 deletions and 1 duplication), the array confirmed the prior results. In the remaining patient, the normal CGH array result was correct, and the prior assessment was a false positive quantitative polymerase chain reaction result. We conclude that high‐density CGH array analysis is more sensitive than FISH analysis for detecting deletions and provides clinically useful results on the extent of the deletion. We suggest that high‐density CGH array analysis should replace FISH analysis for assessment of deletions and duplications in patients with contiguous gene syndromes caused by variable deletions. PMID:17098889

Adult-onset renal cell carcinoma associated with Xp11.2 translocations/TFE3 gene fusion with smooth muscle stroma and abnormal vessels.

PubMed

Kuroda, Naoto; Tamura, Masato; Tanaka, Yukichi; Hes, Ondrej; Michal, Michal; Inoue, Kaori; Ohara, Masahiko; Mizuno, Keiko; Lee, Gang-Hong

2009-07-01

Renal cell carcinoma (RCC) associated with Xp11.2 translocation/TFE3 gene fusion has been recently identified. Herein is presented a case of RCC with Xp11.2 translocations/TFE3 gene fusions with unusual histological findings. A 68-year-old Japanese woman was incidentally found to have a renal mass on CT. Histological examination showed clear cell neoplasm with alveolar and papillary growth patterns. The nuclear atypia corresponded to Fuhrman grade 3. Additionally, smooth muscle stroma was observed and abnormal vessels showing a heterogeniety in thickness were also identified. On immunohistochemistry, neoplastic cells were diffusely positive for transcription factor E3 (TFE3) and Melan A, and focally positive for CD10 and RCC marker. The smooth muscle stroma was positive for alpha-smooth muscle actin and h-caldesmon, but reverse transcription-polymerase chain reaction of the tumor using frozen material could not detect any previously reported chimeric transcripts including ASPL-TFE3, PRCC-TFE3, CLTC-TFE3, PSF-TFE3 or NoNo-TFE3. G-band karyotype was unsuccessful. Pathologists should pay attention to the afore-described unusual stromal reaction of adult-onset RCC associated with Xp11.2 translocations/TFE3 gene fusions.

Diagnostic pitfall on the histological spectrum of adult-onset renal carcinoma associated with Xp11.2 translocations/TFE3 gene fusions.

PubMed

Kuroda, Naoto; Katto, Kazunobu; Tanaka, Yukichi; Yamaguchi, Tadanori; Inoue, Kaori; Ohara, Masahiko; Mizuno, Keiko; Hes, Ondrej; Michal, Michal; Lee, Gang-Hong

2010-06-01

Renal cell carcinoma (RCC) associated with Xp11.2 translocation/TFE3 gene fusion recently has been found. In this article, we demonstrate an unusual features of such a case. A 73-year-old Japanese woman presented with macroscopic hematuria. The imaging examinations disclosed the renal tumor. Histological examination showed the finding of ASPL-TFE3 RCC, which was characterized by papillary, alveolar, or solid growth of voluminous cell with clear and eosinophilic cells, and stromal psammoma body and hyaline nodules. Additionally, shrunken nuclei, thick cell border, and perinuclear clearing characteristic of chromophobe renal cell carcinoma were observed in the alveolar growth area and the transitional zone between stromal hyalinization, and osseous metaplasia was identified. Immunohistochemically, nuclei of tumorous cell were diffusely positive for TFE3. A RT-PCR study revealed the ASPL-TFE3 chimeric transcript. Finally, pathologists should recognize that the histology of RCC associated with Xp11.2 translocation/TFE3 gene fusion may focally resemble that of chromophobe RCC, but TFE3 immunohistochemistry and molecular genetic study may be helpful in the differential diagnosis. Moreover, osseous metaplasia as well as psammoma bodies should be added to the histological spectrum of the stromal change in RCC associated with Xp11.2 translocations/TFE3 gene fusions.

Temsirolimus in the treatment of renal cell carcinoma associated with Xp11.2 translocation/TFE gene fusion proteins: a case report and review of literature.

PubMed

Parikh, Jigarkumar; Coleman, Teresa; Messias, Nidia; Brown, James

2009-12-28

Xp11.2 translocation renal cell carcinomas (TRCCs) are a rare family of tumors newly recognized by the World Health Organization (WHO) in 2004. These tumors result in the fusion of partner genes to the TFE3 gene located on Xp11.2. They are most common in the pediatric population, but have been recently implicated in adult renal cell carcinoma (RCC) presenting at an early age. TFE3-mediated direct transcriptional upregulation of the Met tyrosine kinase receptor triggers dramatic activation of downstream signaling pathways including the protein kinase B (Akt)/phosphatidylinositol-3 kinase (PI3K) and mammalian target of rapamycin (mTOR) pathways. Temsirolimus is an inhibitor of mammalian target of rapamycin (mTOR) kinase, a component of intracellular signaling pathways involved in the growth and proliferation of malignant cells. Here we present a case of a 22-year old female who has been treated with temsirolimus for her Xp11.2/TFE3 gene fusion RCC.

Temsirolimus in the treatment of renal cell carcinoma associated with Xp11.2 translocation/TFE gene fusion proteins: a case report and review of literature

PubMed Central

Parikh, Jigarkumar; Coleman, Teresa; Messias, Nidia; Brown, James

2009-01-01

Xp11.2 translocation renal cell carcinomas (TRCCs) are a rare family of tumors newly recognized by the World Health Organization (WHO) in 2004. These tumors result in the fusion of partner genes to the TFE3 gene located on Xp11.2. They are most common in the pediatric population, but have been recently implicated in adult renal cell carcinoma (RCC) presenting at an early age. TFE3-mediated direct transcriptional upregulation of the Met tyrosine kinase receptor triggers dramatic activation of downstream signaling pathways including the protein kinase B (Akt)/phosphatidylinositol-3 kinase (PI3K) and mammalian target of rapamycin (mTOR) pathways. Temsirolimus is an inhibitor of mammalian target of rapamycin (mTOR) kinase, a component of intracellular signaling pathways involved in the growth and proliferation of malignant cells. Here we present a case of a 22-year old female who has been treated with temsirolimus for her Xp11.2/TFE3 gene fusion RCC. PMID:21139932

A family with X-linked optic atrophy linked to the OPA2 locus Xp11.4-Xp11.2.

PubMed

Katz, Bradley J; Zhao, Yu; Warner, Judith E A; Tong, Zongzhong; Yang, Zhenglin; Zhang, Kang

2006-10-15

Autosomal dominant optic atrophy (ADOA) is the most common inherited optic atrophy. Clinical features of ADOA include a slowly progressive bilateral loss of visual acuity, constriction of peripheral visual fields, central scotomas, and color vision abnormalities. Although ADOA is the most commonly inherited optic atrophy, autosomal recessive, X-linked, mitochondrial, and sporadic forms have also been reported. Four families with X-linked optic atrophy (XLOA) were previously described. One family was subsequently linked to Xp11.4-Xp11.2 (OPA2). This investigation studied one multi-generation family with an apparently X-linked form of optic atrophy and compared their clinical characteristics with those of the previously described families, and determined whether this family was linked to the same genetic locus. Fifteen individuals in a three-generation Idaho family underwent complete eye examination, color vision testing, automated perimetry, and fundus photography. Polymorphic markers were used to genotype each individual and to determine linkage. Visual acuities ranged from 20/30 to 20/100. All affected subjects had significant optic nerve pallor. Obligate female carriers were clinically unaffected. Preliminary linkage analysis (LOD score = 1.8) revealed that the disease gene localized to the OPA2 locus on Xp11.4-Xp11.2. Four forms of inherited optic neuropathy, ADOA, autosomal recessive optic atrophy (Costeff Syndrome), Leber hereditary optic neuropathy, and Charcot-Marie-Tooth disease with optic atrophy, are associated with mitochondrial dysfunction. Future identification of the XLOA gene will reveal whether this form of optic atrophy is also associated with a mitochondrial defect. Identification of the XLOA gene will advance our understanding of the inherited optic neuropathies and perhaps suggest treatments for these diseases. An improved understanding of inherited optic neuropathies may in turn advance our understanding of acquired optic nerve diseases, such

Xp11.2 translocation renal carcinoma with placental metastasis: a case report.

PubMed

Bovio, Ian M; Allan, Robert W; Oliai, Bahram R; Hampton, Troy; Rush, Demaretta S

2011-02-01

Renal cell carcinomas with sporadic Xp11.2 translocations are uncommon malignancies in children and young adults associated with several different reciprocal translocations involving the TFE3 gene located on chromosome Xp11.2. Placental metastases are extremely rare, with only a handful of cases reported. This study reports the case of a 20-year-old woman with an Xp11.2 translocation renal carcinoma that metastasized to the placenta. This is the first reported case of a renal cell carcinoma metastatic to the placenta and highlights the aggressive behavior of Xp11 translocation renal cell carcinomas.

Identification and characterization of a novel serine-threonine kinase gene from the Xp22 region.

PubMed

Montini, E; Andolfi, G; Caruso, A; Buchner, G; Walpole, S M; Mariani, M; Consalez, G; Trump, D; Ballabio, A; Franco, B

1998-08-01

Eukaryotic protein kinases are part of a large and expanding family of proteins. Through our transcriptional mapping effort in the Xp22 region, we have isolated and sequenced the full-length transcript of STK9, a novel cDNA highly homologous to serine-threonine kinases. A number of human genetic disorders have been mapped to the region where STK9 has been localized including Nance-Horan (NH) syndrome, oral-facial-digital syndrome type 1 (OFD1), and a novel locus for nonsyndromic sensorineural deafness (DFN6). To evaluate the possible involvement of STK9 in any of the above-mentioned disorders, a 2416-bp full-length cDNA was assembled. The entire genomic structure of the gene, which is composed of 20 coding exons, was determined. Northern analysis revealed a transcript larger than 9.5 kb in several tissues including brain, lung, and kidney. The mouse homologue (Stk9) was identified and mapped in the mouse in the region syntenic to human Xp. This location is compatible with the location of the Xcat mutant, which shows congenital cataracts very similar to those observed in NH patients. Sequence homologies, expression pattern, and mapping information in both human and mouse make STK9 a candidate gene for the above-mentioned disorders. Copyright 1998 Academic Press.

Renal Cell Carcinoma Associated with Xp11.2 Translocation/TFE3 Gene Fusion: A Rare Case Report with Review of the Literature.

PubMed

Ahluwalia, Puneet; Nair, Balagopal; Kumar, Ginil

2013-01-01

Introduction. The recently recognized renal cell carcinomas associated with Xp11.2 translocations are rare tumors predominantly reported in children. Chromosome Xp11.2 translocation results in gene fusion related to transcription factor E3 (TFE3) that plays an important role in proliferation and survival. Case Report. Herein, we present two cases of a TFE3 translocation-associated RCC in young female adults, one detected incidentally and the other one presenting with gross hematuria. Tumor is characterized by immunohistochemistry and a literature review with optimal treatment regimen is presented. Discussion. Xp11.2 translocation RCCs in adult patients are associated with advanced stages, large tumors, and extracapsular disease and usually have an aggressive clinical course. Conclusion. In TFE3 RCC, the genetic background may not only contribute to tumorigenesis, but also determine the response to chemotherapy and targeted therapy. Therefore it is necessary to diagnose this tumor entity accurately. Because of the small number of TFE3 gene fusion-related renal tumors described in the literature, the exact biologic behavior and impact of current treatment modalities remain to be uncertain.

Renal Cell Carcinoma Associated with Xp11.2 Translocation/TFE3 Gene Fusion: A Rare Case Report with Review of the Literature

PubMed Central

Ahluwalia, Puneet; Nair, Balagopal; Kumar, Ginil

2013-01-01

Introduction. The recently recognized renal cell carcinomas associated with Xp11.2 translocations are rare tumors predominantly reported in children. Chromosome Xp11.2 translocation results in gene fusion related to transcription factor E3 (TFE3) that plays an important role in proliferation and survival. Case Report. Herein, we present two cases of a TFE3 translocation-associated RCC in young female adults, one detected incidentally and the other one presenting with gross hematuria. Tumor is characterized by immunohistochemistry and a literature review with optimal treatment regimen is presented. Discussion. Xp11.2 translocation RCCs in adult patients are associated with advanced stages, large tumors, and extracapsular disease and usually have an aggressive clinical course. Conclusion. In TFE3 RCC, the genetic background may not only contribute to tumorigenesis, but also determine the response to chemotherapy and targeted therapy. Therefore it is necessary to diagnose this tumor entity accurately. Because of the small number of TFE3 gene fusion-related renal tumors described in the literature, the exact biologic behavior and impact of current treatment modalities remain to be uncertain. PMID:24455396

Location interval at Xp22.3 for X-linked chondrodysplasia punctata

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sheffield, L.; Hutchison, W.; Holloway, A.

1994-09-01

The literature shows that there is a gene for chondropdysplasia punctata (CDP) located at Xp22.3 from the study of chromosomal rearrangements involving Xp. It is also suspected that there are genes for short stature and mental retardation nearby. Petit has described a family of brachytelephalangic CDP that was due to a submicroscopic interstitial deletion of Xp22.3. Symmetrical (mild) CDP seems to be identical to brachytelephalangic CDP clinically, has variable features of short stature and mental retardation, and has a preponderance of affected males. We describe results using DNA probes from Xp22.3 in 10 patients with radiologically proven symmetrical CDP. Othermore » known genes in this region have a high proportion of deletions as we screened our patients for deletions in DXYS20, MIC2, PABX, DXYS159X, DXS283, DXS285, J502(PCR), DXS31, DXS43 (listed distally to proximally). No deletions were found. We have also studied a fetus with proven CDP who has a X,Y translocation (46,V,t(X;Y)(p22.3;q12)mat). This patient was deleted for all distal probes up to J502(PCR). It is not yet known where the breakpoint lies but it may be just proximal to the CDP gene. The results of the 10 symmetrical CDPs and the X;Y translocation fetus are presented with further definition of the X chromosomal breakpoint in the translocation.« less

[MRI findings of renal cell carcinoma associated with Xp11.2 translocations/TFE3 gene fusions].

PubMed

Zhong, Y; Wang, H Y; Chen, X; Guo, A T; Ma, L; Wang, Y W; Ye, H Y

2016-09-06

Objective: To analyze MRI findings of renal cell carcinoma associated with Xp11.2 translocation-TFE gene fusion(Xp11.2 RCC). Methods: MR imaging features of eleven patients with pathologically-proved Xp11.2 RCC were retrospectively analyzed from December 2008 to December 2015. The following MRI features of the lesions were analyzed in the study: location, maximal diameter, signal intensity, hemorrhage, necrosis, cystic change, enhancement features and metastasis. The data was analyzed by using t test. Results: Four men and seven women (mean age, 35.2 years; age range, 15-49 years) were included. Tumors occurred in the right kidney in 5 cases and the left kidney in 6 cases. On T 1 WI tumors showed heterogeneously hypo-intensity and iso-intensity, hyper-intensity in 10 cases, 1 cases, respectively. On T 2 WI tumors showed heterogeneously slight hypo-intensity, heterogeneously slight hyper-intensity and hyper-intensity in 6 cases, 4 cases, 1 case, respectively. On DWI tumors showed hyper-intensity and heterogeneously slight hype-intensity in 2 cases, 9 cases, respectively. ADC value of the tumors were statistically significant lower than that of renal cortex(×10 -3 mm 2 /s)(1.35±0.20 vs 2.09±0.11, P <0.05). Imaging findings were suggestive of hemorrhage( n =4) or necrosis ( n =1) or cystic change ( n =6) or lipid( n =1) in the tumors. On dynamic contrast-enhanced imaging, tumors showed lower signal intensity change (96%±93%, 110%±86% and 103%±46%, respectively) than did renal cortex (285%±109%, 254%±97% and 225%±90%, respectively) ( P <0.05). Tumor capsule showed in 7 cases. Enlarged lymph node was found in renal hilum in one case. Conclusion: MRI findings may show characteristic features of Xp11.2 RCC combined with patients' age and assist in preoperative correct diagnosis.

Dataset of proinflammatory cytokine and cytokine receptor gene expression in rainbow trout (Oncorhynchus mykiss) measured using a novel GeXP multiplex, RT-PCR assay

USDA-ARS?s Scientific Manuscript database

A GeXP multiplex, RT-PCR assay was developed and optimized that simultaneously measures expression of a suite of immune-relevant genes in rainbow trout (Oncorhynchus mykiss), concentrating on tumor necrosis factor and interleukin-1 ligand/receptor systems and acute phase response genes. The dataset ...

Sirt1 suppresses RNA synthesis after UV irradiation in combined xeroderma pigmentosum group D/Cockayne syndrome (XP-D/CS) cells.

PubMed

Vélez-Cruz, Renier; Zadorin, Anton S; Coin, Frédéric; Egly, Jean-Marc

2013-01-15

Specific mutations in the XPD subunit of transcription factor IIH result in combined xeroderma pigmentosum (XP)/Cockayne syndrome (CS), a severe DNA repair disorder characterized at the cellular level by a transcriptional arrest following UV irradiation. This transcriptional arrest has always been thought to be the result of faulty transcription-coupled repair. In the present study, we showed that, following UV irradiation, XP-D/CS cells displayed a gross transcriptional dysregulation compared with "pure" XP-D cells or WT cells. Furthermore, global RNA-sequencing analysis showed that XP-D/CS cells repressed the majority of genes after UV, whereas pure XP-D cells did not. By using housekeeping genes as a model, we demonstrated that XP-D/CS cells were unable to reassemble these gene promoters and thus to restart transcription after UV irradiation. Furthermore, we found that the repression of these promoters in XP-D/CS cells was not a simple consequence of deficient repair but rather an active heterochromatinization process mediated by the histone deacetylase Sirt1. Indeed, RNA-sequencing analysis showed that inhibition of and/or silencing of Sirt1 changed the chromatin environment at these promoters and restored the transcription of a large portion of the repressed genes in XP-D/CS cells after UV irradiation. Our work demonstrates that a significant part of the transcriptional arrest displayed by XP-D/CS cells arises as a result of an active repression process and not simply as a result of a DNA repair deficiency. This dysregulation of Sirt1 function that results in transcriptional repression may be the cause of various severe clinical features in patients with XP-D/CS that cannot be explained by a DNA repair defect.

[A case of xp11.2 translocation renal cell carcinoma].

PubMed

Horie, Kengo; Kikuchi, Mina; Miwa, Kosei; Minamidate, Yuzuru; Yokoi, Shigeaki; Nakano, Masahiro; Deguchi, Takashi; Ehara, Hidetoshi; Asano, Nami; Hirose, Yoshinobu

2011-03-01

Xp11.2/TFE3 translocation renal cell carcinoma (RCC), a recently classified distinct subtype, is a rare tumor that usually affects children and adolescents. The morphology and biological behavior are not widely recognized, Xp11.2 translocation RCC is suggestive of early metastases despite the small tumor size. The definitive diagnosis requires the evidence of several different reciprocal translocations involving the TFE3 gene located on chromosome Xp11.2. Here, we present a case of Xp11.2 translocation RCC in an 18-yearold male. He was referred to our hospital because of a right renal tumor with macroscopic hematuria and right flank colic. The radiographic evaluation including magnetic resonance imaging (MRI) suggested it to be a typical papillary renal cell carcinoma or benign renal tumor. He underwent laparoscopic nephrectomy against the repeat symptom in spite of small tumor (3.5 cm in diameter). The immunohistochemical study revealed nuclear staining for TFE3 protein in the cancer cells. The urologic and radiologic outcomes were satisfactory after more than 1 year of follow-up.

[Renal cell carcinoma associated with Xp11.2 translocations/TFE3 gene fusions: a study of 11 cases and review of literature].

PubMed

Rao, Qiu; Zhou, Xiao-jun; Wu, Bo; Ma, Heng-hui; Zhou, Hang-bo; Liu, Xiao-hong; Chen, Jie-yu

2007-04-01

To study the clinicopathologic features, differential diagnosis and prognosis of renal cell carcinoma associated with Xp11.2 translocations/TFE3 gene fusions. The histopathologic findings and immunophenotype of 11 cases of renal cell carcinoma associated with Xp11.2 translocations/TFE3 gene fusions were studied. Follow-up data (ranged from 10 to 112 months) were also analyzed. There were a total of 7 females and 4 males. The age of patients ranged from 8 to 26 years (mean = 16.3 years). The diameter of the tumors varied from 2.5 to 6.0 cm. Histologically, two morphologic patterns were seen. The first pattern consisted of alveolar, papillary or nested architecture. The tumor cells contained voluminous, clear to eosinophilic cytoplasm, distinct cell borders, vesicular chromatin, and prominent nucleoli. Psammoma bodies were frequently found and could be abundant. In contrast, the second pattern was composed of nested and compact architecture. The tumor cells possessed less abundant cytoplasm and inconspicuous nucleoli. Few psammoma bodies were detected. Immunohistochemical study showed that all cases strongly expressed TFE3, CD10 and P504s. Variable positivity for pan-cytokeratin, epithelial membrane antigen and vimentin was also noted. None of them expressed CK7, Ksp-cadherin and CD117. Renal cell carcinoma associated with Xp11.2 translocations/TFE3 gene fusions is a newly described but rarely encountered subtype of renal cell carcinoma. Pathologic diagnosis can be established when taken age of the patients, histopathologic findings and immunoreactivity for TFE3 protein into consideration.

[Differential diagnosis between renal cell carcinoma associated with XP11.2 translocation/TFE gene fusion and papillary renal cell carcinoma based on CT and MRI findings].

PubMed

Zhu, Qingqiang; Zhu, Wenrong; Wu, Jingtao; Fu, Jianxiong; Chen, Wenxin; Wang, Zhongqiu

2014-05-20

To comparative study of CT and MRI appearances in renal cell carcinoma associated with XP11.2 translocation/TFE gene fusion (XP11.2 RCC) and papillary renal cell carcinoma (PRCC). 12 patients with XP11.2 RCC and 18 patients with PRCC were retrospectively studied, and the data was analyzed by AVONA and chi-square text. 12 patients with XP11.2 RCC and 18 patients with PRCC, cystic components (2 vs 11, P < 0.05), calcification (0 vs 6, P < 0.05), hemorrhage (9 vs 5, P < 0.05), homogeneous enhancement (10 vs 7, P < 0.05) and had lymph node (3 vs 0) or hepatic metastasis (1vs 0) (P < 0.05). On unenhanced CT, the density of XP11.2 RCC was greater than PRCC, normal renal cortex or medulla (P < 0.05). Their degree of enhancement were less than normal renal cortex on all enhanced phases (P < 0.05). The enhancement degree of XP11.2 RCC was higher than PRCC (on all phases) and renal medulla (on cortical and medullary phase) (P < 0.05), but less than normal renal medulla on the delayed phase (P < 0.05). The enhancement degree of PRCC was lower than renal medulla on all phases (P < 0.05). The XP11.2 RCC was isointense on T1-weighted imaging, hypointense on T2-weighted imaging. The PRCC was isointense or hypointense on T1-weighted imaging, isointense on T2-weighted imaging. The CT and MRI could show imagings features of XP11.2 RCC and PRCC, and these features were helpful in predicting a specific subtype of renal cell carcinoma.

Xp11.2 microduplications including IQSEC2, TSPYL2 and KDM5C genes in patients with neurodevelopmental disorders

PubMed Central

Moey, Ching; Hinze, Susan J; Brueton, Louise; Morton, Jenny; McMullan, Dominic J; Kamien, Benjamin; Barnett, Christopher P; Brunetti-Pierri, Nicola; Nicholl, Jillian; Gecz, Jozef; Shoubridge, Cheryl

2016-01-01

Copy number variations are a common cause of intellectual disability (ID). Determining the contribution of copy number variants (CNVs), particularly gains, to disease remains challenging. Here, we report four males with ID with sub-microscopic duplications at Xp11.2 and review the few cases with overlapping duplications reported to date. We established the extent of the duplicated regions in each case encompassing a minimum of three known disease genes TSPYL2, KDM5C and IQSEC2 with one case also duplicating the known disease gene HUWE1. Patients with a duplication encompassing TSPYL2, KDM5C and IQSEC2 without gains of nearby SMC1A and HUWE1 genes have not been reported thus far. All cases presented with ID and significant deficits of speech development. Some patients also manifested behavioral disturbances such as hyperactivity and attention-deficit/hyperactivity disorder. Lymphoblastic cell lines from patients show markedly elevated levels of TSPYL2, KDM5C and SMC1A, transcripts consistent with the extent of their CNVs. The duplicated region in our patients contains several genes known to escape X-inactivation, including KDM5C, IQSEC2 and SMC1A. In silico analysis of expression data in selected gene expression omnibus series indicates that dosage of these genes, especially IQSEC2, is similar in males and females despite the fact they escape from X-inactivation in females. Taken together, the data suggest that gains in Xp11.22 including IQSEC2 cause ID and are associated with hyperactivity and attention-deficit/hyperactivity disorder, and are likely to be dosage-sensitive in males. PMID:26059843

Xp11.2 microduplications including IQSEC2, TSPYL2 and KDM5C genes in patients with neurodevelopmental disorders.

PubMed

Moey, Ching; Hinze, Susan J; Brueton, Louise; Morton, Jenny; McMullan, Dominic J; Kamien, Benjamin; Barnett, Christopher P; Brunetti-Pierri, Nicola; Nicholl, Jillian; Gecz, Jozef; Shoubridge, Cheryl

2016-03-01

Copy number variations are a common cause of intellectual disability (ID). Determining the contribution of copy number variants (CNVs), particularly gains, to disease remains challenging. Here, we report four males with ID with sub-microscopic duplications at Xp11.2 and review the few cases with overlapping duplications reported to date. We established the extent of the duplicated regions in each case encompassing a minimum of three known disease genes TSPYL2, KDM5C and IQSEC2 with one case also duplicating the known disease gene HUWE1. Patients with a duplication encompassing TSPYL2, KDM5C and IQSEC2 without gains of nearby SMC1A and HUWE1 genes have not been reported thus far. All cases presented with ID and significant deficits of speech development. Some patients also manifested behavioral disturbances such as hyperactivity and attention-deficit/hyperactivity disorder. Lymphoblastic cell lines from patients show markedly elevated levels of TSPYL2, KDM5C and SMC1A, transcripts consistent with the extent of their CNVs. The duplicated region in our patients contains several genes known to escape X-inactivation, including KDM5C, IQSEC2 and SMC1A. In silico analysis of expression data in selected gene expression omnibus series indicates that dosage of these genes, especially IQSEC2, is similar in males and females despite the fact they escape from X-inactivation in females. Taken together, the data suggest that gains in Xp11.22 including IQSEC2 cause ID and are associated with hyperactivity and attention-deficit/hyperactivity disorder, and are likely to be dosage-sensitive in males.

First reported case of intrachromosomal cryptic inv dup del Xp in a boy with developmental retardation.

PubMed

Dupont, Celine; Lebbar, Aziza; Teinturier, Cecile; Baverel, Françoise; Viot, Geraldine; Le Tessier, Dominique; Le Bozec, Jerome; Cuisset, Laurence; Dupont, Jean-Michel

2007-06-01

We report here on a 6-year-old boy referred to the laboratory for karyotyping and SHOX microdeletion testing. The most significant clinical findings in this boy were small stature, Madelung deformity, facial dysmorphism, mild mental retardation and behavioral problems. R-, G- and RTBG-banding chromosome analysis showed a normal male karyotype. Fine molecular characterization, by FISH, of terminal Xp microdeletion revealed an associated partial duplication. Further refinement of the molecular analysis indicated an inverted duplication of the Xp22.31-Xp22.32 (13.7 Mb) region including the STS, VCX-A and KAL1 genes, associated with a terminal Xp deletion Xp22.33-Xpter (3.6 Mb) encompassing the SHOX and ARSE genes. Such rearrangements have been characterized for other chromosomal pairs, but this is the first reported male patient involving the short arm of the X chromosome. Molecular analysis of the maternal and patient's microsatellite markers showed interchromatid mispairing leading to non-allelic homologous recombination to be the most likely mechanism underlying this rearrangement. This case highlights the importance of clinically driven FISH investigations in order to uncover cryptic micro-rearrangements. Copyright (c) 2007 Wiley-Liss, Inc.

Nephron-sparing surgery in the treatment of pediatric renal cell carcinoma associated with Xp11.2 translocation/TFE3 gene fusions.

PubMed

Liu, Chao; Zhang, Weiping; Song, Hongcheng

2017-09-01

To investigate the safety and efficacy of nephron-sparing surgery (NSS) in the treatment of pediatric Xp11.2 translocation renal cell carcinoma (RCC). Clinical characteristics of 9 RCC children (7 males and 2 females) with Xp11.2 translocation who received NSS between January 1973 and December 2015 were retrospectively analyzed. The mean age was 7.8years (range: 4.5-13.5years). Xp11.2 translocation RCC was found in the left side in 4 patients and right in 5. 3 tumors were located in the upper pole of the kidney, 1 in the middle dorsal, 1 in the middle ventral and 4 in the lower pole. RCC presented with painless gross hematuria in 4 patients, abdominal mass in 1, and as an incidental finding by ultrasound examination in 4 patients. The mean course of hematuria was 3months (range: 1-7months). The mean tumor diameters were 3.7cm (range: 2.2-6.9cm). All the patients received NSS with open transperitoneal approach. The mean operative time and estimated blood loss were 115min and 40ml, respectively. The time of renal pedicle clamping was 19-25min (mean: 21.5min). No complications (such as leakage of urine, prolonged drainage or secondary bleeding) were noted. No patients experienced local recurrence during the mean of 50.1-month follow-up (range: 13-117months). Intravenous urography (IVU) or contrast-enhanced CT was conducted at 6months after surgery which showed favorable kidney function in all patients. Xp11.2 translocation RCC is a predominant pathological but biologically inert type of pediatric RCC. For Xp11.2 translocation RCC sized <4-7cm in diameter and located in one pole, NSS is safe and feasible. Treatment Studies, LEVEL IV. Copyright © 2017 Elsevier Inc. All rights reserved.

Xeroderma Pigmentosum: Low Prevalence of Germline XPA Mutations in a Brazilian XP Population

PubMed Central

Santiago, Karina Miranda; França de Nóbrega, Amanda; Rocha, Rafael Malagoli; Rogatto, Silvia Regina; Achatz, Maria Isabel

2015-01-01

Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder characterized by DNA repair defects that cause photophobia, sunlight-induced cancers, and neurodegeneration. Prevalence of germline mutations in the nucleotide excision repair gene XPA vary significantly in different populations. No Brazilian patients have been reported to carry a germline mutation in this gene. In this study, the germline mutational status of XPA was determined in Brazilian patients exhibiting major clinical features of XP syndrome. The study was conducted on 27 unrelated patients from select Brazilian families. A biallelic inactivating transition mutation c.619C>T (p.Arg207Ter) was identified in only one patient with a history of neurological impairment and mild skin abnormalities. These findings suggest that XP syndrome is rarely associated with inherited disease-causing XPA mutations in the Brazilian population. Additionally, this report demonstrates the effectiveness of genotype-phenotype correlation as a valuable tool to guide direct genetic screening. PMID:25913378

Xeroderma pigmentosum: low prevalence of germline XPA mutations in a Brazilian XP population.

PubMed

Santiago, Karina Miranda; França de Nóbrega, Amanda; Rocha, Rafael Malagoli; Rogatto, Silvia Regina; Achatz, Maria Isabel

2015-04-22

Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder characterized by DNA repair defects that cause photophobia, sunlight-induced cancers, and neurodegeneration. Prevalence of germline mutations in the nucleotide excision repair gene XPA vary significantly in different populations. No Brazilian patients have been reported to carry a germline mutation in this gene. In this study, the germline mutational status of XPA was determined in Brazilian patients exhibiting major clinical features of XP syndrome. The study was conducted on 27 unrelated patients from select Brazilian families. A biallelic inactivating transition mutation c.619C>T (p.Arg207Ter) was identified in only one patient with a history of neurological impairment and mild skin abnormalities. These findings suggest that XP syndrome is rarely associated with inherited disease-causing XPA mutations in the Brazilian population. Additionally, this report demonstrates the effectiveness of genotype-phenotype correlation as a valuable tool to guide direct genetic screening.

[Application of polyclonal break-apart probes in the diagnosis of Xp11.2 translocation renal cell carcinoma].

PubMed

Chen, Xiancheng; Gan, Weidong; Ye, Qing; Yang, Jun; Guo, Hongqian; Li, Dongmei

2014-12-16

To explore the value of self-designed fluorescent in situ hybridization (FISH) polyclonal break-apart probes specific for TFE3 gene in the diagnosis of Xp11.2 translocation renal cell carcinoma. All tissue samples were collected from 2006 to 2013, including Xp11.2 translocation renal cell carcinoma (n = 10), renal clear cell carcinoma (n = 10) and renal papillary cell carcinoma (n = 10). FISH was conducted for paraffin-embedded tumor tissue sections with probes. The types of fluorescence were observed by fluorescent microscopy to determine the existence or non-existence of translocated TFE3 gene. All sections were successfully probed. The split red and green signals within a single nucleus were detected simultaneously in 9 cases of Xp11.2 translocation renal cell carcinoma as diagnosed by traditional pathological and immunohistochemical methods. And it was consistent with the initial diagnosis. Detection of fusion signal in 1/10 and negative FISH result did not conform to the initial diagnosis. The fluorescent types of renal clear cell carcinoma and renal papillary cell carcinoma were all fusion signals. FISH tests were negative for renal clear and papillary cell carcinomas. Xp11.2 translocation renal cell carcinomas diagnosed by traditional pathological and immunohistochemical methods are sometimes misdiagnosed. Detecting the translocation of TFE3 gene with FISH polyclonal break-apart probes is both accurate and reliable for diagnosing Xp11.2 translocation renal cell carcinoma.

Cardiopulmonary bypass-assisted surgery for the treatment of Xp11.2 translocation/TFE3 gene fusion renal cell carcinoma with a tumor thrombus within the inferior vena cava: A case report.

PubMed

Zhu, Guanchen; Qiu, Xuefeng; Chen, Xianchen; Liu, Guangxiang; Zhang, Gutian; Gan, Weidong; Guo, Hongqian

2015-12-01

Renal cell carcinoma (RCC) accounts for 85-90% of kidney cancers, which in turn account for 2-3% of all malignant tumors in adults. Xp11.2 translocation/TFE3 gene fusion RCC is currently classified as a distinct type of RCC. RCC is capable of invading the renal vein and inferior vena cava to form a tumor thrombus. The incidence of RCC with tumor thrombi within the renal vein or inferior vena cava is 7-10% in China. In the present case report, the patient underwent radical resection of the renal tumor and removal of the tumor thrombus, assisted by cardiopulmonary bypass, for the treatment of Xp11.2 translocation/TFE3 gene fusion RCC. The patient was followed-up for 12 months subsequent to treatment. The patient's renal function remained within the normal range, and computed tomography examination revealed no evidence of disease recurrence or metastases. The present case report aimed to provide a reference for the development of guidelines for the diagnosis and treatment of Xp11.2 translocation/TFE3 gene fusion RCC.

Cardiopulmonary bypass-assisted surgery for the treatment of Xp11.2 translocation/TFE3 gene fusion renal cell carcinoma with a tumor thrombus within the inferior vena cava: A case report

PubMed Central

ZHU, GUANCHEN; QIU, XUEFENG; CHEN, XIANCHEN; LIU, GUANGXIANG; ZHANG, GUTIAN; GAN, WEIDONG; GUO, HONGQIAN

2015-01-01

Renal cell carcinoma (RCC) accounts for 85–90% of kidney cancers, which in turn account for 2–3% of all malignant tumors in adults. Xp11.2 translocation/TFE3 gene fusion RCC is currently classified as a distinct type of RCC. RCC is capable of invading the renal vein and inferior vena cava to form a tumor thrombus. The incidence of RCC with tumor thrombi within the renal vein or inferior vena cava is 7–10% in China. In the present case report, the patient underwent radical resection of the renal tumor and removal of the tumor thrombus, assisted by cardiopulmonary bypass, for the treatment of Xp11.2 translocation/TFE3 gene fusion RCC. The patient was followed-up for 12 months subsequent to treatment. The patient's renal function remained within the normal range, and computed tomography examination revealed no evidence of disease recurrence or metastases. The present case report aimed to provide a reference for the development of guidelines for the diagnosis and treatment of Xp11.2 translocation/TFE3 gene fusion RCC. PMID:26788164

A novel Xp22.13 microdeletion in Nance-Horan syndrome.

PubMed

Accogli, Andrea; Traverso, Monica; Madia, Francesca; Bellini, Tommaso; Vari, Maria Stella; Pinto, Francesca; Capra, Valeria

2017-07-03

Nance-Horan syndrome (NHS) is a rare X-linked developmental disorder characterized by congenital cataract, dental anomalies and facial dysmorphisms. Notably, up to 30% of NHS patients have intellectual disability and a few patients have been reported to have congenital cardiac defects. Nance-Horan syndrome is caused by mutations in the NHS gene that is highly expressed in the midbrain, retina, lens, tooth, and is conserved across vertebrate species. Although most pathogenic mutations are nonsense mutations, a few genomic rearrangements involving NHS locus have been reported, suggesting a possible pathogenic role of the flanking genes. Here, we report a microdeletion of 170,6 Kb at Xp22.13 (17.733.948-17.904.576) (GRCh37/hg19), detected by array-based comparative genomic hybridization in an Italian boy with NHS syndrome. The microdeletion harbors the NHS, SCLML1, and RAI2 genes and results in a phenotype consistent with NSH syndrome and developmental delay. We compare our case with the previous Xp22.13 microdeletions and discuss the possible pathogenetic role of the flanking genes. Birth Defects Research 109:866-868, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Renal carcinomas associated with Xp11.2 translocations/TFE3 gene fusions: findings on MRI and computed tomography imaging.

PubMed

Liu, Kefu; Xie, Ping; Peng, Weijun; Zhou, Zhengrong

2014-08-01

To retrospectively analyze MRI and computed tomographic (CT) findings from renal carcinomas associated with Xp11.2 translocations/TFE3 gene fusions (Xp11-RCC). Institutional review board permission was obtained to review patient medical records, and the requirement for informed consent was waved . The clinical and MRI/CT features of five cases with Xp11-RCC that were confirmed by pathology were analyzed retrospectively. The image characteristics included the lesion location and size, contribution of cystic and solid components, intratumoral necrosis or hemorrhage, invasion of perinephric tissue and renal sinus, lymphadenopathy, major venous or arterial vascular invasion, pattern of the tumor growth, intratumor calcification and lipids, homogeneity of SI on T2-weighted images, attenuation and SI of the mass with respect to the normal renal cortex on precontrast and contrasted CT/MRI images, tumor SIs, tumor attenuations and tumor-to-cortex indices, homogeneity of enhancement on the contrasted images. The mean age was 32 years (range, 15-47 years). Most patients (4/5) were women. All tumors showed a cortical location. The average tumor size was 9 cm (range, 4-18 cm). Four tumors comprised a predominantly solid lesion with focal necrosis, and one tumor comprised a solid lesion with significant necrosis. All tumors showed intertumor hemorrhage, infiltrative growth and invasion of the perirenal adipose/renal sinus. Four cases showed retroperitoneal lymphadenopathy, of which one case showed simultaneous mediastinal and supraclavicular lymphadenopathy. All tumors from four cases showed mild hyperintensity on T1-weighted MRI images, and three tumors showed hypointensity on T2-weighted MRI images relative to the renal cortex except for 1 tumor that showed significant hemorrhage and a relative hyperintensity. For 3 cases who were imaged with CT, two tumors imaged using nonenhanced CT images showed mild hyperdensity relative to the renal cortex. Calcification was noted in all

A 1.8-Mb YAC contig in Xp11.23: identification of CpG islands and physical mapping of CA repeats in a region of high gene density.

PubMed

Coleman, M P; Németh, A H; Campbell, L; Raut, C P; Weissenbach, J; Davies, K E

1994-05-15

The genes ARAF1, SYN1, TIMP, and PFC are clustered within 70 kb of one another, and, as reported in the accompanying paper (J. Knight et al., 1994, Genomics 21: 180-187), at least four more genes map within 400 kb: a cluster of Krüppel-type zinc finger genes (including ZNF21, ZNF41, and ZNF81) and ELK-1, a member of the ets oncogene superfamily. This gene-rich region is of particular interest because of the large number of disease genes mapping to Xp11.23: at least three eye diseases (retinitis pigmentosa type 2, congenital stationary night blindness CSNB1, and Aland Island eye disease), Wiskott-Aldrich syndrome, X-linked nephrolithiasis, and a translocation breakpoint associated with synovial sarcoma. We have constructed a 1.8-Mb YAC contig in this region, confirming the link between TIMP and OATL1 reported by Knight et al. (1994) and extending the map in the distal direction. To investigate the likelihood that more genes are located within this region, we have carried out detailed mapping of rare-cutter restriction sites in these YACs and identified seven CpG islands. At least six of these islands are located over 50 kb from any known gene locations, suggesting that the region contains at least this many as yet unidentified genes. We have also mapped the physical locations of six highly polymorphic CA repeats within the contig, thus integrating the physical, genetic, and transcriptional maps of the region and facilitating the mapping and identification of disease genes.(ABSTRACT TRUNCATED AT 250 WORDS)

Epileptic encephalopathy in a girl with an interstitial deletion of Xp22 comprising promoter and exon 1 of the CDKL5 gene.

PubMed

Bahi-Buisson, Nadia; Girard, Benoit; Gautier, Agnes; Nectoux, Juliette; Fichou, Yann; Saillour, Yoann; Poirier, Karine; Chelly, Jamel; Bienvenu, Thierry

2010-01-05

We report a 2-year-old girl with early onset seizures variant of Rett syndrome with a deletion at Xp22 detected by multiplex ligation-dependent probe amplification (MLPA) technique. This patient presented with tonic seizures at 7 days of life. Subsequently, she developed infantile spasms at three months and finally refractory myoclonic epilepsy. She demonstrated severe encephalopathy with hypotonia, deceleration of head growth, with eye gaze but limited eye pursuit, no language, limited hand use, and intermittent hand stereotypies. This combination of clinical features, suggestive of early onset variant of Rett syndrome led us to screen the CDKL5 gene. In a first step, screening of the whole coding sequence of the CDKL5 gene revealed no point mutations. In a second step, we searched gross rearrangements by MLPA and identified a microdeletion affecting both the promoter and exon 1 in CDKL5. Subsequent analysis on a Nimblegen HD2 microarray confirmed a deletion of approximately 300 kb at Xp22, including the BEND2, SCML2, and CDKL5 genes. In conclusion, our report suggests that searching for large rearrangements in CDKL5 should be considered in girls with early onset seizures and Rett-like features. (c) 2009 Wiley-Liss, Inc.

Renal Cell Carcinoma Associated With Xp11.2 Translocation/TFE3 Gene-fusion: A Long Response to mammalian target of rapamycin (mTOR) Inhibitors.

PubMed

Rua Fernández, Oliver R; Escala Cornejo, Roberto; Navarro Martín, Miguel; García Muñoz, María; Antunez Plaza, Patricia; García Dominguez, Aracely Rocío; Cruz Hernández, Juan J

2018-04-24

To demonstrate that patients with Xp11.2/TFE3 gene-fusion translocation renal cell carcinoma (RCC), despite having an aggressive course in young adults, could have valid treatment options such as mammalian target of rapamycin (mTOR) inhibitors with good outcomes. Furthermore, to explain possible mechanisms of action of mTOR inhibitors in this type of RCC. We report a case of a 44-year-old man who has been treated with everolimus for a Xp11.2 translocation/TFE3 gene-fusion RCC after 2 previous failed treatments with tyrosine kinase inhibitor. During the follow-up, we evaluated type and duration of response with everolimus. The patient obtained a long-lasting response of disease of 25 months with everolimus without any symptom. We believe that mTOR inhibitors could be a good line option treatment to consider for this type of patients. Copyright © 2018 Elsevier Inc. All rights reserved.

Validation and utilization of a TFE3 break-apart FISH assay for Xp11.2 translocation renal cell carcinoma and alveolar soft part sarcoma.

PubMed

Pradhan, Dinesh; Roy, Somak; Quiroga-Garza, Gabriela; Cieply, Kathleen; Mahaffey, Alyssa L; Bastacky, Sheldon; Dhir, Rajiv; Parwani, Anil V

2015-09-29

Xp11.2 or TFE3 translocation renal cell carcinomas (RCC) and alveolar soft part sarcoma (ASPS) are characterized by chromosome translocations involving the Xp11.2 breakpoint resulting in transcription factor TFE3 gene fusions. The most common translocations documented in TFE3 RCCs are t(X;1) (p11.2;q21) and t(X;17) (p11.2;q25) which leads to fusion of TFE3 gene on Xp11.2 with PRCC or ASPL respectively. TFE3 immunohistochemistry (IHC) has been inconsistent over time due to background staining problems in part related to fixation issues. Karyotyping to detect TFE3 gene rearrangement requires typically unavailable fresh tissue. Reverse transcriptase-polymerase chain reaction (RT-PCR) is generally very challenging due to degradation of RNA in archival material. The study objective was to develop and validate a TFE3 break-apart fluorescence in situ hybridization (FISH) assay to confirm Xp11 translocation RCCs and ASPS. Representative sections of formalin-fixed paraffin-embedded tissue blocks were selected in 40 possible cases. Approximately 60 tumor cells were analyzed in the targeted region. The validation of TFE3 FISH was done with 11 negative and two positive cases. Cut off for a positive result was validated as >7.15 % positive nuclei with any pattern of break-apart signals. FISH evaluation was done blinded of the immunohistochemical or karyotype data. Three out of forty cases were positive for the TFE3 break-apart signals by FISH. The negative cases were reported as clear cell RCC with papillary features (10), clear cell RCC with sarcomatoid areas (2), Papillary RCC with clear cell areas (9), Chromophobe RCC (2), RCC, unclassified type (3) and renal medullary carcinoma (1). 3 of the negative cases were consultation cases for renal tumor with unknown histology. Seven negative cases were soft tissue tumor suspicious for ASPS. Our study validates the utility of TFE3 break-apart FISH on formalin-fixed paraffin-embedded tissue sections for diagnosis and confirmation of

Xp11 translocation renal cell carcinoma in adults: a clinicopathological and comparative genomic hybridization study.

PubMed

Zou, Hong; Kang, Xueling; Pang, Li-Juan; Hu, Wenhao; Zhao, Jin; Qi, Yan; Hu, Jianming; Liu, Chunxia; Li, Hongan; Liang, Weihua; Yuan, Xianglin; Li, Feng

2014-01-01

To study the clinicopathological and genomic characteristics of Xp11.2 translocation renal cell carcinoma (Xp11.2 RCC) in adults, we analyzed 9 Xp11.2 RCCs, confirmed by transcription factor E3 (TFE3) immunohistochemistry, in patients aged ≥20 years. TFE3 expression was also determined in 12 cases of alveolar soft part sarcoma (ASPS) served as a positive control. Comparative genomic hybridization (CGH) was used to investigate genomic imbalances in all Xp11.2 RCC cases. Most of our Xp11.2 RCC patients (5/9) presented with TNM stages 3-4, and 6 patients died 10 months to 7 years after their operation. Histologically, Xp11.2 RCC was composed of a mixed papillary nested/alveolar growth pattern (8/9). Immunostaining showed that all Xp11.2 RCC and ASPS cases had strong TFE3 expression and high positive ratios for p53 and vimentin. However, there were significant differences in the expression of AMACR (p<0.001), AE1/AE3 (p=0.002), and CD10 (p=0.024) between the 2 diseases. CGH profiles showed chromosomal imbalances in all 9 Xp11.2 RCC cases; gains were observed in chromosomes Xp11 (6/9), 7q20-25, 12q25-31 (5/9), 7p16-24 (4/9), 8p12-13, 8q20-21, 16q20-22, 17q25-26, 20q22-23 (4/9), and losses occurred frequently on chromosomes 3p12-16, 9q31-32, 14q22-24 (4/9). Our Conclusions show Xp11.2 RCC that occur in adults may be aggressive cancers, the expressions of AMACR, CD10, AE1/AE3 are helpful in the differential diagnosis between Xp11.2 RCC and ASPS, and CGH assay is a useful complementary method for confirming the diagnosis of Xp11.2 RCC.

Xp11 translocation renal cell carcinoma in adults: a clinicopathological and comparative genomic hybridization study

PubMed Central

Zou, Hong; Kang, Xueling; Pang, Li-Juan; Hu, Wenhao; Zhao, Jin; Qi, Yan; Hu, Jianming; Liu, Chunxia; Li, Hongan; Liang, Weihua; Yuan, Xianglin; Li, Feng

2014-01-01

To study the clinicopathological and genomic characteristics of Xp11.2 translocation renal cell carcinoma (Xp11.2 RCC) in adults, we analyzed 9 Xp11.2 RCCs, confirmed by transcription factor E3 (TFE3) immunohistochemistry, in patients aged ≥20 years. TFE3 expression was also determined in 12 cases of alveolar soft part sarcoma (ASPS) served as a positive control. Comparative genomic hybridization (CGH) was used to investigate genomic imbalances in all Xp11.2 RCC cases. Most of our Xp11.2 RCC patients (5/9) presented with TNM stages 3-4, and 6 patients died 10 months to 7 years after their operation. Histologically, Xp11.2 RCC was composed of a mixed papillary nested/alveolar growth pattern (8/9). Immunostaining showed that all Xp11.2 RCC and ASPS cases had strong TFE3 expression and high positive ratios for p53 and vimentin. However, there were significant differences in the expression of AMACR (p<0.001), AE1/AE3 (p=0.002), and CD10 (p=0.024) between the 2 diseases. CGH profiles showed chromosomal imbalances in all 9 Xp11.2 RCC cases; gains were observed in chromosomes Xp11 (6/9), 7q20-25, 12q25-31 (5/9), 7p16-24 (4/9), 8p12-13, 8q20-21, 16q20-22, 17q25-26, 20q22-23 (4/9), and losses occurred frequently on chromosomes 3p12-16, 9q31-32, 14q22-24 (4/9). Our Conclusions show Xp11.2 RCC that occur in adults may be aggressive cancers, the expressions of AMACR, CD10, AE1/AE3 are helpful in the differential diagnosis between Xp11.2 RCC and ASPS, and CGH assay is a useful complementary method for confirming the diagnosis of Xp11.2 RCC. PMID:24427344

Ablation of XP-V gene causes adipose tissue senescence and metabolic abnormalities

PubMed Central

Chen, Yih-Wen; Harris, Robert A.; Hatahet, Zafer; Chou, Kai-ming

2015-01-01

Obesity and the metabolic syndrome have evolved to be major health issues throughout the world. Whether loss of genome integrity contributes to this epidemic is an open question. DNA polymerase η (pol η), encoded by the xeroderma pigmentosum (XP-V) gene, plays an essential role in preventing cutaneous cancer caused by UV radiation-induced DNA damage. Herein, we demonstrate that pol η deficiency in mice (pol η−/−) causes obesity with visceral fat accumulation, hepatic steatosis, hyperleptinemia, hyperinsulinemia, and glucose intolerance. In comparison to WT mice, adipose tissue from pol η−/− mice exhibits increased DNA damage and a greater DNA damage response, indicated by up-regulation and/or phosphorylation of ataxia telangiectasia mutated (ATM), phosphorylated H2AX (γH2AX), and poly[ADP-ribose] polymerase 1 (PARP-1). Concomitantly, increased cellular senescence in the adipose tissue from pol η−/− mice was observed and measured by up-regulation of senescence markers, including p53, p16Ink4a, p21, senescence-associated (SA) β-gal activity, and SA secretion of proinflammatory cytokines interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) as early as 4 wk of age. Treatment of pol η−/− mice with a p53 inhibitor, pifithrin-α, reduced adipocyte senescence and attenuated the metabolic abnormalities. Furthermore, elevation of adipocyte DNA damage with a high-fat diet or sodium arsenite exacerbated adipocyte senescence and metabolic abnormalities in pol η−/− mice. In contrast, reduction of adipose DNA damage with N-acetylcysteine or metformin ameliorated cellular senescence and metabolic abnormalities. These studies indicate that elevated DNA damage is a root cause of adipocyte senescence, which plays a determining role in the development of obesity and insulin resistance. PMID:26240351

Encephalopathy and bilateral cataract in a boy with an interstitial deletion of Xp22 comprising the CDKL5 and NHS genes.

PubMed

Van Esch, Hilde; Jansen, Anna; Bauters, Marijke; Froyen, Guy; Fryns, Jean-Pierre

2007-02-15

We describe a male patient with a deletion at Xp22, detected by high resolution X-array CGH. The clinical phenotype present in this infant boy, consists of severe encephalopathy, congenital cataracts and tetralogy of Fallot and can be attributed to the deletion of the genes within the interval. Among these deleted genes are the gene for Nance-Horan syndrome and the cyclin-dependent kinase-like 5 gene (CDKL5), responsible for the early seizure variant of Rett syndrome. This is the first description of a male patient with a deletion of these genes, showing the involvement of CDKL5 in severe epileptic encephalopathy in males. Moreover it illustrates the added value of high resolution array-CGH in molecular diagnosis of mental retardation-multiple congenital anomaly cases. (c) 2007 Wiley-Liss, Inc.

Sex determining gene on the X chromosome short arm: dosage sensitive sex reversal.

PubMed

Ogata, T; Matsuo, N

1996-08-01

The present review article summarizes current knowledge concerning the sex determining gene on Xp21, termed DSS (dosage sensitive sex reversal). The presence of DSS has been based on the finding that, in the presence of SRY, partial active Xp duplications encompassing the middle part of Xp result in sex reversal, whereas those of the distal or proximal part of Xp permit male sex development. Because Klinefelter patients develop as males, it is believed that DSS is normally subject to X-inactivation, and that two active copies of DSS override the function of SRY, resulting in gonadal dysgenesis because of meiotic pairing failure. It may be possible that DSS encodes a target sequence for repressing function of SRY or that DSS is involved in an X chromosome-counting mechanism. Molecular approaches have localized DSS to a 160 kb region and isolated candidate genes such as DAX-1 and MAGE-Xp, but there has been no formal evidence equating the candidate gene with DSS. In addition to its clinical importance, the exploration of DSS must provide a useful clue to phylogenetic studies of sex chromosomes and dosage compensation.

The Norrie disease gene maps to a 150 kb region on chromosome Xp11.3.

PubMed

Sims, K B; Lebo, R V; Benson, G; Shalish, C; Schuback, D; Chen, Z Y; Bruns, G; Craig, I W; Golbus, M S; Breakefield, X O

1992-05-01

Norrie disease is a human X-linked recessive disorder of unknown etiology characterized by congenital blindness, sensory neural deafness and mental retardation. This disease gene was previously linked to the DXS7 (L1.28) locus and the MAO genes in band Xp11.3. We report here fine physical mapping of the obligate region containing the Norrie disease gene (NDP) defined by a recombination and by the smallest submicroscopic chromosomal deletion associated with Norrie disease identified to date. Analysis, using in addition two overlapping YAC clones from this region, allowed orientation of the MAOA and MAOB genes in a 5'-3'-3'-5' configuration. A recombination event between a (GT)n polymorphism in intron 2 of the MAOB gene and the NDP locus, in a family previously reported to have a recombination between DXS7 and NDP, delineates a flanking marker telomeric to this disease gene. An anonymous DNA probe, dc12, present in one of the YACs and in a patient with a submicroscopic deletion which includes MAOA and MAOB but not L1.28, serves as a flanking marker centromeric to the disease gene. An Alu-PCR fragment from the right arm of the MAO YAC (YMAO.AluR) is not deleted in this patient and also delineates the centromeric extent of the obligate disease region. The apparent order of these loci is telomere ... DXS7-MAOA-MAOB-NDP-dc12-YMAO.AluR ... centromere. Together these data define the obligate region containing the NDP gene to a chromosomal segment less than 150 kb.

Xp11.2 translocation renal cell carcinoma with multiple bone metastases: A case report.

PubMed

Liu, Jiaju; Su, Zhengming; Li, Yifan; Chen, Duqun; Ni, Liangchao; Mao, Xiangming; Yang, Shangqi; Lai, Yongqing

2016-03-01

Xp11.2 translocation/transcription factor enhancer 3 (TFE3) fusion gene associated with renal cell carcinoma (Xp11.2 translocation RCC) is rare and occurs predominantly in children and adolescents. The current study reports the case of a 14-year-old male with Xp11.2 translocation RCC, who presented with chest pain that had persisted for 1 month. A solid neoplasm was located in the left kidney of the patient. Contrast-enhanced computed tomography revealed the presence of a solid mass in the kidney, with uneven enhancement. Destruction of multiple bones was also observed. The patient was treated with a radical nephrectomy. The pathological examination of the tumor revealed that the tumor cells contained an eosinophilic cytoplasm in the renal interstitial tissue. Immunohistochemistry revealed that the tumor cells expressed P504S, cluster of differentiation 10, pan-cytokeratin, vimentin and TFE3. In conclusion, Xp11.2 translocation RCC is a rare type of kidney cancer. Diagnosing this disease prior to surgery is challenging, and providing a definite diagnosis requires histopathological and immunohistochemical examination, while genetic analysis may also be required.

14 CFR 99.43 - Contiguous U.S. ADIZ.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Contiguous U.S. ADIZ. 99.43 Section 99.43 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIR TRAFFIC... Zones § 99.43 Contiguous U.S. ADIZ. The area bounded by a line from 43°15′N, 65°55′W; 44°21′N; 67°16′W...

Xp11.2 translocation renal cell carcinoma with multiple bone metastases: A case report

PubMed Central

LIU, JIAJU; SU, ZHENGMING; LI, YIFAN; CHEN, DUQUN; NI, LIANGCHAO; MAO, XIANGMING; YANG, SHANGQI; LAI, YONGQING

2016-01-01

Xp11.2 translocation/transcription factor enhancer 3 (TFE3) fusion gene associated with renal cell carcinoma (Xp11.2 translocation RCC) is rare and occurs predominantly in children and adolescents. The current study reports the case of a 14-year-old male with Xp11.2 translocation RCC, who presented with chest pain that had persisted for 1 month. A solid neoplasm was located in the left kidney of the patient. Contrast-enhanced computed tomography revealed the presence of a solid mass in the kidney, with uneven enhancement. Destruction of multiple bones was also observed. The patient was treated with a radical nephrectomy. The pathological examination of the tumor revealed that the tumor cells contained an eosinophilic cytoplasm in the renal interstitial tissue. Immunohistochemistry revealed that the tumor cells expressed P504S, cluster of differentiation 10, pan-cytokeratin, vimentin and TFE3. In conclusion, Xp11.2 translocation RCC is a rare type of kidney cancer. Diagnosing this disease prior to surgery is challenging, and providing a definite diagnosis requires histopathological and immunohistochemical examination, while genetic analysis may also be required. PMID:26998154

Xp11.2 translocation renal cell carcinomas in young adults.

PubMed

Xu, Linfeng; Yang, Rong; Gan, Weidong; Chen, Xiancheng; Qiu, Xuefeng; Fu, Kai; Huang, Jin; Zhu, Guancheng; Guo, Hongqian

2015-07-01

Little is known about the biological behavior of Xp11.2 translocation renal cell carcinomas (RCCs) as few clinical studies have been performed using a large sample size. This study included 103 consecutive young adult patients (age ≤ 45 years) with RCC who underwent partial or radical nephrectomy at our institution from 2008 to 2013. Five patients without complete clinical data were excluded. Of the 98 remaining patients, 16 and 82 patients were included in the Xp11.2 translocation and non-Xp11.2 translocation groups, respectively. Clinicopathologic data were collected, including age, gender, tumor size, laterality, symptoms at diagnosis, surgical procedure, pathologic stage, tumor grade, time of recurrence and death. Xp11.2 translocation RCCs were associated with higher tumor grade and pathologic stage (P < 0.05, Fisher's exact test). During the median follow-up of 36 months (range: 3-71 months), the number of cancer-related deaths was 4 (4.9%) and 3 (18.7%) in the non-Xp11.2 translocation and Xp11.2 translocation groups, respectively. The Kaplan-Meier cancer specific survival curves revealed a significant difference between non-Xp11.2 translocation RCCs and Xp11.2 translocation RCCs in young adults (P = 0.042). Compared with non-Xp11.2 translocation RCCs, the Xp11.2 translocation RCCs seemingly showed a higher tumor grade and pathologic stage and have similar recurrence-free survival rates but poorer cancer-specific survival rates in young adults.

Imprint cytologic features in renal cell carcinoma associated with Xp11.2 translocation/TFE3 gene fusion in an adult: a case report.

PubMed

Yamaguchi, Tadanori; Kuroda, Naoto; Imamura, Yoshiaki; Hes, Ondrej; Kawada, Takako; Nakayama, Keizou

2009-01-01

Adult-onset renal cell carcinoma (RCC) associated with Xp11.2 translocation/TFE3 gene fusion is a very rare tumor. To date, there are no reports on immunocytochemical study of the primary tumor. We describe such a case that we diagnosed by immunocytochemistry of imprint cytology material. A 46-year-old man was found to have a mass in the lower pole of the right kidney. Magnetic resonance imaging (MRI) T2-weighted images showed a hypointense area in the tumor, and papillary RCC was suspected. Imprint cytology showed tumor cells that were isolated or arranged in large or small papillary clusters. Irregularly shaped large oval nuclei, finely granular chromatin and a single large nucleolus were noted. Cytoplasm was abundant and admixed with clear and granular eosinophilic patterns and scattered large vacuolated cells. Almost all tumor cells diffusely expressed immunocytochemical reactivity to TFE3 protein. Hyaline nodules were observed in the stroma. Ultrastructurally, neoplastic cells contained rhomboid crystals identical to those of alveolar soft part sarcoma. The immunocytochemistry of TFE3 protein may be a powerful tool for accurate diagnosis when RCC associated with Xp11.2 translocation/TFE3 gene fusion is suspected by imprint cytology even in adult-onset cases, and cytotechnologists should accurately recognize cytologic findings of this tumor.

New X-linked mental retardation syndrome with the gene mapped tentatively in Xp22.3

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wittwer, B.; Kircheisen, R.; Leutelt, J.

1996-07-12

X-linked mental retardation (XLMR) is genetically heterogeneous and clinically variable. We describe a new XLMR syndrome of severe mental retardation and multiple congenital anomalies. Two sisters have (with 3 different partners) 3 severely handicapped sons. In 2 cases, oligohydramnios and intrauterine growth retardation were noted. Common anomalies included a square-shaped face, high and broad forehead, frontal bossing, downward slant of palpebral fissures, hypertelorism, epicanthic folds, long philtrum, thin upper lip, and apparently low-set ears. One boy has bilateral microphthalmos and sclerocornea, and his cousin has atrophy of the optic nerve. All 3 patients are blind and have profound statomotor andmore » mental retardation, seizures, and a grossly abnormal electroencephalographic pattern. Additional findings are short stature, delayed bone matuation, hydronephrosis, vesicorenal reflux, cryptorchidism, clinodactyly of the 5th fingers, and transverse palmar creases. The karyotype is normal (46,XY). Segregation analysis showed perfect coinheritance between the clinical phenotype and alleles at several loci in Xp22.3, whereas recombinants were identified with marker loci from Xp22.2-qter. Analysis of multiple informative meioses suggests that the disease locus maps in Xp22.3 distal to DXS16. 9 refs., 5 figs., 2 tabs.« less

Alport syndrome, mental retardation, midface hypoplasia, and elliptocytosis: a new X linked contiguous gene deletion syndrome?

PubMed Central

Jonsson, J J; Renieri, A; Gallagher, P G; Kashtan, C E; Cherniske, E M; Bruttini, M; Piccini, M; Vitelli, F; Ballabio, A; Pober, B R

1998-01-01

We describe a family with four members, a mother, two sons, and a daughter, who show clinical features consistent with X linked Alport syndrome. The two males presented with additional features including mental retardation, dysmorphic facies with marked midface hypoplasia, and elliptocytosis. The elliptocytosis was not associated with any detectable abnormalities in red cell membrane proteins; red cell membrane stability and rigidity was normal on ektacytometry. Molecular characterisation suggests a submicroscopic X chromosome deletion encompassing the entire COL4A5 gene. We propose that the additional abnormalities found in the affected males of this family are attributable to deletion or disruption of X linked recessive genes adjacent to the COL4A5 gene and that this constellation of findings may represent a new X linked contiguous gene deletion syndrome. Images PMID:9598718

Renal cell carcinoma associated with transcription factor E3 expression and Xp11.2 translocation: incidence, characteristics, and prognosis.

PubMed

Klatte, Tobias; Streubel, Berthold; Wrba, Friedrich; Remzi, Mesut; Krammer, Barbara; de Martino, Michela; Waldert, Matthias; Marberger, Michael; Susani, Martin; Haitel, Andrea

2012-05-01

We studied the characteristics and prognosis of renal cell carcinoma (RCC) associated with Xp11.2 translocation and transcription factor E3 (TFE3) expression and determined the need for genetic analysis in routine diagnostics. Of 848 consecutive cases, 75 showed microscopic features suggestive of Xp11.2 translocation RCC or occurred in patients 40 years or younger. Of these cases, 17 (23%) showed strong nuclear TFE3 immunostaining, which was associated with more advanced tumors and inverse prognosis in univariate (P = .032) but not multivariate (P = .404) analysis. With fluorescence in situ hybridization and polymerase chain reaction, only 2 cases showed alterations of the X chromosome and the ASPL-TFE3 gene fusion, respectively. In our laboratory, the predictive value of TFE3 expression for the Xp11.2 translocation was 12%. Strong nuclear TFE3 expression is associated with metastatic spread and a poor prognosis. In our laboratory, TFE3 is not diagnostic for Xp11.2 translocation RCC. Diagnosis of Xp11.2 translocation RCC may be made only genetically.

Rapidly progressing renal cell carcinoma associated with Xp11.2 translocations: a case report

PubMed Central

2012-01-01

Introduction Renal cell carcinoma associated with Xp11.2 translocations is frequently reported in children, but adult-onset is rare. Here, the case of an adult male who developed a renal cell carcinoma associated with Xp11.2 translocations is presented. Case presentation A 38-year-old Asian man presented with left back pain and macroscopic hematuria. Computed tomography revealed a left renal tumor (T3N2M0), and a left radical nephrectomy was performed. Hematoxylin-eosin staining revealed papillary architecture and clear or eosinophilic cytoplasm, and the diagnosis of renal cell carcinoma associated with Xp11.2 translocations/TFE3 gene fusion was made by the immunohistochemical determination of transcription factor E3 protein. In spite of adjuvant therapy with α-interferon, a recurrent tumor was found in his left lung by computed tomography three months after the nephrectomy. Interleukin-2, tyrosine kinase inhibitors and mammalian target of rapamycin inhibitors showed no effect on tumor progression. Conclusions Renal cell carcinomas associated with Xp11.2 translocations have an aggressive clinical course in adults. Strict diagnosis using the immunohistochemistry of transcription factor E3 protein is important to predict the prognosis of such patients and new strategies need to be determined to treat patients with these tumors PMID:22738297

Rapidly progressing renal cell carcinoma associated with Xp11.2 translocations: a case report.

PubMed

Morii, Akihiro; Fujiuchi, Yasuyoshi; Nomoto, Kazuhiro; Komiya, Akira; Fuse, Hideki

2012-06-27

Renal cell carcinoma associated with Xp11.2 translocations is frequently reported in children, but adult-onset is rare. Here, the case of an adult male who developed a renal cell carcinoma associated with Xp11.2 translocations is presented. A 38-year-old Asian man presented with left back pain and macroscopic hematuria. Computed tomography revealed a left renal tumor (T3N2M0), and a left radical nephrectomy was performed. Hematoxylin-eosin staining revealed papillary architecture and clear or eosinophilic cytoplasm, and the diagnosis of renal cell carcinoma associated with Xp11.2 translocations/TFE3 gene fusion was made by the immunohistochemical determination of transcription factor E3 protein. In spite of adjuvant therapy with α-interferon, a recurrent tumor was found in his left lung by computed tomography three months after the nephrectomy. Interleukin-2, tyrosine kinase inhibitors and mammalian target of rapamycin inhibitors showed no effect on tumor progression. Renal cell carcinomas associated with Xp11.2 translocations have an aggressive clinical course in adults. Strict diagnosis using the immunohistochemistry of transcription factor E3 protein is important to predict the prognosis of such patients and new strategies need to be determined to treat patients with these tumors.

Improving draft genome contiguity with reference-derived in silico mate-pair libraries.

PubMed

Grau, José Horacio; Hackl, Thomas; Koepfli, Klaus-Peter; Hofreiter, Michael

2018-05-01

Contiguous genome assemblies are a highly valued biological resource because of the higher number of completely annotated genes and genomic elements that are usable compared to fragmented draft genomes. Nonetheless, contiguity is difficult to obtain if only low coverage data and/or only distantly related reference genome assemblies are available. In order to improve genome contiguity, we have developed Cross-Species Scaffolding-a new pipeline that imports long-range distance information directly into the de novo assembly process by constructing mate-pair libraries in silico. We show how genome assembly metrics and gene prediction dramatically improve with our pipeline by assembling two primate genomes solely based on ∼30x coverage of shotgun sequencing data.

Identification of a microdeletion at Xp22.13 in a Taiwanese family presenting with Nance-Horan syndrome.

PubMed

Liao, Hsiao-Mei; Niu, Dau-Ming; Chen, Yan-Jang; Fang, Jye-Siung; Chen, Shih-Jen; Chen, Chia-Hsiang

2011-01-01

Nance-Horan syndrome (NHS) is a rare X-linked disorder characterized by congenital cataracts, dental anomalies and mental retardation. The disease has been linked to a novel gene termed NHS located at Xp22.13. The majority of pathogenic mutations of the disease include nonsense mutations and small deletions and insertions that lead to truncation of the NHS protein. In this study, we identified a microdeletion of ∼ 0.92 Mb at Xp22.13 detected by array-based comparative genomic hybridization in two brothers presenting congenital cataract, dental anomalies, facial dysmorphisms and mental retardation. The deleted region encompasses the REPS2, NHS, SCML1 and RAI2 genes, and was transmitted from their carrier mother who presented only mild cataract. Our findings are in line with several recent case reports to indicate that genomic rearrangement involving the NHS gene is an important genetic etiology underlying NHS.

Usefulness of a break-apart FISH assay in the diagnosis of Xp11.2 translocation renal cell carcinoma.

PubMed

Kim, Soo Hee; Choi, Yoomi; Jeong, Hae Yeon; Lee, Kyoungbun; Chae, Ji Youn; Moon, Kyung Chul

2011-09-01

Xp11.2 translocation renal cell carcinoma (RCC) is a rare subtype of RCC predominantly reported in young patients. It results from gene fusions between the transcription factor E3 (TFE3) gene, which is located on chromosome Xp11.2, and various fusion partners. Recently, a dual color, break-apart fluorescence in situ hybridization (FISH) assay to detect Xp11.2 translocation was reported. We performed this study to evaluate the usefulness of the FISH assay in the diagnosis of Xp11.2 translocation RCC using a commercially available TFE3 break-apart probe. We immunohistochemically analyzed TFE3 nuclear expression in 809 cases of RCCs using 14 tissue microarray blocks and selected nine cases those showed moderate to strong positive nuclear immunoreactivity for TFE3. The extent of TFE3 nuclear expression was variable. The TFE3 FISH assay was performed in these 9 selected cases and 44 negative control cases. Only four out of nine selected cases showed the TFE3 break-apart signal. TFE3 FISH-positive cases mainly showed diffuse and strong TFE3 immunopositivity, but one case revealed focal and moderate TFE3 staining. On the contrary, TFE3 FISH-negative cases mainly revealed focal and moderate TFE3 immunoreactivity, however, one FISH-negative case revealed diffuse and strong TFE3 nuclear immunopositivity. All negative control cases revealed normal TFE3 FISH results. Our results reveal that TFE3 immunohistochemistry can show false-positive results, and that the TFE3 break-apart FISH assay is a useful complementary method for confirming the diagnosis of Xp11.2 translocation RCC.

Clinical characteristics of XP11.2 translocation/TFE3 gene fusion renal cell carcinoma: a systematic review and meta-analysis of observational studies.

PubMed

Cheng, Xiangming; Gan, Weidong; Zhang, Gutian; Li, Xiaogong; Guo, Hongqian

2016-07-11

Renal cell carcinoma (RCC) associated with Xp11.2 translocation/TFE3 gene fusion (Xp11.2 RCC) is a rare subtype of RCC which is firstly described as a distinct entity in 2004 so that clinical characteristics of Xp11.2 RCC in different gender and age are unknown. The purpose of systematic review and meta-analysis is to provide a comprehensive assessment on them. MEDLINE, EMBASE and Cochrane databases were searched for studies which evaluate the clinical characteristics of Xp11.2 RCC. The literature published between July 2004 and May 2014 was searched. A total of 15 studies with 147 participants were included. The meta-analysis demonstrated that number of patients of all age in female was higher than in male with pooled OR of 3.93(95 % CI = 1.66-9.34). However, incidence of distant metastases (OR = 0.34, 95 % CI = 0.12-1.57) and lymphatic metastases (OR = 0.51, 95 % CI = 0.14-1.91), tumor stage (OR = 0.85, 95 % CI = 0.34-2.15) and overall survival (OS) (OR = 0.46, 95 % CI = 0.05-4.34) between male and female were comparable. Incidence in female was higher than in male with pooled OR of 5.13(95 % CI = 1.67-15.72) in adults, while in children no gender-related predominance (OR = 1.19, 95 % CI = 0.38-3.72) was observed. In addition, incidence of distant metastases (OR = 1.00, 95 % CI = 0.13-7.84) and lymphatic metastases (OR = 1.00, 95 % CI = 0.07-13.67) and tumor stage (OR = 1.94, 95 % CI = 0.20-19.03) between children and adults were comparable. Survival curves presented comparable outcomes between male and female (P = 0.707) as well as between children and adults (P = 0.383). Female patients with Xp11.2 RCC in adults exhibit a high incidence compared to male, but not in children. Comparable clinical characteristics including incidence of distant and lymphatic metastases, tumor stage and prognosis is presented between male and female as well as between children and adults.

Development of a YAC contig covering the minimal region of a CSNB1 locus in Xp11

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boycott, K.M.; Gratton, K.J.; Moore, B.J.

1994-09-01

X-linked congenital stationary night blindness (CSNB1) is an eye disorder that includes impairment of night vision, reduced visual acuity and, in some cases, myopia and congenital nystagmus. Electroretinography reveals a marked reduction of the b-wave in affected individuals suggesting that X-linked CSNB is due to a molecular defect in the bipolar layer of the retina. Based on our studies of a large four generation family with X-linked CSNB, a CSNB1 locus was mapped to a 4-5 cM region at Xp11.23-Xp11.22 bounded telomerically by DXS426 and centromerically by DXS988. Using a panel of radiation and conventional somatic cell hybrids, a detailedmore » map of new and published STSs has been generated for the minimal region of CSNB1. PCR primer pairs for STSs has been generated for the minimal region of CSNB1. PCR primer pairs for twenty-five STSs, including eleven end-clones, were used to isolate YAC clones from CEPH, mega-CEPH, and X chromosome-specific YAC libraries. In total, fifty-two YACs were characterized for STS overlaps and assembled to provide a minimum of 3 Mb of physical coverage in the region between DXS426 and DXS988. Five gaps proximal to SYP are still to be closed. Our physical map suggests the following gene order: Xpter-OTAL1-GF1-DXS1011E-MG81-HUMCRAS2P-SYP-Xcen. STS analysis of the YACs revealed three subregions of the physical map which appear to be particularly susceptible to internal deletions and end-clone analysis demonstrated chimerism in six of seventeen YACs. A physical map of Xp11.23-Xp11.22 will provide a resource for the isolation of candidate genes for the X-linked CSNB gene which maps to this region.« less

RBM10-TFE3 Renal Cell Carcinoma: A Potential Diagnostic Pitfall Due to Cryptic Intrachromosomal Xp11.2 Inversion Resulting in False-negative TFE3 FISH.

PubMed

Argani, Pedram; Zhang, Lei; Reuter, Victor E; Tickoo, Satish K; Antonescu, Cristina R

2017-05-01

Xp11 translocation renal cell carcinoma (RCC) are defined by chromosome translocations involving the Xp11 breakpoint which results in one of a variety of TFE3 gene fusions. TFE3 break-apart florescence in situ hybridization (FISH) assays are generally preferred to TFE3 immunohistochemistry (IHC) as a means of confirming the diagnosis in archival material, as FISH is less sensitive to the variable fixation which can result in false positive or false negative IHC. Prompted by a case report in the cytogenetics literature, we identify 3 cases of Xp11 translocation RCC characterized by a subtle chromosomal inversion involving the short arm of the X chromosome, resulting in an RBM10-TFE3 gene fusion. TFE3 rearrangement was not detected by conventional TFE3 break-apart FISH, but was suggested by strong diffuse TFE3 immunoreactivity in a clean background. We then developed novel fosmid probes to detect the RBM10-TFE3 gene fusion in archival material. These cases validate RBM10-TFE3 as a recurrent gene fusion in Xp11 translocation RCC, illustrate a source of false-negative TFE3 break-apart FISH, and highlight the complementary role of TFE3 IHC and TFE3 FISH.

Further mapping of the properdin deficiency gene in a Tunisian Jewish family--evidence for genetic homogeneity.

PubMed

Ash, S; Johnson, C; Shohat, M; Shohat, T; Schlesinger, M

1994-08-01

The properdin deficiency gene has been localized to Xp21.1-Xcen; however, it is not clear whether the mutation responsible for the disease co-maps exactly with the structural properdin gene. Based on a recent study on a total of six families, the gene was found linked to DXS255 (theta = 0.00). As only a few families have been studied, it is not known whether the same gene is responsible for the disease in all families. In order to better localize the disease gene in Israel, we studied a Tunisian Jewish family with properdin deficiency for linkage with various X-markers. A maximum lod score of 1.93 at theta = 0.00 was calculated with the DXS7 probe while there was one recombination with DXS255. This study helps to better localize the properdin deficiency gene to Xp11.3-p21.1 proximal to DXS255 locus and confirms that there is no indication of genetic heterogeneity. Whether the properdin structural gene (PFC) and properdin deficiency locus are one and the same await demonstration of mutations in the structural gene in patients with properdin deficiency.

Simultaneous detection of eight avian influenza A virus subtypes by multiplex reverse transcription-PCR using a GeXP analyser.

PubMed

Li, Meng; Xie, Zhixun; Xie, Zhiqin; Liu, Jiabo; Xie, Liji; Deng, Xianwen; Luo, Sisi; Fan, Qing; Huang, Li; Huang, Jiaoling; Zhang, Yanfang; Zeng, Tingting; Wang, Sheng

2018-04-18

Recent studies have demonstrated that at least eight subtypes of avian influenza virus (AIV) can infect humans, including H1, H2, H3, H5, H6, H7, H9 and H10. A GeXP analyser-based multiplex reverse transcription (RT)-PCR (GeXP-multiplex RT-PCR) assay was developed in our recent studies to simultaneously detect these eight AIV subtypes using the haemagglutinin (HA) gene. The assay consists of chimeric primer-based PCR amplification with fluorescent labelling and capillary electrophoresis separation. RNA was extracted from chick embryo allantoic fluid or liquid cultures of viral isolates. In addition, RNA synthesised via in vitro transcription was used to determine the specificity and sensitivity of the assay. After selecting the primer pairs, their concentrations and GeXP-multiplex RT-PCR conditions were optimised. The established GeXP-multiplex RT-PCR assay can detect as few as 100 copies of premixed RNA templates. In the present study, 120 clinical specimens collected from domestic poultry at live bird markets and from wild birds were used to evaluate the performance of the assay. The GeXP-multiplex RT-PCR assay specificity was the same as that of conventional RT-PCR. Thus, the GeXP-multiplex RT-PCR assay is a rapid and relatively high-throughput method for detecting and identifying eight AIV subtypes that may infect humans.

A candidate gene for X-linked Ocular Albinism (OA1)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bassi, M.T.; Schiaffino, V.; Rugarli, E.

1994-09-01

Ocular Albinism of the Nettleship-Fall type 1 (OA1) is the most common form of ocular albinism. It is transmitted as an X-linked recessive trait with affected males showing severe reduction of visual acuity, nystagmus, strabismus, photophobia. Ophthalmologic examination reveals foveal hypoplasia, hypopigmentation of the retina and iris translucency. Microscopic examination of melanocytes suggests that the underlying defect in OA1 is an abnormality in melanosome formation. Recently we assembled a 350 kb cosmid contig spanning the entire critical region on Xp22.3, which measures approximately 110 kb. A minimum set of cosmids was used to identify transcribed sequences using both cDNA selectionmore » and exon amplification. Two putative exons recovered by exon amplification strategy were found to be highly conserved throughout evolution and, therefore, they were used as probes for the screening of fetal and adult retina cDNA libraries. This led to the isolation of clones spanning a full-length cDNA which measures 7.6 kb. Sequence analysis revealed that the predicted protein product shows homology with syntrophines and a Xenopus laevis apical protein. The gene covers approximately 170 kb of DNA and spans the entire critical region for OA1, being deleted in two patients with contiguous gene deletion including OA1 and in one patient with isolated OA1. Therefore, this new gene represents a very strong candidate for involvement in OA1 (an alternative, but unlikely possibility to be considered is that the true OA1 gene lies within an intron of the former). Northern analysis revealed very high level of expression in retina and melanoma. Unlike most Xp22.3 genes, this gene is conserved in the mouse. We are currently performing SSCP analysis and direct sequencing of exons on DNAs from approximately 60 unrelated patients with OA1 for mutation detection.« less

A recessive contiguous gene deletion causing infantile hyperinsulinism, enteropathy and deafness identifies the Usher type 1C gene.

PubMed

Bitner-Glindzicz, M; Lindley, K J; Rutland, P; Blaydon, D; Smith, V V; Milla, P J; Hussain, K; Furth-Lavi, J; Cosgrove, K E; Shepherd, R M; Barnes, P D; O'Brien, R E; Farndon, P A; Sowden, J; Liu, X Z; Scanlan, M J; Malcolm, S; Dunne, M J; Aynsley-Green, A; Glaser, B

2000-09-01

Usher syndrome type 1 describes the association of profound, congenital sensorineural deafness, vestibular hypofunction and childhood onset retinitis pigmentosa. It is an autosomal recessive condition and is subdivided on the basis of linkage analysis into types 1A through 1E. Usher type 1C maps to the region containing the genes ABCC8 and KCNJ11 (encoding components of ATP-sensitive K + (KATP) channels), which may be mutated in patients with hyperinsulinism. We identified three individuals from two consanguineous families with severe hyperinsulinism, profound congenital sensorineural deafness, enteropathy and renal tubular dysfunction. The molecular basis of the disorder is a homozygous 122-kb deletion of 11p14-15, which includes part of ABCC8 and overlaps with the locus for Usher syndrome type 1C and DFNB18. The centromeric boundary of this deletion includes part of a gene shown to be mutated in families with type 1C Usher syndrome, and is hence assigned the name USH1C. The pattern of expression of the USH1C protein is consistent with the clinical features exhibited by individuals with the contiguous gene deletion and with isolated Usher type 1C.

Diagnosis of a terminal deletion of 4p with duplication of Xp22.31 in a patient with findings of Opitz G/BBB syndrome and Wolf-Hirschhorn syndrome.

PubMed

So, Joyce; Müller, Ines; Kunath, Melanie; Herrmann, Susanne; Ullmann, Reinhard; Schweiger, Susann

2008-01-01

Opitz G/BBB syndrome (OS) is a congenital midline malformation syndrome characterized by hypertelorism, hypospadias, cleft lip/palate, laryngotracheoesophageal abnormalities, imperforate anus, developmental delay and cardiac defects. The X-linked form is caused by mutations in the MID1 gene, while no gene has yet been identified for the autosomal dominant form. Here, we report on a 15-year-old boy who was referred for MID1 mutation analysis with findings typical of OS, including apparent hypertelorism, hypospadias, a history of feeding difficulties, dysphagia secondary to esophageal arteria lusoria, growth retardation and developmental delay. No MID1 mutation was found, but subsequent sub-megabase resolution array CGH unexpectedly documented a 2.34 Mb terminal 4p deletion, suggesting a diagnosis of WHS, and a duplication in Xp22.31. Wolf-Hirschhorn syndrome (WHS) is a contiguous gene deletion syndrome involving terminal chromosome 4p deletions, in particular 4p16.3. WHS is characterized by typical facial appearance ("Greek helmet facies"), mental retardation, congenital hypotonia, and growth retardation. While the severity of developmental delay in this patient supports the diagnosis of WHS rather than OS, this case illustrates the striking similarities of clinical findings in seemingly unrelated syndromes, suggesting common or interacting pathways at the molecular and pathogenetic level. This is the first report of arteria lusoria (esophageal vascular ring) in a patient with WHS. (c) 2007 Wiley-Liss, Inc.

Novel contiguous gene deletion in peruvian girl with Trichothiodystrophy type 4 and glutaric aciduria type 3.

PubMed

La Serna-Infantes, Jorge; Pastor, Miguel Chávez; Trubnykova, Milana; Velásquez, Félix Chavesta; Sotomayor, Flor Vásquez; Barriga, Hugo Abarca

2018-07-01

Trichothiodystrophy type 4 is a rare autosomal recessive and ectodermal disorder, characterized by dry, brittle, sparse and sulfur-deficient hair and other features like intellectual disability, ichthyotic skin and short stature, caused by a homozygous mutation in MPLKIP gene. Glutaric aciduria type 3 is caused by a homozygous mutation in SUGCT gene with no distinctive phenotype. Both genes are localized on chromosome 7 (7p14). We report an 8-year-old female with short stature, microcephaly, development delay, intellectual disability and hair characterized for dark, short, coarse, sparse and brittle associated to classical trichorrhexis microscopy pattern. Chromosome microarray analysis showed a 125 kb homozygous pathogenic deletion, which includes genes MPLKIP and SUGCT, not described before. This is the first case described in Peru of a novel contiguous gene deletion of Trichothiodystrophy type 4 and Glutaric aciduria type 3 performed by chromosome microarray analysis, highlighting the contribution and importance of molecular technologies on diagnosis of rare genetic conditions. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Analysis of Parent-of-Origin Effects on the X Chromosome in Asian and European Orofacial Cleft Triads Identifies Associations with DMD, FGF13, EGFL6, and Additional Loci at Xp22.2.

PubMed

Skare, Øivind; Lie, Rolv T; Haaland, Øystein A; Gjerdevik, Miriam; Romanowska, Julia; Gjessing, Håkon K; Jugessur, Astanand

2018-01-01

Background: Although both the mother's and father's alleles are present in the offspring, they may not operate at the same level. These parent-of-origin (PoO) effects have not yet been explored on the X chromosome, which motivated us to develop new methods for detecting such effects. Orofacial clefts (OFCs) exhibit sex-specific differences in prevalence and are examples of traits where a search for various types of effects on the X chromosome might be relevant. Materials and Methods: We upgraded our R-package Haplin to enable genome-wide analyses of PoO effects, as well as power simulations for different statistical models. 14,486 X-chromosome SNPs in 1,291 Asian and 1,118 European case-parent triads of isolated OFCs were available from a previous GWAS. For each ethnicity, cleft lip with or without cleft palate (CL/P) and cleft palate only (CPO) were analyzed separately using two X-inactivation models and a sliding-window approach to haplotype analysis. In addition, we performed analyses restricted to female offspring. Results: Associations were identified in "Dystrophin" ( DMD , Xp21.2-p21.1), "Fibroblast growth factor 13" ( FGF13 , Xq26.3-q27.1) and "EGF-like domain multiple 6" ( EGFL6 , Xp22.2), with biologically plausible links to OFCs. Unlike EGFL6 , the other associations on chromosomal region Xp22.2 had no apparent connections to OFCs. However, the Xp22.2 region itself is of potential interest because it contains genes for clefting syndromes [for example, "Oral-facial-digital syndrome 1" ( OFD1 ) and "Midline 1" ( MID1 )]. Overall, the identified associations were highly specific for ethnicity, cleft subtype and X-inactivation model, except for DMD in which associations were identified in both CPO and CL/P, in the model with X-inactivation and in Europeans only. Discussion/Conclusion: The specificity of the associations for ethnicity, cleft subtype and X-inactivation model underscores the utility of conducting subanalyses, despite the ensuing need to adjust

Large inverted repeats within Xp11.2 are present at the breakpoints of isodicentric X chromosomes in Turner syndrome.

PubMed

Scott, Stuart A; Cohen, Ninette; Brandt, Tracy; Warburton, Peter E; Edelmann, Lisa

2010-09-01

Turner syndrome (TS) results from whole or partial monosomy X and is mediated by haploinsufficiency of genes that normally escape X-inactivation. Although a 45,X karyotype is observed in half of all TS cases, the most frequent variant TS karyotype includes the isodicentric X chromosome alone [46,X,idic(X)(p11)] or as a mosaic [46,X,idic(X)(p11)/45,X]. Given the mechanism of idic(X)(p11) rearrangement is poorly understood and breakpoint sequence information is unknown, this study sought to investigate the molecular mechanism of idic(X)(p11) formation by determining their precise breakpoint intervals. Karyotype analysis and fluorescence in situ hybridization mapping of eight idic(X)(p11) cell lines and three unbalanced Xp11.2 translocation lines identified the majority of breakpoints within a 5 Mb region, from approximately 53 to 58 Mb, in Xp11.1-p11.22, clustering into four regions. To further refine the breakpoints, a high-resolution oligonucleotide microarray (average of approximately 350 bp) was designed and array-based comparative genomic hybridization (aCGH) was performed on all 11 idic(X)(p11) and Xp11.2 translocation lines. aCGH analyses identified all breakpoint regions, including an idic(X)(p11) line with two potential breakpoints, one breakpoint shared between two idic(X)(p11) lines and two Xp translocations that shared breakpoints with idic(X)(p11) lines. Four of the breakpoint regions included large inverted repeats composed of repetitive gene clusters and segmental duplications, which corresponded to regions of copy-number variation. These data indicate that the rearrangement sites on Xp11.2 that lead to isodicentric chromosome formation and translocations are probably not random and suggest that the complex repetitive architecture of this region predisposes it to rearrangements, some of which are recurrent.

XP11.2 translocation renal cell carcinoma: clinical experience of Taipei Veterans General Hospital.

PubMed

Hung, Chia-Chen; Pan, Chin-Chen; Lin, Chih-Chieh; Lin, Alex T L; Chen, Kuang-Kuo; Chang, Yen-Hwa

2011-11-01

Xp11.2 translocation renal cell carcinoma (RCC), a recently recognized distinct subtype of RCC, is characterized by various translocations, all involving the TFE3 transcription factor gene. These rare cancers occur predominantly in children and young adults and comprise about one-third of pediatric RCCs. In the present study, we review the clinical course of Xp11.2 translocation renal cell carcinoma in our institution. We identified eight cases with Xp11.2 translocation RCC between 2007 and 2010 from the pathological archives of the Taipei Veterans General Hospital. We retrospectively analyzed the patients' characteristics, clinical manifestations, and specific pathological features for definitive diagnosis, surgical and systemic treatment and clinical outcome of these rare cancers. Patients were aged 20 years to 49 years (mean age 28 years) with female predominance (6 females, 2 males). One patient presented with asymptomatic renal mass detected incidentally during abdominal sonography. Four patients complained of flank or abdominal pain, and the other three complained of gross hematuria at initial presentation. The mean tumor size was 9.2 cm (range, 4 cm-17 cm). Seven patients underwent radical nephrectomy for the primary tumor, while one presented with multiple metastases. All cases were confirmed by TFE3 immunohistochemistry, a sensitive and specific marker of tumors with TFE3 gene fusion, which showed positive nuclear staining. Three patients presented initially with metastatic diseases, and another three patients progressed to lung, liver and bone metastases at eight, seven and nine months postoperatively. Although RT-PCR and DNA sequencing are the final diagnoses of the molecular identity of Xp11.2 translocation RCC, experienced pathologists could confirm the histologic diagnosis based on the distinctive morphologic features with positive TFE3 immunochemical nuclear stain. Surgical resection is the only treatment. The role of systemic therapy for local

Substance P and Calcitonin gene-related peptide expression in human periodontal ligament after root canal preparation with Reciproc Blue, WaveOne Gold, XP EndoShaper and hand files.

PubMed

Caviedes-Bucheli, J; Rios-Osorio, N; Rey-Rojas, M; Laguna-Rivero, F; Azuero-Holguin, M M; Diaz, L E; Curtidor, H; Castaneda-Ramirez, J J; Munoz, H R

2018-05-17

To quantify Substance P (SP) and Calcitonin gene-related peptide (CGRP) expression in healthy human periodontal ligament from premolars after root canal preparation with Reciproc Blue, WaveOne Gold, XP EndoShaper and hand files. A total of 50 human periodontal ligament samples were obtained from healthy mandibular premolars where extraction was indicated for orthodontic reasons. Prior to extraction, 40 of these premolars were equally divided into four groups, and root canals were prepared using four different systems: Reciproc Blue, WaveOne Gold, XP EndoShaper and a hand instrumentation technique. The remaining 10 healthy premolars were extracted without treatment and served as a negative control group. All periodontal ligament samples were processed, and SP and CGRP were measured by radioimmunoassay. The Kruskal-Wallis test was used to establish significant differences between groups and LSD post hoc comparisons were also performed. Greater SP and CGRP values were found in the hand instrumentation group, followed by the XP EndoShaper, WaveOne Gold and the Reciproc groups. The lower SP and CGRP values were for the healthy periodontal ligament group. The Kruskal-Wallis test revealed significant differences between groups (P < 0.05). Post hoc Least Significant Difference (LSD) tests revealed significant differences (P < 0.05) in SP and CGRP expression between all the comparisons except for the Reciproc Blue and WaveOne Gold group (P > 0.05). All the root canal preparation techniques tested increased SP and CGRP expression in human periodontal ligament, with hand files and XP EndoShaper instruments being associated with greater neuropeptide release compared to Reciproc Blue and WaveOne Gold files. © 2018 International Endodontic Journal. Published by John Wiley & Sons Ltd.

Correction of xeroderma pigmentosum complementation group D mutant cell phenotypes by chromosome and gene transfer: Involvement of the human ERCC2 DNA repair gene

DOE Office of Scientific and Technical Information (OSTI.GOV)

Flejter, W.L.; McDaniel, L.D.; Johns, D.

1992-01-01

Cultured cells from individuals afflicted with the genetically heterogeneous autosomal recessive disorder xeroderma pigmentosum (XP) exhibit sensitivity to UV radiation and defective nucleotide excision repair. Complementation of these mutant phenotypes after the introduction of single human chromosomes from repair-proficient cells into XP cells has provided a means of mapping the genes involved in this disease. The authors now report the phenotypic correction of XP cells from genetic complementation group D (XP-D) by a single human chromosome designated Tneo. Detailed molecular characterization of Tneo revealed a rearranged structure involving human chromosomes 16 and 19, including the excision repair cross-complementing 2 (ERCC2)more » gene from the previously described human DNA repair gene cluster at 19q13.2-q13.3. Direct transfer of a cosmid bearing the ERCC2 gene conferred UV resistance to XP-D cells.« less

Biological characteristics of pediatric renal cell carcinoma associated with Xp11.2 translocations/TFE3 gene fusions.

PubMed

Song, Hong Cheng; Sun, Ning; Zhang, Wei Ping; He, LeJian; Fu, Libing; Huang, ChengRu

2014-04-01

To investigate the clinical features of pediatric Xp11.2 translocation renal cell carcinoma (RCC). A retrospective review of 22 cases over 35 years. Xp11.2 translocation RCCs were identified in 13 boys and 9 girls with a median age of 10.5 years (range: 2.5-16 years). RCC presented with hematuria in 17, abdominal mass in 1, abdominal masses with hematuria in 2, abdominal pain with hematuria in 1, and as an incidental finding in 1 patient. Ten patients were classified stage I, 10 were stage III, and two were stage IV. Of the 10 patients with stage I RCCs, 3 patients with tumor measuring less than 7 cm had nephron-sparing surgery (NSS) and 17 patients underwent simple nephrectomy. A 15-cm tumor was incompletely removed in one patient and another patient with a 25-cm × 18-cm × 15-cm tumor had gross residual. Of the 15 patients followed up between 6 months and 35 years, 13 were still living and 2 had died after surgery. Xp11.2 translocation RCC is the predominant form of pediatric RCC, associated with advanced stage at presentation. Nephrectomy is the usual treatment for RCC but NSS is an option for patients with tumors measuring<7 cm. Patients with N+M0 maintained a favorable prognosis following surgery alone. © 2014.

Characterization of large rearrangements in autosomal dominant polycystic kidney disease and the PKD1/TSC2 contiguous gene syndrome

PubMed Central

Consugar, Mark B.; Wong, Wai C.; Lundquist, Patrick A.; Rossetti, Sandro; Kubly, Vickie J.; Walker, Denise L.; Rangel, Laureano J.; Aspinwall, Richard; Niaudet, W. Patrick; Özen, Seza; David, Albert; Velinov, Milen; Bergstralh, Eric J.; Bae, Kyongtae T.; Chapman, Arlene B.; Guay-Woodford, Lisa M.; Grantham, Jared J.; Torres, Vicente E.; Sampson, Julian R.; Dawson, Brian D.; Harris, Peter C.

2009-01-01

Large DNA rearrangements account for about 8% of disease mutations and are more common in duplicated genomic regions, where they are difficult to detect. Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in either PKD1 or PKD2. PKD1 is located in an intrachromosomally duplicated region. A tuberous sclerosis gene, TSC2, lies immediately adjacent to PKD1 and large deletions can result in the PKD1/TSC2 contiguous gene deletion syndrome. To rapidly identify large rearrangements, a multiplex ligation-dependent probe amplification assay was developed employing base-pair differences between PKD1 and the six pseudogenes to generate PKD1-specific probes. All changes in a set of 25 previously defined deletions in PKD1, PKD2 and PKD1/TSC2 were detected by this assay and we also found 14 new mutations at these loci. About 4% of the ADPKD patients in the CRISP study were found to have gross rearrangements, and these accounted for about a third of base-pair mutation negative families. Sensitivity of the assay showed that about 40% of PKD1/TSC contiguous gene deletion syndrome families contained mosaic cases. Characterization of a family found to be mosaic for a PKD1 deletion is discussed here to illustrate family risk and donor selection considerations. Our assay improves detection levels and the reliability of molecular testing of patients with ADPKD. PMID:18818683

Inversion (X)(p11.4q22) associated with Norrie disease in a four generation family.

PubMed

Pettenati, M J; Rao, P N; Weaver, R G; Thomas, I T; McMahan, M R

1993-03-01

We report on a 4-generation family in which Norrie disease occurs together with a pericentric inversion of the X chromosome in all affected males and carrier females. The breakpoint in the short arm of the X chromosome appears to be at the purported location of the Norrie disease gene. This is the second report of an association between Norrie disease and a chromosome aberration involving Xp11, and the first report of a specific gene disruption, thus physical gene location, due to a pericentric chromosome inversion.

[Research advances in Xp11.2 translocation renal cell carcinoma].

PubMed

Huang, Jian-Hua; Zhou, Fang-Jian

2008-09-01

Xp11.2 translocation renal cell carcinoma (RCC) is a newly identified category of RCC described in the 2004 WHO Classification of Kidney Tumors. Although the incidence is very rare, it accounts about one third of pediatric RCCs. It is different from other RCCs in clinical manifestations, histopathologic features, biological behaviour and prognosis. At present, Xp11.2 translocation RCC has seldom been reported. This review analyzed recent researches on Xp11.2 translocation RCC, described its classification and summarized the characteristics of epidemiology, clinical manifestations, histopathology, diagnosis, treatment and prognosis.

A locus for isolated cataract on human Xp

PubMed Central

Francis, P; Berry, V; Hardcastle, A; Maher, E; Moore, A; Bhattacharya, S

2002-01-01

Purpose: To genetically map the gene causing isolated X linked cataract in a large European pedigree. Methods: Using the patient registers at Birmingham Women's Hospital, UK, we identified and examined 23 members of a four generation family with nuclear cataract. Four of six affected males also had complex congenital heart disease. Pedigree data were collated and leucocyte DNA extracted from venous blood. Linkage analysis by PCR based microsatellite marker genotyping was used to identify the disease locus and mutations within candidate genes screened by direct sequencing. Results: The disease locus was genetically refined to chromosome Xp22, within a 3 cM linkage interval flanked by markers DXS9902 and DXS999 (Zmax=3.64 at θ=0 for marker DXS8036). Conclusions: This is the first report of a locus for isolated inherited cataract on the X chromosome. The disease interval lies within the Nance-Horan locus suggesting allelic heterogeneity. The apparent association with congenital cardiac anomalies suggests a possible new oculocardiac syndrome. PMID:11836358

A locus for isolated cataract on human Xp.

PubMed

Francis, P J; Berry, V; Hardcastle, A J; Maher, E R; Moore, A T; Bhattacharya, S S

2002-02-01

To genetically map the gene causing isolated X linked cataract in a large European pedigree. Using the patient registers at Birmingham Women's Hospital, UK, we identified and examined 23 members of a four generation family with nuclear cataract. Four of six affected males also had complex congenital heart disease. Pedigree data were collated and leucocyte DNA extracted from venous blood. Linkage analysis by PCR based microsatellite marker genotyping was used to identify the disease locus and mutations within candidate genes screened by direct sequencing. The disease locus was genetically refined to chromosome Xp22, within a 3 cM linkage interval flanked by markers DXS9902 and DXS999 (Zmax=3.64 at theta=0 for marker DXS8036). This is the first report of a locus for isolated inherited cataract on the X chromosome. The disease interval lies within the Nance-Horan locus suggesting allelic heterogeneity. The apparent association with congenital cardiac anomalies suggests a possible new oculocardiac syndrome.

Pediatric renal cell carcinomas with Xp11.2 rearrangements are immunoreactive for hMLH1 and hMSH2 proteins.

PubMed

Rakheja, Dinesh; Kapur, Payal; Tomlinson, Gail E; Margraf, Linda R

2005-01-01

Alveolar soft part sarcoma and pediatric renal cell carcinoma share a similar chromosomal abnormality, t(X;17)(p11.2;q25). Recently, it has been suggested that the inactivation of DNA mismatch repair genes hMLH1 and hMSH2 may play an additional role in the pathogenesis of alveolar soft part sarcoma. Immunohistochemical expression of the proteins hMLH1 and hMSH2 is indicative of the activation status of the corresponding genes. We performed immunohistochemistry for hMLH1 and hMSH2 in 4 cases of pediatric renal cell carcinomas with Xp11.2 rearrangements. All cases showed nuclear immunoreactivity for both proteins, although the staining was patchy. Our study demonstrates that inactivation of the DNA mismatch repair genes hMLH1 and hMSH2 does not appear to play a role in the tumorigenesis of pediatric renal cell carcinomas with Xp11.2 rearrangements.

Chance, destiny, and the inner workings of ClpXP.

PubMed

Russell, Rick; Matouschek, Andreas

2014-07-31

AAA+ proteases are responsible for protein degradation in all branches of life. Using single-molecule and ensemble assays, Cordova et al. investigate how the bacterial protease ClpXP steps through a substrate's polypeptide chain and construct a quantitative kinetic model that recapitulates the interplay between stochastic and deterministic behaviors of ClpXP. Copyright © 2014 Elsevier Inc. All rights reserved.

Analysis of Extreme Phenotype Bulk Copy Number Variation (XP-CNV) Identified the Association of rp1 with Resistance to Goss's Wilt of Maize.

PubMed

Hu, Ying; Ren, Jie; Peng, Zhao; Umana, Arnoldo A; Le, Ha; Danilova, Tatiana; Fu, Junjie; Wang, Haiyan; Robertson, Alison; Hulbert, Scot H; White, Frank F; Liu, Sanzhen

2018-01-01

Goss's wilt (GW) of maize is caused by the Gram-positive bacterium Clavibacter michiganensis subsp. nebraskensis (Cmn) and has spread in recent years throughout the Great Plains, posing a threat to production. The genetic basis of plant resistance is unknown. Here, a simple method for quantifying disease symptoms was developed and used to select cohorts of highly resistant and highly susceptible lines known as extreme phenotypes (XP). Copy number variation (CNV) analyses using whole genome sequences of bulked XP revealed 141 genes containing CNV between the two XP groups. The CNV genes include the previously identified common rust resistant locus rp1 . Multiple Rp1 accessions with distinct rp1 haplotypes in an otherwise susceptible accession exhibited hypersensitive responses upon inoculation. GW provides an excellent system for the genetic dissection of diseases caused by closely related subspecies of C. michiganesis . Further work will facilitate breeding strategies to control GW and provide needed insight into the resistance mechanism of important related diseases such as bacterial canker of tomato and bacterial ring rot of potato.

Preclinical Corrective Gene Transfer in Xeroderma Pigmentosum Human Skin Stem Cells

PubMed Central

Warrick, Emilie; Garcia, Marta; Chagnoleau, Corinne; Chevallier, Odile; Bergoglio, Valérie; Sartori, Daniela; Mavilio, Fulvio; Angulo, Jaime F; Avril, Marie-Françoise; Sarasin, Alain; Larcher, Fernando; Del Rio, Marcela; Bernerd, Françoise; Magnaldo, Thierry

2012-01-01

Xeroderma pigmentosum (XP) is a devastating disease associated with dramatic skin cancer proneness. XP cells are deficient in nucleotide excision repair (NER) of bulky DNA adducts including ultraviolet (UV)-induced mutagenic lesions. Approaches of corrective gene transfer in NER-deficient keratinocyte stem cells hold great hope for the long-term treatment of XP patients. To face this challenge, we developed a retrovirus-based strategy to safely transduce the wild-type XPC gene into clonogenic human primary XP-C keratinocytes. De novo expression of XPC was maintained in both mass population and derived independent candidate stem cells (holoclones) after more than 130 population doublings (PD) in culture upon serial propagation (>1040 cells). Analyses of retrovirus integration sequences in isolated keratinocyte stem cells suggested the absence of adverse effects such as oncogenic activation or clonal expansion. Furthermore, corrected XP-C keratinocytes exhibited full NER capacity as well as normal features of epidermal differentiation in both organotypic skin cultures and in a preclinical murine model of human skin regeneration in vivo. The achievement of a long-term genetic correction of XP-C epidermal stem cells constitutes the first preclinical model of ex vivo gene therapy for XP-C patients. PMID:22068429

Cloning and characterization of the mouse XPAC gene.

PubMed Central

van Oostrom, C T; de Vries, A; Verbeek, S J; van Kreijl, C F; van Steeg, H

1994-01-01

Xeroderma Pigmentosum is a human disease, which is, among others, characterized by a high incidence of (sunlight induced) skin cancer, due to a defect in nucleotide excision repair (NER). The human DNA repair gene XPAC corrects this defect in cells isolated from Xeroderma Pigmentosum complementation group A (XP-A) patients. To enable the development of a transgenic mouse model for XP-A by gene targeting in embryonic stem cells, we cloned and characterized the mouse homologue of the XPAC gene. The mouse XPAC gene was found to consist of 6 exons, spanning approximately 21 kb. The nucleotide sequence of the exons is identical to that of the also cloned the mouse XPAC cDNA. Furthermore, the deduced amino acid sequence of the XPAC protein is the same as the one published previously by Tanaka et al. From CAT assay analysis, the promoter of the XPAC gene appeared to be located within 313 bp upstream of the assumed transcriptional start site. Like the promoters of other eukaryotic DNA repair genes (i.e. ERCC-1 and XPBC/ERCC-3), the mouse XPAC promoter region lacks classical promoter elements like TATA-, GC- and CAAT boxes. However, it contains an unique polypyrimidine-rich box, which is so far only found in genes encoding DNA repair enzymes. The function of this box in the regulation of transcription is still unclear. PMID:8127648

Remapping of the RP15 Locus for X-Linked Cone-Rod Degeneration to Xp11.4-p21.1, and Identification of a De Novo Insertion in the RPGR Exon ORF15

PubMed Central

Mears, Alan J.; Hiriyanna, Suja; Vervoort, Raf; Yashar, Beverly; Gieser, Linn; Fahrner, Stacey; Daiger, Stephen P.; Heckenlively, John R.; Sieving, Paul A.; Wright, Alan F.; Swaroop, Anand

2000-01-01

X-linked forms of retinitis pigmentosa (XLRP) are among the most severe, because of their early onset, often leading to significant vision loss before the 4th decade. Previously, the RP15 locus was assigned to Xp22, by linkage analysis of a single pedigree with “X-linked dominant cone-rod degeneration.” After clinical reevaluation of a female in this pedigree identified her as affected, we remapped the disease to a 19.5-cM interval (DXS1219–DXS993) at Xp11.4-p21.1. This new interval overlapped both RP3 (RPGR) and COD1. Sequencing of the previously published exons of RPGR revealed no mutations, but a de novo insertion was detected in the new RPGR exon, ORF15. The identification of an RPGR mutation in a family with a severe form of cone and rod degeneration suggests that RPGR mutations may encompass a broader phenotypic spectrum than has previously been recognized in “typical” retinitis pigmentosa. PMID:10970770

The XP spaceplane: A near term multi-purpose suborbital RLV

NASA Astrophysics Data System (ADS)

Lauer, Charles J.

2007-06-01

This paper will describe the history, technology and design features of the XP spaceplane being developed by Rocketplane Ltd. in Oklahoma. The XP is a four seat fighter-sized spaceplane that uses turbojets for takeoff and landing and a liquid oxygen/kerosene rocket engine for main propulsion during its ascent to a 100 km apogee suborbital space flight. The XP is intended to serve a variety of markets including suborbital tourist flights, intermediate duration microgravity research, remote sensing, astronomy, and microsatellite launch missions. Changes in vehicle configuration and flight profile for serving each of these markets will be described. The prototype XP will have its rollout ceremony at the end of 2007 and will begin test flights in early 2008. Commercial space flight operations are expected to begin in fall 2008 with tourist flights and microgravity research flights being the early customer base. The spaceplane's flight systems, safety systems, and operating procedures will be reviewed. In addition, key elements of the Rocketplane business and financial model will be discussed.

Extreme-phenotype genome-wide association study (XP-GWAS): a method for identifying trait-associated variants by sequencing pools of individuals selected from a diversity panel.

PubMed

Yang, Jinliang; Jiang, Haiying; Yeh, Cheng-Ting; Yu, Jianming; Jeddeloh, Jeffrey A; Nettleton, Dan; Schnable, Patrick S

2015-11-01

Although approaches for performing genome-wide association studies (GWAS) are well developed, conventional GWAS requires high-density genotyping of large numbers of individuals from a diversity panel. Here we report a method for performing GWAS that does not require genotyping of large numbers of individuals. Instead XP-GWAS (extreme-phenotype GWAS) relies on genotyping pools of individuals from a diversity panel that have extreme phenotypes. This analysis measures allele frequencies in the extreme pools, enabling discovery of associations between genetic variants and traits of interest. This method was evaluated in maize (Zea mays) using the well-characterized kernel row number trait, which was selected to enable comparisons between the results of XP-GWAS and conventional GWAS. An exome-sequencing strategy was used to focus sequencing resources on genes and their flanking regions. A total of 0.94 million variants were identified and served as evaluation markers; comparisons among pools showed that 145 of these variants were statistically associated with the kernel row number phenotype. These trait-associated variants were significantly enriched in regions identified by conventional GWAS. XP-GWAS was able to resolve several linked QTL and detect trait-associated variants within a single gene under a QTL peak. XP-GWAS is expected to be particularly valuable for detecting genes or alleles responsible for quantitative variation in species for which extensive genotyping resources are not available, such as wild progenitors of crops, orphan crops, and other poorly characterized species such as those of ecological interest. © 2015 The Authors The Plant Journal published by Society for Experimental Biology and John Wiley & Sons Ltd.

Genotype-phenotype characterization in 13 individuals with chromosome Xp11.22 duplications.

PubMed

Grams, Sarah E; Argiropoulos, Bob; Lines, Matthew; Chakraborty, Pranesh; Mcgowan-Jordan, Jean; Geraghty, Michael T; Tsang, Marilyn; Eswara, Marthand; Tezcan, Kamer; Adams, Kelly L; Linck, Leesa; Himes, Patricia; Kostiner, Dana; Zand, Dina J; Stalker, Heather; Driscoll, Daniel J; Huang, Taosheng; Rosenfeld, Jill A; Li, Xu; Chen, Emily

2016-04-01

We report 13 new individuals with duplications in Xp11.22-p11.23. The index family has one male and two female members in three generations with mild-severe intellectual disability (ID), speech delay, dysmorphic features, early puberty, constipation, and/or hand and foot abnormalities. Affected individuals were found to have two small duplications in Xp11.22 at nucleotide position (hg19) 50,112,063-50,456,458 bp (distal) and 53,160,114-53,713,154 bp (proximal). Collectively, these two regions include 14 RefSeq genes, prompting collection of a larger cohort of patients, in an attempt to delineate critical genes associated with the observed phenotype. In total, we have collected data on nine individuals with duplications overlapping the distal duplication region containing SHROOM4 and DGKK and eight individuals overlapping the proximal region including HUWE1. Duplications of HUWE1 have been previously associated with non-syndromic ID. Our data, with previously published reports, suggest that duplications involving SHROOM4 and DGKK may represent a new syndromic X-linked ID critical region associated with mild to severe ID, speech delay +/- dysarthria, attention deficit disorder, precocious puberty, constipation, and motor delay. We frequently observed foot abnormalities, 5th finger clinodactyly, tapering fingers, constipation, and exercise intolerance in patients with duplications of these two genes. Regarding duplications including the proximal region, our observations agree with previous studies, which have found associations with intellectual disability. In addition, expressive language delay, failure to thrive, motor delay, and 5th finger clinodactyly were also frequently observed in patients with the proximal duplication. © 2015 Wiley Periodicals, Inc.

Translocation (X;6) in a female with Duchenne muscular dystrophy: implications for the localisation of the DMD locus.

PubMed Central

Zatz, M; Vianna-Morgante, A M; Campos, P; Diament, A J

1981-01-01

A female with Duchenne muscular dystrophy who was a carrier of a balanced translocation t(X;6)(p21;q21) is reported. Four other previously described (X;A) translocations associated with DMD share with the present case a breakpoint at Xp21. The extremely low probability of five independent (X;A) translocations having a breakpoint at Xp21 points to a non-rand association of this site with the DMD phenotype. A DMD locus at Xp21 could be damaged by the translocation, giving rise to Duchenne muscular dystrophy. Alternatively, a pre-existing DMD gene could weaken the chromosome, favouring breaks at Xp21. Images PMID:7334502

Lake shoreline in the contiguous United States: Quantity, distribution and sensitivity to observation resolution

USGS Publications Warehouse

Winslow, Luke A.; Read, Jordan S.; Hanson, Paul C.; Stanley, Emily H.

2013-01-01

1. Quantifying lake biogeochemical processing at broad spatial scales requires that we scale processes along with physical metrics. Past work has primarily scaled lentic processes using estimates of lake surface area. However, many processes important to lakes, such as material, energy and biological fluxes and biogeochemical cycling, scale with lake perimeter. 2. We estimate the total lake perimeter for the contiguous United States (U.S.) and examine the sensitivity of this estimate to measurement resolution. At the original mapping resolution, lakes in the contiguous U.S. have a total perimeter of over 1.8 million km. 3. The change in measured perimeter versus measurement resolution for the contiguous U.S. had a log-log slope (also known as the fractal dimension) of 0.21, generally less than previously reported estimates. With changing observation resolution, total measured perimeter was most sensitive to the inclusion or exclusion of small lakes, not shoreline complexity. 4. The total aquatic–terrestrial interface in lakes is less than one-tenth that of streams and rivers, which collectively account for over 21 million km of shoreline in the contiguous U.S. This study further describes the distribution of lake perimeter and proposes a technique that can contribute to understanding continental-scale processes.

X-Linked Syndrome of Polyendocrinopathy, Immune Dysfunction, and Diarrhea Maps to Xp11.23-Xq13.3

PubMed Central

Bennett, Craig L.; Yoshioka, Ritsuko; Kiyosawa, Hidenori; Barker, David F.; Fain, Pamela R.; Shigeoka, Ann O.; Chance, Phillip F.

2000-01-01

Summary We describe genetic analysis of a large pedigree with an X-linked syndrome of polyendocrinopathy, immune dysfunction, and diarrhea (XPID), which frequently results in death during infancy or childhood. Linkage analysis mapped the XPID gene to a 17-cM interval defined by markers DXS8083 and DXS8107 on the X chromosome, at Xp11.23-Xq13.3. The maximum LOD score was 3.99 (recombination fraction0) at DXS1235. Because this interval also harbors the gene for Wiskott-Aldrich syndrome (WAS), we investigated mutations in the WASP gene, as the molecular basis of XPID. Northern blot analysis detected the same relative amount and the same-sized WASP message in patients with XPID and in a control. Analysis of the WASP coding sequence, an alternate promoter, and an untranslated upstream first exon was carried out, and no mutations were found in patients with XPID. A C→T transition within the alternate translation start site cosegregated with the XPID phenotype in this family; however, the same transition site was detected in a normal control male. We conclude that XPID maps to Xp11.23-Xq13.3 and that mutations of WASP are not associated with XPID. PMID:10677306

Xp22.33p22.12 Duplication in a Patient with Intellectual Disability and Dysmorphic Facial Features

PubMed Central

Lintas, Carla; Picinelli, Chiara; Piras, Ignazio S.; Sacco, Roberto; Gabriele, Stefano; Verdecchia, Magda; Persico, Antonio M.

2016-01-01

A novel 19.98-Mb duplication in chromosome Xp22.33p22.12 was detected by array CGH in a 30-year-old man affected by intellectual disability, congenital hypotonia and dysmorphic features. The duplication encompasses more than 100 known genes. Many of these genes (such as neuroligin 4, cyclin-dependent kinase like 5, and others) have already correlated with X-linked intellectual disability and/or neurodevelopmental disorders. Due to the high number of potentially pathogenic genes involved in the reported duplication, we cannot correlate the clinical phenotype to a single gene. Indeed, we suggest that the resulting clinical phenotype may have arisen from the overexpression and consequent perturbation of fine gene dosage. PMID:26997944

Xp22.33p22.12 Duplication in a Patient with Intellectual Disability and Dysmorphic Facial Features.

PubMed

Lintas, Carla; Picinelli, Chiara; Piras, Ignazio S; Sacco, Roberto; Gabriele, Stefano; Verdecchia, Magda; Persico, Antonio M

2016-02-01

A novel 19.98-Mb duplication in chromosome Xp22.33p22.12 was detected by array CGH in a 30-year-old man affected by intellectual disability, congenital hypotonia and dysmorphic features. The duplication encompasses more than 100 known genes. Many of these genes (such as neuroligin 4, cyclin-dependent kinase like 5, and others) have already correlated with X-linked intellectual disability and/or neurodevelopmental disorders. Due to the high number of potentially pathogenic genes involved in the reported duplication, we cannot correlate the clinical phenotype to a single gene. Indeed, we suggest that the resulting clinical phenotype may have arisen from the overexpression and consequent perturbation of fine gene dosage.

Adult-onset renal cell carcinoma associated with Xp11.2 translocation/TFE3 gene fusion: 3 case reports and review of literature.

PubMed

Gong, Pengfeng; Zhuang, Qianfeng; Wang, Kun; Xu, Renfang; Chen, Yiming; Wang, Xiaogang; Yin, Shuai

2018-06-01

Renal cell carcinoma associated with Xp11.2 translocations/TFE3 gene fusions is a rare subtype of renal cell carcinoma. This predominantly occurs in juveniles, but rarely seen in adults with lymph node or organic metastasis and a worsened prognosis. Herein, we presented 3 adult cases of Xp11-RCC. Two patients were in early stage and good condition, and the third patient had lymph node metastasis but showed no recurrence after a 3-month follow-up. Case 1: A 50-year-old female without any lumbago and gross hematuria was incidentally detected by left renal mass by ultrasonography. Case 2: A 31-year-old female with 2-year hemodialysis was detected with right renal carcinoma during preoperative examination of renal transplant. Case 3: A 45-year-old male with right lumbago for 1 month was detected with a mass in the lower pole of right kidney by ultrasonography. The characteristics of these 3 images are not consistent with each other, and showed some differences with the previous ones. All these 3 patients underwent laparoscopic radical nephrectomy, and case 1 patient underwent renal hilar lymphnode dissection at the same time. Immunohistochemistry was performed on all the 3 tumors, revealing that the tumor cells were positive for TFE3 and Melan-A. Case 1 showed lymph node metastasis, and received mTOR inhibitors. The 3 patients had no recurrent and new metastasis in other organs after follow-up for 3 months, 2 months, and 11 months, respectively. Whether the adult-onset Xp-RCC has an aggressive clinical course still remains controversial. Characteristics of the images of the 3 adult cases showed some uniformity but still have some differences. Immunohistochemistry results revealed tumor cell positive for TFE3, but have no consistency in carbonic anhydrase IX, CD117, Ki67, CK8/18 AE1/AE3 and so on. Therefore, the uniform and definitive diagnostic standards of the tumors are uncertain. Hence, more cases and findings are required to elaborate the standards of all the

Understanding Xeroderma Pigmentosum Complementation Groups Using Gene Expression Profiling after UV-Light Exposure.

PubMed

Bowden, Nikola A; Beveridge, Natalie J; Ashton, Katie A; Baines, Katherine J; Scott, Rodney J

2015-07-14

Children with the recessive genetic disorder Xeroderma Pigmentosum (XP) have extreme sensitivity to UV-light, a 10,000-fold increase in skin cancers from age 2 and rarely live beyond 30 years. There are seven genetic subgroups of XP, which are all resultant of pathogenic mutations in genes in the nucleotide excision repair (NER) pathway and a XP variant resultant of a mutation in translesion synthesis, POLH. The clinical symptoms and severity of the disease is varied across the subgroups, which does not correlate with the functional position of the affected protein in the NER pathway. The aim of this study was to further understand the biology of XP subgroups, particularly those that manifest with neurological symptoms. Whole genome gene expression profiling of fibroblasts from each XP complementation group was assessed before and after UV-light exposure. The biological pathways with altered gene expression after UV-light exposure were distinct for each subtype and contained oncogenic related functions such as perturbation of cell cycle, apoptosis, proliferation and differentiation. Patients from the subgroups XP-B and XP-F were the only subgroups to have transcripts associated with neuronal activity altered after UV-light exposure. This study will assist in furthering our understanding of the different subtypes of XP which will lead to better diagnosis, treatment and management of the disease.

Understanding Xeroderma Pigmentosum Complementation Groups Using Gene Expression Profiling after UV-Light Exposure

PubMed Central

Bowden, Nikola A.; Beveridge, Natalie J.; Ashton, Katie A.; Baines, Katherine J.; Scott, Rodney J.

2015-01-01

Children with the recessive genetic disorder Xeroderma Pigmentosum (XP) have extreme sensitivity to UV-light, a 10,000-fold increase in skin cancers from age 2 and rarely live beyond 30 years. There are seven genetic subgroups of XP, which are all resultant of pathogenic mutations in genes in the nucleotide excision repair (NER) pathway and a XP variant resultant of a mutation in translesion synthesis, POLH. The clinical symptoms and severity of the disease is varied across the subgroups, which does not correlate with the functional position of the affected protein in the NER pathway. The aim of this study was to further understand the biology of XP subgroups, particularly those that manifest with neurological symptoms. Whole genome gene expression profiling of fibroblasts from each XP complementation group was assessed before and after UV-light exposure. The biological pathways with altered gene expression after UV-light exposure were distinct for each subtype and contained oncogenic related functions such as perturbation of cell cycle, apoptosis, proliferation and differentiation. Patients from the subgroups XP-B and XP-F were the only subgroups to have transcripts associated with neuronal activity altered after UV-light exposure. This study will assist in furthering our understanding of the different subtypes of XP which will lead to better diagnosis, treatment and management of the disease. PMID:26184184

Mental retardation in a boy with an interstitial deletion at Xp22.3 involving STS, KAL1, and OA1: Implication for the MRX locus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Muroya, Koji; Ogata, Tsutomu; Natsuo, Nobutake

Although genotype-phenotype correlations in male patients with various types of nullisomy for Xp22.3 have assigned a locus for X-linked mental retardation (MRX) to an approximately 3-Mb region between DXS31 and STS, the precise location has not been determined. In this paper, we describe a 14 7/12 year old Japanese boy with mental retardation and an interstitial deletion at Xp22.3 involving STS, KAL1, and OA1, and compare the deletion map with that of previously reported three familial male patients with low-normal intelligence and a similar interstitial deletion at Xp22.3. The results suggest that the MRX gene is further localized to themore » roughly 1.5-Mb region between DXS1060 and DXS1139. 31 refs., 4 figs.« less

Newly Designed Break-Apart and ASPL-TFE3 Dual-Fusion FISH Assay Are Useful in Diagnosing Xp11.2 Translocation Renal Cell Carcinoma and ASPL-TFE3 Renal Cell Carcinoma

PubMed Central

Chen, Xiancheng; Yang, Yang; Gan, Weidong; Xu, Linfeng; Ye, Qing; Guo, Hongqian

2015-01-01

Abstract The diagnosis of Xp11.2 translocation renal cell carcinoma (tRCC), which relies on morphology and immunohistochemistry (IHC), is often either missed in the diagnosis or misdiagnosed. To improve the accuracy of diagnosis of Xp11.2 tRCC and ASPL-TFE3 renal cell carcinoma (RCC), we investigated newly designed fluorescence in situ hybridization (FISH) probes (diagnostic accuracy study). Based on the genetic characteristics of Xp11.2 tRCC and the ASPL-TFE3 RCC, a new break-apart TFE3 FISH probe and an ASPL-TFE3 dual-fusion FISH probe were designed and applied to 65 patients with RCC who were <45 years old or showed suspicious microscopic features of Xp11.2 tRCC in our hospital. To test the accuracy of the probes, we further performed reverse transcriptase–polymerase chain reaction (PCR) on 8 cases for which frozen tissues were available. Among the 65 cases diagnosed with RCC, TFE3 IHC was positive in 24 cases. Twenty-two cases were confirmed as Xp11.2 tRCC by break-apart TFE3 FISH, and 6 of these cases were further diagnosed as ASPL-TFE3 RCC by ASPL-TFE3 dual-fusion FISH detection. Importantly, reverse transcriptase–PCR showed concordant results with the results of FISH assay in the 8 available frozen cases. The break-apart and ASPL-TFE3 dual-fusion FISH assay can accurately detect the translocation of the TFE3 gene and ASPL-TFE3 fusion gene and can thus serve as a valid complementary method for diagnosing Xp11.2 tRCC and ASPL-TFE3 RCC. PMID:25984679

Xp11.2 Translocation Renal Cell Carcinoma Diagnosed by Immunohistochemistry and Cytogenetics.

PubMed

Dey, Biswajit; Badhe, Bhawana; Govindarajan, Krishna Kumar; Ramesh, Ranjith Arumbakkam

2016-01-01

Xp11.2 translocation renal cell carcinomas (TRCCs) are a group of neoplasms with distinct clinical, histopathological appearance, immunohistochemical, and cytogenetic profile. We report a case of Xp11.2 translocation TRCC in an 11-year-old male diagnosed based on immunohistochemistry and fluorescence in situ hybridization.

An Xp11.2 translocation renal cell carcinoma with SMARCB1 (INI1) inactivation in adult end-stage renal disease: a case report.

PubMed

Yu, Lu; Li, Jun; Xu, Sanpeng; Navia Miranda, Mariajose; Wang, Guoping; Duan, Yaqi

2016-10-12

Xp11.2 translocation/transcription factor E3 (TFE3) rearrangement renal cell carcinoma (RCC) is a rare subtype of RCC with limited clinical and pathological data. Here we present an unusual high-grade Xp11.2 translocation RCC with a rhabdoid feature and SMARCB1 (INI1) inactivation in a 40-year-old man with end-stage kidney disease. The histological examination of the dissected left renal tumor showed an organoid architecture of the eosinophilic or clear neoplastic cells with necrosis and high mitotic activity. In some areas, non-adhesive tumor cells with eccentric nuclei were observed. Immunohistochemically (IHC), the tumor cells are positive for TFE3 and the renal tubular markers (PAX2 and PAX8), and completely negative for SMARCB1, an oncosuppressor protein. Break-apart florescence in situ hybridization and reverse transcription polymerase chain reaction confirmed TFE3 rearrangement on Xp11.2 and the presence of ASPSCR1-TFE3 fusion gene. DNA sequencing revealed a frameshift mutation in exon 4 of SMARCB1 gene. It is important to recognize this rare RCC with both TFE3 rearrangement and SMARCB1 inactivation, as the prognosis and therapeutic strategies, particularly targeted therapies for such tumors, might be different.

PSF/SFPQ is a very common gene fusion partner in TFE3 rearrangement-associated perivascular epithelioid cell tumors (PEComas) and melanotic Xp11 translocation renal cancers: clinicopathologic, immunohistochemical, and molecular characteristics suggesting classification as a distinct entity.

PubMed

Rao, Qiu; Shen, Qin; Xia, Qiu-yuan; Wang, Zi-yu; Liu, Biao; Shi, Shan-shan; Shi, Qun-li; Yin, Hong-lin; Wu, Bo; Ye, Sheng-bing; Li, Li; Chen, Jie-Yu; Pan, Min-hong; Li, Qing; Li, Rui; Wang, Xuan; Zhang, Ru-song; Yu, Bo; Ma, Heng-hui; Lu, Zhen-feng; Zhou, Xiao-jun

2015-09-01

An increasing number of TFE3 rearrangement-associated tumors, such as TFE3 rearrangement-associated perivascular epithelioid cell tumors (PEComas), melanotic Xp11 translocation renal cancers, and melanotic Xp11 neoplasms, have recently been reported. We examined 12 such cases, including 5 TFE3 rearrangement-associated PEComas located in the pancreas, cervix, or pelvis and 7 melanotic Xp11 translocation renal cancers, using clinicopathologic, immunohistochemical, and molecular analyses. All the tumors shared a similar morphology, including a purely nested or sheet-like architecture separated by a delicate vascular network, purely epithelioid cells displaying a clear or granular eosinophilic cytoplasm, a lack of papillary structures and spindle cell or fat components, uniform round or oval nuclei containing small visible nucleoli, and, in most cases (11/12), melanin pigmentation. The levels of mitotic activity and necrosis varied. All 12 cases displayed moderately (2+) or strongly (3+) positive immunoreactivity for TFE3 and cathepsin K. One case labeled focally for HMB45 and Melan-A, whereas the others typically labeled moderately (2+) or strongly (3+) for 1 of these markers. None of the cases were immunoreactive for smooth muscle actin, desmin, CKpan, S100, or PAX8. PSF-TFE3 fusion genes were confirmed by reverse transcription polymerase chain reaction in cases (7/7) in which a novel PSF-TFE3 fusion point was identified. All of the cases displayed TFE3 rearrangement associated with Xp11 translocation. Furthermore, we developed a PSF-TFE3 fusion fluorescence in situ hybridization assay for the detection of the PSF-TFE3 fusion gene and detected it in all 12 cases. Clinical follow-up data were available for 7 patients. Three patients died, and 2 patients (cases 1 and 3) remained alive with no evidence of disease after initial resection. Case 2 experienced recurrence and remained alive with disease. Case 5, a recent case, remained alive with extensive abdominal cavity

Xp11.2 Translocation Renal Cell Carcinoma Diagnosed by Immunohistochemistry and Cytogenetics

PubMed Central

Dey, Biswajit; Badhe, Bhawana; Govindarajan, Krishna Kumar; Ramesh, Ranjith Arumbakkam

2016-01-01

Xp11.2 translocation renal cell carcinomas (TRCCs) are a group of neoplasms with distinct clinical, histopathological appearance, immunohistochemical, and cytogenetic profile. We report a case of Xp11.2 translocation TRCC in an 11-year-old male diagnosed based on immunohistochemistry and fluorescence in situ hybridization. PMID:27365924

The protease ClpXP and the PAS-domain protein DivL regulate CtrA and gene transfer agent production in Rhodobacter capsulatus.

PubMed

Westbye, A B; Kater, L; Wiesmann, C; Ding, H; Yip, C K; Beatty, J T

2018-04-06

Several members of the Rhodobacterales ( Alphaproteobacteria ) produce a conserved horizontal gene transfer vector, called gene transfer agent (GTA), that appears to have evolved from a bacteriophage. The model system to study GTA biology is the R. capsulatus GTA (RcGTA), a small, tailed bacteriophage-like particle produced by a subset of the cells in a culture. The response regulator CtrA is conserved in the Alphaproteobacteria and is an essential regulator of RcGTA production: it controls production and maturation of the RcGTA particle and RcGTA release from cells. CtrA also controls the natural transformation-like system required for cells to receive RcGTA-donated DNA. Here, we report that a dysregulation of the CckA-ChpT-CtrA phosphorelay - either by loss of the PAS-domain protein DivL or by substituting the autophosphorylation residue of the hybrid histidine kinase CckA - decreased CtrA phosphorylation and greatly increased RcGTA protein production in R. capsulatus We show that a loss of the ClpXP protease or the three C-terminal residues of CtrA resulted in increased CtrA levels in R. capsulatus, and identify ClpX(P) as essential for maturation of RcGTA particles. Furthermore, we show that CtrA phosphorylation is important for head spike production. Our results provide novel insight into the regulation of CtrA and GTAs in the Rhodobacterales Importance Members of the Rhodobacterales are abundant in ocean and fresh water environments. The conserved GTA produced by many Rhodobacterales may have an important role in horizontal gene transfer (HGT) in aquatic environments and provide a significant contribution to their adaptation. GTA production is controlled by bacterial regulatory systems, including the conserved CckA-ChpT-CtrA phosphorelay, however several questions about GTA regulation remains. Our identification that a 'short' DivL homologue and ClpXP regulate CtrA in R. capsulatus extends the model of CtrA regulation from Caulobacter crescentus to a member

Multilevel non-contiguous spinal injuries: incidence and patterns based on whole spine MRI.

PubMed

Kanna, Rishi Mugesh; Gaike, Chandrasekar V; Mahesh, Anupama; Shetty, Ajoy Prasad; Rajasekaran, S

2016-04-01

Multi-level non-contiguous spinal injuries are not uncommon and their incidence varies from 1.6 to 77% depending on the type of imaging modality used. Delayed diagnosis and missed spinal injuries in non-contiguous spine fractures have been frequently described which can result in significant pain, deformity and neurological deficit. The efficacy of whole spine MRI in detecting asymptomatic significant vertebral fractures is not known. Consecutive spinal injury patients treated between 2011 and 2013 were retrospectively evaluated based on clinical and radiographic records. Patients' demographics, mode of injury, presence of associated injuries, clinical symptoms and the presence of neurological deficit were studied. Radiographs of the fractured region and whole spine MRI were evaluated for the presence of multi-level injuries. Among 484 patients, 95 (19.62%) patients had multilevel injuries including 86 (17.76%) with non-contiguous injuries. Five common patterns of non-contiguous spinal injuries were observed. Pattern I: cervical and thoracic--29.1%, Pattern II: thoracolumbar and lumbosacral--22.1%, Pattern III: thoracic and thoracolumbar--12.8 %, Pattern IV: cervical and thoracolumbar--9.1% and Pattern V: lumbosacral and associated injuries--9.0 %. The incidence of intra-regional non-contiguous injuries was 17.4%. Whole spine MRI scan detected 24 (28.6%) missed secondary injuries of which 5 were unstable. The incidence of multilevel non-contiguous spine injury using whole spine MRI imaging is 17.76%. Five different patterns of multi-level non-contiguous injuries were found with the most common pattern being the cervical and thoracic level injuries. The incidence of unstable injuries can be as high as 21% of missed secondary injuries.

A case study of metastatic Xp11.2 translocation renal cell carcinoma effectively treated with sunitinib.

PubMed

Numakura, Kazuyuki; Tsuchiya, Norihiko; Yuasa, Takeshi; Saito, Mitsuru; Obara, Takashi; Tsuruta, Hiroshi; Narita, Shintaro; Horikawa, Yohei; Satoh, Shigeru; Habuchi, Tomonori

2011-10-01

We report a case of Xp11.2 translocation renal cell carcinoma (RCC) whose lung metastases were effectively treated with sunitinib. A 43-year-old woman presenting with upper abdominal pain was diagnosed with a left renal tumor. Laparoscopic left radical nephrectomy was performed. Histopathological examination of the surgical specimen revealed a clear-cell carcinoma of the left kidney. Two years later, multiple lung metastases were detected and the patient was treated daily with 50 mg sunitinib. A computed tomography scan performed after 2 cycles of sunitinib treatment revealed partial regression of these metastases. The partial regression has been maintained for >3 years. In retrospective evaluation of the primary RCC, tumor cells showed strong nuclear staining for transcription factor E3 (TFE3) protein and TFE3 split-fluorescence in-situ hybridization revealed translocation involving the TFE3 gene. These findings strongly support diagnosis of Xp11.2 translocation RCC.

Applications Performance on NAS Intel Paragon XP/S - 15#

NASA Technical Reports Server (NTRS)

Saini, Subhash; Simon, Horst D.; Copper, D. M. (Technical Monitor)

1994-01-01

The Numerical Aerodynamic Simulation (NAS) Systems Division received an Intel Touchstone Sigma prototype model Paragon XP/S- 15 in February, 1993. The i860 XP microprocessor with an integrated floating point unit and operating in dual -instruction mode gives peak performance of 75 million floating point operations (NIFLOPS) per second for 64 bit floating point arithmetic. It is used in the Paragon XP/S-15 which has been installed at NAS, NASA Ames Research Center. The NAS Paragon has 208 nodes and its peak performance is 15.6 GFLOPS. Here, we will report on early experience using the Paragon XP/S- 15. We have tested its performance using both kernels and applications of interest to NAS. We have measured the performance of BLAS 1, 2 and 3 both assembly-coded and Fortran coded on NAS Paragon XP/S- 15. Furthermore, we have investigated the performance of a single node one-dimensional FFT, a distributed two-dimensional FFT and a distributed three-dimensional FFT Finally, we measured the performance of NAS Parallel Benchmarks (NPB) on the Paragon and compare it with the performance obtained on other highly parallel machines, such as CM-5, CRAY T3D, IBM SP I, etc. In particular, we investigated the following issues, which can strongly affect the performance of the Paragon: a. Impact of the operating system: Intel currently uses as a default an operating system OSF/1 AD from the Open Software Foundation. The paging of Open Software Foundation (OSF) server at 22 MB to make more memory available for the application degrades the performance. We found that when the limit of 26 NIB per node out of 32 MB available is reached, the application is paged out of main memory using virtual memory. When the application starts paging, the performance is considerably reduced. We found that dynamic memory allocation can help applications performance under certain circumstances. b. Impact of data cache on the i860/XP: We measured the performance of the BLAS both assembly coded and Fortran

Validation of a TFE3 break-apart FISH assay for Xp11.2 translocation renal cell carcinomas.

PubMed

Mosquera, Juan-Miguel; Dal Cin, Paola; Mertz, Kirsten D; Perner, Sven; Davis, Ian J; Fisher, David E; Rubin, Mark A; Hirsch, Michelle S

2011-09-01

Renal cell carcinomas (RCCs) with an Xp11.2 translocation predominantly affect young patients, and can present at an advanced stage. However, more cases in older patients and incidentally detected cancers at earlier stages are also being identified. As the histology of Xp11.2 RCCs overlaps with clear cell and papillary RCCs, it is not infrequent that Xp11.2 RCCs are overlooked and misdiagnosed. The objective of this study was to validate the use of fluorescence in-situ hybridization (FISH) for identifying Xp11.2 RCCs. One hundred fifty-eight consecutive, unselected renal tumors were evaluated in tissue microarrays, including 109 clear cell RCCs, 20 papillary RCCs, 3 RCCs with mixed papillary and clear cell features, 1 Xp11.2 translocation RCC, 8 chromophobe RCCs, 10 oncocytomas, and 7 angiomyolipomas. FISH evaluation was performed blinded to karyotype data, available in about two-thirds of cases. Furthermore, conventional sections of 4 Xp11.2 RCCs, 4 RCCs with mixed papillary and clear cell features, and 4 cases of alveolar soft part sarcoma (the latter for control purposes) were also assessed by FISH. Break-apart signals were homogeneously identified throughout tumor cells in 2 cases from the tissue microarrays including 1 known Xp11.2 RCC and 1 misdiagnosed Xp11.2 RCC. All conventional sections from the Xp11.2 RCC and alveolar soft part sarcoma cases were positive for the TFE3 rearrangement by FISH. All remaining cases were negative. Our study shows the clinical application of FISH in formalin-fixed, paraffin-embedded tissue for detection of Xp11.2 translocation RCCs and other tumors with this genetic aberration.

46 CFR 154.174 - Transverse contiguous hull structure.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false Transverse contiguous hull structure. 154.174 Section... Equipment Hull Structure § 154.174 Transverse contiguous hull structure. (a) The transverse contiguous hull...) The transverse contiguous hull structure of a vessel having cargo containment systems with secondary...

Cyclic and Torsional Fatigue Resistance of XP-endo Shaper and TRUShape Instruments.

PubMed

Silva, Emmanuel João Nogueira Leal; Vieira, Victor Talarico Leal; Belladonna, Felipe Gonçalves; Zuolo, Arthur de Siqueira; Antunes, Henrique Dos Santos; Cavalcante, Daniele Moreira; Elias, Carlos Nelson; De-Deus, Gustavo

2018-01-01

The purpose of this study was to evaluate the cyclic and torsional fatigue resistance of the XP-endo Shaper (FKG Dentaire, La Chaux-de-Fonds, Switzerland) and TRUShape (Dentsply Tulsa Dental Specialties, Tulsa, OK) instruments. Twenty XP-endo Shaper (30/0.01) instruments and 20 TRUShape (30/0.06v) instruments were used. Cyclic fatigue resistance was tested by measuring the number of cycles and time to fracture in an artificial stainless steel canal with a 60° angle and a 5-mm radius of curvature (n = 10). The torque and angle of rotation at failure of new instruments (n = 10) were measured according to ISO 3630-1. The fracture surface of all fragments was examined with a scanning electron microscope. Results were statistically analyzed using the Student t test at a significance level of P < .05. The XP-endo Shaper instruments showed a significantly longer number of cycles to fracture and time to failure in seconds than the TRUShape instruments (P < .05). The XP-endo Shaper also presented a lower maximum torque load (P < .05) but a significantly higher angular rotation to fracture than TRUShape (P < .05). The XP-endo Shaper instruments showed a higher cyclic fatigue resistance and angle of rotation to fracture but lower torque to failure than TRUShape instruments. Copyright © 2017 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Altered expression of key cell cycle regulators in renal cell carcinoma associated with Xp11.2 translocation.

PubMed

Barroca, H; Castedo, S; Vieira, J; Teixeira, M; Müller-Höcker, J

2009-01-01

Renal cell carcinoma (RCC) is a rare tumor in the pediatric population. Recently, a phenotypically and genetically distinct kidney carcinoma, mainly prevalent in children and associated with an Xp11.2 translocation or TFE3 gene fusion, has been described. It has been advanced that in this subtype of RCC, there is an accumulation of cyclin D1, cyclin D3, and p21 ((wafl/cip1)). The aim of the present study was to figure out in two pediatric RCC recently diagnosed in our department (one clear cell-type RCC and one TFE3-positive RCC) whether those features are indeed specific of the latter tumor or occur in pediatric RCC irrespective of the tumor type. The following immunostains were performed in both cases: Ki67, p16(ink4a), p21 ((wafl/cip1)), p27(kip1), p53, p63, mdm2, cyclin D1, cyclin D3, TFE3, CD10, vimentin, E-cadherin, and RCC-antigen. We observed in the TFE3-positive carcinoma an intense immunoreaction for p21 ((wafl/cip1)), cyclin D1, and cyclin D3, without expression for p53, p16, p27(kip1), and mdm2, whereas the immunoexpression profile observed in the classic RCC was similar to that of clear cell, adult-type RCC. Our study confirms that TFE3-positive RCC exhibits a deregulation of the cell cycle apparently unrelated to the young age of the patients.

Xp11.2 translocation renal cell carcinoma with NONO-TFE3 gene fusion: morphology, prognosis, and potential pitfall in detecting TFE3 gene rearrangement.

PubMed

Xia, Qiu-Yuan; Wang, Zhe; Chen, Ni; Gan, Hua-Lei; Teng, Xiao-Dong; Shi, Shan-Shan; Wang, Xuan; Wei, Xue; Ye, Sheng-Bing; Li, Rui; Ma, Heng-Hui; Lu, Zhen-Feng; Zhou, Xiao-Jun; Rao, Qiu

2017-03-01

Xp11 translocation renal cell carcinomas are characterized by several different translocations involving the TFE3 gene. Tumors with different specific gene fusions may have different clinicopathological manifestations. Fewer than 10 renal cell carcinoma cases with NONO-TFE3 have been described. Here we examined eight additional cases of this rare tumor using clinicopathological, immunohistochemical, and molecular analyses. The male-to-female ratio of our study cohort was 1:1, and the median age was 30 years. The most distinctive feature of the tumors was that they exhibited glandular/tubular or papillary architecture that was lined with small-to-medium cuboidal to high columnar cells with indistinct cell borders and an abundantly clear or flocculent eosinophilic cytoplasm. The nuclei were oriented toward the luminal surface and were round and uniform in shape, which resulted in the appearance of secretory endometrioid subnuclear vacuolization. The distinct glandular/tubular or papillary architecture was often accompanied by sheets of epithelial cells that presented a biphasic pattern. Immunohistochemically, all eight cases demonstrated moderate (2+) or strong (3+) positive staining for TFE3, CD10, RCC marker, and PAX-8. None of the tumors were immunoreactive for CK7, Cathepsin K, Melan-A, HMB45, Ksp-cadherin, Vimentin, CA9, 34βE12 or CD117. NONO-TFE3 fusion transcripts were identified in six cases by RT-PCR. All eight cases showed equivocal split signals with a distance of nearly 2 signal diameters and sometimes had false-negative results. Furthermore, we developed a fluorescence in situ hybridization (FISH) assay to serve as an adjunct diagnostic tool for the detection of the NONO-TFE3 fusion gene and used this method to detect the fusion gene in all eight cases. Long-term follow-up (range, 10-102 months) was available for 7 patients. All 7 patients were alive with no evidence of recurrent disease or disease progression after their initial resection. This report

Renal cell carcinoma associated with Xp11.2 translocations, report of a case.

PubMed

Jing, Hongbiao; Tai, Yanhong; Xu, Dazhou; Yang, Fan; Geng, Ming

2010-07-01

Renal cell carcinomas (RCCs) associated with Xp11.2 translocations (Xp11.2 translocation RCCs) are rare and occur predominantly in children and adolescents. A case of such tumor in a 12-year boy is reported. Grossly the cut surface of the ill-defined mass was polychromatic, containing areas of hemorrhage and necrosis. Microscopically, the tumor was composed of epithelioid cells with clear to weakly eosinophilic cytoplasm arranged in nested, alveolar, and pseudopapillary formations. Immunohistochemically, the neoplastic cells were positive for transcription factor E3 and CD10. We concluded that this case was an Xp11.2 translocation RCC. Copyright 2010 Elsevier Inc. All rights reserved.

Newly designed break-apart and ASPL-TFE3 dual-fusion FISH assay are useful in diagnosing Xp11.2 translocation renal cell carcinoma and ASPL-TFE3 renal cell carcinoma: a STARD-compliant article.

PubMed

Chen, Xiancheng; Yang, Yang; Gan, Weidong; Xu, Linfeng; Ye, Qing; Guo, Hongqian

2015-05-01

The diagnosis of Xp11.2 translocation renal cell carcinoma (tRCC), which relies on morphology and immunohistochemistry (IHC), is often either missed in the diagnosis or misdiagnosed. To improve the accuracy of diagnosis of Xp11.2 tRCC and ASPL-TFE3 renal cell carcinoma (RCC), we investigated newly designed fluorescence in situ hybridization (FISH) probes (diagnostic accuracy study).Based on the genetic characteristics of Xp11.2 tRCC and the ASPL-TFE3 RCC, a new break-apart TFE3 FISH probe and an ASPL-TFE3 dual-fusion FISH probe were designed and applied to 65 patients with RCC who were <45 years old or showed suspicious microscopic features of Xp11.2 tRCC in our hospital. To test the accuracy of the probes, we further performed reverse transcriptase-polymerase chain reaction (PCR) on 8 cases for which frozen tissues were available.Among the 65 cases diagnosed with RCC, TFE3 IHC was positive in 24 cases. Twenty-two cases were confirmed as Xp11.2 tRCC by break-apart TFE3 FISH, and 6 of these cases were further diagnosed as ASPL-TFE3 RCC by ASPL-TFE3 dual-fusion FISH detection. Importantly, reverse transcriptase-PCR showed concordant results with the results of FISH assay in the 8 available frozen cases.The break-apart and ASPL-TFE3 dual-fusion FISH assay can accurately detect the translocation of the TFE3 gene and ASPL-TFE3 fusion gene and can thus serve as a valid complementary method for diagnosing Xp11.2 tRCC and ASPL-TFE3 RCC.

Linking species richness curves from non-contiguous sampling to contiguous-nested SAR: An empirical study

NASA Astrophysics Data System (ADS)

Lazarina, Maria; Kallimanis, Athanasios S.; Pantis, John D.; Sgardelis, Stefanos P.

2014-11-01

The species-area relationship (SAR) is one of the few generalizations in ecology. However, many different relationships are denoted as SARs. Here, we empirically evaluated the differences between SARs derived from nested-contiguous and non-contiguous sampling designs, using plants, birds and butterflies datasets from Great Britain, Greece, Massachusetts, New York and San Diego. The shape of SAR depends on the sampling scheme, but there is little empirical documentation on the magnitude of the deviation between different types of SARs and the factors affecting it. We implemented a strictly nested sampling design to construct nested-contiguous SAR (SACR), and systematic nested but non-contiguous, and random designs to construct non-contiguous species richness curves (SASRs for systematic and SACs for random designs) per dataset. The SACR lay below any SASR and most of the SACs. The deviation between them was related to the exponent f of the power law relationship between sampled area and extent. The lower the exponent f, the higher was the deviation between the curves. We linked SACR to SASR and SAC through the concept of "effective" area (Ae), i.e. the nested-contiguous area containing equal number of species with the accumulated sampled area (AS) of a non-contiguous sampling. The relationship between effective and sampled area was modeled as log(Ae) = klog(AS). A Generalized Linear Model was used to estimate the values of k from sampling design and dataset properties. The parameter k increased with the average distance between samples and with beta diversity, while k decreased with f. For both systematic and random sampling, the model performed well in predicting effective area in both the training set and in the test set which was totally independent from the training one. Through effective area, we can link different types of species richness curves based on sampling design properties, sampling effort, spatial scale and beta diversity patterns.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lindsay, E.A.; Grillo, A.; Ferrero, G.B.

The microphthalmia with linear skin defects (MLS) syndrome (MIM309801) is a severe developmental disorder observed in XX individuals with distal Xp segmental monosomy. The phenotype of this syndrome overlaps with that of both Aicardi (MIM 305050) and Goltz (MIM 305600) syndromes, two X-linked dominant, male-lethal disorders. Here the authors report the clinical, cytogenetic, and molecular characterization of 3 patients with this syndrome. Two of these patients are females with a terminal Xpter-p22.2 deletion. One of these 2 patients had an aborted fetus with anencephaly and the same chromosome abnormality. The third patient is an XX male with Xp/Yp exchange spanningmore » the SRY gene which results in distal Xp monosomy. The extensive clinical variability observed in these patients and the results of the molecular analysis suggest that X-inactivation plays an important role in determining the phenotype of the MLS syndrome. The authors propose that the MLS, Aicardi, and Goltz syndromes are due to the involvement of the same gene(s), and that different patterns of X-inactivation are responsible for the phenotypic differences observed in these 3 disorders. However, they cannot rule out that each component of the MLS phenotype is caused by deletion of a different gene (a contiguous gene syndrome). 24 refs., 4 figs., 1 tab.« less

NDP gene mutations in 14 French families with Norrie disease.

PubMed

Royer, Ghislaine; Hanein, Sylvain; Raclin, Valérie; Gigarel, Nadine; Rozet, Jean-Michel; Munnich, Arnold; Steffann, Julie; Dufier, Jean-Louis; Kaplan, Josseline; Bonnefont, Jean-Paul

2003-12-01

Norrie disease is a rare X-inked recessive condition characterized by congenital blindness and occasionally deafness and mental retardation in males. This disease has been ascribed to mutations in the NDP gene on chromosome Xp11.1. Previous investigations of the NDP gene have identified largely sixty disease-causing sequence variants. Here, we report on ten different NDP gene allelic variants in fourteen of a series of 21 families fulfilling inclusion criteria. Two alterations were intragenic deletions and eight were nucleotide substitutions or splicing variants, six of them being hitherto unreported, namely c.112C>T (p.Arg38Cys), c.129C>G (p.His43Gln), c.133G>A (p.Val45Met), c.268C>T (p.Arg90Cys), c.382T>C (p.Cys128Arg), c.23479-1G>C (unknown). No NDP gene sequence variant was found in seven of the 21 families. This observation raises the issue of misdiagnosis, phenocopies, or existence of other X-linked or autosomal genes, the mutations of which would mimic the Norrie disease phenotype. Copyright 2003 Wiley-Liss, Inc.

Xp11.22 deletions encompassing CENPVL1, CENPVL2, MAGED1 and GSPT2 as a cause of syndromic X-linked intellectual disability.

PubMed

Grau, Christina; Starkovich, Molly; Azamian, Mahshid S; Xia, Fan; Cheung, Sau Wai; Evans, Patricia; Henderson, Alex; Lalani, Seema R; Scott, Daryl A

2017-01-01

By searching a clinical database of over 60,000 individuals referred for array-based CNV analyses and online resources, we identified four males from three families with intellectual disability, developmental delay, hypotonia, joint hypermobility and relative macrocephaly who carried small, overlapping deletions of Xp11.22. The maximum region of overlap between their deletions spanned ~430 kb and included two pseudogenes, CENPVL1 and CENPVL2, whose functions are not known, and two protein coding genes-the G1 to S phase transition 2 gene (GSPT2) and the MAGE family member D1 gene (MAGED1). Deletions of this ~430 kb region have not been previously implicated in human disease. Duplications of GSPT2 have been documented in individuals with intellectual disability, but the phenotypic consequences of a loss of GSPT2 function have not been elucidated in humans or mouse models. Changes in MAGED1 have not been associated with intellectual disability in humans, but loss of MAGED1 function is associated with neurocognitive and neurobehavioral phenotypes in mice. In all cases, the Xp11.22 deletion was inherited from an unaffected mother. Studies performed on DNA from one of these mothers did not show evidence of skewed X-inactivation. These results suggest that deletions of an ~430 kb region on chromosome Xp11.22 that encompass CENPVL1, CENPVL2, GSPT2 and MAGED1 cause a distinct X-linked syndrome characterized by intellectual disability, developmental delay, hypotonia, joint hypermobility and relative macrocephaly. Loss of GSPT2 and/or MAGED1 function may contribute to the intellectual disability and developmental delay seen in males with these deletions.

Clinicopathologic Characteristics and Prognosis of Xp11.2 Translocation Renal Cell Carcinoma: Multicenter, Propensity Score Matching Analysis.

PubMed

Choo, Min Soo; Jeong, Chang Wook; Song, Cheryn; Jeon, Hwang Gyun; Seo, Seong Il; Hong, Sung Kyu; Byun, Seok-Soo; Chung, Jin Soo; Hong, Sung-Hoo; Hwang, Eu Chang; Kim, Hyeon Hoe; Kwak, Cheol

2017-10-01

We evaluated the clinicopathologic characteristics and prognosis of Xp11.2 translocation (Xp11.2t) renal cell carcinoma (RCC) from a multicenter study and compare them with clear-cell RCC using a propensity score matching analysis. Between 2004 and 2013, 8384 consecutive patients from 7 institutions who were diagnosed with RCC were reviewed, and the pathologically confirmed Xp11.2t cases were enrolled. The oncological outcomes of Xp11.2t were compared with those of clear-cell RCC by selecting matched cases using 1:3 propensity score matching methods in a precollected clear-cell RCC data set from our hospital. The patients were divided into 2 subgroups on the basis of age of onset, either before (early) or after (late) 45 years old. Xp11.2t was found in 61 cases, corresponding to 0.72% of RCC cases for the 10 years. The mean age was 38.2 ± 19.4 years, and the mean tumor size was 6.2 ± 3.9 cm. The Xp11.2t cases were at more advanced stages and showed tendencies to involve lymph nodes at diagnosis. After the matching, there were no significant differences in recurrence-free and overall survival compared with clear-cell RCC. The age of incidence for Xp11.2t had a bimodal distribution, which was most common in the 30s and smaller peak in the 60s. Xp11.2t corresponded to a significantly worse prognosis for overall survival in late onset (after 45 years) subgroup (P = .038; hazard ratio, 3.199; 95% confidence interval, 1.065-9.609). This neoplasm has more aggressive clinicopathologic features at diagnosis. In older patients with onset age > 45 years, Xp11.2t showed a significantly worse prognosis than clear-cell RCC. Copyright © 2017 Elsevier Inc. All rights reserved.

Analysis of Pax6 contiguous gene deletions in the mouse, Mus musculus, identifies regions distinct from Pax6 responsible for extreme small-eye and belly-spotting phenotypes.

PubMed

Favor, Jack; Bradley, Alan; Conte, Nathalie; Janik, Dirk; Pretsch, Walter; Reitmeir, Peter; Rosemann, Michael; Schmahl, Wolfgang; Wienberg, Johannes; Zaus, Irmgard

2009-08-01

In the mouse Pax6 function is critical in a dose-dependent manner for proper eye development. Pax6 contiguous gene deletions were shown to be homozygous lethal at an early embryonic stage. Heterozygotes express belly spotting and extreme microphthalmia. The eye phenotype is more severe than in heterozygous Pax6 intragenic null mutants, raising the possibility that deletions are functionally different from intragenic null mutations or that a region distinct from Pax6 included in the deletions affects eye phenotype. We recovered and identified the exact regions deleted in three new Pax6 deletions. All are homozygous lethal at an early embryonic stage. None express belly spotting. One expresses extreme microphthalmia and two express the milder eye phenotype similar to Pax6 intragenic null mutants. Analysis of Pax6 expression levels and the major isoforms excluded the hypothesis that the deletions expressing extreme microphthalmia are directly due to the action of Pax6 and functionally different from intragenic null mutations. A region distinct from Pax6 containing eight genes was identified for belly spotting. A second region containing one gene (Rcn1) was identified for the extreme microphthalmia phenotype. Rcn1 is a Ca(+2)-binding protein, resident in the endoplasmic reticulum, participates in the secretory pathway and expressed in the eye. Our results suggest that deletion of Rcn1 directly or indirectly contributes to the eye phenotype in Pax6 contiguous gene deletions.

Unusual X-chromosome inactivation pattern in patients with Xp11.23-p11.22 duplication: Report and review.

PubMed

Di-Battista, Adriana; Meloni, Vera Ayres; da Silva, Magnus Dias; Moysés-Oliveira, Mariana; Melaragno, Maria Isabel

2016-12-01

In females carrying structural rearrangements of an X-chromosome, cells with the best dosage balance are preferentially selected, frequently resulting in a skewed inactivation pattern and amelioration of the phenotype. The Xp11.23-p11.22 region is involved in a recently described microduplication syndrome associated with severe clinical consequences in males and females, causing intellectual disability, behavior problems, epilepsy with electroencephalogram anomalies, minor facial anomalies, and early onset of puberty. Female carriers usually present an unusual X-chromosome inactivation pattern in favor of the aberrant chromosome, resulting in functional disomy of the duplicated segment. Here, we describe a girl carrying a de novo ∼9.7 Mb Xp11.3-p11.22 duplication of paternal origin and skewed X-chromosome inactivation pattern of the normal X-chromosome. We reviewed other cases previously reported and determined the minimal critical region possibly responsible for this unusual inactivation pattern. The critical region encompasses 36 RefSeq genes, including at least 10 oncogenes and/or genes related to the cell cycle control. We discuss the molecular mechanisms that underlie the positive selection of the cells with the active duplicated chromosome. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

A causal contiguity effect that persists across time scales.

PubMed

Kiliç, Asli; Criss, Amy H; Howard, Marc W

2013-01-01

The contiguity effect refers to the tendency to recall an item from nearby study positions of the just recalled item. Causal models of contiguity suggest that recalled items are used as probes, causing a change in the memory state for subsequent recall attempts. Noncausal models of the contiguity effect assume the memory state is unaffected by recall per se, relying instead on the correlation between the memory states at study and at test to drive contiguity. We examined the contiguity effect in a probed recall task in which the correlation between the study context and the test context was disrupted. After study of several lists of words, participants were given probe words in a random order and were instructed to recall a word from the same list as the probe. The results showed both short-term and long-term contiguity effects. Because study order and test order are uncorrelated, these contiguity effects require a causal contiguity mechanism that operates across time scales.

46 CFR 154.176 - Longitudinal contiguous hull structure.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false Longitudinal contiguous hull structure. 154.176 Section... Equipment Hull Structure § 154.176 Longitudinal contiguous hull structure. (a) The longitudinal contiguous hull structure of a vessel having cargo containment systems without secondary barriers must meet the...

46 CFR 154.176 - Longitudinal contiguous hull structure.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 5 2011-10-01 2011-10-01 false Longitudinal contiguous hull structure. 154.176 Section... Equipment Hull Structure § 154.176 Longitudinal contiguous hull structure. (a) The longitudinal contiguous hull structure of a vessel having cargo containment systems without secondary barriers must meet the...

46 CFR 154.176 - Longitudinal contiguous hull structure.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 5 2014-10-01 2014-10-01 false Longitudinal contiguous hull structure. 154.176 Section... Equipment Hull Structure § 154.176 Longitudinal contiguous hull structure. (a) The longitudinal contiguous hull structure of a vessel having cargo containment systems without secondary barriers must meet the...

46 CFR 154.176 - Longitudinal contiguous hull structure.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 5 2012-10-01 2012-10-01 false Longitudinal contiguous hull structure. 154.176 Section... Equipment Hull Structure § 154.176 Longitudinal contiguous hull structure. (a) The longitudinal contiguous hull structure of a vessel having cargo containment systems without secondary barriers must meet the...

46 CFR 154.176 - Longitudinal contiguous hull structure.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 5 2013-10-01 2013-10-01 false Longitudinal contiguous hull structure. 154.176 Section... Equipment Hull Structure § 154.176 Longitudinal contiguous hull structure. (a) The longitudinal contiguous hull structure of a vessel having cargo containment systems without secondary barriers must meet the...

46 CFR 154.174 - Transverse contiguous hull structure.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 5 2014-10-01 2014-10-01 false Transverse contiguous hull structure. 154.174 Section... Equipment Hull Structure § 154.174 Transverse contiguous hull structure. (a) The transverse contiguous hull structure of a vessel having cargo containment systems without secondary barriers must meet the standards of...

46 CFR 154.174 - Transverse contiguous hull structure.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 5 2012-10-01 2012-10-01 false Transverse contiguous hull structure. 154.174 Section... Equipment Hull Structure § 154.174 Transverse contiguous hull structure. (a) The transverse contiguous hull structure of a vessel having cargo containment systems without secondary barriers must meet the standards of...

46 CFR 154.174 - Transverse contiguous hull structure.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 5 2011-10-01 2011-10-01 false Transverse contiguous hull structure. 154.174 Section... Equipment Hull Structure § 154.174 Transverse contiguous hull structure. (a) The transverse contiguous hull structure of a vessel having cargo containment systems without secondary barriers must meet the standards of...

46 CFR 154.174 - Transverse contiguous hull structure.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 5 2013-10-01 2013-10-01 false Transverse contiguous hull structure. 154.174 Section... Equipment Hull Structure § 154.174 Transverse contiguous hull structure. (a) The transverse contiguous hull structure of a vessel having cargo containment systems without secondary barriers must meet the standards of...

Schools Facing the Expiration of Windows XP

ERIC Educational Resources Information Center

Cavanagh, Sean

2013-01-01

Microsoft's plans to end support for Windows XP, believed to be the dominant computer operating system in K-12 education, could pose big technological and financial challenges for districts nationwide--issues that many school systems have yet to confront. The giant software company has made it clear for years that it plans to stop supporting XP…

ENVIRONMENTAL TECHNOLOGY VERIFICATION REPORT: EVALUATION OF THE XP-SWMM STORMWATER WASTEWATER MANAGEMENT MODEL, VERSION 8.2, 2000, FROM XP SOFTWARE, INC.

EPA Science Inventory

XP-SWMM is a commercial software package used throughout the United States and around the world for simulation of storm, sanitary and combined sewer systems. It was designed based on the EPA Storm Water Management Model (EPA SWMM), but has enhancements and additional algorithms f...

Genes Involved in Degradation of para-Nitrophenol Are Differentially Arranged in Form of Non-Contiguous Gene Clusters in Burkholderia sp. strain SJ98

PubMed Central

Vikram, Surendra; Pandey, Janmejay; Kumar, Shailesh; Raghava, Gajendra Pal Singh

2013-01-01

Biodegradation of para-Nitrophenol (PNP) proceeds via two distinct pathways, having 1,2,3-benzenetriol (BT) and hydroquinone (HQ) as their respective terminal aromatic intermediates. Genes involved in these pathways have already been studied in different PNP degrading bacteria. Burkholderia sp. strain SJ98 degrades PNP via both the pathways. Earlier, we have sequenced and analyzed a ~41 kb fragment from the genomic library of strain SJ98. This DNA fragment was found to harbor all the lower pathway genes; however, genes responsible for the initial transformation of PNP could not be identified within this fragment. Now, we have sequenced and annotated the whole genome of strain SJ98 and found two ORFs (viz., pnpA and pnpB) showing maximum identity at amino acid level with p-nitrophenol 4-monooxygenase (PnpM) and p-benzoquinone reductase (BqR). Unlike the other PNP gene clusters reported earlier in different bacteria, these two ORFs in SJ98 genome are physically separated from the other genes of PNP degradation pathway. In order to ascertain the identity of ORFs pnpA and pnpB, we have performed in-vitro assays using recombinant proteins heterologously expressed and purified to homogeneity. Purified PnpA was found to be a functional PnpM and transformed PNP into benzoquinone (BQ), while PnpB was found to be a functional BqR which catalyzed the transformation of BQ into hydroquinone (HQ). Noticeably, PnpM from strain SJ98 could also transform a number of PNP analogues. Based on the above observations, we propose that the genes for PNP degradation in strain SJ98 are arranged differentially in form of non-contiguous gene clusters. This is the first report for such arrangement for gene clusters involved in PNP degradation. Therefore, we propose that PNP degradation in strain SJ98 could be an important model system for further studies on differential evolution of PNP degradation functions. PMID:24376843

46 CFR 154.172 - Contiguous steel hull structure.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 5 2014-10-01 2014-10-01 false Contiguous steel hull structure. 154.172 Section 154.172... Structure § 154.172 Contiguous steel hull structure. (a) Except as allowed in paragraphs (b) and (c) of this... construction of the contiguous steel hull structure must meet the thickness and steel grade in Table 1 for the...

46 CFR 154.172 - Contiguous steel hull structure.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 5 2013-10-01 2013-10-01 false Contiguous steel hull structure. 154.172 Section 154.172... Structure § 154.172 Contiguous steel hull structure. (a) Except as allowed in paragraphs (b) and (c) of this... construction of the contiguous steel hull structure must meet the thickness and steel grade in Table 1 for the...

46 CFR 154.172 - Contiguous steel hull structure.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 5 2012-10-01 2012-10-01 false Contiguous steel hull structure. 154.172 Section 154.172... Structure § 154.172 Contiguous steel hull structure. (a) Except as allowed in paragraphs (b) and (c) of this... construction of the contiguous steel hull structure must meet the thickness and steel grade in Table 1 for the...

46 CFR 154.172 - Contiguous steel hull structure.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 5 2011-10-01 2011-10-01 false Contiguous steel hull structure. 154.172 Section 154.172... Structure § 154.172 Contiguous steel hull structure. (a) Except as allowed in paragraphs (b) and (c) of this... construction of the contiguous steel hull structure must meet the thickness and steel grade in Table 1 for the...

Clinical heterogeneity within xeroderma pigmentosum associated with mutations in the DNA repair and transcription gene ERCC3

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vermeulen, W.; Kleijer, W.J.; Bootsma, D.

1994-02-01

The human DNA excision repair gene ERCC3 specifically corrects the nucleotide excision repair (NER) defect of xeroderma pigmentosum (XP) complementation group B. In addition to its function in NER, the ERCC3 DNA helicase was recently identified as one of the components of the human BTF2/TFIIH transcription factor complex, which is required for initiation of transcription of class II genes. To date, a single patient (XP11BE) has been assigned to this XP group B (XP-B), with the remarkable conjunction of two autosomal recessive DNA repair deficiency disorders: XP and Cockayne syndrome (CS). The intriguing involvement of the ERCC3 protein in themore » vital process of transcription may provide an explanation for the rarity, severity, and wide spectrum of clinical features in this complementation group. Here the authors report the identification of two new XP-B patients: XPCS1BA and XPCS2BA (siblings), by microneedle injection of the cloned ERCC3 repair gene as well as by cell hybridization. Molecular analysis of the ERCC3 gene in both patients revealed a single base substitution causing a missense mutation in a region that is completely conserved in yeast, Drosophila, mouse, and human ERCC3. As in patient XP11BE, the expression of only one allele (paternal) is detected. The mutation causes a virtually complete inactivation of the NER function of the protein. Despite this severe NER defect, both patients display a late onset of neurologic impairment, mild cutaneous symptoms, and a striking absence of skin tumors even at an age of >40 years. Analysis of the frequency of hprt[sup [minus

33 CFR 2.28 - Contiguous zone.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Contiguous zone. 2.28 Section 2.28 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY GENERAL JURISDICTION Jurisdictional Terms § 2.28 Contiguous zone. (a) For the purposes of the Federal Water Pollution Control Act (33...

46 CFR 108.175 - Contiguous locations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 4 2010-10-01 2010-10-01 false Contiguous locations. 108.175 Section 108.175 Shipping... EQUIPMENT Construction and Arrangement Classified Locations § 108.175 Contiguous locations. An enclosed space that has direct access to a Division 1 or Division 2 location is the same division as that...

Uncommon Localization of Extrarenal Xp11.2 Translocation-associated Renal Cell Carcinoma (RCC): Case Report.

PubMed

Al-Maghrabi, Jaudah Ahmed; Khabaz, Mohamad Nidal

2017-09-04

The World Health Organization has recognized Xp11.2 translocation-associated renal cell carcinoma (RCC) as a distinct neoplasm that arises within the kidney. Although many reports of extrarenal carcinoma may be found in the literature, to the best of our knowledge, Xp11 translocation-associated RCC with intact kidneys has not been documented. This report describes a multilobulated right retroperitoneal soft tissue mass (7.9×5.3×12.6 cm) of a 37-year-old man complaining of abdominal pain in the right side. The patient underwent a computed tomography-guided biopsy. Microscopic evaluation reveals a tumor with papillary and sheaths architectures with cells revealing clear to eosinophilic cytoplasm. Immunohistochemical evaluation on the biopsy reveals that the tumor is positive for PAX-8, CD10, and TFE3. It is negative for CK7, EMA, Vimentin, RCC, CK8/18, D20, CD3, PLAP, OCT4, CD30, MART-1, Inhibin, S-100, HMB-45, Desmin, SMA, and DOG-1. The diagnosis was malignant epithelioid neoplasm and the diagnosis of translocation RCC was suggested. Excision was recommended. The patient underwent right radical nephrectomy with removal of this large mass. Pathologic examination showed a large cystic and solid, nonhomogenous mass with some necrotic areas, originating from the perirenal fat between the adrenal gland and the kidney. Microscopic features showed a tumor with papillary, rhabdoid, and clear cell features. Immunohistochemical stains showed that the tumor cells positively expressed AMACR, PAX-8, CD10, RCC, and TFE3, but were negative for cytokeratins, vimentin, HMB-45, desmin, SMA, EMA, and MSA. Cytogenetic studies confirmed the diagnosis of Xp11.2 translocation-associated RCC with positive TFE3 gene rearrangement. To the best of our knowledge, this type of extrarenal tumor has never been reported.

Diagnosis of Xp11.2 Translocation Renal Cell Carcinomas in the Thai Patients.

PubMed

Junthaworn, Boontarika; Pradniwat, Kanapon; Hanamornroongruang, Suchanan

2015-11-01

Xp11.2 translocation renal cell carcinomas (TRCCs) are rare tumors recently accepted as a separated tumor type in 2004 WHO classification. To diagnose these tumors, histological recognition and confirmation of translocation are necessary. While the incidence of overall renal cell carcinomas (RCCs) is increased after the age of 40, Xp11.2 TRCCs are predominantly reported in young patients. The incidence of these tumors in Thailand has not been evaluated. To identify the frequency of Xp11.2 TRCCs, clinical presentation and follow-up information in 40 year-old or younger patients by using TFE3 immunostaining to confirm the translocation. All cases of 0- to 40-years-old patients diagnosed as RCCs from nephrectomy specimens between 2001 and 2011 at Siriraj Hospital were reviewed by one pathology resident and two pathologists. Immunohistochemical staining for TFE3 was performed on cases morphologically suspected for TRCC or showing unusual histology. Four cases consistent with Xp11.2 TRCC were identified by TFE3 immunostaining from all 31 cases (12.9%). Three cases were females and one was male. Two cases were at stage 4 and passed away several months after the operation. The other two patients were at stage 2. One patient is alive without recurrence for at least 36 months after surgery alone. The other died from underlying SLE. TFE3 immunostaining is a useful andpractical toolfor screening and diagnosis of Xp11.2 TRCCs, but staining results can be difficult to interpret. Thus, genetic analysis is still necessary especially when immunostaining shows problematic result. Fresh tumor tissue sampling in all young patients is recommended in case of further genetic studies needed.

ClpXP-Dependent RpoS Degradation Enables Full Activation of Type III Secretion System, Amylovoran Production, and Motility in Erwinia amylovora.

PubMed

Lee, Jae Hoon; Zhao, Youfu

2017-11-01

Erwinia amylovora, the causal agent of fire blight disease of apple and pear, employs intracellular proteases, including Lon and ClpXP, for posttranslational regulation of various cellular proteins. It has been shown that Lon plays a critical role in E. amylovora virulence by directly targeting type III secretion system (T3SS) proteins and the Rcs phosphorelay system. In this study, we genetically examined the role of ClpXP and its potential interaction with Lon in E. amylovora. Mutation in clpXP diminished the expression of the T3SS, reduced exopolysaccharide amylovoran production and motility, and resulted in delayed disease progress. Western blot analyses showed highly accumulated RpoS proteins in the clpXP mutant. Moreover, mutation of rpoS in the clpXP mutant background rescued the expression of the T3SS and amylovoran production, suggesting that ClpXP-dependent RpoS degradation positively affects virulence traits. Interestingly, lack of both ClpXP and Lon resulted in significantly reduced virulence but increased expression of the T3SS and amylovoran production. However, this phenomenon was independent of RpoS accumulation, suggesting that ClpXP and Lon are indispensable for full virulence in E. amylovora.

Diagnosis of adults Xp11.2 translocation renal cell carcinoma by immunohistochemistry and FISH assays: clinicopathological data from ethnic Chinese population.

PubMed

Qu, Yuanyuan; Gu, Chengyuan; Wang, Hongkai; Chang, Kun; Yang, Xiaoqun; Zhou, Xiaoyan; Dai, Bo; Zhu, Yao; Shi, Guohai; Zhang, Hailiang; Ye, Dingwei

2016-02-16

This study aimed to assess the utility of transcription factor E3 (TFE3) break-apart fluorescence in situ hybridization (FISH) assay in diagnosis of Xp11.2 translocation renal cell carcinoma (Xp11.2 RCC) and to compare the clinicopathological features between adult Xp11.2 RCC and non-Xp11.2 RCC. 76 pathologically suspected Xp11.2 RCCs were recruited from our institution. Both TFE3 immunohistochemistry (IHC) and TFE3 FISH assay were performed for the entire cohort. The progression-free survival (PFS) and overall survival (OS) curves were estimated using the Kaplan-Meier method. FISH analysis confirmed 30 Xp11.2 RCCs, including 28 cases with positive TFE3 immunostaining and 2 cases with negative immunostaining. The false-positive and false-negative rates were 6.7% (2/30) and 4.3% (2/46), respectively, for TFE3 IHC compared with FISH assay. Xp11.2 RCC was significantly associated with higher pathological stage and Fuhrman nuclear grade compared with non-Xp11.2 RCC (P < 0.05). The median PFS and OS for TFE3 FISH-positive group were 13.0 months (95% CI, 8.4-17.6 months) and 50.0 months (95% CI, 27.6-72.4 months), respectively, while the median PFS and OS had not been reached for TFE3 FISH-negative group. In conclusion, TFE3 break-apart FISH assay is a highly useful and standard diagnostic method for Xp11.2 RCC. Adult Xp11.2 RCC is clinically aggressive and often presents at advanced stage with poor prognosis.

Sunitinib-induced nephrotic syndrome in association with drug response in a patient with Xp11.2 translocation renal cell carcinoma.

PubMed

Liu, Yao-Chung; Chang, Peter Mu-Hsin; Liu, Chun-Yu; Yang, Chih-Yu; Chen, Ming-Han; Pan, Chin-Chen; Chen, Ming-Huang

2011-11-01

We report the case of a patient with metastatic renal cell carcinoma with Xp11.2 translocation/transcription factor E3 (TFE3) gene fusion who had presented with sunitinib-induced nephrotic syndrome in association with favorable and durable treatment response. The nephrotic syndrome was managed successfully by discontinuing sunitinib and symptomatic treatment. The 27-year-old female patient presenting with right upper abdominal pain was diagnosed with Xp11.2 translocation renal cell carcinoma on the right side with multiple pulmonary and hepatic metastases. She underwent radical nephrectomy and took a daily dose of 37.5 mg sunitinib. Partial response to sunitinib was achieved and maintained for 5 months, but when nephrotic syndrome occurred, drug intake was discontinued. The nephrotic syndrome gradually resolved around 2 months after discontinuation of sunitinib and medical management. Our case highlighted the favorable response of a particular non-clear cell type renal cell carcinoma to sunitinib and the specific toxicity associated with the antiangiogenic effect of sunitinib.

Coupling between nucleotide excision repair and gene expression.

PubMed

Cambindo Botto, Adrián E; Muñoz, Juan C; Muñoz, Manuel J

2018-05-17

Gene expression and DNA repair are fundamental processes for life. During the last decade, accumulating experimental evidence point towards different modes of coupling between these processes. Here we discuss the molecular mechanisms by which RNAPII-dependent transcription affects repair by the Nucleotide Excision Repair system (NER) and how NER activity, through the generation of single stranded DNA intermediates and activation of the DNA damage response kinase ATR, drives gene expression in a genotoxic scenario. Since NER-dependent repair is compromised in Xeroderma Pigmentosum (XP) patients, and having in mind that these patients present a high degree of clinical heterogeneity, we speculate that some of the clinical features of XP patients can be explained by misregulation of gene expression.

PD-L1 expression in Xp11.2 translocation renal cell carcinoma: Indicator of tumor aggressiveness.

PubMed

Chang, Kun; Qu, Yuanyuan; Dai, Bo; Zhao, Jian-Yuan; Gan, Hualei; Shi, Guohai; Zhu, Yiping; Shen, Yijun; Zhu, Yao; Zhang, Hailiang; Ye, Dingwei

2017-05-18

Programmed death ligand-1 (PD-L1), a promising antitumor target, has proven clinical value against many malignancies. However, the PD-L1 content of Xp11.2 translocation renal cell carcinoma (Xp11.2 RCC) and its correlation with clinical outcomes remain unclear. This study aimed to investigate PD-L1 expression in Xp11.2 RCC and to assess its prognostic value. Formalin-fixed paraffin-embedded specimens from 36 adult patients that were histologically confirmed (by fluorescence in situ hybridization) were subjected to immunohistochemical analysis. Of the 36 Xp11.2 RCC patients, 9 (25.0%) had tumors with positive PD-L1 expression and 27 (75.0%) had tumors with negative PD-L1 expression. Positive PD-L1 expression correlated with advanced tumor stage (P = 0.001), regional lymph node metastasis (P < 0.001), and distant metastasis (P < 0.001). A multivariate analysis identified positive PD-L1 expression was an independent adverse prognostic factor for both progression free survival (hazard ratio: 3.7, P = 0.018) and overall survival (hazard ratio: 4.5, P = 0.034). The median PFS and OS for the whole cohort were 13.0 months (95% confidence interval [CI], 9.4-16.6 months) and 36.0 months (95% CI, 23.9-48.1 months), respectively. Our findings suggest that positive PD-L1 expression is indicative of worse clinical outcome in Xp11.2 RCC. Further studies are needed to explore the potential efficacy of targeting PD-L1 in Xp11.2 RCC.

Diagnosis of adults Xp11.2 translocation renal cell carcinoma by immunohistochemistry and FISH assays: clinicopathological data from ethnic Chinese population

PubMed Central

Qu, Yuanyuan; Gu, Chengyuan; Wang, Hongkai; Chang, Kun; Yang, Xiaoqun; Zhou, Xiaoyan; Dai, Bo; Zhu, Yao; Shi, Guohai; Zhang, Hailiang; Ye, Dingwei

2016-01-01

This study aimed to assess the utility of transcription factor E3 (TFE3) break-apart fluorescence in situ hybridization (FISH) assay in diagnosis of Xp11.2 translocation renal cell carcinoma (Xp11.2 RCC) and to compare the clinicopathological features between adult Xp11.2 RCC and non-Xp11.2 RCC. 76 pathologically suspected Xp11.2 RCCs were recruited from our institution. Both TFE3 immunohistochemistry (IHC) and TFE3 FISH assay were performed for the entire cohort. The progression-free survival (PFS) and overall survival (OS) curves were estimated using the Kaplan-Meier method. FISH analysis confirmed 30 Xp11.2 RCCs, including 28 cases with positive TFE3 immunostaining and 2 cases with negative immunostaining. The false-positive and false-negative rates were 6.7% (2/30) and 4.3% (2/46), respectively, for TFE3 IHC compared with FISH assay. Xp11.2 RCC was significantly associated with higher pathological stage and Fuhrman nuclear grade compared with non-Xp11.2 RCC (P < 0.05). The median PFS and OS for TFE3 FISH-positive group were 13.0 months (95% CI, 8.4–17.6 months) and 50.0 months (95% CI, 27.6–72.4 months), respectively, while the median PFS and OS had not been reached for TFE3 FISH-negative group. In conclusion, TFE3 break-apart FISH assay is a highly useful and standard diagnostic method for Xp11.2 RCC. Adult Xp11.2 RCC is clinically aggressive and often presents at advanced stage with poor prognosis. PMID:26880493

46 CFR 154.178 - Contiguous hull structure: Heating system.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false Contiguous hull structure: Heating system. 154.178... Equipment Hull Structure § 154.178 Contiguous hull structure: Heating system. The heating system for transverse and longitudinal contiguous hull structure must: (a) Be shown by a heat load calculation to have...

Short stature in a mother and daughter with terminal deletion of Xp22.3

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schwinger, E.; Kirschstein, M.; Konermann, T.

1996-05-03

Short stature in females is often caused by homozygosity for the terminal portion of Xp due to monosomy X or a deletion. We report on a mother and daughter with short stature as sole phenotypic abnormality and deletion of bands Xp22.32-p22.33 demonstrated by classic and molecular cytogenetic analysis. In both individuals, the deleted X chromosome was late replicating. Molecular analysis suggested that the deletion is terminal and the breakpoint was localized between the STS and DXS7470 loci in Xp22.32. Chromosome analysis is often done on females with short stature to exclude Ullrich-Turner syndrome. Small deletions, terminal or interstitial, are easilymore » missed by conventional cytogenetic investigation; thus molecular analyses are useful to detect those cases. 8 refs., 3 figs.« less

Melanotic Xp11 translocation renal cancer: report of a case with a unique intratumoral sarcoid-like reaction.

PubMed

Ritterhouse, Lauren L; Cykowski, Matthew D; Hassell, Lewis A; Slobodov, Gennady; Bane, Barbara L

2014-04-15

Melanotic Xp11 translocation renal cancer is a rare tumor belonging to the family of microphthalmia-associated transcription factor (MiTF)/transcription factor E (TFE) neoplasms. This tumor family also includes alveolar soft part sarcoma, perivascular epithelioid cell neoplasms, Xp11 translocation renal cell carcinoma, and melanoma. To date, six confirmed melanotic Xp11 translocation cancers (five renal, one ovarian) have been reported in the literature. Here, we report the clinical, histologic, immunohistochemical, and molecular features of a unique melanotic Xp11 translocation renal cancer arising in a 34-year-old African-American female. Histologically, the tumor was composed of epithelioid tumor cells arranged in a nested pattern. The cells had clear to eosinophilic granular cytoplasm, vesicular nuclear chromatin, and prominent nucleoli. Multifocal intracytoplasmic deposits of granular brown melanin pigment were identified and confirmed by Fontana-Masson stain. An unusual histologic feature, not previously reported in melanotic Xp11 translocation renal cancer, was a sarcoid-like granulomatous reaction consisting of tight epithelioid granulomas with lymphocytic cuffing, numerous giant cells, and calcifications. Nuclear transcription factor E3 expression was identified by immunohistochemistry and TFE3 rearrangement was confirmed by fluorescence in situ hybridization. Additional immunohistochemical findings included immunoreactivity for HMB45, cathepsin K, and progesterone receptor; negative staining was seen with actin, desmin, cytokeratins, epithelial membrane antigen, CD10, vimentin, and PAX-8. The patient is currently free of disease, two years following initial clinicoradiologic presentation and twenty-two months following partial nephrectomy without additional therapy. This report further expands the spectrum of morphologic and clinical findings previously described in melanotic Xp11 translocation renal cancer, a distinctive tumor showing overlapping

Cu3-xP Nanocrystals as a Material Platform for Near-Infrared Plasmonics and Cation Exchange Reactions

PubMed Central

2015-01-01

Synthesis approaches to colloidal Cu3P nanocrystals (NCs) have been recently developed, and their optical absorption features in the near-infrared (NIR) have been interpreted as arising from a localized surface plasmon resonance (LSPR). Our pump–probe measurements on platelet-shaped Cu3-xP NCs corroborate the plasmonic character of this absorption. In accordance with studies on crystal structure analysis of Cu3P dating back to the 1970s, our density functional calculations indicate that this material is substoichiometric in copper, since the energy of formation of Cu vacancies in certain crystallographic sites is negative, that is, they are thermodynamically favored. Also, thermoelectric measurements point to a p-type behavior of the majority carriers from films of Cu3-xP NCs. It is likely that both the LSPR and the p-type character of our Cu3-xP NCs arise from the presence of a large number of Cu vacancies in such NCs. Motivated by the presence of Cu vacancies that facilitate the ion diffusion, we have additionally exploited Cu3-xP NCs as a starting material on which to probe cation exchange reactions. We demonstrate here that Cu3-xP NCs can be easily cation-exchanged to hexagonal wurtzite InP NCs, with preservation of the anion framework (the anion framework in Cu3-xP is very close to that of wurtzite InP). Intermediate steps in this reaction are represented by Cu3-xP/InP heterostructures, as a consequence of the fact that the exchange between Cu+ and In3+ ions starts from the peripheral corners of each NC and gradually evolves toward the center. The feasibility of this transformation makes Cu3-xP NCs an interesting material platform from which to access other metal phosphides by cation exchange. PMID:25960605

Non-contiguous finished genome sequence and contextual data of the filamentous soil bacterium Ktedonobacter racemifer type strain (SOSP1-21).

PubMed

Chang, Yun-Juan; Land, Miriam; Hauser, Loren; Chertkov, Olga; Del Rio, Tijana Glavina; Nolan, Matt; Copeland, Alex; Tice, Hope; Cheng, Jan-Fang; Lucas, Susan; Han, Cliff; Goodwin, Lynne; Pitluck, Sam; Ivanova, Natalia; Ovchinikova, Galina; Pati, Amrita; Chen, Amy; Palaniappan, Krishna; Mavromatis, Konstantinos; Liolios, Konstantinos; Brettin, Thomas; Fiebig, Anne; Rohde, Manfred; Abt, Birte; Göker, Markus; Detter, John C; Woyke, Tanja; Bristow, James; Eisen, Jonathan A; Markowitz, Victor; Hugenholtz, Philip; Kyrpides, Nikos C; Klenk, Hans-Peter; Lapidus, Alla

2011-10-15

Ktedonobacter racemifer corrig. Cavaletti et al. 2007 is the type species of the genus Ktedonobacter, which in turn is the type genus of the family Ktedonobacteraceae, the type family of the order Ktedonobacterales within the class Ktedonobacteria in the phylum 'Chloroflexi'. Although K. racemifer shares some morphological features with the actinobacteria, it is of special interest because it was the first cultivated representative of a deep branching unclassified lineage of otherwise uncultivated environmental phylotypes tentatively located within the phylum 'Chloroflexi'. The aerobic, filamentous, non-motile, spore-forming Gram-positive heterotroph was isolated from soil in Italy. The 13,661,586 bp long non-contiguous finished genome consists of ten contigs and is the first reported genome sequence from a member of the class Ktedonobacteria. With its 11,453 protein-coding and 87 RNA genes, it is the largest prokaryotic genome reported so far. It comprises a large number of over-represented COGs, particularly genes associated with transposons, causing the genetic redundancy within the genome being considerably larger than expected by chance. This work is a part of the Genomic Encyclopedia of Bacteria and Archaea project.

TFE3 break-apart FISH has a higher sensitivity for Xp11.2 translocation-associated renal cell carcinoma compared with TFE3 or cathepsin K immunohistochemical staining alone: expanding the morphologic spectrum.

PubMed

Rao, Qiu; Williamson, Sean R; Zhang, Shaobo; Eble, John N; Grignon, David J; Wang, Mingsheng; Zhou, Xiao-Jun; Huang, Wenbin; Tan, Puay-Hoon; Maclennan, Gregory T; Cheng, Liang

2013-06-01

Renal cell carcinoma (RCC) associated with Xp11.2 translocation is uncommon, characterized by several different translocations involving the TFE3 gene. We assessed the utility of break-apart fluorescence in situ hybridization (FISH) in establishing the diagnosis for suspected or unclassified cases with negative or equivocal TFE3 immunostaining by analyzing 24 renal cancers with break-apart TFE3 FISH and comparing the molecular findings with the results of TFE3 and cathepsin K immunostaining in the same tumors. Ten tumors were originally diagnosed as Xp11.2 RCC on the basis of positive TFE3 immunostaining, and 14 were originally considered unclassified RCCs with negative or equivocal TFE3 staining, but with a range of features suspicious for Xp11.2 RCC. Seventeen cases showed TFE3 rearrangement associated with Xp11.2 translocation by FISH, including all 13 tumors with moderate or strong TFE3 (n=10) or cathepsin K (n=7) immunoreactivity. FISH-positive cases showed negative or equivocal immunoreactivity for TFE3 or cathepsin K in 7 and 10 tumors, respectively (both=3). None had positive immunohistochemistry but negative FISH. Morphologic features were typical for Xp11.2 RCC in 10/17 tumors. Unusual features included 1 melanotic Xp11.2 renal cancer, 1 tumor with mixed features of Xp11.2 RCC and clear cell RCC, and other tumors mimicking clear cell RCC, multilocular cystic RCC, or high-grade urothelial carcinoma. Morphology mimicking high-grade urothelial carcinoma has not been previously reported in these tumors. Psammoma bodies, hyalinized stroma, and intracellular pigment were preferentially identified in FISH-positive cases compared with FISH-negative cases. Our results support the clinical application of a TFE3 break-apart FISH assay for diagnosis and confirmation of Xp11.2 RCC and further expand the histopathologic spectrum of these neoplasms to include tumors with unusual features. A renal tumor with pathologic or clinical features highly suggestive of

DNA damage and gene therapy of xeroderma pigmentosum, a human DNA repair-deficient disease.

PubMed

Dupuy, Aurélie; Sarasin, Alain

2015-06-01

Xeroderma pigmentosum (XP) is a genetic disease characterized by hypersensitivity to ultra-violet and a very high risk of skin cancer induction on exposed body sites. This syndrome is caused by germinal mutations on nucleotide excision repair genes. No cure is available for these patients except a complete protection from all types of UV radiations. We reviewed the various techniques to complement or to correct the genetic defect in XP cells. We, particularly, developed the correction of XP-C skin cells using the fidelity of the homologous recombination pathway during repair of double-strand break (DSB) in the presence of XPC wild type sequences. We used engineered nucleases (meganuclease or TALE nuclease) to induce a DSB located at 90 bp of the mutation to be corrected. Expression of specific TALE nuclease in the presence of a repair matrix containing a long stretch of homologous wild type XPC sequences allowed us a successful gene correction of the original TG deletion found in numerous North African XP patients. Some engineered nucleases are sensitive to epigenetic modifications, such as cytosine methylation. In case of methylated sequences to be corrected, modified nucleases or demethylation of the whole genome should be envisaged. Overall, we showed that specifically-designed TALE-nuclease allowed us to correct a 2 bp deletion in the XPC gene leading to patient's cells proficient for DNA repair and showing normal UV-sensitivity. The corrected gene is still in the same position in the human genome and under the regulation of its physiological promoter. This result is a first step toward gene therapy in XP patients. Copyright © 2014 Elsevier B.V. All rights reserved.

46 CFR 154.180 - Contiguous hull structure: Welding procedure.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false Contiguous hull structure: Welding procedure. 154.180... Equipment Hull Structure § 154.180 Contiguous hull structure: Welding procedure. Welding procedure tests for contiguous hull structure designed for a temperature colder than −18 °C (0 °F) must meet § 54.05-15 and...

A Causal Contiguity Effect That Persists across Time Scales

ERIC Educational Resources Information Center

Kilic, Asli; Criss, Amy H.; Howard, Marc W.

2013-01-01

The contiguity effect refers to the tendency to recall an item from nearby study positions of the just recalled item. Causal models of contiguity suggest that recalled items are used as probes, causing a change in the memory state for subsequent recall attempts. Noncausal models of the contiguity effect assume the memory state is unaffected by…

Three genes in the human MHC class III region near the junction with the class II: Gene for receptor of advanced glycosylation end products, PBX2 homeobox gene and a notch homolog, human counterpart of mouse mammary tumor gene int-3

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sugaya, K.; Fukagawa, T.; Matsumoto, K.

Cosmid walking of about 250 kb from MHC class III gene CYP21 to class II was conducted. The gene for receptor of advanced glycosylation end products of proteins (RAGE, a member of immunoglobulin super-family molecules), the PBX2 homeobox gene designated HOX12, and the human counterpart of the mouse mammary tumor gene int-3 were found. The contiguous RAGE and HOX12 genes were completely sequenced, and the human int-3 counterpart was partially sequenced and assigned to a Notch homolog. This human Notch homolog, designated NOTCH3, showed both the intracellular portion present in the mouse int-3 sequence and the extracellular portion absent inmore » the int-3. It thus corresponds to the intact form of a Notch-type transmembrane protein. About 20 kb of dense Alu clustering was found just centromeric to the NOTCH3. 48 refs., 9 figs., 2 tabs.« less

Characterizations of 9p21 candidate genes in familial melanoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Walker, G.J.; Flores, J.F.; Glendening, J.M.

We have previously collected and characterized 16 melanoma families for the inheritance of a familial melanoma predisposition gene on 9p21. Clear evidence for genetic linkage has been detected in 8 of these families with the 9p21 markers D9S126 and 1FNA, while linkage of the remaining families to this region is less certain. A candidate for the 9p21 familial melanoma gene, the cyclin kinase inhibitor gene p16 (also known as the multiple tumor suppressor 1 (MTS1) gene), has been recently indentified. Notably, a nonsense mutation within the p16 gene has been detected in the lymphoblastoid cell line DNA from a dysplasticmore » nevus syndrome (DNS), or familial melanoma, patient. The p16 gene is also known to be frequently deleted or mutated in a variety of tumor cell lines (including melanoma) and resides within a region that has been defined as harboring the 9p21 melanoma predisposition locus. This region is delineated on the distal side by the marker D9S736 (which resides just distal to the p16 gene) and extends in a proximal direction to the marker D9S171. Overall, the entire distance between these two loci is estimated at 3-5Mb. Preliminary analysis of our two largest 9p21-linked melanoma kindreds (by direct sequencing of PCR products) has not yet revealed mutations within the coding region of the p16 gene. Others have reported that 8/11 unrelated 9p21-linked melanoma families do not appear to carry p16 mutations; thus the possibility exists that p16 is not a melanoma susceptibility gene per se, although it appears to play some role in melanoma tumor progression. Our melanoma kindred DNAs are currently being analyzed by SSCP using primers that amplify exons of other candidate genes from the 9p21 region implicated in familial melanoma. These novel genes reside within a distinct critical region of homozygous loss in melanoma which is located >2 Mb from the p16 gene on 9p21.« less

Characterization of contiguous gene deletions in COL4A6 and COL4A5 in Alport syndrome-diffuse leiomyomatosis.

PubMed

Nozu, Kandai; Minamikawa, Shogo; Yamada, Shiro; Oka, Masafumi; Yanagita, Motoko; Morisada, Naoya; Fujinaga, Shuichiro; Nagano, China; Gotoh, Yoshimitsu; Takahashi, Eihiko; Morishita, Takahiro; Yamamura, Tomohiko; Ninchoji, Takeshi; Kaito, Hiroshi; Morioka, Ichiro; Nakanishi, Koichi; Vorechovsky, Igor; Iijima, Kazumoto

2017-07-01

Alport syndrome-diffuse leiomyomatosis (AS-DL, OMIM: 308940) is a rare variant of the X-linked Alport syndrome that shows overgrowth of visceral smooth muscles in the gastrointestinal, respiratory and female reproductive tracts in addition to renal symptoms. AS-DL results from deletions that encompass the 5' ends of the COL4A5 and COL4A6 genes, but deletion breakpoints between COL4A5 and COL4A6 have been determined in only four cases. Here, we characterize deletion breakpoints in five AS-DL patients and show a contiguous COL4A6/COL4A5 deletion in each case. We also demonstrate that eight out of nine deletion alleles involved sequences homologous between COL4A5 and COL4A6. Most breakpoints took place in recognizable transposed elements, including long and short interspersed repeats, DNA transposons and long-terminal repeat retrotransposons. Because deletions involved the bidirectional promoter region in each case, we suggest that the occurrence of leiomyomatosis in AS-DL requires inactivation of both genes. Altogether, our study highlights the importance of homologous recombination involving multiple transposed elements for the development of this continuous gene syndrome and other atypical loss-of-function phenotypes.

Structure and Barr body formation of an Xp + chromosome with two inactivation centers.

PubMed Central

Daly, R F; Patau, K; Therman, E; Sarto, G E

1977-01-01

A patients with seizures, Von Willebrand disease, and symptoms of Turner syndrome was a chromosomal mosaic. In blood culture (1974), 56% of the cells were 45, X 33% 46, XXp+ and 11% 47,XXp + Xp +; in the skin, no cells with 47 chromosomes were found. Presumably the Xp + chromosome arose through a break in the Q-banded dark region next to the centromere on Xp to which an Xq had been attached. The abnormal X was late-labeling and formed a larger than normal Barr body. Of the chromatin-positive fibroblasts, 18.2% showed bipartite Barr bodies, which agrees with the hypothesis that the X inactivation center lies on the proximal part of the Xq. On the basis of the structure and behavior of the bipartite bodies in the present patient, as compared to those formed by other chromosomes with two presumed inactivation centers, we propose that the dark region next to the centromere of Xp remains active in the inactive X. In cells with 45,X and 46,XY, this region has the same relative size, whereas it is significantly shorter in the active X of three females, including the present patient, with one abnormal X. We propose that this region on the active X reveals different states of activity, as reflected in its length, depending on how many other X chromosomes are in the cell. Images Fig. 1 Fig. 2 Fig. 3 PMID:299980

A rare cause of childhood renal cysts: Xp11.2 translocation renal cell carcinoma.

PubMed

Taşkınlar, Hakan; Avlan, Dinçer; Çıtak, Çağlar; Polat, Ayşe; Naycı, Ali

2015-01-01

Pediatric renal cysts are rare, usually asymptomatic and incidentally detected in children. Cyst associated renal cell carcinoma (RCC) or cystic RCC is extremely rare in children. Bosniak classification system has been accepted for the management of cystic renal masses. Xp11.2 translocation RCC is a recently classified distinct subtype and usually affects children and adolescents. We report the case of a 10-year-old girl with Xp11.2 translocation RCC from a cyst of the right kidney.

A recombination outside the BB deletion refines the location of the X-linked retinitis pigmentosa locus RP3

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fujita, R.; Bingham, E.; Forsythe, P.

1996-07-01

Genetic loci for X-linked retinitis pigmentosa (XLRP) have been mapped between Xp11.22 and Xp22.13 (RP2, RP3, RP6, and RP15). The RP3 gene, which is responsible for the predominant form of XLRP in most Caucasian populations, has been localized to Xp21.1 by linkage analysis and the map positions of chromosomal deletions associated with the disease. Previous linkage studies have suggested that RP3 is flanked by the markers DXS1110 (distal) and OTC (proximal). Patient BB was though to have RP because of a lesion at the RP3 locus, in addition to chronic granulomatous disease, Duchenne muscular dystrophy (DMD), mild mental retardation, andmore » the McLeod phenotype. This patient carried a deletion extending {approximately}3 Mb from DMD in Xp21.3 to Xp21.1, with the proximal breakpoint located {approximately}40 kb centromeric to DXS1110. The RP3 gene, therefore, is believed to reside between DXS1110 and the proximal breakpoint of the BB deletion. In order to refine the location of RP3 and to ascertain patients with RP3, we have been analyzing several XLRP families for linkage to Xp markers. Linkage analysis in an American family of 27 individuals demonstrates segregation of XLRP with markers in Xp21.1, consistent with the RP3 subtype. One affected male shows a recombination event proximal to DXS1110. Additional markers within the DXS1110-OTC interval show that the crossover is between two novel polymorphic markers, DXS8349 and M6, both of which are present in BB DNA and lie centromeric to the proximal breakpoint. This recombination places the XLRP mutation in this family outside the BB deletion and redefines the location of RP3. 22 refs., 3 figs., 2 tabs.« less

Magnetic resonance imaging and computed tomography characteristics of renal cell carcinoma associated with Xp11.2 translocation/TFE3 gene fusion.

PubMed

Wang, Wei; Ding, Jianhui; Li, Yuan; Wang, Chaofu; Zhou, Liangping; Zhu, Hui; Peng, Weijun

2014-01-01

To characterize Xp11.2 translocation renal cell carcinoma (RCC) using magnetic resonance imaging (MRI) and computed tomography (CT). This study retrospectively collected the MRI and CT data of twelve patients with Xp11.2 translocation RCC confirmed by pathology. Nine cases underwent dynamic contrast-enhanced MRI (DCE-MRI) and 6 cases underwent CT, of which 3 cases underwent MRI and CT simultaneously. The MRI and CT findings were analyzed in regard to tumor position, size, hemorrhagic, cystic or necrotic components, calcification, tumor density, signal intensity and enhancement features. The age of the 12 patients ranged from 13 to 46 years (mean age: 23 years). T2WI revealed heterogeneous intensity, hyper-intensity, and slight hypo-intensity in 6 cases, 2 cases, and 1 case, respectively. On DCE-MR images, mild, moderate, and marked rim enhancement of the tumor in the corticomedullary phase (CMP) were observed in 1, 6, and 2 cases, respectively. The tumor parenchyma showed iso-attenuation (n = 4) or slight hyper-attenuation (n = 1) compared to the normal renal cortex on non-contrast CT images. Imaging findings were suggestive of hemorrhage (n = 4) or necrosis (n = 8) in the tumors, and there was evidence of calcification in 8 cases by CT (n = 3) and pathology (n = 8). On dynamic contrast-enhanced CT images, 3 cases and 1 case manifested moderate and strong CMP enhancement, respectively. Nine tumors by MRI and 4 tumors by CT showed prolonged enhancement. Three neoplasms presented at stage I, 2 at stage II, 3 at stage III, and 4 at stage IV according the 2010 AJCC staging criteria. XP11.2 translocation RCC should be considered when a child or young adult patient presents with a renal tumor with heterogeneous features such as hemorrhage, necrosis, cystic changes, and calcification on CT and MRI and/or is accompanied by metastatic evidence.

Magnetic Resonance Imaging and Computed Tomography Characteristics of Renal Cell Carcinoma Associated with Xp11.2 Translocation/TFE3 Gene Fusion

PubMed Central

Li, Yuan; Wang, Chaofu; Zhou, Liangping; Zhu, Hui; Peng, Weijun

2014-01-01

Purpose To characterize Xp11.2 translocation renal cell carcinoma (RCC) using magnetic resonance imaging (MRI) and computed tomography (CT). Methods This study retrospectively collected the MRI and CT data of twelve patients with Xp11.2 translocation RCC confirmed by pathology. Nine cases underwent dynamic contrast-enhanced MRI (DCE-MRI) and 6 cases underwent CT, of which 3 cases underwent MRI and CT simultaneously. The MRI and CT findings were analyzed in regard to tumor position, size, hemorrhagic, cystic or necrotic components, calcification, tumor density, signal intensity and enhancement features. Results The age of the 12 patients ranged from 13 to 46 years (mean age: 23 years). T2WI revealed heterogeneous intensity, hyper-intensity, and slight hypo-intensity in 6 cases, 2 cases, and 1 case, respectively. On DCE-MR images, mild, moderate, and marked rim enhancement of the tumor in the corticomedullary phase (CMP) were observed in 1, 6, and 2 cases, respectively. The tumor parenchyma showed iso-attenuation (n = 4) or slight hyper-attenuation (n = 1) compared to the normal renal cortex on non-contrast CT images. Imaging findings were suggestive of hemorrhage (n = 4) or necrosis (n = 8) in the tumors, and there was evidence of calcification in 8 cases by CT (n = 3) and pathology (n = 8). On dynamic contrast-enhanced CT images, 3 cases and 1 case manifested moderate and strong CMP enhancement, respectively. Nine tumors by MRI and 4 tumors by CT showed prolonged enhancement. Three neoplasms presented at stage I, 2 at stage II, 3 at stage III, and 4 at stage IV according the 2010 AJCC staging criteria. Conclusions XP11.2 translocation RCC should be considered when a child or young adult patient presents with a renal tumor with heterogeneous features such as hemorrhage, necrosis, cystic changes, and calcification on CT and MRI and/or is accompanied by metastatic evidence. PMID:24926688

A rare cause of childhood renal cysts: Xp11.2 translocation renal cell carcinoma

PubMed Central

Taşkınlar, Hakan; Avlan, Dinçer; Çıtak, Çağlar; Polat, Ayşe; Naycı, Ali

2015-01-01

Pediatric renal cysts are rare, usually asymptomatic and incidentally detected in children. Cyst associated renal cell carcinoma (RCC) or cystic RCC is extremely rare in children. Bosniak classification system has been accepted for the management of cystic renal masses. Xp11.2 translocation RCC is a recently classified distinct subtype and usually affects children and adolescents. We report the case of a 10-year-old girl with Xp11.2 translocation RCC from a cyst of the right kidney. PMID:25624966

Laparoscopic radiofrequency ablation-assisted enucleation of Xp11.2 translocation renal cell carcinoma: A case report

PubMed Central

XU, LINFENG; YANG, RONG; WANG, WEI; ZHANG, YIFEN; GAN, WEIDONG

2014-01-01

The current study presents a case of Xp11.2 translocation renal cell carcinoma (Xp11.2 RCC) in a 30-year-old female. The patient was referred to The Affiliated Drum Tower Hospital of the Medical College of Nanjing University (Nanjing, Jiangsu, China) due to a right renal tumor without evident symptoms, which was found by a routine physical examination. A computed tomography (CT) scan indicated that the mass exhibited cystic and solid components. The patient underwent laparoscopic radiofrequency ablation-assisted enucleation. Immunohistochemistry revealed intense nuclear staining for transcription factor E3 protein in the cancer cells. The patient was diagnosed with Xp11.2 RCC. The urological and radiological outcomes remained satisfactory after >2.5 years of follow-up. PMID:25120696

Laparoscopic radiofrequency ablation-assisted enucleation of Xp11.2 translocation renal cell carcinoma: A case report.

PubMed

Xu, Linfeng; Yang, Rong; Wang, Wei; Zhang, Yifen; Gan, Weidong

2014-09-01

The current study presents a case of Xp11.2 translocation renal cell carcinoma (Xp11.2 RCC) in a 30-year-old female. The patient was referred to The Affiliated Drum Tower Hospital of the Medical College of Nanjing University (Nanjing, Jiangsu, China) due to a right renal tumor without evident symptoms, which was found by a routine physical examination. A computed tomography (CT) scan indicated that the mass exhibited cystic and solid components. The patient underwent laparoscopic radiofrequency ablation-assisted enucleation. Immunohistochemistry revealed intense nuclear staining for transcription factor E3 protein in the cancer cells. The patient was diagnosed with Xp11.2 RCC. The urological and radiological outcomes remained satisfactory after >2.5 years of follow-up.

Refinement of the X-linked cataract locus (CXN) and gene analysis for CXN and Nance-Horan syndrome (NHS).

PubMed

Brooks, Simon; Ebenezer, Neil; Poopalasundaram, Subathra; Maher, Eamonn; Francis, Peter; Moore, Anthony; Hardcastle, Alison

2004-06-01

The X-linked congenital cataract (CXN) locus has been mapped to a 3-cM (approximately 3.5 Mb) interval on chromosome Xp22.13, which is syntenic to the mouse cataract disease locus Xcat and encompasses the recently refined Nance-Horan syndrome (NHS) locus. A positional cloning strategy has been adopted to identify the causative gene. In an attempt to refine the CXN locus, seven microsatellites were analysed within 21 individuals of a CXN family. Haplotypes were reconstructed confirming disease segregation with markers on Xp22.13. In addition, a proximal cross-over was observed between markers S3 and S4, thereby refining the CXN disease interval by approximately 400 Kb to 3.2 Mb, flanked by markers DXS9902 and S4. Two known genes (RAI2 and RBBP7) and a novel gene (TL1) were screened for mutations within an affected male from the CXN family and an NHS family by direct sequencing of coding exons and intron- exon splice sites. No mutations or polymorphisms were identified, therefore excluding them as disease-causative in CXN and NHS. In conclusion, the CXN locus has been successfully refined and excludes PPEF1 as a candidate gene. A further three candidates were excluded based on sequence analysis. Future positional cloning efforts will focus on the region of overlap between CXN, Xcat, and NHS.

46 CFR 154.182 - Contiguous hull structure: Production weld test.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false Contiguous hull structure: Production weld test. 154.182... Equipment Hull Structure § 154.182 Contiguous hull structure: Production weld test. If a portion of the contiguous hull structure is designed for a temperature colder than −34 °C (−30 °F) and is not part of the...

46 CFR 154.182 - Contiguous hull structure: Production weld test.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 5 2011-10-01 2011-10-01 false Contiguous hull structure: Production weld test. 154.182... Equipment Hull Structure § 154.182 Contiguous hull structure: Production weld test. If a portion of the contiguous hull structure is designed for a temperature colder than −34 °C (−30 °F) and is not part of the...

46 CFR 154.182 - Contiguous hull structure: Production weld test.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 5 2012-10-01 2012-10-01 false Contiguous hull structure: Production weld test. 154.182... Equipment Hull Structure § 154.182 Contiguous hull structure: Production weld test. If a portion of the contiguous hull structure is designed for a temperature colder than −34 °C (−30 °F) and is not part of the...

46 CFR 154.182 - Contiguous hull structure: Production weld test.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 5 2014-10-01 2014-10-01 false Contiguous hull structure: Production weld test. 154.182... Equipment Hull Structure § 154.182 Contiguous hull structure: Production weld test. If a portion of the contiguous hull structure is designed for a temperature colder than −34 °C (−30 °F) and is not part of the...

46 CFR 154.182 - Contiguous hull structure: Production weld test.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 5 2013-10-01 2013-10-01 false Contiguous hull structure: Production weld test. 154.182... Equipment Hull Structure § 154.182 Contiguous hull structure: Production weld test. If a portion of the contiguous hull structure is designed for a temperature colder than −34 °C (−30 °F) and is not part of the...

Xp11.2 Translocation renal cell carcinomas have a poorer prognosis than non-Xp11.2 translocation carcinomas in children and young adults: a meta-analysis.

PubMed

Qiu Rao; Bing Guan; Zhou, Xiao-jun

2010-12-01

Renal cell carcinomas (RCCs) in children and adolescents are much rarer than in adults. In this age group, Xp11.2 translocation RCCs were the most common subtype of pediatric RCCs. Information regarding the clinical behavior of pediatric RCCs remains controversial because of their relatively rare incidence. The authors aimed to perform a systematic review and meta-analysis to better define the biological features of pediatric RCCs. Eligible studies were identified through multiple search strategies. Studies were assessed for quality using the Jadad Quality Scale. Data were collected comparing overall survival (OS), disease-free survival (DFS), and stage in patients with TFE3 + pediatric RCCs and TFE3 - RCCs. A total of 4 studies were included for meta-analysis, and pooled odds ratios (ORs) with 95% confidence interval (CI) were calculated. The meta-analysis outcomes showed that TFE3 + pediatric RCCs were significantly associated with poorer outcomes (OS and DFS) and a higher stage (III/IV) than TFE3 - RCCs (pooled ORs for each group: 4.59 [95% CI = 1.46-14.42] for OS; 5.79 [95% CI = 1.85-18.16] for DFS; and 5.89 [95% CI = 2.23-15.52] for stage). This result was also confirmed by OS and DFS curves (P = .005 and P = .001). Xp11.2 translocation carcinomas appear to have a poorer prognosis than non-Xp11.2 translocation carcinomas in children and young adults.

Pediatric renal cell carcinoma associated with Xp11.2 translocation/TFE3 gene fusion.

PubMed

Winarti, Ni Wayan; Argani, Pedram; De Marzo, Angelo M; Hicks, Jessica; Mulyadi, Ketut

2008-01-01

Renal cell carcinoma (RCC) in children and young adults is rare and pathologically problematic. RCC can be either hereditary or sporadic and has a guarded prognosis because appropriate management has not been established. A case of RCC in an 11-year-old is reported. The clinical presentation was a right abdominal mass, hematuria, urinary tract infection, and wasting. Radio-logically, the mass was found within the right kidney with calcification and paraaortic lymphadenopathy. The postsurgical diagnosis was Wilms' tumor stage T4N2M0. On gross inspection, the tumor was ill defined, extending across Gerota's fascia and into the ureter lumina. Microscopically, the tumor consisted of malignant epithelial cells with clear and eosinophilic cytoplasm in nested, papillary, and alveolar configuration. Hyaline nodules, psammoma bodies, vascular invasion, capsular invasion, and extension into the ureter were also found. Immunohistochemically, the cells showed strong nuclear immunoreactivity for TFE3. We concluded that this case was an RCC associated with Xp11.2 translocation/TFE3 fusion, Fuhrman grade 3, stage IV.

Gene of a new X-linked syndrome with multiple congenital anomalies and severe mental retardation maps in Xp22-pter

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wittwer, B.; Kircheisen, R.; Leutelt, J.

1994-09-01

We report on a family with 3 males presenting with a not yet described new X-chromosomal syndrome of multiple congenital anomalies and severe mental retardation. Two sisters have (with 3 different partners) 3 severely handicapped sons. In each case, oligohydramnios and intrauterine growth retardation were observed. Delivery was in the 34th, 31st, and 38th gestational week, respectively. Two of the patients had microcephaly (head circumference of the third case at birth is unknown). On physical examination, high and broad forehead, frontal bossing, downslanting palpebral fissures, long philtrum, thin upper lip, high arched palate, and deeply set anteverted ears were seen.more » One of the boys has microphthalmos and sclerocornea, while his cousin shows atrophy of the optic nerve. All three patients show a severe statomotor and mental retardation, they are most likely deaf and blind, have pathologic EEG, and seizures. Important additional findings are hydronephrosis, renal duplication, vesicorenal reflux, and agenesis of corpus callosum. The karyotype is normal (46,XY). We performed a segregation analysis in the family using more than 20 DNA polymorphisms distributed over the X chromosome. Linkage without recombination was found to KAL, DXS278, and DXS16 in Xp22. Analysis of multiple informative meioses suggested a location of the disease locus distal to DXS207. Recombinants were identified with all other marker loci from Xp22-Xpter.« less

33 CFR 117.17 - Signalling for contiguous drawbridges.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Signalling for contiguous... SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS General Requirements § 117.17 Signalling for contiguous drawbridges. When a vessel must past two or more drawbridges close together, the opening signal is given for...

33 CFR 117.17 - Signalling for contiguous drawbridges.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Signalling for contiguous... SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS General Requirements § 117.17 Signalling for contiguous drawbridges. When a vessel must past two or more drawbridges close together, the opening signal is given for...

33 CFR 117.17 - Signalling for contiguous drawbridges.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 33 Navigation and Navigable Waters 1 2014-07-01 2014-07-01 false Signalling for contiguous... SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS General Requirements § 117.17 Signalling for contiguous drawbridges. When a vessel must past two or more drawbridges close together, the opening signal is given for...

33 CFR 117.17 - Signalling for contiguous drawbridges.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 33 Navigation and Navigable Waters 1 2012-07-01 2012-07-01 false Signalling for contiguous... SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS General Requirements § 117.17 Signalling for contiguous drawbridges. When a vessel must past two or more drawbridges close together, the opening signal is given for...

33 CFR 117.17 - Signalling for contiguous drawbridges.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 33 Navigation and Navigable Waters 1 2013-07-01 2013-07-01 false Signalling for contiguous... SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS General Requirements § 117.17 Signalling for contiguous drawbridges. When a vessel must past two or more drawbridges close together, the opening signal is given for...

Comparative mapping of powdery mildew resistance gene Pm21 and functional characterization of resistance-related genes in wheat.

PubMed

He, Huagang; Zhu, Shanying; Jiang, Zhengning; Ji, Yaoyong; Wang, Feng; Zhao, Renhui; Bie, Tongde

2016-04-01

The powdery mildew resistance gene Pm21 was physically and comparatively mapped by newly developed markers. Seven candidate genes were verified to be required for Pm21 -mediated resistance to wheat powdery mildew. Pm21, a gene derived from wheat wild relative Dasypyrum villosum, has been transferred into common wheat and widely utilized in wheat resistance breeding for powdery mildew. Previously, Pm21 has been located to the bin FL0.45-0.58 of 6VS by using deletion stocks. However, its fine mapping is still a hard work. In the present study, 30 gene-derived 6VS-specific markers were obtained based on the collinearity among genomes of Brachypodium distachyon, Oryza and Triticeae, and then physically and comparatively mapped in the bin FL0.45-0.58 and its nearby chromosome region. According to the maps, the bin FL0.45-0.58 carrying Pm21 was closely flanked by the markers 6VS-03 and 6VS-23, which further narrowed the orthologous regions to 1.06 Mb in Brachypodium and 1.38 Mb in rice, respectively. Among the conserved genes shared by Brachypodium and rice, four serine/threonine protein kinase genes (DvMPK1, DvMLPK, DvUPK and DvPSYR1), one protein phosphatase gene (DvPP2C) and two transcription factor genes (DvGATA and DvWHY) were confirmed to be required for Pm21-mediated resistance to wheat powdery mildew by barley stripe mosaic virus-induced gene silencing (BSMV-VIGS) and transcriptional pattern analyses. In summary, this study gives new insights into the genetic basis of the Pm21 locus and the disease resistance pathways mediated by Pm21.

Xp11.2 translocation renal cell carcinoma occurring during pregnancy with a novel translocation involving chromosome 19: a case report with review of the literature

PubMed Central

Armah, Henry B; Parwani, Anil V; Surti, Urvashi; Bastacky, Sheldon I

2009-01-01

The recently recognized renal cell carcinomas (RCCs) associated with Xp11.2 translocations (TFE3 transcription factor gene fusions) are rare tumors predominantly reported in children. They comprise at least one-third of pediatric RCCs and only few adult cases have been reported. Here, we present a case of Xp11.2 translocation RCC in 26-year-old pregnant female. Her routine antenatal ultrasonography accidentally found a complex cystic right renal mass. Further radiologic studies revealed unilocular cyst with multiple mural nodules at inferior pole of right kidney, which was suspicious for RCC. She underwent right radical nephrectomy at 15 weeks gestation. Macroscopically, the cystic tumor was well encapsulated with multiple friable mural nodules on its inner surface. Microscopically, the tumor consisted of clear and eosinophilic/oncocytic voluminous cells arranged in papillary, trabecular, and nested/alveolar patterns. Occasional hyaline nodules and numerous psammoma bodies were present. Immunohistochemically, the tumor showed strong nuclear positivity for TFE3. Epithelial membrane antigen, CD10, and E-cadherin were strongly positive. Cytokeratin AE1/AE3, cytokeratin CAM-5.2, calveolin, and parvalbumin were moderately positive. Cytokeratin 7, renal cell carcinoma antigen, and colloidal iron were focally weakly positive. BerEP4 and carbonic anhydrase IX were negative. Cytogenetically, the tumor harbored a novel variant translocation involving chromosomes X and 19, t(X;19)(p11.2;q13.1). Interphase FISH analysis performed on cultured and uncultured tumor cells using a dual-color break-apart DNA probe within the BCL3 gene on 19q13.3 was negative for the BCL3 gene rearrangement. She received no adjuvant therapy, delivered a normal term baby five months later, and is alive without evidence of disease 27 months after diagnosis and surgery. Unlike most recently reported Xp11.2 translocation RCCs in adult patients with aggressive clinical course, this adult case occurring

Xp11.2 translocation renal cell carcinoma occurring during pregnancy with a novel translocation involving chromosome 19: a case report with review of the literature.

PubMed

Armah, Henry B; Parwani, Anil V; Surti, Urvashi; Bastacky, Sheldon I

2009-05-18

The recently recognized renal cell carcinomas (RCCs) associated with Xp11.2 translocations (TFE3 transcription factor gene fusions) are rare tumors predominantly reported in children. They comprise at least one-third of pediatric RCCs and only few adult cases have been reported. Here, we present a case of Xp11.2 translocation RCC in 26-year-old pregnant female. Her routine antenatal ultrasonography accidentally found a complex cystic right renal mass. Further radiologic studies revealed unilocular cyst with multiple mural nodules at inferior pole of right kidney, which was suspicious for RCC. She underwent right radical nephrectomy at 15 weeks gestation. Macroscopically, the cystic tumor was well encapsulated with multiple friable mural nodules on its inner surface. Microscopically, the tumor consisted of clear and eosinophilic/oncocytic voluminous cells arranged in papillary, trabecular, and nested/alveolar patterns. Occasional hyaline nodules and numerous psammoma bodies were present.Immunohistochemically, the tumor showed strong nuclear positivity for TFE3. Epithelial membrane antigen, CD10, and E-cadherin were strongly positive. Cytokeratin AE1/AE3, cytokeratin CAM-5.2, calveolin, and parvalbumin were moderately positive. Cytokeratin 7, renal cell carcinoma antigen, and colloidal iron were focally weakly positive. BerEP4 and carbonic anhydrase IX were negative. Cytogenetically, the tumor harbored a novel variant translocation involving chromosomes X and 19, t(X;19)(p11.2;q13.1). Interphase FISH analysis performed on cultured and uncultured tumor cells using a dual-color break-apart DNA probe within the BCL3 gene on 19q13.3 was negative for the BCL3 gene rearrangement. She received no adjuvant therapy, delivered a normal term baby five months later, and is alive without evidence of disease 27 months after diagnosis and surgery. Unlike most recently reported Xp11.2 translocation RCCs in adult patients with aggressive clinical course, this adult case occurring

p21 as a Transcriptional Co-Repressor of S-Phase and Mitotic Control Genes

PubMed Central

Ferrándiz, Nuria; Caraballo, Juan M.; García-Gutierrez, Lucía; Devgan, Vikram; Rodriguez-Paredes, Manuel; Lafita, M. Carmen; Bretones, Gabriel; Quintanilla, Andrea; Muñoz-Alonso, M. Jose; Blanco, Rosa; Reyes, Jose C.; Agell, Neus; Delgado, M. Dolores; Dotto, G. Paolo; León, Javier

2012-01-01

It has been previously described that p21 functions not only as a CDK inhibitor but also as a transcriptional co-repressor in some systems. To investigate the roles of p21 in transcriptional control, we studied the gene expression changes in two human cell systems. Using a human leukemia cell line (K562) with inducible p21 expression and human primary keratinocytes with adenoviral-mediated p21 expression, we carried out microarray-based gene expression profiling. We found that p21 rapidly and strongly repressed the mRNA levels of a number of genes involved in cell cycle and mitosis. One of the most strongly down-regulated genes was CCNE2 (cyclin E2 gene). Mutational analysis in K562 cells showed that the N-terminal region of p21 is required for repression of gene expression of CCNE2 and other genes. Chromatin immunoprecipitation assays indicated that p21 was bound to human CCNE2 and other p21-repressed genes gene in the vicinity of the transcription start site. Moreover, p21 repressed human CCNE2 promoter-luciferase constructs in K562 cells. Bioinformatic analysis revealed that the CDE motif is present in most of the promoters of the p21-regulated genes. Altogether, the results suggest that p21 exerts a repressive effect on a relevant number of genes controlling S phase and mitosis. Thus, p21 activity as inhibitor of cell cycle progression would be mediated not only by the inhibition of CDKs but also by the transcriptional down-regulation of key genes. PMID:22662213

Renal carcinomas associated with Xp11.2 translocations: are CT findings suggestive of the diagnosis?

PubMed

He, J; Huan, Y; Qiao, Q; Zhang, J; Zhang, J S

2014-01-01

The purpose of the present study was to summarize the computed tomography (CT) features of renal carcinomas associated with Xp11.2 translocations, and determine whether the diagnosis can be reliably deduced from imaging findings. Radiological studies of six patients (aged from 9-29 years) with renal carcinoma associated with Xp11.2 translocations were retrospectively analysed. The tumours varied in size from 3.3-11 cm (mean 5.4 cm). Unenhanced CT and cortical, medullary, and pelvic-phase contrast-enhanced CT imaging was undertaken in all cases. Unenhanced CT revealed that tumours had a relatively increased radiodensity (4/6, ranged from 45-60 HU) and suggested the possibility of diffuse haemorrhage. Three of the six cases showed irregular and boundary calcification of the lesion. Contrast-enhanced CT showed relatively well demarcated tumours with heterogeneous enhancement (6/6). Prolonged enhancement of tumours might be a common sign (6/6) in Xp11.2 translocations. Three out of the six cases were combined with retroperitoneal lymph nodes metastasis. Renal carcinomas associated with Xp11.2 translocations should be considered, particularly in children and young patients, when the lesion has calcification and is hyper-dense on unenhanced CT, and has prolonged enhancement on contrast-enhanced images. Copyright © 2013 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Spatial Contiguity and Incidental Learning in Multimedia Environments

ERIC Educational Resources Information Center

Paek, Seungoh; Hoffman, Daniel L.; Saravanos, Antonios

2017-01-01

Drawing on dual-process theories of cognitive function, the degree to which spatial contiguity influences incidental learning outcomes was examined. It was hypothesized that spatial contiguity would mediate what was learned even in the absence of an explicit learning goal. To test this hypothesis, 149 adults completed a multimedia-related task…

46 CFR 154.172 - Contiguous steel hull structure.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false Contiguous steel hull structure. 154.172 Section 154.172... STANDARDS FOR SELF-PROPELLED VESSELS CARRYING BULK LIQUEFIED GASES Design, Construction and Equipment Hull Structure § 154.172 Contiguous steel hull structure. (a) Except as allowed in paragraphs (b) and (c) of this...

Localization of a gene responsible for nonspecific mental retardation (MRX9) to the pericentromeric region of the X chromosome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Willems, P.; Vits, L.; Buntinx, I.

1993-11-01

Nonspecific X-linked mental retardation (MRX) includes several distinct entities with mental retardation but without additional distinguishing features. The MRX family reported here has been classified previously as MRX9. In this study, the authors performed linkage analysis of MRX9 with a panel of 43 polymorphic DNA markers dispersed over chromosome X. Two-point linkage analysis revealed lod scores of 3.52 and 3.82 at 0% recombination for OATL1 and MAOA, both located in Xp11.2-p11.4. Lod scores for linkage with PGK1P1, DXS106, and DXS132, all located in Xq11-q13, were 3.83, 3.82, and 3.52, respectively, all at 0% recombination. Multipoint linkage analysis showed two peaksmore » with MAOA and DXS132/DXS106, respectively. Analysis of recombinational events indicated a position of the MRX9 gene between DXS164 and DXS453. These findings are compatible with a location of the MRX9 gene in the pericentromeric region of the X chromosome at Xp21-q13. 26 refs., 3 figs., 2 tabs.« less

XPC gene mutations in families with xeroderma pigmentosum from Pakistan; prevalent founder effect.

PubMed

Ijaz, Ambreen; Basit, Sulman; Gul, Ajab; Batool, Lilas; Hussain, Abrar; Afzal, Sibtain; Ramzan, Khushnooda; Ahmad, Jamil; Wali, Abdul

2018-03-23

Xeroderma pigmentosum (XP) is a rare autosomal recessive skin disorder characterized by hyperpigmentation, premature skin aging, ocular and cutaneous photosensitivity, and increased risk of skin carcinoma. We investigated seven consanguineous XP families with nine patients from Pakistan. All the Patients exhibited typical clinical symptoms of XP since first year of life. Whole genome SNP genotyping identified a 14 Mb autozygous region segregating with the disease phenotype on chromosome 3p25.1. DNA sequencing of XPC gene revealed a founder homozygous splice site mutation (c.2251-1G>C) in patients from six families (A-F) and a homozygous nonsense mutation (c.1399C>T; p.Gln467*) in patients of family G. This is the first report of XPC mutations, underlying XP phenotype, in Pakistani population. © 2018 Japanese Teratology Society.

Xeroderma pigmentosum complementation group C cells remove pyrimidine dimers selectively from the transcribed strand of active genes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Venema, J.; van Hoffen, A.; Karcagi, V.

1991-08-01

The authors have measured the removal of UV-induced pyrimidine dimers from DNA fragments of the adenosine deaminase (ADA) and dihydrofolate reductase (DHFR) genes in primary normal human and xeroderma pigmentosum complementation group C (XP-C) cells. Using strand-specific probes, we show that in normal cells, preferential repair of the 5{prime} part of the ADA gene is due to the rapid and efficient repair of the transcribed strand. Within 8 h after irradiation with UV at 10 J m-2, 70% of the pyrimidine dimers in this strand are removed. The nontranscribed strand is repaired at a much slower rate, with 30% dimersmore » removed after 8 h. Repair of the transcribed strand in XP-C cells occurs at a rate indistinguishable from that in normal cells, but the nontranscribed strand is not repaired significantly in these cells. Similar results were obtained for the DHFR gene. In the 3{prime} part of the ADA gene, however, both normal and XP-C cells perform fast and efficient repair of either strand, which is likely to be caused by the presence of transcription units on both strands. The factor defective in XP-C cells is apparently involved in the processing of DNA damage in inactive parts of the genome, including nontranscribed strands of active genes. These findings have important implications for the understanding of the mechanism of UV-induced excision repair and mutagenesis in mammalian cells.« less

Vascular endothelial growth factor (VEGF)-targeted therapy for the treatment of adult metastatic Xp11.2 translocation renal cell carcinoma

PubMed Central

Choueiri, Toni K.; Lim, Zita Dubauskas; Hirsch, Michelle S.; Tamboli, Pheroze; Jonasch, Eric; McDermott, David F.; Cin, Paola Dal; Corn, Paul; Vaishampayan, Ulka; Heng, Daniel Y.C.; Tannir, Nizar M.

2015-01-01

Introduction Adult “translocation” renal cell carcinoma (RCC), bearing TFE3 gene fusions at Xp11.2, is a recently recognized unique entity for which prognosis and therapy remain poorly understood. We investigated the effect of vascular-endothelial growth factor (VEGF)-targeted therapy in this distinct subtype of RCC. Patients and Methods We conducted a retrospective review to describe the clinical characteristics and outcome of adult patients with metastatic Xp11.2 RCC, who had strong TFE-3 nuclear immunostaining, and received anti-VEGF therapy. Tumor response to anti-VEGF therapy was evaluated by RECIST. Kaplan-Meier methods were used to estimate progression-free survival (PFS) and overall survival (OS) distributions. Results Fifteen patients were identified of which 10, 3, and 2 received sunitinib, sorafenib and monoclonal anti-VEGF antibodies, respectively. The median follow-up was 19.1 months, the median age of the patients was 41 years, and the female:male ratio was 4:1. Initial histologic description included clear cell (n=8), papillary (n=1) or mixed clear cell/papillary RCC (n=6). Five patients had prior systemic therapy. Five patients had FISH analysis and all demonstrated a translocation involving chromosome Xp11.2. When treated with VEGF-targeted therapy, 3 patients had a partial response, 7 patients had stable disease and 5 patients had progressive disease. The median PFS and OS of the entire cohort were 7.1 months and 14.3 months respectively. Conclusion Adult-onset translocation-associated metastatic RCC is an aggressive disease that affects a younger population of patients with a female predominance. VEGF-targeted agents demonstrated some efficacy in this small retrospective series. PMID:20665500

Structure and Function of the Two Tandem WW Domains of the Pre-mRNA Splicing Factor FBP21 (Formin-binding Protein 21)*

PubMed Central

Huang, Xiaojuan; Beullens, Monique; Zhang, Jiahai; Zhou, Yi; Nicolaescu, Emilia; Lesage, Bart; Hu, Qi; Wu, Jihui; Bollen, Mathieu; Shi, Yunyu

2009-01-01

Human FBP21 (formin-binding protein 21) contains a matrin-type zinc finger and two tandem WW domains. It is a component of the spliceosomes and interacts with several established splicing factors. Here we demonstrate for the first time that FBP21 is an activator of pre-mRNA splicing in vivo and that its splicing activation function and interaction with the splicing factor SIPP1 (splicing factor that interacts with PQBP1 and PP1) are both mediated by the two tandem WW domains of group III. We determined the solution structure of the tandem WW domains of FBP21 and found that the WW domains recognize peptide ligands containing either group II (PPLP) or group III (PPR) motifs. The binding interfaces involve both the XP and XP2 grooves of the two WW domains. Significantly, the tandem WW domains of FBP21 are connected by a highly flexible region, enabling their simultaneous interaction with two proline-rich motifs of SIPP1. The strong interaction between SIPP1 and FBP21 can be explained by the conjugation of two low affinity interactions with the tandem WW domains. Our study provides a structural basis for understanding the molecular mechanism underlying the functional implication of FBP21 and the biological specificity of tandem WW domains. PMID:19592703

Nucleotide Excision Repair Proteins Rapidly Accumulate but Fail to Persist in Human XP-E (DDB2 Mutant) Cells

PubMed Central

Oh, Kyu-Seon; Imoto, Kyoko; Emmert, Steffen; Tamura, Deborah; DiGiovanna, John J.; Kraemer, Kenneth. H.

2011-01-01

The XP-E DNA damage binding protein (DDB2) is involved in early recognition of global genome DNA damage during DNA nucleotide excision repair (NER). We found that skin fibroblasts from 4 newly reported XP-E patients with numerous skin cancers and DDB2 mutations had slow repair of 6-4 photoproducts (6-4PP) and markedly reduced repair of cyclobutane pyrimidine dimers (CPD). NER proteins (XPC, XPB, XPG, XPA, and XPF) co-localized to CPD and 6-4PP positive regions immediately (< 0.1h) after localized UV irradiation in cells from the XP-E patients and normal controls. While these proteins persist in normal cells, surprisingly, within 0.5h these repair proteins were no longer detectable at the sites of DNA damage in XP-E cells. Our results indicate that DDB2 is not required for the rapid recruitment of NER proteins to sites of UV photoproducts or for partial repair of 6-4PP but is essential for normal persistence of these proteins for CPD photoproduct removal. PMID:21388382

Vascular endothelial growth factor-targeted therapy for the treatment of adult metastatic Xp11.2 translocation renal cell carcinoma.

PubMed

Choueiri, Toni K; Lim, Zita Dubauskas; Hirsch, Michelle S; Tamboli, Pheroze; Jonasch, Eric; McDermott, David F; Dal Cin, Paola; Corn, Paul; Vaishampayan, Ulka; Heng, Daniel Y C; Tannir, Nizar M

2010-11-15

Adult "translocation" renal cell carcinoma (RCC), bearing transcription factor E3 (TFE3) gene fusions at Xp11.2, is a recently recognized, unique entity for which prognosis and therapy remain poorly understood. In the current study, the authors investigated the effect of vascular endothelial growth factor (VEGF)-targeted therapy in this distinct subtype of RCC. A retrospective review was conducted to describe the clinical characteristics and outcome of adult patients with metastatic Xp11.2 RCC who had strong TFE3 nuclear immunostaining and received anti-VEGF therapy. Tumor response to anti-VEGF therapy was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) criteria. The Kaplan-Meier method was used to estimate progression-free survival (PFS) and overall survival (OS) distributions. Fifteen patients were identified, of whom 10, 3, and 2 received sunitinib, sorafenib, and monoclonal anti-VEGF antibodies, respectively. The median follow-up was 19.1 months, the median age of the patients was 41 years, and the female:male ratio was 4:1. Initial histologic description included clear cell (n = 8 patients), papillary (n = 1 patient), or mixed clear cell/papillary RCC (n = 6 patients). Five patients had received prior systemic therapy. Five patients had undergone fluorescent in situ hybridization analysis and all demonstrated a translocation involving chromosome Xp11.2. When treated with VEGF-targeted therapy, 3 patients achieved a partial response, 7 patients had stable disease, and 5 patients developed progressive disease. The median PFS and OS of the entire cohort were 7.1 months and 14.3 months, respectively. Adult-onset, translocation-associated metastatic RCC is an aggressive disease that affects a younger population of patients with a female predominance. In the current study, VEGF-targeted agents appeared to demonstrate some efficacy. Copyright © 2010 American Cancer Society.

Identification of an Imprinted Gene Cluster in the X-Inactivation Center

PubMed Central

Kobayashi, Shin; Totoki, Yasushi; Soma, Miki; Matsumoto, Kazuya; Fujihara, Yoshitaka; Toyoda, Atsushi; Sakaki, Yoshiyuki; Okabe, Masaru; Ishino, Fumitoshi

2013-01-01

Mammalian development is strongly influenced by the epigenetic phenomenon called genomic imprinting, in which either the paternal or the maternal allele of imprinted genes is expressed. Paternally expressed Xist, an imprinted gene, has been considered as a single cis-acting factor to inactivate the paternally inherited X chromosome (Xp) in preimplantation mouse embryos. This means that X-chromosome inactivation also entails gene imprinting at a very early developmental stage. However, the precise mechanism of imprinted X-chromosome inactivation remains unknown and there is little information about imprinted genes on X chromosomes. In this study, we examined whether there are other imprinted genes than Xist expressed from the inactive paternal X chromosome and expressed in female embryos at the preimplantation stage. We focused on small RNAs and compared their expression patterns between sexes by tagging the female X chromosome with green fluorescent protein. As a result, we identified two micro (mi)RNAs–miR-374-5p and miR-421-3p–mapped adjacent to Xist that were predominantly expressed in female blastocysts. Allelic expression analysis revealed that these miRNAs were indeed imprinted and expressed from the Xp. Further analysis of the imprinting status of adjacent locus led to the discovery of a large cluster of imprinted genes expressed from the Xp: Jpx, Ftx and Zcchc13. To our knowledge, this is the first identified cluster of imprinted genes in the cis-acting regulatory region termed the X-inactivation center. This finding may help in understanding the molecular mechanisms regulating imprinted X-chromosome inactivation during early mammalian development. PMID:23940725

Identification of an imprinted gene cluster in the X-inactivation center.

PubMed

Kobayashi, Shin; Totoki, Yasushi; Soma, Miki; Matsumoto, Kazuya; Fujihara, Yoshitaka; Toyoda, Atsushi; Sakaki, Yoshiyuki; Okabe, Masaru; Ishino, Fumitoshi

2013-01-01

Mammalian development is strongly influenced by the epigenetic phenomenon called genomic imprinting, in which either the paternal or the maternal allele of imprinted genes is expressed. Paternally expressed Xist, an imprinted gene, has been considered as a single cis-acting factor to inactivate the paternally inherited X chromosome (Xp) in preimplantation mouse embryos. This means that X-chromosome inactivation also entails gene imprinting at a very early developmental stage. However, the precise mechanism of imprinted X-chromosome inactivation remains unknown and there is little information about imprinted genes on X chromosomes. In this study, we examined whether there are other imprinted genes than Xist expressed from the inactive paternal X chromosome and expressed in female embryos at the preimplantation stage. We focused on small RNAs and compared their expression patterns between sexes by tagging the female X chromosome with green fluorescent protein. As a result, we identified two micro (mi)RNAs-miR-374-5p and miR-421-3p-mapped adjacent to Xist that were predominantly expressed in female blastocysts. Allelic expression analysis revealed that these miRNAs were indeed imprinted and expressed from the Xp. Further analysis of the imprinting status of adjacent locus led to the discovery of a large cluster of imprinted genes expressed from the Xp: Jpx, Ftx and Zcchc13. To our knowledge, this is the first identified cluster of imprinted genes in the cis-acting regulatory region termed the X-inactivation center. This finding may help in understanding the molecular mechanisms regulating imprinted X-chromosome inactivation during early mammalian development.

In silico characterization of a novel pathogenic deletion mutation identified in XPA gene in a Pakistani family with severe xeroderma pigmentosum.

PubMed

Nasir, Muhammad; Ahmad, Nafees; Sieber, Christian M K; Latif, Amir; Malik, Salman Akbar; Hameed, Abdul

2013-09-24

Xeroderma Pigmentosum (XP) is a rare skin disorder characterized by skin hypersensitivity to sunlight and abnormal pigmentation. The aim of this study was to investigate the genetic cause of a severe XP phenotype in a consanguineous Pakistani family and in silico characterization of any identified disease-associated mutation. The XP complementation group was assigned by genotyping of family for known XP loci. Genotyping data mapped the family to complementation group A locus, involving XPA gene. Mutation analysis of the candidate XP gene by DNA sequencing revealed a novel deletion mutation (c.654del A) in exon 5 of XPA gene. The c.654del A, causes frameshift, which pre-maturely terminates protein and result into a truncated product of 222 amino acid (aa) residues instead of 273 (p.Lys218AsnfsX5). In silico tools were applied to study the likelihood of changes in structural motifs and thus interaction of mutated protein with binding partners. In silico analysis of mutant protein sequence, predicted to affect the aa residue which attains coiled coil structure. The coiled coil structure has an important role in key cellular interactions, especially with DNA damage-binding protein 2 (DDB2), which has important role in DDB-mediated nucleotide excision repair (NER) system. Our findings support the fact of genetic and clinical heterogeneity in XP. The study also predicts the critical role of DDB2 binding region of XPA protein in NER pathway and opens an avenue for further research to study the functional role of the mutated protein domain.

In silico characterization of a novel pathogenic deletion mutation identified in XPA gene in a Pakistani family with severe xeroderma pigmentosum

PubMed Central

2013-01-01

Background Xeroderma Pigmentosum (XP) is a rare skin disorder characterized by skin hypersensitivity to sunlight and abnormal pigmentation. The aim of this study was to investigate the genetic cause of a severe XP phenotype in a consanguineous Pakistani family and in silico characterization of any identified disease-associated mutation. Results The XP complementation group was assigned by genotyping of family for known XP loci. Genotyping data mapped the family to complementation group A locus, involving XPA gene. Mutation analysis of the candidate XP gene by DNA sequencing revealed a novel deletion mutation (c.654del A) in exon 5 of XPA gene. The c.654del A, causes frameshift, which pre-maturely terminates protein and result into a truncated product of 222 amino acid (aa) residues instead of 273 (p.Lys218AsnfsX5). In silico tools were applied to study the likelihood of changes in structural motifs and thus interaction of mutated protein with binding partners. In silico analysis of mutant protein sequence, predicted to affect the aa residue which attains coiled coil structure. The coiled coil structure has an important role in key cellular interactions, especially with DNA damage-binding protein 2 (DDB2), which has important role in DDB-mediated nucleotide excision repair (NER) system. Conclusions Our findings support the fact of genetic and clinical heterogeneity in XP. The study also predicts the critical role of DDB2 binding region of XPA protein in NER pathway and opens an avenue for further research to study the functional role of the mutated protein domain. PMID:24063568

46 CFR 154.180 - Contiguous hull structure: Welding procedure.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 5 2012-10-01 2012-10-01 false Contiguous hull structure: Welding procedure. 154.180 Section 154.180 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS... Equipment Hull Structure § 154.180 Contiguous hull structure: Welding procedure. Welding procedure tests for...

46 CFR 154.180 - Contiguous hull structure: Welding procedure.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 5 2013-10-01 2013-10-01 false Contiguous hull structure: Welding procedure. 154.180 Section 154.180 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS... Equipment Hull Structure § 154.180 Contiguous hull structure: Welding procedure. Welding procedure tests for...

46 CFR 154.180 - Contiguous hull structure: Welding procedure.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 5 2011-10-01 2011-10-01 false Contiguous hull structure: Welding procedure. 154.180 Section 154.180 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS... Equipment Hull Structure § 154.180 Contiguous hull structure: Welding procedure. Welding procedure tests for...

46 CFR 154.180 - Contiguous hull structure: Welding procedure.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 5 2014-10-01 2014-10-01 false Contiguous hull structure: Welding procedure. 154.180 Section 154.180 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS... Equipment Hull Structure § 154.180 Contiguous hull structure: Welding procedure. Welding procedure tests for...

Chromosomal localization of three repair genes: The xeroderma pigmentosum group C gene and two human homologs of yeast RAD23

DOE Office of Scientific and Technical Information (OSTI.GOV)

Spek, P.J. van der; Smit, E.M.E.; Beverloo, H.B.

1994-10-01

The nucleotide excision repair (NER) disorder xeroderma pigmentosum (XP) is characterized by sun (UV) sensitivity, predisposition to skin cancer, and extensive genetic heterogeneity. Recently, we reported the cloning and analysis of three human NER genes, XPC, HHR23A, and HHR23B. The previously cloned XPC gene is involved in the common XP complementation group C, which is defective in excision repair of nontranscribed sequences in the genome. The XPC protein was found to be complexed with the product of HHR23B, one of the two human homologs of the Saccharomyes cerevisiae NER gene RAD23. Here we present the chromosomal localization by in situmore » hybridization using haptenized probes of all three genes. The HHR23A gene was assigned to chromosome 19p13.2. Interestingly, the HHR23B and XPC genes, the product of which forms a tight complex, were found to colocalize on band 3p25.1. Pulsed-field gel electrophoresis revealed that the HHR23B and XPC genes possibly share a MluI restriction fragment of about 625 kb. Potential involvement of the HHR23 genes in human genetic disorders is discussed. 53 refs., 4 figs., 2 tabs.« less

Computed tomography and magnetic resonance imaging of adult renal cell carcinoma associated with Xp11.2 translocation.

PubMed

Dang, Trien T; Ziv, Etay; Weinstein, Stefanie; Meng, Maxwell V; Wang, Zhen; Coakley, Fergus V

2012-01-01

This study aimed to report the computed tomography (CT) and magnetic resonance imaging (MRI) findings of renal cell carcinoma associated with Xp11.2 translocation in adults. We retrospectively identified 9 adults with renal cell carcinoma associated with Xp11.2 translocation who underwent baseline cross-sectional imaging with CT (n = 9) or MRI (n = 3). All available clinical, imaging, and histopathological records were reviewed. Mean patient age was 24 years (range, 18-45 years). Eight of 9 cancers demonstrated imaging findings of hemorrhage or necrosis (n = 3), advanced stage disease (n = 2), or both (n = 3) at CT or MRI. The possibility of renal cell carcinoma associated with Xp11.2 translocation should be considered for a renal mass seen in a patient 45 years or younger, which demonstrates hemorrhage or necrosis or advanced stage disease at CT or MRI.

Regional projections of the likelihood of very large wildland fires under a changing climate in the contiguous Western United States

Treesearch

Donald McKenzie; John T. Abatzoglou; E. Natasha Stavros; Narasimhan K. Larkin

2014-01-01

Seasonal changes in the climatic potential for very large wildfires (VLWF >= 50,000 ac~20,234 ha) across the western contiguous United States are projected over the 21st century using generalized linear models and downscaled climate projections for two representative concentration pathways (RCPs). Significant (p

Atypical Clinical Presentation of Xeroderma Pigmentosum in a Patient Harboring a Novel Missense Mutation in the XPC Gene: The Importance of Clinical Suspicion.

PubMed

Meneses, Marina; Chavez-Bourgeois, Marion; Badenas, Celia; Villablanca, Salvador; Aguilera, Paula; Bennàssar, Antoni; Alos, Llucia; Puig, Susana; Malvehy, Josep; Carrera, Cristina

2015-01-01

Xeroderma pigmentosum (XP) is a genodermatosis caused by abnormal DNA repair. XP complementation group C (XPC) is the most frequent type in Mediterranean countries. We describe a case with a novel mutation in the XPC gene. A healthy Caucasian male patient was diagnosed with multiple primary melanomas. Digital follow-up and molecular studies were carried out. During digital follow-up 8 more additional melanomas were diagnosed. Molecular studies did not identify mutations in CDKN2A, CDK4 or MITF genes. Two heterozygous mutations in the XPC gene were detected: c.2287delC (p.Leu763Cysfs*4) frameshift and c.2212A>G (p.Thr738Ala) missense mutations. The p.Thr738Ala missense mutation has not been previously described. Missense mutations in the XPC gene may allow partial functionality that could explain this unusual late onset XP. Atypical clinical presentation of XPC could be misdiagnosed when genetic aberrations allow partial DNA repair capacity. © 2015 S. Karger AG, Basel.

[Xp11.2 translocation renal carcinoma in adults over 50 years of age: about four cases].

PubMed

Arnoux, V; Long, J-A; Fiard, G; Pasquier, D; Bensaadi, L; Terrier, N; Rambeaud, J-J; Descotes, J-L

2012-11-01

To describe demographic, therapeutic and follow-up data of four cases of renal cell carcinoma with Xp11.2 translocation in adults older than 50 years of age. Between January 2008 and December 2011, 170 patients underwent surgery for renal cell carcinoma in our center. Systematic histopathologic analysis of specimen removed was performed. Complementary immunohistochemical analysis was performed only in cases with uncertain diagnosis or in patients younger than 40 years of age. Among these 170 patients with a median age of 59years old (21-89), immunohistochemistry helped find a TFE3 translocation in four cases (2.4%). There were three women and one man of 53, 71, 75 and 86years old respectively. One patient was metastatic at diagnosis. Radical nephrectomy was first performed in all cases. TNM staging was T3aN2R0, T3bN0R0, T2N2R0 and T3aN2R2, with a Furhman grade of 4. Two patients progressed with metastasis 5 and 7months after surgery, and two with lymphatic invasion 2 and 9months after nephrectomy. One patient died during follow-up. Xp11.2 translocation renal cell carcinoma was uncommon after 50years of age in our series, but probably under estimated. It seemed to be associated with a poor prognosis. Larger studies must be performed to optimize its specific treatment. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Common variants of xeroderma pigmentosum genes and prostate cancer risk.

PubMed

Mirecka, Aneta; Paszkowska-Szczur, Katarzyna; Scott, Rodney J; Górski, Bohdan; van de Wetering, Thierry; Wokołorczyk, Dominika; Gromowski, Tomasz; Serrano-Fernandez, Pablo; Cybulski, Cezary; Kashyap, Aniruddh; Gupta, Satish; Gołąb, Adam; Słojewski, Marcin; Sikorski, Andrzej; Lubiński, Jan; Dębniak, Tadeusz

2014-08-10

The genetic basis of prostate cancer (PC) is complex and appears to involve multiple susceptibility genes. A number of studies have evaluated a possible correlation between several NER gene polymorphisms and PC risk, but most of them evaluated only single SNPs among XP genes and the results remain inconsistent. Out of 94 SNPs located in seven XP genes (XPA-XPG) a total of 15 SNPs were assayed in 720 unselected patients with PC and compared to 1121 healthy adults. An increased risk of disease was associated with the XPD SNP, rs1799793 (Asp312Asn) AG genotype (OR=2.60; p<0.001) and with the AA genotype (OR=531; p<0.0001) compared to the control population. Haplotype analysis of XPD revealed one protective haplotype and four associated with an increased disease risk, which showed that the A allele (XPD rs1799793) appeared to drive the main effect on promoting prostate cancer risk. Polymorphism in XPD gene appears to be associated with the risk of prostate cancer. Copyright © 2014. Published by Elsevier B.V.

Effect of ProTaper Gold, Self-Adjusting File, and XP-endo Shaper Instruments on Dentinal Microcrack Formation: A Micro-computed Tomographic Study.

PubMed

Bayram, H Melike; Bayram, Emre; Ocak, Mert; Uygun, Ahmet Demirhan; Celik, Hakan Hamdi

2017-07-01

The aim of the present study was to evaluate the frequency of dentinal microcracks observed after root canal preparation with ProTaper Universal (PTU; Dentsply Tulsa Dental Specialties, Tulsa, OK), ProTaper Gold (PTG; Dentsply Tulsa Dental Specialties), Self-Adjusting File (SAF; ReDent Nova, Ra'anana, Israel), and XP-endo Shaper (XP; FKG Dentaire, La Chaux-de-Fonds, Switzerland) instruments using micro-computed tomographic (CT) analysis. Forty extracted human mandibular premolars having single-canal and straight root were randomly assigned to 4 experimental groups (n = 10) according to the different nickel-titanium systems used for root canal preparation: PTU, PTG, SAF, and XP. In the SAF and XP groups, the canals were first prepared with a K-file until #25 at the working length, and then the SAF or XP files were used. The specimens were scanned using high-resolution micro-computed tomographic imaging before and after root canal preparation. Afterward, preoperative and postoperative cross-sectional images of the teeth were screened to identify the presence of dentinal defects. For each group, the number of microcracks was determined as a percentage rate. The McNemar test was used to determine significant differences before and after instrumentation. The level of significance was set at P ≤ .05. The PTU system significantly increased the percentage rate of microcracks compared with preoperative specimens (P < .05). No new dentinal microcracks were observed in the PTG, SAF, or XP groups. Root canal preparations with the PTG, SAF, and XP systems did not induce the formation of new dentinal microcracks on straight root canals of mandibular premolars. Copyright © 2017 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

The Langer-Giedion syndrome: Molecular dissection of a contiguous gene syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Luedecke, H.J.; Pillo, B.L.; Nardmann, J.

The tricho-rhino-phalangeal syndromes TRPS I and II, which are characterized by craniofacial dysmorphism and skeletal abnormalities, are caused by genetic defects in 8q24.1. The presence of multiple exostoses (EXT) distinguishes TRPS II (Langer-Giedion syndrome, LGS) from TRPS I. Multiple exostoses also occur as an autosomal dominant trait displaying genetic heterogeneity. One of the EXT loci maps to 8q24.1. Previously, we had determined a probe order (cen-D8S50-D8S98-D8S51-D8S67-D8S43-tel) for the Langer-Giedion syndrome chromosome region. The shortest region of deletion overlap in LGS patients is defined by D8S51 and D8S67. Interestingly, a patient with TRPS I and a large deletion was found tomore » be intact for these two loci, but deleted for more proximal loci. We have now constructed a complete yeast artificial chromosome (YAC) contig for the entire LGCR. Some of these YACs were used to perform fluorescence in situ hybridization analyses in patients with chromosomal abnormalities associated with TRPS I, TRPS II and EXT. One YAC containing D8S98 spans the translocation breakpoint in a patient with TRPS I and (8;18)(q24.11;q13.3;q21.13). The translocation breakpoint in a patient with TRPS II and t(4;8)(p15.3;q24.1) is covered by a D8S67 YAC. Interestingly, this YAC also spans the inversion breakpoint in a patient with EXT and inv(8)(p23;q24.1). The data indicate that most of the putative TRPS I gene is located between D8S98 and D8S51, that the putative EXT gene maps to D8S67, and that both genes are 1.5 Mbp apart. We are currently analyzing putative gene sequences in the vicinity of the chromosomal breakpoints.« less

Identification of the gene for Nance-Horan syndrome (NHS).

PubMed

Brooks, S P; Ebenezer, N D; Poopalasundaram, S; Lehmann, O J; Moore, A T; Hardcastle, A J

2004-10-01

The disease intervals for Nance-Horan syndrome (NHS [MIM 302350]) and X linked congenital cataract (CXN) overlap on Xp22. To identify the gene or genes responsible for these diseases. Families with NHS were ascertained. The refined locus for CXN was used to focus the search for candidate genes, which were screened by polymerase chain reaction and direct sequencing of potential exons and intron-exon splice sites. Genomic structures and homologies were determined using bioinformatics. Expression studies were undertaken using specific exonic primers to amplify human fetal cDNA and mouse RNA. A novel gene NHS, with no known function, was identified as causative for NHS. Protein truncating mutations were detected in all three NHS pedigrees, but no mutation was identified in a CXN family, raising the possibility that NHS and CXN may not be allelic. The NHS gene forms a new gene family with a closely related novel gene NHS-Like1 (NHSL1). NHS and NHSL1 lie in paralogous duplicated chromosomal intervals on Xp22 and 6q24, and NHSL1 is more broadly expressed than NHS in human fetal tissues. This study reports the independent identification of the gene causative for Nance-Horan syndrome and extends the number of mutations identified.

Identification of the gene for Nance-Horan syndrome (NHS)

PubMed Central

Brooks, S; Ebenezer, N; Poopalasundaram, S; Lehmann, O; Moore, A; Hardcastle, A

2004-01-01

Background: The disease intervals for Nance-Horan syndrome (NHS [MIM 302350]) and X linked congenital cataract (CXN) overlap on Xp22. Objective: To identify the gene or genes responsible for these diseases. Methods: Families with NHS were ascertained. The refined locus for CXN was used to focus the search for candidate genes, which were screened by polymerase chain reaction and direct sequencing of potential exons and intron-exon splice sites. Genomic structures and homologies were determined using bioinformatics. Expression studies were undertaken using specific exonic primers to amplify human fetal cDNA and mouse RNA. Results: A novel gene NHS, with no known function, was identified as causative for NHS. Protein truncating mutations were detected in all three NHS pedigrees, but no mutation was identified in a CXN family, raising the possibility that NHS and CXN may not be allelic. The NHS gene forms a new gene family with a closely related novel gene NHS-Like1 (NHSL1). NHS and NHSL1 lie in paralogous duplicated chromosomal intervals on Xp22 and 6q24, and NHSL1 is more broadly expressed than NHS in human fetal tissues. Conclusions: This study reports the independent identification of the gene causative for Nance-Horan syndrome and extends the number of mutations identified. PMID:15466011

Are MAO-A deficiency states in the general population and in putative high-risk populations highly uncommon?

PubMed

Murphy, D L; Sims, K; Eisenhofer, G; Greenberg, B D; George, T; Berlin, F; Zametkin, A; Ernst, M; Breakefield, X O

1998-01-01

Lack of monoamine oxidase A (MAO-A) due to either Xp chromosomal deletions or alterations in the coding sequence of the gene for this enzyme are associated with marked changes in monoamine metabolism and appear to be associated with variable cognitive deficits and behavioral changes in humans and in transgenic mice. In mice, some of the most marked behavioral changes are ameliorated by pharmacologically-induced reductions in serotonin synthesis during early development, raising the question of possible therapeutic interventions in humans with MAO deficiency states. At the present time, only one multi-generational family and a few other individuals with marked MAO-A deficiency states have been identified and studied in detail. Although MAO deficiency states associated with Xp chromosomal deletions were identified by distinct symptoms (including blindness in infancy) produced by the contiguous Norrie disease gene, the primarily behavioral phenotype of individuals with the MAO mutation is less obvious. This paper reports a sequential research design and preliminary results from screening several hundred volunteers in the general population and from putative high-risk groups for possible MAO deficiency states. These preliminary results suggest that marked MAO deficiency states are very rare.

A case of metastatic Xp11.2 translocation renal cell carcinoma successfully managed by cytoreductive nephrectomy followed by axitinib therapy.

PubMed

Nishimura, Koichi; Takagi, Toshio; Toda, Naohiro; Yamamoto, Tomoko; Kondo, Tsunenori; Ishida, Hideki; Nagashima, Yoji; Tanabe, Kazunari

2017-03-01

Targeted medications for metastatic adult Xp11.2 translocation renal cell carcinoma (RCC) remain to be identified. We herein report a case of metastatic Xp11.2 translocation RCC controlled with cytoreductive nephrectomy (CN) and axitinib therapy. A 57-year-old woman complained of fatigue and low back pain. Imaging studies revealed a right renal tumor, with multiple lung and mediastinal lymph node metastases. Although the patient received 10 mg axitinib therapy for 5 months at the hospital she was initially admitted to, the size of the primary and metastatic lesions was not reduced. Thus, she was referred to the Tokyo Women's Medical University Hospital (Tokyo, Japan) for further treatment, where she underwent CN. On macroscopic examination, almost the entire kidney was replaced by a yellowish brown tumor >80 mm in diameter. Immunohistochemical examination confirmed the diagnosis of Xp11.2 translocation RCC. One month after surgery, axitinib therapy was resumed and the size of the metastatic lesions gradually decreased. These findings suggest that axitinib therapy is effective for adult Xp11.2 translocation RCC.

A case of metastatic Xp11.2 translocation renal cell carcinoma successfully managed by cytoreductive nephrectomy followed by axitinib therapy

PubMed Central

Nishimura, Koichi; Takagi, Toshio; Toda, Naohiro; Yamamoto, Tomoko; Kondo, Tsunenori; Ishida, Hideki; Nagashima, Yoji; Tanabe, Kazunari

2017-01-01

Targeted medications for metastatic adult Xp11.2 translocation renal cell carcinoma (RCC) remain to be identified. We herein report a case of metastatic Xp11.2 translocation RCC controlled with cytoreductive nephrectomy (CN) and axitinib therapy. A 57-year-old woman complained of fatigue and low back pain. Imaging studies revealed a right renal tumor, with multiple lung and mediastinal lymph node metastases. Although the patient received 10 mg axitinib therapy for 5 months at the hospital she was initially admitted to, the size of the primary and metastatic lesions was not reduced. Thus, she was referred to the Tokyo Women's Medical University Hospital (Tokyo, Japan) for further treatment, where she underwent CN. On macroscopic examination, almost the entire kidney was replaced by a yellowish brown tumor >80 mm in diameter. Immunohistochemical examination confirmed the diagnosis of Xp11.2 translocation RCC. One month after surgery, axitinib therapy was resumed and the size of the metastatic lesions gradually decreased. These findings suggest that axitinib therapy is effective for adult Xp11.2 translocation RCC. PMID:28451413

Spin and Recovery Characteristics of the Curtiss-Wright XP-87 Airplane

NASA Technical Reports Server (NTRS)

Berman, Theodore

1947-01-01

The spin and recovery characteristics of the Curtiss-Wright XP-87 airplane, as well as the spin-recovery parachute requirements, the control forces that would be encountered in the spin, and the best method for the crew to attempt an emergency escape, are presented in this report. The characteristics were estimated rather than determined by model tests because the XP-87 dimensional and mass characteristics were considered to be noncritical and because data were available from model tests of several similar airplanes. The study indicated that the recovery characteristics of the airplane will be satisfactory for all loadings if the controls are reversed fully and rapidly. The control forces, however, will probably be beyond the capabilities of the pilot unless some additional balance or a booster is used. A 6-foot tail parachute or a 3.5-foot wing-tip parachute with a drag coefficient of 0.7 will be a satisfactory, emergency spin-recovery device for spin demonstrations. If it is necessary for the crew to abandon the spinning airplane, they should leave from the outboard side of the cockpit.

Chimeric mitochondrial peptides from contiguous regular and swinger RNA.

PubMed

Seligmann, Hervé

2016-01-01

Previous mass spectrometry analyses described human mitochondrial peptides entirely translated from swinger RNAs, RNAs where polymerization systematically exchanged nucleotides. Exchanges follow one among 23 bijective transformation rules, nine symmetric exchanges (X ↔ Y, e.g. A ↔ C) and fourteen asymmetric exchanges (X → Y → Z → X, e.g. A → C → G → A), multiplying by 24 DNA's protein coding potential. Abrupt switches from regular to swinger polymerization produce chimeric RNAs. Here, human mitochondrial proteomic analyses assuming abrupt switches between regular and swinger transcriptions, detect chimeric peptides, encoded by part regular, part swinger RNA. Contiguous regular- and swinger-encoded residues within single peptides are stronger evidence for translation of swinger RNA than previously detected, entirely swinger-encoded peptides: regular parts are positive controls matched with contiguous swinger parts, increasing confidence in results. Chimeric peptides are 200 × rarer than swinger peptides (3/100,000 versus 6/1000). Among 186 peptides with > 8 residues for each regular and swinger parts, regular parts of eleven chimeric peptides correspond to six among the thirteen recognized, mitochondrial protein-coding genes. Chimeric peptides matching partly regular proteins are rarer and less expressed than chimeric peptides matching non-coding sequences, suggesting targeted degradation of misfolded proteins. Present results strengthen hypotheses that the short mitogenome encodes far more proteins than hitherto assumed. Entirely swinger-encoded proteins could exist.

Effect of p–d hybridization, structural distortion and cation electronegativity on electronic properties of ZnSnX{sub 2} (X=P, As, Sb) chalcopyrite semiconductors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mishra, S.; Ganguli, B., E-mail: biplabg@nitrkl.ac.in

2013-04-15

Significant effects of p–d hybridization, structural distortion and cation-electro-negativity are found on band gap in ZnSnX{sub 2} (X=P, As, Sb). Our study suggests these compounds to be direct band gap semiconductors with band gaps of 1.23, 0.68 and 0.19 eV respectively. Lattice constants, tetragonal distortion (η), anion displacement, bond lengths and bulk moduli are calculated by Density Functional Theory based on Tight binding Linear Muffin-Tin orbital method. Our result of structural properties is in good agreement with the available experimental and other theoretical results. Calculated band gaps also agree well with the experimental works within LDA limitation. Unlike other semiconductorsmore » in the group II–IV–V{sub 2}, there is a reduction in the band gap of 0.22, 0.20 and 0.24 eV respectively in ZnSnX{sub 2} (X=P, As, Sb) due to p–d hybridization. Structural distortion decreases band gap by 0.20, 0.12 and 0.10 eV respectively. We find that cation electronegativity effect is responsible for increasing the band gap relative to their binary analogs GaInP{sub 2}, InGaAs{sub 2} and GaInSb{sub 2} respectively and increment are 0.13, 0.04 and 0.13 eV respectively. - Graphical abstract: One unit cell of ZnSnX{sub 2} (X=P, As, Sb) chalcopyrite semiconductor. Semiconductors ZnSnX{sub 2} (X=P, As, Sb) are found to be direct band gap semiconductors with band gaps 1.23, 0.68 and 0.19 eV respectively. The quantitative estimate of effects of p–d hybridization, structural distortion and cation electronegativity shows band gaps change significantly due to these effects. Highlights: ► ZnSnX{sub 2} (X=P, As, Sb) are direct band gap semiconductors. ► These have band gaps of 1.23 eV, 0.68 eV and 0.19 eV respectively. ► The band gap reduction due to p–d hybridization is 13.41%, 18.51% and 40% respectively. ► Band gap reduction due to structural distortion is 12.12%, 11.11% and 16.66% respectively. ► Band gap increases 8.38%, 3.70% and 21

Xp11.2 translocation tumor: a rare cause of gross hematuria.

PubMed

Asaki, Howard E; Moshero, Gianni; Stanton, Melissa L; Humphreys, Mitchell R

2014-02-01

Xp11.2 translocation tumor is a rare but aggressive form of renal cell carcinoma that predominantly occurs in children but also may be found in young adults. Because this type of cancer is diagnosed via histologic and chromosomal analysis, clinicians should consider translocation tumor in the differential diagnosis of patients with renal lesions and gross hematuria.

46, XX true hermaphroditism associated with a terminal deletion of the short arm of the X chromosome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barbaux, S.; Vilain, E.; McElreavey, K.

1994-09-01

Testes are determined by the activity of the SRY gene product encoded by the Y chromosome. Mutations in SRY can lead to XY sex reversal (XY females) and the presence of the SRY gene in some XX individuals can lead either to complete (XX males) or incomplete (XX true hermaphrodites) sex reversal. Approximately 10% of XX true hermaphrodites contain a portion of the Y chromosome, including SRY, in their genome. The etiology of the remaining cases is unestablished but may be caused by mutations in other as yet unidentied sex determining genes downstream of SRY. Here we describe an SRY-negativemore » true hermaphrodite with a 46,X,del(X)(p21.1-pter). The patient also presented with severe mental retardation, abnormal skin pigmentation and below average height. Histological examination of the gonad revealed bilateral ovotestis. We postulate that the Xp deletion has unmasked a recessive allele on the apparently normal X chromosome generating the intersex phenotype. This observation together with recent findings of certain XY females carrying duplications of Xp21.3 suggests that there may be a loci on Xp which acts as a switch in the testis/ovarian determination pathways.« less

Effect of Pressure on Some Optical Properties of GaxIn1-xP Semiconductors

NASA Astrophysics Data System (ADS)

Vyas, P.; Gajjar, P.; Jani, A.

2013-06-01

A theoretical procedure is presented for the study of optical properties of ternary alloy GaxIn1-xP. The calculations are based on the pseudopotential formalism in which local potential coupled with the virtual crystal approximation (VCA) is applied to evaluate the effect of pressure on the optical properties like refractive index, electronic polarizability, plasmon energy, dielectric constant and equation of state for gallium concentration x = 0, 0.25, 0.50, 0.75 and 1 of the ternary alloy GaxIn1-xP. To incorporate the screening effect, local field correction functions due to Hartree, Taylor, Ichimaru et al. and Nagy are employed. The refractive index, electronic polarizability and dielectric constant computed for the parent binary compounds GaP and InP are found to be satisfactorily agreeing with the experimental report. It is seen that the refractive index of GaxIn1-xP decreases nonlinearly with the increase in pressure. The results obtained using Hartree's screening functions are not very close to the experimental data as it does not include any exchange and correlation effects. Overall good agreement with the experimental and other theoretical findings confirms the application. The author P. S. Vyas is thankful to UGC, New Delhi, India for providing financial support under minor research project No. F.: 47-651/08(WRO).

Tornado climatology of the contiguous United States

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ramsdell, J.V.; Andrews, G.L.

1986-05-01

The characteristics of tornadoes that were reported in the contiguous United States for the period from January 1, 1954, through December 31, 1983, have been computed from data in the National Severe Storms Forecast Center tornado data base. The characteristics summarized in this report include frequency and locations of tornadoes, and their lengths, widths, and areas. Tornado strike and intensity probabilities have been estimated on a regional basis, and these estimates have been used to compute wind speeds with 10/sup -5/, 10/sup -6/, and 10/sup -7/ yr/sup -1/ probabilities of occurrence. The 10/sup -7/ yr/sup -1/ wind speeds range frommore » below 200 mph in the western United States to about 330 mph in the vicinity of Kansas and Nebraska. The appendices contain extensive tabulations of tornado statistics. Variations of the characteristics within the contiguous United States are presented in the summaries. Separate tabulations are provided for the contiguous United States, for each state, for each 5/sup 0/ and 1/sup 0/ latitude and longitude box, and for the eastern and western United States.« less

33 CFR 2.28 - Contiguous zone.

Code of Federal Regulations, 2010 CFR

2010-07-01

... from the territorial sea baseline. (b) For all other purposes, contiguous zone means all waters within... nautical miles from the territorial sea baseline, but in no case extending within the territorial sea of...

LincRNA-p21 activates p21 in cis to promote Polycomb target gene expression and to enforce the G1/S checkpoint

PubMed Central

Dimitrova, Nadya; Zamudio, Jesse R.; Jong, Robyn M.; Soukup, Dylan; Resnick, Rebecca; Sarma, Kavitha; Ward, Amanda J.; Raj, Arjun; Lee, Jeannie; Sharp, Phillip A.; Jacks, Tyler

2014-01-01

SUMMARY The p53-regulated long non-coding RNA lincRNA-p21 has been proposed to act in trans via several mechanisms ranging from repressing genes in the p53 transcriptional network to regulating mRNA translation and protein stability. To further examine lincRNA-p21 function we generated a conditional knockout mouse model. We find that lincRNA-p21 predominantly functions in cis to activate expression of its neighboring gene, p21. Mechanistically, we show that lincRNA-p21 acts in concert with hnRNP-K as a co-activator for p53-dependent p21 transcription. Additional phenotypes of lincRNA-p21 deficiency could be attributed to diminished p21 levels, including deregulated expression and altered chromatin state of some Polycomb target genes, defective G1/S checkpoint, increased proliferation rates, and enhanced reprogramming efficiency. These findings indicate that lincRNA-p21 affects global gene expression and influences the p53 tumor suppressor pathway by acting in cis as a locus-restricted co-activator for p53-mediated p21 expression. PMID:24857549

Semantic Cuing and the Scale Insensitivity of Recency and Contiguity

PubMed Central

Polyn, Sean M.; Erlikhman, Gennady; Kahana, Michael J.

2012-01-01

In recalling a set of previously experienced events, people exhibit striking effects of recency, contiguity, and similarity: Recent items tend to be recalled best and first, and items that were studied in neighboring positions or that are similar to one another in some other way tend to evoke one another during recall. Effects of recency and contiguity have most often been investigated in tasks that require people to recall random word lists. Similarity effects have most often been studied in tasks that require people to recall categorized word lists. Here we examine recency and contiguity effects in lists composed of items drawn from 3 distinct taxonomic categories and in which items from a given category are temporally separated from one another by items from other categories, all of which are tested for recall. We find evidence for long-term recency and for long-range contiguity, bolstering support for temporally sensitive models of memory and highlighting the importance of understanding the interaction between temporal and semantic information during memory search. PMID:21299330

Perivascular epithelioid cell tumor (PEComa) of the urinary bladder associated with Xp11 translocation.

PubMed

Russell, Christopher M; Buethe, David D; Dickinson, Shohreh; Sexton, Wade J

2014-01-01

Perivascular epithelioid cell-containing tumors (PEComas) represent a rare family of neoplasms. Their dichotomous phenotypic features, including both myogenic and mylanocytic features, can make a definitive diagnosis difficult. Such tumors have been associated with the overexpression of transcription factor E3 (TFE3). An Xp11 translocation could account for the aberrant activity of TFE3 but has never before been described in affiliation with a PEComa of the urinary bladder. While PEComas of the bladder have exhibited benign clinical courses to date, here we present an intravesical PEComa shown to have an Xp11 translocation and resultant overexpression of TFE3, indicating an aggressive, metastatic nature. No consistent tumor characteristics have proven accurate at identifying aggressive tumors. However, mTOR inhibitors offer a mechanistic management strategy when systemic therapy is warranted.

Structural and magnetic phase transitions near optimal superconductivity in BaFe 2(As 1-xP x) 2

DOE PAGES

Hu, Ding; Lu, Xingye; Zhang, Wenliang; ...

2015-04-17

In this study, we use nuclear magnetic resonance (NMR), high-resolution x-ray and neutron scattering to study structural and magnetic phase transitions in phosphorus-doped BaFe 2(As 1-xP x) 2. Thus, previous transport, NMR, specific heat, and magnetic penetration depth measurements have provided compelling evidence for the presence of a quantum critical point (QCP) near optimal superconductivity at x = 0.3. However, we show that the tetragonal-to-orthorhombic structural (T s) and paramagnetic to antiferromagnetic (AF, T N) transitions in BaFe 2(As 1-xP x) 2 are always coupled and approach to T N ≈ T s ≥ T c (≈ 29 K) formore » x = 0.29 before vanishing abruptly for x ≥ 0.3. These results suggest that AF order in BaFe 2(As 1-xP x) 2 disappears in a weakly first order fashion near optimal superconductivity, much like the electron-doped iron pnictides with an avoided QCP.« less

Long-term survival in a patient with node-positive adult-onset Xp11.2 translocation renal cell carcinoma.

PubMed

Aoyagi, Toshiki; Shinohara, Nobuo; Kubota-Chikai, Kanako; Kuroda, Naoto; Nonomura, Katsuya

2011-01-01

Adult-onset Xp11.2 translocation renal cell carcinoma is a rare malignancy that has an aggressive clinical course and poor prognosis. The reasons for this include the fact that most patients have an advanced clinical stage at diagnosis and also that there is a lack of effective systemic therapy. We herein present the case of a 32-year-old woman suffering from node-positive Xp11.2 translocation renal cell carcinoma who underwent radical nephrectomy with an extensive retroperitoneal lymph node dissection, followed by two times of surgical resection for recurrent nodal disease. The patient has experienced no recurrent disease 4.5 years after the last operation and remains free of disease. Surgical approach to recurrent disease, if the recurrent site can be judged to be limited, might be one of the feasible treatment options in patients with Xp11.2 translocation renal cell carcinoma. Copyright © 2011 S. Karger AG, Basel.

A mutation in the XPB/ERCC3 DNA repair transcription gene, associated with trichothiodystrophy.

PubMed Central

Weeda, G; Eveno, E; Donker, I; Vermeulen, W; Chevallier-Lagente, O; Taïeb, A; Stary, A; Hoeijmakers, J H; Mezzina, M; Sarasin, A

1997-01-01

Trichothiodystrophy (TTD) is a rare, autosomal recessive disorder characterized by sulfur-deficient brittle hair and nails, mental retardation, impaired sexual development, and ichthyosis. Photosensitivity has been reported in approximately 50% of the cases, but no skin cancer is associated with TTD. Virtually all photosensitive TTD patients have a deficiency in the nucleotide excision repair (NER) of UV-induced DNA damage that is indistinguishable from that of xeroderma pigmentosum (XP) complementation group D (XP-D) patients. DNA repair defects in XP-D are associated with two additional, quite different diseases; XP, a sun-sensitive and cancer-prone repair disorder, and Cockayne syndrome (CS), a photosensitive condition characterized by physical and mental retardation and wizened facial appearance. One photosensitive TTD case constitutes a new repair-deficient complementation group, TTD-A. Remarkably, both TTD-A and XP-D defects are associated with subunits of TFIIH, a basal transcription factor with a second function in DNA repair. Thus, mutations in TFIIH components may, on top of a repair defect, also cause transcriptional insufficiency, which may explain part of the non-XP clinical features of TTD. Besides XPD and TTDA, the XPB gene product is also part of TFIIH. To date, three patients with the remarkable conjunction of XP and CS but not TTD have been assigned to XP complementation group B (XP-B). Here we present the characterization of the NER defect in two mild TTD patients (TTD6VI and TTD4VI) and confirm the assignment to X-PB. The causative mutation was found to be a single base substitution resulting in a missense mutation (T119P) in a region of the XPB protein completely conserved in yeast, Drosophila, mouse, and man. These findings define a third TTD complementation group, extend the clinical heterogeneity associated with XP-B, stress the exclusive relationship between TTD and mutations in subunits of repair/transcription factor TFIIH, and strongly

Molecular cytogenetic analysis for TFE3 rearrangement in Xp11.2 renal cell carcinoma and alveolar soft part sarcoma: validation and clinical experience with 75 cases.

PubMed

Hodge, Jennelle C; Pearce, Kathryn E; Wang, Xiaoke; Wiktor, Anne E; Oliveira, Andre M; Greipp, Patricia T

2014-01-01

Renal cell carcinoma with TFE3 rearrangement at Xp11.2 is a distinct subtype manifesting an indolent clinical course in children, with recent reports suggesting a more aggressive entity in adults. This subtype is morphologically heterogeneous and can be misclassified as clear cell or papillary renal cell carcinoma. TFE3 is also rearranged in alveolar soft part sarcoma. To aid in diagnosis, a break-apart strategy fluorescence in situ hybridization (FISH) probe set specific for TFE3 rearrangement and a reflex dual-color, single-fusion strategy probe set involving the most common TFE3 partner gene, ASPSCR1, were validated on formalin-fixed, paraffin-embedded tissues from nine alveolar soft part sarcoma, two suspected Xp11.2 renal cell carcinoma, and nine tumors in the differential diagnosis. The impact of tissue cut artifact was reduced through inclusion of a chromosome X centromere control probe. Analysis of the UOK-109 renal carcinoma cell line confirmed the break-apart TFE3 probe set can distinguish the subtle TFE3/NONO fusion-associated inversion of chromosome X. Subsequent extensive clinical experience was gained through analysis of 75 cases with an indication of Xp11.2 renal cell carcinoma (n=54), alveolar soft part sarcoma (n=13), perivascular epithelioid cell neoplasms (n=2), chordoma (n=1), or unspecified (n=5). We observed balanced and unbalanced chromosome X;17 translocations in both Xp11.2 renal cell carcinoma and alveolar soft part sarcoma, supporting a preference but not a necessity for the translocation to be balanced in the carcinoma and unbalanced in the sarcoma. We further demonstrate the unbalanced separation is atypical, with TFE3/ASPSCR1 fusion and loss of the derivative X chromosome but also an unanticipated normal X chromosome gain in both males and females. Other diverse sex chromosome copy number combinations were observed. Our TFE3 FISH assay is a useful adjunct to morphologic analysis of such challenging cases and will be applicable to

The isolation of cDNAs from OATL1 at Xp11.2 using a 480-kb YAC

DOE Office of Scientific and Technical Information (OSTI.GOV)

Geraghty, M.T.; Brody, L.C.; Martin, L.S.

1993-05-01

Using an ornithine-{delta}-aminotransferase (OAT) cDNA, the authors identified five YACs that cover two nonadjacent OAT-related loci in Xp11.2-p11.3, designated OATL1 (distal) and OATL2 (proximal). Because several retinal degenerative disorders map to this region, they used YAC2 (480 kb), which covers the most distal part of OATL1, as a probe to screen a retinal cDNA library. From 8 {times} 10{sup 4} plaques screened, they isolated 13 clones. Two were OAT cDNAs. The remaining 11 were divided into eight groups by cross-hybridization. Groups 1-4 contain cDNAs that originate from single-copy X-linked genes in YAC2. Each has an open reading frame of >500more » bp and detects one or more transcripts on a Northern blot. The gene for each was sublocalized and ordered in YAC2. The cDNAs in groups 5-8 contained two or more Alu sequences, had no open reading frames, and did not detect transcripts. The cDNAs from groups 1-4 provide expressed sequence tags and identify candidate genes for the genetic disorders that map to this region. 28 refs., 5 figs., 1 tab.« less

[Reconstruction of Leptospira interrogans lipL21 gene and characteristics of its expression product].

PubMed

Luo, Dong-jiao; Hu, Ye; Dennin, R H; Yan, Jie

2007-09-01

To reconstruct the nucleotide sequence of Leptospira interrogans lipL21 gene for increasing the output of prokaryotic expression and to understand the changes on immunogenicity of the expression products before and after reconstruction, and to determine the position of envelope lipoprotein LipL21 on the surface of leptospiral body. According to the preferred codons of E.coli, the nucleotide sequence of lipL21 gene was designed and synthesized, and then its prokaryotic expression system was constructed. By using SDS-PAGE plus BioRad agarose image analysor, the expression level changes of lipL21 genes before and after reconstruction were measured. A Western blot assay using rabbit anti-TR/Patoc I serum as the first antibody was performed to identify the immunoreactivity of the two target recombinant proteins rLipL21s before and after reconstruction. The changes of cross agglutination titers of antisera against two rLipL21s before and after reconstruction to the different leptospiral serogroups were demonstrated using microscope agglutination test (MAT). Immuno-electronmicroscopy was applied to confirm the location of LipL21s. The expression outputs of original and reconstructed lipL21 genes were 8.5 % and 46.5 % of the total bacterial proteins, respectively. Both the two rLipL21s could take place immune conjugation reaction with TR/Patoc I antiserum. After immunization with each of the two rLipL21s in rabbits, the animals could produce specific antibody. Similar MAT titers with 1:80 - 1:320 of the two antisera against rLipL21s were present. LipL21 was confirmed to locate on the surface of leptospiral envelope. LipL21 is a superficial antigen of Leptospira interrogans. The expression output of the reconstructed lipL21 gene is remarkably increased. The expression rLipL21 maintains fine antigenicity and immunoreactivity and its antibody still shows an extensive cross immunoagglutination activity. The high expression of the reconstructed lipL21 gene will offer a

21 CFR 862.1163 - Cardiac allograft gene expression profiling test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Cardiac allograft gene expression profiling test... Chemistry Test Systems § 862.1163 Cardiac allograft gene expression profiling test system. (a) Identification. A cardiac allograft gene expression profiling test system is a device that measures the...

Report: Passaic Valley Sewerage Commissioners – Unallowable Costs Claimed Under EPA Grant XP98237601

EPA Pesticide Factsheets

Report #08-2-0226, August 6, 2008. The grantee claimed $2,385,634 for pre-award costs under Grant XP98237601 that were incurred prior to the grant award and thus were unallowable under the grant administrative conditions and OMB Circular A-87.

Towards isolation of the gene for X-linked retinitis pigmentosa (RP3)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dry, K.L.; Aldred, M.A.; Hardwick, L.J.

1994-09-01

Until recently the region of interest containing the gene for X-linked retinitis pigmentosa (RP3) was thought to lie between CYBB (Xp21.1) and the proximal end of the deletion in patient BB (JBBprox). This region was thought to span 100-150 kb. Here we present new mapping data to show that the distance between the 5{prime} (most proximal) end of CYBB and JBBprox is only 50 kb. Recently Roux et al. (1994) have described the isolation of a gene within this region but this showed no disease-associated changes. Further evidence from mapping the deletion in patient NF (who suffered from McLead`s syndromemore » and CGD but not RP) and from linkage analysis of our RP3 families with a new dinucleotide repeat suggests that the gene must extend proximally from JBBprox. In order to extend the region of search we have constructed a YAC contig spanning 800 kb to OTC. We are continuing our search for the RP3 gene using a variety of strategies including exon trapping and cDNA enrichment as well as direct screening of cDNA libraries with subclones from this region.« less

Interspecies synteny mapping identifies a quantitative trait locus for bone mineral density on human chromosome Xp22.

PubMed

Parsons, Claire A; Mroczkowski, H Joel; McGuigan, Fiona E A; Albagha, Omar M E; Manolagas, Stavros; Reid, David M; Ralston, Stuart H; Shmookler Reis, Robert J

2005-11-01

Bone mineral density (BMD) is a complex trait with a strong genetic component and an important predictor of osteoporotic fracture risk. Here we report the use of a cross-species strategy to identify genes that regulate BMD, proceeding from quantitative trait mapping in mice to association mapping of the syntenic region in the human genome. We identified a quantitative trait locus (QTL) on the mouse X-chromosome for post-maturity change in spine BMD in a cross of SAMP6 and AKR/J mice and conducted association mapping of the syntenic region on human chromosome Xp22. We studied 76 single nucleotide polymorphisms (SNP) from the human region in two sets of DNA pools prepared from individuals with lumbar spine-BMD (LS-BMD) values falling into the top and bottom 13th percentiles of a population-based study of 3100 post-menopausal women. This procedure identified a region of significant association for two adjacent SNP (rs234494 and rs234495) within the Xp22 locus (P<0.001). Individual genotyping for rs234494 in the BMD pools confirmed the presence of an association for alleles (P=0.018) and genotypes (P=0.008). Analysis of rs234494 and rs234495 in 1053 women derived from the same population who were not selected for BMD values showed an association with LS-BMD for rs234495 (P=0.01) and for haplotypes defined by both SNP (P=0.002). Our study illustrates that interspecies synteny can be used to identify and refine QTL for complex traits and represents the first example where a human QTL for BMD regulation has been mapped using this approach.

Autism in Two Females with Duplications Involving Xp11.22-p11.23

ERIC Educational Resources Information Center

Edens, Anna C.; Lyons, Michael J.; Duron, Reyna M.; DuPont, Barbara R.; Holden, Kenton R.

2011-01-01

We present two phenotypically similar females with Xp duplication who have autism and epilepsy. Case 1 is a 14-year-old Honduran female with autism and medically refractory complex partial, secondarily generalized epilepsy. Case 2 is a 3-year-old Austrian female with autism and medically refractory complex partial epilepsy. Both patients also…

Cytologic Features of Renal Carcinoma Associated with Xp11.2 Translocations/ TFE3 Gene Fusions: A Case Report with Voided and Catheterized Urine Cytology and a Literature Review.

PubMed

Kuwamoto, Satoshi; Murai, Yuki; Endo, Yukari; Masago, Toshihiko; Kuroda, Naoto; Horie, Yasushi

2014-01-01

Renal carcinomas associated with Xp11.2 translocations/TFE3 gene fusions are rare subtypes of renal neoplasm that predominantly occur in younger individuals. There are very few reports describing the cytologic features of these tumors. A 27-year-old man presented with hematuria and was found to have a mass in the lower part of the right kidney. Cytology of catheterized urine obtained from the right renal pelvis showed clusters of cells with abundant clear or eosinophilic granular cytoplasm, large round nuclei and prominent nucleoli. Papillary clusters containing thin fibrous stroma were occasionally seen. Voided urine cytology showed similar cell clusters but degeneration made the features obscure. Nephroureterectomy revealed a renal tumor showing a mixed papillary and nested architecture. The diagnosis was confirmed by immunohistochemistry and fluorescence in situ hybridization. The present case indicates that the characteristic features of these tumor subtypes can be retained in urine cytology. Cytology may be enough to suspect these tumors as part of the differential diagnosis when the patient's age and imaging findings are taken into account and may facilitate further studies for a definitive diagnosis. © 2014 S. Karger AG, Basel.

Integrated Analysis of Genome-wide Copy Number Alterations and Gene Expression in MSS, CIMP-negative Colon Cancer

PubMed Central

Loo, Lenora WM; Tiirikainen, Maarit; Cheng, Iona; Lum-Jones, Annette; Seifried, Ann; Church, James M; Gryfe, Robert; Weisenberger, Daniel J; Lindor, Noralane M; Gallinger, Steven; Haile, Robert W; Duggan, David J; Thibodeau, Stephen N; Casey, Graham; Le Marchand, Loïc

2014-01-01

Microsatellite stable (MSS), CpG island methylator phenotype (CIMP)-negative colorectal tumors, the most prevalent molecular subtype of colorectal cancer, are associated with extensive copy number alteration (CNA) events and aneuploidy. We report on the identification of characteristic recurrent CNA (with frequency >25%) events and associated gene expression profiles for a total of 40 paired tumor and adjacent normal colon tissues using genome-wide microarrays. We observed recurrent CNAs, namely gains at 1q, 7p, 7q, 8p12-11, 8q, 12p13, 13q, 20p, 20q, Xp, and Xq and losses at 1p36, 1p31, 1p21, 4p15-12, 4q12-35, 5q21-22, 6q26, 8p, 14q, 15q11-12, 17p, 18p, 18q, 21q21-22, and 22q. Within these genomic regions we identified 356 genes with significant differential expression (P<0.0001 and ±1.5 fold change) in the tumor compared to adjacent normal tissue. Gene ontology and pathway analyses indicated that many of these genes were involved in functional mechanisms that regulate cell cycle, cell death, and metabolism. An amplicon present in >70% of the tumor samples at 20q11-20q13 contained several cancer-related genes (AHCY, POFUT1, RPN2, TH1L and PRPF6) that were up-regulated and demonstrated a significant linear correlation (P<0.05) for gene dosage and gene expression. Copy number loss at 8p, a CNA associated with adenocarcinoma and poor prognosis, was observed in >50% of the tumor samples and demonstrated a significant linear correlation for gene dosage and gene expression for two potential tumor suppressor genes, MTUS1 (8p22) and PPP2CB (8p12). The results from our integration analysis illustrate the complex relationship between genomic alterations and gene expression in colon cancer. PMID:23341073

Chromosomal arrangement of leghemoglobin genes in soybean.

PubMed Central

Lee, J S; Brown, G G; Verma, D P

1983-01-01

A cluster of four different leghemoglobin (Lb) genes was isolated from AluI-HaeIII and EcoRI genomic libraries of soybean in a set of overlapping clones which together include 45 kilobases (kb) of contiguous DNA. These four genes, including a pseudogene, are present in the same orientation and are arranged in the order: 5'-Lba-Lbc1-Lb psi-Lbc3-3'. The intergenic regions average 2.5 kb. In addition to this main Lb locus, there are other Lb genes which do not appear to be contiguous to this locus. A sequence probably common to the 3' region of Lb loci was found flanking the Lbc3 gene. The 3' flanking region of the main Lb locus also contains a sequence that appears to be expressed more abundantly in root tissue. Another sequence which is primarily expressed in root and leaf is found 5' to two Lb loci. Overall, the main leghemoglobin locus is similar in structure to the mammalian globin gene loci. Images PMID:6310504

40 CFR 408.130 - Applicability; description of the breaded shrimp processing in the contiguous States subcategory.

Code of Federal Regulations, 2010 CFR

2010-07-01

... breaded shrimp processing in the contiguous States subcategory. 408.130 Section 408.130 Protection of... SEAFOOD PROCESSING POINT SOURCE CATEGORY Breaded Shrimp Processing in the Contiguous States Subcategory § 408.130 Applicability; description of the breaded shrimp processing in the contiguous States...

40 CFR 408.130 - Applicability; description of the breaded shrimp processing in the contiguous States subcategory.

Code of Federal Regulations, 2011 CFR

2011-07-01

... breaded shrimp processing in the contiguous States subcategory. 408.130 Section 408.130 Protection of... SEAFOOD PROCESSING POINT SOURCE CATEGORY Breaded Shrimp Processing in the Contiguous States Subcategory § 408.130 Applicability; description of the breaded shrimp processing in the contiguous States...

40 CFR 408.110 - Applicability; description of the Northern shrimp processing in the contiguous States subcategory.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Northern shrimp processing in the contiguous States subcategory. 408.110 Section 408.110 Protection of... SEAFOOD PROCESSING POINT SOURCE CATEGORY Northern Shrimp Processing in the Contiguous States Subcategory § 408.110 Applicability; description of the Northern shrimp processing in the contiguous States...

40 CFR 408.110 - Applicability; description of the Northern shrimp processing in the contiguous States subcategory.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Northern shrimp processing in the contiguous States subcategory. 408.110 Section 408.110 Protection of... SEAFOOD PROCESSING POINT SOURCE CATEGORY Northern Shrimp Processing in the Contiguous States Subcategory § 408.110 Applicability; description of the Northern shrimp processing in the contiguous States...

A case report: Becker muscular dystrophy presenting with epilepsy and dysgnosia induced by duplication mutation of Dystrophin gene.

PubMed

Miao, Jing; Feng, Jia-Chun; Zhu, Dan; Yu, Xue-Fan

2016-12-12

Becker muscular dystrophy (BMD), a genetic disorder of X-linked recessive inheritance, typically presents with gradually progressive muscle weakness. The condition is caused by mutations of Dystrophin gene located at Xp21.2. Epilepsy is an infrequent manifestation of BMD, while cases of BMD with dysgnosia are extremely rare. We describe a 9-year-old boy with BMD, who presented with epilepsy and dysgnosia. Serum creatine kinase level was markedly elevated (3665 U/L). Wechsler intelligence tests showed a low intelligence quotient (IQ = 65). Electromyogram showed slight myogenic changes and skeletal muscle biopsy revealed muscular dystrophy. Immunohistochemical staining showed partial positivity of sarcolemma for dystrophin-N. Multiplex ligation-dependent probe amplification revealed a duplication mutation in exons 37-44 in the Dystrophin gene. The present case report helps to better understand the clinical and genetic features of BMD.

UniGene Tabulator: a full parser for the UniGene format.

PubMed

Lenzi, Luca; Frabetti, Flavia; Facchin, Federica; Casadei, Raffaella; Vitale, Lorenza; Canaider, Silvia; Carinci, Paolo; Zannotti, Maria; Strippoli, Pierluigi

2006-10-15

UniGene Tabulator 1.0 provides a solution for full parsing of UniGene flat file format; it implements a structured graphical representation of each data field present in UniGene following import into a common database managing system usable in a personal computer. This database includes related tables for sequence, protein similarity, sequence-tagged site (STS) and transcript map interval (TXMAP) data, plus a summary table where each record represents a UniGene cluster. UniGene Tabulator enables full local management of UniGene data, allowing parsing, querying, indexing, retrieving, exporting and analysis of UniGene data in a relational database form, usable on Macintosh (OS X 10.3.9 or later) and Windows (2000, with service pack 4, XP, with service pack 2 or later) operating systems-based computers. The current release, including both the FileMaker runtime applications, is freely available at http://apollo11.isto.unibo.it/software/

Unassisted Water Splitting Using a GaSb xP (1- x ) Photoanode

DOE PAGES

Martinez-Garcia, Alejandro; Russell, Harry B.; Paxton, William; ...

2018-02-21

Here in this work, unbiased water splitting with 2% solar-to-hydrogen efficiency under AM 1.5 G illumination using new materials based on GaSb 0.03P 0.97 alloy is reported. Freestanding GaSb xP 1-x is grown using halide vapor phase epitaxy. The native conductivity type of the alloy is modified by silicon doping, resulting in an open-circuit potential (OCP) of 750 mV, photocurrents of 7 mA cm -2 at 10 sun illumination, and corrosion resistance in an aqueous acidic environment. Alloying GaP with Sb at 3 at% improves the absorption of high-energy photons above 2.68 eV compared to pure GaP material. Electrochemical Impedancemore » Spectroscopy and illuminated OCP measurements show that the conduction band of GaSb xP 1-x is at -0.55 V versus RHE irrespective of the Sb concentration, while photocurrent spectroscopy indicates that only radiation with photon energies greater than 2.68 eV generate mobile and extractable charges, thus suggesting that the higher-laying conduction bands in the Γ 1 valley of the alloys are responsible for exciton generation.« less

Unassisted Water Splitting Using a GaSb xP (1- x ) Photoanode

DOE Office of Scientific and Technical Information (OSTI.GOV)

Martinez-Garcia, Alejandro; Russell, Harry B.; Paxton, William

Here in this work, unbiased water splitting with 2% solar-to-hydrogen efficiency under AM 1.5 G illumination using new materials based on GaSb 0.03P 0.97 alloy is reported. Freestanding GaSb xP 1-x is grown using halide vapor phase epitaxy. The native conductivity type of the alloy is modified by silicon doping, resulting in an open-circuit potential (OCP) of 750 mV, photocurrents of 7 mA cm -2 at 10 sun illumination, and corrosion resistance in an aqueous acidic environment. Alloying GaP with Sb at 3 at% improves the absorption of high-energy photons above 2.68 eV compared to pure GaP material. Electrochemical Impedancemore » Spectroscopy and illuminated OCP measurements show that the conduction band of GaSb xP 1-x is at -0.55 V versus RHE irrespective of the Sb concentration, while photocurrent spectroscopy indicates that only radiation with photon energies greater than 2.68 eV generate mobile and extractable charges, thus suggesting that the higher-laying conduction bands in the Γ 1 valley of the alloys are responsible for exciton generation.« less

Molecular genetics of X-linked retinitis pigmentosa: Progress towards cloning the RP3 gene

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fujita, R.; Yan, D.; McHenry, C.

1994-09-01

Our goal is to identify the X-linked retinitis pigmentosa (XLRP) gene RP3. The location of RP3 is genetically delimited to a region of 1 Mb, distal to DXS140, CYBB and tctex-1-like gene and proximal to the gene OTC. It is currently thought that RP3 is within 40 kb of the proximal deletion breakpoint of a patient BB. However, a more proximal location of the gene, closer to OTC, is not ruled out. We initiated the isolation of the genomic region between DXS140 to OTC in YACs. One of the clones from DXS140 region (55B) is 460 kb and spans aboutmore » 200 kb at each side of BB patient`s proximal breakpoint. It contains CYBB, tctex-1-like genes and two additional CpG islands. The 55B clone has been covered by cosmid and phage subclones. Another YAC clone from the OTC region (OTCC) spans about 1 Mb and contains at least 5 CpG islands. In situ hybridization performed with OTCC showed its location in Xp21; however, several derivative cosmids map to chromosome 7, indicating that it is a chimeric YAC. No overlap is evident between 55B and OTCC. We have isolated the YAC end-sequences and isolation of clones to close the gap is in progress. Cosmids are being used for screening eye tissue cDNA libraries, mainly from retina. Screening is done by hybridization to replica filters or by cDNA enrichment methods. Several cDNA clones have been isolated and are being characterized. Exon-amplification is also being used with the cosmids and phages. Genetic analysis is being performed to determine RP3 patients from clinically indistinguishable RP2, located in Xp11.23-p11.4, and to reduce the genetic distance of current flanking markers. For this we are analyzing a number of XLRP families with established markers in the region and with new microsatellites.« less

Comparative Sequence and X-Inactivation Analyses of a Domain of Escape in Human Xp11.2 and the Conserved Segment in Mouse

PubMed Central

Tsuchiya, Karen D.; Greally, John M.; Yi, Yajun; Noel, Kevin P.; Truong, Jean-Pierre; Disteche, Christine M.

2004-01-01

We have performed X-inactivation and sequence analyses on 350 kb of sequence from human Xp11.2, a region shown previously to contain a cluster of genes that escape X inactivation, and we compared this region with the region of conserved synteny in mouse. We identified several new transcripts from this region in human and in mouse, which defined the full extent of the domain escaping X inactivation in both species. In human, escape from X inactivation involves an uninterrupted 235-kb domain of multiple genes. Despite highly conserved gene content and order between the two species, Smcx is the only mouse gene from the conserved segment that escapes inactivation. As repetitive sequences are believed to facilitate spreading of X inactivation along the chromosome, we compared the repetitive sequence composition of this region between the two species. We found that long terminal repeats (LTRs) were decreased in the human domain of escape, but not in the majority of the conserved mouse region adjacent to Smcx in which genes were subject to X inactivation, suggesting that these repeats might be excluded from escape domains to prevent spreading of silencing. Our findings indicate that genomic context, as well as gene-specific regulatory elements, interact to determine expression of a gene from the inactive X-chromosome. PMID:15197169

A new CYP21A1P/CYP21A2 chimeric gene identified in an Italian woman suffering from classical congenital adrenal hyperplasia form

PubMed Central

Concolino, Paola; Mello, Enrica; Minucci, Angelo; Giardina, Emiliano; Zuppi, Cecilia; Toscano, Vincenzo; Capoluongo, Ettore

2009-01-01

Background More than 90% of Congenital Adrenal Hyperplasia (CAH) cases are associated with mutations in the 21-hydroxylase gene (CYP21A2) in the HLA class III area on the short arm of chromosome 6p21.3. In this region, a 30 kb deletion produces a non functional chimeric gene with its 5' and 3' ends corresponding to CYP21A1P pseudogene and CYP21A2, respectively. To date, five different CYP21A1P/CYP21A2 chimeric genes have been found and characterized in recent studies. In this paper, we describe a new CYP21A1P/CYP21A2 chimera (CH-6) found in an Italian CAH patient. Methods Southern blot analysis and CYP21A2 sequencing were performed on the patient. In addition, in order to isolate the new CH-6 chimeric gene, two different strategies were used. Results The CYP21A2 sequencing analysis showed that the patient was homozygote for the g.655C/A>G mutation and heterozygote for the p.P30L missense mutation. In addition, the promoter sequence revealed the presence, in heterozygosis, of 13 SNPs generally produced by microconversion events between gene and pseudogene. Southern blot analysis showed that the woman was heterozygote for the classic 30-kb deletion producing a new CYP21A1P/CYP21A2 chimeric gene (CH-6). The hybrid junction site was located between the end of intron 2 pseudogene, after the g.656C/A>G mutation, and the beginning of exon 3, before the 8 bp deletion. Consequently, CH-6 carries three mutations: the weak pseudogene promoter region, the p.P30L and the g.655C/A>G splice mutation. Conclusion We describe a new CYP21A1P/CYP21A2 chimera (CH-6), associated with the HLA-B15, DR13 haplotype, in a young Italian CAH patient. PMID:19624807

Symmetry-Breaking Transitions in RECuAs 2-xP x (RE=Sm, Gd, Ho, and Er)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mozharivskyj, Yurij

Structural changes resulting in lower symmetries can be understood in terms of electronic instabilities and Coulomb interactions. The interplay of these two interrelated factors is complicated and difficult to analyze. The RECuAs 2-xP x phases, because of the variation in the chemical content (As/P substitution), allow, with the aid of band structures, Madelung energies and Landau theory, a partial unraveling of the forces important in the symmetry-breaking transitions in RECuAs 2-xP x (RE = Sm, Gd, Ho and Er). Distortions of the P layers in SmCu 1.15P 2, GdCuP 2.20 and ErCuP 2 are usefully thought of asmore » generalized Peierls distortions, i.e., they lower the electronic (and total) energy and lead to more stable structures. On the other hand, the P4/nmm → Pmmn transitions, which are observed in all studied arsenophosphide series and occur upon substitution of P for As, originate from the B1g vibrational mode and are structural adaptations to smaller P atoms. These transitions provide tighter atomic packing and better Coulomb interactions. Configurational contribution to the entropy becomes important in stabilizing the mixed occupancy in the RECuAs 2-xP x arsenophosphides. While geometric and electronic factors favor separation of the As and P atoms over two different crystallographic sites, configurational entropy stabilizes the As/P mixing on these two sites.;Progress in the research on RECuAs 2-xP x was dependent upon the ability of Landau theory to predict, explain and dismiss structural models and transitions. The space group Pmmn (arising from the B 1g vibrational mode) in all mixed arsenophosphides and the existence of these mixed arsenophosphides followed from the analysis of GdCuAs 2 and GdCuP 2, using Landau theory. The impossibility of obtaining the high-symmetry structure (P4/nmm) and the low symmetry structure (Pnmm) at the same temperature for the displacive continuous symmetry-breaking transition P4/ nmm → Pmmn led to the conclusion, later

Contribution of the TTC21B gene to glomerular and cystic kidney diseases.

PubMed

Bullich, Gemma; Vargas, Iván; Trujillano, Daniel; Mendizábal, Santiago; Piñero-Fernández, Juan Alberto; Fraga, Gloria; García-Solano, José; Ballarín, José; Estivill, Xavier; Torra, Roser; Ars, Elisabet

2017-01-01

The TTC21B gene was initially described as causative of nephronophthisis (NPHP). Recently, the homozygous TTC21B p.P209L mutation has been identified in families with focal segmental glomerulosclerosis (FSGS) and tubulointerstitial lesions. Heterozygous TTC21B variants have been proposed as genetic modifiers in ciliopathies. We aimed to study the causative and modifying role of the TTC21B gene in glomerular and cystic kidney diseases. Mutation analysis of the TTC21B gene was performed by massive parallel sequencing. We studied the causative role of the TTC21B gene in 17 patients with primary diagnosis of FSGS or NPHP and its modifying role in 184 patients with inherited glomerular or cystic kidney diseases. Disease-causing TTC21B mutations were identified in three families presenting nephrotic proteinuria with FSGS and tubulointerstitial lesions in which some family members presented hypertension and myopia. Two families carried the homozygous p.P209L and the third was compound heterozygous for the p.P209L and a novel p.H426D mutation. Rare heterozygous TTC21B variants predicted to be pathogenic were found in five patients. These TTC21B variants were significantly more frequent in renal patients compared with controls (P = 0.0349). Two patients with a heterozygous deleterious TTC21B variant in addition to the disease-causing mutation presented a more severe phenotype than expected. Our results confirm the causal role of the homozygous p.P209L TTC21B mutation in two new families with FSGS and tubulointerstitial disease. We identified a novel TTC21B mutation demonstrating that p.P209L is not the unique causative mutation of this nephropathy. Thus, TTC21B mutation analysis should be considered for the genetic diagnosis of families with FSGS and tubulointerstitial lesions. Finally, we provide evidence that heterozygous deleterious TTC21B variants may act as genetic modifiers of the severity of glomerular and cystic kidney diseases. © The Author 2016. Published by

DOE Office of Scientific and Technical Information (OSTI.GOV)

Milatovich, A.; Becker, T.; Kaufman, A.

There have been 15 reports in the literature of patients with microphthalmia and linear skin defects (MLS) who have deletions of the distal region of the short arm of the X chromosome, Xp22.3-pter. Since there appears to be some overlap of features between MLS, Goltz and Aicardi syndromes, it has been suggested that these syndromes represent a contiguous gene syndrome. At least three individuals have been reported with t(X;Y) and some common clinical features. We have seen a female infant with several anterior chamber anomalies including microcornea and sclerocornea, who also has an unbalanced translocation between the X and Ymore » chromosomes, 46,X,der(X)t(X;Y) (p22.3;q11.2). Q-banding and fluorescence in situ hybridization (FISH) with a Y chromosome cocktail (Oncor) confirmed the identity of this derivative chromosome. X-inactivation studies done by RBG-banding showed that the der(X) is preferentially inactivated in all 50 metaphase cells examined from PHA-stimulated lymphocytes. It is likely some gene(s) on the distal Xp do not escape inactivation and when deleted result in anterior chamber abnormalities. X-inactivation patterns may be different in different tissues or at different times during development. Molecular studies will be helpful in determining what gene(s) are actually deleted in this case. This case is important because the clinical findings are limited to the development of the eyes and may help to define the critical regions and/or minimum region of overlap among MLS, Goltz and Aicardi syndromes.« less

Location of Dual Sites in E. coli FtsZ Important for Degradation by ClpXP; One at the C-Terminus and One in the Disordered Linker

PubMed Central

Camberg, Jodi L.; Viola, Marissa G.; Rea, Leslie; Hoskins, Joel R.; Wickner, Sue

2014-01-01

ClpXP is a two-component ATP-dependent protease that unfolds and degrades proteins bearing specific recognition signals. One substrate degraded by Escherichia coli ClpXP is FtsZ, an essential cell division protein. FtsZ forms polymers that assemble into a large ring-like structure, termed the Z-ring, during cell division at the site of constriction. The FtsZ monomer is composed of an N-terminal polymerization domain, an unstructured linker region and a C-terminal conserved region. To better understand substrate selection by ClpXP, we engineered FtsZ mutant proteins containing amino acid substitutions or deletions near the FtsZ C-terminus. We identified two discrete regions of FtsZ important for degradation of both FtsZ monomers and polymers by ClpXP in vitro. One region is located 30 residues away from the C-terminus in the unstructured linker region that connects the polymerization domain to the C-terminal region. The other region is near the FtsZ C-terminus and partially overlaps the recognition sites for several other FtsZ-interacting proteins, including MinC, ZipA and FtsA. Mutation of either region caused the protein to be more stable and mutation of both caused an additive effect, suggesting that both regions are important. We also observed that in vitro MinC inhibits degradation of FtsZ by ClpXP, suggesting that some of the same residues in the C-terminal site that are important for degradation by ClpXP are important for binding MinC. PMID:24722340

Evidence for the evolutionary origin of human chromosome 21 from comparative gene mapping in the cow and mouse

DOE Office of Scientific and Technical Information (OSTI.GOV)

Threadgill, D.S.; Womack, J.E.; Kraus, J.P.

1991-01-01

To determine the extent of conservation between bovine syntenic group U10, human chromosome 21 (HSA 21), and mouse chromosome 16(MMU 16), 11 genes were physically mapped by segregation analysis in a bovine-hamster hybrid somatic cell panel. The genes chosen for study span MMU 16 and represent virtually the entire q arm of HSA 21. Because the somatostatin gene (SST), an HSA 3/MMU 16 locus, was previously shown to be in U10, the transferrin gene (TF), an HSA 3/MMU 9 marker, was also mapped to determine whether U10 contains any HSA 3 genes not represented on MMU 16. With the exceptionmore » of the protamine gene PRM1 (HSA 16/MMU 16), all of the genes studies were syntenic on bovine U10. Thus, all homologous loci from HSA 21 that have been studied in the cow are on a single chromosome. The bovine homolog of HSA 21 also carries several HSA 3 genes, two of which have homologous loci on MMU 16. The syntenic association of genes from the q arm of HSA 3 with HSAS 21 genes in two mammalian species, the mouse and the cow, indicates that HSA 21 may have evolved from a larger ancestral mammalian chromosome that contained genes now residing on HSA 3. Additionally, the syntenic association of TF with SST in the cow permits the prediction that the rhodopsin gene (RHO) is proximal to TF on HSA 3q.« less

Cost-effectiveness of the 21-gene assay for guiding adjuvant chemotherapy decisions in early breast cancer.

PubMed

Paulden, Mike; Franek, Jacob; Pham, Ba'; Bedard, Philippe L; Trudeau, Maureen; Krahn, Murray

2013-01-01

Adjuvant chemotherapy decisions in early breast cancer are complex. The 21-gene assay can potentially aid such decisions, but costs US $4175 per patient. Adjuvant! Online is a freely available decision aid. We evaluate the cost-effectiveness of using the 21-gene assay in conjunction with Adjuvant! Online, and of providing adjuvant chemotherapy conditional upon risk classification. A probabilistic Markov decision model simulated risk classification, treatment, and the natural history of breast cancer in a hypothetical cohort of 50-year-old women with lymph node-negative, estrogen receptor- and/or progesterone receptor-positive, human epidermal growth factor receptor 2/neu-negative early breast cancer. Cost-effectiveness was considered from an Ontario public-payer perspective by deriving the lifetime incremental cost (2012 Canadian dollars) per quality-adjusted life-year (QALY) for each strategy, and the probability each strategy is cost-effective, assuming a willingness-to-pay of $50,000 per QALY. The 21-gene assay has an incremental cost per QALY in patients at low, intermediate, or high Adjuvant Online! risk of $22,440 (probability cost-effective 78.46%), $2,526 (99.40%), or $1,111 (99.82%), respectively. In patients at low (high) 21-gene assay risk, adjuvant chemotherapy increases (reduces) costs and worsens (improves) health outcomes. For patients at intermediate 21-gene assay risk and low, intermediate, or high Adjuvant! Online risk, chemotherapy has an incremental cost per QALY of $44,088 (50.59%), $1,776 (77.65%), or $1,778 (82.31%), respectively. The 21-gene assay appears cost-effective, regardless of Adjuvant! Online risk. Adjuvant chemotherapy appears cost-effective for patients at intermediate or high 21-gene assay risk, although this finding is uncertain in patients at intermediate 21-gene assay and low Adjuvant! Online risk. Copyright © 2013 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights

Chromosomal mapping of the human M6 genes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Olinsky, S.; Loop, B.T.; DeKosky, A.

1996-05-01

M6 is a neuronal membrane glycoprotein that may have an important role in neural development. This molecule was initially defined by a monoclonal antibody that affected the survival of cultured cerebellar neurons and the outgrowth of neurites. The nature of the antigen was discovered by expression cDNA cloning using this monoclonal antibody. Two distinct murine M6 cDNAs (designated M6a and M6b) whose deduced amino acid sequences were remarkably similar to that of the myelin proteolipid protein human cDNA and genomic clones encoding M6a and M6b and have characterized them by restriction mapping, Southern hybridization with cDNA probes, and sequence analysis.more » We have localized these genes within the human genome by FISH (fluorescence in situ hybridization). The human M6a gene is located at 4q34, and the M6b gene is located at Xp22.2 A number of human neurological disorders have been mapped to the Xp22 region, including Aicardi syndrome (MIM 304050), Rett syndrome (MIM 312750), X-linked Charcot-Marie-Tooth neuropathy (MIM 302801), and X-linked mental retardation syndromes (MRX1, MIM 309530). This raises the possibility that a defect in the M6b gene is responsible for one of these neurological disorders. 8 refs., 3 figs.« less

Discovery and identification of O, O-diethyl O-(4-(5-phenyl-4, 5-dihydroisoxazol-3-yl) phenyl) phosphorothioate (XP-1408) as a novel mode of action of organophosphorus insecticides.

PubMed

Zeng, Zhigang; Yan, Ying; Wang, Bingfeng; Liu, Niu; Xu, Hanhong

2017-06-15

Organophosphorus (OP) insecticides play an important role in pest control. Many OP insecticides have been removed from the market because of their high toxicity to humans. We designed and synthesized a new OP insecticide with the goal of providing a low cost, and less toxic insecticide. The mode of action of O, O-diethyl O-(4-(5-phenyl-4, 5-dihydroisoxazol-3-yl) phenyl) phosphorothioate (XP-1408) was studied in Drosophila melanogaster. Bioassays showed that XP-1408 at a concentration of 50 mg/L delayed larval development. Molecular docking into Drosophila acetylcholinesterase (AChE) and voltage-gated sodium channels suggested that XP-1408 fitted into their active sites and could be inhibitory. Whole-cell patch clamp recordings indicated that XP-1408 exhibited synergistic effects involving the inhibition of cholinergic synaptic transmission and blockage of voltage-gated potassium (K v ) channels and sodium (Na v ) channels. In conclusion, the multiple actions of XP-1408 rendered it as a lead compound for formulating OP insecticides with a novel mode of action.

Chitosan nanoparticle-based delivery of fused NKG2D–IL-21 gene suppresses colon cancer growth in mice

PubMed Central

Tan, Lunmei; Han, Sen; Ding, Shizhen; Xiao, Weiming; Ding, Yanbing; Qian, Li; Wang, Chenming; Gong, Weijuan

2017-01-01

Nanoparticles can be loaded with exogenous DNA for the potential expression of cytokines with immune-stimulatory function. NKG2D identifies major histocompatibility complex class I chain-related protein in human and retinoic acid early induced transcript-1 in mouse, which acts as tumor-associated antigens. Biologic agents based on interleukin 21 (IL-21) have displayed antitumor activities through lymphocyte activation. The NKG2D–IL-21 fusion protein theoretically identifies tumor cells through NKG2D moiety and activates T cells through IL-21 moiety. In this study, double-gene fragments that encode the extracellular domains of NKG2D and IL-21 genes were connected and then inserted into the pcDNA3.1(−) plasmid. PcDNA3.1–dsNKG2D–IL-21 plasmid nanoparticles based on chitosan were generated. Tumor cells pretransfected with dsNKG2D–IL-21 gene nanoparticles can activate natural killer (NK) and CD8+ T cells in vitro. Serum IL-21 levels were enhanced in mice intramuscularly injected with the gene nanoparticles. DsNKG2D–IL-21 gene nanoparticles accumulated in tumor tissues after being intravenously injected for ~4–24 h. Treatment of dsNKG2D–IL-21 gene nanoparticles also retarded tumor growth and elongated the life span of tumor-bearing mice by activating NK and T cells in vivo. Thus, the dsNKG2D–IL-21 gene nanoparticles exerted efficient antitumor activities and would be potentially used for tumor therapy. PMID:28450784

An adult Xp11.2 translocation renal carcinoma showing response to treatment with sunitinib.

PubMed

Pwint, Thinn P; Macaulay, Valentine; Roberts, Ian S D; Sullivan, Mark; Protheroe, Andrew

2011-01-01

A rare variant of renal cell carcinoma (RCC) with a translocation involving Xp11.2 has become increasingly recognized as a separate entity in the 2004 World Health Organization (WHO) kidney carcinoma classification. These tumors predominantly affect children and young adults and tend to present with advanced stage disease. Although reported to be indolent in children, adult cases run a more aggressive course. Little is known about their natural history, prognosis and response to therapy. We report a case of Xp11 translocation renal cancer in a 33-year-old male patient who presented with widespread rapidly progressive metastatic disease involving extensive intra-thoracic lymph nodes, supra-clavicular, retroperitoneal lymph nodes, lung nodules, and peritoneal mass. He had failed to respond to treatment with high dose interleukin 2, but showed a significant clinical response to treatment with the multikinase inhibitor sunitinib. CT scan performed after 3 cycles (18 weeks) of therapy revealed more than 65% reduction of measurable disease by response evaluation criteria in solid tumors (RECIST) criteria, resolution of other assessable lesions, and a clinical benefit that lasted for over 13 months. But unfortunately, this was subsequently followed by a rapidly progressive course. The well-recognized clinical efficacy of multikinase inhibitors such as sunitinib and sorafenib is based on the outcomes in patients with clear cell histology. There is limited data on efficacy in non-clear cell RCC, but activity in translocation RCC has not been reported. To our knowledge, this is the first documented case of Xp11 translocation carcinoma to have demonstrated an objective durable response to sunitinib. It remains unclear how resistance to sunitinib develops, but the results to date support further evaluation of sunitinib in cases of translocation RCC. Copyright © 2011 Elsevier Inc. All rights reserved.

XA21-specific induction of stress-related genes following Xanthomonas infection of detached rice leaves.

PubMed

Thomas, Nicholas C; Schwessinger, Benjamin; Liu, Furong; Chen, Huamin; Wei, Tong; Nguyen, Yen P; Shaker, Isaac W F; Ronald, Pamela C

2016-01-01

The rice XA21 receptor kinase confers robust resistance to the bacterial pathogen Xanthomonas oryzae pv. oryzae ( Xoo ). We developed a detached leaf infection assay to quickly and reliably measure activation of the XA21-mediated immune response using genetic markers. We used RNA sequencing of elf18 treated EFR:XA21:GFP plants to identify candidate genes that could serve as markers for XA21 activation. From this analysis, we identified eight genes that are up-regulated in both in elf18 treated EFR:XA21:GFP rice leaves and Xoo infected XA21 rice leaves. These results provide a rapid and reliable method to assess bacterial-rice interactions.

Phosphorylated 4EBP1 is associated with tumor progression and poor prognosis in Xp11.2 translocation renal cell carcinoma.

PubMed

Qu, Yuanyuan; Zhao, Rui; Wang, Hongkai; Chang, Kun; Yang, Xiaoqun; Zhou, Xiaoyan; Dai, Bo; Zhu, Yao; Shi, Guohai; Zhang, Hailiang; Ye, Dingwei

2016-03-30

Two main signaling pathways, PI3K-AKT-mTOR and RAS-MAPK, are involved in transmitting the proliferative signals which play critical roles in human cancers. However, the functions of these pathways in Xp11.2 RCC remain undefined. This study aimed to explore the expression of mTOR and MAPK cascades in Xp11.2 RCC and to assess the prognostic significance of proteins evaluated. Immunohistochemistry was performed to evaluate the expression of 4EBP1, p-4EBP1, p-mTOR, p-S6K and p-MAPK in 36 adult Xp11.2 RCC patients who were confirmed by FISH assay. Cox regression models were used to evaluate the prognostic value of all covariates. Among 36 assessed patients, 14 (38.9%), 26 (72.2%), 16 (44.4%), 19 (52.8%), and 9 (25.0%) patients showed high expression of 4EBP1, p-4EBP1, p-mTOR, p-S6K, and p-MAPK, respectively. We noted that p-4EBP1 expression was significantly correlated with lymph node metastases (P = 0.027). Multivariate analysis showed that high p-4EBP1 expression was an independent adverse prognostic factor for both PFS (HR = 33.750, P = 0.017) and OS (HR = 56.111, P = 0.026). Our findings suggest that p-4EBP1 may serve as a funnel factor that converge the upstream proliferative oncogenic signals. Effective inhibition of the pathways responsible for 4E-BP1 phosphorylation might be a useful strategy to improve the outcome of Xp11.2 RCC patients.

Gene localization in the Snyder-Robinson syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Arena, J.F.; Lubs, H.A.; Schwartz, C.

1994-07-15

A family described as non-specific XLMR by Snyder and Robinson was re-evaluated 23 years later. Clinical and DNA studies were conducted on 17 family members; 6 affected males, 3 carrier females, and 8 normal males. All carrier females were clinically normal and the pattern of inheritance was clearly X-linked. Initial localization studies indicated linkage to the region near the DMD locus in Xp21.22. Further analysis focused on this region using (CA)n repeat polymorphisms for the dystrophin gene and for two markers distal to the gene. The dystrophin markers detected recombination across the entire gene, making it unlikely that the DMDmore » locus was involved in the Snyder-Robinson syndrome. Normal dystrophin staining in a muscle biopsy in one affected male confirmed this observation. Multipoint analysis also indicate that the SRS (Snyder-Robinson Syndrome) locus was distal to DMD, and located near locus DXS41 (lod score = 4.00 at theta = 0.00). The presence of mild to moderate mental retardation, asthenic body build, diminished muscle bulk, nasal speech, high narrow/cleft palate, long thin fingers and great toes and mild to severe scoliosis permitted the delineation of a specific syndrome associated with this previously non-specific disorder. It is important, therefore, to recognize that today`s {open_quotes}non-specific{close_quotes} family may be tomorrow`s syndrome.« less

SR450 and Superhawk XP applications of Bacillus thuringiensis israelensis de Barjac against Culex quinquefasciatus Say

USDA-ARS?s Scientific Manuscript database

Sprayer comparisons and larval morality assays were conducted following SR450 backpack mist blower and Superhawk XP thermal fogger applications of Vectobac® WDG Bacillus thuringiensis israelensis (Bti) de Barjac against Culex quinquefasciatus Say. Bacillus thuringiensis israelensis was applied at m...

Performance evaluation of the Sysmex(®) XP-300 in an oncology setting: evaluation and comparison of hematological parameters with the Sysmex(®) XN-3000.

PubMed

van Dievoet, M A; Louagie, H; Ghys, T

2016-10-01

The Sysmex XP-300(®) (XP-300) is a new, fully automated hematology analyzer, designed to generate complete blood counts (CBC) with 3-part differential. In our study, the XP-300 was evaluated as a point-of-care (POC) analyzer in an oncology setting. In which blood samples from patients with different pathologies and treatments, affecting hematopoiesis, were analyzed. Performance was evaluated according to the International Council for Standardization in Haematology (ICSH) guidelines and CLSI protocol H20-A2 . Beside precision, linearity and carry-over, a comparison study with the Sysmex(®) XN-3000 (XN-3000) and a manual reference leukocyte differential was performed. Flagging performance was also evaluated. XP-300 showed excellent precision and linearity results. For within- and between-run precision, the criteria, according to Ricos et al. , were met for all parameters tested, except for platelets in the low level. Less than or equal to 0.5% carry-over was seen for all parameters tested. Comparison studies showed an acceptable correlation with both XN-3000 and the manual reference leukocyte count. A suboptimal flagging performance was demonstrated. In the context of diagnosing cytopenia due to myelosuppressing agents or leukocytosis due to infection, the XP-300 showed good analytical performance. However, in the thrombocytopenic range, precision was suboptimal. In follow-up of hematological malignancies with the occurrence of abnormal cells, we advise verification with a more advanced analyzer or with microscopic review, although further studies with a higher prevalence of abnormal cells are needed. © 2016 John Wiley & Sons Ltd.

Norrie disease gene is distinct from the monoamine oxidase genes.

PubMed

Sims, K B; Ozelius, L; Corey, T; Rinehart, W B; Liberfarb, R; Haines, J; Chen, W J; Norio, R; Sankila, E; de la Chapelle, A

1989-09-01

The genes for MAO-A and MAO-B appear to be very close to the Norrie disease gene, on the basis of loss and/or disruption of the MAO genes and activities in atypical Norrie disease patients deleted for the DXS7 locus; linkage among the MAO genes, the Norrie disease gene, and the DXS7 locus; and mapping of all these loci to the chromosomal region Xp11. The present study provides evidence that the MAO genes are not disrupted in "classic" Norrie disease patients. Genomic DNA from these "nondeletion" Norrie disease patients did not show rearrangements at the MAOA or DXS7 loci. Normal levels of MAO-A activities, as well as normal amounts and size of the MAO-A mRNA, were observed in cultured skin fibroblasts from these patients, and MAO-B activity in their platelets was normal. Catecholamine metabolites evaluated in plasma and urine were in the control range. Thus, although some atypical Norrie disease patients lack both MAO-A and MAO-B activities, MAO does not appear to be an etiologic factor in classic Norrie disease.

Increased UV resistance of a xeroderma pigmentosum revertant cell line is correlated with selective repair of the transcribed strand of an expressed gene

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lommel, L.; Hanawalt, P.C.

1993-02-01

People that suffer from xeroderma pigmentosum (XP) are sun sensitive and experience elevated incidences of cancer, particularly skin cancers on sun-light exposed parts of their bodies. Cultured cells from XP patients are found to be subtantially more sensitive to lethal and mutagenic effects of ultraviolet (UV) radiation than are cells from unaffected individuals. Using the cells from XP individuals, researchers study the roles that cyclobutane pyrimidine dimers (CPDs) and 6-4 photoproducts play in UV resistance. The results demonstrate that overall repair measurements can be misleading, and they support the hypothesis that removal of CPDs form the transcribed strands of expressedmore » genes is essential for UV resistance. 36 refs., 5 figs., 1 tab.« less

High-speed Photometric Analysis for Minor Planets 1586 Thiele, 4246 Telemann, (10662) 32-1 T-2, and (49880) 1999 XP 135

NASA Astrophysics Data System (ADS)

Childers, Daniel; Church, Alyssia

2007-12-01

Photometric observations of 1586 Thiele, 4246 Telemann, (10662) 3201 T-2, and (49880) 1999 XP135 were performed in September and October of 2005. The periods and amplitudes found were: 1586 Thiele 3.086 ± 0.038 h, 0.136 ± 0.011 mag; 4246 Telemann 8.960 ± 0.038 h, 0.109 ± 0.027 mag; (10662) 3201 T-2, 3.072 ± 0.038 h, 0.151 ± 0.04 mag; and (49880) 1999 XP135, 11.111 ± 0.038 h, 0.102 ± 0.035 mag.

A Rare Combination of Functional Disomy Xp, Deletion Xq13.2-q28 Spanning the XIST Gene, and Duplication 3q25.33-q29 in a Female with der(X)t(X;3)(q13.2;q25.33).

PubMed

Peterson, Jess F; Basel, Donald G; Bick, David P; Chirempes, Brett; Lorier, Rachel B; Zemlicka, Nykula; Grignon, John W; Weik, LuAnn; Kappes, Ulrike

2018-03-01

We report a 19-year-old female patient with a history of short stature, primary ovarian insufficiency, sensorineural hearing loss, sacral teratoma, neurogenic bladder, and intellectual disability with underlying mosaicism for der(X)t(X;3)(q13.2;q25.33), a ring X chromosome, and monosomy X. Derivative X chromosomes from unbalanced X-autosomal translocations are preferentially silenced by the XIST gene (Xq13.2) located within the X-inactivation center. The unbalanced X-autosomal translocation in our case resulted in loss of the XIST gene thus precluding the inactivation of the derivative X chromosome. As a result, clinical features of functional disomy Xp, Turner's syndrome, and duplication 3q syndrome were observed. Importantly, indications of the derivative X chromosome were revealed by microarray analysis following an initial diagnosis of Turner's syndrome made by conventional cytogenetic studies approximately 18 months earlier. This case demonstrates the importance of utilizing microarray analysis as a first-line test in patients with clinical features beyond the scope of a well-defined genetic syndrome.

Seamless contiguity method for parallel segmentation of remote sensing image

NASA Astrophysics Data System (ADS)

Wang, Geng; Wang, Guanghui; Yu, Mei; Cui, Chengling

2015-12-01

Seamless contiguity is the key technology for parallel segmentation of remote sensing data with large quantities. It can be effectively integrate fragments of the parallel processing into reasonable results for subsequent processes. There are numerous methods reported in the literature for seamless contiguity, such as establishing buffer, area boundary merging and data sewing. et. We proposed a new method which was also based on building buffers. The seamless contiguity processes we adopt are based on the principle: ensuring the accuracy of the boundary, ensuring the correctness of topology. Firstly, block number is computed based on data processing ability, unlike establishing buffer on both sides of block line, buffer is established just on the right side and underside of the line. Each block of data is segmented respectively and then gets the segmentation objects and their label value. Secondly, choose one block(called master block) and do stitching on the adjacent blocks(called slave block), process the rest of the block in sequence. Through the above processing, topological relationship and boundaries of master block are guaranteed. Thirdly, if the master block polygons boundaries intersect with buffer boundary and the slave blocks polygons boundaries intersect with block line, we adopt certain rules to merge and trade-offs them. Fourthly, check the topology and boundary in the buffer area. Finally, a set of experiments were conducted and prove the feasibility of this method. This novel seamless contiguity algorithm provides an applicable and practical solution for efficient segmentation of massive remote sensing image.

The Design and Realization of Radio Telescope Control Software in Windows XP System with VC++

NASA Astrophysics Data System (ADS)

Zhao, Rong-Bing; Aili, Yu; Zhang, Jin; Yu, Yun

2007-03-01

The main function of the radio telescope control software is to drive the radio telescope to track the target accurately. The design of radio telescope control software is based on Windows XP system with VC++. The functions of the software, communication mode and the user interface is introduced in this article.

Contiguity and Entire Separability of States on von Neumann Algebras

NASA Astrophysics Data System (ADS)

Haliullin, Samigulla

2017-12-01

We introduce the notions of the contiguity and entirely separability for two sequences of states on von Neumann algebras. The ultraproducts technique allows us to reduce the study of the contiguity to investigation of the equivalence for two states. Here we apply the Ocneanu ultraproduct and the Groh-Raynaud ultraproduct (see Ocneanu (1985), Groh (J. Operator Theory, 11, 2, 395-404 1984), Raynaud (J. Operator Theory, 48, 1, 41-68, 2002), Ando and Haagerup (J. Funct. Anal., 266, 12, 6842-6913, 2014)), as well as the technique developed in Mushtari and Haliullin (Lobachevskii J. Math., 35, 2, 138-146, 2014).

Torsional resistance of XP-endo Shaper at body temperature compared with several nickel-titanium rotary instruments.

PubMed

Elnaghy, A M; Elsaka, S E

2018-05-01

To compare the torsional resistance of XP-endo Shaper (XPS; size 30, .01 taper, FKG Dentaire, La Chaux-de-Fonds, Switzerland) instruments at body temperature with TRUShape (TRS; size 30, .06 taper, Dentsply Tulsa Dental Specialties, Tulsa, OK, USA), ProFile Vortex (PV; size 30, .04 taper, Dentsply Tulsa Dental Specialties) and FlexMaster (FM; size 30, .04 taper, VDW GmbH, Munich, Germany) nickel-titanium rotary instruments. A metal block with a square-shaped mould (5 mm × 5 mm × 5 mm) was positioned inside a glass container. Five millimetres of the tip of each instrument was held inside the metal block by filling the mould with a resin composite. The instruments were tested for torsional resistance in saline solution at 37 °C. Data were analysed using one-way analysis of variance (anova) and Tukey post hoc tests. The significance level was set at P < 0.05. FM had the greatest torsional resistance amongst the instruments tested (P < 0.001). There was no significant difference between FM and PV instruments (P = 0.211). The ranking for torsional resistance values was: FM > PV > TRS > XPS. FlexMaster and ProFile Vortex instruments were more resistant to torsional stress compared with TRUShape and XP-endo Shaper instruments. The manufacturing process used to produce XP-endo Shaper instruments did not enhance their resistance to torsional stress as compared with the other instruments. © 2017 International Endodontic Journal. Published by John Wiley & Sons Ltd.

Hydrodynamic Delivery of FGF21 Gene Alleviates Obesity and Fatty Liver in Mice Fed a High-fat Diet

PubMed Central

Gao, Mingming; Ma, Yongjie; Cui, Ran; Liu, Dexi

2014-01-01

FGF21 is a secreted protein that plays critical roles in regulating glucose and lipid metabolism. In this study, we evaluated the effects of FGF21 gene transfer on C57BL/6 mice fed a high fat diet (HFD). We demonstrate that transfer of the FGF21 gene using a hydrodynamics-based procedure increased mRNA levels of FGF21 exclusively in the liver, consequently generating a sustained high level of FGF21 protein in blood that peaked at 500 ng/ml one day after injection, leading to a variety of beneficial effects including blockade of HFD-induced obesity, alleviation of fatty liver and improvement in glucose homeostasis. These effects were associated with altered expression of Ucp1, Dio2, Pgc1α, Pparγ2, Mgat1, F4/80, Mcp1 and Tnfα, which are involved in thermogenesis, lipogensis and chronic inflammation in the liver and adipose tissues. Transfer of the FGF21 gene in HFD-induced obese mice greatly increased expression of thermogenic genes in adipose tissue, resulting in similar improvements in systemic metabolism including reduction of adiposity, alleviation of fatty liver and attenuation of insulin resistance. Mechanistic studies on the effects of FGF21 gene transfer in lean mice revealed that mice transferred with FGF21 gene displayed suppressed lipogenesis in the liver and enhanced thermogenesis in brown adipose tissue which was coincident with a significant improvement in glucose tolerance. Collectively, our results suggest transfer of the FGF21 gene could be considered a promising approach for treating obesity and its complications. PMID:24747761

Phase II trial of capecitabine plus modified cisplatin (mXP) as first-line therapy in Japanese patients with metastatic gastric cancer (KSCC1104).

PubMed

Satake, Hironaga; Iwatsuki, Masaaki; Uenosono, Yoshikazu; Shiraishi, Takeshi; Tanioka, Hiroaki; Saeki, Hiroshi; Sugimachi, Keishi; Kitagawa, Dai; Shimokawa, Mototsugu; Oki, Eiji; Emi, Yasunori; Kakeji, Yoshihiro; Tsuji, Akihito; Akagi, Yoshito; Natsugoe, Shoji; Baba, Hideo; Maehara, Yoshihiko

2017-01-01

Capecitabine plus cisplatin (XP) is a standard therapy for metastatic gastric cancer (mGC). However, while results from previous phase III trials suggested that the cisplatin dosage should be reduced in Japanese patients, no clinical data exist to support this. Here, we conducted a multicenter study to evaluate the efficacy and safety of modified XP (mXP) in Japanese patients with mGC. Patients with previously untreated mGC received mXP (cisplatin 60 mg/m 2 on day 1 plus capecitabine 1000 mg/m 2 twice daily on days 1-14) every 3 weeks. The primary endpoint was the Response Evaluation Criteria in Solid Tumors-confirmed overall response rate (ORR). A sample size of 40 was planned for a threshold ORR of 30% and an expected value of 50%, with a one-sided α of 0.05 and a beta of approximately 0.2. Forty-two patients were enrolled. One patient did not fulfill the eligibility criteria; therefore, a total of 41 patients were assessed. The results were as follows: complete response in 2 patients, partial response in 16, stable disease in 14, progressive disease in 8, and no evaluation in 1. The confirmed ORR was 43.9% (95% confidence interval 28.7-59.1%). The median progression-free survival and median overall survival were 4.6 and 11.3 months, respectively. The most common grade 3 or 4 adverse events were neutropenia (37.5%), anemia (24.4%), anorexia (24.4%), and nausea (12.2%). First-line chemotherapy with mXP in Japanese patients with mGC did not reach its primary objective. However, it did show a promising response rate and an acceptable tolerability profile.

Silencing of the Rice Gene LRR1 Compromises Rice Xa21 Transcript Accumulation and XA21-Mediated Immunity.

PubMed

Caddell, Daniel F; Park, Chang-Jin; Thomas, Nicholas C; Canlas, Patrick E; Ronald, Pamela C

2017-12-01

The rice immune receptor XA21 confers resistance to Xanthomonas oryzae pv. oryzae (Xoo), the causal agent of bacterial leaf blight. We previously demonstrated that an auxilin-like protein, XA21 BINDING PROTEIN 21 (XB21), positively regulates resistance to Xoo. To further investigate the function of XB21, we performed a yeast two-hybrid screen. We identified 22 unique XB21 interacting proteins, including LEUCINE-RICH REPEAT PROTEIN 1 (LRR1), which we selected for further analysis. Silencing of LRR1 in the XA21 genetic background (XA21-LRR1Ri) compromises resistance to Xoo compared with control XA21 plants. XA21-LRR1Ri plants have reduced Xa21 transcript levels and reduced expression of genes that serve as markers of XA21-mediated activation. Overexpression of LRR1 is insufficient to alter resistance to Xoo in rice lines lacking XA21. Taken together, our results indicate that LRR1 is required for wild-type Xa21 transcript expression and XA21-mediated immunity.

Compound haplotypes at Xp11.23 and human population growth in Eurasia.

PubMed

Alonso, S; Armour, J A L

2004-09-01

To investigate patterns of diversity and the evolutionary history of Eurasians, we have sequenced a 2.8 kb region at Xp11.23 in a sample of African and Eurasian chromosomes. This region is in a long intron of CLCN5 and is immediately flanked by a highly variable minisatellite, DXS255, and a human-specific Ta0 LINE. Compared to Africans, Eurasians showed a marked reduction in sequence diversity. The main Euro-Asiatic haplotype seems to be the ancestral haplotype for the whole sample. Coalescent simulations, including recombination and exponential growth, indicate a median length of strong linkage disequilibrium, up to approximately 9 kb for this area. The Ka/Ks ratio between the coding sequence of human CLCN5 and its mouse orthologue is much less than 1. This implies that the region sequenced is unlikely to be under the strong influence of positive selective processes on CLCN5, mutations in which have been associated with disorders such as Dent's disease. In contrast, a scenario based on a population bottleneck and exponential growth seems a more likely explanation for the reduced diversity observed in Eurasians. Coalescent analysis and linked minisatellite diversity (which reaches a gene diversity value greater than 98% in Eurasians) suggest an estimated age of origin of the Euro-Asiatic diversity compatible with a recent out-of-Africa model for colonization of Eurasia by modern Homo sapiens.

Renal angiomyolipoma bleeding in a patient with TSC2/PKD1 contiguous gene syndrome after 17 years of renal replacement therapy.

PubMed

Furlano, Mónica; Barreiro, Yaima; Martí, Teresa; Facundo, Carme; Ruiz-García, César; DaSilva, Iara; Ayasreh, Nadia; Cabrera-López, Cristina; Ballarín, José; Ars, Elisabet; Torra, Roser

We report the case of a 32-year-old male diagnosed with TSC2/PKD1 contiguous gene syndrome, presenting with tuberous sclerosis (TS) and autosomal dominant polycystic kidney disease simultaneously. He progressed to end-stage renal disease and received a kidney transplant at the age of 12. The native kidneys presented angiomyolipomas (AML), which are common benign tumours in patients with TS. Seventeen years after transplantation, he presented with abdominal pain, anaemia and a retroperitoneal haematoma, the latter caused by renal AML bleeding. Selective embolisation was performed. Our patient could have benefited from the administration of mTOR inhibitors at transplant. This therapy is immunosuppressive and reduces the size of benign tumours in TS as well as the risk of rupture and bleeding. This patient did not receive mTOR inhibitors at the time of the transplant because the relationship between mTOR inhibitors and TS was unknown at that time. This case confirms the persistent risk of renal AML bleeding for both transplanted patients and patients on dialysis. As a result, we would recommend routine check-ups of native kidneys and nephrectomy assessment. Copyright © 2017 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Phosphorylated 4EBP1 is associated with tumor progression and poor prognosis in Xp11.2 translocation renal cell carcinoma

PubMed Central

Qu, Yuanyuan; Zhao, Rui; Wang, Hongkai; Chang, Kun; Yang, Xiaoqun; Zhou, Xiaoyan; Dai, Bo; Zhu, Yao; Shi, Guohai; Zhang, Hailiang; Ye, Dingwei

2016-01-01

Two main signaling pathways, PI3K-AKT-mTOR and RAS-MAPK, are involved in transmitting the proliferative signals which play critical roles in human cancers. However, the functions of these pathways in Xp11.2 RCC remain undefined. This study aimed to explore the expression of mTOR and MAPK cascades in Xp11.2 RCC and to assess the prognostic significance of proteins evaluated. Immunohistochemistry was performed to evaluate the expression of 4EBP1, p-4EBP1, p-mTOR, p-S6K and p-MAPK in 36 adult Xp11.2 RCC patients who were confirmed by FISH assay. Cox regression models were used to evaluate the prognostic value of all covariates. Among 36 assessed patients, 14 (38.9%), 26 (72.2%), 16 (44.4%), 19 (52.8%), and 9 (25.0%) patients showed high expression of 4EBP1, p-4EBP1, p-mTOR, p-S6K, and p-MAPK, respectively. We noted that p-4EBP1 expression was significantly correlated with lymph node metastases (P = 0.027). Multivariate analysis showed that high p-4EBP1 expression was an independent adverse prognostic factor for both PFS (HR = 33.750, P = 0.017) and OS (HR = 56.111, P = 0.026). Our findings suggest that p-4EBP1 may serve as a funnel factor that converge the upstream proliferative oncogenic signals. Effective inhibition of the pathways responsible for 4E-BP1 phosphorylation might be a useful strategy to improve the outcome of Xp11.2 RCC patients. PMID:27026382

Low temperature growth of Ga 1- xIn xP bulk crystals from InSb-rich melt

NASA Astrophysics Data System (ADS)

Gennett, A.; Lewis, D.; Dutta, P. S.

2010-04-01

Bulk growth of phosphorus and arsenic based ternary III-V semiconductor crystals using pseudo-binary melts such as GaP-InP, GaP-GaAs, AlAs-GaAs, etc. is significantly challenging due to the high vapor pressures of group V species in conjunction with slow growth rates and the need for melt replenishment and mixing during growth. Lowering the growth temperature is desirable such that the vapor pressures of P and As can be easily handled. Low growth temperatures could be achieved by using Ga or In rich solutions. However, this approach is less attractive for growing bulk crystals due to several experimental difficulties including sticking of the growth solution to the crucible wall and to the grown crystal, making it challenging for crystal extraction. Growth of ternary crystals from low temperature quaternary melts has been found to be attractive. In this paper, we will present a new method for the growth of Ga 1- xIn xP from InSb rich Ga 1- xIn xP ySb 1- y melts at low growth temperatures in the range of 800-1050 °C. Thermodynamic phase diagrams calculated at various temperatures using a Gibbs free energy minimization software and materials databases commercially available from Thermo-Calc software will be presented along with experimental validation for Ga 1- xIn xP crystals grown at 1000 °C.

A 13-year-old female with Xp11.2 translocation renal cell carcinoma; the first case diagnosed at Siriraj Hospital.

PubMed

Hanamornroongruang, Suchanan; Treetipsatit, Jitsupa; Pongtanakul, Bunchoo; Seangchai, Napakorn

2012-07-01

Xp11.2 translocation renal cell carcinomas are rare tumors characterized by translocations involving chromosome Xp11.2. These tumors are predominantly reported in pediatric patients. The authors report Xp11.2 translocation renal cell carcinoma in a 13-year-old girl who presented with asymptomatic palpable right renal mass. Right radical nephrectomy was performed and revealed a well-defined solid mass at the lower pole of the kidney. Microscopically, the tumor was composed of sheets and nests of clear to pale eosinophilic cells with some alveolar growth pattern. Psammoma bodies were detected. Immunohistochemically, the tumor cells marked with TFE3, focally marked with smooth muscle actin, HMB-45, CD68, progesterone receptor (PR) and CD10 but did not mark with epithelial markers (AE1/AE3, EMA and CAM5.2), vimentin, S-100 and p53. The presence of psammoma bodies is an important diagnostic clue for these tumors. Cytogenetic study and/or immunohistochemistry for TFE3 protein are needed for confirming the diagnosis. Currently, surgery seems to be the most effective therapy Pediatric patients with these tumors are believed to have a favorable prognosis.

Verification of Bioanalytical Method for Quantification of Exogenous Insulin (Insulin Aspart) by the Analyser Advia Centaur® XP.

PubMed

Mihailov, Rossen; Stoeva, Dilyana; Pencheva, Blagovesta; Pentchev, Eugeni

2018-03-01

In a number of cases the monitoring of patients with type I diabetes mellitus requires measurement of the exogenous insulin levels. For the purpose of a clinical investigation of the efficacy of a medical device for application of exogenous insulin aspart, a verification of the method for measurement of this synthetic analogue of the hormone was needed. The information in the available medical literature for the measurement of the different exogenous insulin analogs is insufficient. Thus, verification was required to be in compliance with the active standards in Republic of Bulgaria. A manufactured method developed for ADVIA Centaur XP Immunoassay, Siemens Healthcare, was used which we verified using standard solutions and a patient serum pool by adding the appropriate quantity exogenous insulin aspart. The method was verified in accordance with the bioanalytical method verification criteria and regulatory requirements for using a standard method: CLIA chemiluminescence immunoassay ADVIA Centaur® XP. The following parameters are determined and monitored: intra-day precision and accuracy, inter-day precision and accuracy, limit of detection and lower limit of quantification, linearity, analytical recovery. The routine application of the method for measurement of immunoreactive insulin using the analyzer ADVIA Centaur® XP is directed to the measurement of endogenous insulin. The method is applicable for measuring different types of exogenous insulin, including insulin aspart.

Detection of steroid 21-hydroxylase alleles using gene-specific PCR and a multiplexed ligation detection reaction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Day, D.J.; Barany, F.; Speiser, P.W.

Steroid 21-hydroxylase deficiency is the most common cause of congenital adrenal hyperplasia, an inherited inability to synthesize cortisol that occurs in 1 in 10,000-15,000 births. Affected females are born with ambiguous genitalia, a condition that can be ameliorated by administering dexamethasone to the mother for most of gestation. Prenatal diagnosis is required for accurate treatment of affected females as well as for genetic counseling purposes. Approximately 95% of mutations causing this disorder result from recombinations between the gene encoding the 21-hydroxylase enzyme (CYP21) and a linked, highly homologous pseudogene (CYP21P). Approximately 20% of these mutations are gene deletions, and themore » remainder are gene conversions that transfer any of nine deleterious mutations from the CYP21P pseudogene to CYP21. We describe a methodology for genetic diagnosis of 21-hydroxylase deficiency that utilizes gene-specific PCR amplification in conjunction with thermostable DNA ligase to discriminate single nucleotide variations in a multiplexed ligation detection assay. The assay has been designed to be used with either fluorescent or radioactive detection of ligation products by electrophoresis on denaturing acrylamide gels and is readily adaptable for use in other disease systems. 30 refs., 5 figs.« less

Electric power supply and demand for the contiguous United States, 1981 - 1990

NASA Astrophysics Data System (ADS)

1981-07-01

The outlook for electric power supply and demand in the United States decade 1981 to 1990 is reviewed from the perspective of reliability and adequacy of service. Electric power supply adequacy as projected for the nine Regional Reliability Council areas of the contiguous United States is reported as well as interruptible load data reported by the Councils. cogeneration is discussed. Each of the 27 electric regions (sub-areas of the nine Council areas) in the contiguous US are studied. A glossary of terms is given. Appendices describe the Council structure, and include a copy of the ERA-411 Manual, which contains all the items to which the Councils were asked to respond. The utilities with included data, the Staff Report, Estimated Electric Demand and Supply for Summer 1981, Contiguous United States dated May 1981 are included.

Interleukin-21 gene polymorphism rs2221903 is associated with disease activity in patients with rheumatoid arthritis.

PubMed

Malinowski, Damian; Paradowska-Gorycka, Agnieszka; Safranow, Krzysztof; Pawlik, Andrzej

2017-08-01

Interleukin-21 (IL-21) is a cytokine which plays a significant role in the pathogenesis and disease activity of rheumatoid arthritis (RA). Genetic polymorphisms in the IL-21 gene may alter the synthesis of IL-21. The aim of this study was to examine IL-21 and IL-21R polymorphisms in patients with RA. We examined 422 patients with RA and 338 healthy controls. Single nucleotide polymorphisms (SNPs) within the IL-21 (rs6822844 G>T, rs6840978 C>T, rs2221903 T>C) and IL-21R (rs2285452 G>A) genes were genotyped using TaqMan genotyping assays. There were no statistically significant differences in the distribution of studied genotypes and alleles between RA patients and the control group. To examine whether IL-21 polymorphisms affect disease activity in RA patients, we compared the distribution of IL-21 genotypes between patients with DAS28 ≤ 2.5 (patients with remission of disease symptoms) and patients with DAS28 > 2.5 (patients with active RA). Among patients with DAS28 > 2.5, increased prevalence of rs2221903 CT and CC genotypes was observed (OR = 1.54; 95% CI: 1.04-2.28; p = 0.035). The results of this study suggest that IL-21 and IL-21R gene polymorphisms are not risk loci for RA susceptibility, whereas the IL-21 rs2221903 polymorphism is associated with disease activity.

Severe visual impairment and retinal changes in a boy with a deletion of the gene for Nance-Horan syndrome.

PubMed

Mathys, R; Deconinck, H; Keymolen, K; Jansen, A; Van Esch, H

2007-01-01

We present the ophthalmologic findings in a boy with a deletion of Xp22 comprising the gene for Nance-Horan syndrome. Different mechanisms underlying the visual impairment in Nance-Horan syndrome are discussed.

Magnetic properties of x(Fe2O3).(100-x)[P2O5.Li2O] and x(Fe2O3).(100-x)[P2O5.CaO] glass systems

NASA Astrophysics Data System (ADS)

Andronache, Constantin; Racolta, Dania; Ardelean, Gheorghe

2017-12-01

Magnetic properties of x(Fe2O3).(100-x)[P2O5 .Li2O] and x(Fe2O3).(100-x)[P2O5 .CaO] with 0 < x ≤ 50 mol % were investigated using magnetic susceptibility measurements. The both glass systems were prepared in the same condition. The valence states and the distribution of iron ions in the glass matrix depend on the Fe2O3 content. For the P2O5.CaO glass matrix with x≤35mol%, the data revealed iron ions as isolated or participating in dipole-dipole interaction. For x > 35 mol% an antiferromagnetic coupling is observed. For the P2O5.Li2O glass matrix, the iron ions behave magnetically similarly as in other oxide glasses, but concentration of Fe2O3 over which magnetic superexchange interactions occur is lower. The absolute magnitude of θp values increases when content of Fe2O3 are increased. If the content of the magnetic ions is increased in the glass, the exchange integral increased and as a result the magnitude of the θP increases.

The Role of the 21-Gene Recurrence Score in Breast Cancer Treatment.

PubMed

Ethier, Josee-Lyne; Amir, Eitan

2016-08-01

Several multi-gene assays have been developed to predict the risk of recurrence in patients with estrogen receptor-positive early breast cancer and in whom endocrine therapy is planned. The 21-gene assay is widely used and its prognostic value has been retrospectively validated, showing significant differences in the risk of distant recurrence for patients at high versus low risk. Its role in predicting chemotherapy benefit has also been established, showing a clear benefit for high-risk patients and minimal benefit in those at low risk. These findings have been prospectively investigated in TAILORx (Trial Assigning Individualized Options for Treatment), where available data from the low-risk cohort confirms the prognostic value of this diagnostic test. The prognostic utility of the 21-gene assay increases when combined with clinicopathologic variables, and data from integrated models suggest that its use should be limited to patients with tumor characteristics suggestive of potential chemotherapy benefit. Furthermore, the 21-gene assay has been shown to impact clinical decision making in a cost-effective manner, although direct evidence of benefit from modified treatment recommendations is yet to be proven. The prognostic value of this test has also been shown in populations with node-positive or locally advanced disease treated with neoadjuvant chemotherapy, and ongoing trials aim to prospectively validate these findings.

Clinicopathological characteristics of Xp11.2 translocation renal cell carcinoma in adolescents and adults: Diagnosis using immunostaining of transcription factor E3 and fluorescence in situ hybridization analysis.

PubMed

Hirobe, Megumi; Masumori, Naoya; Tanaka, Toshiaki; Kitamura, Hiroshi; Tonooka, Akiko; Hasegawa, Tadashi; Tsukamoto, Taiji

2016-02-01

To determine the rate and clinicopathological features of Xp11.2 translocation carcinoma using immunostaining of transcription factor E3 and fluorescence in situ hybridization analysis. We evaluated 638 patients with renal cell carcinoma treated at Sapporo Medical University Hospital, Sapporo, Japan, from 1990 to 2009 by reviewing all hematoxylin-eosin-stained sections and carrying out immunostaining of transcription factor E3 for all cases. Fluorescence in situ hybridization analysis was carried out for patients with positive immunostaining or with findings suspicious for Xp11.2 translocation carcinoma on hematoxylin-eosin-stained sections. In this analysis, we set a cut-off level for split signals of at least 10% of nuclei. Of the 631 patients, 20 (3.2%) were positive for immunostaining. Finally, five patients were diagnosed with Xp11.2 translocation carcinoma (0.8%). Four of these patients were female and aged less than 50 years, and three cases were diagnosed as stage IV with multiple regional lymph nodal or visceral metastases. The positive predictive value of immunostaining was 25%. Patients with Xp11 translocation renal cell carcinoma tend to be younger, more frequently female and diagnosed at a more advanced stage. Immunostaining followed by fluorescence in situ hybridization analysis is an accurate and cost-effective approach for diagnosis of Xp11 translocation renal cell carcinoma. © 2015 The Japanese Urological Association.

Isolated p.H62L Mutation in the CYP21A2 Gene in a Simple Virilizing 21-Hydroxylase Deficient Patient.

PubMed

Taboas, Melisa; Fernández, Cecilia; Belli, Susana; Buzzalino, Noemi; Alba, Liliana; Dain, Liliana

2013-01-01

Congenital adrenal hyperplasia due to 21-hydroxylase deficiency accounts for 90%-95% of cases. This autosomal recessive disorder has a broad spectrum of clinical forms, ranging from severe or classical, which includes the salt-wasting and simple virilizing forms, to the mild late onset or nonclassical form. Most of the disease-causing mutations described are likely to be the consequence of nonhomologous recombination or gene conversion events between the active CYP21A2 gene and its homologous CYP21A1P pseudogene. Nevertheless, an increasing number of naturally occurring mutations have been found. The change p.H62L is one of the most frequent rare mutations of the CYP21A2 gene. It was suggested that the p.H62L represents a mild mutation that may be responsible for a more severe enzymatic impairment when presented with another mild mutation on the same allele. In this report, a 20-year-old woman carrying an isolated p.H62L mutation in compound heterozygosity with c.283-13A/C>G mutation is described. Although a mildly nonclassical phenotype was expected, clinical signs and hormonal profile of the patient are consistent with a more severe simple virilizing form of 21-hydroxylase deficiency. The study of genotype-phenotype correlation in additional patients would help in defining the role of p.H62L in disease manifestation.

Monoamine oxidase deficiency in males with an X chromosome deletion.

PubMed

Sims, K B; de la Chapelle, A; Norio, R; Sankila, E M; Hsu, Y P; Rinehart, W B; Corey, T J; Ozelius, L; Powell, J F; Bruns, G

1989-01-01

Mapping of the human MAOA gene to chromosomal region Xp21-p11 prompted our study of two affected males in a family previously reported to have Norrie disease resulting from a submicroscopic deletion in this chromosomal region. In this investigation we demonstrate in these cousins deletion of the MAOA gene, undetectable levels of MAO-A and MAO-B activities in their fibroblasts and platelets, respectively, loss of mRNA for MAO-A in fibroblasts, and substantial alterations in urinary catecholamine metabolites. The present study documents that a marked deficiency of MAO activity is compatible with life and that genes for MAO-A and MAO-B are near each other in this Xp chromosomal region. Some of the clinical features of these MAO deletion patients may help to identify X-linked MAO deficiency diseases in humans.

Classification of upper Mississippi River pools based on contiguous aquatic/geomorphic habitats

USGS Publications Warehouse

Koel, Todd M.

2001-01-01

Navigation pools of the upper Mississippi River (UMR) vary greatly in terms of available contiguous aquatic/geomorphic habitats. These habitats are critical for the biotic diversity and overall productivity of the floodplain corridor of each pool. In this study, similarities among pools 4-26 and an open river reach (river kilometer 47-129) of the UMR were determined from multivariate analysis of eleven habitat types that were hydrologically-contiguous (non-leveed). Isolated floodplain habitats were not included in final analyses because this isolation limits their contribution to overall riverine productivity, in part due to a lack of hydrological connectivity to the main channel during the flood pulse. Cluster analysis based on simple Euclidean distance was used to produce two major pool groups and five pool subgroups. Important habitat variables in defining pool groups, as interpreted from principal components analysis (PCA) axis 1, were contiguous floodplain shallow aquatic area and contiguous impounded area. The habitat variable most important in defining pool subgroups, as interpreted from PCA axis 2, was tertiary channel. Most notably, pool 6 was more similar to pools 14-24 than other upper pools, and pools 19 and 25 were more similar to pools 4-13 than other lower pools. These results were quite different from those of two previous investigators, primarily because only areas of non-isolated aquatic habitat were considered.

Force Tests of a 1/5-Scale Model of the McDonnell XP-85 Airplane with Conventional Tail Assembly in the Langley Free-Flight Tunnel

NASA Technical Reports Server (NTRS)

Paulson, John W.; Johnson, Joseph L.

1947-01-01

At the request of the Air Materiel Command, Army Air Forces an investigation of the low-speed, power-off stability and control characteristics of the McDonnell XP-85 airplane is being conducted in the Langley free-flight tunnel. The XP-85 airplane is a parasite fighter carried in a bomb bay of the B-36 airplane. As a part of the investigation a few force tests were made of a 1/5 scale model of the XP-85 with a conventional tail assembly installed in place of the original design five-unit tail assembly. The total area of the conventional assembly was approximately 80 percent of the area of the five-unit assembly. The results of this investigation showed that the conventional tail assembly gave about the same longitudinal stability characteristics as the original configuration and improved the directional and lateral stability.

Interleukin-21 gene polymorphism rs2221903 is associated with disease activity in patients with rheumatoid arthritis

PubMed Central

Malinowski, Damian; Paradowska-Gorycka, Agnieszka; Safranow, Krzysztof

2017-01-01

Introduction Interleukin-21 (IL-21) is a cytokine which plays a significant role in the pathogenesis and disease activity of rheumatoid arthritis (RA). Genetic polymorphisms in the IL-21 gene may alter the synthesis of IL-21. The aim of this study was to examine IL-21 and IL-21R polymorphisms in patients with RA. Material and methods We examined 422 patients with RA and 338 healthy controls. Single nucleotide polymorphisms (SNPs) within the IL-21 (rs6822844 G>T, rs6840978 C>T, rs2221903 T>C) and IL-21R (rs2285452 G>A) genes were genotyped using TaqMan genotyping assays. Results There were no statistically significant differences in the distribution of studied genotypes and alleles between RA patients and the control group. To examine whether IL-21 polymorphisms affect disease activity in RA patients, we compared the distribution of IL-21 genotypes between patients with DAS28 ≤ 2.5 (patients with remission of disease symptoms) and patients with DAS28 > 2.5 (patients with active RA). Among patients with DAS28 > 2.5, increased prevalence of rs2221903 CT and CC genotypes was observed (OR = 1.54; 95% CI: 1.04–2.28; p = 0.035). Conclusions The results of this study suggest that IL-21 and IL-21R gene polymorphisms are not risk loci for RA susceptibility, whereas the IL-21 rs2221903 polymorphism is associated with disease activity. PMID:28883856

Norrie disease gene is distinct from the monoamine oxidase genes

PubMed Central

Sims, Katherine B.; Ozelius, Laurie; Corey, Timothy; Rinehart, William B.; Liberfarb, Ruth; Haines, Jonathan; Chen, Wei Jane; Norio, Reijo; Sankila, Eeva; de la Chapelle, Albert; Murphy, Dennis L.; Gusella, James; Breakefield, Xandra O.

1989-01-01

The genes for MAO-A and MAO-B appear to be very close to the Norrie disease gene, on the basis of loss and /or disruption of the MAO genes and activities in atypical Norrie disease patients deleted for the DXS7 locus; linkage among the MAO genes, the Norrie disease gene, and the DXS7 locus; and mapping of all these loci to the chromosomal region Xp11. The present study provides evidence that the MAO genes are not disrupted in “classic” Norrie disease patients. Genomic DNA from these “nondeletion” Norrie disease patients did not show rearrangements at the MAOA or DXS7 loci. Normal levels of MAO-A activities, as well as normal amounts and size of the MAO-A mRNA, were observed in cultured skin fibroblasts from these patients, and MAO-B activity in their platelets was normal. Catecholamine metabolites evaluated in plasma and urine were in the control range. Thus, although some atypical Norrie disease patients lack both MAO-A and MAO-B activities, MAO does not appear to be an etiologic factor in classic Norrie disease. ImagesFigure 2Figure 3 PMID:2773935

Human ETS2 gene on chromosome 21 is not rearranged in Alzheimer disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sacchi, N.; Nalbantoglu, J.; Sergovich, F.R.

1988-10-01

The human ETS2 gene, a member of the ETS gene family, with sequence homology with the retroviral ets sequence of the avian erythroblastosis retrovirus E26 is located on chromosome 21. Molecular genetic analysis of Down syndrome (DS) patients with partial trisomy 21 allowed us to reinforce the supposition that ETS2 may be a gene of the minimal DS genetic region. It was originally proposed that a duplication of a portion of the DS region represents the genetic basis of Alzheimer disease, a condition associated also with DS. No evidence of either rearrangements or duplications of ETS2 could be detected inmore » DNA from fibroblasts and brain tissue of Alzheimer disease patients with either the sporadic or the familiar form of the disease. Thus, an altered ETS2 gene dosage does not seem to be a genetic cause or component of Alzheimer disease.« less

Identification of two novel mammalian genes establishes a subfamily of KH-domain RNA-binding proteins.

PubMed

Makeyev, A V; Liebhaber, S A

2000-08-01

We have identified two novel human genes encoding proteins with a high level of sequence identity to two previously characterized RNA-binding proteins, alphaCP-1 and alphaCP-2. Both of these novel genes, alphaCP-3 and alphaCP-4, are predicted to encode proteins with triplicated KH domains. The number and organization of the KH domains, their sequences, and the sequences of the contiguous regions are conserved among all four alphaCP proteins. The common evolutionary origin of these proteins is substantiated by conservation of exon-intron organization in the corresponding genes. The map positions of alphaCP-1 and alphaCP-2 (previously reported) and those of alphaCP-3 and alphaCP-4 (present report) reveal that the four alphaCP loci are dispersed in the human genome; alphaCP-3 and alphaCP-4 mapped to 21q22.3 and 3p21, and the respective mouse orthologues mapped to syntenic regions of the mouse genome, 10B5 and 9F1-F2, respectively. Two additional loci in the human genome were identified as alphaCP-2 processed pseudogenes (PCBP2P1, 21q22.3, and PCBP2P2, 8q21-q22). Although the overall levels of alphaCP-3 and alphaCP-4 mRNAs are substantially lower than those of alphaCP-1 and alphaCP-2, transcripts of alphaCP-3 and alphaCP-4 were found in all mouse tissues tested. These data establish a new subfamily of genes predicted to encode closely related KH-containing RNA-binding proteins with potential functions in posttranscriptional controls. Copyright 2000 Academic Press.

The performance of approximations of farm contiguity compared to contiguity defined using detailed geographical information in two sample areas in Scotland: implications for foot-and-mouth disease modelling.

PubMed

Flood, Jessica S; Porphyre, Thibaud; Tildesley, Michael J; Woolhouse, Mark E J

2013-10-08

When modelling infectious diseases, accurately capturing the pattern of dissemination through space is key to providing optimal recommendations for control. Mathematical models of disease spread in livestock, such as for foot-and-mouth disease (FMD), have done this by incorporating a transmission kernel which describes the decay in transmission rate with increasing Euclidean distance from an infected premises (IP). However, this assumes a homogenous landscape, and is based on the distance between point locations of farms. Indeed, underlying the spatial pattern of spread are the contact networks involved in transmission. Accordingly, area-weighted tessellation around farm point locations has been used to approximate field-contiguity and simulate the effect of contiguous premises (CP) culling for FMD. Here, geographic data were used to determine contiguity based on distance between premises' fields and presence of landscape features for two sample areas in Scotland. Sensitivity, positive predictive value, and the True Skill Statistic (TSS) were calculated to determine how point distance measures and area-weighted tessellation compared to the 'gold standard' of the map-based measures in identifying CPs. In addition, the mean degree and density of the different contact networks were calculated. Utilising point distances <1 km and <5 km as a measure for contiguity resulted in poor discrimination between map-based CPs/non-CPs (TSS 0.279-0.344 and 0.385-0.400, respectively). Point distance <1 km missed a high proportion of map-based CPs; <5 km point distance picked up a high proportion of map-based non-CPs as CPs. Area-weighted tessellation performed best, with reasonable discrimination between map-based CPs/non-CPs (TSS 0.617-0.737) and comparable mean degree and density. Landscape features altered network properties considerably when taken into account. The farming landscape is not homogeneous. Basing contiguity on geographic locations of field boundaries and including

Constitutional chromothripsis involving the critical region of 9q21.13 microdeletion syndrome.

PubMed

Genesio, Rita; Fontana, Paolo; Mormile, Angela; Casertano, Alberto; Falco, Mariateresa; Conti, Anna; Franzese, Adriana; Mozzillo, Enza; Nitsch, Lucio; Melis, Daniela

2015-01-01

The chromothripsis is a biological phenomenon, first observed in tumors and then rapidly described in congenital disorders. The principle of the chromothripsis process is the occurrence of a local shattering to pieces and rebuilding of chromosomes in a random order. Congenital chromothripsis rearrangements often involve reciprocal rearrangements on multiple chromosomes and have been described as cause of contiguous gene syndromes. We hypothesize that chromothripsis could be responsible for known 9q21.13 microdeletion syndrome, causing a composite phenotype with additional features. The case reported is a 16- years-old female with a complex genomic rearrangement of chromosome 9 including the critical region of 9q21.13 microdeletion syndrome. The patient presents with platelet disorder and thyroid dysfunction in addition to the classical neurobehavioral phenotype of the syndrome. The presence of multiple rearrangements on the same chromosome 9 and the rebuilding of chromosome in a random order suggested that the rearrangement could origin from an event of chromthripsis. To our knowledge this is the first report of congenital chromothripsis involving chromosome 9. Furthermore this is the only case of 9q21.13 microdeletion syndrome due to chromothripsis.

ABACAS: algorithm-based automatic contiguation of assembled sequences

PubMed Central

Assefa, Samuel; Keane, Thomas M.; Otto, Thomas D.; Newbold, Chris; Berriman, Matthew

2009-01-01

Summary: Due to the availability of new sequencing technologies, we are now increasingly interested in sequencing closely related strains of existing finished genomes. Recently a number of de novo and mapping-based assemblers have been developed to produce high quality draft genomes from new sequencing technology reads. New tools are necessary to take contigs from a draft assembly through to a fully contiguated genome sequence. ABACAS is intended as a tool to rapidly contiguate (align, order, orientate), visualize and design primers to close gaps on shotgun assembled contigs based on a reference sequence. The input to ABACAS is a set of contigs which will be aligned to the reference genome, ordered and orientated, visualized in the ACT comparative browser, and optimal primer sequences are automatically generated. Availability and Implementation: ABACAS is implemented in Perl and is freely available for download from http://abacas.sourceforge.net Contact: sa4@sanger.ac.uk PMID:19497936

McDonald XP-85 Airplane in 40x80 foot Wind Tunnel.

NASA Image and Video Library

1948-04-08

Front View of McDonald XP-85 Plan Model. Parasite Airplane designed to be carried in the B-36 bombay (never built) At the time it was the smallest Jet powered airplane. The McDonnell XF-85 Goblin was an American prototype fighter aircraft conceived during World War II by McDonnell Aircraft. It was intended to be deployed from the bomb bay of the giant Convair B-36 bomber as a parasite fighter. The XF-85's intended role was to defend bombers from hostile interceptor aircraft, a need demonstrated during World War II

Norrie disease and MAO genes: nearest neighbors.

PubMed

Chen, Z Y; Denney, R M; Breakefield, X O

1995-01-01

The Norrie disease and MAO genes are tandemly arranged in the p11.4-p11.3 region of the human X chromosome in the order tel-MAOA-MAOB-NDP-cent. This relationship is conserved in the mouse in the order tel-MAOB-MAOA-NDP-cent. The MAO genes appear to have arisen by tandem duplication of an ancestral MAO gene, but their positional relationship to NDP appears to be random. Distinctive X-linked syndromes have been described for mutations in the MAOA and NDP genes, and in addition, individuals have been identified with contiguous gene syndromes due to chromosomal deletions which encompass two or three of these genes. Loss of function of the NDP gene causes a syndrome of congenital blindness and progressive hearing loss, sometimes accompanied by signs of CNS dysfunction, including variable mental retardation and psychiatric symptoms. Other mutations in the NDP gene have been found to underlie another X-linked eye disease, exudative vitreo-retinopathy. An MAOA deficiency state has been described in one family to date, with features of altered amine and amine metabolite levels, low normal intelligence, apparent difficulty in impulse control and cardiovascular difficulty in affected males. A contiguous gene syndrome in which all three genes are lacking, as well as other as yet unidentified flanking genes, results in severe mental retardation, small stature, seizures and congenital blindness, as well as altered amine and amine metabolites. Issues that remain to be resolved are the function of the NDP gene product, the frequency and phenotype of the MAOA deficiency state, and the possible occurrence and phenotype of an MAOB deficiency state.

Isolated p.H62L Mutation in the CYP21A2 Gene in a Simple Virilizing 21-Hydroxylase Deficient Patient

PubMed Central

Fernández, Cecilia; Belli, Susana; Buzzalino, Noemi; Dain, Liliana

2013-01-01

Congenital adrenal hyperplasia due to 21-hydroxylase deficiency accounts for 90%–95% of cases. This autosomal recessive disorder has a broad spectrum of clinical forms, ranging from severe or classical, which includes the salt-wasting and simple virilizing forms, to the mild late onset or nonclassical form. Most of the disease-causing mutations described are likely to be the consequence of nonhomologous recombination or gene conversion events between the active CYP21A2 gene and its homologous CYP21A1P pseudogene. Nevertheless, an increasing number of naturally occurring mutations have been found. The change p.H62L is one of the most frequent rare mutations of the CYP21A2 gene. It was suggested that the p.H62L represents a mild mutation that may be responsible for a more severe enzymatic impairment when presented with another mild mutation on the same allele. In this report, a 20-year-old woman carrying an isolated p.H62L mutation in compound heterozygosity with c.283-13A/C>G mutation is described. Although a mildly nonclassical phenotype was expected, clinical signs and hormonal profile of the patient are consistent with a more severe simple virilizing form of 21-hydroxylase deficiency. The study of genotype-phenotype correlation in additional patients would help in defining the role of p.H62L in disease manifestation. PMID:23936690

SFPQ/PSF-TFE3 renal cell carcinoma: a clinicopathologic study emphasizing extended morphology and reviewing the differences between SFPQ-TFE3 RCC and the corresponding mesenchymal neoplasm despite an identical gene fusion.

PubMed

Wang, Xiao-Tong; Xia, Qiu-Yuan; Ni, Hao; Ye, Sheng-Bing; Li, Rui; Wang, Xuan; Shi, Shan-Shan; Zhou, Xiao-Jun; Rao, Qiu

2017-05-01

Xp11 translocation renal cell carcinoma (RCC) with SFPQ/PSF-TFE3 gene fusion is a rare epithelial tumor. Of note, the appearance of the gene fusion does not necessarily mean that it is renal cell carcinoma. The corresponding mesenchymal neoplasms, including Xp11 neoplasm with melanocytic differentiation, TFE3 rearrangement-associated perivascular epithelioid cell tumor (PEComa) and melanotic Xp11 translocation renal cancer, can also harbor the identical gene fusion. However, the differences between Xp11 translocation RCC and the corresponding mesenchymal neoplasm have only recently been described. Herein, we examined 5 additional cases of SFPQ-TFE3 RCCs using clinicopathologic, immunohistochemical, and molecular analyses. One tumor had the typical morphologic features of SFPQ-TFE3 RCC, whereas other 3 cases demonstrated the unusual morphologic features associated with pseudorosettes formation or clusters of smaller cells, mimicking TFEB RCC. The remaining one showed branching tubules and papillary structure composed of clear and eosinophilic tumor cells. Immunohistochemically, all 5 cases demonstrated moderate (2+) or strong (3+) positive staining for TFE3, PAX-8 and CD10, whereas no cases demonstrated TFEB, Cathepsin K, CA-IX, CK7, Melan-A, or HMB-45 expression. Genetically, the fusion transcripts were identified in 3 cases by reverse-transcription polymerase chain reaction (RT-PCR). On the basis of fluorescence in situ hybridization (FISH) analysis, all the cases were detected with SFPQ-TFE3 gene fusion. Clinical follow-up data were available for all the patients, and no one developed tumor recurrence, progression, or metastasis. We also review the differences between SFPQ-TFE3 RCC and the corresponding mesenchymal neoplasm despite the identical gene fusion. The presence of pseudorosettes also expands the known histological features of SFPQ-TFE3 RCC. Copyright © 2017 Elsevier Inc. All rights reserved.

A rare de novo interstitial duplication of 15q15.3q21.2 in a boy with severe short stature, hypogonadism, global developmental delay and intellectual disability.

PubMed

Yuan, Haiming; Meng, Zhe; Zhang, Lina; Luo, Xiangyang; Liu, Liping; Chen, Mengfan; Li, Xinwei; Zhao, Weiwei; Liang, Liyang

2016-01-01

Interstitial duplications distal to 15q13 are very rare. Here, we reported a 14-year-old boy with severe short stature, delayed bone age, hypogonadism, global developmental delay and intellectual disability. His had distinctive facial features including macrocephaly, broad forehead, deep-set and widely spaced eyes, broad nose bridge, shallow philtrum and thick lips. A de novo 6.4 Mb interstitial duplication of 15q15.3q21.2 was detected by chromosomal microarray analysis. We compared our patient's clinical phenotypes with those of several individuals with overlapping duplications and several candidate genes responsible for the phenotypes were identified as well. The results suggest a novel contiguous gene duplication syndrome characterized with shared features including short stature, hypogonadism, global developmental delay and other congenital anomalies.

Dependence of prevalence of contiguous pathways in proteins on structural complexity.

PubMed

Thayer, Kelly M; Galganov, Jesse C; Stein, Avram J

2017-01-01

Allostery is a regulatory mechanism in proteins where an effector molecule binds distal from an active site to modulate its activity. Allosteric signaling may occur via a continuous path of residues linking the active and allosteric sites, which has been suggested by large conformational changes evident in crystal structures. An alternate possibility is that the signal occurs in the realm of ensemble dynamics via an energy landscape change. While the latter was first proposed on theoretical grounds, increasing evidence suggests that such a control mechanism is plausible. A major difficulty for testing the two methods is the ability to definitively determine that a residue is directly involved in allosteric signal transduction. Statistical Coupling Analysis (SCA) is a method that has been successful at predicting pathways, and experimental tests involving mutagenesis or domain substitution provide the best available evidence of signaling pathways. However, ascertaining energetic pathways which need not be contiguous is far more difficult. To date, simple estimates of the statistical significance of a pathway in a protein remain to be established. The focus of this work is to estimate such benchmarks for the statistical significance of contiguous pathways for the null model of selecting residues at random. We found that when 20% of residues in proteins are randomly selected, contiguous pathways at the 6 Å cutoff level were found with success rates of 51% in PDZ, 30% in p53, and 3% in MutS. The results suggest that the significance of pathways may have system specific factors involved. Furthermore, the possible existence of false positives for contiguous pathways implies that signaling could be occurring via alternate routes including those consistent with the energetic landscape model.

Method for prefetching non-contiguous data structures

DOEpatents

Blumrich, Matthias A [Ridgefield, CT; Chen, Dong [Croton On Hudson, NY; Coteus, Paul W [Yorktown Heights, NY; Gara, Alan G [Mount Kisco, NY; Giampapa, Mark E [Irvington, NY; Heidelberger, Philip [Cortlandt Manor, NY; Hoenicke, Dirk [Ossining, NY; Ohmacht, Martin [Brewster, NY; Steinmacher-Burow, Burkhard D [Mount Kisco, NY; Takken, Todd E [Mount Kisco, NY; Vranas, Pavlos M [Bedford Hills, NY

2009-05-05

A low latency memory system access is provided in association with a weakly-ordered multiprocessor system. Each processor in the multiprocessor shares resources, and each shared resource has an associated lock within a locking device that provides support for synchronization between the multiple processors in the multiprocessor and the orderly sharing of the resources. A processor only has permission to access a resource when it owns the lock associated with that resource, and an attempt by a processor to own a lock requires only a single load operation, rather than a traditional atomic load followed by store, such that the processor only performs a read operation and the hardware locking device performs a subsequent write operation rather than the processor. A simple perfecting for non-contiguous data structures is also disclosed. A memory line is redefined so that in addition to the normal physical memory data, every line includes a pointer that is large enough to point to any other line in the memory, wherein the pointers to determine which memory line to prefect rather than some other predictive algorithm. This enables hardware to effectively prefect memory access patterns that are non-contiguous, but repetitive.

Gene context conservation of a higher order than operons.

PubMed

Lathe, W C; Snel, B; Bork, P

2000-10-01

Operons, co-transcribed and co-regulated contiguous sets of genes, are poorly conserved over short periods of evolutionary time. The gene order, gene content and regulatory mechanisms of operons can be very different, even in closely related species. Here, we present several lines of evidence which suggest that, although an operon and its individual genes and regulatory structures are rearranged when comparing the genomes of different species, this rearrangement is a conservative process. Genomic rearrangements invariably maintain individual genes in very specific functional and regulatory contexts. We call this conserved context an uber-operon.

Identification and characterization of wheat stem rust resistance gene Sr21 effective against the Ug99 race group at high temperature

PubMed Central

Chen, Shisheng; Zhang, Wenjun; Bolus, Stephen; Rouse, Matthew N.

2018-01-01

Wheat stem rust, caused by Puccinia graminis f. sp. tritici (Pgt), is a devastating foliar disease. The Ug99 race group has combined virulence to most stem rust (Sr) resistance genes deployed in wheat and is a threat to global wheat production. Here we identified a coiled-coil, nucleotide-binding leucine-rich repeat protein (NLR) completely linked to the Ug99 resistance gene Sr21 from Triticum monococcum. Loss-of-function mutations and transgenic complementation confirmed that this gene is Sr21. Sr21 transcripts were significantly higher at high temperatures, and this was associated with significant upregulation of pathogenesis related (PR) genes and increased levels of resistance at those temperatures. Introgression of Sr21 into hexaploid wheat resulted in lower levels of resistance than in diploid wheat, but transgenic hexaploid wheat lines with high levels of Sr21 expression showed high levels of resistance. Sr21 can be a valuable component of transgenic cassettes or gene pyramids combining multiple resistance genes against Ug99. PMID:29614079

A patient with de-novo partial deletion of Xp (p11.4-pter) and partial duplication of 22q (q11.2-qter).

PubMed

Armour, Christine M; McGowan-Jordan, Jean; Lawrence, Sarah E; Bouchard, Amélie; Basik, Mark; Allanson, Judith E

2008-01-01

We report on a girl with partial deletion of Xp and partial duplication of 22q. Family studies demonstrate that both the patient's mother and her nonidentical twin sister carry the corresponding balanced translocation; 46,X,t(X;22)(p11.4;q11.2). This girl has developmental delay, microcephaly, mild dysmorphisms and hearing loss but otherwise shows few of the features described in individuals with duplications of the long arm of chromosome 22. She does manifest characteristics, such as short stature and biochemical evidence of ovarian failure, which are seen in partial or complete Xp deletions and Turner's syndrome.

Xeroderma pigmentosum genes and melanoma risk.

PubMed

Paszkowska-Szczur, K; Scott, R J; Serrano-Fernandez, P; Mirecka, A; Gapska, P; Górski, B; Cybulski, C; Maleszka, R; Sulikowski, M; Nagay, L; Lubinski, J; Dębniak, T

2013-09-01

Xeroderma pigmentosum is a rare autosomal recessive disease that is associated with a severe deficiency in nucleotide excision repair. The presence of a distinct the nucleotide excision repair (NER) mutation signature in melanoma suggests that perturbations in this critical repair process are likely to be involved with disease risk. We hypothesized that persons with polymorphic NER gene(s) are likely to have reduced NER activity and are consequently at an increased risk of melanoma development. We assessed the association between 94 SNPs within seven XP genes (XPA-XPG) and the melanoma risk in the Polish population. We genotyped 714 unselected melanoma patients and 1,841 healthy adults to determine if there were any polymorphisms differentially represented in the disease group. We found that a significantly decreased risk of melanoma was associated with the Xeroderma pigmentosum complementation (XPC) rs2228000_CT genotype (odds ratio [OR] = 0.15; p < 0.001) and the rs2228000_TT genotype (OR = 0.11; p < 0.001) compared to the reference genotype. Haplotype analysis within XPC revealed the rs2228001_A + G1475A_G + G2061A_A + rs2228000_T + rs3731062_C haplotype (OR = 0.26; p < 0.05) was associated with a significantly decreased disease risk. The haplotype analysis within the Xeroderma pigmentosum group D (XPD) showed a modest association between two haplotypes and a decrease in melanoma risk. There were no major differences between the prevalence of the XP polymorphisms among young or older patients with melanoma. Linkage disequilibrium of XPC: rs2228001, G1475A, G2061A, rs2228000 and rs3731062 was found. The data from our study support the notion that only XPC and XPD genes are associated with melanoma susceptibility. Copyright © 2013 UICC.

Wind-Tunnel Development of Ailerons for the Curtiss XP-60 Airplanem Special Report

NASA Technical Reports Server (NTRS)

Rogallo, F. M.; Lowry, John G.

1942-01-01

An investigation was made in the LWAL 7- by 10-foot tunnel of internally balanced, sealed ailerons for the Curtiss XP-60 airplane. Ailerons with tabs and. with various amounts of balance were tested. Stick forces were estimated for several aileron arrangements including an arrangement recommended for the airplane. Flight tests of the recommended arrangement are discussed briefly in an appendix, The results of the wind-tunnel and flight tests indicate that the ailerons of large or fast airplanes may be satisfactorily balanced by the method developed.

Extemporaneous transposition flap for closing two contiguous surgical excision.

PubMed

Boggio, Paolo; Veronese, Federica; Miglino, Benedetta; Graziola, Francesca; Tiberio, Rossana; Colombo, Enrico

2018-08-01

The authors present a surgical procedure to remove two contiguous cutaneous lesions using a single transposition flap and suture line without an evident scar. This method is useful when rhomboid surgical exeresis could not represent the best choice to obtain an optimum aesthetic result.

Effects of insulin and exercise training on FGF21, its receptors and target genes in obesity and type 2 diabetes.

PubMed

Kruse, Rikke; Vienberg, Sara G; Vind, Birgitte F; Andersen, Birgitte; Højlund, Kurt

2017-10-01

Pharmacological doses of FGF21 improve glucose tolerance, lipid metabolism and energy expenditure in rodents. Induced expression and secretion of FGF21 from muscle may increase browning of white adipose tissue (WAT) in a myokine-like manner. Recent studies have reported that insulin and exercise increase FGF21 in plasma. Obesity and type 2 diabetes are potentially FGF21-resistant states, but to what extent FGF21 responses to insulin and exercise training are preserved, and whether FGF21, its receptors and target genes are altered, remains to be established. The effects of insulin during euglycaemic-hyperinsulinaemic clamps and 10 week endurance training on serum FGF21 were examined in individuals with type 2 diabetes and in glucose tolerant overweight/obese and lean individuals. Gene expression of FGF21, its receptors and target genes in muscle and WAT biopsies was evaluated by quantitative real-time PCR (qPCR). Insulin increased serum and muscle FGF21 independent of overweight/obesity or type 2 diabetes, and there were no effects associated with exercise training. The insulin-induced increases in serum FGF21 and muscle FGF21 expression correlated tightly (p < 0.001). In WAT, overweight/obesity with and without type 2 diabetes led to reduced expression of KLB, but increased FGFR1c expression. However, the expression of most FGF21 target genes was unaltered except for reduced CIDEA expression in individuals with type 2 diabetes. Insulin-induced expression of muscle FGF21 correlates strongly with a rise in serum FGF21, and this response appears intact in overweight/obesity and type 2 diabetes. FGF21 resistance may involve reduced KLB expression in WAT. However, increased FGFR1c expression or other mechanisms seem to ensure adequate expression of most FGF21 target genes in WAT.

Cloning of the cDNA for a human homologue of the Drosophila white gene and mapping to chromosome 21q22.3

DOE Office of Scientific and Technical Information (OSTI.GOV)

Haiming Chen; Lalioti, M.D.; Perrin, G.

1996-07-01

In an effort to contribute to the transcript map of human chromosome 21 and the understanding of the pathophysiology of trisomy 21, we have used exon trapping to identify fragments of chromosome 21 genes. Two trapped exons, from pools of chromosome 21-specific cosmids, showed homology to the Drosophila white (w) gene. We subsequently cloned the corresponding cDNA for a human homologue of the Drosophila w gene (hW) from human retina and fetal brain cDNA libraries. The gene belongs to the ATP-binding cassette transporter gene family and is homologous to Drosophila w (and to 2 genes from other species) and tomore » a lesser extent to Drosophila brown (bw) and scarlet (st) genes that are all involved in the transport of eye pigment precursor molecules. A DNA polymorphism with 62% heterozygosity due to variation of a poly (T) region in the 3{prime} UTR of the hW has been identified and used for the incorporation of this gene to the genetic map of chromosome 21. The hW is located at 21q22.3 between DNA markers D21S212 and D21S49 in a P1 clone that also contains marker BCEI. The gene is expressed at various levels in many human tissues. The contributions of this gene to the Down syndrome phenotypes, to human eye color, and to the resulting phenotypes of null or missense mutations are presently unknown. 56 refs., 8 figs., 1 tab.« less

Relevance of miR-21 in regulation of tumor suppressor gene PTEN in human cervical cancer cells.

PubMed

Peralta-Zaragoza, Oscar; Deas, Jessica; Meneses-Acosta, Angélica; De la O-Gómez, Faustino; Fernández-Tilapa, Gloria; Gómez-Cerón, Claudia; Benítez-Boijseauneau, Odelia; Burguete-García, Ana; Torres-Poveda, Kirvis; Bermúdez-Morales, Victor Hugo; Madrid-Marina, Vicente; Rodríguez-Dorantes, Mauricio; Hidalgo-Miranda, Alfredo; Pérez-Plasencia, Carlos

2016-03-14

Expression of the microRNA miR-21 has been found to be altered in almost all types of cancers and it has been classified as an oncogenic microRNA or oncomir. Due to the critical functions of its target proteins in various signaling pathways, miR-21 is an attractive target for genetic and pharmacological modulation in various cancers. Cervical cancer is the second most common cause of death from cancer in women worldwide and persistent HPV infection is the main etiologic agent. This malignancy merits special attention for the development of new treatment strategies. In the present study we analyze the role of miR-21 in cervical cancer cells. To identify the downstream cellular target genes of upstream miR-21, we silenced endogenous miR-21 expression in a cervical intraepithelial neoplasia-derived cell lines using siRNAs. The effect of miR-21 on gene expression was assessed in cervical cancer cells transfected with the siRNA expression plasmid pSIMIR21. We identified the tumor suppressor gene PTEN as a target of miR-21 and determined the mechanism of its regulation throughout reporter construct plasmids. Using this model, we analyzed the expression of miR-21 and PTEN as well as functional effects such as autophagy and apoptosis induction. In SiHa cells, there was an inverse correlation between miR-21 expression and PTEN mRNA level as well as PTEN protein expression in cervical cancer cells. Transfection with the pSIMIR21 plasmid increased luciferase reporter activity in construct plasmids containing the PTEN-3'-UTR microRNA response elements MRE21-1 and MRE21-2. The role of miR-21 in cell proliferation was also analyzed in SiHa and HeLa cells transfected with the pSIMIR21 plasmid, and tumor cells exhibited markedly reduced cell proliferation along with autophagy and apoptosis induction. We conclude that miR-21 post-transcriptionally down-regulates the expression of PTEN to promote cell proliferation and cervical cancer cell survival. Therefore, it may be a potential

Demonstration of a novel Xp22.2 microdeletion as the cause of familial extreme skewing of X-inactivation utilizing case-parent trio SNP microarray analysis.

PubMed

Mason, Jane A; Aung, Hnin T; Nandini, Adayapalam; Woods, Rickie G; Fairbairn, David J; Rowell, John A; Young, David; Susman, Rachel D; Brown, Simon A; Hyland, Valentine J; Robertson, Jeremy D

2018-05-01

We report a kindred referred for molecular investigation of severe hemophilia A in a young female in which extremely skewed X-inactivation was observed in both the proband and her clinically normal mother. Bidirectional Sanger sequencing of all F8 gene coding regions and exon/intron boundaries was undertaken. Methylation-sensitive restriction enzymes were utilized to investigate skewed X-inactivation using both a classical human androgen receptor (HUMARA) assay, and a novel method targeting differential methylation patterns in multiple informative X-chromosome SNPs. Illumina Whole-Genome Infinium microarray analysis was performed in the case-parent trio (proband and both parents), and the proband's maternal grandmother. The proband was a cytogenetically normal female with severe hemophilia A resulting from a heterozygous F8 pathogenic variant inherited from her similarly affected father. No F8 mutation was identified in the proband's mother, however, both the proband and her mother both demonstrated completely skewed X-chromosome inactivation (100%) in association with a previously unreported 2.3 Mb deletion at Xp22.2. At least three disease-associated genes (FANCB, AP1S2, and PIGA) were contained within the deleted region. We hypothesize that true "extreme" skewing of X-inactivation (≥95%) is a rare occurrence, but when defined correctly there is a high probability of finding an X-chromosome disease-causing variant or larger deletion resulting in X-inactivation through a survival disadvantage or cell lethal mechanism. We postulate that the 2.3 Mb Xp22.2 deletion identified in our kindred arose de novo in the proband's mother (on the grandfather's homolog), and produced extreme skewing of X-inactivation via a "cell lethal" mechanism. We introduce a novel multitarget approach for X-inactivation analysis using multiple informative differentially methylated SNPs, as an alternative to the classical single locus (HUMARA) method. We propose that for females with

Alterations in Hepatic FGF21, Co-Regulated Genes, and Upstream Metabolic Genes in Response to Nutrition, Ketosis and Inflammation in Peripartal Holstein Cows

PubMed Central

Akbar, Haji; Batistel, Fernanda; Drackley, James K.; Loor, Juan J.

2015-01-01

In rodents, fibroblast growth factor 21 (FGF21) has emerged as a key metabolic regulator produced by liver. To gather preliminary data on the potential importance of FGF1, co-regulated genes, and upstream metabolic genes, we examined the hepatic mRNA expression in response to nutrition and inflammation in dairy cows. In experiment 1, induction of ketosis through feed restriction on d 5 postpartum upregulated FGF21, its co-receptor KLB, and PPARA but only elicited a numerical increase in serum FGF21 concentration. In experiment 2, cows in control (CON) or receiving 50 g/d of L-carnitine (C50) from -14 through 21 d had increased FGF21, PPARA, and NFIL3 on d 10 compared with d 2 postpartum. In contrast, compared with CON and C50, 100 g/d L-carnitine (C100) resulted in lower FGF21, KLB, ANGPTL4, and ARNTL expression on d 10. In experiment 3, cows were fed during the dry period either a higher-energy (OVE; 1.62 Mcal/kg DM) or lower-energy (CON; 1.34 Mcal/kg DM) diet and received 0 (OVE:N, CON:N) or 200 μg of LPS (OVE:Y, CON:Y) into the mammary gland at d 7 postpartum. For FGF21 mRNA expression in CON, the LPS challenge (CON:Y) prevented a decrease in expression between d 7 and 14 postpartum such that cows in CON:N had a 4-fold lower expression on d 14 compared with d 7. The inflammatory stimulus induced by LPS in CON:Y resulted in upregulation of PPARA on d 14 to a similar level as cows in OVE:N. In OVE:Y, expression of PPARA was lower than CON:N on d 7 and remained unchanged on d 14. On d 7, LPS led to a 4-fold greater serum FGF21 only in OVE but not in CON cows. In fact, OVE:Y reached the same serum FGF21 concentration as CON:N, suggesting a carryover effect of dietary energy level on signaling mechanisms within liver. Overall, results indicate that nutrition, ketosis, and inflammation during the peripartal period can alter hepatic FGF21, co-regulated genes, and upstream metabolic genes to various extents. The functional outcome of these changes merits further study

Alterations in Hepatic FGF21, Co-Regulated Genes, and Upstream Metabolic Genes in Response to Nutrition, Ketosis and Inflammation in Peripartal Holstein Cows.

PubMed

Akbar, Haji; Batistel, Fernanda; Drackley, James K; Loor, Juan J

2015-01-01

In rodents, fibroblast growth factor 21 (FGF21) has emerged as a key metabolic regulator produced by liver. To gather preliminary data on the potential importance of FGF1, co-regulated genes, and upstream metabolic genes, we examined the hepatic mRNA expression in response to nutrition and inflammation in dairy cows. In experiment 1, induction of ketosis through feed restriction on d 5 postpartum upregulated FGF21, its co-receptor KLB, and PPARA but only elicited a numerical increase in serum FGF21 concentration. In experiment 2, cows in control (CON) or receiving 50 g/d of L-carnitine (C50) from -14 through 21 d had increased FGF21, PPARA, and NFIL3 on d 10 compared with d 2 postpartum. In contrast, compared with CON and C50, 100 g/d L-carnitine (C100) resulted in lower FGF21, KLB, ANGPTL4, and ARNTL expression on d 10. In experiment 3, cows were fed during the dry period either a higher-energy (OVE; 1.62 Mcal/kg DM) or lower-energy (CON; 1.34 Mcal/kg DM) diet and received 0 (OVE:N, CON:N) or 200 μg of LPS (OVE:Y, CON:Y) into the mammary gland at d 7 postpartum. For FGF21 mRNA expression in CON, the LPS challenge (CON:Y) prevented a decrease in expression between d 7 and 14 postpartum such that cows in CON:N had a 4-fold lower expression on d 14 compared with d 7. The inflammatory stimulus induced by LPS in CON:Y resulted in upregulation of PPARA on d 14 to a similar level as cows in OVE:N. In OVE:Y, expression of PPARA was lower than CON:N on d 7 and remained unchanged on d 14. On d 7, LPS led to a 4-fold greater serum FGF21 only in OVE but not in CON cows. In fact, OVE:Y reached the same serum FGF21 concentration as CON:N, suggesting a carryover effect of dietary energy level on signaling mechanisms within liver. Overall, results indicate that nutrition, ketosis, and inflammation during the peripartal period can alter hepatic FGF21, co-regulated genes, and upstream metabolic genes to various extents. The functional outcome of these changes merits further study

40 CFR 408.120 - Applicability; description of the Southern non-breaded shrimp processing in the contiguous States...

Code of Federal Regulations, 2010 CFR

2010-07-01

... Southern non-breaded shrimp processing in the contiguous States subcategory. 408.120 Section 408.120... CANNED AND PRESERVED SEAFOOD PROCESSING POINT SOURCE CATEGORY Southern Non-Breaded Shrimp Processing in... shrimp processing in the contiguous States subcategory. The provisions of this subpart are applicable to...

40 CFR 408.120 - Applicability; description of the Southern non-breaded shrimp processing in the contiguous States...

Code of Federal Regulations, 2011 CFR

2011-07-01

... Southern non-breaded shrimp processing in the contiguous States subcategory. 408.120 Section 408.120... CANNED AND PRESERVED SEAFOOD PROCESSING POINT SOURCE CATEGORY Southern Non-Breaded Shrimp Processing in... shrimp processing in the contiguous States subcategory. The provisions of this subpart are applicable to...

MI-ANFIS: A Multiple Instance Adaptive Neuro-Fuzzy Inference System

DTIC Science & Technology

2015-08-02

AUTHORS 7. PERFORMING ORGANIZATION NAMES AND ADDRESSES 15. SUBJECT TERMS b. ABSTRACT 2 . REPORT TYPE 17. LIMITATION OF ABSTRACT 15. NUMBER OF...fuzzy logic can deal with the uncertainty of human cognition [ 2 ]. ANFIS offers an alternative to rules’ identification. While Mamdani [3] and Sugeno [4...dimensional vector with elements xpjk corresponding to features, i.e., Bp =  xp11 xp12 . . . xp1D xp21 xp22 . . . xp2D ... ... . . . ... xpMp1

Double separate versus contiguous pituitary adenomas: MRI features and endocrinological follow up.

PubMed

Roberts, Sammie; Borges, Manuel Thomas; Lillehei, Kevin O; Kleinschmidt-DeMasters, B K

2016-10-01

Double pituitary adenomas are defined as two adenomas within a gland. These have distinct light microscopic and immunohistochemical features and may be clearly-separate or contiguous. Most reports have focused on the various hormonal combinations in double tumors rather than on any potential increased risk for residual mass or endocrinopathy. Departmental files were searched to identify all double adenomas from 1/1/2000 to 3/1/2016, with review of magnetic resonance imaging (MRI) to determine if the dual nature of the lesions could be discerned retrospectively after histologic diagnosis of double adenoma. All cases were immunostained for standard anterior pituitary hormones. Eight cases were identified: 2 follicle-stimulating hormone (FSH)/alpha subunit (ASU) + prolactinoma (PRL); 1 PRL + corticotroph (ACTH); 1 hormone-negative + PRL; 1 ACTH + ASU/growth hormone (GH)/PRL; 1 GH/PR + PRL; 1 FSH/ASU, + ACTH; 1 GH + luteinizing hormone (LH). One patient had clearly-separate lesions identified preoperatively and required two surgical procedures for gross total resection. A second patient had 2 lesions recognized at surgery and afterwards on retrospective neuroimaging. The remaining 6 patients had double adenomas discovered at the time of histologic examination that were not resolvable at surgery or on retrospective neuroimaging. Four patients, 2 with clearly-separate and 2 with contiguous double adenomas, had persistent MRI abnormalities, and one had continued endocrine abnormalities. Double contiguous pituitary adenomas are difficult to anticipate preoperatively or to resolve intraoperatively. Although double contiguous adenomas are much more common than double separate lesions, both have a risk for subtotal resection and, thus, residual mass and/or endocrinopathy may ensue.

A novel nonsense mutation in the NDP gene in a Chinese family with Norrie disease.

PubMed

Liu, Deyuan; Hu, Zhengmao; Peng, Yu; Yu, Changhong; Liu, Yalan; Mo, Xiaoyun; Li, Xiaoping; Lu, Lina; Xu, Xiaojuan; Su, Wei; Pan, Qian; Xia, Kun

2010-12-08

Norrie disease (ND), a rare X-linked recessive disorder, is characterized by congenital blindness and, occasionally, mental retardation and hearing loss. ND is caused by the Norrie Disease Protein gene (NDP), which codes for norrin, a cysteine-rich protein involved in ocular vascular development. Here, we report a novel mutation of NDP that was identified in a Chinese family in which three members displayed typical ND symptoms and other complex phenotypes, such as cerebellar atrophy, motor disorders, and mental disorders. We conducted an extensive clinical examination of the proband and performed a computed tomography (CT) scan of his brain. Additionally, we performed ophthalmic examinations, haplotype analyses, and NDP DNA sequencing for 26 individuals from the proband's extended family. The proband's computed tomography scan, in which the fifth ventricle could be observed, indicated cerebellar atrophy. Genome scans and haplotype analyses traced the disease to chromosome Xp21.1-p11.22. Mutation screening of the NDP gene identified a novel nonsense mutation, c.343C>T, in this region. Although recent research has shown that multiple different mutations can be responsible for the ND phenotype, additional research is needed to understand the mechanism responsible for the diverse phenotypes caused by mutations in the NDP gene.

The complete sequence and promoter activity of the human A-raf-1 gene (ARAF1)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, J.E.; Beck, T.W.; Brennscheidt, U.

1994-03-01

The raf proto-oncogenes encode cytoplasmic protein serine/threonine kinases, which play a critical role in cell growth and development. One of these, A-raf-1 (human gene symbol, ARAF1), which is predominantly expressed in mouse urogenital tissues, has been mapped to an evolutionarily conserved linkage group composed of ARAF1, SYN1, TIMP, and properdin located at human chromosome Xp11.2. The authors have isolated human genomic DNA clones containing the expressed gene (ARAF1) on the X chromosome and a pseudogene (ARAF2) on chromosome 7p12-q11.21. Analysis of the nucleotide sequence from the ARAF1 genomic clones demonstrated that it consists of 16 exons encoded by minimally 10,776more » nucleotides. The major transcriptional start site (+1) was determined by RNase protection and primer extension assays. Promoter activity was confirmed by functional assays using DNA fragments fused to a CAT reporter gene. The ARAF1 minimal promoter, located between nucleotides -59 and +93, has a low G + C content and lacks consensus TATA and Inr sequences but shows sequence similarity at position -1 to the E box that is known to interact with USF and TFII-I transcription factors. 65 refs., 7 figs., 1 tab.« less

A novel nonsense mutation in the NDP gene in a Chinese family with Norrie disease

PubMed Central

Liu, Deyuan; Hu, Zhengmao; Peng, Yu; Yu, Changhong; Liu, Yalan; Mo, Xiaoyun; Li, Xiaoping; Lu, Lina; Xu, Xiaojuan; Su, Wei; Pan, Qian

2010-01-01

Purpose Norrie disease (ND), a rare X-linked recessive disorder, is characterized by congenital blindness and, occasionally, mental retardation and hearing loss. ND is caused by the Norrie Disease Protein gene (NDP), which codes for norrin, a cysteine-rich protein involved in ocular vascular development. Here, we report a novel mutation of NDP that was identified in a Chinese family in which three members displayed typical ND symptoms and other complex phenotypes, such as cerebellar atrophy, motor disorders, and mental disorders. Methods We conducted an extensive clinical examination of the proband and performed a computed tomography (CT) scan of his brain. Additionally, we performed ophthalmic examinations, haplotype analyses, and NDP DNA sequencing for 26 individuals from the proband’s extended family. Results The proband’s computed tomography scan, in which the fifth ventricle could be observed, indicated cerebellar atrophy. Genome scans and haplotype analyses traced the disease to chromosome Xp21.1-p11.22. Mutation screening of the NDP gene identified a novel nonsense mutation, c.343C>T, in this region. Conclusions Although recent research has shown that multiple different mutations can be responsible for the ND phenotype, additional research is needed to understand the mechanism responsible for the diverse phenotypes caused by mutations in the NDP gene. PMID:21179243

Complementation of DNA repair defect in xeroderma pigmentosum cells of group C by the transfer of human chromosome 5

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kaur, G.P.; Athwal, R.S.

1993-01-01

Complementation of DNA excision repair defect in xeroderma pigmentosum cells of group C (XP-C) has been achieved by the transfer of human chromosome 5. Individual human chromosomes tagged with a selectable marker were transferred to XP-C cells by microcell fusion from mouse-human hybrid cell lines each bearing a single different human chromosome. Analysis of the chromosome transfer clones revealed that introduction of chromosome 5 into XP-C cells corrected the DNA repair defect as well as UV-sensitive phenotypes, while chromosomes 2, 6, 7, 9, 13, 15, 17, and 21 failed to complement. The introduced chromosome 5 in complemented UV[sup r] clonesmore » was distinguished from the parental XP-C chromosomes by polymorphism for dinucleotide (CA)[sub n] repeats at two loci, D5S117 and D5S209. In addition, an intact marked chromosome 5 was rescued into mouse cells from a complemented UV[sup r] clone by microcell fusion. Five subclones of a complemented clone that had lost the marked chromosome 5 exhibited UV-sensitive and repair-deficient phenotypes identical to parental XP-C cells. Concordant loss of the transferred chromosome and reappearance of XP-C phenotype further confirmed the presence of a DNA repair gene on human chromosome 5. 38 refs., 7 figs., 1 tab.« less

Hypermutation in shark immunoglobulin light chain genes results in contiguous substitutions.

PubMed

Lee, Susan S; Tranchina, Daniel; Ohta, Yuko; Flajnik, Martin F; Hsu, Ellen

2002-04-01

Among 631 substitutions present in 90 nurse shark immunoglobulin light chain somatic mutants, 338 constitute 2-4 bp stretches of adjacent changes. An absence of mutations in perinatal sequences and the bias for one mutating V gene in adults suggest that the diversification is antigen dependent. The substitutions shared no patterns, and the absence of donor sequences, including from family members, supports the idea that most changes arose from nontemplated mutation. The tandem mutations as a group are distinguished by consistently fewer transition changes and an A bias. We suggest this is one of several pathways of hypermutation diversifying shark antigen-receptor genes--point mutations, tandem mutations, and mutations with a G-C preference--that coevolved with or preceded gene rearrangement.

High-density array-CGH with targeted NGS unmask multiple noncontiguous minute deletions on chromosome 3p21 in mesothelioma.

PubMed

Yoshikawa, Yoshie; Emi, Mitsuru; Hashimoto-Tamaoki, Tomoko; Ohmuraya, Masaki; Sato, Ayuko; Tsujimura, Tohru; Hasegawa, Seiki; Nakano, Takashi; Nasu, Masaki; Pastorino, Sandra; Szymiczek, Agata; Bononi, Angela; Tanji, Mika; Pagano, Ian; Gaudino, Giovanni; Napolitano, Andrea; Goparaju, Chandra; Pass, Harvey I; Yang, Haining; Carbone, Michele

2016-11-22

We used a custom-made comparative genomic hybridization array (aCGH; average probe interval 254 bp) to screen 33 malignant mesothelioma (MM) biopsies for somatic copy number loss throughout the 3p21 region (10.7 Mb) that harbors 251 genes, including BRCA1 (breast cancer 1)-associated protein 1 (BAP1), the most commonly mutated gene in MM. We identified frequent minute biallelic deletions (<3 kb) in 46 of 251 genes: four were cancer-associated genes: SETD2 (SET domain-containing protein 2) (7 of 33), BAP1 (8 of 33), PBRM1 (polybromo 1) (3 of 33), and SMARCC1 (switch/sucrose nonfermentable- SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily c, member 1) (2 of 33). These four genes were further investigated by targeted next-generation sequencing (tNGS), which revealed sequence-level mutations causing biallelic inactivation. Combined high-density aCGH and tNGS revealed biallelic gene inactivation in SETD2 (9 of 33, 27%), BAP1 (16 of 33, 48%), PBRM1 (5 of 33, 15%), and SMARCC1 (2 of 33, 6%). The incidence of genetic alterations detected is much higher than reported in the literature because minute deletions are not detected by NGS or commercial aCGH. Many of these minute deletions were not contiguous, but rather alternated with segments showing oscillating copy number changes along the 3p21 region. In summary, we found that in MM: (i) multiple minute simultaneous biallelic deletions are frequent in chromosome 3p21, where they occur as distinct events involving multiple genes; (ii) in addition to BAP1, mutations of SETD2, PBRM1, and SMARCC1 are frequent in MM; and (iii) our results suggest that high-density aCGH combined with tNGS provides a more precise estimate of the frequency and types of genes inactivated in human cancer than approaches based exclusively on NGS strategy.

The first missense mutation of NHS gene in a Tunisian family with clinical features of NHS syndrome including cardiac anomaly

PubMed Central

Chograni, Manèl; Rejeb, Imen; Jemaa, Lamia Ben; Châabouni, Myriam; Bouhamed, Habiba Chaabouni

2011-01-01

Nance-Horan Syndrome (NHS) or X-linked cataract-dental syndrome is a disease of unknown gene action mechanism, characterized by congenital cataract, dental anomalies, dysmorphic features and, in some cases, mental retardation. We performed linkage analysis in a Tunisian family with NHS in which affected males and obligate carrier female share a common haplotype in the Xp22.32-p11.21 region that contains the NHS gene. Direct sequencing of NHS coding exons and flanking intronic sequences allowed us to identify the first missense mutation (P551S) and a reported SNP-polymorphism (L1319F) in exon 6, a reported UTR–SNP (c.7422 C>T) and a novel one (c.8239 T>A) in exon 8. Both variations P551S and c.8239 T>A segregate with NHS phenotype in this family. Although truncations, frame-shift and copy number variants have been reported in this gene, no missense mutations have been found to segregate previously. This is the first report of a missense NHS mutation causing NHS phenotype (including cardiac defects). We hypothesize also that the non-reported UTR–SNP of the exon 8 (3′-UTR) is specific to the Tunisian population. PMID:21559051

The first missense mutation of NHS gene in a Tunisian family with clinical features of NHS syndrome including cardiac anomaly.

PubMed

Chograni, Manèl; Rejeb, Imen; Jemaa, Lamia Ben; Châabouni, Myriam; Bouhamed, Habiba Chaabouni

2011-08-01

Nance-Horan Syndrome (NHS) or X-linked cataract-dental syndrome is a disease of unknown gene action mechanism, characterized by congenital cataract, dental anomalies, dysmorphic features and, in some cases, mental retardation. We performed linkage analysis in a Tunisian family with NHS in which affected males and obligate carrier female share a common haplotype in the Xp22.32-p11.21 region that contains the NHS gene. Direct sequencing of NHS coding exons and flanking intronic sequences allowed us to identify the first missense mutation (P551S) and a reported SNP-polymorphism (L1319F) in exon 6, a reported UTR-SNP (c.7422 C>T) and a novel one (c.8239 T>A) in exon 8. Both variations P551S and c.8239 T>A segregate with NHS phenotype in this family. Although truncations, frame-shift and copy number variants have been reported in this gene, no missense mutations have been found to segregate previously. This is the first report of a missense NHS mutation causing NHS phenotype (including cardiac defects). We hypothesize also that the non-reported UTR-SNP of the exon 8 (3'-UTR) is specific to the Tunisian population.

Does the Fuhrman or World Health Organization/International Society of Urological Pathology Grading System Apply to the Xp11.2 Translocation Renal Cell Carcinoma?: A 10-Year Single-Center Study.

PubMed

Liu, Ning; Gan, Weidong; Qu, Feng; Wang, Zhen; Zhuang, Wenyuan; Agizamhan, Sezim; Xu, Linfeng; Yin, Juanjuan; Guo, Hongqian; Li, Dongmei

2018-04-01

The Fuhrman and World Health Organization/International Society of Urological Pathology (WHO/ISUP) grading systems are widely used to predict survival for patients with conventional renal cell carcinoma. To determine the validity of nuclear grading systems (both the Fuhrman and the WHO/ISUP) and the individual components of the Fuhrman grading system in predicting the prognosis of Xp11.2 translocation renal cell carcinoma (Xp11.2 tRCC), we identified and followed up 47 patients with Xp11.2 tRCC in our center from January 2007 to June 2017. The Fuhrman and WHO/ISUP grading was reassigned by two pathologists. Nuclear size and shape were determined for each case based on the greatest degree of nuclear pleomorphism using image analysis software. Univariate and multivariate analyses were performed to evaluate the capacity of the grading systems and nuclear parameters to predict overall survival and progression-free survival. On univariate Cox regression analysis, the parameters of nuclear size were associated significantly with overall survival and progression-free survival, whereas the grading systems and the parameters of nuclear shape failed to reach a significant correlation. On multivariate analysis, however, none of the parameters was associated independently with survival. Our findings indicate that neither the Fuhrman nor the WHO/ISUP grading system is applicable to Xp11.2 tRCC. The assessment of nuclear size instead may be novel outcome predictors for patients with Xp11.2 tRCC. Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Cloning and sequencing of a gene encoding a 21-kilodalton outer membrane protein from Bordetella avium and expression of the gene in Salmonella typhimurium.

PubMed Central

Gentry-Weeks, C R; Hultsch, A L; Kelly, S M; Keith, J M; Curtiss, R

1992-01-01

Three gene libraries of Bordetella avium 197 DNA were prepared in Escherichia coli LE392 by using the cosmid vectors pCP13 and pYA2329, a derivative of pCP13 specifying spectinomycin resistance. The cosmid libraries were screened with convalescent-phase anti-B. avium turkey sera and polyclonal rabbit antisera against B. avium 197 outer membrane proteins. One E. coli recombinant clone produced a 56-kDa protein which reacted with convalescent-phase serum from a turkey infected with B. avium 197. In addition, five E. coli recombinant clones were identified which produced B. avium outer membrane proteins with molecular masses of 21, 38, 40, 43, and 48 kDa. At least one of these E. coli clones, which encoded the 21-kDa protein, reacted with both convalescent-phase turkey sera and antibody against B. avium 197 outer membrane proteins. The gene for the 21-kDa outer membrane protein was localized by Tn5seq1 mutagenesis, and the nucleotide sequence was determined by dideoxy sequencing. DNA sequence analysis of the 21-kDa protein revealed an open reading frame of 582 bases that resulted in a predicted protein of 194 amino acids. Comparison of the predicted amino acid sequence of the gene encoding the 21-kDa outer membrane protein with protein sequences in the National Biomedical Research Foundation protein sequence data base indicated significant homology to the OmpA proteins of Shigella dysenteriae, Enterobacter aerogenes, E. coli, and Salmonella typhimurium and to Neisseria gonorrhoeae outer membrane protein III, Haemophilus influenzae protein P6, and Pseudomonas aeruginosa porin protein F. The gene (ompA) encoding the B. avium 21-kDa protein hybridized with 4.1-kb DNA fragments from EcoRI-digested, chromosomal DNA of Bordetella pertussis and Bordetella bronchiseptica and with 6.0- and 3.2-kb DNA fragments from EcoRI-digested, chromosomal DNA of B. avium and B. avium-like DNA, respectively. A 6.75-kb DNA fragment encoding the B. avium 21-kDa protein was subcloned into the

Genome-wide DNA methylation analysis reveals estrogen-mediated epigenetic repression of metallothionein-1 gene cluster in breast cancer.

PubMed

Jadhav, Rohit R; Ye, Zhenqing; Huang, Rui-Lan; Liu, Joseph; Hsu, Pei-Yin; Huang, Yi-Wen; Rangel, Leticia B; Lai, Hung-Cheng; Roa, Juan Carlos; Kirma, Nameer B; Huang, Tim Hui-Ming; Jin, Victor X

2015-01-01

Recent genome-wide analysis has shown that DNA methylation spans long stretches of chromosome regions consisting of clusters of contiguous CpG islands or gene families. Hypermethylation of various gene clusters has been reported in many types of cancer. In this study, we conducted methyl-binding domain capture (MBDCap) sequencing (MBD-seq) analysis on a breast cancer cohort consisting of 77 patients and 10 normal controls, as well as a panel of 38 breast cancer cell lines. Bioinformatics analysis determined seven gene clusters with a significant difference in overall survival (OS) and further revealed a distinct feature that the conservation of a large gene cluster (approximately 70 kb) metallothionein-1 (MT1) among 45 species is much lower than the average of all RefSeq genes. Furthermore, we found that DNA methylation is an important epigenetic regulator contributing to gene repression of MT1 gene cluster in both ERα positive (ERα+) and ERα negative (ERα-) breast tumors. In silico analysis revealed much lower gene expression of this cluster in The Cancer Genome Atlas (TCGA) cohort for ERα + tumors. To further investigate the role of estrogen, we conducted 17β-estradiol (E2) and demethylating agent 5-aza-2'-deoxycytidine (DAC) treatment in various breast cancer cell types. Cell proliferation and invasion assays suggested MT1F and MT1M may play an anti-oncogenic role in breast cancer. Our data suggests that DNA methylation in large contiguous gene clusters can be potential prognostic markers of breast cancer. Further investigation of these clusters revealed that estrogen mediates epigenetic repression of MT1 cluster in ERα + breast cancer cell lines. In all, our studies identify thousands of breast tumor hypermethylated regions for the first time, in particular, discovering seven large contiguous hypermethylated gene clusters.

Wheat-specific gene, ribosomal protein l21, used as the endogenous reference gene for qualitative and real-time quantitative polymerase chain reaction detection of transgenes.

PubMed

Liu, Yi-Ke; Li, He-Ping; Huang, Tao; Cheng, Wei; Gao, Chun-Sheng; Zuo, Dong-Yun; Zhao, Zheng-Xi; Liao, Yu-Cai

2014-10-29

Wheat-specific ribosomal protein L21 (RPL21) is an endogenous reference gene suitable for genetically modified (GM) wheat identification. This taxon-specific RPL21 sequence displayed high homogeneity in different wheat varieties. Southern blots revealed 1 or 3 copies, and sequence analyses showed one amplicon in common wheat. Combined analyses with sequences from common wheat (AABBDD) and three diploid ancestral species, Triticum urartu (AA), Aegilops speltoides (BB), and Aegilops tauschii (DD), demonstrated the presence of this amplicon in the AA genome. Using conventional qualitative polymerase chain reaction (PCR), the limit of detection was 2 copies of wheat haploid genome per reaction. In the quantitative real-time PCR assay, limits of detection and quantification were about 2 and 8 haploid genome copies, respectively, the latter of which is 2.5-4-fold lower than other reported wheat endogenous reference genes. Construct-specific PCR assays were developed using RPL21 as an endogenous reference gene, and as little as 0.5% of GM wheat contents containing Arabidopsis NPR1 were properly quantified.

13 CFR 123.600 - Are economic injury disaster loans under this subpart limited to the geographic areas contiguous...

Code of Federal Regulations, 2010 CFR

2010-01-01

... the declared disaster areas and the contiguous geographic areas to small business concerns that have... under this subpart limited to the geographic areas contiguous to the declared disaster areas? 123.600 Section 123.600 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION DISASTER LOAN PROGRAM...

Cyclic fatigue resistance of XP-endo Shaper compared with different nickel-titanium alloy instruments.

PubMed

Elnaghy, Amr; Elsaka, Shaymaa

2018-04-01

The aims of this study were to assess and compare the resistance to cyclic fatigue of XP-endo Shaper (XPS; FKG Dentaire, La Chaux-de-Fonds, Switzerland) instruments with TRUShape (TRS; Dentsply Tulsa Dental Specialties, Tulsa, OK, USA), HyFlex CM (HCM; Coltene, Cuyahoga Falls, OH, USA), Vortex Blue (VB; Dentsply Tulsa Dental Specialties), and iRace (iR; FKG Dentaire) nickel-titanium rotary instruments at body temperature. Size 30, 0.01 taper of XPS, size 30, 0.04 taper of HCM, VB, iR, and size 30, 0.06 taper of TRS instruments were immersed in saline at 37 ± 1 °C during cyclic fatigue testing. The instruments were tested with 60° angle of curvature and a 3-mm radius of curvature. The number of cycles to failure (NCF) was calculated and the length of the fractured segment was measured. Fractographic examination of the fractured surface was performed using a scanning electron microscope. The data were analyzed statistically using Kruskal-Wallis H test and Mann-Whitney U tests. Statistical significance was set at P < 0.05. XPS had a significantly greater NCF compared with the other instruments (P < 0.001). The topographic appearance of the fracture surfaces of tested instruments revealed ductile fracture of cyclic fatigue failure. XPS instruments exhibited greater cyclic fatigue resistance compared with the other tested instruments. XP-endo Shaper instruments could be used more safely in curved canals due to their higher fatigue resistance.

Novel gene fusion of PRCC-MITF defines a new member of MiT family translocation renal cell carcinoma: clinicopathological analysis and detection of the gene fusion by RNA sequencing and FISH.

PubMed

Xia, Qiu-Yuan; Wang, Xiao-Tong; Ye, Sheng-Bing; Wang, Xuan; Li, Rui; Shi, Shan-Shan; Fang, Ru; Zhang, Ru-Song; Ma, Heng-Hui; Lu, Zhen-Feng; Shen, Qin; Bao, Wei; Zhou, Xiao-Jun; Rao, Qiu

2018-04-01

MITF, TFE3, TFEB and TFEC belong to the same microphthalmia-associated transcription factor family (MiT). Two transcription factors in this family have been identified in two unusual types of renal cell carcinoma (RCC): Xp11 translocation RCC harbouring TFE3 gene fusions and t(6;11) RCC harbouring a MALAT1-TFEB gene fusion. The 2016 World Health Organisation classification of renal neoplasia grouped these two neoplasms together under the category of MiT family translocation RCC. RCCs associated with the other two MiT family members, MITF and TFEC, have rarely been reported. Herein, we identify a case of MITF translocation RCC with the novel PRCC-MITF gene fusion by RNA sequencing. Histological examination of the present tumour showed typical features of MiT family translocation RCCs, overlapping with Xp11 translocation RCC and t(6;11) RCC. However, this tumour showed negative results in TFE3 and TFEB immunochemistry and split fluorescence in-situ hybridisation (FISH) assays. The other MiT family members, MITF and TFEC, were tested further immunochemically and also showed negative results. RNA sequencing and reverse transcription-polymerase chain reaction confirmed the presence of a PRCC-MITF gene fusion: a fusion of PRCC exon 5 to MITF exon 4. We then developed FISH assays covering MITF break-apart probes and PRCC-MITF fusion probes to detect the MITF gene rearrangement. This study both proves the recurring existence of MITF translocation RCC and expands the genotype spectrum of MiT family translocation RCCs. © 2017 John Wiley & Sons Ltd.

Regulation of Spi 2.1 and 2.2 gene expression after turpentine inflammation: discordant responses to IL-6.

PubMed

Berry, S A; Bergad, P L; Stolz, A M; Towle, H C; Schwarzenberg, S J

1999-06-01

The rat serine protease inhibitor (Spi) 2 gene family includes both positive (Spi 2.2) and negative (Spi 2.1) acute phase reactants, facilitating modeling of regulation of hepatic acute phase response (APR). To examine the role of signal transducer and activation of transcription (STAT) proteins in the divergent regulation of these model genes after induction of APR, we evaluated the proximal promoters of the genes, focusing on STAT binding sites contained in these promoter elements. Induction of APR by turpentine injection includes activation of a STAT3 complex that can bind to a gamma-activated sequence (GAS) in the Spi 2.2 gene promoter, although the Spi 2.2 GAS site can bind STAT1 or STAT5 as well. To create an in vitro model of APR, primary hepatocytes were treated with combinations of cytokines and hormones to mimic the hormonal milieu of the whole animal after APR induction. Incubation of primary rat hepatocytes with interleukin (IL)-6, a critical APR cytokine, leads to activation of STAT3 and a 28-fold induction of a chloramphenicol acetyltransferase reporter construct containing the -319 to +85 region of the Spi 2.2 promoter. This suggests the turpentine-induced increase of Spi 2.2 is mediated primarily by IL-6. In contrast, although turpentine treatment reduces Spi 2.1 mRNA in vivo and IL-6 does not increase Spi 2.1 mRNA in primary rat hepatocytes, treatment of hepatocytes with IL-6 results in a 5. 4-fold induction of Spi 2.1 promoter activity mediated through the paired GAS elements in this promoter. Differential regulation of Spi 2.1 and 2.2 genes is due in part to differences in the promoters of these genes at the GAS sites. IL-6 alone fails to reproduce the pattern of rat Spi 2 gene expression that results from turpentine-induced inflammation.

An investigation of the predictors of photoprotection and UVR dose to the face in patients with XP: a protocol using observational mixed methods.

PubMed

Walburn, Jessica; Sarkany, Robert; Norton, Sam; Foster, Lesley; Morgan, Myfanwy; Sainsbury, Kirby; Araújo-Soares, Vera; Anderson, Rebecca; Garrood, Isabel; Heydenreich, Jakob; Sniehotta, Falko F; Vieira, Rute; Wulf, Hans Christian; Weinman, John

2017-08-21

Xeroderma pigmentosum (XP) is a rare genetic condition caused by defective nucleotide excision repair and characterised by skin cancer, ocular and neurological involvement. Stringent ultraviolet protection is the only way to prevent skin cancer. Despite the risks, some patients' photoprotection is poor, with a potentially devastating impact on their prognosis. The aim of this research is to identify disease-specific and psychosocial predictors of photoprotection behaviour and ultraviolet radiation (UVR) dose to the face. Mixed methods research based on 45 UK patients will involve qualitative interviews to identify individuals' experience of XP and the influences on their photoprotection behaviours and a cross-sectional quantitative survey to assess biopsychosocial correlates of these behaviours at baseline. This will be followed by objective measurement of UVR exposure for 21 days by wrist-worn dosimeter and daily recording of photoprotection behaviours and psychological variables for up to 50 days in the summer months. This novel methodology will enable UVR dose reaching the face to be calculated and analysed as a clinically relevant endpoint. A range of qualitative and quantitative analytical approaches will be used, reflecting the mixed methods (eg, cross-sectional qualitative interviews, n-of-1 studies). Framework analysis will be used to analyse the qualitative interviews; mixed-effects longitudinal models will be used to examine the association of clinical and psychosocial factors with the average daily UVR dose; dynamic logistic regression models will be used to investigate participant-specific psychosocial factors associated with photoprotection behaviours. This research has been approved by Camden and King's Cross Research Ethics Committee 15/LO/1395. The findings will be published in peer-reviewed journals and presented at national and international scientific conferences. © Article author(s) (or their employer(s) unless otherwise stated in the text of

An investigation of the predictors of photoprotection and UVR dose to the face in patients with XP: a protocol using observational mixed methods

PubMed Central

Walburn, Jessica; Sarkany, Robert; Norton, Sam; Foster, Lesley; Morgan, Myfanwy; Sainsbury, Kirby; Araújo-Soares, Vera; Anderson, Rebecca; Garrood, Isabel; Heydenreich, Jakob; Sniehotta, Falko F; Vieira, Rute; Wulf, Hans Christian; Weinman, John

2017-01-01

Introduction Xeroderma pigmentosum (XP) is a rare genetic condition caused by defective nucleotide excision repair and characterised by skin cancer, ocular and neurological involvement. Stringent ultraviolet protection is the only way to prevent skin cancer. Despite the risks, some patients’ photoprotection is poor, with a potentially devastating impact on their prognosis. The aim of this research is to identify disease-specific and psychosocial predictors of photoprotection behaviour and ultraviolet radiation (UVR) dose to the face. Methods and analysis Mixed methods research based on 45 UK patients will involve qualitative interviews to identify individuals’ experience of XP and the influences on their photoprotection behaviours and a cross-sectional quantitative survey to assess biopsychosocial correlates of these behaviours at baseline. This will be followed by objective measurement of UVR exposure for 21 days by wrist-worn dosimeter and daily recording of photoprotection behaviours and psychological variables for up to 50 days in the summer months. This novel methodology will enable UVR dose reaching the face to be calculated and analysed as a clinically relevant endpoint. A range of qualitative and quantitative analytical approaches will be used, reflecting the mixed methods (eg, cross-sectional qualitative interviews, n-of-1 studies). Framework analysis will be used to analyse the qualitative interviews; mixed-effects longitudinal models will be used to examine the association of clinical and psychosocial factors with the average daily UVR dose; dynamic logistic regression models will be used to investigate participant-specific psychosocial factors associated with photoprotection behaviours. Ethics and dissemination This research has been approved by Camden and King’s Cross Research Ethics Committee 15/LO/1395. The findings will be published in peer-reviewed journals and presented at national and international scientific conferences. PMID:28827277

Overexpression of Rice Auxilin-Like Protein, XB21, Induces Necrotic Lesions, up-Regulates Endocytosis-Related Genes, and Confers Enhanced Resistance to Xanthomonas oryzae pv. oryzae.

PubMed

Park, Chang-Jin; Wei, Tong; Sharma, Rita; Ronald, Pamela C

2017-12-01

The rice immune receptor XA21 confers resistance to the bacterial pathogen, Xanthomonas oryzae pv. oryzae (Xoo). To elucidate the mechanism of XA21-mediated immunity, we previously performed a yeast two-hybrid screening for XA21 interactors and identified XA21 binding protein 21 (XB21). Here, we report that XB21 is an auxilin-like protein predicted to function in clathrin-mediated endocytosis. We demonstrate an XA21/XB21 in vivo interaction using co-immunoprecipitation in rice. Overexpression of XB21 in rice variety Kitaake and a Kitaake transgenic line expressing XA21 confers a necrotic lesion phenotype and enhances resistance to Xoo. RNA sequencing reveals that XB21 overexpression results in the differential expression of 8735 genes (4939 genes up- and 3846 genes down-regulated) (≥2-folds, FDR ≤0.01). The up-regulated genes include those predicted to be involved in 'cell death' and 'vesicle-mediated transport'. These results indicate that XB21 plays a role in the plant immune response and in regulation of cell death. The up-regulation of genes controlling 'vesicle-mediated transport' in XB21 overexpression lines is consistent with a functional role for XB21 as an auxilin.

Ectopic Expression of Homeobox Gene NKX2-1 in Diffuse Large B-Cell Lymphoma Is Mediated by Aberrant Chromatin Modifications

PubMed Central

Nagel, Stefan; Ehrentraut, Stefan; Tomasch, Jürgen; Quentmeier, Hilmar; Meyer, Corinna; Kaufmann, Maren; Drexler, Hans G.; MacLeod, Roderick A. F.

2013-01-01

Homeobox genes encode transcription factors ubiquitously involved in basic developmental processes, deregulation of which promotes cell transformation in multiple cancers including hematopoietic malignancies. In particular, NKL-family homeobox genes TLX1, TLX3 and NKX2-5 are ectopically activated by chromosomal rearrangements in T-cell neoplasias. Here, using transcriptional microarray profiling and RQ-PCR we identified ectopic expression of NKL-family member NKX2-1, in a diffuse large B-cell lymphoma (DLBCL) cell line SU-DHL-5. Moreover, in silico analysis demonstrated NKX2-1 overexpression in 5% of examined DLBCL patient samples. NKX2-1 is physiologically expressed in lung and thyroid tissues where it regulates differentiation. Chromosomal and genomic analyses excluded rearrangements at the NKX2-1 locus in SU-DHL-5, implying alternative activation. Comparative expression profiling implicated several candidate genes in NKX2-1 regulation, variously encoding transcription factors, chromatin modifiers and signaling components. Accordingly, siRNA-mediated knockdown and overexpression studies confirmed involvement of transcription factor HEY1, histone methyltransferase MLL and ubiquitinated histone H2B in NKX2-1 deregulation. Chromosomal aberrations targeting MLL at 11q23 and the histone gene cluster HIST1 at 6p22 which we observed in SU-DHL-5 may, therefore, represent fundamental mutations mediating an aberrant chromatin structure at NKX2-1. Taken together, we identified ectopic expression of NKX2-1 in DLBCL cells, representing the central player in an oncogenic regulative network compromising B-cell differentiation. Thus, our data extend the paradigm of NKL homeobox gene deregulation in lymphoid malignancies. PMID:23637834

Ectopic expression of homeobox gene NKX2-1 in diffuse large B-cell lymphoma is mediated by aberrant chromatin modifications.

PubMed

Nagel, Stefan; Ehrentraut, Stefan; Tomasch, Jürgen; Quentmeier, Hilmar; Meyer, Corinna; Kaufmann, Maren; Drexler, Hans G; MacLeod, Roderick A F

2013-01-01

Homeobox genes encode transcription factors ubiquitously involved in basic developmental processes, deregulation of which promotes cell transformation in multiple cancers including hematopoietic malignancies. In particular, NKL-family homeobox genes TLX1, TLX3 and NKX2-5 are ectopically activated by chromosomal rearrangements in T-cell neoplasias. Here, using transcriptional microarray profiling and RQ-PCR we identified ectopic expression of NKL-family member NKX2-1, in a diffuse large B-cell lymphoma (DLBCL) cell line SU-DHL-5. Moreover, in silico analysis demonstrated NKX2-1 overexpression in 5% of examined DLBCL patient samples. NKX2-1 is physiologically expressed in lung and thyroid tissues where it regulates differentiation. Chromosomal and genomic analyses excluded rearrangements at the NKX2-1 locus in SU-DHL-5, implying alternative activation. Comparative expression profiling implicated several candidate genes in NKX2-1 regulation, variously encoding transcription factors, chromatin modifiers and signaling components. Accordingly, siRNA-mediated knockdown and overexpression studies confirmed involvement of transcription factor HEY1, histone methyltransferase MLL and ubiquitinated histone H2B in NKX2-1 deregulation. Chromosomal aberrations targeting MLL at 11q23 and the histone gene cluster HIST1 at 6p22 which we observed in SU-DHL-5 may, therefore, represent fundamental mutations mediating an aberrant chromatin structure at NKX2-1. Taken together, we identified ectopic expression of NKX2-1 in DLBCL cells, representing the central player in an oncogenic regulative network compromising B-cell differentiation. Thus, our data extend the paradigm of NKL homeobox gene deregulation in lymphoid malignancies.

Cost-effectiveness of the 21-gene breast cancer assay in Mexico.

PubMed

Bargalló-Rocha, Juan Enrique; Lara-Medina, Fernando; Pérez-Sánchez, Victor; Vázquez-Romo, Rafael; Villarreal-Garza, Cynthia; Martínez-Said, Hector; Shaw-Dulin, Robin J; Mohar-Betancourt, Alejandro; Hunt, Barnaby; Plun-Favreau, Juliette; Valentine, William J

2015-03-01

The 21-gene breast cancer assay (Oncotype DX(®); Genomic Health, Inc.) is a validated diagnostic test that predicts the likelihood of adjuvant chemotherapy benefit and 10-year risk of distant recurrence in patients with hormone-receptor-positive, human epidermal growth receptor 2-negative, early-stage breast cancer. The aim of this analysis was to evaluate the cost-effectiveness of using the assay to inform adjuvant chemotherapy decisions in Mexico. A Markov model was developed to make long-term projections of distant recurrence, survival, and direct costs in scenarios using conventional diagnostic procedures or the 21-gene assay to inform adjuvant chemotherapy recommendations. Transition probabilities and risk adjustment were taken from published landmark trials. Costs [2011 Mexican Pesos (MXN)] were estimated from an Instituto Mexicano del Seguro Social perspective. Costs and clinical benefits were discounted at 5% annually. Following assay testing, approximately 66% of patients previously receiving chemotherapy were recommended to receive hormone therapy only after consideration of assay results. Furthermore, approximately 10% of those previously allocated hormone therapy alone had their recommendation changed to add chemotherapy. This optimized therapy allocation led to improved mean life expectancy by 0.068 years per patient and increased direct costs by MXN 1707 [2011 United States Dollars (USD) 129] per patient versus usual care. This is equated to an incremental cost-effectiveness ratio (ICER) of MXN 25,244 (USD 1914) per life-year gained. In early-stage breast cancer patients in Mexico, guiding decision making on adjuvant therapy using the 21-gene assay was projected to improve life expectancy in comparison with the current standard of care, with an ICER of MXN 25,244 (USD 1914) per life-year gained, which is within the range generally considered cost-effective.

Mapping severe fire potential across the contiguous United States

Treesearch

Brett H. Davis

2016-01-01

The Fire Severity Mapping System (FIRESEV) project is an effort to provide critical information and tools to fire managers that enhance their ability to assess potential ecological effects of wildland fire. A major component of FIRESEV is the development of a Severe Fire Potential Map (SFPM), a geographic dataset covering the contiguous United States (CONUS) that...

Multiple focal and macroreentrant left atrial tachycardias originating from a spontaneous scar at the contiguous aorta-left atrium area in a patient with hypertrophic cardiomyopathy: a case report.

PubMed

Yazaki, Kyoichiro; Ajiro, Yoichi; Mori, Fumiaki; Watanabe, Masahiro; Tsukamoto, Kei; Saito, Takashi; Mizobuchi, Keiko; Iwade, Kazunori

2017-01-17

Spontaneous scar-related left atrial tachycardia (AT) is a rare arrhythmia. We describe a patient with hypertrophic cardiomyopathy (HCM) who developed multiple, both focal and macroreentrant left ATs associated with a spontaneous scar located at the aorta-left atrium (LA) contiguous area. A 65-year-old man with HCM complained of palpitations. Twelve-lead electrocardiogram showed narrow QRS tachycardia with 2:1 atrioventricular conduction. Two sessions of radiofrequency ablation (RFA) were required to eliminate all left ATs. In the first session, 3-dimensional electroanatomical mapping fused with the image constructed by multi-detector computed tomography showed a clockwise macroreentrant AT (AT1) associated with a low-voltage or dense scar area located along the aorta-LA contiguous area. AT1 was eliminated by RFA to the narrow isthmus with slow conduction velocity within the scar. Additional ATs (AT2-AT4) occurred 1 month after the first ablation. In the second session, AT2 and AT3 were identified as focal ATs with centrifugal propagation and few accompanying fragmentations, and AT4 as a macroreentrant AT with features similar to AT1. AT2 and AT3 were successfully eliminated by performing RFA to the earliest activation site, and AT4 was terminated by performing RFA to the narrow isthmus with slow conduction velocity. No ATs have recurred for 11 months after these RFAs. Interestingly, the substrate for all left ATs was associated with the aorta-LA contiguous area. To our knowledge, this is the first case of multiple, both focal and macroreentrant left ATs associated with a contiguous aorta-LA spontaneous scar area in a patient with HCM.

Identification of new risk factors for rolandic epilepsy: CNV at Xp22.31 and alterations at cholinergic synapses.

PubMed

Addis, Laura; Sproviero, William; Thomas, Sanjeev V; Caraballo, Roberto H; Newhouse, Stephen J; Gomez, Kumudini; Hughes, Elaine; Kinali, Maria; McCormick, David; Hannan, Siobhan; Cossu, Silvia; Taylor, Jacqueline; Akman, Cigdem I; Wolf, Steven M; Mandelbaum, David E; Gupta, Rajesh; van der Spek, Rick A; Pruna, Dario; Pal, Deb K

2018-05-22

Rolandic epilepsy (RE) is the most common genetic childhood epilepsy, consisting of focal, nocturnal seizures and frequent neurodevelopmental impairments in speech, language, literacy and attention. A complex genetic aetiology is presumed in most, with monogenic mutations in GRIN2A accounting for >5% of cases. To identify rare, causal CNV in patients with RE. We used high-density SNP arrays to analyse the presence of rare CNVs in 186 patients with RE from the UK, the USA, Sardinia, Argentina and Kerala, India. We identified 84 patients with one or more rare CNVs, and, within this group, 14 (7.5%) with recurrent risk factor CNVs and 15 (8.0%) with likely pathogenic CNVs. Nine patients carried recurrent hotspot CNVs including at 16p13.11 and 1p36, with the most striking finding that four individuals (three from Sardinia) carried a duplication, and one a deletion, at Xp22.31. Five patients with RE carried a rare CNV that disrupted genes associated with other epilepsies ( KCTD7 , ARHGEF15 , CACNA2D1, GRIN2A and ARHGEF4 ), and 17 cases carried CNVs that disrupted genes associated with other neurological conditions or that are involved in neuronal signalling/development. Network analysis of disrupted genes with high brain expression identified significant enrichment in pathways of the cholinergic synapse, guanine-exchange factor activation and the mammalian target of rapamycin. Our results provide a CNV profile of an ethnically diverse cohort of patients with RE, uncovering new areas of research focus, and emphasise the importance of studying non-western European populations in oligogenic disorders to uncover a full picture of risk variation. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

A highly polymorphic dinucleotide repeat on the proximal short arm of the human X chromosome: linkage mapping of the synapsin I/A-raf-1 genes.

PubMed Central

Kirchgessner, C U; Trofatter, J A; Mahtani, M M; Willard, H F; DeGennaro, L J

1991-01-01

A compound (AC)n repeat located 1,000 bp downstream from the human synapsin I gene and within the last intron of the A-raf-1 gene has been identified. DNA data-base comparisons of the sequences surrounding the repeat indicate that the synapsin I gene and the A-raf-1 gene lie immediately adjacent to each other, in opposite orientation. PCR amplification of this synapsin I/A-raf-1 associated repeat by using total genomic DNA from members of the 40 reference pedigree families of the Centre d'Etude du Polymorphisme Humaine showed it to be highly polymorphic, with a PIC value of .84 and a minimum of eight alleles. Because the synapsin I gene has been mapped previously to the short arm of the human X chromosome at Xp11.2, linkage analysis was performed with markers on the proximal short arm of the X chromosome. The most likely gene order is DXS7SYN/ARAF1TIMPDXS255DXS146, with a relative probability of 5 x 10(8) as compared with the next most likely order. This highly informative repeat should serve as a valuable marker for disease loci mapped to the Xp11 region. Images Figure 2 PMID:1905878

Exclusion of RAI2 as the causative gene for Nance-Horan syndrome.

PubMed

Walpole, S M; Ronce, N; Grayson, C; Dessay, B; Yates, J R; Trump, D; Toutain, A

1999-05-01

Nance-Horan syndrome (NHS) is an X-linked condition characterised by congenital cataracts, microphthalmia and/or microcornea, unusual dental morphology, dysmorphic facial features, and developmental delay in some cases. Recent linkage studies have mapped the NHS disease gene to a 3.5-cM interval on Xp22.2 between DXS1053 and DXS443. We previously identified a human homologue of a mouse retinoic-acid-induced gene (RAI2) within the NHS critical flanking interval and have tested the gene as a candidate for Nance-Horan syndrome in nine NHS-affected families. Direct sequencing of the RAI2 gene and predicted promoter region has revealed no mutations in the families screened; RAI2 is therefore unlikely to be associated with NHS.

Radiologic-pathologic correlation of renal cell carcinoma associated with Xp11.2 translocation.

PubMed

Koo, Hyun Jung; Choi, Hyuck Jae; Kim, Mi-hyun; Cho, Kyoung-Sik

2013-09-01

The prognosis of translocation RCCs in adult patients is relatively poor compared to that of other subtypes of RCCs. Although there have been several reports regarding radiologic findings of translocation RCC, studies with histologic correlation could help to understand the imaging features. To explore the correlation between radiologic and pathologic findings in Xp11.2 translocation renal cell carcinoma (RCC) and provide clues for translocation RCC diagnosis. CT scans of six patients (one man and five women; age range, 8-71 years; mean age, 34 years) with histologically-proven Xp11.2 translocation RCCs were retrospectively evaluated in consensus by two radiologists. Tumor size, presence of necrosis, hemorrhage, fat or calcification, enhancement patterns of the tumor, presence of lymphadenopathy, and distant metastases were evaluated. The average size of the tumors was 6 cm (range, 2.7-12 cm). All six tumors appeared as well-defined masses with areas of low attenuation representing hemorrhage or necrosis. Four tumors contained high attenuating solid portions, compared to the surrounding renal cortex seen on unenhanced images, where representing dense cellular component on microscopic examination. Peripheral rim enhancement pattern that correlated with histologic finding of a fibrous capsule was seen in five cases. In two patients who underwent kidney MR, the masses showed low signal intensity on T2-weighted images. One patient had lymphadenopathy. No distant metastasis was noted in any patient. Translocation RCC appeared as a well-defined mass that contain high attenuating solid portions on unenhanced images and low attenuating necrotic or hemorrhagic foci; the tumor also showed gradual peripheral rim enhancement due to a fibrous capsule surrounding the tumor.

Overexpression of Rice Auxilin-Like Protein, XB21, Induces Necrotic Lesions, up-Regulates Endocytosis-Related Genes, and Confers Enhanced Resistance to Xanthomonas oryzae pv. oryzae

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, Chang-Jin; Wei, Tong; Sharma, Rita

The rice immune receptor XA21 confers resistance to the bacterial pathogen, Xanthomonas oryzae pv. oryzae (Xoo). To elucidate the mechanism of XA21-mediated immunity, we previously performed a yeast two-hybrid screening for XA21 interactors and identified XA21 binding protein 21 (XB21). Here, we report that XB21 is an auxilin-like protein predicted to function in clathrin-mediated endocytosis. We demonstrate an XA21/XB21 in vivo interaction using co-immunoprecipitation in rice. Overexpression of XB21 in rice variety Kitaake and a Kitaake transgenic line expressing XA21 confers a necrotic lesion phenotype and enhances resistance to Xoo. RNA sequencing reveals that XB21 overexpression results in the differentialmore » expression of 8735 genes (4939 genes up- and 3846 genes down-regulated) (≥2-folds, FDR ≤0.01). The up-regulated genes include those predicted to be involved in ‘cell death’ and ‘vesicle-mediated transport’. These results indicate that XB21 plays a role in the plant immune response and in regulation of cell death. The up-regulation of genes controlling ‘vesicle-mediated transport’ in XB21 overexpression lines is consistent with a functional role for XB21 as an auxilin.« less

Overexpression of Rice Auxilin-Like Protein, XB21, Induces Necrotic Lesions, up-Regulates Endocytosis-Related Genes, and Confers Enhanced Resistance to Xanthomonas oryzae pv. oryzae

DOE PAGES

Park, Chang-Jin; Wei, Tong; Sharma, Rita; ...

2017-06-02

The rice immune receptor XA21 confers resistance to the bacterial pathogen, Xanthomonas oryzae pv. oryzae (Xoo). To elucidate the mechanism of XA21-mediated immunity, we previously performed a yeast two-hybrid screening for XA21 interactors and identified XA21 binding protein 21 (XB21). Here, we report that XB21 is an auxilin-like protein predicted to function in clathrin-mediated endocytosis. We demonstrate an XA21/XB21 in vivo interaction using co-immunoprecipitation in rice. Overexpression of XB21 in rice variety Kitaake and a Kitaake transgenic line expressing XA21 confers a necrotic lesion phenotype and enhances resistance to Xoo. RNA sequencing reveals that XB21 overexpression results in the differentialmore » expression of 8735 genes (4939 genes up- and 3846 genes down-regulated) (≥2-folds, FDR ≤0.01). The up-regulated genes include those predicted to be involved in ‘cell death’ and ‘vesicle-mediated transport’. These results indicate that XB21 plays a role in the plant immune response and in regulation of cell death. The up-regulation of genes controlling ‘vesicle-mediated transport’ in XB21 overexpression lines is consistent with a functional role for XB21 as an auxilin.« less

Non-contiguous finished genome sequence of the opportunistic oral pathogen Prevotella multisaccharivorax type strain (PPPA20T)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pati, Amrita; Gronow, Sabine; Lu, Megan

2011-01-01

Prevotella multisaccharivorax Sakamoto et al. 2005 is a species of the large genus Prevotella, which belongs to the family Prevotellaceae. The species is of medical interest because its members are able to cause diseases in the human oral cavity such as periodontitis, root caries and others. Although 77 Prevotella genomes have already been sequenced or are targeted for sequencing, this is only the second completed genome sequence of a type strain of a species within the genus Prevotella to be published. The 3,388,644 bp long genome is assembled in three non-contiguous contigs, harbors 2,876 protein-coding and 75 RNA genes andmore » is a part of the Genomic Encyclopedia of Bacteria and Archaea project.« less

Generation of induced pluripotent stem cells from a Becker muscular dystrophy patient carrying a deletion of exons 45-55 of the dystrophin gene (CCMi002BMD-A-9 ∆45-55).

PubMed

Gowran, Aoife; Spaltro, Gabriella; Casalnuovo, Federica; Vigorelli, Vera; Spinelli, Pietro; Castiglioni, Elisa; Rovina, Davide; Paganini, Stefania; Di Segni, Marina; Gervasini, Cristina; Nigro, Patrizia; Pompilio, Giulio

2018-04-01

Becker muscular dystrophy (BMD) is a dystrophinopathy caused by mutations in the dystrophin gene on chromosome Xp21. BMD mutations result in truncated semi-functional dystrophin isoforms. Consequently, less severe clinical symptoms become apparent later in life compared to Duchenne muscular dystrophy. Dermal fibroblasts from a BMD patient were electroporated with episomal plasmids containing reprogramming factors to create the induced pluripotent stem cell line: CCMi002BMD-A-9 that showed pluripotent markers, were karyotypically normal and capable of trilineage differentiation. MLPA analyses performed on DNA extracted from CCMi002BMD-A-9 showed an in-frame deletion of exons 45 to 55 (CCMi002BMD-A-9 Δ45-55). Copyright © 2018 The Author(s). Published by Elsevier B.V. All rights reserved.

Xeroderma pigmentosum complementation group G associated with Cockayne syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vermeulen, W.; Jaspers, N.G.J.; Bootsma, D.

1993-07-01

Xeroderma pigmentosum (XP) and Cockayne syndrome (CS) are two rare inherited disorders with a clinical and cellular hypersensitivity to the UV component of the sunlight spectrum. Although the two traits are generally considered as clinically and genetically distinct entities, on the biochemical level a defect in the nucleotide excision-repair (NER) pathway is involved in both. Classical CS patients are primarily deficient in the preferential repair of DNA damage in actively transcribed genes, whereas in most XP patients the genetic defect affects both [open quotes]preferential[close quotes] and [open quotes]overall[close quotes] NER modalities. Here the authors report a genetic study of twomore » unrelated, severely affected patients with the clinical characteristics of CS but with a biochemical defect typical of XP. By complementation analysis, using somatic cell fusion and nuclear microinjection of cloned repair genes, they assign these two patients to XP complementation group G, which previously was not associated with CS. This observation extends the earlier identification of two patients with a rare combined XP/CS phenotype within XP complementation groups B and D, respectively. It indicates that some mutations in at least three of the seven genes known to be involved in XP also can result in a picture of partial or even full-blown CS. It is concluded that the syndromes XP and CS are biochemically closely related and may be part of a broader clinical disease spectrum. The authors suggest, as a possible molecular mechanism underlying this relation, that the XPGC repair gene has an additional vital function, as shown for some other NER genes. 33 refs., 5 tabs.« less

Characterization of a splicing mutation in group A xeroderma pigmentosum

DOE Office of Scientific and Technical Information (OSTI.GOV)

Satokata, Ichiro; Tanaka, Kiyoji; Miura, Naoyuki

1990-12-01

The molecular basis of group A xeroderma pigmentosum (WP) was investigated by comparison of the nucleotide sequences of multiple clones of the XP group A complementing gene (XPAC) from a patient with group A XP with that of a normal gene. The clones showed a G {r arrow} C substitution at the 3{prime} splice acceptor site of intron 3, which altered the obligatory AG acceptor dinucleotide to AC. Nucleotide sequencing of cDNAs amplified by the polymerase chain reaction revealed that this single base substitution abolishes the canonical 3{prime} splice site, thus creating two abnormally spliced mRNA forms. The larger formmore » is identical with normal mRNA except for a dinucleotide deletion at the 5{prime} end of exon 4. This deletion results in a frameshift with premature translation termination in exon 4. The smaller form has a deletion of the entire exon 3 and the dinucleotide at the 5{prime} end of exon 4. The result of a transfection study provided additional evidence that this single base substitution is the disease-causing mutation. This single base substitution creates a new cleavage site for the restriction nuclease AlwNI. Analysis of AlwNI restriction fragment length polymorphism showed a high frequency of this mutation in Japanese patients with group A XP: 16 of 21 unrelated Japanese patients were homozygous and 4 were heterozygous for this mutation. However, 11 Caucasians and 2 Blacks with group A XP did not have this mutant allele. The polymorphic AlwNI restriction fragments are concluded to be useful for diagnosis of group A XP in Japanese subjects, including prenatal cases and carriers.« less

Reactive Collision Avoidance of UAVs withStereovision Sensing

DTIC Science & Technology

2014-01-17

terms of homogeneous coordinates. Mxw = 0 Where M =  m11 m12 m13 m14 m21 m22 m23 m24 m31 m32 m33 m34 m41 m42 m43 m44  (4.15) 50 m11 = p11 − xp...1 p31 , m12 = p12 − xp 1 p32 m13 = p13 − xp 1 p33 , m14 = p14 − xp 1 p34 m21 = p21 − yp 1 p31 , m22 = p22 − yp 1 p32 m23 = p23 − yp 1 p33 , m24 = p24

The genetic characteristics of congenital hypothyroidism in China by comprehensive screening of 21 candidate genes.

PubMed

Sun, Feng; Zhang, Jun-Xiu; Yang, Chang-Yi; Gao, Guan-Qi; Zhu, Wen-Bin; Han, Bing; Zhang, Le-Le; Wan, Yue-Yue; Ye, Xiao-Ping; Ma, Yu-Ru; Zhang, Man-Man; Yang, Liu; Zhang, Qian-Yue; Liu, Wei; Guo, Cui-Cui; Chen, Gang; Zhao, Shuang-Xia; Song, Ke-Yi; Song, Huai-Dong

2018-06-01

Congenital hypothyroidism (CH), the most common neonatal metabolic disorder, is characterized by impaired neurodevelopment. Although several candidate genes have been associated with CH, comprehensive screening of causative genes has been limited. One hundred ten patients with primary CH were recruited in this study. All exons and exon-intron boundaries of 21 candidate genes for CH were analyzed by next-generation sequencing. And the inheritance pattern of causative genes was analyzed by the study of family pedigrees. Our results showed that 57 patients (51.82%) carried biallelic mutations (containing compound heterozygous mutations and homozygous mutations) in six genes ( DUOX2 , DUOXA2 , DUOXA1 , TG , TPO and TSHR ) involved in thyroid hormone synthesis. Autosomal recessive inheritance of CH caused by mutations in DUOX2 , DUOXA2 , TG and TPO was confirmed by analysis of 22 family pedigrees. Notably, eight mutations in four genes ( FOXE1 , NKX2-1 , PAX8 and HHEX ) that lead to thyroid dysgenesis were identified in eight probands. These mutations were heterozygous in all cases and hypothyroidism was not observed in parents of these probands. Most cases of congenital hypothyroidism in China were caused by thyroid dyshormonogenesis rather than thyroid dysgenesis. This study identified previously reported causative genes for 57/110 Chinese patients and revealed DUOX2 was the most frequently mutated gene in these patients. Our study expanded the mutation spectrum of CH in Chinese patients, which was significantly different from Western countries. © 2018 The authors.

Stability and Control Characteristics of a 1/10-Scale Model of the McDonnell XP-85 Airplane While Attached to the Trapeze

NASA Technical Reports Server (NTRS)

Johnson, Joseph L.

1947-01-01

At the request of the Air Materiel Command, Army Air Forces, an investigation of the low-speed, power-off, stability and control characteristics of the McDonnell XP-85 airplane has been conducted in the Langley free-flight tunnel. The results of the portion of the investigation consisting of tests of a 1/10-scale model to study the stability of the XP-85 when attached to the trapeze and during retraction into the B-36 bomb bay are presented herein. In the power-off condition the stability was satisfactory with all oscillations well damped and the nose-restraining collar could be placed in position without difficulty. In a simulated power-on condition the model had a constant-amplitude rolling and sidewise motion and when the collar was layered, a violent motion resulted if the collar struck the model but failed to hold it in the proper manner. Folding of the wings and retraction into the bomb bay offered no problem once the airplane was properly held by the collar. It is recommended that the power be cut immediately after hooking on and that a restricting mechanism be incorporated in the center of the trapeze to eliminate the sidewise motion. It also appears desirable to have the retracting procedure controlled by the XP-85 pilot or an observer in the mother ship to insure that the parasite is in proper position after hooking up before bringing the collar down.

Extermination and recovery of red wolf and grey wolf in the contiguous United States

USGS Publications Warehouse

Phillips, Michael K.; Bangs, Edward E.; Mech, L. David; Kelly, Brian T.; Fazio, Buddy B.; Macdonald, David W.; Sillero-Zubiri, Claudio

2004-01-01

About 150 years ago, the grey wolf (Canis lupus) was distributed throughout the contiguous United States, except for in southeastern US from central Texas to the Atlantic coast, where the red wolf (Canis rufus) occurred. Conflict with agricultural interests resulted in government-supported eradication campaigns beginning in colonial Massachusetts in 1630. Over the next 300 years, the campaigns were extended throughout the US resulting in the near extermination of both species. In recent decades, efforts to recover the red and grey wolf were carried out. This chapter summarizes extermination and recovery efforts for both species in the contiguous US.

Modulation of early cortical processing during divided attention to non-contiguous locations

PubMed Central

Frey, Hans-Peter; Schmid, Anita M.; Murphy, Jeremy W.; Molholm, Sophie; Lalor, Edmund C.; Foxe, John J.

2015-01-01

We often face the challenge of simultaneously attending to multiple non-contiguous regions of space. There is ongoing debate as to how spatial attention is divided under these situations. While for several years the predominant view was that humans could divide the attentional spotlight, several recent studies argue in favor of a unitary spotlight that rhythmically samples relevant locations. Here, this issue was addressed using high-density electrophysiology in concert with the multifocal m-sequence technique to examine visual evoked responses to multiple simultaneous streams of stimulation. Concurrently, we assayed the topographic distribution of alpha-band oscillatory mechanisms, a measure of attentional suppression. Participants performed a difficult detection task that required simultaneous attention to two stimuli in contiguous (undivided) or non-contiguous parts of space. In the undivided condition, the classical pattern of attentional modulation was observed, with increased amplitude of the early visual evoked response and increased alpha amplitude ipsilateral to the attended hemifield. For the divided condition, early visual responses to attended stimuli were also enhanced and the observed multifocal topographic distribution of alpha suppression was in line with the divided attention hypothesis. These results support the existence of divided attentional spotlights, providing evidence that the corresponding modulation occurs during initial sensory processing timeframes in hierarchically early visual regions and that suppressive mechanisms of visual attention selectively target distracter locations during divided spatial attention. PMID:24606564

Genotype-phenotype correlation of xeroderma pigmentosum in a Chinese Han population.

PubMed

Sun, Z; Zhang, J; Guo, Y; Ni, C; Liang, J; Cheng, R; Li, M; Yao, Z

2015-04-01

Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder characterized by extreme sensitivity to sunlight, freckle-like pigmentation and a greatly increased incidence of skin cancers. Genetic mutation detection and genotype-phenotype analysis of XP are rarely reported in the Chinese Han population. To investigate the mutational spectrum of XP in a Chinese Han population, to discover any genotype-phenotype correlation and, consequently, to propose a simple and effective tool for the molecular diagnosis of XP. This study was carried out on 12 unrelated Chinese families that included 13 patients with clinically suspected XP. Genomic DNA was extracted from peripheral blood samples. Mutation screening was performed by direct sequencing of exons and flanking intron-exon boundaries for the entire coding region of eight XP genes. In 12 patients, direct sequencing of the whole coding region of eight XP genes revealed pathogenic mutations, including seven compound heterozygous mutations, three homozygous mutations and a Japanese founder mutation. Thirteen mutations have not been previously identified. This cohort was composed of four patients with XP-C (XPC), two with XP-G (ERCC5), three with XP-A (XPA) and three with XP-V (POLH). This study identified 13 novel mutations and extended the mutation spectrum of XP in the Chinese Han population. In this cohort, we found that patients with XP-G have no neurological symptoms, and patients with XP-A and XP-V have a high incidence of malignancy. Furthermore, lack of stringent protection against sunlight, late diagnosis and long duration of disease play an important role. © 2014 British Association of Dermatologists.

TCF21 and the environmental sensor aryl-hydrocarbon receptor cooperate to activate a pro-inflammatory gene expression program in coronary artery smooth muscle cells

PubMed Central

Nguyen, Trieu; Iyer, Dharini; Liu, Boxiang; Wang, Ting; Sazonova, Olga; Matic, Ljubica Perisic; Maegdefessel, Lars; Quertermous, Thomas

2017-01-01

Both environmental factors and genetic loci have been associated with coronary artery disease (CAD), however gene-gene and gene-environment interactions that might identify molecular mechanisms of risk are not easily studied by human genetic approaches. We have previously identified the transcription factor TCF21 as the causal CAD gene at 6q23.2 and characterized its downstream transcriptional network that is enriched for CAD GWAS genes. Here we investigate the hypothesis that TCF21 interacts with a downstream target gene, the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor that mediates the cellular response to environmental contaminants, including dioxin and polycyclic aromatic hydrocarbons (e.g., tobacco smoke). Perturbation of TCF21 expression in human coronary artery smooth muscle cells (HCASMC) revealed that TCF21 promotes expression of AHR, its heterodimerization partner ARNT, and cooperates with these factors to upregulate a number of inflammatory downstream disease related genes including IL1A, MMP1, and CYP1A1. TCF21 was shown to bind in AHR, ARNT and downstream target gene loci, and co-localization was noted for AHR-ARNT and TCF21 binding sites genome-wide in regions of HCASMC open chromatin. These regions of co-localization were found to be enriched for GWAS signals associated with cardio-metabolic as well as chronic inflammatory disease phenotypes. Finally, we show that similar to TCF21, AHR gene expression is increased in atherosclerotic lesions in mice in vivo using laser capture microdissection, and AHR protein is localized in human carotid atherosclerotic lesions where it is associated with protein kinases with a critical role in innate immune response. These data suggest that TCF21 can cooperate with AHR to activate an inflammatory gene expression program that is exacerbated by environmental stimuli, and may contribute to the overall risk for CAD. PMID:28481916

Building a Potential Wetland Restoration Indicator for the Contiguous United States

EPA Science Inventory

Wetlands provide key functions in the landscape from improving water quality, to regulating flows, to providing wildlife habitat. Over half of the wetlands in the contiguous United States (CONUS) have been converted to agricultural and urban land uses. However, over the last seve...

48 CFR 242.1402 - Volume movements within the contiguous United States.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Volume movements within the contiguous United States. 242.1402 Section 242.1402 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE CONTRACT MANAGEMENT CONTRACT ADMINISTRATION AND AUDIT...

Variability of wildland fire emissions across the contiguous United States

Treesearch

YongQiang Liu

2004-01-01

This study analyzes spatial and temporal variability of emissions from wildland fires across the contiguous US. The emissions are estimates based on a recently constructed dataset of historical fire records collected by multiple US governlnental agencies. Both wildfire and prescribed fires have the highest emissions over the Pacific coastal states. Prescribed fire...

Modeling xeroderma pigmentosum associated neurological pathologies with patients-derived iPSCs.

PubMed

Fu, Lina; Xu, Xiuling; Ren, Ruotong; Wu, Jun; Zhang, Weiqi; Yang, Jiping; Ren, Xiaoqing; Wang, Si; Zhao, Yang; Sun, Liang; Yu, Yang; Wang, Zhaoxia; Yang, Ze; Yuan, Yun; Qiao, Jie; Izpisua Belmonte, Juan Carlos; Qu, Jing; Liu, Guang-Hui

2016-03-01

Xeroderma pigmentosum (XP) is a group of genetic disorders caused by mutations of XP-associated genes, resulting in impairment of DNA repair. XP patients frequently exhibit neurological degeneration, but the underlying mechanism is unknown, in part due to lack of proper disease models. Here, we generated patient-specific induced pluripotent stem cells (iPSCs) harboring mutations in five different XP genes including XPA, XPB, XPC, XPG, and XPV. These iPSCs were further differentiated to neural cells, and their susceptibility to DNA damage stress was investigated. Mutation of XPA in either neural stem cells (NSCs) or neurons resulted in severe DNA damage repair defects, and these neural cells with mutant XPA were hyper-sensitive to DNA damage-induced apoptosis. Thus, XP-mutant neural cells represent valuable tools to clarify the molecular mechanisms of neurological abnormalities in the XP patients.

A foetus with 18p11.32-q21.2 duplication and Xp22.33-p11.1 deletion derived from a maternal reciprocal translocation t(X;18)(q13;q21.3).

PubMed

Chen, Jun-Kun; Liu, Ping; Hu, Li-Qin; Xie, Qing; Huang, Quan-Fei; Liu, Hai-Liang

2018-01-01

Non-invasive prenatal testing (NIPT) evaluates circulating cell-free DNA (cfDNA) and has been widely applied, with highly accurate results for detecting foetal trisomies 21, 18 and 13. Recently, increasing attention has been paid to the clinical application of the non-invasive detection of foetal sub-chromosomal duplications and deletions beyond common aneuploidies. A 32-year-old healthy pregnant woman was referred to the Medical Genetic Centre of Ganzhou Maternal and Child Health Care Hospital. As routine practice, ultrasound examination at a gestational age of 16 weeks showed that the foetus is normal. To avoid invasive prenatal diagnosis procedures, an NIPT was offered to further screen for common foetal chromosomal abnormalities. The result showed that there was an approximately 50.94 Mb duplication in p11.32-q21.2 of chromosome 18 and an approximately 58.46 Mb deletion in p22.33-p11.1 of chromosome X. In addition, the chromosome karyotypes of the parents and foetus were also analysed. Chromosome karyotype analysis results showed that foetal karyotype was 46,X,der(18), the maternal karyotype was 46,XX,t(X;18)(q13;q21.3), and the paternal karyotype revealed no obvious abnormality. In this case, we successfully detected a healthy pregnant woman with balanced translocation X;18(q13;q21.3) and described the foetal karyotype as 46,X,der(18)t(X;18)(q11;q21.1)mat. Our report illustrated these cases which present complex X;autosome balance translocation and X;autosome unbalance translocation which may contribute to severe clinical phenotypes. In addition, our report also proved that the interruption of genes in the Xq critical region is not only reason of primary infertility. Finally, we prompted that NIPT might play a role in the first trimester screening of sub-chromosomal rearrangement.

New process of preparation, X-ray characterisation, structure and vibrational studies of a solid solution LiTiOAs 1-xP xO 4 (0⩽ x⩽1)

NASA Astrophysics Data System (ADS)

Chakir, M.; El Jazouli, A.; Chaminade, J. P.; Bouree, F.; de Waal, D.

2006-01-01

LiTiOAs 1-xP xO 4 (0⩽ x⩽1) compounds have been prepared using solutions of Li, Ti, As and P elements as starting products. Selected compositions have been investigated by powder X-ray or neutrons diffraction analysis, Raman and infrared spectroscopy. The structure of LiTiOAs 1-xP xO 4 ( x=0, 0.5 and 1) samples determined by Rietveld analysis is orthorhombic with Pnma space group. It is formed by a 3D network of TiO 6 octahedra and XO 4 ( X=As 1-xP x) tetrahedra where octahedral cavities are occupied by lithium atoms. TiO 6 octahedra are linked together by corners and form infinite chains along a-axis. Ti atoms are displaced from the centre of octahedral units in alternating short (1.700-1.709 Å) and long (2.301-2.275 Å) Ti-O bonds. Raman and infrared studies confirm the existence of Ti-O-Ti chains. Thermal stability of LiTiOAsO 4 has been reported.

Malfunction of Nuclease ERCC1-XPF Results in Diverse Clinical Manifestations and Causes Cockayne Syndrome, Xeroderma Pigmentosum, and Fanconi Anemia

PubMed Central

Kashiyama, Kazuya; Nakazawa, Yuka; Pilz, Daniela T.; Guo, Chaowan; Shimada, Mayuko; Sasaki, Kensaku; Fawcett, Heather; Wing, Jonathan F.; Lewin, Susan O.; Carr, Lucinda; Li, Tao-Sheng; Yoshiura, Koh-ichiro; Utani, Atsushi; Hirano, Akiyoshi; Yamashita, Shunichi; Greenblatt, Danielle; Nardo, Tiziana; Stefanini, Miria; McGibbon, David; Sarkany, Robert; Fassihi, Hiva; Takahashi, Yoshito; Nagayama, Yuji; Mitsutake, Norisato; Lehmann, Alan R.; Ogi, Tomoo

2013-01-01

Cockayne syndrome (CS) is a genetic disorder characterized by developmental abnormalities and photodermatosis resulting from the lack of transcription-coupled nucleotide excision repair, which is responsible for the removal of photodamage from actively transcribed genes. To date, all identified causative mutations for CS have been in the two known CS-associated genes, ERCC8 (CSA) and ERCC6 (CSB). For the rare combined xeroderma pigmentosum (XP) and CS phenotype, all identified mutations are in three of the XP-associated genes, ERCC3 (XPB), ERCC2 (XPD), and ERCC5 (XPG). In a previous report, we identified several CS cases who did not have mutations in any of these genes. In this paper, we describe three CS individuals deficient in ERCC1 or ERCC4 (XPF). Remarkably, one of these individuals with XP complementation group F (XP-F) had clinical features of three different DNA-repair disorders—CS, XP, and Fanconi anemia (FA). Our results, together with those from Bogliolo et al., who describe XPF alterations resulting in FA alone, indicate a multifunctional role for XPF. PMID:23623389

48 CFR 242.1402 - Volume movements within the contiguous United States.

Code of Federal Regulations, 2011 CFR

2011-10-01

... administration office submits a volume movement report when— (1) Significant changes are made to the movement... 48 Federal Acquisition Regulations System 3 2011-10-01 2011-10-01 false Volume movements within... SERVICES Traffic and Transportation Management 242.1402 Volume movements within the contiguous United...

Viscous constitutive relations of solid-liquid composites in terms of grain boundary contiguity: 1. Grain boundary diffusion control model

NASA Astrophysics Data System (ADS)

Takei, Yasuko; Holtzman, Benjamin K.

2009-06-01

Viscous constitutive relations of partially molten rocks deforming in the regime of grain boundary (GB) diffusion creep are derived theoretically on the basis of microstructural processes at the grain scale. The viscous constitutive relation developed in this study is based on contiguity as an internal state variable, which enables us to take into account the detailed effects of grain-scale melt distribution observed in experiments. Compared to the elasticities derived previously for the same microstructural model, the viscosities are much more sensitive to the presence of melt and variations in contiguity. As explored in this series of three companion papers, this "contiguity" model predicts that a very small amount of melt (ϕ < 0.01) significantly reduces the bulk and shear viscosities. Furthermore, a large anisotropy in viscosity is produced by anisotropy in contiguity, which occurs in deforming partially molten rocks. These results have important implications for deformation and melt extraction at small melt fractions, as well as for shear-induced melt segregation. The viscous and elastic constitutive relations derived in terms of contiguity bridge microscopic grain-scale and macroscopic continuum properties. These constitutive relations are essential for investigating melt migration dynamics in a forward sense on the basis of the basic equations of two-phase dynamics and in an inverse sense on the basis of seismological observations.

Assignment of xeroderma pigmentosum group C(XPC) gene to chromosome 3p25

DOE Office of Scientific and Technical Information (OSTI.GOV)

Legerski, R.J.; Liu, P.; Li, L.

1994-05-01

The human gene XPC (formerly designated XPCC), which corrects the repair deficiency of xeroderma pigmentosum (XP) group C cells, was mapped to 3p25. A cDNA probe for Southern blot hybridization and diagnostic PCR analyses of hybrid clone panels informative for human chromosomes in general and portions of chromosome 3 in particular produced the initial results. Fluorescence in situ hybridization utilizing both a yeast artificial chromosome DNA containing the gene and XPC cDNA as probes provided verification and specific regional assignment. A conflicting assignment of XPC to chromosome 5 is discussed in light of inadequacies in the exclusive use of microcell-mediatedmore » chromosome transfer for gene mapping. 12 refs., 3 figs.« less

Subcellular Localization of Large Yellow Croaker ( Larimichthys crocea) TLR21 and Expression Profiling of Its Gene in Immune Response

NASA Astrophysics Data System (ADS)

Sun, Qingxue; Fan, Zejun; Yao, Cuiluan

2018-04-01

Toll-like receptor 21 (TLR21) is a non-mammalian type TLR, and plays an important role in innate immune response in fish. In this paper, the full-length cDNA sequence of TLR21 gene was identified and characterized from large yellow croaker, Larimichthys crocea and was termed as LcTLR21. It consists of 3365 bp, including a 5'-terminal untranslated region (UTR) of 97 bp, a 3'-terminal UTR of 331 bp, and an open reading frame (ORF) of 2937 bp encoding a polypeptide of 978 amino acid residues. The deduced LcTLR21 contains a signal peptide domain at N-terminal, 12 leucine-rich repeats (LRRs) at the extracellular region, a transmembrane domain and a cytoplasmic toll-interleukin-1 receptor (TIR) domain at the C-terminal. Subcellular localization analysis revealed that the LcTLR21-GFP was constitutively expressed in cytoplasm. Tissue expression analysis indicated that LcTLR21 gene broadly expressed in most of the examined tissues, with the most predominant abundance in spleen, followed by head-kidney and liver, while the weakest expression was detected in brain. The expression level of LcTLR21 after LPS, poly I:C and Vibrio parahaemolyticus challenges was investigated in spleen, head-kidney and liver. LcTLR21 gene transcripts increased significantly in all examined tissues after the challenges, and the highest expression level was detected in liver at 24 h after poly I:C stimulation ( P < 0.05), suggesting that LcTLR21 might play a crucial role in fish resistance to viral and bacterial infections.

Expression of Immune Genes on Chromosome 6p21.3-22.1 in Schizophrenia

PubMed Central

Sinkus, Melissa L.; Adams, Catherine E.; Logel, Judith; Freedman, Robert; Leonard, Sherry

2013-01-01

Schizophrenia is a common mental illness with a large genetic component. Three genome-wide association studies have implicated the major histocompatibility complex gene region on chromosome 6p21.3-22.1 in schizophrenia. In addition, nicotine, which is commonly abused in schizophrenia, affects the expression of central nervous system immune genes. Messenger RNA levels for genes in the 6p21.3-22.1 region were measured in human postmortem hippocampus of 89 subjects. The effects of schizophrenia diagnosis, smoking and systemic inflammatory illness were compared. Cell-specific expression patterns for the class I major histocompatibility complex gene HLA-A were explored utilizing in situ hybridization. Expression of five genes was altered in schizophrenic subjects. Messenger RNA levels for the class I major histocompatibility complex antigen HLA-B were increased in schizophrenic nonsmokers, while levels for smokers were indistinguishable from those of controls. β2 microglobulin, HLA-A and Notch4 were all expressed in a pattern where inflammatory illness was associated with increased expression in controls but not in subjects with schizophrenia. Schizophrenia was also associated with increased expression of Butyrophilin 2A2. HLA-A was expressed in glutamatergic and GABAergic neurons in the dentate gyrus, hilus, and the stratum pyramidale of the CA1-CA4 regions of the hippocampus, but not in astrocytes. In conclusion, the expression of genes from the major histocompatibility complex region of chromosome 6 with likely roles in synaptic development is altered in schizophrenia. There were also significant interactions between schizophrenia diagnosis and both inflammatory illness and smoking. PMID:23395714

Semantic Cuing and the Scale Insensitivity of Recency and Contiguity

ERIC Educational Resources Information Center

Polyn, Sean M.; Erlikhman, Gennady; Kahana, Michael J.

2011-01-01

In recalling a set of previously experienced events, people exhibit striking effects of recency, contiguity, and similarity: Recent items tend to be recalled best and first, and items that were studied in neighboring positions or that are similar to one another in some other way tend to evoke one another during recall. Effects of recency and…

A family of oculofaciocardiodental syndrome (OFCD) with a novel BCOR mutation and genomic rearrangements involving NHS.

PubMed

Kondo, Yukiko; Saitsu, Hirotomo; Miyamoto, Toshinobu; Nishiyama, Kiyomi; Tsurusaki, Yoshinori; Doi, Hiroshi; Miyake, Noriko; Ryoo, Na-Kyung; Kim, Jeong Hun; Yu, Young Suk; Matsumoto, Naomichi

2012-03-01

Oculofaciocardiodental syndrome (OFCD) is an X-linked dominant disorder associated with male lethality, presenting with congenital cataract, dysmorphic face, dental abnormalities and septal heart defects. Mutations in BCOR (encoding BCL-6-interacting corepressor) cause OFCD. Here, we report on a Korean family with common features of OFCD including bilateral 2nd-3rd toe syndactyly and septal heart defects in three affected females (mother and two daughters). Through the mutation screening and copy number analysis using genomic microarray, we identified a novel heterozygous mutation, c.888delG, in the BCOR gene and two interstitial microduplications at Xp22.2-22.13 and Xp21.3 in all the three affected females. The BCOR mutation may lead to a premature stop codon (p.N297IfsX80). The duplication at Xp22.2-22.13 involved the NHS gene causative for Nance-Horan syndrome, which is an X-linked disorder showing similar clinical features with OFCD in affected males, and in carrier females with milder presentation. Considering the presence of bilateral 2nd-3rd toe syndactyly and septal heart defects, which is unique to OFCD, the mutation in BCOR is likely to be the major determinant for the phenotypes in this family.

Modulation of early cortical processing during divided attention to non-contiguous locations.

PubMed

Frey, Hans-Peter; Schmid, Anita M; Murphy, Jeremy W; Molholm, Sophie; Lalor, Edmund C; Foxe, John J

2014-05-01

We often face the challenge of simultaneously attending to multiple non-contiguous regions of space. There is ongoing debate as to how spatial attention is divided under these situations. Whereas, for several years, the predominant view was that humans could divide the attentional spotlight, several recent studies argue in favor of a unitary spotlight that rhythmically samples relevant locations. Here, this issue was addressed by the use of high-density electrophysiology in concert with the multifocal m-sequence technique to examine visual evoked responses to multiple simultaneous streams of stimulation. Concurrently, we assayed the topographic distribution of alpha-band oscillatory mechanisms, a measure of attentional suppression. Participants performed a difficult detection task that required simultaneous attention to two stimuli in contiguous (undivided) or non-contiguous parts of space. In the undivided condition, the classic pattern of attentional modulation was observed, with increased amplitude of the early visual evoked response and increased alpha amplitude ipsilateral to the attended hemifield. For the divided condition, early visual responses to attended stimuli were also enhanced, and the observed multifocal topographic distribution of alpha suppression was in line with the divided attention hypothesis. These results support the existence of divided attentional spotlights, providing evidence that the corresponding modulation occurs during initial sensory processing time-frames in hierarchically early visual regions, and that suppressive mechanisms of visual attention selectively target distracter locations during divided spatial attention. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Antisense imaging of epidermal growth factor-induced p21(WAF-1/CIP-1) gene expression in MDA-MB-468 human breast cancer xenografts.

PubMed

Wang, Judy; Chen, Paul; Mrkobrada, Marko; Hu, Meiduo; Vallis, Katherine A; Reilly, Raymond M

2003-09-01

Molecular imaging of the expression of key genes which determine the response to DNA damage following cancer treatment may predict the effectiveness of a particular treatment strategy. A prominent early response gene for DNA damage is the gene encoding p21(WAF-1/CIP-1), a cyclin-dependent kinase inhibitor that regulates progression through the cell cycle. In this study, we explored the feasibility of imaging p21(WAF-1/CIP-1) gene expression at the mRNA level using an 18-mer phosphorothioated antisense oligodeoxynucleotide (ODN) labeled with (111)In. The known induction of the p21(WAF-1/CIP-1) gene in MDA-MB-468 human breast cancer cells following exposure to epidermal growth factor (EGF) was used as an experimental tool. Treatment of MDA-MB-468 cells in vitro with EGF (20 n M) increased the ratio of p21(WAF-1/CIP-1) mRNA/beta-actin mRNA threefold within 2 h as measured by the reverse transcription polymerase chain reaction (RT-PCR). A concentration-dependent inhibition of EGF-induced p21(WAF-1/CIP-1) protein expression was achieved in MDA-MB-468 cells by treatment with antisense ODNs with up to a tenfold decrease observed at 1 microM. There was a fourfold lower inhibition of p21(WAF-1/CIP-1) protein expression by control sense or random sequence ODNs. Intratumoral injections of EGF (15 microg/dayx3 days) were employed to induce p21(WAF-1/CIP-1) gene expression in MDA-MB-468 xenografts implanted subcutaneously into athymic mice. RT-PCR of explanted tumors showed a threefold increased level of p21(WAF-1/CIP-1) mRNA compared with normal saline-treated tumors. Successful imaging of EGF-induced p21(WAF-1/CIP-1) gene expression in MDA-MB-468 xenografts was achieved at 48 h post injection of (111)In-labeled antisense ODNs (3.7 MBq; 2 microg). Tumors displaying basal levels of p21(WAF-1/CIP-1) gene expression in the absence of EGF treatment could not be visualized. Biodistribution studies showed a significantly higher tumor accumulation of (111)In-labeled antisense ODNs in

The legumin gene family: structure of a B type gene of Vicia faba and a possible legumin gene specific regulatory element.

PubMed Central

Bäumlein, H; Wobus, U; Pustell, J; Kafatos, F C

1986-01-01

The field bean, Vicia faba L. var. minor, possesses two sub-families of 11 S legumin genes named A and B. We isolated from a genomic library a B-type gene (LeB4) and determined its primary DNA sequence. Gene LeB4 codes for a 484 amino acid residue prepropolypeptide, encompassing a signal peptide of 22 amino acid residues, an acidic, very hydrophilic alpha-chain of 281 residues and a basic, somewhat hydrophobic beta-chain of 181 residues. The latter two coding regions are immediately contiguous, but each is interrupted by a short intron. Type A legumin genes from soybean and pea are known to have introns in the same two positions, in addition to an extra intron (within the alpha-coding sequence). Sequence comparisons of legumin genes from these three plants revealed a highly conserved sequence element of at least 28 bp, centered at approximately 100 bp upstream of each cap site. The element is absent from the equivalent position of all non-legumin and other plant and fungal genes examined. We tentatively name this element "legumin box" and suggest that it may have a function in the regulation of legumin gene expression. PMID:3960730

An XPA gene splicing mutation resulting in trace protein expression in an elderly patient with xeroderma pigmentosum group A without neurological abnormalities.

PubMed

Takahashi, Y; Endo, Y; Kusaka-Kikushima, A; Nakamaura, S; Nakazawa, Y; Ogi, T; Uryu, M; Tsuji, G; Furue, M; Moriwaki, S

2017-07-01

A certain relationship between XPA gene mutations and the severity of symptoms has been observed in patients with xeroderma pigmentosum group A (XP-A). Patients with mutations within the DNA-binding domain usually exhibit severe symptoms, whereas splicing mutations in the same domain sometimes cause very mild symptoms. This inconsistency can be explained by a small amount of functional XPA protein produced from normally spliced transcripts. We herein report the case of an adult Japanese patient with XP-A with unusually mild symptoms. We identified a homozygous c.529G>A mutation in exon 4 of the XPA gene, which resulted in aberrant splicing with a 29-bp deletion in exon 4 causing a frameshift. Intact mRNA was observable, but a Western blot analysis failed to detect any normal XPA protein. We therefore evaluated the DNA repair capacity in normal cells in which the XPA expression was artificially diminished. The repair capacity was still present in cells with trace levels of the XPA protein. The repair capacity of the cells derived from our patient with mild symptoms was poor by comparison, but still significant compared with that of the cells derived from a patient with XP-A with severe symptoms. These results provide strong evidence that a trace level of XPA protein can still exert a relatively strong repair capacity, resulting in only a mild phenotype. © 2016 British Association of Dermatologists.

Lentiviral CRISPR/Cas9 vector mediated miR-21 gene editing inhibits the epithelial to mesenchymal transition in ovarian cancer cells.

PubMed

Huo, Wenying; Zhao, Guannan; Yin, Jinggang; Ouyang, Xuan; Wang, Yinan; Yang, Chuanhe; Wang, Baojing; Dong, Peixin; Wang, Zhixiang; Watari, Hidemichi; Chaum, Edward; Pfeffer, Lawrence M; Yue, Junming

2017-01-01

CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats) mediated genome editing is a powerful approach for loss of function studies. Here we report that lentiviral CRISPR/Cas9 vectors are highly efficient in introducing mutations in the precursor miRNA sequence, thus leading to the loss of miRNA expression and function. We constructed four different lentiviral CRISPR/Cas9 vectors that target different regions of the precursor miR-21 sequence and found that these lentiviral CRISPR/Cas9 miR-21 gRNA vectors induced mutations in the precursor sequences as shown by DNA surveyor mutation assay and Sanger sequencing. Two miR-21 lentiviral CRISPR/Cas9 gRNA vectors were selected to probe miR-21 function in ovarian cancer SKOV3 and OVCAR3 cell lines. Our data demonstrate that disruption of pre-miR-21 sequences leads to reduced cell proliferation, migration and invasion. Moreover, CRISPR/Cas9-mediated miR-21 gene editing sensitizes both SKOV3 and OVCAR3 cells to chemotherapeutic drug treatment. Disruption of miR-21 leads to the inhibition of epithelial to mesenchymal transition (EMT) in both SKOV3 and OVCAR3 cells as evidenced by the upregulation of epithelial cell marker E-cadherin and downregulation of mesenchymal marker genes, vimentin and Snai2. The miR-21 target genes PDCD4 and SPRY2 were upregulated in cells transduced with miR-21gRNAs compared to controls. Our study indicates that lentiviral CRISPR/Cas9-mediated miRNA gene editing is an effective approach to address miRNA function, and disruption of miR-21 inhibits EMT in ovarian cancer cells.

Lentiviral CRISPR/Cas9 vector mediated miR-21 gene editing inhibits the epithelial to mesenchymal transition in ovarian cancer cells

PubMed Central

Huo, Wenying; Zhao, Guannan; Yin, Jinggang; Ouyang, Xuan; Wang, Yinan; Yang, Chuanhe; Wang, Baojing; Dong, Peixin; Wang, Zhixiang; Watari, Hidemichi; Chaum, Edward; Pfeffer, Lawrence M.; Yue, Junming

2017-01-01

CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats) mediated genome editing is a powerful approach for loss of function studies. Here we report that lentiviral CRISPR/Cas9 vectors are highly efficient in introducing mutations in the precursor miRNA sequence, thus leading to the loss of miRNA expression and function. We constructed four different lentiviral CRISPR/Cas9 vectors that target different regions of the precursor miR-21 sequence and found that these lentiviral CRISPR/Cas9 miR-21 gRNA vectors induced mutations in the precursor sequences as shown by DNA surveyor mutation assay and Sanger sequencing. Two miR-21 lentiviral CRISPR/Cas9 gRNA vectors were selected to probe miR-21 function in ovarian cancer SKOV3 and OVCAR3 cell lines. Our data demonstrate that disruption of pre-miR-21 sequences leads to reduced cell proliferation, migration and invasion. Moreover, CRISPR/Cas9-mediated miR-21 gene editing sensitizes both SKOV3 and OVCAR3 cells to chemotherapeutic drug treatment. Disruption of miR-21 leads to the inhibition of epithelial to mesenchymal transition (EMT) in both SKOV3 and OVCAR3 cells as evidenced by the upregulation of epithelial cell marker E-cadherin and downregulation of mesenchymal marker genes, vimentin and Snai2. The miR-21 target genes PDCD4 and SPRY2 were upregulated in cells transduced with miR-21gRNAs compared to controls. Our study indicates that lentiviral CRISPR/Cas9-mediated miRNA gene editing is an effective approach to address miRNA function, and disruption of miR-21 inhibits EMT in ovarian cancer cells. PMID:28123598

[Effect of sodium phenylbutyrate on the apoptosis of human tongue squamous cancer cell line and expression of p21 and survivin genes].

PubMed

Chen, Wei-qiang; Feng, Feng-lan; Gu, Hong-biao; Pan, De-shun

2010-07-01

To examine the effects of sodium phenylbutyrate on the apoptosis of human tongue squamous cancer cell line and expression of p21 and survivin genes. The inhibition effects of sodium phenylbutyrate on Tca8113 and human tongue squamous cell carcinoma (TCSSA) cell lines were detected by methyl thiazoly terazolium (MTT) and the apoptosis of the cancer cells after being induced by sodium phenylbutyrate examined by flow cytometry (FCM). The expression of p21 and survivin genes were observed with Western blotting and RT-PCR. Compared with control group, the level of p21 mRNA and protein of Tca8113 cellline increased to 0.09 ± 0.08 and increased 0.72 ± 0.10, that of TCSSA cellline increased 1.34 ± 0.12 and 1.56 ± 0.09 (P < 0.05). Compared with control group, the level of surrive mRNA and protein of Tca8113 cellline decreased to 1.10 ± 0.05 and 1.14 ± 1.10, that of TCSSA cellline decreased to 0.12 ± 0.08 and 0.94 ± 0.09 (P < 0.05). Sodium phenylbutyrate inhibited the cell proliferation, promoted cell apoptosis and arrested the cells in G₁/G₀ phase. The amount of p21 mRNA and protein were increased, and the expression of survivin gene was decreased. Sodium phenylbutyrate exhibited remarkable inhibitory effects on human tongue squamous cancer cell proliferation and induced cancer cell apoptosis. The mechanism may be due to up-regulation of p21 gene and down-regulation of survivin gene. The mRNA level of p21 gene and survivin gene showed a strong correlation.

Cutaneous metastases during an aggressive course of Xp11.2 translocation renal cell carcinoma in a teenager.

PubMed

Sudour-Bonnange, Helene; Leroy, Xavier; Chauvet, Marie-Pierre; Classe, Marion; Robin, P M; Leblond, Pierre

2014-09-01

We reported a rare case of cutaneous metastases of renal cell carcinoma (RCC) with an Xp11.2 translocation in a 15-year-old female. Clinicians should be aware of the possibility of this uncommon site of metastasis, which can indicate multivisceral dissemination of the disease. We discuss the feasibility and opportunity of treating such a patient with multiple line of tyrosine kinase inhibitor (TKI) targeting vascular endothelial and platelet-derived growth factor receptors. © 2014 Wiley Periodicals, Inc.

Molecular defects of the CYP21A2 gene in Greek-Cypriot patients with congenital adrenal hyperplasia.

PubMed

Skordis, Nicos; Kyriakou, Andreas; Tardy, Véronique; Ioannou, Yiannis S; Varvaresou, Athanasia; Dracopoulou-Vabouli, Maria; Patsalis, Philippos C; Shammas, Christos; Neocleous, Vassos; Phylactou, Leonidas A

2011-01-01

To determine the mutations in the CYP21A2 gene in Greek-Cypriots with congenital adrenal hyperplasia (CAH) and attempt a genotype-phenotype correlation. Molecular analysis was performed by multiplex ligation-dependent probe amplification and direct sequencing of PCR products of the CYP21A2 gene in 32 CAH patients. The most frequent genetic defect in the classic salt-wasting and simple virilizing forms was the IVS2-13A/C>G (55%) mutation, followed by Large lesion (20%) and in the non-classical form, the p.V281L (79.5%). Genotypes were categorized in 4 mutation groups (null, A, B and C). All 3 patients in the null group manifested the salt-wasting form and all 6 patients in mutation group A presented with the classical form. One patient in group B had the simple virilizing form and 22 patients in group C exhibited the non-classical form. The spectrum of mutations of the CYP21A2 gene in our population is comparable to the most common reported in similar ethnic groups. The knowledge of the ethnic specificity of the CYP21A2 mutations represents a valuable diagnostic tool for all forms of CAH. Copyright © 2010 S. Karger AG, Basel.

Economic impact of 21-gene recurrence score testing on early-stage breast cancer in Ireland.

PubMed

Smyth, Lillian; Watson, Geoff; Walsh, Elaine M; Kelly, Catherine M; Keane, Maccon; Kennedy, M John; Grogan, Liam; Hennessy, Bryan T; O'Reilly, Seamus; Coate, Linda E; O'Connor, Miriam; Quinn, Cecily; Verleger, Katharina; Schoeman, Olaf; O'Reilly, Susan; Walshe, Janice M

2015-10-01

The 21-gene test is a validated multi-gene diagnostic test that predicts chemotherapy (CT) benefit in oestrogen receptor positive (ER+), lymph node-negative (N0) breast cancer (BC) patients (pts). Ireland was the first public health care system to reimburse this test in Europe. Study objectives were to assess the impact of this test on decision-making and to analyse the economic impact of testing. Between October 2011 and February 2013, a national, retrospective, cross-sectional observational study of ER+, N0 BC pts tested with the 21-gene test was conducted. Surveyed breast medical oncologists, provided the assumption for the decision impact analysis that grade (G) 1 pts would not have received CT before testing and G2/3 pts would have received CT before testing. Descriptive statistical analyses were performed. 592 pts were identified; Low, intermediate and high recurrence score were identified in 53, 36 and 10 % pts, respectively. 384 (70 %) pts had G2, 129 (22 %) G3 and 76 (13 %) G1 tumours. Post testing, 345 pts (59 %) experienced a change in CT decision; 339 changed to hormone therapy alone and 6 advised to receive CT. 172 (30 %) pts received CT, 12 (3.9 %) of pts with low scores, 108 (50.9 %) of intermediate risk and 50 (90.9 %) of pts with high risk scores. Net reduction in CT use was 58 % and net savings achieved were €793,565. Since public reimbursement, the introduction of the 21-gene test has resulted in a significant reduction in chemotherapy administration and cost savings for the Irish public healthcare system.