Solution structure of a zinc‐finger domain that binds to poly‐ADP‐ribose

Poly‐ADP‐ribosylation is a unique post‐translational modification that controls various nuclear events such as repair of DNA single‐strand breaks. Recently, the protein containing the poly‐ADP‐ribose (pADPr)‐binding zinc‐finger (PBZ) domain was shown to be a novel AP endonuclease and involved in a cell cycle checkpoint. Here, we determined the three‐dimensional structure of the PBZ domain from Drosophila melanogaster CG1218‐PA using NMR spectroscopy. The domain folds into a C2H2‐type zinc‐finger structure in an S configuration, containing a characteristic loop between the zinc‐coordinating cysteine and histidine residues. This is distinct from the structure of other C2H2‐type zinc fingers. NMR signal changes that occur when pADPr binds to the PBZ domains from CG1218‐PA and human checkpoint with FHA (forkhead‐associated) and ring finger (CHFR) and mutagenesis suggest that a surface relatively well conserved among PBZ domains may serve as a major interface with pADPr.     

Virological outcomes in patients infected chronically with hepatitis B virus genotype A in comparison with genotypes B and C

In a single hospital in Tokyo, the 87 patients infected persistently with hepatitis B virus (HBV) genotype A, the 413 with B, and the 3,389 with C were compared for virological outcome. Hepatitis B surface antigen (HBsAg) was cleared from the serum in 12% (3/26), 2% (2/112), and 3% (23/826) of patients with genotypes A, B, and C, respectively, at 5 years of follow-up (P = 0.0395). Hepatitis B e antigen (HBeAg) was cleared from serum more frequently in patients with genotype B than those with A or C (78% [32/41] vs. 58% [11/19] or 45% [251/562], P = 0.00001) at 5 years. Of the 45 individuals infected with genotype A and followed for 3 years or longer, HBeAg was more frequent (16% [3/19] vs. 73% [19/26], P = 0.0002) and levels of HBV DNA higher (median <2.6 [range: <2.6-5.6] vs. >7.6 [<2.6->7.6] log copies/ml, P = 0.001) in the 26 patients with biopsy-proven chronic hepatitis than the 19 asymptomatic carriers. Among the 26 hepatitis patients infected with HBV genotype A, decreases in HBV DNA were less frequent (20% [1/5] vs. 93% [13/14] or 86% [6/7], P = 0.0095) and increases in serum levels of hyaluronic acid > or =10 ng/ml commoner (80% [4/5] vs. 14% [2/14] or 14% [1/7], P = 0.017) in the patients who kept HBeAg than in those who seroconverted or who remained HBeAg-negative. In conclusion, patients persistently infected with HBV genotype A fare better than those with genotype B or C. However, high levels of HBV DNA continue in those in whom HBeAg persists along with fibrosis in the liver.     

Evaluation of a non-invasive hemoglobin measurement device for pre-deposited autologous blood donation

A non-invasive hemoglobin measurement instrument (Sysmex Co.Ltd., Kobe, Japan) was used for the evaluation of hemoglobin levels just before blood drawing for repeat autologous blood donation. There was a statistically significant correlation (r = 0.598) between the hemoglobin levels determined with the non-invasive instrument (NINV-Hb) and true Hb levels (T-Hb) evaluated by direct analysis with automatic hematology analyzer, KX-21 (Sysmex). The analysis used 156 data obtained from 66 patients. Ten patients whose differences between NINV-Hb and T-Hb of the first blood donation were more than 2.1 g/dl were excluded from further analysis. Imaging analysis indicated difficulties with the detection of appropriate blood vessel images in one of these patients, but the reasons for other patients were not apparent. There was a closer relationship between NINV-Hb and T-Hb for the 76 measurements for the second or third blood donation obtained from 56 patients (r = 0.704) than for the entire data (r = 0.598). When 12 g/dl was used as the cut off value for NINV-Hb, sensitivity and specificity for the detection of 1l g/dl of T-Hb, which is considered the critical level for drawing autologous blood for donation, were 83.6% and 77.8%, respectively. We conclude, therefore, that NINV-Hb evaluation can be expected to be useful for repeated autologous blood donation of limited patients, however, it is strongly expected to develop a new system having more sensitive and accurately detectable ability.     

Molecular cytogenetic analysis of oral squamous cell carcinomas by comparative genomic hybridization, spectral karyotyping, and fluorescence in situ hybridization

We investigated relationships between DNA copy number aberrations and chromosomal structural rearrangements in 11 different cell lines derived from oral squamous cell carcinoma (OSCC) by comparative genomic hybridization (CGH), spectral karyotyping (SKY), and fluorescence in situ hybridization (FISH). CGH frequently showed recurrent chromosomal gains of 5p, 20q12, 8q23 approximately qter, 20p11 approximately p12, 7p15, 11p13 approximately p14, and 14q21, as well as losses of 4q, 18q, 4p11 approximately p15, 19p13, 8p21 approximately pter, and 16p11 approximately p12. SKY identified the following recurrent chromosomal abnormalities: i(5)(p10), i(5)(q10), i(8)(q10), der(X;1)(q10;p10), der(3;5)(p10;p10), and der(3;18)(q10;p10). In addition, breakpoints detected by SKY were clustered in 11q13 and around centromeric regions, including 5p10/q10, 3p10/q10, 8p10/q10 14q10, 1p10/1q10, and 16p10/16q10. Cell lines with i(5)(p10) and i(8)(q10) showed gains of the entire chromosome arms of 5p and 8q by CGH. Moreover, breakages near the centromeres of chromosomes 5 and 8 may be associated with 5p gain, 8q gain, and 8p loss in OSCC. FISH with a DNA probe from a BAC clone mapping to 5p15 showed a significant correlation between the average numbers of i(5)(p10) and 5p15 (R(2) = 0.8693, P< 0.01) in these cell lines, indicating that DNA copy number of 5p depends upon isochromosome formation in OSCC.     

Cerebral oxygenation changes in response to post-hemodialysis standing

Journal of Artificial Organs - Few reports have examined the association between changes in cerebral oxygenation and clinical factors, including blood pressure (BP), upon standing after...     

Molecular basis of carotid body tumor and associated clinical features in Japan identified by genomic,immunohistochemical, and clinical analyses

Carotid body tumor (CBT) is classified as a paraganglioma (PGL). Here, we report the genetic background, protein expression pattern, and clinical findings of 30 Japanese CBT cases. Germline pathogenic or likely pathogenic (P/LP) variants of genes encoding succinate dehydrogenase subunits (SDHs) were detected in 15 of 30 cases (50%). The SDHB variants were the most frequently detected, followed by SDHA and SDHD variants. One case with SDHAF2 variant was bilateral CBT, and other two multiple PGL cases were not detected P/LP variants. The three cases with germline variants that could be tested did not have somatic P/LP variants of the same genes. Immunohistochemical analysis showed negative SDHB signals in CBT tissues in five cases with germline P/LP variants of SDHB, SDHD, or SDHA. In addition, SDHB signals in CBT tissues were negative in four of nine cases without germline P/LP variants of SDHs. These findings suggest the involvement of unidentified molecular mechanisms affecting SDHs.     

Antimetastatic effect of defibrinogenation with batroxobin depends on the natural killer activity of host in mice

Summary Using batroxobin, a thrombin-like enzyme found in snake venom, the effects of defibrinogenation on artificial lung metastasis in mice were studied. The role of natural killer (NK) cells in the inhibitory effects of defibrinogenation on metastasis was also investigated. Artificial lung metastasis experiments were performed by inoculating either B16-F10 cells or B16-BL/6 cells, highly metastatic strains of B16 melanoma cells, into C57BL/6 mice via the tail vein. The administration of batroxobin significantly inhibited lung metastasis, as did NK activity augmented by poly (I) · poly (C) administration. When both batroxobin and poly (I) · poly (C) were administered, lung metastasis was more markedly inhibited. When NK activity was suppressed by administration of anti-(asialo GM₁) antibody, lung metastasis was markedly increased. When batroxobin was administered with anti-(asialo GM₁) antibody, no inhibitory effects on lung metastasis, such as those seen with batroxobin alone, were observed. The administration of batroxobin had no effect at all on spleen lymphocyte NK activity. These results indicated that defibrinogenation due to batroxobin inhibits lung metastasis, and these effects depend on NK activity of the host.Abbreviations used NK natural killer - BU batroxobin units - FCS fetal calf serum     

Color change of airborne particle–abraded acrylic resin surfaces: A palatography method

Statement of problem

A palatogram aids prosthodontists and speech pathologists in evaluating the precise prosthetic treatment needed and the effectiveness of such treatment to improve speech intelligibility. Powder is commonly used to visualize tongue-palate contact, where wetted areas of powder in the oral cavity reveal such contact during palatography. However, discomfort and the risk of aspiration are among the shortcomings of this method, and an improved method is needed.

Simultaneous analysis of mitragynine, 7-hydroxymitragynine,and other alkaloids in the psychotropic plant “kratom” (<Emphasis Type="Italic">Mitragyna speciosa</Emphasis>) by LC-ESI-MS

The leaves of Mitragyna speciosa, a tropical plant known as “kratom,” have been traditionally used as a substitute for opium in Thailand and Malaysia. Mitragynine, a major constituent of M. speciosa, has an opioid agonistic activity, and its derivative 7-hydroxymitragynine (7-OH-mitragynine) (a minor constituent) is much more potent than mitragynine or morphine. Recently, many products containing this plant have been distributed as “incense” on the drug market in Japan for their expected narcotic effects. Despite their potency and their wide distribution for abuse, there are no reports on the quantitative analysis of mitragynine and 7-OH-mitragynine in the raw materials or in the commercial products of kratom. In this study, a method for simultaneous analysis of mitragynine, 7-OH-mitragynine, and other indole alkaloids (speciogynine, speciociliatine, and paynantheine), present in the raw materials and commercial products of kratom, was developed using liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS). By this method, mitragynine, 7-OH-mitragynine, and the other alkaloids were detected in 11 of the 13 products. The content of mitragynine in the products ranged from 1% to 6%, and that of 7-OH-mitragynine from 0.01% to 0.04%. Because 7-OH-mitragynine is much more potent than morphine, M. speciosa abuse is a matter of major concern. The present analytical method is considered useful for the screening of M. speciosa products in the drug market.     

MR appearance of parasymphyseal insufficiency fractures of the os pubis

 Objective. To clarify the MRI features of parasymphyseal insufficiency fractures of the os pubis. Design and patients. MRI was performed in four postmenopausal women with parasymphyseal insufficiency fractures. The diagnosis was confirmed with plain films in every patient. T1-weighted and T2-weighted images were obtained in four patients using a 1.5-T unit. Postcontrast T1-weighted imaging was also done in three patients. Results and conclusions. MRI of pubic parasymphyseal insufficiency fracture characteristically demonstrates a hyperintense mass lesion with a hypointense rim on T2-weighted imaging, showing peripheral and septal enhancement after contrast administration. It is important to have this entity in mind in patients with osteoporosis, especially in patients with a history of pelvic irradiation for malignant disease, so as not to misinterpret it as a chondroid tumor or bone metastasis.