Effect of 1alphaOH-vitamin D3 in a case of pseudohypoparathyroidism.

A 37-year-old woman with typical features of pseudohypoparathyroidism (chronic tetany, paresthesia, persistent hypocalcemia, round face, short stature, short metacarpals and metatarsals, cucutaneous calcification and lack of response to exogenous and endogenous parathyroid hormone as regards urinary phosphate and cyclic AMP excretion) was treated with oral administration of 2 microgram/day of 1alphaOH-vitamin D3. Serum calcium started to rise within 3 days returning to the normal level with disappearance of symptoms referrable to hypocalcemia. Such a favorable effect of a small dose of 1alphaOH-vitamin D3 in a patient with typical hypoparathyroidism suggests an important role of disturbance of 1alpha-hydroxylation of vitamin D3 by the kidney in the pathogenesis of calcium and phosphorus abnormality in this disease. Forty-four cases of pseudohypoparathyroidism in the Japanese literature were briefly reviewed.     

Microflow system promotes acetaminophen crystal nucleation

It is known that interfaces have various impacts on crystallization from a solution. Here, we describe crystallization of acetaminophen using a microflow channel, in which two liquids meet and form a liquid–liquid interface due to laminar flow, resulting in uniform mixing of solvents on the molecular scale. In the anti‐solvent method, the microflow mixing promoted the crystallization more than bulk mixing. Furthermore, increased flow rate encouraged crystal formation, and a metastable form appeared under a certain flow condition. This means that interface management by the microchannel could be a beneficial tool for crystallization and polymorph control.     

Rapid establishment of introgression lines using cytoplasmic male sterility and a restorer gene in Oryza sativa cv. Nipponbare

Quantitative trait locus (QTL) analyses have greatly enhanced our understanding of complex traits in rice (Oryza sativa). In parallel, the development of introgression lines has provided a powerful tool for elucidation of complicated genetic networks and identification of QTL. We recently developed a biotron breeding system that allows rapid indoor cultivation of rice plants. The system, however, has two relatively weak points in its application to marker-assisted breeding in rice: first, variation in generation times among cultivars; second, the low number of seeds produced by crosses. To compensate for these weaknesses, we propose utilizing cytoplasmic male sterility (CMS) and restorer (Rf) lines with a cv. Nipponbare genetic background. Through use of the Nipponbare genetic background, rice generation times of 2 months can be achieved regardless of any differences in the genetic background of the donor rice plant. This CMS–Rf system confers a high yield of hybrid seeds, avoids the need for emasculation and precludes accidental crosses. Our results demonstrate that this new methodology can markedly accelerate many different aspects of rice research, especially in functional genomics. The combination of biotron breeding system, early flowering habit and CMS will be of great value for screening candidate genes associated with QTL and for introducing useful QTL into elite cultivars.     

Factors Associated with Dengue Shock Syndrome: A Systematic Review and Meta-Analysis

Background

The pathogenesis of dengue shock syndrome (DSS, grade 3 and 4) is not yet completely understood. Several factors are reportedly associated with DSS, a more severe form of dengue infection that reportedly causes 50 times higher mortality compared to that of dengue patients without DSS. However, the results from these reports remain inconclusive. To better understand the epidemiology, clinical manifestation, and pathogenesis of DSS for development of new therapy, we systematically reviewed and performed a meta-analysis of relevant studies that reported factors in both DSS and dengue hemorrhagic fever (DHF, grade 1 and 2) patients.

Methods and Findings

PubMed, EMBASE, Scopus, Google Scholar, Dengue Bulletin, Cochrane Library, Virtual Health Library, and a manual search of reference lists of articles published before September 2010 were used to retrieve relevant studies. A meta-analysis using fixed- or random-effects models was used to calculate pooled odds ratios (OR) or event rate with corresponding 95% confidence intervals. Assessment of heterogeneity and publication bias, meta-regression analysis, subgroup analysis, sensitivity analysis, and analysis of factor-specific relationships were further performed. There were 198 studies constituting 203 data sets that met our eligibility criteria. Our meta-regression analysis showed a sustained reduction of DSS/dengue hemorrhagic fever (DHF) ratio over a period of 40 years in Southeast Asia, especially in Thailand. The meta-analysis revealed that age, female sex, neurological signs, nausea/vomiting, abdominal pain, gastrointestinal bleeding, hemoconcentration, ascites, pleural effusion, hypoalbuminemia, hypoproteinemia, hepatomegaly, levels of alanine transaminase and aspartate transaminase, thrombocytopenia, prothrombin time, activated partial thromboplastin time, fibrinogen level, primary/secondary infection, and dengue virus serotype-2 were significantly associated with DSS when pooling all original relevant studies.

Conclusions

The results improve our knowledge of the pathogenesis of DSS by identifying the association between the epidemiology, clinical signs, and biomarkers involved in DSS.     

Identification of a Novel Subgroup of Koala Retrovirus from Koalas in Japanese Zoos

We identified a new subgroup of koala retrovirus (KoRV), named KoRV-J, which utilizes thiamine transport protein 1 as a receptor instead of the Pit-1 receptor used by KoRV (KoRV-A). By subgroup-specific PCR, KoRV-J and KoRV-A were detected in 67.5 and 100% of koalas originating from koalas from northern Australia, respectively. Altogether, our results indicate that the invasion of the koala population by KoRV-J may have occurred more recently than invasion by KoRV-A.     

Discovery and structure–activity relationship of thienopyridine derivatives as bone anabolic agents

A cell-based assay was performed for the discovery of novel bone anabolic agents. Alkaline phosphatase (ALPase) activity of ST2 cells was utilized as an indicator of osteoblastic differentiation, and thienopyridine derivative 1 was identified as a hit compound. 3-Aminothieno[2,3-b]pyridine-2-carboxamide was confirmed to be a necessary core structure for the enhancement of ALPase activity, and then optimization of the C4-substituent on the thienopyridine ring was carried out. Introduction of cyclic amino groups to the C4-position of the thienopyridine ring improved the activity. Especially, N-phenyl-homopiperazine derivatives were found to be strong enhancers of ALPase among this new series. Furthermore, 3-amino-4-(4-phenyl-1,4-diazepan-1-yl)thieno[2,3-b]pyridine-2-carboxamide (15k) was orally administered to ovariectomized (OVX) rats over 6 weeks for evaluating the effects on areal bone mineral density (aBMD), and statistically significant improvements in aBMD were observed from the dosage of 10 mg/kg/day.     

NOTCH3 Is Induced in Cancer-Associated Fibroblasts and Promotes Angiogenesis in Oral Squamous Cell Carcinoma

Recent studies have shown that Notch signaling is involved in many types of cancers, including oral squamous cell carcinomas (OSCCs). However, the role of Notch signaling in the tumor microenvironment is not yet fully understood. In this study, we investigated the roles of NOTCH3 signaling in cancer associated fibroblasts (CAFs) in OSCCs. Immunohistochemical study of 93 human tongue OSCC cases indicated that about one third of OSCCs showed NOTCH3 expression in CAFs, and that this expression significantly correlated with tumor-size. In vitro study showed that OSCC cell lines, especially HO1-N-1 cells stimulated NOTCH3 expression in normal human dermal fibroblasts (NHDFs) through direct cell-to-cell contact. Immunohistochemical and morphometric analysis using human OSCC samples demonstrated that NOTCH3 expression in CAFs significantly correlated with micro-vessel density in cancer stroma. In vitro angiogenesis assays involving co-culture of NHDFs with HO1-N-1 and human umbilical endothelial cells (HUVECs), and NOTCH3 knockdown in NHDFs using siRNA, demonstrated that HO1-N-1 cells significantly promoted tube formation dependent on NOTCH3-expression in NHDFs. Moreover, NOTCH3 expression in CAFs was related to poor prognosis of the OSCC patients. This work provides a new insight into the role of Notch signaling in CAFs associated with tumor angiogenesis and the possibility of NOTCH3-targeted molecular therapy in OSCCs.     

Effects of ozone nano-bubble water on mucositis induced by cancer chemotherapy

No effective, reliable treatment for stomatitis associated with cancer therapy has been established. This study focused on the its effectiveness of ozone nano-bubble water (ONBW) for the treatment of chemotherapy-induced stomatitis. Oral mucositis was induced in 14-week-old male Sprague-Dawley rats (N = 21). The animals were randomly divided into 3 groups: 7 without treatment (control); 7 treated with physiological salt solution (saline); and 7 treated with ONBW. Animals were weighed on Days 7, 9, 11, and 16. Stomatitis grade evaluation and bacterial count measurements were performed before rinsing in all animals 3, 5, and 10 days after acetic acid irritation (Days 9, 11, and 17 respectively). Weight loss after stomatitis creation was observed in all groups, with significant differences between the control and ONBW groups and between the saline and ONBW groups on Day 16. The stomatitis grade did not worsen during the experimental period in any group, with the lowest grades in the ONBW group on Days 11 and 16. Significant differences were identified between the control and ONBW groups and between the saline and ONBW groups on Days 11 and 16. Oral bacterial counts tended to decrease over time in all three groups, with the greatest decrease in the ONBW group, followed by the saline group. The decrease in the bacterial count was steepest in the ONBW group. Rinsing out the oral cavity with ONBW decreased bacterial counts and encouraged the healing of oral chemotherapy-induced stomatitis. ONBW may be an effective treatment for chemotherapy-induced stomatitis.     

Genome-wide association study of idiopathic hypersomnia in a Japanese population

Sleep and Biological Rhythms - Idiopathic hypersomnia (IH) is a rare sleep disorder characterized by excessive daytime sleepiness, great difficulty upon awakening, and prolonged sleep time. In...