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Biomedical subjects

H Mori

Publications and source records attributed to H Mori.

At least 253 records · Page 14Linked to original sources

Suppression of N-nitrosomethylbenzylamine-induced rat esophageal tumorigenesis by dietary feeding of 1'-acetoxychavicol acetate.

The modifying effects of 1'-acetoxychavicol acetate (ACA) on N-nitrosomethylbenzylamine (NMBA)-induced esophageal tumorigenesis were investigated in male F344 rats. At 5 weeks of age, all test animals, except those given the test chemical alone, and the control rats received s.c. injections of NMBA (0.5 mg/kg body weight/injection, three times per week) for 5 weeks. At the termination of the study (20 weeks), 75% of rats treated with NMBA alone had esophageal neoplasms (papillomas). However, the groups given a dose of 500 ppm ACA during the initiation phase developed a significantly reduced incidence of tumors (29%; P<0.01). Exposure to ACA (500 ppm) during the post-initiation phase also decreased the frequency of the tumors (38%; P<0.05). A reduction of the incidence of preneoplastic lesions (hyperplasia or dysplasia) was obtained when ACA was administered in the initiation phase (P<0.01). Cell proliferation in the esophageal epithelium, determined by assay of proliferating cell nuclear antigen (PCNA), was lowered by ACA (P<0.05). Blood polyamine contents in rats given NMBA and the test compound were also smaller than those of rats given the carcinogen (P<0.05). These findings suggest that dietary ACA is effective in inhibiting the development of esophageal tumors by NMBA when given during the initiation or post-initiation phase, and such inhibition is related to suppression of cell proliferation in the esophageal epithelium.

Animals↗

Chemopreventive effect of curcumin on N-nitrosomethylbenzylamine-induced esophageal carcinogenesis in rats.

Modifying effects of curcumin (derived from the rhizome of Curcuma longa L.) during the initiation or post-initiation phase of N-nitrosomethylbenzylamine (NMBA)-induced esophageal carcinogenesis were investigated in male F344 rats. Five-week-old rats were divided into 5 groups, and groups 1, 2 and 3 were given intraperitoneal injections of NMBA (0.5 mg / kg body weight / injection 15 times) for 5 weeks from 7 weeks old to induce esophageal neoplasms. Groups 2 and 3 were fed the diet containing 500 ppm curcumin during the initiation and post-initiation phases, respectively. Group 4 was given the diet containing curcumin throughout the experiment, and group 5 was kept on the basal diet alone and served as an untreated control. Incidence and multiplicity of esophageal neoplasms of group 1 (NMBA alone) were 66.7% and 0.83 +/- 0.70, respectively. Those of groups 2 and 3 were significantly less than those of group 1 (39.3%, 0.46 +/- 0.64, P < 0.05; 33.3%, 0.36 +/- 0.56, P < 0.05, respectively). Furthermore, the incidence and multiplicity of esophageal preneoplastic lesions (moderate or severe epithelial dysplasia) of group 2 (57.1%, 0.61 +/- 0.57; 40%, 0.29 +/- 0.46) or 3 (56.7%, 0.67 +/- 0.66; 23.3%, 0.23 +/- 0.43) were less than those of group 1 (100%, 1.67 +/- 0.70; 70.8%, 0.92 +/- 0.72) (P < 0.05). In this experiment, feeding of curcumin significantly decreased the expression of cell proliferation biomarkers (5-bromo-2'-deoxyuridine labeling index) in the non-lesional esophageal epithelium (P < 0.01). These findings indicate that curcumin inhibits NMBA-induced esophageal carcinogenesis when given during the post initiation as well as initiation phase. This inhibition may be related to suppression of the increased cell proliferation induced by NMBA in the esophageal epithelium.

Animals↗

[Detection of genotypic and phenotypic drug-resistant HIV-1 in patients receiving antiretroviral therapy].

We have analyzed the sequences of HIV-1 reverse transcriptase and protease genes in peripheral blood mononuclear cells obtained from patients receiving antiretroviral therapy to evaluate the drug resistance-associated mutations. Of 84 HIV-1-infected individuals treated with reverse transcriptase inhibitors, 43 (51.2%) have been found to carry amino acid substitutions predicted to acquire drug-resistances. One to 3 mutations at amino acid residues reported to be associated with protease inhibitor-resistance were detected in more than 80% of protease inhibitor-naive patients. However, these pre-existing mutations did not seem to raise a real resistance after the initiation of therapy with protease inhibitors. Phenotypic resistance assay was performed with 6 clinical isolates to compare with genotypic resistance. In most of the cases, phenotype was correlated with genotypic changes, however, two strains which were isolated from patients having no experience of chemotherapy showed a decrease in susceptibility to several drugs without any resistance-related mutations detected in their genes. Taken together, determination of phenotypic resistance is necessary, especially when a newly-infected patients starts antiviral therapy.

Acquired Immunodeficiency Syndrome↗

[Evaluation of antiretroviral chemotherapy based on the profile of virus isolation from HIV-1 infected individuals].

It is well-known that the biological characteristics of HIV-1 persistently infected in the host have often changed into a rapid growth in vitro, T-cell line tropism and marked syncytium inducing (SI) ability accompanied by the progress of clinical stages from AC to ARC or AIDS. We have developed a follow-up diagnostic test using the clinical markers based on the virus phenotypes mentioned above, and reported that the test was significantly useful for determining the clinical status of HIV infected individuals. Recently, highly active antiretroviral therapy (HAART) was introduced into HIV-1 chemotherapy, and has been reported to be a markedly effective treatment for HIV infected individuals. In this study, we carried out an investigation to see whether the follow-up diagnosis was useful even after introducing the HAART in Japan in 1997. The results by the laboratory diagnosis on 139 HIV infected individuals who were clinically observed over a long period showed that the positive rate of virus isolation and MT-4 cell tropism in the isolates during the two years between 1997 and 1998 were significantly lower than that of the nine years from 1988 to 1996 before the implementation of HAART. In addition, we obtained data that the effect of HAART reflects the biological profiles of virus isolation more than the CD4+ T cell counts. These results suggest that data of clinical examination using virus isolation as a parameter are useful not only for predicting the development of AIDS but also for evaluating the effects of HAART, particularly in patients showing no association between the CD4+ T cell counts and the plasma viral load.

Acquired Immunodeficiency Syndrome↗

A mutation in secY that causes enhanced SecA insertion and impaired late functions in protein translocation.

A cold-sensitive secY mutant (secY125) with an amino acid substitution in the first periplasmic domain causes in vivo retardation of protein export. Inverted membrane vesicles prepared from this mutant were as active as the wild-type membrane vesicles in translocation of a minute amount of radioactive preprotein. The mutant membrane also allowed enhanced insertion of SecA, and this SecA insertion was dependent on the SecD and SecF functions. These and other observations suggested that the early events in translocation, such as SecA-dependent insertion of the signal sequence region, is actually enhanced by the SecY125 alteration. In contrast, since the mutant membrane vesicles had decreased capacity to translocate chemical quantity of pro-OmpA and since they were readily inactivated by pretreatment of the vesicles under the conditions in which a pro-OmpA translocation intermediate once accumulated, the late translocation functions appear to be impaired. We conclude that this periplasmic secY mutation causes unbalanced early and late functions in translocation, compromising the translocase's ability to catalyze multiple rounds of reactions.

Adenosine Triphosphatases↗

Transmyocardial revascularization aggravates myocardial ischemia around the channels in the immediate phase.

We examined whether transmyocardial revascularization (TMR) relieves myocardial ischemia by increasing regional perfusion via the transmural channels in acute canine experiments. Regional blood flow during transient coronary ligation (2 min) was compared before and 30 min after TMR, and at the third transient ischemia the mid-left ventricle (LV) was cut and immediately frozen along the short axis for the analysis of NADH fluorescence in the regions around the TMR channels. In low-resolution analysis (2-4 g tissue or 2-3 cm(2) area), regional perfusion was not significantly altered after TMR, and NADH fluorescence was observed throughout the ischemic region without significant spatial variation. High-resolution analysis (2.8 mg, 1 mm x 1 mm) revealed that the flow after TMR was lower, and NADH fluorescence was higher in the regions close to the channels (1-2 mm) than in the regions 3-4 mm away from them. Creating TMR channels did not improve the regional perfusion and rather aggravated the local ischemia in the vicinity of the channels in the immediate phase.

Analysis of Variance↗

Effects of increased pressure inside or outside ventricles on total and regional myocardial blood flow.

Increasing pressures to 30 mmHg in right (RV) and left (LV) ventricles and surrounding heart (SH) in isolated, arrested, maximally vasodilated, blood-perfused dog hearts shifted pressure-flow (PF) curves rightward and increased zero flow pressure (P(zf)) by an amount equal to the RV applied pressure, SH applied pressure, or two-thirds of the LV applied pressure. There were comparable increases in coronary venous pressures. Increasing LV or SH pressures decreased coronary blood flows, especially in the subendocardium. Decreases in driving pressure decreased flows in all layers, but even with driving pressure of 5 mmHg, a few subepicardial pieces had flow. We conclude with the following: 1) raising pressures inside or outside the heart shifts PF curves and raises P(zf) by increasing coronary venous pressure; 2) the effects are most prominent in the subendocardial muscle layer; and 3) as driving pressures are decreased, there is a range of P(zf) in the heart with the final P(zf) recorded due to the last little piece of muscle to be perfused.

Animals↗

The effects of a novel cyclohexane dicarboximide derivative, ST-6, on hypoxia/reoxygenation injury in perfused rat heart.

The present study was undertaken to test if some cyclohexane dicarboximide derivatives may have a cardioprotective effect against hypoxia/reoxygenation injury. Isolated rat hearts were subjected to 20-min of hypoxia followed by 45-min reoxygenation, and their recovery of post-hypoxic cardiac contractile function was examined. Treatment with agents was carried out from 3 min after the onset of hypoxia to the end of hypoxia (17 min during hypoxia). Among the 17 compounds, 2-[4-[4-(4-chlorophenyl)-4-hydroxy-1-piperidinyl]butyl]hexahydro-1H-i soindol-1,3(2H)-dione (ST-6) showed a significant enhancement of post-hypoxic contractile force. This was associated with attenuation of the releases of creatine kinase and purine nucleosides and bases from the perfused heart. Hypoxia-induced increase in myocardial sodium and decrease in potassium ion content was suppressed by ST-6 treatment. The results suggest that ST-6 is capable of protecting the heart against hypoxia/reoxygenation injury possibly through a mechanism by which sodium overload during hypoxia is suppressed.

Animals↗

Expression of YAV proteins and vaccination against viral ascites among cultured juvenile yellowtail.

Yellowtail ascites virus (YAV) is a member of the family Birnaviridae and causes viral ascites among juvenile yellowtail (Seriola quinqueradiata). We have reported the cloning and expression of two viral cDNAs, the first being segment A encoding a polyprotein of viral capsid proteins (VP2 and VP3) and a protease (NS), and the second being VP2-epitope encoding serotype-specific epitope region on VP2, using a baculovirus expression system. Another viral cDNA encoding a polyprotein of NS and VP3 was cloned and expressed in this study. For the expression of NS/VP3 (YAV nt 1626 to 3066) in insect cells a 31-kDa protein, corresponding to VP3 was detected, indicating an appropriate posttranslational processing of NS/VP3 polypeptide by NS protease itself. The analysis of the N-terminal amino acid sequence of this protein showed that NS protease may cleave an Ala-Ser bond. A study of the potential for vaccination of yellowtail fry by injection of insect cell lysates infected with baculovirus, containing either cDNA of segment A, VP2-epitope, or NS/VP3 was undertaken. Only a vaccination with cell lysates infected with a recombinant virus carrying the full length of YAV segment A gene demonstrated approximately the same effect as that of inactivated YAV. This result suggested that all proteins VP2, VP3, and NS are required for an effective vaccination.

Animals↗

Kurosu, a traditional vinegar produced from unpolished rice, suppresses lipid peroxidation in vitro and in mouse skin.

The in vitro antioxidative activities of various kinds of vinegar were investigated by using a linoleic acid autoxidation model detected by the thiobarbituric acid (TBA) method and the 1,1-diphenyl-2-picrylhydrazyl radical system. An ethyl acetate extract of Kurosu (EK), a vinegar made from unpolished rice, exhibited the highest antioxidative activity in both systems. EK (5 mg) inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced edema formation (14%) and myeloperoxidase activity (52%, P< 0.01) in female ICR mouse skin. Furthermore, EK significantly suppressed double TPA application-induced H2O2 generation (53%, P< 0.01) and lipid peroxidation determined by the TBA-reacting substance level (95 %, P< 0.01). In a two-stage carcinogenesis experiment with dimethylbenz[a]anthracene/TPA, EK significantly reduced the number of tumors per mouse by 36% (P<0.05) at 15 weeks after promotion. These results suggest that the antitumor-promoting effect may be partially due to the antioxidative properties of EK such as the decomposition of free radicals and interference with free radical-generating leukocytes.

9,10-Dimethyl-1,2-benzanthracene↗

Cloning and expression of the Momordica charantia trypsin inhibitor II gene in silkworm by using a baculovirus vector.

MCTI-II (Momordica charantia trypsin inhibitor II) isolated from bitter gourd (Momordica charantia LINN.) seeds is one of the serine protease inhibitors of the squash family. We cloned cDNA that encodes MCTI-II and constructed an expression system for MCTI-II by using a baculovirus vector. The recombinant baculovirus was inoculated to early fifth-instar larvae of the silkworm (strain: Shunrei x Shougetsu). Four days after infection, the hemolymph of silkworm larvae was collected and the recombinant protein was purified. Two kinds of expressed MCTI-II protein were obtained. An amino acid sequence analysis of the two proteins indicates that both were similar to the authentic inhibitor, except for the addition of a tripeptide derived from the vector at the N-terminus. One of the two inhibitors (MCTI-II A) resulted in a single PTH-amino acid in each Edman degradation cycle, while the other (MCTI-II B) resulted in two PTH-amino acids, suggesting the occurrence of cleavage of the reactive site. The inhibitory activities of MCTI-II expressed toward trypsin are examined in terms of the Ki value, these being 6.4 x 10(-10)M for MCTI-II A and 5.2 x 10(-10) M for MCTI-II B.

Amino Acid Sequence↗

Enzymatic production of trans-4-hydroxy-L-proline by regio- and stereospecific hydroxylation of L-proline.

A proline 4-hydroxylase gene, which was cloned from Dactylosporangium sp. RH1, was overexpressed in Escherichia coli W1485 on a plasmid under a tryptophan tandem promoter after the codon usage of the 5' end of the gene was optimized. The proline 4-hydroxylase activity was l600-fold higher than that in Dactylosporangium sp. RH1. trans-4-Hydroxy-L-proline(Hyp) was produced and accumulated to 41 g/L (87% yield from L-proline) in 100 h when the recombinant E. coli was cultivated in a medium containing L-proline and glucose. 2-Oxoglutarate, which is necessary for the hydroxylation of L-proline by proline 4-hydroxylase, was apparently supplied from glucose through the cellular metabolic pathway. The putA mutant of W1485, which is not able to degrade L-proline, has allowed the quantitative conversion of L-proline to Hyp. The formation of other isomers of hydroxyproline was not observed. Productivity of Hyp was almost the same in a larger-scale culture. The method of manufacturing Hyp from L-proline was established.

Amino Acid Sequence↗

Effect of liquid paraffin on antibody responses and local adverse reactions of bivalent oil adjuvanted vaccines containing newcastle disease virus and infectious bronchitis virus.

Effects of liquid paraffin on antibody responses and local adverse reactions after intramuscular injection of oil adjuvanted vaccines containing Newcastle disease (ND) and infectious bronchitis (IB) virus were investigated in chickens. Each vaccine was prepared with a liquid paraffin such as Carnation, Crystol 52 and Lytol. These vaccines induced sustained antibody responses against ND and IB. Among local adverse reactions, Lytol induced granulomatous reactions and abscesses, but Carnation and Crystol 52 did not. The residual weight of liquid paraffin at the injection site decreased in the order Carnation, Crystol 52, Lytol. Crystol 52 was composed of relatively few short-chain hydrocarbons (i.e., n-C20H42). The vaccine with liquid paraffin mainly composed of n-C16H34-n-C20H42 was suggested to induce fewer adverse reactions.

Adjuvants, Immunologic↗

Relation between antigen release and immune response of oil adjuvanted vaccines in chickens.

The relationship between release properties of the model antigen, bovine serum albumin (BSA), from formulations in vitro and immune response after administration of various oil adjuvanted vaccines containing liquid paraffin was examined in chickens. The vaccine prepared at an hydrophile-lipophile-balance (HLB) number of 4.8 showed slower release of BSA and higher immune response on injected chickens than that with an HLB number of 6.0. Decreases of aqueous volume ratio in the formulation also led to slower release of BSA and higher immune response. The slower release rate of BSA showed higher ELISA antibody titer even at 20 weeks after vaccination. The ELISA antibody titer inversely was related to the constant release rate, k, calculated from the in vitro release test. The correlation coefficient was 0.863. The immune response of oil adjuvanted vaccines containing Haemophilus paragallinarum agreed well with these results with BSA. Our results indicated that a stronger and more prolonged immune response of oil adjuvanted vaccines was achieved by slower release rate of antigen from the formulation. In addition, there was a good correlation between immune response and the value of k.

Adjuvants, Immunologic↗

Adjuvanticity and inflammatory response following administration of water-in-oil emulsions prepared with saturated hydrocarbons in chickens.

Water-in-oil emulsions containing bovine serum albumin (BSA) as a model antigen were prepared using aliphatic saturated hydrocarbons with carbon number from 12 to 18, and were tested in chickens. Straight-chain hydrocarbons induced higher antibody titers against BSA after administration than branched-chain hydrocarbons. n-C16H34 and n-C18H38 maintained high antibody titers even at 32 weeks after administration, compared with n-C12H26, n-C14H30 and n-C15H32. n-C12H26 and n-C14H30 raised concentrations of sialic acid and creatine kinase in plasma, both of which are important markers of inflammatory responses, immediately after administration. n-C16H34 and n-C18H38 did not raise the values of these markers. These results indicated that n-C16H34 and n-C18H38 induced elevated and sustained immune responses without severe adverse reactions in chickens.

Adjuvants, Immunologic↗

Radiation-induced diffuse brain injury in the neonatal rat model--radiation-induced apoptosis of oligodendrocytes.

The mechanism of radiation-induced diffuse brain injury was investigated using a model of delayed myelination in the irradiated neonatal rat brain in which the number of oligodendrocytes decreases without associated necrosis of the cerebral white matter. Immunohistochemical analysis using antibody against the large myelin-associated glycoprotein, a specific marker of oligodendrocytes at an early stage of development, showed that the number of the oligodendrocytes associated with myelination decreased in the irradiated hemisphere 1 day after irradiation and remained low until 5 days after irradiation. In situ terminal deoxynucleotidyl transferase-mediated nick end-labeling assay revealed that apoptosis mainly occurred in the cerebral white matter of the irradiated hemisphere. Three hours after irradiation, apoptotic cells were found in the subcortical white matter and the periventricular white matter. Six hours after irradiation, apoptotic cells were found in the internal capsule, and the numbers of apoptotic cells in the periventricular white matter and subcortical white matter increased. One day after irradiation, the number of apoptotic cells in the periventricular white matter decreased. Three days after irradiation, apoptotic cells were not observed in the cerebral white matter. These results suggest that the oligodendrocytes associated with myelination may be damaged via radiation-induced apoptosis, and depletion of the oligodendrocytes may cause delay of myelination.

Animals↗

CT assessment of the inferior peripancreatic veins: clinical significance.

OBJECTIVE: The purpose of this study was to evaluate and clarify the clinical significance of CT scans of the inferior peripancreatic veins. MATERIALS AND METHODS: Forty-three patients with suspected pancreatic disease underwent three-phase helical CT (collimation, 5 mm; reconstruction, 2.5 mm; scan delay, 30, 60, and 150 sec). The frequency of visualization on CT of the anterior and posterior inferior pancreaticoduodenal veins, inferior pancreaticoduodenal vein, and first jejunal trunk was assessed and correlated with angiographic and pathologic findings. RESULTS: The frequency of visualization of normal inferior peripancreatic veins in patients (n = 22) with a normal portomesenteric vein was 36% for the anteroinferior pancreaticoduodenal vein, 36% for the posteroinferior pancreaticoduodenal vein, 59% for the inferior pancreaticoduodenal vein, and 100% for the first jejunal trunk. The smaller inferior peripancreatic veins were frequently not visualized when normal. In patients (n = 13) with pancreatic carcinoma involving the portosuperior mesenteric vein, all of the inferior peripancreatic veins were dilated and easily recognizable. When the tumor did not involve the portosuperior mesenteric vein but did involve the anteroinferior pancreaticoduodenal, posteroinferior pancreaticoduodenal, and inferior pancreaticoduodenal veins (n = 8), some of the other peripancreatic veins (first jejunal trunk, anterior and posterior superior pancreaticoduodenal veins, and gastrocolic trunk) were dilated. Dilatation indicated tumor extension to the third portion of the duodenum. In patients (n = 7) with involvement of the inferior pancreaticoduodenal vein, the first jejunal trunk, or both without the involvement of the portosuperior mesenteric vein, dilatation of the other peripancreatic veins (anteroinferior pancreaticoduodenal vein, posteroinferior pancreaticoduodenal vein, anterosuperior pancreaticoduodenal vein, posterosuperior pancreaticoduodenal vein, and gastrocolic trunk) indicated tumor invasion of only the second portion of the extrapancreatic nerve plexus (n = 4) and tumor invasion of both the second portion of the extrapancreatic nerve and the mesenteric root (n = 3). CONCLUSION: Dilatation of peripancreatic veins with nonvisualization of inferior peripancreatic veins suggests tumor invasion of peripancreatic tissue.

Adult↗