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Biomedical subjects

T Yano

Publications and source records attributed to T Yano.

At least 271 records · Page 15Linked to original sources
PubMed1998

Relapsed acute promyelocytic leukemia previously treated with all-trans retinoic acid: clinical experience with a new synthetic retinoid, Am-80.

All-trans retinoic acid (ATRA), a potent differentiating drug for acute promyelocytic leukemia (APL), induces a high incidence of complete remission (CR) in patients with APL and is now established as a first-line therapy. However, ATRA resistance has become a clinical problem. Patients who relapsed after ATRA-induced CR have had difficulty in obtaining a second CR with ATRA therapy. Although several mechanisms have been postulated, treatment strategies to overcome resistance have not been established. We used a new synthetic retinoid, Am-80, as reinduction therapy for APL relapse after from ATRA-induced CR. Am-80 was several times more potent than ATRA in inducing differentiation in vitro. At a 6 mg/m2 dose, there were 24 evaluable patients; 14 (58%) achieved CR between days 20 and 58 (median, 37 days). Clinical response correlated with the in vitro response to Am-80. Adverse effects included retinoic acid syndrome (n = 1), hyperleukocytosis (n = 1), xerosis (n = 9), cheilitis (n = 8), hypertriglyceridemia (n = 16), and hypercholesterolemia (n = 15). Am-80 is active in APL after relapse from ATRA-induced CR. Further clinical trials are needed to establish strategies to overcome ATRA resistance.

Adult↗
PubMed1998

Direct percutaneous transluminal angioplasty for acute middle cerebral artery occlusion.

PURPOSE: We review our initial experience with direct percutaneous transluminal angioplasty (PTA) as a reperfusion treatment for acute occlusion of the middle cerebral artery. METHODS: Ten patients in whom successful thrombolysis might not be expected because of the risk of hemorrhagic complications or reocclusion were treated with direct PTA. When early ischemic findings were present on the initial CT scans and/or when lenticulostriate arteries were involved, we performed direct PTA rather than thrombolytic therapy. Direct PTA was also performed when superselective local angiography via a Tracker catheter advanced just distal to the occlusion site showed the presence of a large embolus or high-grade stenosis suggestive of thrombosis. Angioplasty was performed with a Stealth balloon catheter with a maximum diameter of 2.0 to 2.5 mm. The balloon catheter was advanced into the site of occlusion and inflated to 2 atm initially, and subsequently up to 3 atm. Two to six inflations, each of 30 seconds' duration, were performed. RESULTS: Although the rate of initial recanalization was 100% (10 of 10), reocclusion occurred in two patients with atherothrombotic M2 occlusion. The final angiographic success rate of direct PTA was 80% (8 of 10). There were no hemorrhagic or technical complications, and five of 10 patients showed marked clinical improvement. In two of seven patients with cardioembolic M1 trunk occlusion, crushed fragments of the embolus obstructed M2 portions after direct PTA, necessitating local thrombolysis. CONCLUSION: Direct PTA may be performed safely as an alternative to thrombolytic therapy in patients with acute occlusion of the middle cerebral artery when early CT findings and/or lenticulostriate artery involvement are present or when superselective local angiography shows the presence of a large embolus or high-grade stenosis.

Acute Disease↗
PubMed1998

[Sudden ventricular tachyarrhythmia immediately following hepatectomy in a patient with hypomagnesemia].

A 57-year-old male without pre- or intraoperative arrhythmia developed ventricular tachyarrhythmia immediately following hepatectomy. Postoperative examination of plasma electrolytes revealed severe hypomagnesemia (0.16 mmol.l-1). The arrhythmia may have been caused by hypomagnesemia and an imbalance between supply and demand of oxygen in the myocardium, due to hypovolemia and severe anemia from massive hemorrhage. We recommend that measurement of plasma magnesium concentration be included in all perioperative laboratory examinations.

Carcinoma, Hepatocellular↗
PubMed1998

[A case of osteolytic metastases from breast cancer effectively treated with pamidronate].

A 55-year-old woman complained of neck pain ten years after the mastectomy. She was diagnosed as multiple bone metastases and received chemoendocrine therapy with 5'-DFUR and tamoxifen. Bone scintigram showed progressive disease, so we attempted biweekly administration of fadrozole and pamidronate (30 mg). After four months, pamidronate administration relieved her neck pain. CT revealed that all lytic lesions of cervical and thoracic vertebra showed sclerosis 11 months after pamidronate infusion. New lytic lesions are not defined, and the sclerosis has continued thus far. Pamidronate therapy is promising as an effective treatment in patients with osteolytic metastasis from breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

[Altered electrocardiogram during general anesthesia in a patient with intermittent Wolff-Parkinson-White conduction].

A delta wave, which had not been detected in the preoperative electrocardiogram (ECG), was observed just before induction of anesthesia in a 53-year-old male scheduled for partial pancreatectomy. His ECG, diagnosed as intermittent Wolff-Parkinson-White (WPW) conduction, varied markedly displaying different wide QRS complexes with a short PR interval, and then returned abruptly to normal during anesthesia. WPW syndrome belongs to the category of pre-excitation syndromes, which is characterized by the accelerated abnormal conduction to the ventricle and paroxysmal tachyarrhythmias caused by an accessory pathway. We should consider the influence of anesthesia-related agents on atrioventricular conduction, and aim at preventing and managing tachyarrhythmias caused by this syndrome.

Anesthesia, General↗
PubMed1997

Effects of vitamin E deficiency and glutathione depletion on stress protein heme oxygenase 1 mRNA expression in rat liver and kidney.

Heme oxygenase 1 (HO-1) is a stress protein and has been suggested to provide defense mechanisms against agents that may induce oxidative injury. Vitamin E (VE) is considered to function as an important cellular antioxidant. Rats were fed a VE-deficient (0E) or a VE-sufficient (10E) diet for 6 weeks and then were intraperitoneally administered buthionine sulfoximine (BSO), a glutathione (GSH)-depleting reagent. Whereas HO-1 mRNA levels were undetectable in untreated 0E and 10E rat livers, BSO administration induced HO-1 mRNA expression in both 0E and 10E rat livers. High levels of HO-1 mRNA expression were observed in particular in BSO-treated 0E rat livers. The time-course of changes in HO-1 mRNA expression in 0E rat liver after BSO administration showed that HO-1 mRNA expression was transiently induced at 2.5 hr after BSO treatment, the earliest time examined. In addition, to determine whether VE deficiency and GSH depletion affect the expression of HO-1 mRNA in other tissues, we also examined the time-course of HO-1 mRNA expression in BSO-treated 0E rat kidney. The expression pattern of HO-1 mRNA in the kidney was very similar to that in the liver, and the peak was also observed at about 2.5 hr after BSO administration. Interestingly, histologic assessment of liver and kidney showed that VE deficiency and GSH depletion induced injury in the kidney, but not in the liver.

Animals↗
PubMed1997

Regulation and immunohistochemical analysis of stress protein heme oxygenase-1 in rat kidney with myoglobinuric acute renal failure.

Intramuscular injection of hypertonic glycerol solution to rats results in acute renal injury. In this model, the proximal tubules are characteristically damaged. After glycerol injection renal glutathione (GSH) levels drastically decreased. On the other hand, stress protein heme oxygenase-1 (HO-1) was induced. When N-acetyl cysteine was administered to rats before 1 h glycerol injection, renal function was obviously improved. In this condition, the renal GSH content were sustained in the normal levels and HO-1 protein levels were decreased compared with those of glycerol-treated rats. Induction of HO-1 was accompanied by reduced renal GSH content. In addition, to investigate whether the location of HO-1 protein induced by glycerol injection is restricted to injured region or not in the kidney, we determined the localization of HO-1 protein using immunohistochemical staining. HO-1 protein was identified in the epithelia of the distal tubules, Henle's loop and collecting ducts, but not in the injured proximal tubules.

Acetylcysteine↗
PubMed1997

Cytoskeletal rearrangements and transcriptional activation of c-fos serum response element by Rho-kinase.

The small GTPase Rho is implicated in cytoskeletal rearrangements including stress fiber and focal adhesion formation and in the transcriptional activation of c-fos serum response element. In vitro, Rho-kinase, which is activated by Rho, phosphorylates not only myosin light chain (MLC) (thereby activating myosin ATPase) but also myosin phosphatase, thus inactivating myosin phosphatase. Rho-kinase is involved in the formation of stress fibers and focal adhesions in fibroblasts. Here we show that the expression of constitutively active Rho-kinase increased the level of MLC phosphorylation. The activity of Rho-kinase was necessary for maintaining the vinculin-containing focal adhesions, whereas organized actin stress fibers were not necessary for this. The microinjection of constitutively active Rho-kinase into fibroblasts induced the formation of focal adhesions to some extent under the conditions where organized actin stress fibers were disrupted. The expression of constitutively active Rho-kinase also stimulated the transcriptional activity of c-fos serum response element. These results suggest that Rho-kinase has distinct roles in divergent pathways downstream of Rho, which include MLC phosphorylation leading to stress fiber formation, focal adhesion formation, and gene expression.

3T3 Cells↗
PubMed1997

Structure and expression pattern of human ALR, a novel gene with strong homology to ALL-1 involved in acute leukemia and to Drosophila trithorax.

The ALL-1 gene is involved in human acute leukemia through chromosome translocations or internal rearrangements. ALL-1 is the human homologue of Drosophila trithorax. The latter is a member of the trithorax group (trx-G) genes which together with the Polycomb group (Pc-G) genes act as positive and negative regulators, respectively, to determine the body structure of Drosophila. We have cloned a novel human gene, ALR, which encodes a gigantic 5262 amino acid long protein containing a SET domain, five PHD fingers, potential zinc fingers, and a very long run of glutamines interrupted by hydrophobic residues, mostly leucine. The SET motif, PDH fingers, zinc fingers and two other regions are most similar to domains of ALL-1 and TRX. The first two motifs are also found in other trx-G and Pc-G proteins. The ALR gene was mapped to chromosome band 12q12-13, adjacent to the VDR gene. This region is involved in duplications and translocations associated with cancer. The analysis of ALR expression showed that its approximately 18 kb long mRNA is expressed, like ALL-1, in most adult tissues, including a variety of hematopoietic cells, with the exception of the liver. Whole mount in situ hybridization to early mouse embryos indicates expression in multiple tissues. Based on similarities in structure and expression pattern, ALR is likely to play a similar role to ALL-1 and trx, although its target genes have yet to be identified.

Age Factors↗
PubMed1997

Nuclear punctate distribution of ALL-1 is conferred by distinct elements at the N terminus of the protein.

The ALL-1 gene positioned at 11q23 is directly involved in human acute leukemia either through a variety of chromosome translocations or by partial tandem duplications. ALL-1 is the human homologue of Drosophila trithorax which plays a critical role in maintaining proper spatial and temporal expression of the Antennapedia-bithorax homeotic genes determining the fruit fly's body pattern. Utilizing specific antibodies, we found that the ALL-1 protein distributes in cultured cells in a nuclear punctate pattern. Several chimeric ALL-1 proteins encoded by products of the chromosome translocations and expressed in transfected cells showed similar speckles. Dissection of the ALL-1 protein identified within its approximately 1,100 N-terminal residues three polypeptides directing nuclear localization and at least two main domains conferring distribution in dots. The latter spanned two short sequences conserved with TRITHORAX. Enforced nuclear expression of other domains of ALL-1, such as the PHD (zinc) fingers and the SET motif, resulted in uniform nonpunctate patterns. This indicates that positioning of the ALL-1 protein in subnuclear structures is mediated via interactions of ALL-1 N-terminal elements. We suggest that the speckles represent protein complexes which contain multiple copies of the ALL-1 protein and are positioned at ALL-1 target sites on the chromatin. Therefore, the role of the N-terminal portion of ALL-1 is to direct the protein to its target genes.

Amino Acid Sequence↗
PubMed1997

The modulation effect of vitamin E on prostaglandin E2 level and ornithine decarboxylase activity at the promotion phase of lung tumorigenesis in mice.

The present study was undertaken to investigate a mechanism of the inhibitory effect of vitamin E in urethane-induced lung tumorigenesis in mice. We assayed ornithine decarboxylase (ODC) activity and the prostaglandin E2 (PGE2) level in lung at 8 weeks after urethane injection (promotion phase). Excessive vitamin E feeding or indomethacin treatment suppressed the urethane-induced increase in ODC activity, while exogenous PGE2 overcame the effect of vitamin E on ODC activity. Furthermore, the amount of PGE, and the level of ODC activity were well correlated. These results indicate that the vitamin E-induced decrease in PGE2 level probably contributes to the inhibition of ODC induction and the prevention of tumor development in the lung.

Animals↗
PubMed1997

Purification and characterisation of cathepsin B mRNA 3'-untranslated-region-binding protein (CBBP), a protein that represses cathepsin B mRNA translation.

We reported that the 3'-untranslated region (3'-UTR) of cathepsin B mRNA of Sarcophaga peregrina (flesh fly) is necessary for the repression of its translation, and detected the 3'-UTR-binding protein in lysates of larval hemocytes in which cathepsin B mRNA translation was repressed [Yano, T., Kurata, S. & Natori, S. (1995) Eur. J. Biochem. 234, 39-43]. In this study, we purified the 3'-UTR-binding protein from an embryonic cell line of Sarcophaga. The purified protein (CBBP) was found to repress cathepsin B mRNA translation in a rabbit reticulocyte lysate. We found that the CBBP contents of the hemocytes did not change during metamorphosis, although the cathepsin B mRNA became translatable only at the pupal stage. Moreover, we found that pupal, but not larval hemocytes, contained a factor that inhibited the binding of CBBP to the 3'-UTR. A regulatory mechanism of cathepsin B expression in Sarcophaga hemocytes is discussed.

Animals↗
PubMed1997

The inhibitory effect of vitamin E on pulmonary polyamine biosynthesis, cell proliferation and carcinogenesis in mice.

We investigated the modulating effect of vitamin E on pulmonary polyamine biosynthesis, cell proliferation and carcinogenesis in mice treated with urethane. Pulmonary ornithine decarboxylase induction and subsequent polyamine accumulation were observed during the initiation and promotion phases of the urethane-induced lung carcinogenesis in mice. The increases of ODC activity and polyamine level during both phases were almost inhibited when a high vitamin E diet was provided. The urethane-increased level of pulmonary proliferating cell nuclear antigen as a marker of cell proliferation during the carcinogenesis was inhibited by vitamin E treatment. Also, vitamin E suppressed the urethane-induced elevation of pulmonary cyclooxygenase activity as a marker of tumor promotion. In conjugation with these events, vitamin E reduced the development of lung tumors in mice treated with urethane. These results indicated that vitamin E could act as a useful chemopreventive agent against lung carcinogenesis in mice due to the regulation of cell proliferation.

Animals↗