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Biomedical subjects

Y Yoshida

Publications and source records attributed to Y Yoshida.

At least 505 records · Page 28Linked to original sources
PubMed1997

Experimental approaches for the treatment of murine B16 melanomas of various sizes. II: Injection of ethanol with combinations of beta-interferon and microwaval hyperthermia for B16 melanomas with a size of greater than 10 mm in diameter.

Although ethanol injection in combination with microwaval hyperthermia and systemic administration of interleukin-2 was found to be very effective in suppressing the growth of B16 melanoma nodules with a size of less than 7 mm in diameter in our previous experiments, the growth of B16 melanomas with a size of greater than 10 mm in diameter was very difficult to control with any of the therapeutic modalities examined. In subsequent experiments, we investigated whether ethanol injection (150 microliters/injection) in combination with local injection of beta-interferon (2 x 10(4) IU/injection) and local microwaval hyperthermia at 43 degrees C for 15 min was able to suppress the growth of melanoma nodules and to prolong survival times of melanoma-burdened mice. The results were that we successfully suppressed the growth of melanoma nodules of that size for the first time with combinations of the therapeutic modalities described above. Infiltration of immunocompetent cells such as T lymphocytes and NK cells was clearly observed in the melanoma tissues treated with the therapeutic combination. These experimental results should be applied to the treatment of human melanomas in advanced stages which have no indications for surgical operation.

Animals↗
PubMed1997

Occurrence of high ratio of males after introduction of minocycline in a colony of Leptotrombidium fletcheri infected with Orientia tsutsugamushi.

In colonies of Leptotrombidium fletcheri mites infected with Orientia tsutsugamushi (Ot), the agent of scrub typhus, males rarely appear. In the present study, the development of a high ratio of males was observed after introduction of minocycline (MC). A high dose of MC was injected subcutaneously into a mouse, and by feeding unfed larvae from an infected mite colony on this mouse, the Ot in the mites were successfully killed. Of a total of 130 unfed larvae attached to the mouse, 29 developed into females; of these, 9 laid an average of 112.4 eggs/female. Unfed larvae in the succeeding generations were attached to untreated mice. All adults in the P and F1 generation were females, and males started to appear at the F2 generation. The ratio of males to females was 332:7, 108:13, 263:61 and 71:9 at the F2, F3, F4 and F5 generations, respectively. These data suggest that Ot in the ovary or gonad may suppress the development of males.

Animals↗
PubMed1997

Dental application of polyfunctional urethane comonomers to composite resin veneering materials.

Urethane monomer/diluent monomer mixtures were used in dental composite resin veneering materials filled with various ratios of powder (filler)/liquid (comonomer), P/L. Hardness values of unfilled resins containing benzoyl peroxide only (BP0; 0.5 wt%), and filled resins (included trimethylol propane trimethacrylate (TMPT) composite filler) were tested. Significant increases in hardness were obtained with the use of TMPT composite filler in the resins. Also, their modulus values measured by bend test showed an increasing trend, compared to a commercial composite resin veneering material (a control sample; CONT) with a lower filler content (50 wt%). The DME-DPMDC/HPDM comonomer (dimethacryloxyethyl diphenylmethane-4,4'-dicarbamate/hydroxypropyl dimethacrylate), which showed a smaller fraction of surface porosity, gave greater mechanical strength values at P/L ratios of 0.55 (17.8 wt% filler content) to 1.20 (27.3 wt%) than a CONT resin. The coefficient of thermal expansion was smaller in urethane-based filling materials than a CONT resin. Also, greater activation energy of thermal decomposition was observed in the resin samples with P/L ratio 0.75 to 1.20 than in a CONT resin. Thermally-induced decomposition occurred with smaller weight loss in the experimental filled resins than in a CONT resin.

Journal Article↗
PubMed1997

Blood pressure, insulin, and haematocrit values in Japanese subjects over 60 years of age.

Many studies have suggested an association between blood pressure (BP) and both insulinaemia and haematocrit values in Western populations. However, relatively few data regarding such associations for the Japanese population are available. We investigated the relationship between BP and various parameters, including insulin and haematocrit, in 269 healthy Japanese individuals (113 men and 156 women) over 60 years of age. The data were analysed by stepwise multiple regression analysis. In men, the most important determinant of systolic BP (SBP) and diastolic BP (DBP) was the plasma insulin concentration (beta = 0.32, F = 12.4, P < 0.001 and beta = 0.32, F = 13, P < 0.001, respectively), and haematocrit was found to be associated with DBP (beta = 0.21, F = 5.3, P < 0.05). In women, fasting insulins were unrelated to BP, but fasting plasma glucose and triglyceride concentrations and age were associated with SBP (beta = 0.29, F = 15.5, P < 0.001, beta = 0.27, F = 14.3, P < 0.001, and beta = 0.2, F = 7.8, P < 0.01, respectively), and haematocrit, fasting plasma glucose concentration and age were associated with DBP (beta = 0.29, F = 14, P < 0.001, beta = 0.2, F = 6.9, P < 0.01 and beta = 0.2, F = 6.3, P < 0.05, respectively). These results suggest that the insulin-BP associations in healthy Japanese subjects over 60 years of age differ according to sex, and that haematocrit is an important determinant of DBP in both sexes in our population.

Aged↗
PubMed1997

Comparison of ranitidine and lansoprazole in short-term low-dose triple therapy for Helicobacter pylori infection.

AIM: To evaluate the efficacy and safety of two 1-week low-dose triple-therapy drug regimens involving antisecretory drugs for Helicobacter pylori infection. 99 patients with H. pylori infection were treated with either lansoprazole or ranitidine used together with clarithromycin and metronidazole. METHODS: The drug combination and administration periods in the proton pump inhibitor group were lansoprazole 30 mg o.m., clarithromycin 200 mg b.d. and metronidazole 250 mg b.d., all given for 7 days (LCM group). The ranitidine group received ranitidine 150 mg b.d., clarithromycin 200 mg b.d. and metronidazole 250 mg b.d. also for 7 days (RCM group). The presence or absence of H. pylori was determined from gastric biopsy specimens taken from both the antrum and the body, by smear, culture and tissue section (Giemsa stain). Cure was defined as failure to find evidence of H. pylori infection 4 weeks after antimicrobial therapy had ended. RESULTS: The cure of H. pylori infection was 88% in the LCM group (44 of 50; 95% confidence interval (CI) = 79-97%) and 92% in the RCM group (45 of 49; 95% CI = 84-99%). The incidence of adverse events was 16% and 18% for the two groups, respectively. CONCLUSIONS: No significant differences in cure rate and safety profiles were noted between the two regimens, suggesting that moderate acid inhibition using an H2-blocker is sufficient to achieve optimal H. pylori eradication.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1997

Polysialic acid synthase (ST8Sia II/STX) mRNA expression in the developing mouse central nervous system.

A comparative study was undertaken to correlate the immunohistochemical localization of polysialic acid (PSA) and the in situ localization of ST8Sia II mRNA. In situ hybridization of postnatal day 3 mouse brain showed high levels of ST8Sia II mRNA expression in the cerebral neocortex, striatum, hippocampus, subiculum, medial habenular nucleus, thalamus, pontine nuclei, and inferior colliculus; intermediate-level expression in the olfactory bulb, hypothalamus, superior colliculus, and cerebellum; and low-level expression in other regions. The distribution of ST8Sia II mRNA in the neocortex and cerebellum coincided with the immunohistochemical localization of PSA. During brain development, ST8Sia II mRNA started decreasing and had almost disappeared by postnatal day 14. Comparison between ST8Sia II and IV mRNA expression was also undertaken by northern blot analysis and competitive PCR analysis. During the late embryonic to early postnatal stages of the mouse CNS, the ST8Sia II mRNA showed abundant mRNA expression compared with the ST8Sia IV mRNA. Competitive PCR analysis of the adult mouse CNS showed weak expression of the two genes in the olfactory bulb, thalamus, hippocampus, and eyes. The regional and transient expression of ST8Sia II mRNA coincides with that of PSA, suggesting that ST8Sia II is closely involved in the biosynthesis and expression of PSA in the developing mouse CNS.

Aging↗
PubMed1997

A new experimental model of a true myocutaneous flap in the rat: the gluteus maximus myocutaneous flap.

Rat myocutaneous flap models are relatively rare. The authors describe the development of a new myocutaneous flap model using the gluteus muscle in rats. A description of the anatomy of the gluteus maximus is included, along with a method of producing skin-island gluteus maximus myocutaneous flaps that can be pedicled or free. This flap model may serve as a useful tool in laboratory studies of the physiologic or pathologic changes in myocutaneous flaps, and may help to narrow the gap between experimental and clinical applications.

Animals↗
PubMed1997

Structural and evolutionary studies on sterol 14-demethylase P450 (CYP51), the most conserved P450 monooxygenase: I. Structural analyses of the gene and multiple sizes of mRNA.

The structure of rat CYP51 gene encoding sterol 14-demethylase was examined. The CYP51 gene spanned about 18 kb and contained 10 exons. The copy number of CYP51 in the rat genome was determined to be one. In addition, one CYP51 processed (intron-less) pseudogene covering the coding and ca. 600-bp 3'-noncoding sequences of CYP51 cDNA was found in the rat genome. Multiple transcription initiation sites were predicted by primer extension and 5'-RACE methods using poly(A)+ RNA from liver, ovary, and testis, and the major ones were located at 126 and 123 nucleotides upstream from the initiation ATG codon. The primer extension also showed several minor sites around the major ones. In addition to these sites, other minor initiation sites were also predicted at around 330 and 460 nucleotides upstream from the initiation ATG codon. No TATA box was found in the putative promoter region, but multiple GC boxes were found around the cap sites, supporting the previously inferred housekeeping nature of CYP51 gene and the existence of the multiple transcription initiation sites. A few consensus transcription regulatory elements such as CRE were found in the 5'-flanking region. Four polyadenylation signals were found in the 3'-noncoding region by the 3'-RACE method. Three of them were used to generate 3.1-, 2.7-, and 2.3-kb mRNAs in liver and ovary. The remaining one was used only in testis to generate 1.9-kb mRNA having an unusually short trailer sequence, suggesting a specific regulatory mechanism for generating CYP51 mRNA in testis different from that in liver and ovary.

Amino Acid Sequence↗
PubMed1997

Structural and evolutionary studies on sterol 14-demethylase P450 (CYP51), the most conserved P450 monooxygenase: II. Evolutionary analysis of protein and gene structures.

Phylogenetic analyses based on protein sequence data indicated that sterol 14-demethylase P450 (CYP51) and bacterial CYP51-like protein were joined into a distinctive evolutionary cluster, CYP51 cluster, within the CYP protein superfamily. The most probable branch topology of the CYP51 phylogenetic tree was (bacteria, (plants, (fungi, mammals))), which is comparable to the phylogeny of major kingdoms of living matter, suggesting that CYP51 has been conserved from the era of prokaryotic evolution. This may be strong evidence supporting the prokaryotic origin of P450. Structure of flanking regions and the number and insertion sites of introns are quite different between mammalian and fungal CYP51s. This fact indicates that different mechanisms are operative in evolution of protein sequences and gene structures. CYP51 is the first example violating the well-documented rule that the basic structure of a gene, including intron insertion sites, is well conserved in each P450 family. One CYP51 processed a pseudogene was found in rat genome. Nonsynonymous nucleotide divergence observed between the pseudogene and CYP51 cDNA was less than one-fifth of the synonymous divergence. This unusually low rate of nonsynonymous nucleotide changes in the pseudogene suggests that it may be derived from another CYP51, which might have been active for a significant duration in the past.

Amino Acid Sequence↗
PubMed1997

Increasing vasoconstrictor response to ergonovine with oxidative injury in canine coronary artery.

BACKGROUND: The effects of oxygen free radicals on coronary vasoreactivity remain unknown. OBJECTIVE: To examine whether oxygen free radicals increase coronary arterial tone and sensitivity to vasoconstrictor stimulation in closed-chest dogs. METHODS: Oxygen radicals were generated by the reaction of xanthine plus xanthine oxidase (XXO) and effects of these substances on the left coronary artery (the percentage diameter change) and on the constrictor effect of ergonovine were examined in vivo in 19 anesthetized, closed-chest dogs by selective coronary angiography. The effects of XXO solution and ergonovine were assessed in a cumulative fashion using 100, 200, and 300 ml XXO and 50, 100, 150, and 200 micrograms ergonovine, in 5 (group I) and 6 dogs (group II), respectively. The effects of XXO on the constrictor responses elicited by 50 micrograms ergonovine were examined in eight dogs (group III). Changes in the vascular endothelium were examined by postmortem electron microscopic examination. RESULTS: Oxidative injury alone produced slight constriction of the coronary artery, but the change was not significant. However, ergonovine-induced vasoconstriction was enhanced after administration of 100 and 200 ml (cumulative amount) XXO solution (P < 0.05, group II versus group III). The enhancement was no longer observed after administration of 300 ml (cumulative amount) XXO solution. Scanning and transmission electron microscopies revealed the formation of blebs and ulceration in the coronary endothelium after administration of XXO solution. CONCLUSION: These results suggest that oxygen radicals can enhance the ergonovine-induced coronary vasoconstriction in a concentration-dependent manner. There seems to be a critical level of oxygen radicals for the production of the effect.

Animals↗
PubMed1997

Efficient retrovirus-mediated cytokine-gene transduction of primary-cultured human glioma cells for tumor vaccination therapy.

In order to realize a novel vaccination treatment for malignant gliomas using tumor cells genetically modified to express certain cytokines, it is essential to achieve an efficient gene transduction into primary cultured cells. We investigated the feasibility of preparing a glioma vaccine through retrovirus-mediated gene transduction. Glioma cells were cultured primarily from surgically resected tumor tissues of six patients. We obtained more than 1000-fold proliferation of cultures within eight weeks in all six cases. In vitro infection with a recombinant retrovirus GKlacZ carrying an Escherichia coli beta-galactosidase marker gene resulted in over 65% gene transfer to the primary cultured glioma cells. Further enrichment (approximately 90%) of transduced cells was possible by employing repeated infections or using vectors with neo' marker gene. Two cytokine genes, granulocyte-macrophage colony-stimulating factor and interleukin-4, were introduced into glioma cells by sequential transduction with two single-expression GK vectors. The transduced glioma cells produced high levels of both cytokines. We also evaluated simultaneous introduction of two genes with double-expression GK vectors containing internal ribosomal entry site (IRES) or internal promoter (PGK). Although the cells transduced with double-expression vectors secreted both cytokines, the level of the gene product following IRES or PGK was 10 times lower than that of the upstream gene product. The transduced cells retained cytokine secretion in vitro for 14 days after 100 Gy irradiation. Our data indicate the feasibility of retrovirus-mediated preparation of gene-modified tumor vaccines from clinical glioma materials, which could be useful for potentiating antitumor immunity in glioma patients.

Base Sequence↗
PubMed1997

Acute fulminant ulcerative colitis with toxic megacolon.

An 11-year-old boy with acute fulminant ulcerative colitis (UC) is presented. He had systemic deterioration with frequent diarrhea and lethargy. Acute fulminant UC associated with toxic megacolon was diagnosed by rectal endoscopy and biopsied specimen. He was treated with intensive intravenous administration of prednisolone and total parenteral nutrition. He recovered completely without any surgical intervention.

Acute Disease↗
PubMed1997

The efficacy and safety of one-week triple therapy with lansoprazole, clarithromycin, and metronidazole for the treatment of Helicobacter pylori infection in Japanese patients.

BACKGROUND: The aim of this study was to evaluate the efficacy and tolerability of 1-week, low-dose triple therapy with lansoprazole, clarithromycin, and metronidazole (LCM) for the cure of H. pylori infection and to establish the adequate dosage of a new triple therapy for Japanese patients. MATERIALS AND METHODS: One hundred four H. pylori-positive Japanese patients were assigned alternatively to one of two groups: one to receive either 30 mg lansoprazole once in the morning, 200 mg clarithromycin twice daily, and 250 mg metronidazole twice daily for 1 week (LCM1; n = 52); the other to receive 30 mg lansoprazole once in the morning, 200 mg clarithromycin twice daily, and 500 mg metronidazole twice daily for 1 week (LCM2; n = 52). H. pylori infection was assessed by smear, culture, and histological assessment (Giemsa stain) performed before and 4 weeks after cessation of the therapy. RESULTS: The overall cure rates of H. pylori infection were 92.3% (48 of 52; 95% confidence interval (CI), 85% to 100%) in LCM1 and 92.3% (48 of 52; 95% CI, 85% to 100%) in LCM2. The cure rates in the patients without prior treatment were 95.7% (44 of 46; 95% CI, 89%-100%) in LCM1 and 95.7% (45 of 47; 95% CI, 89%-100%) in LCM2. Minor side effects were observed in 7.7% of LCM1 and 9.6% of LCM2, respectively. CONCLUSION: The LCM1 regimen consisting of 30 mg lansoprazole once daily, 200 mg clarithromycin twice daily, and 250 mg metronidazole twice daily (the regular doses in ordinary use in Japan) is a highly effective and safe regimen for Japanese patients. LCM1 as a new triple therapy is a promising regimen for the first-line treatment of H. pylori infection in Japanese patients.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1997

Ultrastructural study of antral G cells in patients with duodenal ulcer: effect of Helicobacter pylori eradication.

BACKGROUND: It is established now that Helicobacter pylori infection is associated with exaggerated gastrin release to meals and other stimuli and that the abnormal secretion of gastrin is reversed after successful treatment of the infection. By comparing morphology of G cells from the same patients before and after treatment, we were able to investigate the ultrastructural effect of cure of H. pylori on G cells. METHODS: Gastric mucosal biopsy specimens were obtained from 10 patients with duodenal ulcer before and 3, 6, and 9 months after cure of H. pylori infection. Negative controls consisted of four healthy volunteers without H. pylori infection. G cells were evaluated by immunohistochemical and electron microscopy. Treatment with H2-antagonists was continued for 6 months after cure of the H. pylori infection. RESULTS: Ultrastructural studies of secretory granules of antral G cells in controls displayed a broad range of electron density ranging from dark with a full appearance to totally electron-lucent with a "vacuolating" appearance. In duodenal ulcer patients before treatment, electron-lucent vacuolating granules predominated. After elimination of H. pylori, G-cell granules showed a marked increase in electron density close to that of controls. CONCLUSIONS: Our study showed that the density of granules of G cells is decreased in H. pylori-infected duodenal ulcer patients compared to that in H. pylori-negative controls and is consistent with enhanced gastrin release. Cure of H. pylori infection was associated with return to normal density of G-cell granules.

Anti-Bacterial Agents↗
PubMed1997

Treatment of the anemia of aplastic anemia patients with recombinant human erythropoietin in combination with granulocyte colony-stimulating factor: a multicenter randomized controlled study. Multicenter Study Group.

A multicenter randomized controlled study was undertaken in order to determine whether epoetin beta (EPO) ameliorates the anemia in aplastic anemia (AA) patients treated with granulocyte colony-stimulating factor (G-CSF). Enrolled patients were randomized into 3 groups: group C receiving G-CSF alone as the control; group L receiving G-CSF and 200 IU/kg of EPO; group H receiving G-CSF and 400 IU/kg of EPO. Throughout the study, the dose and the administration interval of G-CSF were adjusted to maintain neutrophil counts between 1000 and 5000 microliters EPO was administered subcutaneously for 12 wk as the first step in treatment and when favorable effects were observed over this period, treatment was continued for another 12 wk as the second step in treatment. Significant erythroid responses were defined as increases in untransfused hemoglobin values > 1.0 g/dl or > 50% decreases in RBC transfusion requirements over the treatment period. Of 131 patients enrolled, 88 patients allocated to groups L and H were evaluated for toxicity to EPO and 110 were evaluated for erythroid responses. Four of the 31 patients (12.9%) in group C, 6 of the 41 patients (14.6%) of group L, and 14 of the 38 patients (36.8%) of group H showed erythroid responses in the first step in treatment. The erythroid responses of group H were significantly higher than those of the other 2 groups (p < 0.05). The significant effects of EPO were due to erythroid responses in non-severe AA. Responding patients were significantly different from non-responders with regard to disease severity, hemoglobin concentration, reticulocyte count, serum endogenous erythropoietin levels and serum transferrin receptors; non-severe AA patients were more likely to respond to EPO, and responding patients had lower serum EPO and higher hemoglobin concentration, reticulocyte count and serum transferrin receptors than non-responders. The response rate increased in the second step in treatment, suggesting that long-term treatment improved the efficacy of EPO. No serious side-effects were observed. From these results, we conclude that EPO given in combination with G-CSF is a safe and effective alternative for the treatment of anemia of a subset of AA patients.

Adult↗