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Biomedical subjects

M Ono

Publications and source records attributed to M Ono.

At least 559 records · Page 31Linked to original sources

Effects of verapamil on electrophysiological properties in paroxysmal atrial fibrillation.

Verapamil is used to control ventricular response during atrial fibrillation (AF). Limited data is available on the effects of verapamil on atrial vulnerability in human AF. The effects of intravenous verapamil (0.15 mg/kg) on electrophysiological properties of the atrium were investigated in 12 patients with documented paroxysmal AF by electrophysiological studies. Sinus cycle length, sinus node recovery time, and the effective refractory period of the right atrium were not significantly affected by verapamil. The intraatrial conduction delay zone was significantly increased (33 +/- 20 msec before verapamil versus 50 +/- 22 msec after verapamil, P < 0.01), and the maximal intraatrial conduction delay was also significantly prolonged by verapamil, both to the His bundle region (30 +/- 12 msec before verapamil versus 42 +/- 15 msec after verapamil, P < 0.01) and to the coronary sinus (40 +/- 15 msec before verapamil versus 53 +/- 17 msec after verapamil, P < 0.01). The fragmented atrial activity zone was significantly increased (15 +/- 14 msec before verapamil versus 25 +/- 22 msec after verapamil, P < 0.02), and the percentile fragmented atrial activity was also significantly increased by verapamil (149 +/- 18 msec before verapamil versus 174 +/- 44 msec after verapamil, P < 0.05). The repetitive atrial firing zone remained unchanged. Sustained AF spontaneously occurred in only one patient after the administration of verapamil. Thus, verapamil may modulate the abnormal atrial electrophysiology in paroxysmal AF, and would favor production of atrial reentry.

Aged↗

Aldose reductase inhibition and the phosphorus-31 profile of the intact diabetic rat lens.

Diabetic metabolic change and response to aldose reductase inhibition in the Wistar rat lens were examined with phosphorus-31 (31P) nuclear magnetic resonance (NMR) spectroscopy. To avoid artifacts in sample preparation, we used freshly excised lenses and acquired NMR data for 20 min immediately after lens extraction. The results showed a diabetes-induced time-dependent loss of ATP and phosphorylcholine (PC), an increase in alpha-glycerophosphate (alpha-GP) and inorganic phosphate and the appearance of sorbitol-3-phosphate (S-3-P) and fructose-3-phosphate (F-3-P). Oral but not topical dosing of an aldose reductase inhibitor, 5-(3-ethoxy-4-pentyloxyphenyl)-2,4- thiazolidinedione, resulted in a positive dose-response correlation characterized by a restoration of PC, S-3-P and F-3-P to the prediabetic level; however, alpha-GP and ATP were only partially normalized. The significance of the 31P change was further discussed.

Adenosine Triphosphate↗

Induction of vascular endothelial tubular morphogenesis by human glioma cells. A model system for tumor angiogenesis.

We have developed two different models of tumor angiogenesis by human brain tumors: one being tube formation by bovine aortic endothelial (BAE) cells cocultured with tumor cells in vitro, and other being in vivo angiogenesis in mice when tumor cells are transplanted into the dorsal sac. We investigated whether tube formation could be induced in BAE cells in type I collagen gel when these cells were cocultured with seven human glioma cell lines. Four of the seven glioma cell lines, which had high levels of basic fibroblast growth factor (bFGF) mRNA, induced tube formation by BAE cells. The tube formation was blocked by coadministration of anti-bFGF antibody. In in vivo model system of tumor angiogenesis in mice, these four cell lines were highly angiogenic. In contrast, with the other three glioma cell lines, which had poor expression of bFGF, BAE cells showed no apparent tube formation. These three cell lines did not efficiently develop capillary networks in mice. The results demonstrated a correlative relationship in the tubulogenesis of BAE cells, bFGF mRNA levels and angiogenesis in mice. The present study with two model systems of tumor angiogenesis suggests that the angiogenesis of some human glioma cell lines is mediated by bFGF, possibly via paracrine control.

Animals↗

Brefeldin A protects ricin-induced cytotoxicity in human cancer KB cell line, but not in its resistant counterpart with altered Golgi structures.

Brefeldin A (BFA), an isoprenoid fungal metabolite, dramatically disrupts intracellular protein transport and protein secretion. BFA protects cells from the cytotoxicity of a plant toxin, ricin or pseudomonas toxin, but not that of diphtheria toxin (Yoshida et al., 1991. Expt. Cell Res., 192: 389-395.). In this study, we examined whether BFA could differentially change the cytotoxicity of ricin between BFA-sensitive cells and BFA-resistant cells. As a BFA-resistant cell line, we used a resistant cell line, KB/BF2-2, derived from BFA-sensitive human cancer KB cells. BFA treatment caused the disappearance of typical Golgi cisternae and the concomitant appearance of dilated vesicles in the cytoplasm in KB cells. By contrast, KB/BF2-2 cells had already altered Golgi structures with poor development of cisternae and also many vesicles in the absence of BFA, and BFA treatment did not further induce the morphological changes. Although a plasma membrane-specific marker protein, alpha-adaptin, was localized similarly in KB/BF2-2 as KB, Golgi specific markers such as beta-cop and gamma-adaptin were distributed in the cytoplasmic small vesicles as well as Golgi compartments in KB/BF2-2 cells in the absence of BFA, and the mutant cells showed no apparent changes in the distribution even when exposed to BFA. Ricin inhibited protein synthesis in KB and KB/BF2-2 to similar levels while pretreatment of KB cells with BFA at 0.1 microgram/ml almost completely reversed the inhibitory effect of ricin. By contrast, the pre-exposure of KB/BF2-2 cells to 1.0 microgram/ml BFA only partially rescued the ricin-induced inhibition of protein synthesis. Exposure to BFA at 30 min before ricin addition or at 0 min with ricin rescued the protein synthesis inhibition, but no rescue occurred when BFA was added 30 min after ricin addition. BFA could not rescue the protein synthesis inhibition by another toxin, diphtheria toxin. Our results suggest that BFA-resistant mutation causes a specific change in the endocytic membrane traffic of ricin in human cells, and also that cytotoxicity of diphtheria toxin does not share a common pathway of the intracellular transport with that of ricin.

Adaptor Protein Complex gamma Subunits↗

Synthetic Arg-Gly-Asp-Ser analogues of the cell recognition site of fibronectin that retain antimetastatic and anti-cell adhesive properties.

Synthetic peptide analogues of the Arg-Gly-Asp-Ser (RGDS) sequence of fibronectin in which the amino acid of Gly was substituted with another one, named X, i.e. Arg-X-Asp-Ser (R-X-DS), and N-terminal modified R-X-DS have been synthesized to examine their antimetastatic effects in murine lung or liver metastasis models, as well as the inhibitory effect on tumor cell invasion, migration and adhesion in vitro. R-X-DS [X = Leu (L) or D-Leu (1)], as well as RGDS at a high dose of 3000 micrograms, significantly reduced the number of lung tumor colonies when they were co-injected with B16-BL6 melanoma. At a dose of 1000 micrograms/mouse, N-terminal modified R-X-DS, i.e. acetyl-D-R-X-DS [AcDR-X-DS: X = G, L or I], showed a more potent inhibitory effect on the lung or liver metastasis of B16-BL6 melanoma or L5178Y-ML25 lymphoma cells, respectively, as compared with RGDS or R-X-DS. AcDRLDS and AcDRIDS prevented the invasion of B16-BL6 cells into Matrigel/fibronectin- and Matrigel/laminin- coated filters, haptotactic migration, and the adhesion of the cells to both fibronectin- and laminin-coated substrates, whereas AcDRGDS inhibited only fibronectin-mediated cell functions. The intermittent i.v. administration of a water soluble vinylpolymer [poly(carboxyethylmethacrylamide), poly(CEMA)] containing R-X-DS (X = L or 1) or RGDS, following the subcutaneous inoculation of B16-BL6 cells, significantly inhibited spontaneous Jung metastasis as compared with multiple administrations of RGDS, R-X-DS or the untreated control.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Resin glycosides. XIX. Woodrosins I and II, ether-insoluble resin glycosides from the stems of Ipomoea tuberosa.

Two new ether-insoluble resin glycosides named woodrosins I and II were isolated from the stems of Ipomoea tuberosa L., and their structures were determined on the basis of chemical and spectral data. Contrary to anticipation, they had an intramolecular cyclic ester structure similar to that of ether-soluble resin glycosides (Mayer's jalapin) hitherto isolated. It is proposed to use the terms, "jalapin" and "convolvulin," not according to the solubility in ether (Mayer's classification), but according to the structure, i.e., intramolecular esters and others, respectively.

Carbohydrate Sequence↗

Nucleotide sequence of the glycoprotein C (gC) homologous gene of Marek's disease virus (MDV) serotype 2 and comparison of gC homologous genes among three serotypes of MDV.

The sequence analysis of the genomic region of Marek's disease virus (MDV) serotype 2 (MDV2) which had homology with the gene encoding MDV serotype 1 (MDV1) homologue of glycoprotein C (gC) of herpes simplex virus revealed that there was a single open reading frame (ORF) capable of encoding 479 amino acids. The predicted protein from this ORF had strong hydrophobic regions in both the amino and carboxyl termini and several potential N-linked glycosylation sites, as seen in those from the ORFs of MDV1 and MDV serotype 3 (MDV3 = herpesvirus of turkeys (HVT)) gC homologues. By northern-blot analysis using a DNA fragment located in the MDV2 gC homologue ORF as a probe, 3.6 and 1.9 kb RNA transcripts were identified in MDV2-infected cells. When the alignment of amino acid sequences of the gC homologous genes of three MDV serotypes were compared, the homology between MDV1 and MDV2 and that between MDV1 and HVT showed about 76% identity, whereas that between MDV2 and HVT was about 70% identity. These results suggested a possibility that the evolutionary distance between MDV1 and MDV2 and between MDV1 and HVT is shorter than that between MDV2 and HVT.

Amino Acid Sequence↗

Expression of mRNA coding for pituitary hormones and pituitary-specific transcription factor in the pituitary gland of the rdw rat with hereditary dwarfism.

The rdw rat (gene symbol: rdw) with hereditary dwarfism has been shown immunohistochemically to have subnormal numbers not only of GH- but also of prolactin- and thyrotrophin-positive cells. To characterize the dwarfism of this strain, the expression of pituitary hormone mRNAs was examined by Northern hybridization. The pituitary gland in the rdw rat expressed 30-100 times less GH and prolactin mRNAs than normal controls, whereas mRNAs for pro-opiomelanocortin and the alpha subunit of rat glycoprotein hormone revealed a significant increase. There was a non-significant difference in rat LH-beta subunit and FSH-beta subunit between normal and rdw rats. The suppressed expression of a pituitary-specific transcription factor, Pit-1, is considered to cause hereditary dwarfism in mouse strains Snell and Jackson, whose phenotypes resemble those of the rdw rat. In this study, however, no difference in mRNA expression for Pit-1 was found between rdw rats and controls. This work indicates that the rdw rat may not have the same genotype as the phenotypically similar dwarf mice, Snell, Jackson and Ames.

Animals↗

Inhibition of liver regeneration in mice following extended hepatectomy by transfusion of lymphokine activated killer cells.

Lymphokine activated killer (LAK) cells can destroy not only tumor cells but also syngeneic liver cells. In this study, the effects of passive transfer of LAK cells on liver regeneration were examined by the 3H-thymidine uptake and bromodeoxyuridine (BrdU) labeling methods after resection of 70% of the volume of the liver. LAK cells were infused 12h after hepatectomy and the effects on regeneration of liver cells were examined 36 h later. The transfusion of LAK cells induced significant inhibition of liver regeneration at a dose of 5-10 x 10(7) cells. Neuraminidase treatment of lymphocytes is desirable to enhance the selective entrapment of LAK cells into the liver. When LAK cells were treated with neuraminidase (0.5 units/ml), and transfused into hepatectomized mice, more potent suppression of liver regeneration was induced in comparison with the same dose of LAK cells. The intraperitoneal injection of recombinant interleukin 2 (rIL-2) after partial hepatectomy also inhibited the regeneration of remnant liver. From these results, lymphocytes such as LAK cells appear to regulate liver regeneration.

Animals↗

Induction of different types of glomerulonephritis by monoclonal antibodies derived from an MRL/lpr lupus mouse.

MRL/Mp-lpr/lpr(MRL/lpr) lupus mice develop glomerulonephritis in which the histopathological manifestations of the disease are characterized by diffuse cell-proliferative, crescentic, and/or wire loop-like lesions, resembling those of human lupus nephritis. Although these lesions are thought to be mediated by antibodies, little data is available to explain these regular variations in glomerular lesions induced by antibodies at the monoclonal level. We studied glomerular lesions of normal or severe combined immunodeficient mice injected with nephritogenic immunoglobulin G3-producing hybridoma clones (2B11.3 and 7B6.8), which we previously established from an unmanipulated MRL/lpr mouse. Both clones caused increased serum levels of immunoglobulin G3 with identical patterns over time and both induced glomerular deposits of immunoglobulin G3 and C3. However, 2B11.3 and 7B6.8 induced glomerular lesions that differed in their histopathological manifestations. The 2B11.3 clone generated cell-proliferative lesions associated with marked Mac-2-positive macrophage infiltrates, but the 7B6.8 clone induced lesions characterized by subendothelial hyaline deposits resembling wire loops. The latter was not associated with significant inflammatory cell infiltrates at any point throughout the progression of the lesion. Thus, our findings suggest that the histopathological variation in glomerulonephritis seen in MRL/lpr mice results from clonally expanded B cell clones that produce nephritogenic antibodies with different pathogenic potencies.

Animals↗

[Successful surgical repair of emphysematous giant bullae of the elderly with severely depressed pulmonary function].

A 71-year-old male was admitted to an emergency hospital owing to severe dyspnea of sudden onset. Bilateral tension pneumothorax with two giant bullae occupying more than the third of the right lung was disclosed on the chest X-ray. Bilateral chest drainages and cardiopulmonary resuscitation were performed. He could be freed from ventilatory support several days after tracheostomy and was referred to our hospital. The pulmonary function was severely depressed: VC (%) 1.20 l (40%) and FEV1.0 (%) 0.55 l (46%). In spite of oxygen inhalation he could not keep sitting due to dyspnea (Hugh-Jones grade V). Right multiple bullectomy was performed successfully and his postoperative course was uneventful. He was discharged eight weeks later. Seven months after surgery his pulmonary function was remarkably improved: VC (%) 2.05 l (64%) and FEV1.0 (%) 0.94 l (46%). He became to walk almost equally with a healthy man one year later (Hugh-Jones grade II).

Aged↗

[Effect of cigarette smoking on diffuse pulmonary uptake of 99mTc-HM PAO].

To investigate the clinical significance of pulmonary uptake of 99mTc-HM PAO, we studied the effect of cigarette smoking on pulmonary uptake of 99mTc-HM PAO. This study included 14 volunteers: 4 nonsmokers and 10 smokers (Brinkmann indexes 544 +/- 270.8). Following injection of 99mTc-HM PAO into the antecubital vein, time-activity curve was obtained with the regional activity of one frame/min. for 30 minutes and 64 x 64 matrices. Characteristics of pulmonary clearance curve, described as C(t) = A exp-kt, and lung/liver uptake ratio (Lu/Li index) at 30 min. after injection were determined, and groups of non-smokers and smokers were compared. In smokers, 99mTc-HM PAO clearance was delayed and k was smaller significantly. Lu/Li index was also higher in smokers. Brinkmann index correlated both with k (r = -0.815, p < 0.01) and Lu/Li index (r = 0.911, p < 0.01). In conclusion, the delayed clearance and retention of 99mTc-HM PAO in the lung may indicate metabolic disorders of the lung due to cigarette smoking.

Adult↗

[Immunological effect of recombinant interferon-gamma in renal cell carcinoma].

The immunological effect of interferon-gamma (IFN-gamma) was investigated in 18 cases of renal cell carcinoma before and after the operation. In 6 patients, IFN-gamma was administered preoperatively for 21 days (administration group), while 12 patients underwent nephrectomy alone without preoperative treatment (control group). The peripheral immunological effects were measured at before and 12 days after the operation in the administration group and at 11 days in the control group. In the administration group, a marked increase was noted in the test of antibody dependent cell-mediated cytotoxicity (ADCC) activity and natural killer (NK) activity, and slight increase in CD4/8 and CD11b. In low stage cases, no appreciable effect was obtained by the administration of IFN-gamma. However, in high stage cases, IFN-gamma tended to increase the value of ADCC activity and NK activity. Immunohistochemical studies of tumor infiltrating lymphocytes in renal cell carcinoma showed a high incidence of CD8 and CD11b in the administration group. Moreover, the presence of CD8 was higher than that of CD4 in the administration group in contrast to the results of the peripheral blood analysis.

Carcinoma, Renal Cell↗

[A role of valvuloplasty in surgical treatment of isolated tricuspid regurgitation].

Seven surgical cases of isolated tricuspid regurgitation were reviewed. From pathological point of view, the patients were classified into three groups. Two were due to abnormalities of subvalvular system, four to annular dilatation and one to anomalous leaflet. Among four cases of annular dilatation, two were diagnosed as dilated cardiomyopathy. In one, it was very rare myopathy confined to right ventricle. Three cases, two subvalvular and one leaflet abnormalities, underwent valvuloplasty which included chordal reconstruction using Gore-Tex suture. Among annular dilatation group, three underwent valve replacement (two with mechanical valve and one with bioprosthetic valve), while fourth underwent annuloplasty. When We look at 89 surgical patients with secondary tricuspid regurgitation, thrombosed mechanical valve was seen in two cases, one of them necessitating re-valve replacement. On the other hand, late results of tricuspid annuloplasty with Carpentier-Edwards ring was excellent without re-operation. Although isolated tricuspid regurgitation has very complicated pathological features, we now think it very important to manage to repair regurgitant tricuspid valve utilizing all available techniques including redundant valve tissue resection, chordal reconstruction, and annuloplasty, thus avoiding valve replacement especially with mechanical valve.

Adolescent↗

Debulking surgery and arterial embolization for unresectable liver cancer.

Hepatocellular carcinomas measuring less than 5 cm in diameter became completely necrotic after arterial chemoembolization with Lipiodol, doxorubicin, and gelfoam more often than larger lesions. In 60 patients, we surgically debulked large unresectable tumors, with the aim of subsequently embolizing residual small tumors transarterially. Forty-seven patients were actually embolized. The rate of major non-fatal complications was similar to that seen after radical resections, but the hospital mortality rate was 30%, as compared with 4%. Stage I disease, including non-embolized patients and hospital mortality, had an estimated 5-year survival rate of 27%. This result approached that obtained after curative resections, and was better than that seen after embolization only. Stage II disease had no five-year survivors and its survival curve was intermediate, lying between those of curatively resected and embolization patients. No stage I patients with tumor growth in the portal trunk or lobar branches survived for 2 years. The results warrant further study of this treatment strategy.

Adult↗

[Curative surgery for lung cancer invading the aorta with bilateral emphysematous giant bullae: a case report].

A 56-year-old male patient who had been suffered from giant emphysematous bullae in both lungs was referred to our hospital because of newly developing left lung abnormal shadow, which was adjacent to the aorta on chest X-ray. Lung cancer invading the aorta was suspected on CT scanning and curative operation was scheduled. At left thoracotomy there were large bullae in the upper lobe, part of which covered on and stuck to the tumor mass on the aortic wall. We performed left upper lobectomy, combined with the partial resection of the aortic wall and repaired it with dacron patch using partial extracorporeal circulation with cannulations into the main pulmonary artery and the descending aorta. Pathological diagnosis was large cell carcinoma. Lung cancer invading the aorta can be safely excised using assisting circulatory devices such as extracorporeal circulation. We expect this type of operation will be widely accepted and make better results.

Aorta↗

[An hourglass type intrathoracic lipoma--a case report of surgical treatment].

We report a rare case of hourglass type intrathoracic lipoma. Until now, there are 114 reported cases on intrathoracic lipoma in Japanese literature, among which 22 are hourglass type. The patient was a 43-year-old woman, who was found to have a pleural tumor on her chest X-ray examination for healthy check-up. Computed tomography showed that it had intra- and extrathoracic portion with almost the same density as the subcutaneous fat tissue. The tumor was excised along with pleura, periostia and intercostal muscle approximately 1 cm apart from it. It was dumbbell-shaped and weighed 30 grams. Microscopically it was found to be intramuscular lipoma. According to Fletcher, intramuscular lipoma was classified into two groups of infiltrative and non-infiltrative type. In their cases, infiltrative intramuscular lipomas recurred up to 19%, mainly secondary to incorrect resection. Our case corresponds to infiltrative type. We consider that intrathoracic lipoma, though benign, have to be resected radically with utmost care.

Adolescent↗

[Myxoma originating from right ventricle found incidentally with cardiac murmur--a case report of surgical treatment].

We report a rare case of a 21-year-old male who had myxoma originating from septal band of the right ventricle. He was otherwise healthy young man without any associated symptom. His cardiac murmur was found incidentally upon routine health control mass examination. Subsequently, echocardiography and angiocardiography demonstrated a tumor occupying the right ventricular outflow tract and protruding into the main pulmonary artery in systolic phase. He was operated upon using extracorporeal circulation. By right ventriculotomy the tumor was resected together with septal tissue 5 mm around the stalk, which branched into the myocardium. Resected mass was 4 x 3.7 cm in size and 5 grams in weight. Because of the frozen section of the surgical stump was positive for tumor cells, additional resection of septal myocardium was carried out. The defect was closed using mattress sutures with dacron felt strips. His postoperative course was uneventful. Thirty-two months after the surgery, patient has no sign of recurrence. Right ventricular myxoma is uncommon with only 27 cases appearing in Japanese literature. In review of literature, we discussed the characteristics and management of the right ventricular myxoma.

Adult↗