Ebselen as a glutathione peroxidase mimic and as a scavenger of peroxynitrite.
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Animals↗
Biomedical subjects
H Masumoto
Publications and source records attributed to H Masumoto.
Selenium-containing compounds protect DNA from single-strand breaks caused by peroxynitrite.
Peroxynitrite (ONOO-/ONOOH) is a powerful oxidant that can induce mutations and cause single-strand breaks in plasmid supercoiled DNA. The selenium-containing compound ebselen rapidly reacts with peroxynitrite. Therefore, ebselen [2-phenyl-1,2-benzisoselenazol-3(2H)-one] and other selenium-containing molecules, selenomethionine and selenocystine, were studied as agents protecting DNA from single-strand breaks induced by peroxynitrite. Selenomethionine and selenocystine protected DNA from single-strand breaks more effectively than their sulfur analogs, methionine and cystine, and they also were more effective than glutathione or the hydroxyl radical scavenger mannitol. These results suggest that selenium-containing compounds can protect DNA from damage caused by peroxynitrite.
Cystine↗
Effect of vasopressin on esophageal varices blood flow in patients with cirrhosis: comparisons with the effects on portal vein and superior mesenteric artery blood flow.
BACKGROUND/AIMS: Vasopressin reduces portal pressure which may be due to decreased portal inflow. However, it remains unclear whether vasopressin is able to selectively reduce esophageal varices blood flow. The aim of this study was to address this question. METHODS: Fifteen patients with cirrhosis and esophageal varices were included in this prospective study. Portal vein and superior mesenteric artery flow velocity were measured with a percutaneous echo-Doppler. Esophageal varices flow velocity was measured using a transesophageal echo-Doppler technique. Mean arterial pressure and heart rate were also recorded. These measurements were performed at baseline condition and 15 min after observer blind drug administration. In this study, two groups, six patients receiving placebo and nine patients receiving 0.3 U/min of vasopressin, were randomized according to the coded number. RESULTS: Placebo administration had no effect on systemic and splanchnic circulation. In contrast, vasopressin administration increased mean arterial pressure (p < 0.05) associated with a bradycardia (p < 0.01). In splanchnic circulation, vasopressin decreased portal vein (-32 +/- 3%, p < 0.01), superior mesenteric artery (-30 +/- 2%, p < 0.01), and esophageal varices flow velocity (-48 +/- 5%, p < 0.01). When the magnitude of these reductions was compared, ANOVA showed a significant difference (p < 0.01). Furthermore, the reduction in esophageal varices flow velocity was significantly higher than that in portal vein flow velocity (p < 0.01) and that in superior mesenteric artery flow velocity (p < 0.01). CONCLUSIONS: These data support the view that vasopressin is able to selectively reduce esophageal varices blood flow. This effect, in addition to its well-established portal pressure reducing action, may play a role in its therapeutic efficacy in the treatment of variceal bleeding.
Aged↗
Centromere protein B of African green monkey cells: gene structure, cellular expression, and centromeric localization.
Centromere protein B (CENP-B) is a centromeric DNA-binding protein which recognizes a 17-bp sequence (CENP-B box) in human and mouse centromeric satellite DNA. The African green monkey (AGM) is phylogenetically closer to humans than mice and is known to contain large amounts of alpha-satellite DNA, but there has been no report of CENP-B boxes or CENP-B in the centromere domains of its chromosomes. To elucidate the AGM CENP-B-CENP-B box interaction, we have analyzed the gene structure, expression, biochemical properties, and centromeric localization of its CENP-B. The amino acid sequence deduced from the cloned AGM CENP-B gene was established to be highly homologous to that of human and mouse CENP-B. In particular, the DNA binding and homodimer formation domains demonstrated 100% identity to their human and mouse counterparts. Immunoblotting and DNA mobility shift analyses revealed CENP-B to be expressed in AGM cell lines. As predicted from the gene structure, the AGM CENP-B in the cell extracts exhibited the same DNA binding specificity and homodimer forming activity as human CENP-B. By indirect immunofluorescent staining of AGM mitotic cells with anti-CENP-B antibodies, a centromere-specific localization of AGM CENP-B could be demonstrated. We also isolated AGM alpha-satellite DNA with a CENP-B box-like sequence with CENP-B affinity. These results not only prove that CENP-B functionally persists in AGM cells but also suggest that the AGM genome contains the recognition sequences for CENP-B (CENP-B boxes with the core recognition sequence or CENP-B box variants) in centromeric satellite DNA.
Amino Acid Sequence↗
Hepatic artery hemodynamic responsiveness to altered portal blood flow in normal and cirrhotic livers.
PURPOSE: To compare hepatic artery hemodynamic response to altered portal blood flow in normal and cirrhotic livers. MATERIALS AND METHODS: The portal blood flow and hepatic artery pulsatility index were measured by means of duplex ultrasound before and after subjects (eight control subjects and 10 cirrhotic patients) ingested a 500-kcal mixed-liquid meal and during intravenous infusion of vasopressin at a rate of 0.3 U/min (nine control and nine cirrhotic subjects). The hepatic artery buffer index (ratio of maximum change from baseline in hepatic artery pulsatility index to maximum change from baseline in portal blood flow) was also calculated. RESULTS: Meal consumption increased the portal blood flow and hepatic artery pulsatility index in all subjects. The hepatic artery buffer index, however, was significantly lower in cirrhotic than in control subjects (0.67 min/L +/- 0.06 [standard error of the mean] vs 1.54 min/L +/- 0.20, respectively; P < .01). Vasopressin infusion decreased the portal blood flow and hepatic artery pulsatility index in all subjects. Again, the hepatic artery buffer index was significantly lower in cirrhotic than in control subjects (0.28 min/L +/- 0.07 vs 0.50 min/L +/- 0.04, respectively; P < .05). CONCLUSION: Hepatic artery vascular responsiveness to altered portal blood flow is blunted in cirrhotic livers.
Fasting↗
Postprandial splanchnic hemodynamic response in patients with cirrhosis of the liver: evaluation with "triple-vessel" duplex US.
PURPOSE: To investigate the effect of a meal on splanchnic circulation in patients with cirrhosis of the liver. MATERIALS AND METHODS: Ten adult patients with cirrhosis and 10 adult control subjects (mean age, 54 years) underwent duplex ultrasonography. Flow volumes of the portal vein, superior mesenteric artery, splenic artery, and collateral vessels (difference between the splanchnic inflow [the sum of the superior mesenteric arterial and the splenic arterial blood flows] and the portal venous blood flow) were measured before and after a meal every 15 minutes for 60 minutes. Integrated post-prandial changes (the sum of the changes at each time point) were also calculated. RESULTS: Portal venous blood flow increased after the meal in control subjects (P < .01) and patients (P < .01). The integrated postprandial change in the portal venous blood flow was lower in patients than in control subjects (P < .05). Superior mesenteric arterial blood flow increased after the meal in control subjects (P < .01) and patients (P < .01); the integrated postprandial change in the superior mesenteric arterial blood flow was similar. In the two groups, splenic arterial blood flow remained unchanged after the meal. Collateral blood flow increased after the meal in patients (P < .01). CONCLUSION: Postprandial portal hyperemia is mainly due to mesenteric arterial vasodilation; reduced postprandial portal hyperemia in patients with cirrhosis is attributable to portocollateral runoff.
Adult↗
Cardiac rescue of an infant with fulminant myocarditis using extracorporeal membrane oxygenation.
A 7-month-old boy presented with fulminant myocarditis. He was in cardiac shock and cardiac dysfunction progressed despite aggressive support. Extracorporeal membrane oxygenation (ECMO) was applied for 8 days and he recovered with mild dilated cardiomyopathy.
Extracorporeal Membrane Oxygenation↗
[Diagnostic value of high N-isopropyl-p-[123I] iodoamphetamine (IMP) uptake in brain tumors].
The diagnostic value of high N-isopropyl-p-[123I] iodoamphetamine (123I-IMP) uptake in histologically proven intracranial tumors was evaluated in 54 patients with both early (15-35 min after injection) and delayed (4 hours) SPECT before treatment. Higher uptake in the tumor compared with normal cerebral cortex was observed in early scans in all of the five patients with primary intracranial malignant lymphoma, in two of 16 meningiomas, two of seven astrocytomas, one of three pituitary adenomas, and one central neurocytoma. Among these 11 cases all the malignant lymphomas showed persistent high uptake in delayed scans, whereas other tumors showed decreased uptake in delayed scans. This persistent high 123I-IMP uptake was characteristic of primary intracranial malignant lymphomas and was useful in the diagnosis of intracranial malignant lymphoma.
Adult↗
[Functions of centromere protein B (CENP-B) and control of metaphase progression].
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Animals↗
[Quadricuspid aortic valve: report of a case associated with severe aortic regurgitation].
A case of quadricuspid aortic valve is reported. A 53-year-old man was admitted to our hospital for exertional dyspnea. He had a grade 3/6 to & fro murmur along the left sternal border. Aortogram showed grade 3 aortic regurgitation. The aortic valve consisted of two equal larger cusps and two equal smaller cusps, and a supernumerary cusp located between the right and noncoronary cusps. Aortic valve replacement was performed successfully and his post operative course was uneventful. On histological examination, the resected cusps showed fibrotic thickening and no sign of previous inflammatory disease. Quadricuspid aortic valve has been extremely rare. 27 Japanese cases of quadricuspid aortic valve which were corrected surgically are reviewed.
Aortic Valve↗
[Interesting case of pulmonary alveolar proteinosis].
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Aged↗
Replication slippage between distant short repeats in Saccharomyces cerevisiae depends on the direction of replication and the RAD50 and RAD52 genes.
Small direct repeats, which are frequent in all genomes, are a potential source of genome instability. To study the occurrence and genetic control of repeat-associated deletions, we developed a system in the yeast Saccharomyces cerevisiae that was based on small direct repeats separated by either random sequences or inverted repeats. Deletions were examined in the LYS2 gene, using a set of 31- to 156-bp inserts that included inserts with no apparent potential for secondary structure as well as two quasipalindromes. All inserts were flanked by 6- to 9-bp direct repeats of LYS2 sequence, providing an opportunity for Lys+ reversion via precise excision. Reversions could arise by extended deletions involving either direct repeats or random sequences and by -1-or +2-bp frameshift mutations. The deletion breakpoints were always associated with short (3- to 9-bp) perfect or imperfect direct repeats. Compared with the POL+ strain, deletions between small direct repeats were increased as much as 100-fold, and the spectrum was changed in a temperature-sensitive DNA polymerase delta pol3-t mutant, suggesting a role for replication. The type of deletion depended on orientation relative to the origin of replication. On the basis of these results, we propose (i) that extended deletions between small repeats arise by replication slippage and (ii) that the deletions occur primarily in either the leading or lagging strand. The RAD50 and RAD52 genes, which are required for the recombinational repair of many kinds of DNA double-strand breaks, appeared to be required also for the production of up to 90% of the deletions arising between separated repeats in the pol3-t mutant, suggesting a newly identified role for these genes in genome stability and possibly replication.
Base Sequence↗
Analysis of protein-DNA and protein-protein interactions of centromere protein B (CENP-B) and properties of the DNA-CENP-B complex in the cell cycle.
We previously reported that centromere protein B (CENP-B) forms a stable complex (designated complex A) containing two alphoid DNAs in vitro. Domains in the CENP-B polypeptide involved in the formation of complex A were determined in the present study with truncated derivatives expressed in Escherichia coli and in rabbit reticulocyte lysates. It was revealed by gel mobility shift analyses that polypeptides containing the NH2-terminal DNA-binding domain bind a DNA molecule as a monomer, while dimerizing at a novel hydrophobic domain in the COOH-terminal region of 59 amino acid residues. This polypeptide dimerization activity at the COOH-terminal region was also confirmed with the two-hybrid system in Saccharomyces cerevisiae cells. The results thus proved that CENP-B polypeptides form a homodimer at the COOH-terminal hydrophobic domain, each binding a DNA strand at their NH2-terminal domains. The dimerization and DNA-binding domains fall into two of the three completely conserved sequences found in human and mouse CENP-B, and complex A-forming activity was also detected in nuclear extracts of mouse cells. Metaphase-specific phosphorylation of CENP-B was also detected, but this had no effect on its complex A-forming activity. On the basis of the present results, we propose that CENP-B plays an important role in the assembly of specific centromere structures by forming unique DNA-protein complexes at the sites of CENP-B boxes on the centromeric repetitive DNA both in interphase nuclei and on mitotic chromosomes.
Amino Acid Sequence↗
CENP-B binds a novel centromeric sequence in the Asian mouse Mus caroli.
Minor satellite DNA, found at Mus musculus centromeres, is not present in the genome of the Asian mouse Mus caroli. This repetitive sequence family is speculated to have a role in centromere function by providing an array of binding sites for the centromere-associated protein CENP-B. The apparent absence of CENP-B binding sites in the M. caroli genome poses a major challenge to this hypothesis. Here we describe two abundant satellite DNA sequences present at M. caroli centromeres. These satellites are organized as tandem repeat arrays, over 1 Mb in size, of either 60- or 79-bp monomers. All autosomes carry both satellites and small amounts of a sequence related to the M. musculus major satellite. The Y chromosome contains small amounts of both major satellite and the 60-bp satellite, whereas the X chromosome carries only major satellite sequences. M. caroli chromosomes segregate in M. caroli x M. musculus interspecific hybrid cell lines, indicating that the two sets of chromosomes can interact with the same mitotic spindle. Using a polyclonal CENP-B antiserum, we demonstrate that M. caroli centromeres can bind murine CENP-B in such an interspecific cell line, despite the absence of canonical 17-bp CENP-B binding sites in the M. caroli genome. Sequence analysis of the 79-bp M. caroli satellite reveals a 17-bp motif that contains all nine bases previously shown to be necessary for in vitro binding of CENP-B. This M. caroli motif binds CENP-B from HeLa cell nuclear extract in vitro, as indicated by gel mobility shift analysis. We therefore suggest that this motif also causes CENP-B to associate with M. caroli centromeres in vivo. Despite the sequence differences, M. caroli presents a third, novel mammalian centromeric sequence producing an array of binding sites for CENP-B.
Animals↗
[A case report of primary pulmonary artery sarcoma].
A 49-year-old man was admitted because of dyspnea and generalized edema. CT scan pulmonary scintigram and cardiac catheter examination revealed pulmonary arterial obstruction due to a tumor associated with right heart failure. The tumor was extirpated as much as possible by a pulmonary arteriotomy under cardiopulmonary bypass. Postoperatively, right ventricular pressure decreased to about 40 mmHg while PO2 increased to the normal level. Histological examination of the tumor revealed rhabdomyosarcoma arising from the pulmonary artery. Chemotherapy consisting of a single course of CDDP and adriamycin was administered.
Humans↗
[A case report of traumatic diaphragmatic hernia treated by thoracoscopic surgery].
A 56-year-old man who had been accidentally hit on the right side of the chest about 20 days previously was admitted because of intractable cough. Chest X-ray and CT scan revealed a right-sided diaphragmatic hernia and slight pneumothorax. No other hemorrhagic or perforative complications were detected. On the third hospital day, the patient underwent therapeutic thoracoscopy. Herniated transverse colon and liver were repaired through the abdominal cavity and the lacerated diaphragm was sutured through four thoracoports with video system assistance. The postoperative course was uneventful, and the patient was discharged 28 days later.
Endoscopy↗
[Two cases of traumatic aneurysm of the aortic isthmus].
Two cases with blunt traumatic aneurysm of the aortic isthmus were treated recently. One was operated in early stage using heparin-bounded transient aorto-aorta bypass. The other underwent delayed operation with aorto-aorta bypass using centrifugal pump. Patch closures with Dacron fabric sealed by equine pericardium were performed in both of them with satisfactory results. We discussed the controversial problems, the timing of the operation and the method of adjunct circulation.
Adult↗
[Low-dose FP (5-FU+low-dose CDDP) therapy for far advanced upper gastro-intestinal carcinoma].
Low-dose FP therapy was undertaken in 25 patients with far advanced or recurrent carcinoma (13 stomach, 7 esophagus, 3 colon, 1 gallbladder, 1 pancreas). This therapy consisted of intermittent infusion of CDDP (10 mg/body X 5 days) and continuous infusion of 5-FU (500 mg/body X 5 days) for 5 days with 2-day intervals. Patients were treated with at least 2 courses of low-dose FP therapy. Of the 25 patients, 12 with esophageal (7) or gastric (5) carcinoma, in whom curative resection was considered impossible before the operation, were subjected to neoadjuvant chemotherapy. The response rate in the neoadjuvant therapy was 100% (2 disappeared and 5 decreased in size) in the esophageal cancer and 60% (3 decreased in size) in the gastric cancer. But, in 6 patients with esophageal cancer, radiotherapy was combined. In the neoadjuvant cases, pathological effect of Grade 2 was noted in 3 of the 7 esophageal cancers and 1 of the 5 gastric cancers. Of the remaining 13 unresectable patients, a significant improvement of performance status was found in 6 patients. In 19 patients treated with low-dose FP therapy only, leukopenia of Grade 3 was not observed, and there was no nephrotoxicity. Low-dose FP therapy is safe and useful as a neoadjuvant chemotherapy for patients with far advanced esophageal or gastric cancer.
Adult↗