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Biomedical subjects

T Yamazaki

Publications and source records attributed to T Yamazaki.

At least 343 records · Page 19Linked to original sources
PubMed1997

Effect of hypothermia on the merocyanine 540-mediated purging of hematopoietic cells.

Merocyanine 540 (MC540)-mediated photodynamic therapy (PDT) inactivates experimental leukemia, lymphoma, and neuroblastoma cells by a singlet oxygen-mediated mechanism but is relatively well tolerated by normal pluripotent hematopoietic stem cells and granulocyte/macrophage progenitors (CFU-GM). MC540 is currently undergoing phase I clinical testing for the extracorporeal purging of autologous bone marrow and peripheral blood stem cells. We report here that performing MC540-mediated PDT at 4.7 degrees C (hypothermia) instead of at ambient temperature enhanced the photoinactivation of L1210 cells and CFU-GM but left the photoinactivation of K562 cells unchanged. Hypothermia reduced dye binding in K562 but not in L1210 cells, whereas the photogeneration of lipid hydroperoxides (LOOH) was affected in neither cell line. Post-PDT incubation at 4 degrees C delayed the decay of LOOH and enhanced the photoinactivation of CFU-GM as well as L1210 and K562 cells. Taken together, these results suggest that hypothermia interfered with the repair of potentially lethal photodynamic damage. They stress the importance of temperature control during and immediately after the photochemical purging of autologous bone marrow and peripheral blood stem cells.

Animals↗
PubMed1997

Therapeutic effects of cefozopran against experimental mixed urinary tract infection with Enterococcus faecalis and Pseudomonas aeruginosa in mice.

The therapeutic activity of cefozopran, a new semisynthetic parenteral cephalosporin, was compared with those of ceftazidime, ampicillin, imipenem/cilastatin and ofloxacin against an ascending mixed urinary tract infection induced in mice with Enterococcus faecalis TN2005 and Pseudomonas aeruginosa P9. Cefozopran significantly reduced viable cell counts of both organisms in the kidneys. Ceftazidime, imipenem/cilastatin and ofloxacin were active against only P. aeruginosa, and ampicillin was active against only E. faecalis.

Ampicillin↗
PubMed1997

Molecular cloning, genomic organization, promoter activity, and tissue-specific expression of the mouse ryudocan gene.

Ryudocan, a ubiquitous heparan sulfate proteoglycan, is a member of the syndecan family of cell surface proteoglycans. The full-length cDNA encoding the murine ryudocan core protein has now been cloned and sequenced. The deduced primary structure of mouse ryudocan, including the three glycosaminoglycan attachment sites in the extracellular domain as well as the transmembrane and cytoplasmic regions, is highly similar to those of the rat, human, and chicken proteins. Northern analysis detected a 2.7-kb transcript in all mouse tissues examined, with the highest concentrations apparent in liver, kidney, and lung. The mouse ryudocan gene was shown to span approximately 19.7 kb of genomic DNA and to contain five exons, with an intron-exon organization identical to that of the human gene. The promoter region of the mouse gene contains various cis-acting elements, including a TATA-like box and a GC box as well as potential binding sites for the transcription factors NF-IL6, MyoD, GATA, C/EBP, AP-2, NF-kappaB, AP-1, and Sp1. Transient transfection experiments with a construct containing the 690 bp upstream of the transcription start site fused to a luciferase reporter gene showed functional promoter activity. Deletion analysis suggested that the proximal promoter region including the TATA-like box, the GC box, and other Sp1 binding sites was required for full transcriptional activity. These findings will be useful for the study of ryudocan gene regulation and the generation of mice with targeted disruption of the gene.

Amino Acid Sequence↗
PubMed1997

Structure and function in Escherichia coli of plasmids containing pyrimidine/purine-biased stretch originated from the 5'-flanking region of the basidiomycete ras gene.

The Basidiomycete ras gene possesses a pyrimidine-rich stretch (CT-motif) with a short (7 bases) mirror repeat in which its major transcription start point is contained. To analyze the tertiary structure induced by the CT/AG-biased sequence and its effect on gene expression in supercoiled plasmids in Escherichia coli, the DNA fragment containing the ras CT/AG sequence was inserted into the EcoRI site on pBR322 in both orientations and the resulting pBR322 derivatives, named pBR-CT[ras] and pBR-invCT[ras] were introduced into E. coli strains DM800 (deltatopA gyrB225) and JM109 (topA+ gyrA96). In pBR-CT [ras] the pyrimidine-rich sequence is on the pBR322 tetracycline-resistance gene (tet)coding strand and in pBR-invCT[ras] the complementary purine-rich sequence is on this strand. DNAs of pBR-CT[ras] and pBR-invCT[ras] isolated from DM800 were frequently cleaved with single-strand-specific S1 nuclease within the CT/AG sequence, showing the formation of extended open structure. Compared with those carrying pBR322, DM800 and JM109 carrying pBR-CT [ras] showed much higher levels of tetracycline resistance (Tcr), while both strains carrying pBR-invCT[ras] showed clearly lower levels of Tcr. pBR-CT [ras] and pBR-invCT [ras], however, conferred reduced activity of beta-lactamase on DM800 and JM109. pBR-CT [ras] derivatives lacking the counterpart of the mirror repeat did not form the S1-cleavable open structure within the CT/AG sequence and conferred pBR322-like Tcr and beta-lactamase activity. The tertiary structure formed in the CT/AG sequence via the mirror repeat was suggested to affect the expressions of pBR322-tet and -bla genes.

Base Sequence↗
PubMed1997

Molecular evolution of the Amy multigenes in the subgenus Sophophora of Drosophila.

Molecular evolution of the Amy multigenes in Drosophila was investigated using PCR amplification. Twenty-five partial Amy sequences from 13 species belonging mainly to the subgenus Sophophora were determine, and a molecular phylogeny of the Amy genes in Drosophila was constructed, together with published Amy sequences. Clustering of species are mostly consistent with the traditional classification and that inferred from other genes. From sequence divergence between PCR products, several species, including D. elegans and D. fuyamai, were suggested to have multiple copies of the Amy genes. The loss of an intron took place at least three times after the Sophophora radiation. In order to investigate the mechanism of sequence evolution, the numbers of amino acid replacement and synonymous substitutions in five lineages were estimated. The heterogeneity in the relative numbers of synonymous and replacement substitutions among the lineages was found. Possible roles of selection in the sequence evolution of the Amy gene are discussed.

Animals↗
PubMed1997

Amyloid beta-protein (A beta) accumulation in the leptomeninges during aging and in Alzheimer disease.

The results of well-characterized two-site enzyme immunoassays showed that the crude leptomeninges (consisting of the pia matter, arachnoid matter, and leptomeningeal vessels [LV]) from aged control brains and brains affected by Alzheimer disease (AD) contain very high levels of amyloid beta-protein (A beta). To learn about the source of A beta, we carefully dissected out both leptomeninges (LM) and LV under a dissecting microscope and determined the levels of soluble A beta in each. The purity of these dissected tissues was confirmed by the absence or presence of alpha-smooth muscle actin representing LV by Western blotting. Surprisingly, the amounts of A beta in each dissected sample were nearly equivalent on a weight basis. In each compartment from aged controls the level of A beta 1-42 was comparable to that of A beta 1-40, while in AD brain A beta 1-40 was a predominant species in both LM and LV. In some cases careful immunocytochemical examination revealed the presence of A beta deposits that were immunolabeled by several A beta monoclonal antibodies in leptomeningeal layers (most often in the arachnoid matter). The extent of A beta deposition in LM appeared to be much less than that explained by the soluble A beta levels, suggesting that immunocytochemically undetectable A beta can accumulate in LM. These observations indicate that leptomeninges are a large reservoir of A beta in normal aged individuals and in AD patients.

Adult↗
PubMed1997

Mixed osteoclastic/pleomorphic-type giant cell tumor of the pancreas with ductal adenocarcinoma: histochemical and immunohistochemical study with review of the literature.

We described a rare form of giant cell tumor of the pancreas composed of mixed osteoclastic/pleomorphic-type giant cell tumor with ductal adenocarcinoma. Immunohistochemical study showed positive staining of cytokeratin and epithelial membrane antigen for pleomorphic-type giant cells and ductal adenocarcinoma but negative for osteoclastic-type giant cells. Vimentin stained positive in both types of giant cells but negative in adenocarcinoma. Osteoclastic-type giant cells were strongly positive for CD68 and tartarate-resistant acid phosphatase was present in these cells, suggesting the osteoclast-like character. CD68 was negative for both pleomorphic-type giant cells and ductal adenocarcinoma. From these findings, we consider that this tumor might be a carcinosarcoma-like neoplasm consisting of both an epithelial and a histiocytic-mesenchymal component.

Aged↗
PubMed1997

Pharmacological studies on Puerariae flos III: protective effects of kakkalide on ethanol-induced lethality and acute hepatic injury in mice.

Kakkalide, one of the major isoflavonoid components of Puerariae flos, has been investigated for its effect on ethanol-induced intoxication and on hepatic injury, including hyperglycaemia, in mice. Kakkalide reduced mortality associated with administration of ethanol. At doses of 100 and 200 mg kg-1 the effect of kakkalide was significant. The same dose of kakkalide prevented increased serum glutamic oxaloacetic transaminase and glutamic pyruvic transaminase activity. At a dose of 200 mg kg-1 it also counteracted ethanol-induced elevation of glucose levels. These results suggest that kakkalide might be useful for counteracting the effects of alcohol and might be effective for treating hepatic injury.

Acute Disease↗
PubMed1997

[Clinical features of Japanese children infected with Cryptosporidium parvum during a massive outbreak caused by contaminated water supply].

A massive outbreak of cryptosporidiosis occurred at a local town of Saitama Prefecture, in 1996. During this outbreak, we investigated the clinical features of children seen at Saitama Medical School. Cryptosporidium parvum (C. parvum) was detected from 10 out of 28 (36%) children with diarrhea during June and August, 1996. The average ages of the children who were positive and negative for C. parvum were 6.5 and 5 year old, respectively. Among the children infected with C. parvum, colic pain was observed in 3 children and 4 children had vomiting. However, none of the children showed fever over 38.0 degrees C nor bloody stools. Family members of children infected with C. parvum also had diarrhea and/or vomiting (5/6). C. parvum was repeatedly detected from 2 out of 3 children. All infected children had an improvement of abdominal symptoms in 4 to 10 days. C. parvum should be included as a pathogen which causes enterocolitis in Japanese children.

Adolescent↗
PubMed1997

A new, concise dialysis approach to assessment of cardiac sympathetic nerve terminal abnormalities.

We applied a dialysis technique to the hearts of anesthetized cats and examined whether the concentration of dialysate norepinephrine (NE) reflected NE disposition at the cardiac sympathetic nerve terminals. Dialysis probes were implanted in the left ventricular wall, and dialysate NE concentrations were measured as an index of myocardial interstitial NE levels. Stimulation of stellate ganglia significantly increased dialysate NE responses that were suppressed by local administration of an NE-releasing inhibitor (omega-conotoxin GVIA, 10 microM). Increments in basal dialysate NE levels were correlated with concentrations of a locally administered neuronal uptake blocker (desipramine; 1, 10, and 100 microM). Desipramine (100 microM) augmented stimulation-induced dialysate NE responses. Local administration of a neuronal vesicle uptake blocker (reserpine, 1 and 10 microM) did not alter dialysate NE levels but increased dialysate dihydroxyphenylglycol levels. An NE-releasing amine (tyramine, 100 microg/ml) was locally administered to examine NE storage capacity at the nerve terminal. The tyramine-induced NE-releasing response was completely abolished by pretreatment with reserpine (1 mg/kg i.p.). Thus cardiac dialysis with local administration of a pharmacological tool offers a new, concise approach to assessment of neuronal NE release, uptake, vesicle uptake, and storage capacity by cardiac sympathetic nerve terminals.

Animals↗
PubMed1997

Interstitial norepinephrine level by cardiac microdialysis correlates with ventricular contractility.

Although a cardiac microdialysis technique has made it possible to estimate myocardial interstitial norepinephrine (NE) levels, whether such levels reflect the local NE concentration that would regulate ventricular contractility remains unknown. If such levels indicate locally regulating NE concentration, then ventricular contractility should be a unique function of the interstitial NE level regardless of how the latter is altered. To examine this hypothesis, we altered the interstitial NE level endogenously by stimulating the cardiac sympathetic nerves at 1 and 2 Hz while monitoring ventricular contractility. We also altered the interstitial NE level exogenously by means of intravenous NE infusions at 10 and 40 micrograms.kg-1.h-1. The basal NE levels did not differ between the stimulation and the infusion experiments (42.9 +/- 11.2 vs. 40.1 +/- 6.2 pg/ml, means +/- SE). The slopes of regression lines relating ventricular contractility and interstitial NE level were also not different between the two experiments [1.13 +/- 0.20 vs. 1.17 +/- 0.20%/(pg/ml), means +/- SE]. We conclude that the interstitial NE level estimated by cardiac microdialysis reflects the local NE concentration regulating ventricular contractility.

Animals↗
PubMed1997

Leminoprazole protects cultured gastric mucosal cells against damage caused by ethanol, indometacin and taurocholate.

We examined whether or not leminoprazole (an acid pump inhibitor) protects cultured rabbit gastric mucosal cells against various forms of cell damage. Exposure of mucosal cells to ethanol, indometacin or taurocholate for 1 h caused a reduction in their viability. Pretreatment of the cells with leminoprazole for 2 h concentration-dependently and significantly prevented the viability loss induced by each noxious agent, although the drug alone did not affect cell viability. Cytoprotection by leminoprazole was expressed after a 2-hour lag period. The effects of leminoprazole were potently inhibited by cycloheximide and actinomycin D. These results indicate that leminoprazole directly acts on gastric mucosal cells, making the cells resistant to damage, and that its cytoprotection might be mediated through de novo synthesized proteins.

Animals↗
PubMed1997

Angiotensin II stimulates c-Jun NH2-terminal kinase in cultured cardiac myocytes of neonatal rats.

Many lines of evidence have suggested that angiotensin II (Ang II)plays an important role in cardiac hypertrophy. Ang II not only increases protein synthesis but also induces the reprogramming of gene expression in cultured cardiac myocytes. In the present study, to elucidate the mechanism by which Ang II regulates gene expression in cardiac myocytes, we examined whether Ang II activates c-Jun NH2-terminal kinase (JNK), which is a member of the mitogen-activated protein kinase family and activates the transcription factor, activator protein-1 (AP-1). The activity of JNK increased 5 minutes after the addition of Ang II, peaked at 20 minutes, and gradually decreased thereafter. Examination of the Ang II dose-response relation revealed detectable JNK activation at 10(-9) mol/L and maximal activation at 10(-6) mol/L. Ang II activated JNK through the AT1 receptor, and the activation was attenuated by the downregulation of protein kinase C or the chelation of intracellular Ca2+. Although the addition of either Ca2+ ionophore or phorbol ester resulted in little or no activation of JNK, simultaneous addition of both Ca2+ ionophore and phorbol ester markedly activated JNK. Slight expressions of the c-jun gene were observed in unstimulated cardiac myocytes, and Ang II increased expressions of the c-jun gene as well as the c-fos gene. Ang II increased transcription of the endothelin-1 gene through the AP-1 binding site. In conclusion, Ang II may activate JNK in cultured cardiac myocytes through an increase in intracellular Ca2+ and activation of protein kinase C, and the activated JNK may regulate gene expression by activating AP-1 during Ang II-induced cardiac hypertrophy.

Angiotensin II↗
PubMed1997

Percutaneous transluminal coronary angioplasty for morphologic left anterior descending artery lesion in a patient with dextrocardia. A case report and literature review.

A case report of percutaneous transluminal coronary angioplasty (PTCA) to treat coronary atherosclerotic lesions in a patient with dextrocardia associated with situs inversus totalis is presented. The patient was a sixty-two-year-old man who was admitted with a diagnosis of congestive heart failure. Cardiac catheterization was performed. Left ventriculography showed mild hypokinesis in segments 2 and 3 with ejection fraction of 63%. Coronary arteriography revealed 74% stenosis in segment 7 of the left anterior descending (LAD) artery. PTCA for this lesion was performed. Successful dilation was achieved with the residual stenosis in the LAD reduced from 74% to 34%. Performance of PTCA in patients with dextrocardia is extremely rare, and only 8 cases have been reported to date. However, by visualizing the procedure as a mirror image and choosing a guide catheter that permits good engagement, it appears possible to perform it like ordinary PTCA.

Angioplasty, Balloon, Coronary↗
PubMed1997

Genetic variation in the expression of the six hsp genes in the presence of heat shock in Drosophila melanogaster.

Genetic variation in total mRNA level of the six hsp genes (hsp22, hsp23, hsp26, hsp27, hsp70 and hsp82) in the presence of heat shock was investigated by using seventy-four second- and seventy third-chromosome lines of Drosophila melanogaster which have the same genetic background derived from a highly inbred stock. There was significant variation in all the six hsp genes for both the second- and third-chromosome lines except for the hsp22 gene of the third-chromosome lines. Although all the structural genes of the heat shock proteins are localized on the third chromosome, the estimates of genetic variance for the second-chromosome lines were larger than those for the third-chromosome lines. Highly significant correlations between total mRNA level of the different hsp genes in all the combinations of the six hsp genes using the second-chromosome lines were found, but some of correlations for the third-chromosome lines were not significant. These results suggest that some second chromosome variants have similar effects on the expression of the different genes.

Animals↗
PubMed1997

Two distinct novel splice site mutations in a compound heterozygous patient with protein S deficiency.

Genetic analysis revealed two distinct novel splice site mutations in a compound heterozygous patient with protein S deficiency. The paternal mutation was a G-to-T transition at position-1 of the acceptor splice site of intron N (Mutation I), and the maternal mutation was a G-to-C transversion at position-1 of the donor splice site of intron C (Mutation II). Both splice site mutations decreased the mutated mRNA accumulation to the same extent, approximately 40% of the normal mRNA. However, the mutations were associated with different phenotypical expressions: the paternal mutant protein S was not detected in vivo, while the maternal mutant protein S was present in the plasma in reduced quantity. Because Mutation I caused a cryptic splicing in the mutated mRNA, resulting in a reading frameshift and premature termination, the predicted mutant protein S might be highly unstable. In contrast. Mutation II led to the substitution of Va146 by Leu, which might be much less deleterious for the synthesis, secretion and stability of the predicted mutant protein S. It was supposed that the different post-translational metabolisms produced the distinct phenotypical expressions of the mutations.

Adult↗
PubMed1997

[Quality of life and chemotherapy in terminal stage of gastrointestinal cancers].

A patient in the terminal stage of gastrointestinal cancer is continuously worried by physical and psychological suffering, and asks for treatment to alleviate pain. We have conducted an assessment of the quality of life (QOL) in the terminal stage of cancer, and found a deterioration in active factor and total score of QOL 3 months before death. We have provided active chemotherapy in the terminal stage with the informed consent of the patient. The therapy has aimed at relieving suffering, prolonging survival and maintaining QOL.

Aged↗