Hepatitis C virus quasispecies in cancerous and noncancerous hepatic lesions: the core protein-encoding region.

We have shown that highly proofreading DNA polymerase is required for the polymerase chain reaction in the genetic analysis of hepatitis C virus (HCV). To clarify the status of HCV quasispecies in hepatic tissue using proofreading DNA polymerase, we performed a genetic analysis of the HCV core protein-encoding region in cancerous and noncancerous lesions derived from 4 patients with hepatocellular carcinoma. In contrast to the previously published data, we observed neither deletions nor stop codons in the analyzed region and no significant difference in the complexity of HCV quasispecies between cancerous and noncancerous lesions. This result suggests that the HCV core gene is never structurally defective in hepatic tissues, including cancerous lesions. However, in 3 of the patients, the consensus HCV species differed between cancerous and noncancerous lesions, suggesting that the predominant replicating HCV species differs between these 2 types of lesions. Moreover, during the course of the study, we obtained several interesting variants possessing a substitution at codon 9 of the core gene, whose substitution has been shown to induce the production of the F protein synthesized by a - 2/+1 ribosomal frameshift.</p

Light-Induced Degradation Mechanism in Poly(3-hexylthiophene)/Fullerene Blend Solar Cells

The mechanism of light-induced degradation in organic solar cells based on regioregular poly(3-hexylthiophene) and indene-C60 bisadduct is studied by transient absorption (TA) and electron spin resonance (ESR) measurements. After 45 h light exposure under simulated solar illumination at 100 mW cm-2, the short-circuit current density, open-circuit voltage, and fill factor are all degraded by about 20%-30% relative to the initial photovoltaic parameters. For the assignment of limiting conversion processes in the degraded solar cells, exciton diffusion into a donor/acceptor interface, charge transfer at the interface, charge dissociation into free charge carriers, and charge collection to each electrode are observed before and after the light exposure by the TA measurement. As a result, it is found that the charge collection deteriorates after the light exposure because of light-induced charge trap formation in the bulk of the active layer. The origin of charge traps is further discussed on the basis of ESR measurements and density functional theory calculation

Progressing subglottic and tracheobronchial stenosis in a patient with CHARGE syndrome diagnosed in adulthood

AbstractA 33-year-old woman was admitted for a pseudocroup-like cough and wheezing after general anesthesia. Several months ago, she had undergone cardiac re-operation and turbinectomy, both of which had involved difficult intubations. Bronchoscopy indicated a pin-hall-like subglottic stenosis; therefore, emergency tracheotomy was performed. Six years later, a computed tomography scan demonstrated progressive stenosis of the entire circumference of the trachea and main bronchi. She died at 40 years. Her autopsy revealed marked tracheobronchial stenosis. She had many medical histories that had gone undiagnosed and had been clinically ill with only heart defects. She did not have coloboma but had microphthalmos, atresia choanae, retarded growth development, and deafness; thus, we diagnosed CHARGE syndrome that refers to multiple congenital anomalies, including airway abnormalities, which can lead to secondary complications such as traumatic stenosis after intubation. Physicians should have knowledge of this rare disease and should pay special attention to potential airway problems

Acute non-heparin-induced thrombocytopenia during hemodiafiltration in a patient with multiple myeloma

This report demonstrates that not only heparin‐induced thrombocytopenia, but also hemodialysis conditions (platelet activation due to hemodiafiltration and heparin underdosing) may markedly reduce the platelet count and cause clotting in the hemodialysis circuit in patients in a hypercoagulable state. The clot prevention effects of bortezomib are therefore of great importance

926-24 Clinical and Electrophysiological Characteristics in Patients with Exercise Induced Idiopathic Multiform Ventricular Tachycardia. Differential Effects of Atrial Pacing and Isoproterenol Infusion on QTc Interval and Induction of Ventricular Arrhythmia

Idiopathic multiform ventricular tachycardia (VT) is characterized by normal QT interval at restand 3 or more distinct QRS configuration during VT, which has been distinguished from torsade de pointes in long QT syndrome. Facilitation by exercise and suppression by β-antagonist of this VT suggest that it may depend on rapid heart rate (HR) or increased sympathetic tone. To determine which factors is responsible, we performed atrial pacing (120/min) and isoproterenol (ISP) infusion (0.5 or 1.0μg to attain HR 120/min) in 6 patients (2 males/4 females, mean 15.8 years) and 10 control (4 males/6 females, mean 22.8 years). Inducibility of premature ventricular contraction (PVC) or VT, and response of QTc interval (QT/√RR) were evaluated during the procedures.controlmultiform VTp valuePVCNT inductionAtrial pacing0/71/6n.s.Isoproterenol0/86/60.001OTc (secl/2)Rest0.40±0.02 (n=10)0.40±0.03n.s.Atrial pacing0.43±0.02 (n=7)0.47±003&lt;0.01Isoproterenol0.44±0.01 (n=8)0.50±0.05&lt;0.001ConclusionAlthough both rapid HR and increased sympathetic tone may be responsible for this VT, contribution of the latter is predominant. Differential response of QT interval to atrial pacing and isoproterenol infusion may have a possible role for the occurrence of this VT

Genetic Interactions between Chromosomes 11 and 18 Contribute to Airway Hyperresponsiveness in Mice

We used two-dimensional quantitative trait locus analysis to identify interacting genetic loci that contribute to the native airway constrictor hyperresponsiveness to methacholine that characterizes A/J mice, relative to C57BL/6J mice. We quantified airway responsiveness to intravenous methacholine boluses in eighty-eight (C57BL/6J X A/J) F2 and twenty-seven (A/J X C57BL/6J) F2 mice as well as ten A/J mice and six C57BL/6J mice; all studies were performed in male mice. Mice were genotyped at 384 SNP markers, and from these data two-QTL analyses disclosed one pair of interacting loci on chromosomes 11 and 18; the homozygous A/J genotype at each locus constituted the genetic interaction linked to the hyperresponsive A/J phenotype. Bioinformatic network analysis of potential interactions among proteins encoded by genes in the linked regions disclosed two high priority subnetworks - Myl7, Rock1, Limk2; and Npc1, Npc1l1. Evidence in the literature supports the possibility that either or both networks could contribute to the regulation of airway constrictor responsiveness. Together, these results should stimulate evaluation of the genetic contribution of these networks in the regulation of airway responsiveness in humans.</p

Successful resection of liver metastasis detected by exacerbation of skin symptom in a patient with dermatomyositis accompanied by rectal cancer: a case report and literature review

Abstract Background Dermatomyositis (DM) is a rare syndrome that belongs to the group of idiopathic inflammatory myopathies. The association between DM and malignancy is well recognized, and the severity of DM symptoms has been linked to the progression of metastatic disease. Case presentation We report the case of a 42-year-old man that was diagnosed with dermatomyositis (DM) and rectal cancer. Proctectomy was performed, and DM symptoms were resolved postoperatively. One year and 9\ua0months after the surgery, liver metastasis occurred accompanied by the exacerbation of DM symptom. Partial resection of the liver was performed, and postoperative course was uneventful. DM symptoms improved postoperatively, and no evidence of cancer recurrence or DM symptoms was observed 2\ua0years after the second surgery. To date, few reports have described recurring cases of DM accompanied by colorectal cancer in detail. We reviewed four similar cases that were reported poor prognoses with treatment resistance. However, our case report demonstrates good long-term results with resection of metastatic lesion. Conclusions It is important to check the exacerbation of DM symptoms, as this symptom sometimes preceded cancer relapse during the follow-up of our patient with DM and colorectal cancer

L-Carnitine Prevents Progression of Non-Alcoholic Steatohepatitis in a Mouse Model with Upregulation of Mitochondrial Pathway

Non-alcoholic steatohepatitis (NASH) is a severe form of non-alcoholic fatty liver disease characterized by lobular inflammation, hepatocellular ballooning, and fibrosis with an inherent risk for progression to cirrhosis and hepatocellular carcinoma (HCC). Mitochondrial dysfunction appears to play a role in the progression from simple steatosis to NASH. L-carnitine (L-b-hydroxy-g-N-trimethylaminobutyric acid), an essential nutrient that converts fat into energy in mitochondria, has been shown to ameliorate liver damage. The aim of the present study was to explore the preventive and therapeutic effect of L-carnitine in NASH model mice. Eight-week-old male STAM mice, a NASH-cirrhosis-hepatocarcinogenic model, were divided into 3 experimental groups and fed as follows: 1) high-fat diet (HFD) (control group); 2) HFD mixed with 0.28% L-carnitine (L-carnitine group); and 3) HFD mixed with 0.01% alpha-tocopherol (alpha-tocopherol group). After 4 or 8 weeks, mice were sacrificed. Blood samples and livers were collected, and hepatic tumors were counted and measured. Livers were subjected to histological study, immunohistochemical staining of 4-hydroxynonenal and ferritin, determination of 8-OHdG levels, mRNA and protein expressions for multiple genes, and metabolomic analysis. The intestinal microbiome was also analyzed. L-carnitine increased hepatic expression of genes related to long-chain fatty acid transport, mitochondrial beta-oxidation, and antioxidant enzymes following suppression of hepatic oxidative stress markers and inflammatory cytokines in NASH, and mice treated with L-carnitine developed fewer liver tumors. Although alpha-tocopherol resulted in NASH improvement in the same manner as L-carnitine, it increased periodontitis-related microbiotic changes and hepatic iron transport-related gene expression and led to less effective for anti-hepatocarcinogenesis. Conclusion: L-carnitine prevents progression of non-alcoholic steatohepatitis in a mouse model by upregulating the mitochondrial beta-oxidation and redox system