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Biomedical subjects

K Sano

Publications and source records attributed to K Sano.

At least 73 records · Page 4Linked to original sources

Liver resection without total vascular exclusion: hazardous or beneficial? An analysis of our experience.

OBJECTIVE: To evaluate retrospectively the safety and radicality of liver resection performed without total vascular exclusion (TVE). SUMMARY BACKGROUND DATA: TVE is recommended for safe liver surgery, at least in the case of resection of the paracaval portion of the liver. However, it has some drawbacks because of its invasiveness. METHODS: The authors retrospectively evaluated 329 of 471 consecutive patients who underwent liver resection from October 1994 to October 1999. All of these patients had tumors involving segments 1, 7, or 8 or the cranial portion of segment 4, or underwent major hepatectomies that required exposure of the inferior vena cava (IVC), the main trunks of the hepatic veins, or both. Sixty-four patients underwent resection that included segment 1, with or without the reconstruction of the IVC, the hepatic vein, or both. RESULTS: Three hundred twenty-four of 329 procedures were done under intermittent warm ischemia; no clamping methods were used in 6. TVE was never needed. There were no postoperative 30-day deaths. The complication rate was 25.5%, and only 2.1% had major complications. Only 13 (3.9%) patients required whole blood transfusion. Part of the wall of the IVC was resected in six patients, and the hepatic veins were reconstructed in four. Surgical clearance was achieved in all patients undergoing surgery for a tumor. CONCLUSIONS: These results show that liver surgery performed without TVE is safe and effective even in aggressive procedures for liver tumors involving the cavohepatic junction. Therefore, TVE should be further restricted to exceptional patients.

Adolescent↗

Calibration with currently available low-radiopacity catheters for scaling in digital quantitative coronary angiography.

RATIONALE AND OBJECTIVES: In quantitative coronary angiography, the absolute diameters of coronary artery lumina are obtained by using a catheter as a scaling device. METHODS: We examined the effect of x-ray opacity on the accuracy of calibration methods that use such catheters by varying the concentration of contrast medium in the catheters in phantom experiments with a digital cine imaging system. RESULTS: With contrast-filled, currently available catheters, the average increase in the measured calibration factor from the gold standard (as determined by using a measuring scale) was 1.0% and 0.4% in the 13-cm and 17-cm image-intensifier modes, respectively, compared with -9.9% and -12.4% for catheters without contrast medium. The corresponding figures for catheters of the previous generation that lacked contrast medium were 1.0% and 0.4%, respectively. The image contrast of previous-generation catheters filled with saline was closer to that of current-generation catheters filled with contrast medium than that of current-generation catheters filled with saline. CONCLUSIONS: When used for quantitative coronary angiography by digital angiography, currently available low-radiopacity catheters give more accurate data when filled with contrast medium.

Calibration↗

Genomic anatomy of a premier major histocompatibility complex paralogous region on chromosome 1q21-q22.

Human chromosomes 1q21-q25, 6p21.3-22.2, 9q33-q34, and 19p13.1-p13.4 carry clusters of paralogous loci, to date best defined by the flagship 6p MHC region. They have presumably been created by two rounds of large-scale genomic duplications around the time of vertebrate emergence. Phylogenetically, the 1q21-25 region seems most closely related to the 6p21.3 MHC region, as it is only the MHC paralogous region that includes bona fide MHC class I genes, the CD1 and MR1 loci. Here, to clarify the genomic structure of this model MHC paralogous region as well as to gain insight into the evolutionary dynamics of the entire quadriplication process, a detailed analysis of a critical 1.7 megabase (Mb) region was performed. To this end, a composite, deep, YAC, BAC, and PAC contig encompassing all five CD1 genes and linking the centromeric +P5 locus to the telomeric KRTC7 locus was constructed. Within this contig a 1.1-Mb BAC and PAC core segment joining CD1D to FCER1A was fully sequenced and thoroughly analyzed. This led to the mapping of a total of 41 genes (12 expressed genes, 12 possibly expressed genes, and 17 pseudogenes), among which 31 were novel. The latter include 20 olfactory receptor (OR) genes, 9 of which are potentially expressed. Importantly, CD1, SPTA1, OR, and FCERIA belong to multigene families, which have paralogues in the other three regions. Furthermore, it is noteworthy that 12 of the 13 expressed genes in the 1q21-q22 region around the CD1 loci are immunologically relevant. In addition to CD1A-E, these include SPTA1, MNDA, IFI-16, AIM2, BL1A, FY and FCERIA. This functional convergence of structurally unrelated genes is reminiscent of the 6p MHC region, and perhaps represents the emergence of yet another antigen presentation gene cluster, in this case dedicated to lipid/glycolipid antigens rather than antigen-derived peptides.

Antigens, CD1↗

Anti-human immunodeficiency virus activity of YK-FH312 (a betulinic acid derivative), a novel compound blocking viral maturation.

Betulinic acid, a triterpenoid isolated from the methyl alcohol extract of the leaves of Syzigium claviflorum, was found to have a potent inhibitory activity against human immunodeficiency virus type 1 (HIV-1). Betulinic acid derivatives were synthesized to enhance the anti-HIV activity. Among the derivatives, 3-O-(3',3'-dimethylsuccinyl) betulinic acid, designated YK-FH312, showed the highest activity against HIV-induced cytopathic effects in HIV-1-infected MT-4 cells. To determine the step(s) of HIV replication affected by YK-FH312, a syncytium formation inhibition assay in MOLT-4/HIV-1(IIIB) and MOLT-4 coculture, a multinuclear-activation-of-galactosidase-indicator (MAGI) assay in MAGI-CCR5 cells, electron microscopic observation, and a time-of-addition assay were performed. In the syncytium formation inhibition assay or in the MAGI assay for de novo infection, the compound did not show inhibitory effects against HIV replication. Conversely, no virions were detected in HIV-1-infected cell cultures treated with YK-FH312 either by electron microscopic observation or by viral yield in the supernatant. In accordance with a p24 enzyme-linked immunosorbent assay of culture supernatant in the time-of-addition assay, YK-FH312 inhibited virus expression in the supernatant when it was added 18 h postinfection. However, Western blot analysis of the cells in the time-of-addition assay revealed that the production of viral proteins in the cells was not inhibited completely by YK-FH312. These results suggest that YK-FH312 might affect the step(s) of virion assembly and/or budding of virions, and this is a novel mechanism of action of an anti-HIV compound.

Anti-HIV Agents↗

Heat-shock-induced proteins from Myxococcus xanthus.

Optimal conditions for two-dimensional gel electrophoresis of total cellular proteins from Myxococcus xanthus were established. Using these conditions, we analyzed protein patterns of heat-shocked M. xanthus cells. Eighteen major spots and 15 minor spots were found to be induced by heat shock. From N-terminal sequences of 15 major spots, DnaK, GroEL, GroES, alkyl hydroperoxide reductase, aldehyde dehydrogenase, succinyl coenzyme A (CoA) synthetase, 30S ribosomal protein S6, and ATP synthase alpha subunit were identified. Three of the 18 major spots had an identical N-terminal sequence, indicating that they may be different forms of the same protein. Although a DnaK homologue, SglK, has been identified in M. xanthus (R. M. Weimer, C. Creghton, A. Stassinopoulos, P. Youderian, and P. L. Hartzell, J. Bacteriol. 180:5357-5368, 1998; Z. Yang, Y. Geng, and W. Shi, J. Bacteriol. 180:218-224, 1998), SglK was not induced by heat shock. In addition, there were seven substitutions within the N-terminal 30-residue sequence of the newly identified DnaK. This is the first report to demonstrate that succinyl CoA synthetase, 30S ribosomal protein S6, and ATP synthase alpha subunit are heat shock inducible.

Amino Acid Sequence↗

Cytochrome c release into cytosol with subsequent caspase activation during warm ischemia in rat liver.

Apoptosis plays an important role in liver ischemia and reperfusion (I/R) injury. However, the molecular basis of apoptosis in I/R injury is poorly understood. The aims of this study were to ascertain when and how apoptotic signal transduction occurs in I/R injury. The apoptotic pathway in rats undergoing 90 min of warm ischemia with reperfusion was compared with that of rats undergoing prolonged ischemia alone. During ischemia, mitochondrial cytochrome c was released into the cytosol in a time-dependent manner in hepatocytes and sinusoidal endothelial cells, and caspase-3 and an inhibitor of caspase-activated DNase were cleaved. However, apoptotic manifestation and DNA fragmentation were not observed. After reperfusion, nuclear condensation, cells positive for terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling, and DNA fragmentation were observed and caspase-8 and Bid cleavage occurred. In contrast, prolonged ischemia alone induced necrosis rather than apoptosis. In summary, our results show that release of mitochondrial cytochrome c and caspase activation proceed during ischemia, although apoptosis is manifested after reperfusion.

Animals↗

Post-ischemic administration of DY-9760e, a novel calmodulin antagonist, reduced infarct volume in the permanent focal ischemia model of spontaneously hypertensive rat.

We assessed the effect of a novel calmodulin antagonist, DY-9760e (3-[2-[4-(3-chloro-2-methylphenyl)-1-piperazinyl]ethyl]-5,6-dimethoxy-1-(4-imidazolylmethyl)-1H-indazole dihydrochloride 3.5 hydrate) in a spontaneously hypertensive rat (SHR) permanent focal cerebral ischemia. In experiment I, the left middle cerebral artery was permanently occluded in 62 SHRs. DY-9760e (0.5 mg kg(-1) h(-1)) or vehicle alone were administered continuously i.v. for 6 h, beginning 0, 30, or 60 min after the arterial occlusion. The infarct volume was measured 24 h of ischemia. In experiment II, the effect of DY-9760e on CBF was assessed in 10 SHRs. Administration without a delay resulted in a mean infarct volume of 166.7 +/- 21.0 mm3 (vehicle; n = 10) and 125.1 +/- 31.8 mm3 (DY-9760e; n = 9). Administration with a 30 min delay resulted in a mean infarct volume of 173.2 +/- 32.4 mm3 (vehicle; n = 12) and 143.3 +/- 35.3 mm3 (DY-9760e; n = 11). Dy-9760e significantly reduced the infarct under these conditions (p < 0.05). The administration with a 60 min delay failed to reduce the infarct. DY-9760e had no effect on the CBF. Continuous i.v. administration of DY-9760e reduced infarct volume in a SHR permanent focal ischemia without affecting ischemic CBF.

Animals↗

Metabolism of sulphobromophthalein I: positional isomers of sulphobromophthalein monoglutathione conjugate.

Three positional isomers of sulphobromophthalein glutathione monoconjugate (BSP-mGSH) were detected using a paired-ion HPLC method that employs triethylamine phosphate (TEA-H3PO4) as a pairing agent. To confirm that these compounds were glutathione (GSH) conjugates, sulphobromophthalein (BSP) was incubated with a four-fold volume of GSH under alkaline ammonium hydroxide. At least 6 metabolites (3 di-GSH conjugates and 3 isomers of mono-GSH conjugates) were produced under these conditions. The three mono-GSH conjugates were each purified and identified as compounds with a molecular weight of 1,020 according to FAB mass spectrometry results. Positional isomers of BSP-GSH were provisionally distinguished via the addition of the symbols alpha, beta and delta to the end of each abbreviation, to reflect the amount of isomers present. Thus, the isomer present in the largest quantity was termed BSP-mGSH(alpha), the second most abundant isomer was termed BSP-mGSH(beta) and the third was termed BSP-mGSH(delta). Interestingly, a species difference was recognized in that rat cytosol GSH S-transferase (GST) primarily produced BSP-mGSH(alpha), whereas guinea-pig cytosol generated BSP-mGSH(delta), BSP-mGSH(alpha) and BSP-mGSH(beta) equally and rabbit cytosol mainly produced BSP-mGSH(beta).

Animals↗

Initial intraorgan formation of mercapturic acid.

The disposition of S-benzyl-glutathione (BSG) in male Wistar rats was evaluated by the HPLC method to examine whether the kidney and liver contributed independently to the biosynthesis of S-benzyl-N-acetylcysteine (BNAc), a mercapturic acid (Chart 1). After intravenous injection, BSG was rapidly transported in both the kidney and the liver at a ratio of about 7:3. Simultaneously, a large amount of BNAc was found in both the kidney and the liver. In the kidney, S-benzyl-cysteine (BCys) reached a maximum concentration (Cmax) at 2 min after BSG injection, whereas BNAc reached Cmax within 3 to 5 min. The generation of BNAc was also observed in the liver. While renal BNAc reached Cmax within 3 to 5 min, hepatic BNAc reached Cmax around 5 min after BSG injection. Moreover, the elimination half-life of the BNAc after intravenous injection of the BSG was equivalent to that observed after intravenous injection of the BNAc itself. These results demonstrate that the kidney contributes to the initial intraorgan generation of BNAc and that this mercapturic acid is also synthesized in the liver and preferentially excreted into urine.

Acetylcysteine↗

Mutation analysis of the feedback inhibition site of aspartokinase III of Escherichia coli K-12 and its use in L-threonine production.

Aspartokinase III (AKIII), one of three isozymes of Escherichia coli K-12, is inhibited allosterically by L-lysine. This enzyme is encoded by the lysC gene and has 449 amino acid residues. We analyzed the feedback inhibition site of AKIII by generating various lysC mutants in a plasmid vector. These mutants conferred resistance to L-lysine and/or an L-lysine analogue on their host. The inhibitory effects of L-lysine on and heat tolerance of 14 mutant enzymes were examined and DNA sequencing showed that the types of mutants were 12. Two hot spots, amino acid residue positions 318-325 and 345-352, were detected in the C-terminal region of AKIII and these enzyme regions may be important in L-lysine-mediated feedback inhibition of AKIII. Feedback resistant lysC relieved on L-threonine hyper-producing strain, B-3996, from reduced L-threonine productivity by addition of L-lysine, and furthermore increased L-threonine productivity even when no addition of L-lysine. It suggested that the bottleneck of L-threonine production of B-3996 was AK and feedback resistant lysC was effective because of the strict inhibition by cytoplasmic L-lysine.

Amino Acid Sequence↗

An elderly patient with gastric carcinoma developing multiple metastasis in skeletal muscle.

We present a 70-year-old man with gastric carcinoma developing multiple metastasis in skeletal muscle. He had a right supraclavicular lymph node swelling. Brain, chest and abdomen CT scans revealed metastatic lesions in the brain, lung, liver and bilateral adrenal glands. Further, CT showed a ring enhanced soft-tissue mass in the left lumbar muscle. Needle aspirate of the mass in both the left lumbar muscle and the right enlarged supraclavicular lymph node revealed cells suggestive of poorly differentiated adenocarcinoma. Upper gastrointestinal endoscopic evaluation demonstrated an advanced gastric carcinoma. Two months after admission, the tumor in the left lumbar muscle had grown and some new lesions in the left iliopsoas muscles appeared. Intramuscular metastasis from gastric carcinoma is an extremely rare phenomenon.

Adenocarcinoma↗

Structure of AF3p21, a new member of mixed lineage leukemia (MLL) fusion partner proteins-implication for MLL-induced leukemogenesis.

The Mixed Lineage Leukemia (MLL) gene is frequently rearranged in leukemia, especially in infantile leukemia and therapy-related leukemia. The MLL gene is localized at chromosome 11q23, and is involved in almost all of the chromosomal translocations involving 11q23. Twenty-four fusion partner genes have been identified to date, and the N-terminus of MLL fuses in-frame to the partner genes in all cases. Some of the MLL fusion partner genes encode transcription factors; others encode small GTP binding protein interacting molecules or cytoplasmic proteins, the functions of which are presently unknown. As a result of the diverse features of the MLL fusion partners, the underlying mechanism for leukemogenesis remains obscure. We cloned the MLL fusion partner gene from leukemic cells from a therapy-related leukemia patient with t(3;11)(p21;q23) and designated the gene AF3p21. This patient had a long latency period (9 years) before developing secondary leukemia. The AF3p21 gene encodes a nuclear protein with a molecular mass of 80 kDa, and this protein has SH3 and proline-rich domains. Among MLL fusion partners identified to date, only AF10 and AF17 have a homo-oligomerization domain. AF3p21 also has a homo-oligomerization domain, which was revealed by using a mammalian two-hybrid system. These results suggest that one possible role of the MLL fusion partners is to form an oligomer of truncated MLL. In this review, current knowledge about MLL-involved leukemogenesis is outlined.

Adaptor Proteins, Signal Transducing↗

F13459, a new derivative of mycophenolic acid. I. Taxonomy, isolation, and biological properties.

In the course of screening for inhibitors of intracellular trafficking of glycoprotein, a new inhibitor, F13459 was isolated from the culture broth of a Penicillium sp. It was purified using solvent extraction, silica gel, Sephadex LH-20 and ODS column chromatography. From structural analysis, F13459 was a derivative of mycophenolic acid, an inhibitor of inosine 5'-monophosphate dehydrogenase. F13459 inhibited hemagglutinin synthesis of NDV at concentrations more than 25 microg/ml. However, syncytium formation as a result of cell surface expression of F-glycoprotein of NDV was inhibited at concentrations of F13459 lower than those required for appreciable inhibition of glycoprotein synthesis.

Animals↗

Survival of Shiga toxin-producing Escherichia coli O157 in marine water and frequent detection of the Shiga toxin gene in marine water samples from an estuary port.

Shiga toxin-producing Escherichia coli (STEC) O157 was investigated with respect to its halotolerance and whether it can survive in marine water. STEC O157 could multiply in a medium containing 5% NaCl and in sterilized marine water, and could survive in unsterilized marine water for at least 15 days. On the basis of these results, we postulated that STEC O157 may survive in natural marine water, and attempted to isolate the bacterium and Shiga toxin gene (stx) from marine water in Japan. The stx, comprising stx1 and stx2, was detected from marine water samples by PCR. STEC and other stx-positive bacteria, however, could not be isolated from these samples in this study. These results indicate that stx-positive bacteria may survive in marine water and suggest the necessity of a survey.

Escherichia coli O157↗

Application of the membrane filter technique to bromodeoxyuridine immunochemistry for exfoliative cytology.

The membrane filter technique for smear specimens of tumors in bromodeoxyuridine (BrdU) immunochemistry is described. The staining results of Raji cells processed using the filter technique was compared with that obtained by the conventional cytospin method. Although the BrdU mean labeling index (LI) for in cytospin specimens was almost the same as the LI in membrane filter specimens, filter specimens showed excellent staining and less cell destruction compared with those processed by cytospin. Small amounts of tumor specimens such as squamous cell carcinoma and polymorphous low-grade adenocarcinoma also were processed using the membrane filter appliance. For squamous cell carcinoma, the LI for the filter specimens was 5.36+/-0.38 and that of the paraffin sections was 5.56+/-0.38. The membrane filter technique provided relatively undamaged specimens for exfoliative cytology and will be useful for immunohistochemical evaluation of tumor cells and for routine, noninvasive cytological screening.

Adenocarcinoma↗

[Effect of actarit combination therapy in patients with active rheumatoid arthritis resistant to gold agents].

We investigated the utility of combination therapy of actarit with gold agents in patients with active rheumatoid arthritis resistant to gold agents even after the administration of gold agents for longer than 24 weeks in principle. 1. In the final global improvement rate by the combination therapy of actarit with gold agents, the ratio of "improved" and/or better was 30.8% (12/39). 2. The clinical evaluation items which showed significant improvement were grip strength, ESR, number of painful joints, number of swollen joints, active joint count, duration of morning stiffness and Lansbury's activity index. 3. ADRs were observed in 6 patients per 75 patients (8.0%), but there was no serious ADR.

Aged↗

Involvement of DNA topoisomerase IIbeta in neuronal differentiation.

Two isoforms of DNA topoisomerase II (topo II) have been identified in mammalian cells. While topo IIalpha is essential for chromosome segregation in mitotic cells, in vivo function of topo IIbeta remains to be clarified. Here we demonstrate that the nucleoplasmic topo IIbeta, highly expressed in differentiating cerebellar neurons, is the catalytically competent entity operating directly on chromatin DNA in vivo. When the cells reached terminal differentiation, this in vivo activity decreased to a negligible level with concomitant loss of the nucleoplasmic enzyme. Effects of topo II-specific inhibitors were analyzed in a primary culture of cerebellar granule neurons that can mimic the in vivo situation. Only the beta isoform was expressed in granule cells differentiating in vitro. ICRF-193, a catalytic topo II inhibitor, suppressed the transcriptional induction of amphiphysin I which is essential for mature neuronal activity. The effect decreased significantly as the cells differentiate. Expression profiling with a cDNA macroarray showed that 18% of detectable transcripts were up-regulated during the differentiation and one-third of them were susceptible to ICRF-193. The results suggest that topo IIbeta is involved in an early stage of granule cell differentiation by potentiating inducible neuronal genes to become transcribable probably through alterations in higher order chromatin structure.

Animals↗