Histopathological and immunohistochemical studies were conducted to investigate the local existence and distribution of mast cells, fibroblasts or dendritic cells, and myofibroblasts in scleroderma, while paying particular attention to the interstices around the adnexa. The skin tissues in 15 cases of systemic scleroderma were classified histopathologically into three stages: early, fully developed, and late stage. Mesenchymal cells were distinguished immunohistochemically by 6 markers: tryptase, CD34, factor XIIIa, alpha smooth muscle actin (αSMA), vimentin, and desmin. In scleroderma, there was an increase in the number of tryptase-positive mast cells in the interstices around the adnexa. With no relation to the interstitial sites, there was a significant decrease in the number of CD34-positive cells in the late stage, and a significant increase in αSMA-positive cells in the fully developed stage, but a decrease in the late stage. Results of the present study brought about the following new findings: it was only in the mast cells that there was a significant difference in the cell distribution between the interstices around the adnexa and the interstices in non-adnexal sites. Secondly, it was suggested that mast cells, CD34-positive dendritic cells, and αSMA-positive myofibroblasts were involved in the fibrosis and shrinkage or disappearance of the adnexa when scleroderma developed.

Hepatocellular carcinoma (HCC) has a poor prognosis even after curative surgery, due to the high frequency of early intrahepatic recurrence (IHR). Conventional staging systems are almost completely inadequate, and need to be complemented by novel tools. To this end, many investigators have performed DNA microarray analysis on the basis of genome-wide information. However, so far, few studies have been able to truly account for the clinical efficacy of DNA microarray analysis in HCC. To address this dilemma, we used a supervised learning method with information of 7070 genes from 33 HCC samples, to construct a 12-gene predictor for early IHR, and then evaluated its predictive performance in 27 independent HCC samples. Our 12-gene predictor correctly predicted early IHR or non-recurrence in 25 (93%) of the 27 independent samples. This predictive value is higher than that of any other system currently available, suggesting that our system can serve as a robust tool for accurate prediction of early IHR of HCC. I emphasize in this mini-review that, although there are some technical issues to resolve prior to clinical use, DNA microarray technology can provide molecular basis to initiate “bench to bedside” translation, which cannot be easily reached with other methods.

Application of cell therapy using stem cell into intractable diseases has been noted as the medicine in the next generation taking the place of organ transplantation. Bone marrow cells have been focused as a candidate of the source of this therapy. Liver failure is a terminal state of all advanced liver diseases and thousands of patients are dying of decompensated liver cirrhosis in every year in Japan. Liver transplantation must be the strongest weapon to relieve those patients. However, particularly in Japan, liver transplantation has not been popularized. In this sense, we thought of autologous bone marrow cells transplantation for decompensated liver cirrhosis. Basic studies using animal model revealed that transplanted bone marrow cells into syngenic mouse suffering from liver cirrhosis migrated into the damaged liver and transdifferentiated to the hepatocytes. Based upon the animal studies, clinical trial of this new cell therapy supported by the Ministry of Health, Labor and Welfare is ongoing. It is early to estimate this therapy. However, free from liver failure has been observed in some cases.

Nutrient pollution is one of our most pervasive, expensive, and challenging environmental problems, according to the United States Environmental Protection Agency (EPA). Phosphorus is one of the nutrients that are essential for the growth of living organisms. However, excessive amounts of nutrients released into the environment by human activities can harm ecosystems and impact human health. In surface waters, phosphorus can contribute to an overgrowth of algae called algal "blooms" that can sicken or kill wildlife and endanger aquatic habitats. Algal blooms consume dissolved oxygen in the water, leaving little or no oxygen for fish and other aquatic organisms. Algal blooms can harm aquatic plants by blocking the sunlight they need to grow. Some algae produce toxins and encourage the growth of bacteria that can make people sick who are swimming or drinking water or eating contaminated fish or shellfish. Phosphorus is often a major limiting nutrient freshwater system. Consequently, many of the wastewater treatment plant discharged into freshwater systems such as lakes, ponds, and rivers have phosphorus discharge limits. In an attempt to prevent harmful environmental effects of excess phosphorus, several techniques have been designed to remove phosphorus from wastewater. These techniques range from adsorption and precipitation to enhanced biological phosphorus removal and constructed wetlands. Biological phosphorus removal (BPR) was first used at a few water resource recovery facilities in the late 1960s. A common element in EBPR implementation is the presence of an anaerobic tank (no nitrate and oxygen) before the aeration tank. In the next aerobic phase, these bacteria can accumulate large amounts of polyphosphate in their cells and phosphorus removal is said to be increased. The group of microorganisms that are largely responsible for P removal are known as the phosphorus accumulating organisms (PAOs). One of the options to remove phosphorus is to utilize bacteria from nature, besides being easy to obtain and inexpensive. The application of bacteria from sediment and seawater was able to reduce phosphorus in wastewater. In this study, for screening salt-tolerant phosphorus accumulating organisms (PAOs) and investigating the P release and uptake of the organisms in saline wastewater. The samples used were sediment and seawater from Yamaguchi Bay, Yamaguchi, Japan. Sediment and seawater added 150 mL of artificial saline wastewater with media (anaerobic media). The samples were then cultured and given feed media every three hours day at 25 °C and shaken at 140 rpm. The hydraulic retention time of the cultivation was 16 h and 8 h under anaerobic and aerobic conditions, respectively. 10 sponges made of polyurethane with dimensions of 2 cm were put in Erlenmeyer flasks and was used as a bio-carrier surface for microorganisms to adhere to. Water was passed over the sponge surface to acclimatize the microorganisms growing outside the sponge as well as within its pores, ensuring sufficient growth surface. The cultivation duration was 112 days. Batch experiments were conducted over 98 days in solutions with a salinity of 3.5% and P concentrations of 1, 5, 10, and 20 mg-P/L. The P-uptake ability of microorganisms increased by increasing P concentration from 1 to 20 mg-P/L. A high P removal percentage with an average of 85% was obtained at 10 mg-P/L after day 56. The uptake and release of P were observed in saline wastewater, signifying that salt-tolerant PAOs could grow in the saline solution. Bacterial screening by isolation and sequence analysis using 16S rRNA demonstrated that two cultivated strains, TR1 and MA3, had high similarity with Bacillus sp. and Thioclava sp. EIOx9, respectively. The colony morphology analysis showed that the colonies of TR1 were rod-shaped, milky-colored, round, shiny-viscous, smooth with a defined margin, while colonies of MA3 were cream-colored with smooth surfaces and raised aspect. The TR1 was gram-stain-positive with approximately 6-10 μm long and 1.2 μm wide cells, and MA3 was gram-stain-negative with about 0.9 μm long and 0.5 μm wide cells. The results demonstrated the involvement of Bacillus sp., and Thioclava sp. in the release and uptake of P, owing to their ability to grow in saline wastewater. Furthermore, Bacillus sp. (TR1) and Thioclava sp. (MA3) were assessed for their abiotic adaptability and phosphorus removal efficiency in saline wastewater. The effects of abiotic factors such as carbon source, pH, temperature, and salinity on bacterial growth were examined through a series of batch experiments. Both bacteria used carbon sources such as glucose, sucrose, and CH3COONa for their growth. The pH study indicated that Bacillus sp. (TR1) preferred the pH range of 6 8 and Thioclava sp. (MA3) preferred the pH range of 6-9. Bacillus sp. favorably multiplied in the temperature range of 25- 40 °C, while 25 35 °C was preferred by Thioclava sp. Salinity range of 0% 10% was favorable for TR1, with optimum growth observed at 3.5% 5%, and Thioclava sp. (MA3) preferred the salinity range of 1% 10% with optimal growth at 4%, but was absent in non-saline water. Bacillus sp. and bacterial combination (TR1 and MA3) showed similar values for phosphorus removal efficiency (100%) at 1.0 mg-P/L total P compared to Thioclava sp. (38.2%). The initial phosphorus concentration of 2.5 mg-P / L showed a slightly higher 72.35% P removal efficiency compared to the individual strains. However, phosphorus removal did not increase, but showed a downward trend with increasing at initial phosphorus. The combination possibly built a synergistic activity between the individual strains to remove phosphorus. The results demonstrated that when used individually, Bacillus sp. showed a reasonably high phosphorus removal ability than Thioclava sp., and exhibited good synergy when used in combination to remove phosphorus from saline wastewater.

Incontinentia pigmenti (IP; OMIM# 308300) is a rare inherited disease caused by a mutation of IKBKG, which is also known as NEMO, located on Xq28. IP patients usually present with abnormalities of skin, eyes, nails and central nervous system. The neurological damege, which occur usually from neonatal through the early infantile period, leads to neulogical complication such as development retardation, motor paralysis and epilepsy. However, there has been little study done concerning the effect of therapy for the neural abnormalities. We have investigated the clinical findings in a female IP case with a novel mutation of IKBKG for six years due to disclosing the neurological prognosis and the immunological features. It is hoped that the present study will contribute to a better management of IP patients.

The hippocampal dentate gyrus has been identified to play a critical role in maintaining contextual memory in many mammalian species. To evaluate learninginduced synaptic plasticity of granule cells, we subjected male rats to an inhibitory avoidance (IA) task and prepared acute hippocampal slices. In the presence of 0.5 μM tetrodotoxin, we recorded miniature excitatory post synaptic currents (mEPSCs) and inhibitory post synaptic currents (mIPSCs) in male rats experiencing four groups: untrained, IA-trained, unpaired, and walk-through. Compared with the untrained, IA-trained, unpaired, and walk-through groups, the unpaired group significantly enhanced mean mEPSC amplitudes, suggesting the experience-induced plasticity at AMPA receptor-mediated excitatory synapses. For inhibitory synapses, both unpaired and walk-through groups significantly decreased mean mIPSC amplitudes, showing the experience-induced reduction of postsynaptic GAB A_{A} receptor-mediated currents. Unlike the plasticity at CA1 synapses, it was difficult to explain the learning- specific plasticity at the synapses. However, overall multivariate analysis using four variables of mE(I)PSC responses revealed experience-specific changes in the diversity, suggesting that the diversity of excitatory/inhibitory synapses onto granule cells differs among the past experience of animals include the learning. In comparison with CA1 pyramidal neurons, granule cells consistently showed greater amplitude and frequency of mE(I)PSCs. Fluctuation analysis further revealed that granule cells provide more postsynaptic AMPA receptor channels and greater single-channel current of GABA_{A} receptors of than CA1 pyramidal neurons. These findings show functional differences between two types of principal cells in the hippocampus.

Androgen receptor (AR)-signaling plays an important role in promoting tumor cell survival and the development of castration-resistant prostate cancer (CRPC). Androgen deprivation therapy is the basic therapeutic strategy for AR signaling blockade, but that effects wonʼt last long and most of metastatic prostate cancer show castration resistance. Recently, new agents, AR Axis Targeted agents (ARAT), have been developed. We have been developing our bench-to-bedside translational research to elucidate the mechanisms of drug resistance in prostate cancer. This review describes our investigational results and recent advances in CRPC with ARAT treatment strategy.

Aim: To evaluate the efficacy of quantitative analysis for differentiating pancreatic ductal adenocarcinoma (PDAC) and inflammatory pancreatic masses (IPM) using time intensity curve (TIC) analysis based on contrast-enhanced endoscopic ultrasonography (CE-EUS). Methods: We reviewed 89 patients who had undergone CE-EUS for pancreatic solid lesions at our department between August 2012 and January 2016. CE-EUS images were recorded for 2 minutes after injection of the contrast agent. The diagnostic abilities of the enhanced patterns and TIC analysis were assessed. Results: The enhanced patterns of PDAC were mainly hypovascular and heterogeneous (66/77), while IPM were mainly isovascular and homogeneous (6/12). In PDAC, sensitivity was 77.9%, specificity 83.3%, and accuracy was 78.7%. In TIC analysis, the intensity reduction rate was significantly different at 10 and 30 seconds after peak intensity. After creating a cutoff value (49%) based on the receiver operating characteristic curve for the intensity reduction rate after 30 seconds, diagnosing PDAC with TIC analysis had a sensitivity of 67.5%, specificity of 100%, and accuracy of 71.9%. Combining enhanced pattern analysis with TIC analysis had a sensitivity of 90.9%, pecificity of 83.3%, and accuracy of 89.9%. Conclusion: Combining TIC analysis with CE-EUS improved diagnostic accuracy when differentiating between PDAC and IPM.