Scintigraphic study of regenerative nodules due to fulminant hepatic failure

We report the case of a 25-year-old woman with fulminant hepatic failure (FHF). Liver scintigraphy using ^99mTc-galactosyl human serum albumin (GSA) and ^99mTc-phytate produced interesting findings; regenerative nodules appeared as nodules of increased accumulation of ^99mTc-GSA, whereas these nodules were expressed as defects of accumulation of ^99mTc-phytate. These scintigraphic findings suggested that the functions of hepatocytes in regenerative nodules were maintained, whereas those of Kupffer cells were impaired. Although ^99mTc-GSA scintigraphy indicated hepatic functional reserve enough to survive, she died despite intensive therapy including plasma exchange. Based on this case, it is recommended that not only ^99mTc-GSA scintigraphy but also ^99mTc-phytate scintigraphy is required to evaluate the prognosis of patients with FHF.     

Hepatitis C virus inhibitor synergism suggests multistep interactions between heat-shock protein 90 and hepatitis C virus replication

AIM: To address the effect of heat-shock protein 90(HSP90) inhibitors on the release of the hepatitis C virus(HCV), a cell culture-derived HCV(JFH1/HCVcc) from Huh-7 cells was examined.METHODS: We quantified both the intracellular and extracellular(culture medium) levels of the components(RNA and core) of JFH-1/HCVcc. The intracellular HCV RNA and core levels were determined after the JFH1/HCVcc-infected Huh-7 cells were treated with radicicol for 36 h. The extracellular HCV RNA and core protein levels were determined from the medium of the last 24 h of radicicol treatment. To determine the possible role of the HSP90 inhibitor in HCV release, we examined the effect of a combined application of low doses of the HSP90 inhibitor radicicol and the RNA replication inhibitors cyclosporin A(Cs A) or interferon. Finally, we statistically examined the combined effect of radicicoland Cs A using the combination index(CI) and graphical representation proposed by Chou and Talalay.RESULTS: We found that the HSP90 inhibitors had greater inhibitory effects on the HCV RNA and core protein levels measured in the medium than inside the cells. This inhibitory effect was observed in the presence of a low level of a known RNA replication inhibitor(Cs A or interferon-α). Treating the cells with a combination of radicicol and cyclosporin A for 24 h resulted in significant synergy(CI 1) that affected the release of both the viral RNA and the core protein. CONCLUSION: In addition to having an inhibitory effect on RNA replication, HSP90 inhibitors may interfere with an HCV replication step that occurs after the synthesis of viral RNA, such as assembly and release.     

Comparison of tissue pressure and ablation time between the LeVeen and cool-tip needle methods

Background  

Radio frequency ablation (RFA) has been accepted clinically as a useful local treatment for hepatocellular carcinoma (HCC). However, intrahepatic recurrence after RFA has been reported which might be attributable to increase in intra-tumor pressure during RFA. To reduce the pressure and ablation time, we developed a novel method of RFA, a multi-step method in which a LeVeen needle, an expansion-type electrode, is incrementally and stepwise expanded. We compared the maximal pressure during ablation and the total ablation time among the multi-step method, single-step method (a standard single-step full expansion with a LeVeen needle), and the method with a cool-tip electrode. Finally, we performed a preliminary comparison of the ablation times for these methods in HCC cases.     

Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism in schizophrenia is associated with age at onset and symptoms

The substantia nigra pars reticulata (SNR) plays important roles in movement and, in an age- and sex-dependent manner, in seizure control. GABAergic synaptic transmission is critical in both normal development and seizures. In many neuronal types it is excitatory early in development and later switches to the mature hyperpolarizing type. We assessed the time course of the switch of GABAA receptor-mediated postsynaptic currents (PSCs) in anterior SNR neurons of male and female developing rats using the gramicidin perforated patch clamp technique. The switch occurred in males around postnatal day (PN) 17 and in females around PN10. This sex dimorphism may play a role in several other recognized sex differences in the development of SNR and in its regulatory role in seizures.     

Altered HDAC5 and CREB mRNA expressions in the peripheral leukocytes of major depression

BACKGROUND: Gene expressions of the peripheral leukocytes in depressive patients might reflect the systemic dysfunction of major depression. We determined mRNA expression levels of Histone deacetylase 5 (HDAC5) gene and cyclic AMP response element-binding protein 1 (CREB) gene in the leukocyte of depressive patients. HDAC5 and CREB are reported to be important targets of antidepressants, the latter being located in the downstream of the former in lymphocyte calcium signaling. METHODS: 25 patients with major depression and 25 age- and sex-matched healthy controls were included in this study. Twenty patients were able to be followed up until the 8 week-treatment. The mRNA levels were determined by a quantitative RT-PCR method. RESULT: Levels of HDAC5 and CREB mRNA were significantly higher in drug-free depressive patients than those of controls and the higher mRNA levels decreased to control levels after 8-week paroxetine treatment. There were positive correlation between levels of HDAC5 and CREB. CONCLUSION: Our results suggest the alteration of HDAC5 and CREB gene expression in the systemic pathophysiology of major depression.     

Molecular cloning, tissue distribution, and ontogenic thyroidal expression of the chicken thyrotropin receptor

TSH and the interaction with its receptor (TSHR) in the thyroid gland play a crucial role in the pituitary-thyroid axis of all vertebrates. Released upon stimulation by TSH, thyroid hormones influence numerous processes in the body and are extremely important during the last week of chicken embryonic development. In this study, we have cloned and functionally characterized the chicken TSHR (cTSHR), which was found to be a G protein-coupled receptor consisting of 10 exons. Besides the full-length cDNA, we detected two splice variants lacking either exon 3, or exons 2 and 3, both part of the extracellular domain of the receptor. Bovine TSH increased intracellular cAMP levels in HEK-239 cells transiently expressing the full-length cTSHR (EC50 = 1.43 nm). In situ hybridization showed the expression of cTSHR mRNA in the thyroidal follicular cells. cTSHR mRNA expression, as determined by real-time PCR, was also found in several other tissues such as brain, pituitary, pineal gland, and retina, suggesting that the TSH-TSHR interaction is not only important in regulating thyroid function. TSHR mRNA expression in the thyroid gland did not change significantly during the last week of embryonic development, which suggests that an increased thyroidal sensitivity is not part of the cause of the concomitant increasing T4 levels.     

Additive Effect of Graphene and Lignin-Derived Graphene on Radical Polymerization Behaviors of Methacrylate Monomers

Radical polymerizations of methyl methacrylate (MMA) using graphene or lignin-derived graphene as additives give the corresponding poly(MMA)s of which much wider molecular weight distribution (MWD) than that of the poly(MMA) without additives. The MWD of the resulting poly(MMA) using graphene is wider compared to that using lignin-derived graphene, suggesting that the structural differences between the two graphene compounds affect radical polymerization behavior. Furthermore, the radical polymerizations of methacrylate monomers with different substituents using the two graphene compounds are performed, leading to the additive effect of the two graphene compounds which is relevant to the steric hindrance of the monomer.     

Adjuvant therapy with nivolumab versus ipilimumab after complete resection of stage III/IV melanoma: Japanese subgroup analysis from the phase 3 CheckMate 238 study

The multinational phase 3 CheckMate 238 trial compared adjuvant therapy with nivolumab versus ipilimumab among patients with resected stage III or IV melanoma (N = 906). In this Japanese subgroup analysis of CheckMate 238 (n = 28; nivolumab, n = 18; ipilimumab, n = 10), both the 12‐ and 18‐month recurrence‐free survival rates were 56% for nivolumab and 30% for ipilimumab (hazard ratio, 0.66; 97.56% confidence interval, 0.19–2.24; P = 0.4390). No new safety signals were reported for Japanese patients. Results were consistent with those from the CheckMate 238 global population, indicating that nivolumab has the potential to be a treatment option for Japanese patients with resected melanoma who are at high risk of recurrence.