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Biomedical subjects

Y Kishimoto

Publications and source records attributed to Y Kishimoto.

At least 73 records · Page 4Linked to original sources
PubMed2000

Combination chemotherapy with risk factor-adjusted dose attenuation for high-risk myelodysplastic syndrome and resulting leukemia in the multicenter study of the Japan Adult Leukemia Study Group (JALSG): results of an interim analysis.

Forty-nine adult patients with high-risk myelodysplastic syndrome (MDS) or acute myeloid leukemia that progressed from MDS were registered for the multicenter study of the Japan Adult Leukemia Study Group. Forty-three patients were evaluable for the analysis. Idarubicin 12 mg/m2 per day for 3 days and continuous cytosine arabinoside 100 mg/m2 per day for 7 days were given as induction therapy, followed by postremission chemotherapy after complete remission (CR). Because elderly patients and those with hypoplastic marrow usually have complications after intensive chemotherapy, often causing early death, the treatment dose was reduced to 60% or 80% according to the presence of 3 risk factors: age 60 years or older, performance status 2 or more, or presence of hypoplastic bone marrow. Of the 43 evaluable patients (median age, 58 years), 26 (60%) achieved CR. Two patients (5%) died within 2 months of completion of induction therapy. The CR rates for patients treated with 100%, 80%, and 60% of the chemotherapy dose were 55% (12 of 22), 63% (10 of 16), and 80% (4 of 5), respectively, indicating that the risk factor-adjusted dose attenuation was appropriately applied to those who might have had problems with the original dose, thus reducing regimen-related mortality rate. The median overall survival of the 43 patients was 8 months.

Acute Disease↗
PubMed2000

[Rapid development of multiple meniscal signs complicating invasive pulmonary aspergillosis in a patient receiving chemotherapy for acute leukemia].

This report describes the rapid development of multiple meniscal signs complicating invasive pulmonary aspergillosis in a 53-year-old man receiving chemotherapy for acute leukemia. While undergoing first induction therapy for AML, he developed chest pain, and multiple bilateral infiltrations were seen in chest roentgenograms. Administration of antibiotics, antifungal agents, steroid pulse therapy and G-CSF was begun. Pulmonary cavities with meniscal signs developed. The next day, pneumothorax and hemothorax were noted. Although drainage and mechanical ventilation were performed, the patient died after massive hemoptysis. Invasive pulmonary aspergillosis was diagnosed at autopsy.

Aspergillosis↗
PubMed1999

Role of the kappa-opioid system in the attenuation of the morphine-induced place preference under chronic pain.

We previously reported that the morphine-induced place preference was attenuated under inflammation produced by the unilateral injection of 2.5 % formalin (50 microl) into the hind paw of rats. In the present study, to elucidate the mechanism of this attenuation, the effects of pretreatment with delta- and kappa-opioid receptor antagonists, naltrindole (NTI) and nor-binaltorphimine (nor-BNI), on the development of the morphine-induced place preference under inflammation were examined in rats. Nor-BNI, but not NTI, eliminated the suppression of the morphine-induced place preference in inflamed groups. These results suggest that endogenous kappa-opioid systems may be activated in the presence of chronic inflammatory nociception; as a result, the development of morphine's rewarding effect may be suppressed under inflammation.

Animals↗
PubMed1999

Disopyramide decreases the fasting serum glucose level in man.

The effect of disopyramide, a class Ia antiarrhythmic drug, on the serum glucose level was evaluated in 6 consecutive in-patients. A 19-hour starvation test was repeated with oral administration of sustained-release disopyramide (150 mg) 0 and 12 hours after starting the test. Serum glucose levels during the starvation test decreased with disopyramide administration from a mean value of 96.5 +/- 1.8 to 85.9 +/- 1.4 mg/dl (24 samples, p < 0.05). The average reduction of the serum glucose level by disopyramide in each patient was 9.7 +/- 2.2 mg/dl. The decrease in the serum glucose level was not related to the serum concentration of disopyramide or serum creatinine levels. The decrease in the serum glucose level was larger in older patients (r = 0.75) and in light patients under 45 kg. These results suggested that disopyramide reduced the fasting serum glucose levels even in normal ranges as a common side effect of the drug, and that not only the occurrence of severe hypoglycemia but also the decrease in glucose levels were influenced by multiple factors including age and body weight.

Age Factors↗
PubMed1999

Crystal structure of beta-amylase from Bacillus cereus var. mycoides at 2.2 A resolution.

The crystal structure of beta-amylase from Bacillus cereus var. mycoides was determined by the multiple isomorphous replacement method. The structure was refined to a final R-factor of 0.186 for 102,807 independent reflections with F/sigma(F) > or = 2.0 at 2.2 A resolution with root-mean-square deviations from ideality in bond lengths, and bond angles of 0.014 A and 3.00 degrees, respectively. The asymmetric unit comprises four molecules exhibiting a dimer-of-dimers structure. The enzyme, however, acts as a monomer in solution. The beta-amylase molecule folds into three domains; the first one is the N-terminal catalytic domain with a (beta/alpha)8 barrel, the second one is the excursion part from the first one, and the third one is the C-terminal domain with two almost anti-parallel beta-sheets. The active site cleft, including two putative catalytic residues (Glu172 and Glu367), is located on the carboxyl side of the central beta-sheet in the (beta/alpha)8 barrel, as in most amylases. The active site structure of the enzyme resembles that of soybean beta-amylase with slight differences. One calcium ion is bound per molecule far from the active site. The C-terminal domain has a fold similar to the raw starch binding domains of cyclodextrin glycosyltransferase and glucoamylase.

Amino Acid Sequence↗
PubMed1999

A phase II study employing combination regimens containing KRN8602 in drug-resistant acute myeloid leukemia and acute lymphoblastic leukemia. KRN8602 Leukemia Study Group.

We conducted a phase II multicenter study in order to evaluate the efficacy and toxicity of two combination regimens containing KRN8602 (MX2) for drug-resistant acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). AML was treated with KRN8602, 15 mg/m2 i.v. push for 5 days, and cytarabine (AraC), 100 mg/m2 by 24 h coutinuous infusion for 7 days. ALL was treated with KRN8602, 15 mg/m2 i.v. push for 5 days, vincristine (VCR), 1.4 mg/m2 i.v. push, once weekly, and prednisolone (PSL), 40 mg/m2, 3 h infusion for 5 days. In AML and ALL, the complete remission (CR) rate was 36.4% (16 of 44) and 24.1% (seven of 29), and the overall response rate (CR+PR) was 52.3% (23 of 44) and 51.7% (15 of 29), respectively. Among the 29 relapsed cases of AML, a higher CR rate, 51.7% (15 of 29), was obtained. A high incidence of nausea/vomiting and anorexia was observed, and some patients experienced central nervous system disorders and peripheral neuropathy. There was a low incidence of severe neurotoxicities; all other toxicities were manageable. KRN8602 was found to overcome drug resistance clinically, confirming results based on the preclinical studies. We conclude that KRN8602 is an effective novel anthracycline for drug-resistant acute leukemias.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

Ion explosion and multi-mega-electron-volt ion generation from an underdense plasma layer irradiated by a relativistically intense short-pulse laser.

Ion acceleration and expansion in the interaction of a relativistically intense short-pulse laser with an underdense plasma layer are investigated. Ion and electron dynamics are studied by a two-dimensional particle-in-cell simulation with the real mass ratio. It is shown that the longitudinal electric field induced by electron evacuation due to a large ponderomotive force or light pressure can accelerate ions to several MeV in the direction of the laser propagation. It is after the laser completely passes through the plasma layer that the ion explosion starts to be significant.

Journal Article↗
PubMed1999

Bmp activity establishes a gradient of positional information throughout the entire neural plate.

Bone morphogenetic proteins (Bmps) are key regulators of dorsoventral (DV) patterning. Within the ectoderm, Bmp activity has been shown to inhibit neural development, promote epidermal differentiation and influence the specification of dorsal neurons and neural crest. In this study, we examine the patterning of neural tissue in mutant zebrafish embryos with compromised Bmp signalling activity. We find that although Bmp activity does not influence anteroposterior (AP) patterning, it does affect DV patterning at all AP levels of the neural plate. Thus, we show that Bmp activity is required for specification of cell fates around the margin of the entire neural plate, including forebrain regions that do not form neural crest. Surprisingly, we find that Bmp activity is also required for patterning neurons at all DV levels of the CNS. In swirl/bmp2b(-) (swr(-)) embryos, laterally positioned sensory neurons are absent whereas more medial interneuron populations are hugely expanded. However, in somitabun(-) (sbn(-)) embryos, which probably retain higher residual Bmp activity, it is the sensory neurons and not the interneurons that are expanded. Conversely, in severely Bmp depleted embryos, both interneurons and sensory neurons are absent and it is the most medial neurons that are expanded. These results are consistent with there being a gradient of Bmp-dependent positional information extending throughout the entire neural and non-neural ectoderm.

Animals↗
PubMed1999

The FLS mouse: a new inbred strain with spontaneous fatty liver.

BACKGROUND AND PURPOSE: A new strain of mouse, named FLS (fatty liver Shionogi), which develops spontaneous fatty liver without obesity, was established by inbreeding. Morphologic, physiologic, and genetic characterization of the strain was done. METHODS: Characteristics of male FLS mice were compared with those of the sister strain, dd Shionogi (DS), which does not develop spontaneous fatty liver. A genetic cross experiment was performed by mating FLS with C3H/He/Shi mice. RESULTS: The hepatocytes of neonatal FLS mice contained fine lipid droplets throughout the lobules, and large lipid droplets appeared as mice aged. Liver triglyceride concentrations of FLS mice were fivefold higher than those of DS mice, but serum lipid concentrations and the lipoprotein profile did not indicate abnormalities. Higher plasma aspartate transaminase and alanine transaminase activities in FLS, compared with DS mice, suggested hepatocellular lesions. The genetic cross experiment suggested that the fatty liver formation is a complex polygenic trait. CONCLUSION: The FLS mice develop a progressive hepatic steatosis without obesity and diabetes. The FLS mouse might be a good model for investigating hepatic disorders accompanied by fatty liver unrelated to alcoholism or obesity.

Adipose Tissue↗
PubMed1999

Effects of itopride hydrochloride on the delayed rectifier K+ and L-type CA2+ currents in guinea-pig ventricular myocytes.

The effects of itopride hydrochloride, a new drug used to regulate motility in the gastrointestinal tract, on the delayed rectifier K+ current (I(K)) and the L-type Ca2+ current (I(Ca)) were evaluated in guinea-pig ventricular myocytes at concentrations of 1, 10 and 100 microM to determine whether the drug has a proarrhythmic effect through blockade of I(K). Itopride did not affect I(K) at concentrations of 100 microM or less, and no significant effects of 1, 10 or 100 microM itopride were observed on the inward rectifier K+ current (I(K1)) responsible for the resting potential and final repolarization phase of the action potential. We next investigated the effects of itopride on L-type Ca2+ current (I(Ca)). Significant inhibition of I(Ca) was observed at itopride concentrations greater than 10 microM. These results suggested that itopride hydrochloride has an inhibitory effect on I(Ca) at concentrations much higher than those in clinical use.

Action Potentials↗
PubMed1998

Levels of cyclooxygenase-1 and -2 mRNA expression at various stages of acute gastric injury induced by ischemia-reperfusion in rats.

Recently, the state of cyclooxygenase (COX) mRNA expression has been reported in an acetic acid-induced chronic gastric ulcer model of mice. However, the time course of COX expression during the developmental stage and the subsequent repair process of acute gastric injury is not well understood at present. In this study, we quantitatively investigated the time course of the level of COX-2 and -1 mRNA expression from the developmental stage through the healing stage in ischemia-reperfusion (I-R)-induced acute gastric damage. COX-2 mRNA was expressed at low or undetectable levels in the normal gastric tissues of control rats. The COX-2 expression between 6 and 48 h following I-R was higher than that of the control gastric tissues; the histological findings were erosion during 1-36 h and transitional appearance from erosion to ulcer at 48 h. The maximum expression of COX-2 mRNA was recorded at 24 h (approximately 200-fold elevation). The COX-2 message was very low or undetectable at 72 h (ulcer stage) and at 96 and 120 h (healing stage of ulcer) after I-R. The level of COX-1 mRNA remained stable through all stages of acute gastric damage. These results are potentially useful for understanding the role of COX and evaluating the effects of drugs on expression of COX at various stages of acute gastric injury.

Animals↗
PubMed1998

Cloning, expression and map assignment of chicken prosaposin.

Prosaposin is the precursor of four small glycoproteins, saposins A-D, that activate lysosomal sphingolipid hydrolysis. A full-length cDNA encoding prosaposin from chicken brain was isolated by PCR. The deduced amino acid sequence predicted that, similarly to human and other mammalian species studied, chicken prosaposin contains 518 residues, including four domains that correspond to saposins A-D. There was 59% identity and 76% similarity of human and chicken prosaposin amino acid sequences. The basic three-dimensional structures of these saposins is predicted to be similar on the basis of the conservation of six cysteine residues and an N-glycosylation site. Identity of amino acid sequences was higher among saposins A, B and D than in saposin C. The predicted amino acid sequence of saposin B matched exactly that of purified chicken saposin B protein. The chicken prosaposin gene was mapped to a single locus, PSAP, in chicken linkage group E11C10 and is closely linked to the ACTA2 locus. This confirms the homology between chicken and human prosaposins and defines a new conserved segment with human chromosome 10q21-q24.

Actins↗
PubMed1998

Cloning and genetic mapping of zebrafish BMP-2.

The BMP family of polypeptide growth factors has been shown to play diverse roles in establishing embryonic patterning and tissue fates. We report the cloning of the zebrafish homologue of BMP-2, examine its expression during embryogenesis, and find that it is localized to the distal end of the long arm of zebrafish chromosome 20. A missense mutation of the bmp2 gene has recently been shown to be responsible for the early dorsalized phenotype of the zebrafish swirl mutant [Kishimoto et al., 1997]. Given the dynamic expression of bmp2 in the developing embryo and the complex interactions of BMP signaling response in vertebrates, it is possible that other mutant phenotypes, due to altered bmp2 gene expression, will eventually map to or interact with this genetic locus.

Amino Acid Sequence↗
PubMed1998

Changes of immunological markers after autologous peripheral blood stem cell transplantation.

PURPOSE: Recently high-dose chemotherapy with peripheral blood stem cell transplantation (PBSCT) has become an important treatment for hematological and solid tumors. METHODS: Immunological parameters were examined before and after PBSCT in 9 patients with lung cancer and 13 patients with malignant lymphoma. Findings were compared with those for bone marrow transplantation (BMT). Peripheral blood cells were analyzed for phenotype and the levels of cytokines and soluble factors were measured. RESULTS: After PBSCT, activated T cells (CD3+HLA-DR+ cells, CD8+HLA-DR+ cells) and suppressor/cytotoxic T cells (CD8+CD11b- cells) were significantly higher in the patients with lung cancer than in those with malignant lymphoma. Serum levels of interleukin-4 and soluble interleukin-2 receptor were also significantly higher in the patients with lung cancer than in those with lymphoma. On the other hand, the serum levels of interferon gamma, tumor necrosis factor alpha, interleukin-6, soluble human leukocyte antigen class 1, and soluble thrombomodulin were significantly increased after bone marrow transplantation. The transfused peripheral stem cells of lung cancer and lymphoma patients had a similar number of granulocyte/macrophage-colony-forming units, but lung cancer patients had significantly more CD34-positive cells. CONCLUSION: By reinfusing large numbers of autologous immune cells, PBSCT may accelerate immune reconstitution, with T cells being likely to have a marked therapeutic potential. The changes after PBSCT were greater in patients with lung cancer than in lymphoma patients. These blood cells are potent mediators of anticancer activity and could play an important role in the elimination of autologous malignant cells.

Adult↗
PubMed1998

The role of endogenous acid in the development of acute gastric ulcer induced by ischemia-reperfusion in the rat.

We investigated the role of endogenous gastric acid in the development of gastric ulcer from erosion induced by ischemia-reperfusion of the celiac artery in the rat. A half-hour clamping of the celiac artery (ischemia) caused acute gastric erosions 1 hour after reperfusion and such acute injuries progressed to ulcers 48-72 hours after reperfusion without any necrotizing agents. Gastric acid secretion decreased immediately after ischemia and didn't recover until 12 hours after reperfusion. Intraperitoneal administrations of cimetidine (100 mg/kg, every 12 hours) or omeprazole (30 mg/kg, every 24 hours) were started at 1, 6, or 12 hours after reperfusion. When administrations were started 1 hour after reperfusion, both drugs significantly decreased the total damaged area and prevented the progression of gastric erosions to ulcers. However, administrations started 6 or 12 hours after reperfusion failed to inhibit the total damaged area and to prevent ulcer formation. These results suggest that endogenous gastric acid may play an important role in the progression of gastric erosions to ulcers although ischemia itself reduces acid secretion. Furthermore, treatment with anti-acid-secretory drugs in the early stage of mucosal damage may be important for the prevention of ulcer.

Acute Disease↗
PubMed1998

DNA analysis at p53 locus in carcinomas arising from pleomorphic adenomas of salivary glands: comparison of molecular study and p53 immunostaining.

Where and how frequently p53 abnormalities are involved in the development of pleomorphic adenoma (PA) and its malignant progression to carcinoma was investigated. The presence of p53 gene abnormalities was analyzed in eight patients with carcinoma in pleomorphic adenoma (CPA) by polymerase chain reaction (PCR)-based assays and immunohistochemistry. Normal salivary gland tissue, adenomatous, transitional and carcinomatous areas were microdissected from archival microslides and analyzed for allelic deletions of the p53 gene using two microsatellite markers at the p53 locus; dinucleotide (CA)n repeat and pentanucleotide (AAAAT)n repeat. Loss of heterozygosity (LOH) of the p53 gene was detected in 57% of adenomas, 86% of transitional lesions and 86% of carcinomas. In contrast, overexpression of p53 oncoprotein was noted immunohistochemically in 13% of adenomas, 50% of transitional areas and 75% of carcinomas. All of the tumors with immunoreactivity for p53 oncoprotein demonstrated LOH. Moreover, when LOH was present in adenomatous or transitional areas, the identical LOH was always detected in the corresponding carcinomatous areas in the same CPA tumors. These findings indicate that p53 gene mutation is an early event and occurs frequently at an early stage of precancerous lesions and may be responsible for most cases of malignant transformation of PA.

Adenoma, Pleomorphic↗
PubMed1998

DNA analysis at p53 locus in adenoid cystic carcinoma: comparison of molecular study and p53 immunostaining.

Abnormalities of the p53 tumor suppressor gene were investigated in 22 foci from 14 adenoid cystic carcinomas (ACC) by polymerase chain reaction (PCR)-based assays for dinucleotide (CA)n and pentanucleotide (AAAAT)n repeat polymorphisms and by immunohistochemical staining for oncoprotein expression. Adenoid cystic carcinomas were divided into lower grade (tubular and cribriform) subtypes and higher grade (trabecular and solid) subtypes. Histologically identified tumor cells were precisely microdissected from archival microslides and were used for molecular analysis. The overall frequency of p53 gene mutations detected by PCR-loss-of-heterozygosity (LOH) analysis was 57% and was higher than the frequency of over-expression of p53 oncoprotein detected by immunostaining (43%). In the molecular analysis of individual histological subtype foci, the number of foci with p53 gene mutation was significantly greater in the higher grade subtype foci than in the lower grade subtype foci and was greatest in solid-type foci (100%). In all six tumors in which histologically different foci were present in the same tumors, mutations of the p53 gene were detected. When tumor heterogeneity of the p53 gene was present among different histological foci in the same tumors, the mutations were always detected in the higher grade foci. When lower and higher grade foci were present in the same tumors, the identical mutations detected in the lower grade foci were present in the corresponding higher grade foci. These findings indicate that abnormalities of the p53 gene are involved in carcinogenesis and/or progression of this tumor and, furthermore, suggest that molecular analyses of ACC may provide information of prognostic importance.

Carcinoma, Adenoid Cystic↗