Digital sensory nerve conduction velocity and vibration perception threshold in peripheral neurological test for hand-arm vibration syndrome

To evaluate peripheral neuropathy in patients with vibration syndrome, an examination was conducted of sensory nerve conduction velocity (SCV) in the digital segment of the median nerve in the middle finger and vibration perception threshold (VPT) at 125 Hz on the same middle fingertip. In addition, possible correlations were investigated between the two measurements. SCVs in the digital segment were measured by stimulating at the wrist electrically and recording from two pairs of electrodes in the finger. Fractionated SCVs were also measured in the palm-to-finger, wrist-to-palm, and elbow-to-wrist segments. The subjects were 52 patients with vibration syndrome and 40 healthy controls of similar age. SCVs in the digital segment and the wrist-to-palm segment were significantly slower in the patients than in the controls, and VPTs were higher in the patients. The strongest correlation of VPTs with SCVs among nerve segments measured was shown in the digital segment. With all increase in VPTs. SCVs in the digital segment tended to be slower, and slowed digital SCVs were encountered more frequently: 13% in VPTs below 5.0 dB and 56% in VPTs above 17.5 dB. Slowed digital SCVs were found in 43% of the patients and increased VPTs were encountered in 92%. © 1996 Wiley-Liss, Inc.     

Microsatellite instability in sporadic human breast cancers

Human breast-cancer specimens from 100 patients were analyzed for microsatellite instability (referred to as replication error; RER) at 12 genomic loci on 7 chromosomes, and results were correlated with clinicopathologic characteristics. In 42 of 100 breast-cancer patients, we investigated whether RER was associated with the amplification of oncogenes and/or suppression of tumor-suppressor genes. Of the 100 patients, 8 (8%) were RER-positive at one or more chromosomal loci. The majority of RER-positive patients had early-stage disease with ER-positive tumors, suggesting that RER occurs early in breast tumorigenesis. However, no significant correlation was observed between RER and oncogenes or tumor-suppressor genes. Thus, the mechanism of RER in sporadic human breast cancer may be independent of the multi-step carcinogenesis caused by the alterations of oncogenes and tumor-suppressor genes. © 1996 Wiley-Liss, Inc.     

GET4 is a novel driver gene in colorectal cancer that regulates the localization of BAG6, a nucleocytoplasmic shuttling protein

Colorectal cancer (CRC) is one of the most common types of cancer and a significant cause of cancer mortality worldwide. Further improvements of CRC therapeutic approaches are needed. BCL2‐associated athanogene 6 (BAG6), a multifunctional scaffold protein, plays an important role in tumor progression. However, regulation of BAG6 in malignancies remains unclear. This study showed that guided entry of tail‐anchored proteins factor 4 (GET4), a component of the BAG6 complex, regulates the intercellular localization of BAG6 in CRC. Furthermore, GET4 was identified as a candidate driver gene on the short arm of chromosome 7, which is often amplified in CRC, by our bioinformatics approach using the CRC dataset from The Cancer Genome Atlas. Clinicopathologic and prognostic analyses using CRC datasets showed that GET4 was overexpressed in tumor cells due to an increased DNA copy number. High GET4 expression was an independent poor prognostic factor in CRC, whereas BAG6 was mainly overexpressed in the cytoplasm of tumor cells without gene alteration. The biological significance of GET4 was examined using GET4 KO CRC cells generated with CRISPR‐Cas9 technology or transfected CRC cells. In vitro and in vivo analyses showed that GET4 promoted tumor growth. It appears to facilitate cell cycle progression by cytoplasmic enrichment of BAG6‐mediated p53 acetylation followed by reduced p21 expression. In conclusion, we showed that GET4 is a novel driver gene and a prognostic biomarker that promotes CRC progression by inducing the cytoplasmic transport of BAG6. GET4 could be a promising therapeutic molecular target in CRC.     

Solution-phase synthesis of oligodeoxyribonucleotides using the H-phosphonate method with N-unprotected 5′-phosphite monomers

Recent advances in nucleic acid therapeutics increase the requirements for developing efficient methods for the chemical synthesis of oligodeoxyribonucleotides (ODNs). In this study, we report a new approach for the solution-phase synthesis of ODNs using the H-phosphonate method with N-unprotected 5′-phosphite monomers. The 5′-phosphite monomers are synthesized in a single step from unprotected 2′-deoxyribonucleosides using 5′-O-selective phosphitylation and can be applied to the synthetic cycle of the H-phosphonate method. We synthesized four kinds of 5′-phosphite monomers and then optimized the conditions for the condensation between the 3′-hydroxy groups of the 5′-phosphite monomers and the H-phosphonate monoesters. As a result of various investigations, solution-phase synthesis of trithymidine diphosphate (TTT) and tetramers containing four kinds of nucleobases was achieved according to the procedure consisting of repeated condensation, deprotection, and purification using simple extraction or precipitation.

A new strategy for a solution-phase synthesis of oligodeoxyribonucleotides with 5′-phosphite monomers synthesized in a single step from unprotected 2′-deoxyribonucleosides.     

The wound/burn guidelines – 6: Guidelines for the management of burns

Burns are a common type of skin injury encountered at all levels of medical facilities from private clinics to core hospitals. Minor burns heal by topical treatment alone, but moderate to severe burns require systemic management, and skin grafting is often necessary also for topical treatment. Inappropriate initial treatment or delay of initial treatment may exert adverse effects on the subsequent treatment and course. Therefore, accurate evaluation of the severity and initiation of appropriate treatment are necessary. The Guidelines for the Management of Burn Injuries were issued in March 2009 from the Japanese Society for Burn Injuries as guidelines concerning burns, but they were focused on the treatment for extensive and severe burns in the acute period. Therefore, we prepared guidelines intended to support the appropriate diagnosis and initial treatment for patients with burns that are commonly encountered including minor as well as moderate and severe cases. Because of this intention of the present guidelines, there is no recommendation of individual surgical procedures.     

Comparison of behavioral and psychological symptoms in early-onset and late-onset Alzheimer's disease

BACKGROUND: When comparing with early-onset Alzheimer's disease (EO-AD) and late-onset Alzheimer's disease (LO-AD), some symptomatological differences in clinical features can be seen between them. Rapid progression, more severe language problems or visuospatial dysfunction occur more often in EO-AD patients. However, there have been very few reports about the differences in behavioral and psychological symptoms between these two groups. AIM: The aim of this study was to demonstrate the differences in behavioral symptoms between EO-AD and LO-AD groups. METHOD: Three hundred and seven consecutive outpatients with AD were put into an EO-AD group (46 patients) or a LO-AD group (261 patients). Comprehensive assessment batteries, including the Neuropsychiatric Inventory (NPI), were administered at the first medical assessment. RESULTS: Significant differences were found between the EO-AD and LO-AD groups in terms of NPI total score (EO-AD: 10.3 +/- 10.9, LO-AD: 17.8 +/- 17.0, p = 0.004) and number of patients who experienced each NPI subscale score (delusion; EO-AD: 13.0%, LO-AD: 50.6%, p < 0.001). There were no differences in cognitive functions or dementia severity between two groups. CONCLUSION: In EO-AD, behavioral and psychological symptoms are relatively fewer than LO-AD at the first medical assessment. Copyright (c) 2007 John Wiley & Sons, Ltd.