Association between Vitamin D Receptor Gene Polymorphisms and Renal Osteodystrophy in Patients on Maintenance Hemodialysis

We examined the possible involvement of vitamin D receptor (VDR) gene polymorphisms in patients on maintenance hemodialysis and further investigated the relation between VDR genotypes and bone histology. Two hundred and nine patients undergoing regular hemodialysis (male/female ratio, 124/85) were included in this study. DNA was extracted from peripheral blood leukocytes. VDR genotypes were analyzed as restriction fragment length polymorphisms, by using BsmI, ApaI, TaqI and FokI. Lumbar bone mineral density was measured by dual-energy X-ray absorptiometry, and expressed as a Z-score. Serum 1,25(OH)2D3, osteocalcin and ntact-parathyroid hormone (i-PTH) were determined by an immunoradiometric assay. In 97 patients, bone biopsy as performed and the histology was divided into osteitis fibrosa, mild lesion, dynamic bone disease and osteomalacia. Serum levels of osteocalcin, i-PTH and bone mineral density were significantly lower in the presence of B, A, t and f alleles. However, in this study, we did not find any association between bone histology and the four VDR genotypes. We concluded that renal osteodystrophy in dialysis patients was modified by environmental factors such as medication with active vitamin D, age, gender and duration of chronic renal failure, and that the impact of the VDR allelic effect may play a small role in determining on bone histology

α-Fetoprotein Messenger RNA in the Blood Predicts Poor Prognosis of the Patients with Hepatocellular Carcinoma

α-Fetoprotein (AFP) messenger RNA (mRNA) in the peripheral blood of patients with hepatocellular carcinoma (HCC) may indicate hematogenous spread of HCC. This study examined the presence of AFP mRNA in the blood of 148 patients, in terms of clinical parameters, tumor metastasis and survival rate. For the prospective study, 109 patients with HCC were followed in the period between March 1996 and March 1999. AFP mRNA in the blood was examined by means of nested reverse transcription polymerase chain reaction. AFP mRNA was detected in the blood in 23 (15.5%) of 148 patients with HCC. AFP mRNA in the blood was significantly correlated with protein induced by vitamin K absence or antagonist II level, higher AFP level (200 IU/mL or more) and extrahepatic metastases, but not with tumor size, number of tumor nodules or tumor-nodule-metastasis stage. This prospective study confirmed that intra- and extra-hepatic metastases developed more frequently in the 22 AFP mRNA-positive patients than in the 87 AFP mRNA-negative patients (P < 0.01). The cumulative survival rate was significantly lower in the former than in the latter (P < 0.01). In conclusion, AFP mRNA in the blood is closely related to hematogenous spread and might be a good predictor of metastasis and poorer survival rate in HCC patients

Crystalline Inclusions in Hepatocyte Mitochondria of a Patient with Porphyria Cutanea Tarda

Intramitochondrial crystalline inclusions were found in hepatocytes of a patient with porphyria cutanea tarda (PCT). They were composed of parallel filamentous structures which measured approximately 12 nm in diameter. Each filament was separated from an adjacent filament by a space measuring approximately 5 nm. The mitochondria containing such inclusions were usually elongated and enlarged. It seemed likely that these changes are not particular in PCT, but indicate one reversible pathological finding in the liver

Development of an experimental platform for the investigation of laser-plasma interaction in conditions relevant to shock ignition regime

The shock ignition (SI) approach to inertial confinement fusion is a promising scheme for achieving energy production by nuclear fusion. SI relies on using a high intensity laser pulse (≈1016 W/cm2, with a duration of several hundred ps) at the end of the fuel compression stage. However, during laser-plasma interaction (LPI), several parametric instabilities, such as stimulated Raman scattering and two plasmon decay, nonlinearly generate hot electrons (HEs). The whole behavior of HE under SI conditions, including their generation, transport, and final absorption, is still unclear and needs further experimental investigation. This paper focuses on the development of an experimental platform for SI-related experiments, which simultaneously makes use of multiple diagnostics to characterize LPI and HE generation, transport, and energy deposition. Such diagnostics include optical spectrometers, streaked optical shadowgraph, an x-ray pinhole camera, a two-dimensional x-ray imager, a Cu Kα line spectrometer, two hot-electron spectrometers, a hard x-ray (bremsstrahlung) detector, and a streaked optical pyrometer. Diagnostics successfully operated simultaneously in single-shot mode, revealing the features of HEs under SI-relevant conditions.T. Tamagawa, Y. Hironaka, K. Kawasaki, D. Tanaka, T. Idesaka, N. Ozaki, R. Kodama, R. Takizawa, S. Fujioka, A. Yogo, D. Batani, Ph. Nicolai, G. Cristoforetti, P. Koester, L. A. Gizzi, and K. Shigemori, "Development of an experimental platform for the investigation of laser–plasma interaction in conditions relevant to shock ignition regime", Review of Scientific Instruments 93, 063505 (2022) https://doi.org/10.1063/5.008996

Lung Cancer in Pulmonary Fibrosis: Tales of Epithelial Cell Plasticity

Lung epithelial cells exhibit a high degree of plasticity. Alterations to lung epithelial cell function are critically involved in several chronic lung diseases such as pulmonary fibrosis. Pulmonary fibrosis is characterized by repetitive injury and subsequent impaired repair of epithelial cells, which leads to aberrant growth factor activation and fibroblast accumulation. Increased proliferation and hyper- and metaplasia of epithelial cells upon injury have also been observed in pulmonary fibrosis; this epithelial cell activation might represent the basis for lung cancer development. Indeed, several studies have provided histopathological evidence of an increased incidence of lung cancer in pulmonary fibrosis. The mechanisms involved in the development of cancer in pulmonary fibrosis, however, remain poorly understood. This review highlights recently uncovered molecular mechanisms shared between lung cancer and fibrosis, which extend the current evidence of a common trait of cancer and fibrosis, as provided by histopathological observations. Copyright (C) 2011 S. Karger AG, Base

Shock Hugoniot data for water up to 5 Mbar obtained with quartz standard at high-energy laser facilities

In this work, we present experimental results on the behavior of liquid water at megabar pressure. The experiment was performed using the HIPER (High-Intensity Plasma Experimental Research) laser facility, a uniaxial irradiation chamber of GEKKO XII (GXII) at the Institute of Laser Engineering (ILE), and the PHELIX at GSI (GSI Helmholtz Centre for Heavy Ion Research), a single-beam high-power laser facility, to launch a planar shock into solid multilayered water samples. Equation-of-state data of water (H2O) are obtained in the pressure range 0.50–4.6 Mbar by tuning the laser-drive parameters. The Hugoniot parameters (pressure, density, etc.) and the shock temperature were simultaneously determined by using VISAR and SOP as diagnostic tools and quartz as the standard material for impedance mismatch experiments. Finally, our experimental results are compared with hydrodynamic simulations tested with different equations of state, showing good compatibility with tabulated SESAME tables for water.The authors would like to acknowledge the support of the laser technical team at GEKKO XII (ILE) and PHELIX (GSI). This work received funding from the Euratom Research and Training Program 2014–2018 and 2019-2020 (Grant agreement no. 633053). The involved teams were operated within the framework of the Enabling Research Project ENR-IFE19.CEA-01, Study of Direct Drive and Shock Ignition for IFE: Theory, Simulations, Experiments, Diagnostics Development. JIHT RAS team members were supported by the Ministry of Science and Higher Education of the Russian Federation (State Assignment no. 075-00460-21-00).Peer reviewe

A novel biomarker TERTmRNA is applicable for early detection of hepatoma

<p>Abstract</p> <p>Backgrounds</p> <p>We previously reported a highly sensitive method for serum human telomerase reverse transcriptase (hTERT) mRNA for hepatocellular carcinoma (HCC). α-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP) are good markers for HCC. In this study, we verified the significance of hTERTmRNA in a large scale multi-centered trial, collating quantified values with clinical course.</p> <p>Methods</p> <p>In 638 subjects including 303 patients with HCC, 89 with chronic hepatitis (CH), 45 with liver cirrhosis (LC) and 201 healthy individuals, we quantified serum hTERTmRNA using the real-time RT-PCR. We examined its sensitivity and specificity in HCC diagnosis, clinical significance, ROC curve analysis in comparison with other tumor markers, and its correlations with the clinical parameters using Pearson relative test and multivariate analyses. Furthermore, we performed a prospective and comparative study to observe the change of biomarkers, including hTERTmRNA in HCC patients receiving anti-cancer therapies.</p> <p>Results</p> <p>hTERTmRNA was demonstrated to be independently correlated with clinical parameters; tumor size and tumor differentiation (P < 0.001, each). The sensitivity/specificity of hTERTmRNA in HCC diagnosis showed 90.2%/85.4% for hTERT. hTERTmRNA proved to be superior to AFP, AFP-L3, and DCP in the diagnosis and underwent an indisputable change in response to therapy. The detection rate of small HCC by hTERTmRNA was superior to the other markers.</p> <p>Conclusions</p> <p>hTERTmRNA is superior to conventional tumor markers in the diagnosis and recurrence of HCC at an early stage.</p

Hepatocyte growth factor in transgenic mice

In order to clarify the function of hepatocyte growth factor (HGF) in vivo, we have developed transgenic mice expressing HGF in the liver. The bromodeoxyuridine labelling indices in livers from HGF transgenic mice were doubled, compared to those from wild type mice. Livers of HGF transgenic mice expressed high levels of c-myc, which was the consequence of increased transcription rates through the c-myc promoter. After 70% partial hepatectomy, the livers of HGF transgenic mice recovered in half the time needed for their normal siblings. Since we found that HGF inhibits growth of hepatocellular carcinoma (HCC) cells in vitro, we have made two kinds of double transgenic mice: HGF/TGFα and HGF/c-myc mice. The double transgenic mice expressing both HGF and TGFα had lower tumour yields, compared to TGFα transgenic mice. The HGF/c-myc double transgenic mice had a lower incidence of hepatocellular adenoma (HCA) and HCC in comparison with c-myc transgenic mice. In HGF/c-myc mice, there were more apoptotic cells and less mitotic cells than c-myc transgenic mice. These data indicate that HGF inhibits growth and occurrence of HCC in vivo. We also found that HGF protects liver from D-galactosamine (D-GalN)-induced injury. Hepatic prostaglandin E 2 (PGE2) contents in HGF transgenic mice were much higher than those in wild type mice, and were associated with hepatic HGF contents. An anti-HGF antibody inhibits production of PGE2 in liver after D-GalN administration. These data suggest that HGF protects liver from D-GalN-induced injury through increased liver PGE2 production. The data obtained from HGF transgenic mice suggests the possibility that HGF could be applicable for therapy of human liver diseases in the future