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31.
Thierbach R Schulz TJ Isken F Voigt A Mietzner B Drewes G von Kleist-Retzow JC Wiesner RJ Magnuson MA Puccio H Pfeiffer AF Steinberg P Ristow M 《Human molecular genetics》2005,14(24):3857-3864
We have disrupted expression of the mitochondrial Friedreich ataxia protein frataxin specifically in murine hepatocytes to generate mice with impaired mitochondrial function and decreased oxidative phosphorylation. These animals have a reduced life span and develop multiple hepatic tumors. Livers also show increased oxidative stress, impaired respiration and reduced ATP levels paralleled by reduced activity of iron-sulfur cluster (Fe/S) containing proteins (ISP), which all leads to increased hepatocyte turnover by promoting both apoptosis and proliferation. Accordingly, phosphorylation of the stress-inducible p38 MAP kinase was found to be specifically impaired following disruption of frataxin. Taken together, these findings indicate that frataxin may act as a mitochondrial tumor suppressor protein in mammals. 相似文献
32.
Genome profiles of bilateral dysgerminomas, a unilateral gonadoblastoma, and a metastasis from a 46, XY phenotypic female 总被引:3,自引:0,他引:3
Kildal W Kraggerud SM Abeler VM Heim S Tropé CG Kristensen GB Risberg B Lothe RA Danielsen HE 《Human pathology》2003,34(9):946-949
We present a case report of a 16-year-old, phenotypic female with bilateral dysgerminomas, a unilateral gonadoblastoma, and a peritoneal metastasis. The patient's constitutional karyotype was 46,XY. The chromosomal copy number, examined by the comparative genomic hybridization technique, showed 3 gains in the dysgerminoma of the right ovary, 6 gains in the dysgerminoma of the left ovary, and 2 gains and 1 loss in the gonadoblastoma of the left ovary. The metastasis showed 5 gains of which 4 were also observed in the dysgerminoma of the left ovary. The DNA ploidy classifications of the gonadoblastoma and the dysgerminoma in the right ovary were tetraploid, whereas the dysgerminoma in the left ovary and the metastasis were aneuploid. We therefore propose that the metastasis most probably developed from the dysgerminoma of the left ovary. 相似文献
33.
Comparison of serum hepatitis C virus RNA and core antigen concentrations and determination of whether levels are associated with liver histology or affected by specimen storage time 下载免费PDF全文
Lagging LM Garcia CE Westin J Wejstål R Norkrans G Dhillon AP Lindh M 《Journal of clinical microbiology》2002,40(11):4224-4229
An enzyme immunoassay has recently been developed for the hepatitis C virus (HCV) core antigen. To evaluate the possible association between core antigen and HCV RNA levels with regards to the change in liver histology over time as well as study the effect of duration of storage on viral load results, sequential sera were analyzed from 45 patients with chronic HCV infection who had undergone two or more liver biopsies. A relatively strong association was found between the core antigen and HCV RNA concentrations (r(s) = 0.8), with a core antigen level of 1 pg/ml corresponding to approximately 1,000 IU/ml. All 42 sera with detectable HCV RNA at the time of the second biopsy had core antigen concentrations above 1 pg/ml, and the three sera without detectable HCV RNA had concentrations below 1 pg/ml. No association was found between HCV RNA or core antigen levels and the stage of fibrosis in biopsy samples, progression of fibrosis, necro-inflammatory grade, steatosis, genotype, alanine aminotransferase level, or alcohol consumption. A significant association was demonstrated between the storage time of the samples and both the HCV RNA and core antigen concentrations. The median log HCV RNA concentrations (international units/milliliter) were 3.92 for the sera obtained at the time of the first biopsy (median storage time, 13.0 years) and 4.41 for the sera obtained at the time of the second biopsy (median storage time, 6.6 years) compared to 5.96, the median for 102 different routine clinical patient samples. 相似文献
34.
Micci F Walter CU Teixeira MR Panagopoulos I Bjerkehagen B Saeter G Heim S 《Cancer Genetics and Cytogenetics》2003,144(2):119-124
Endometrial stromal sarcomas (ESS) are rare neoplasms with the capacity both to invade the myometrium locally and to give rise to extrauterine metastases. Cytogenetic abnormalities have been reported in 22 cases of ESS, mostly involving rearrangements of chromosomes 6, 7, and 17. The most characteristic translocation of this tumor type, t(7;17)(p15 approximately p21;q12 approximately q21), was recently shown to generate a JAZF1/JJAZ1 fusion gene. We report three additional cases of ESS with abnormal karyotypes, whose interpretation was based on the combined analysis by conventional cytogenetics and cross-species color banding FISH (RxFISH). The combination of G-banding and RxFISH in every case gave additional information beyond that obtained by either technique alone, determining the identity of even complex inter- as well as intrachromosomal rearrangements. In one of the three tumors, a t(7;17) was seen; molecular genetic studies identified the JAZF1/JJAZ1 fusion gene in this case. Two tumors had aberrations that included structural changes of chromosome arms 6p and 7p. Evidently, karyotypic, and hence pathogenetic, heterogeneity exists for tumors classified as endometrial stromal sarcomas based on their phenotypic features. 相似文献
35.
Usefulness of high-resolution comparative genomic hybridization (CGH) for detecting and characterizing constitutional chromosome abnormalities 总被引:6,自引:0,他引:6
Comparative genomic hybridization (CGH) is a technique for detection of chromosomal imbalances in a genomic DNA sample. We here report the application of the recently developed method of high-resolution CGH on DNA samples from 66 children having various degrees of delayed psychomotor development with or without clear dysmorphic features and congenital malformations. In 5 of 50 patients with apparently normal karyotypes, a deletion or duplication was revealed by CGH. Only one of these cases had a subtelomeric rearrangement. In one of seven cases with a de novo apparently balanced translocation, deletions were found. In all nine cases where the origin of a marker chromosome or additional chromosomal material was difficult to determine, CGH gave a precise identification. The following findings were from cases having a deletion or duplication as the sole chromosomal imbalance; dup(2)(p16p21), del(4)(q21q21), del(6)(q14q15), del(6)(p12p12), dup(6)(q24qter), and dup(15)(q11q13). One case had dup(9)(p11pter) combined with a very small subtelomeric deletion on 6q. In our hands, CGH is highly useful not only for identifying known chromosomal imbalances, but also for finding elusive deletions or duplications in the large group of children with developmental delay with or without congenital abnormalities. In such cases, the diagnostic yield of CGH appears to be higher than what has been reported from subtelomeric FISH screening. 相似文献
36.
Expression of CD44 in effusions of patients diagnosed with serous ovarian carcinoma – diagnostic and prognostic implications 总被引:2,自引:0,他引:2
Berner HS Davidson B Berner A Risberg B Kristensen GB Trope CG Van de Putte G Nesland JM 《Clinical & experimental metastasis》2000,18(2):197-202
CD44 is a family of cell adhesion molecules involved in a variety of cellular functions. The present study analysed the expression
of two CD44 isoforms in serous effusions of patients diagnosed with ovarian carcinoma and corresponding primary and metastatic
lesions. Fifty-eight effusions, 23 primary ovarian tumours, and 44 metastatic lesions were studied for protein expression
of CD44s and v3-10 using immunohistochemistry. Results were correlated with clinical parameters. CD44v3-10 was seen in carcinoma
cells in the majority of cases at all sites. Malignant effusions showed an up-regulation of CD44s compared to both primary
tumours and metastatic solid lesions. Mesothelial cells frequently expressed CD44s, but were rarely immunoreactive for v3-10.
CD44s immunoreactivity in cancer cells in effusions was significantly more often observed in patients with FIGO stage 3 than
in stage 4 patients (P = 0.045). Staining results did not correlate with age, effusion site, metastatic site, tumour grade or residual tumour mass
after initial surgery. Likewise, comparison of overall and disease-free survival with expression of the CD44 isoforms studied
did not reveal any statistically significant associations. The up-regulation in CD44 levels in effusions, primarily in stage
3 disease, suggests that adhesion of ovarian carcinoma cells to mesothelium may be regulated at the level of CD44s expression,
and provides further evidence of phenotypic alteration in the transition from primary tumour cell clones to effusions. The
similar expression profile of CD44 in carcinoma cells in peritoneal and pleural effusions supports our previous observations
and the hypothesis that carcinoma cells in peritoneal effusions are truly metastatic.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
37.
John M. Opitz Gunnar B. Stickler James F. Reynolds 《American journal of medical genetics. Part A》1987,27(4):971-975
We report on a consanguineous Brazilian couple whose 2 children had tibial aplasia-ectrodactyly. Femoral bifurcation was present in one of the affected children. The relationship of tibial aplasia-ectrodactyly to the Gollop-Wolfgang complex is discussed. Clinical and genetic aspects of the conditions involving tibial aplasia and femoral bifurcation are discussed. 相似文献
38.
Gunnar Rockborn 《Archives of virology》1958,8(4):493-499
Summary Studies on serological distemper immunity in an urban dog population are reported. Presumably maternal antibodies were demonstrable in the youngest age groups with successive decrease in rate of immunity as well as in antibody titers with age, insignificant levels being reached at 5 to 6 months after birth. Antibodies in high titers indicating subclinical infections began to appear in year-old animals, and dogs above the age of 2 years showed immunity in 91% of the cases. A study of the age distribution of immunity and reported incidence of clinical disease indicated that distemper infection, frequent in the years preceding 1953, had been relatively rare in the period 1953 to 1955.This work was supported by grants from the Research Fund of the Royal Veterinary College. 相似文献
39.
Stefan Schneider Gunnar Folprecht Georg Krohne Hans Oberleithner 《Pflügers Archiv : European journal of physiology》1995,430(5):795-801
The nuclear envelope functions as a selective barrier separating the nuclear from the cytosolic compartment. Nuclear pore complexes (NPCs) mediate nuclear import and export of macromolecules and, therefore, are potential regulators of gene expression. In this study we applied atomic force microscopy (AFM) to visualize the three dimensional (3D) structure of individual NPCs in the absence and presence of two different antibodies, one directed against a pore protein (gp62) and another directed against Xenopus lamin LIII, a component of the nuclear lamina, a filament meshwork localized on the nucleoplasmic side of the nuclear envelope (NE) adjacent to and interacting with NPCs. Using 12-nm gold-labelled secondary antibodies and transmission electron microscopy we could clearly localize the primary single anti-gp62 antibody on NPCs and the primary single anti-LIII antibody between NPCs. Using AFM, the secondary antibodies against anti-gp62 could be detected as particles 7 nm in height on the nucleoplasmic face of NPCs. The secondary antibodies against anti-LIII could be clearly identified between NPCs. The secondary antibodies, attached to a 12-nm colloidal gold particle and visualized on glass, revealed similar shapes and heights as found on NEs. According to the 3D images, the volume of a single gold particle conjugated with secondary antibodies was 10 203 nm3. This volume is equivalent to the volume of 38 IgG molecules associated with one individual gold particle. A similar volume of 11 987 nm3 was calculated from a model assuming that the 150-kDa IgG molecules perfectly cover the spherical gold particle. We conclude that AFM can be used for identifying antibodies or other macromolecules associated with biomembranes. 相似文献
40.
Höglund M Gisselsson D Soller M Hansen GB Elfving P Mitelman F 《Cancer Genetics and Cytogenetics》2004,154(1):1-9
Molecular cytogenetic analysis frequently shows human papillomavirus (HPV) integration near translocation breakpoints in cervical cancer cells. We have recently described a cluster of HPV18 integrations in the distal end of the common fragile site FRA8C at 8q24 in primary cervical carcinoma samples. Chromosome band 8q24 contains the MYC gene (alias c-MYC), FRA8C, and FRA8D. The MYC gene is frequently deregulated--usually by translocation or amplification--in various tumor types. In the present study, we performed a molecular cytogenetic analysis of HPV18 integration patterns and the 8q24 translocation in a primary cervical carcinoma and in HeLa cells using combined binary ratio-fluorescence in situ hybridization. Our aim was to determine how the chromosomal breaks involved in these events relate physically to the MYC gene; whether they map to the FRA8C site, the FRA8D site, or both; and how they correlate with the occurrence of DNA flexibility domains. The 8q24 translocation breakpoints mapped between stretches of integrated HPV18 sequences in the distal end of FRA8C. This region contained DNA helix flexibility clusters, several of which mapped in the vicinity of HPV integration sites and translocation breakpoints in cervical carcinomas. DNA helix flexibility clusters were also found near known MYC translocation breakpoints in Burkitt lymphomas (BL), but most BL breakpoints mapped clearly outside FRA8C. Our data revealed that FRA8C is involved in HPV integration and chromosomal translocations in cervical carcinoma; however, this fragile site is not involved in classical MYC translocations in most BLs. In the context of the familial nature of cervical cancer, FRA8C may be considered a candidate susceptibility region for cervical carcinoma. 相似文献