612 research outputs found
Особенности аппаратной реализации алгоритмов вычисления контрольной суммы CRC32
Приведено описание аппаратных реализаций матричного и табличного алгоритмов вычисления контрольной суммы CRC32 на ПЛИС Cyclone фирмы Altera макета SDK-6.1. Показаны особенности аппаратной реализации на примере описания блоков вычисления CRC32 и работоспособность спроектированных устройств на конкретных примерах
Clinical Utility Gene Card for: Familial adenomatous polyposis (FAP) and attenuated FAP (AFAP) - update 2014
Cellular mechanisms in basic and clinical gastroenterology and hepatolog
Low-level APC mutational mosaicism is the underlying cause in a substantial fraction of unexplained colorectal adenomatous polyposis cases
BACKGROUND: In 30-50% of patients with colorectal adenomatous polyposis, no germline mutation in the known genes APC, causing familial adenomatous polyposis, MUTYH, causing MUTYH-associated polyposis, or POLE or POLD1, causing polymerase-proofreading-associated polyposis can be identified, although a hereditary aetiology is likely. This study aimed to explore the impact of APC mutational mosaicism in unexplained polyposis. METHODS: To comprehensively screen for somatic low-level APC mosaicism, high-coverage next-generation sequencing of the APC gene was performed using DNA from leucocytes and a total of 53 colorectal tumours from 20 unrelated patients with unexplained sporadic adenomatous polyposis. APC mosaicism was assumed if the same loss-of-function APC mutation was present in ≥2 anatomically separated colorectal adenomas/carcinomas per patient. All mutations were validated using diverse methods. RESULTS: In 25% (5/20) of patients, somatic mosaicism of a pathogenic APC mutation was identified as underlying cause of the disease. In 2/5 cases, the mosaic level in leucocyte DNA was slightly below the sensitivity threshold of Sanger sequencing; while in 3/5 cases, the allelic fraction was either very low (0.1-1%) or no mutations were detectable. The majority of mosaic mutations were located outside the somatic mutation cluster region of the gene. CONCLUSIONS: The present data indicate a high prevalence of pathogenic mosaic APC mutations below the detection thresholds of routine diagnostics in adenomatous polyposis, even if high-coverage sequencing of leucocyte DNA alone is taken into account. This has important implications for both routine work-up and strategies to identify new causative genes in this patient group
A Comparison of Two Wearable Tactile Interfaces with a Complementary Display in Two Orientations
Survival of MUTYH-Associated Polyposis Patients With Colorectal Cancer and Matched Control Colorectal Cancer Patients
Background: MUTYH-associated polyposis is a recessively inherited disorder characterized by a lifetime risk of colorectal cancer that is up to 100%. Because specific histological and molecular genetic features of MUTYH-associated polyposis colorectal cancers might influence tumor behavior and patient survival, we compared survival between patients with MUTYH-associated polyposis colorectal cancer and matched control patients with colorectal cancer from the general population.
Method:s In this retrospective multicenter cohort study from Europe, 147 patients with MUTYH-associated polyposis colorectal cancer were compared with 272 population-based control patients with colorectal cancer who were matched for country, age at diagnosis, year of diagnosis, stage, and subsite of colorectal cancer. Kaplan–Meier survival and Cox regression analyses were used to compare survival between patients with MUTYH-associated polyposis colorectal cancer and control patients with colorectal cancer. All statistical tests were two-sided.
Results: Five-year survival for patients with MUTYH-associated polyposis colorectal cancer was 78% (95% confidence interval [CI] = 70% to 84%) and for control patients was 63% (95% CI = 56% to 69%) (log-rank test, P = .002). After adjustment for differences in age, stage, sex, subsite, country, and year of diagnosis, survival remained better for MUTYH-associated polyposis colorectal cancer patients than for control patients (hazard ratio of death = 0.48, 95% CI = 0.32 to 0.72).
Conclusions: In a European study cohort, we found statistically significantly better survival for patients with MUTYH-associated polyposis colorectal cancer than for matched control patients with colorectal cancer
Novel APC mutations in Czech and Slovak FAP families: clinical and genetic aspects
BACKGROUND: Germline mutations in the adenomatous polyposis gene (APC) result in familial adenomatous polyposis (FAP). FAP is an autosomal dominantly inherited disorder predisposing to colorectal cancer. Typical FAP is characterized by hundreds to thousands of colorectal adenomatous polyps and by several extracolonic manifestations. An attenuated form of polyposis (AFAP) is characterized by less than 100 adenomas and later onset of the disease. METHODS: Here, we analyzed the APC gene for germline mutations in 59 Czech and 15 Slovak FAP patients. In addition, 50 apparently APC mutation negative Czech probands and 3 probands of Slovak origin were screened for large deletions encompassing the APC gene. Mutation screening was performed using denaturing gradient gel electrophoresis and/or protein truncation test. DNA fragments showing an aberrant electrophoretic banding pattern were sequenced. Screening for large deletions was performed by multiplex ligation dependent probe amplification. The extent of deletions was analyzed using following microsatellite markers: D5S299, D5S82, D5S134 and D5S346. RESULTS: In the set of Czech and Slovak patients, we identified 46 germline mutations among 74 unrelated probands. Total mutation capture is 62,2% including large deletions. Thirty seven mutations were detected in 49 patients presenting a classical FAP phenotype (75,5%) and 9 mutations in 25 patients with attenuated FAP (36%). We report 20 novel germline APC mutations and 3 large deletions (6%) encompassing the whole-gene deletions and/or exon 14 deletion. In the patients with novel mutations, correlations of the mutation localization are discussed in context of the classical and/or attenuated phenotype of the disease. CONCLUSION: The results of the molecular genetic testing are used both in the establishment of the predictive diagnosis and in the clinical management of patients. In some cases this study has also shown the difficulty to classify clinically between the classical and the attenuated form of FAP according to the established criteria. Interfamilial and/or intrafamilial phenotype variability was also confirmed in some cases which did not fit well with predicted genotype-phenotype correlation. All these findings have to be taken into consideration both in the genetic counselling and in the patient care
Myocarditis related to Campylobacter jejuni infection: A case report
BACKGROUND: Myocarditis can develop as a complication of various infections and is most commonly linked to enterovirus infections. Myocarditis is rarely associated with bacterial infections; salmonellosis and shigellosis have been the most frequently reported bacterial cause. We report a case of myocarditis related to Campylobacter jejuni enteritis. CASE PRESENTATION: A 30-year-old previously healthy man presented with a history of prolonged chest pain radiating to the jaw and the left arm. Five days prior to the onset of chest pain, he developed bloody diarrhea, fever and chills. Creatine kinase (CK) and CK-MB were elevated to 289 U/L and 28.7 μg/L. Troponin I was 30.2 μg/L. The electrocardiogram (ECG) showed T wave inversion in the lateral and inferior leads. The chest pain resolved within 24 hours of admission. The patient had a completely normal ECG stress test. The patient was initiated on ciprofloxacin 500 mg po bid when Campylobacter jejuni was isolated from the stool. Diarrhea resolved within 48 hours of initiation of ciprofloxacin. The diagnosis of Campylobacter enteritis and related myocarditis was made based on the clinical and laboratory results and the patient was discharged from the hospital in stable condition. CONCLUSION: Myocarditis can be a rare but severe complication of infectious disease and should be considered as a diagnosis in patients presenting with chest pain and elevated cardiac enzymes in the absence of underlying coronary disease. It can lead to cardiomyopathy and congestive heart failure. There are only a few reported cases of myocarditis associated with Campylobacter infection
NS1 Specific CD8(+) T-Cells with Effector Function and TRBV11 Dominance in a Patient with Parvovirus B19 Associated Inflammatory Cardiomyopathy
Background: Parvovirus B19 (B19V) is the most commonly detected virus in endomyocardial biopsies (EMBs) from patients with inflammatory cardiomyopathy (DCMi). Despite the importance of T-cells in antiviral defense, little is known about the role of B19V specific T-cells in this entity.
Methodology and Principal Findings: An exceptionally high B19V viral load in EMBs (115,091 viral copies/mg nucleic acids), peripheral blood mononuclear cells (PBMCs) and serum was measured in a DCMi patient at initial presentation, suggesting B19V viremia. The B19V viral load in EMBs had decreased substantially 6 and 12 months afterwards, and was not traceable in PBMCs and the serum at these times. Using pools of overlapping peptides spanning the whole B19V proteome, strong CD8(+) T-cell responses were elicited to the 10-amico-acid peptides SALKLAIYKA (19.7% of all CD8(+) cells) and QSALKLAIYK (10%) and additional weaker responses to GLCPHCINVG (0.71%) and LLHTDFEQVM (0.06%). Real-time RT-PCR of IFN gamma secretion-assay-enriched T-cells responding to the peptides, SALKLAIYKA and GLCPHCINVG, revealed a disproportionately high T-cell receptor Vbeta (TRBV) 11 expression in this population. Furthermore, dominant expression of type-1 (IFN gamma, IL2, IL27 and Tbet) and of cytotoxic T-cell markers (Perforin and Granzyme B) was found, whereas gene expression indicating type-2 (IL4, GATA3) and regulatory T-cells (FoxP3) was low.
Conclusions: Our results indicate that B19V Ag-specific CD8(+) T-cells with effector function are involved in B19V associated DCMi. In particular, a dominant role of TRBV11 and type-1/CTL effector cells in the T-cell mediated antiviral immune response is suggested. The persistence of B19V in the endomyocardium is a likely antigen source for the maintenance of CD8(+) T-cell responses to the identified epitopes
The longest delay: Re-emergence of coral reef ecosystems after the Late Devonian extinctions
Reefs are an excellent tool for tracking marine-ecosystem changes, especially through mass extinction transitions. Although metazoan reefs proliferated during the Phanerozoic, prolonged metazoan reef-recovery intervals often occurred after extinction events. Here, we document and review the reef-recovery interval following the Late Devonian Frasnian-Famennian (Kellwasser) and end-Famennian (Hangenberg) mass extinctions, which eliminated the largest area of metazoan (stromatoporoid-coral) reefs of the Phanerozoic. Previous reports of the late Visean coral bioconstructions from western Palaeotethys Ocean, may mark the first metazoan reef proliferation after the Hangenberg extinction. In this study, abundant coral reefs, coral frameworks and coral biostromes were described in detail for the first time from the late Visean strata on the South China Block (eastern Palaeotethys Ocean). The occurrence of these coral bioconstructions further suggests that the late Visean coral reef recovery may have been a widespread phenomenon. Based on the high-resolution reef database constructed in this study, three sub-intervals of the Mississippian metazoan reef recovery were distinguished, which are (1) metazoan “reef gap” phase (MRG) without metazoan reefs during the Tournaisian; (2) metazoan reef re-establishment phase (MRR) containing a few metazoan reefs from early Visean to early part of the late Visean; and (3) metazoan reef proliferation phase (MRP) with global coral reef flourishment during the middle part of the late Visean (late Asbian to early Brigantian substages). Hence, coral reef ecosystems proliferated and became dominant in marine ecosystems during the late Asbian to early Brigantian, indicating a prolonged metazoan reef recovery of about 12 Ma and 23 Ma until the MRR and MRP, respectively. Coral reef proliferation at this time shows that the Mississippian was not solely a period dominated by microbial reefs. Late Visean coral reef development coincided with increased nektonic and benthic diversity, showing that metazoan reef recovery closely tracked overall marine ecosystem evolution. Even compared with other slow reef-recovery intervals, such as the middle-late Cambrian and Early-Middle Triassic with the intervals until the MRR and MRP of 5 Ma and 2 Ma, and 15 Ma and 9 Ma respectively, the Mississippian metazoan reef recovery was the longest in reef history. Harsh climatic and oceanic conditions were present during the Mississippian, mainly including the widespread marine anoxia during the middle part of Tournaisian and the following recurrent glacial and interglacial climatic episodes with frequent changes in sea level, sedimentary facies and sea-water surface temperature, which may have stymied metazoan reef recovery during this time. During the late Visean, marine communities flourished during a phase of relative warm conditions and high sea level, and coincided with the long-delayed re-emergence of coral reef ecosystems after the Late Devonian extinctions
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