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Biomedical subjects

N Tani

Publications and source records attributed to N Tani.

At least 19 recordsLinked to original sources

Different antibacterial actions of isoflavones isolated from Erythrina poeppigiana against methicillin-resistant Staphylococcus aureus.

AIMS: To screen six isoflavones isolated from Erythrina poeppigiana (Leguminosae) for their antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). METHODS AND RESULTS: Stem bark of E. poeppigiana was macerated with acetone and the methylene chloride-soluble fraction of the residue was applied to repeated silica gel column chromatography and eluted. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined by a broth dilution method. Inactive compounds that failed inhibiting bacterial growth at 25 microg ml(-1) were further investigated for their combination effects with methicillin and oxacillin. Of the isolated isoflavones, 5,7,4'-trihydroxy-8,3'-di(gamma,gamma-dimethylallyl)isoflavone (isolupalbigenin) exhibited the highest anti-MRSA activity (MICs: 1.56-3.13 microg ml(-1); MBCs: 6.25-12.5 microg ml(-1)), followed by 5,7,4'-trihydroxy-6-gamma,gamma-dimethylallylisoflavone (erythrinin B). Inactive compounds were combined with methicillin or oxacillin, 5,4'-dihydroxy-(3'',4''-dihydro-3''-hydroxy)-2'',2''-dimethylpyrano[5'',6'':6,7]isoflavone (M-Wi-2) intensifying the susceptibility of MRSA strains to these antibiotics. In all but one strain, the MIC values of methicillin were reduced from > or =100 to 6.25-12.5 microg ml(-1) in the presence of M-Wi-2 (25 microg ml(-1)). CONCLUSIONS: Isoflavones from E. poeppigiana showed two different antibacterial activities against MRSA: direct growth inhibition and intensification of methicillin sensitivity. SIGNIFICANCE AND IMPACT OF THE STUDY: Isolupalbigenin and M-Wi-2 could lead to the development of compounds for new approaches against MRSA infection.

Acetone↗

Characterization of the enzymes involved in the in vitro metabolism of amrubicin hydrochloride.

The in vitro metabolism of amrubicin by rat and human liver microsomes and cytosol was examined. The main metabolic routes in both species were reductive deglycosylation and carbonyl group reduction in the side-chain. In vitro metabolism of amrubicinol by rat and human liver microsomes and cytosol was also examined and the main metabolic route of this active metabolite was reductive deglycosylation. Metabolism of amrubicin in human liver microsomes was inhibited by TlCl(3) and that in human liver cytosol was inhibited by dicumarol and quercetin. Generation of amrubicinol was inhibited only by quercetin. The results indicate that metabolism of amrubicin is mediated by NADPH-cytochrome P450 reductase, NADPH:quinone oxidoreductase and carbonyl reductase. In addition, generation of amrubicinol is mediated by carbonyl reductase. Metabolism of amrubicinol in human liver microsomes was inhibited by TlCl(3) and that in human liver cytosol was inhibited by dicumarol. The results indicate that metabolism of amrubicinol is mediated by NADPH-cytochrome P450 reductase and NADPH:quinone oxidoreductase. To investigate the influence of cisplatin on the metabolism of amrubicin and amrubicinol, human liver microsomes and cytosol were pre-incubated with cisplatin. This did not change the rates of amrubicin and amrubicinol metabolism in either human liver microsomes or cytosol.

Adult↗

Half-sib family structure of Fagus crenata saplings in an old-growth beech-dwarf bamboo forest.

Half-sib family structure of Fagus crenata saplings was examined in an old-growth beech-dwarf bamboo (Sasa spp.) forest using microsatellite genotypes in parentage analysis to identify the half-sib families in two 50 x 50 m plots: one with 36 adults, 641 saplings and no Sasa cover, the other with 21 adults, 61 saplings and Sasa cover. For large proportions of the saplings (44.6% and 75.4%, respectively) both of their parents were found within the same plot, indicating that pollination events frequently involved short-range pollen dispersal, probably because of the high density of adults in the study population. Although almost all of the adults had half-sib families, the number of offspring in the families was highly variable. In the plot with no Sasa cover, the variation in the number of offspring was significantly explained by the size of parents, i.e. the reproductive success is higher for large adults than for small adults. The half-sibs were aggregately distributed around their parents and the distribution overlapped among different half-sib families, which may be due to the limited seed dispersal and overlapping seed shadows of this species. As expected, there was weak genetic structure in the plot. By contrast, in the plot with Sasa cover, the half-sibs were distributed sparsely with a low density, and the degree of genetic structure was very weak. The difference in the half-sib family structure and genetic structure among saplings presumably reflects the difference in density that should be affected by regeneration dynamics associated with environmental conditions.

Demography↗

Expression level of integrin alpha 5 on tumour cells affects the rate of metastasis to the kidney.

Tumour metastasis is known clinically to have organ specificity. We hypothesised that integrins might be involved in determining the organ specificity of tumour metastasis. Here, we report the results of spontaneous metastasis tested in nude mice that were inoculated with Chinese hamster ovary (CHO) cells expressing integrin alpha 5 beta 1 at various levels. The growth of the primary tumour inversely correlated with the alpha 5 expression level on CHO cells, which is consistent with a previous report (Schreiner et al, 1991). The rates of pulmonary, lymph node, and adrenal metastases that developed in nude mice were not related to changes of the alpha 5 expression level on CHO cells. Kidney metastasis developed in 40% of nude mice inoculated with alpha 5B2 cells (CHO cells overexpressing alpha 5) and in 20% of mice with CHO-K1 cells (CHO cells expressing native alpha 5), whereas inoculation with CHO-B2 cells (alpha 5-defective mutants) and alpha 5CHO cells with the highest expression of alpha 5 did not lead to development of kidney metastasis. Furthermore, alpha 5CHO, which shows the slowest growth of these cell types, did not lead to primary tumours in nude mice. These findings suggest that there is an appropriate level of alpha 5 expression on tumour cells that leads to metastasis. Microscopic observations revealed that micrometastasis in the kidney was formed in glomeruli. An adhesion assay using frozen sections of the kidney demonstrated that alpha 5B2 cells, but not CHO-B2 cells, effectively adhered to glomeruli. Kidney metastasis in vivo and the adhesion of alpha 5B2 to glomeruli shown ex vivo were significantly suppressed by the administration of GRGDS peptide. Finally, we conclude that the interaction of alpha 5 beta 1 on tumour cells with fibronectin in kidney glomeruli is involved in kidney metastasis and that the tumour has appropriate levels of integrins crucial for metastasis.

Adrenal Gland Neoplasms↗

Genetic diversity of nuclear and mitochondrial genomes in Pinus parviflora Sieb. & Zucc. (Pinaceae) populations.

Genetic diversities of the nuclear and mitochondrial genomes in Pinus parviflora were studied in 16 populations, which were distributed across most of the species' range in Japan. Six mitochondrial DNA haplotypes were identified among the 16 populations. The intrapopulation diversity of allozymes was similar to that of other endemic woody species (H(S)=0.259). Although P. parviflora is distributed in discrete populations, differentiation between these was very low (G(ST)=0.044). In addition, the extent of genetic differentiation between two varieties (var. pentaphylla and var. parviflora) was extremely low (G(VT)=0.001). Intrapopulation diversity of mitochondrial DNA was also very low (H(S)=0.098), but population differentiation was high (G(ST)=0.863). Moreover, the distribution of haplotypes reflected the taxonomic differences between P. parviflora var. pentaphylla and var. parviflora. The populations of var. pentaphylla and var. parviflora contained different haplotypes. Differing modes of inheritance may account for the differences in nuclear and mitochondrial genetic diversity.

Autoradiography↗

Promoter structure and transcription initiation sites of the human death receptor 5/TRAIL-R2 gene.

The death receptor 5 (DR5) is a receptor for tumor necrosis factor-related apoptosis-inducing ligand and is able to induce apoptosis in various tumor cells. The expression of DR5 is up-regulated at the transcriptional level by p53, genotoxic stress and so on. To investigate the structure of the DR5 gene promoter, we screened and sequenced a genomic clone containing the 5'-flanking region of the DR5 gene. RNase protection assays showed two major transcription start sites around -122 and -137 upstream of the translation initiation codon ATG. Transient transfections with serial 5'-deletion mutants identified the minimal promoter element spanning -198 to -116. Site-directed mutagenesis demonstrated that the DR5 gene promoter has no typical TATA-box, but has two Sp1 sites responsible for the basal transcription activity of the DR5 gene promoter.

5' Flanking Region↗

Effects of fibronectin cleaved by neuropsin on cell adhesion and migration.

Neuropsin is a serine protease cloned from the mouse hippocampus. Since neuropsin is a secreted protein which effectively cleaves fibronectin, it may affect cell adhesion or cell migration by modulating the content and/or chemical characteriscs of fibronectin in extracellular matrix (ECM). In adhesion assays, alpha5B2 cells expressing integrin alpha5beta1 bound less effectively to fibronectin teated with neuropsin than intact fibronectin. In Boyden chamber chemotaxis assays, the fibronectin-induced migration of alpha5B2 cells was not affected by neuropsin treatment. These findings suggest that neuropsin regulates the local microenvironment by modulating the interaction between cells and fibronectin in ECM.

Animals↗

Carbohydrate moiety of time-interval measuring enzyme regulates time measurement through Its interaction with time-holding peptide PIN.

An ATPase called EA4 seems to measure time as a diapause-duration timer in the seasonal cycle of the silkworm, Bombyx mori. A peptide named PIN seems to regulate the time measurement of EA4. We characterize the EA4 as the first step to analyse its interaction with PIN. Matrix-assisted laser desorption/ionization-time of flight-mass spectrometry shows EA4 forms an equimolar complex with PIN. The binding affinity of EA4 for PIN is about 460 nM, as measured by surface plasmon resonance. Western blot analysis of EA4 with a variety of biotinylated lectins suggests that EA4 is a glycoprotein containing N-linked oligosaccharide. On enzymatic cleavage of the glycosyl chain, the carbohydrate is revealed to be essential for the regulation of EA4-time measurement through the interaction with PIN. PIN holds the timer by binding to EA4, and the dissociation of the complex could constitute the cue for the time measurement.

Adenosine Triphosphatases↗

Molecular detection of disseminated cancer cells in the peripheral blood and expression of sialylated antigens in colon cancers.

BACKGROUND AND OBJECTIVES: To improve the survival rate of patients with colon cancer, liver metastases must be eradicated in a clinically occult state. This study was designed to find a predictor for potential liver metastases or micrometastases in colon cancer. METHODS: Peripheral blood samples and tumor specimens were obtained from 36 patients with colon cancers. The blood samples were subjected to reverse transcriptase-polymerase chain reaction (RT-PCR) analysis, and the expression of sialylated carbohydrates was also investigated in the tumors immunohistochemically. RESULTS: A carcinoembryonic antigen (CEA)-specific signal in the blood was detected in 9 of 12 (75%) patients with liver metastasis and in 8 of 24 (33%) patients without liver metastasis, respectively (P < 0.05). The positive rates of sialyl Lewis A (sLeA) and sialyl Lewis X (sLeX) were 36.3% and 40% in tumors without liver metastasis vs. 58.3% and 100% with liver metastasis, respectively. Within a year after surgery, liver metastases became clinically evident in three of the four patients without liver metastasis who showed a CEA-positive signal in their blood preoperatively and who had tumors with a strong expression of sLeX. CONCLUSIONS: A combination of both markers may provide prognostic information for liver metastases in colon cancer.

Colonic Neoplasms↗

Local thrombus formation in the site of intravenous injection of chlorpromazine: possible colloid-osmotic lysis of the local endothelial cells.

Since amphiphilic drugs are known to interact with biomembranes, we investigated local vessel damage and thrombosis which might be brought about by intravenous dosing using chlorpromazine (CPZ) as a representative compound. CPZ-induced hemolysis was suppressed by an increase in sucrose concentration in the medium, characterizing this hemolysis to be colloid-osmotic lysis, which includes the enhancement of membrane phospholipid fluidity and consequent small pore formation in the membranes. This was supported by the observation that hemolysis by filipin, not featuring the stage of small pore formation, was not affected by sucrose. [14C]Glucose-entrapping liposomes were degraded by CPZ, and this degradation was enhanced by an increase in the intravesicle glucose concentration. These results indicated that the compound could induce colloid-osmotic lysis in erythrocytes and artificial membrane vesicles. CPZ also injured cultured porcine aortic endothelial cells (PAEC), as evidenced by lactate dehydrogenase (LDH) leakage. This injury was also suppressed by increase in sucrose concentration in the medium, suggesting that colloid-osmotic lysis again occurred. When rats were intravenously injected with CPZ, local endothelial cell (EC) injury and associated thrombus formation were observed, suggesting that CPZ's action was also evident in vivo. To our knowledge, this is the first finding which suggests that an intravenously dosed amphiphilic drug can injure local ECs based on a colloid-osmotic lysis mechanism leading to thrombosis.

Animals↗

[A case study of BRON (cough suppressant) tablet dependence--its social psychiatric and biological aspects].

A case of BRON tablet dependence is demonstrated. BRON is an over-the-counter (OTC) cough suppressant, which contains methylephedrine, dihydrocodeine, chlorpheniramine and caffeine. He took BRON tablet for the first time at the age of 16. In progress, he developed psychomotor excitement twice and finally manifested amotivational syndrome 3 years later from his first use. Longitudinal 123I-IMP SPECT (autoradiography method) findings demonstrated diffuse cerebral blood flow (CBF) decrease and relative hyperactivity in the lower frontal lobe. Diffuse decreased regional CBF, which was unchanged through its course for about 4 months, may show irreversible brain damage due to chronic BRON abuse. The findings of relative hyperactivity in the lower frontal lobe (orbitofrontal lobe) may reflect "craving for BRON" based on abnormal dopaminergic neural system activity. Based on the evidence that orbitofrontal hyperactivity is also seen in cases of cocaine abuse, methylephedrine, which is a cocaine-like central nervous system stimulant, may play the main role in BRON dependence formation. In Japan, BRON syrup abuse and dependence were in fashion for youth in 1980s. After the legal regulation of the market in 1988, it has gone out of fashion. While it is still easy to acquire OTC cough suppressant, reports of BRON tablet abuse and dependence are quite rare through 1980s and 1990s. This case suggests that BRON tablet abuse also could lead to dependence and come into new vogue for youth in the future. We should pay attention to the trend of OTC cough suppressant abuse and may need to regulate the market by law more severely.

Adolescent↗

High expression of alternative transcript of granzyme M in the mouse retina.

We have isolated cDNAs to two transcripts, granzyme M and alternative granzyme M mRNA from the mouse eye. Analysis of genomic DNA revealed these transcripts were derived from alternative transcription initiations. Northern blot analysis and reverse transcription-polymerase chain reactions revealed that both transcripts were expressed in the eye, though the alternative form was the major type. In situ hybridization studies demonstrated that alternative granzyme M mRNA localized exclusively in the photoreceptor cells in the retina and expressed only after the opening of the eye, suggesting that these transcripts are related to the maintenance of the retinal structure or functions of matured photoreceptor cells rather than the development or differentiation of retinal cells.

Alternative Splicing↗

Effects of inflammatory cytokines induced by Helicobacter pylori infection on aminopyrine accumulation in parietal cells isolated from guinea pigs.

The effects of inflammatory cytokines induced by Helicobacter pylori infection on acid secretion have not been well defined. The purpose of this study was to investigate the direct effects of these cytokines on parietal cells isolated from guinea pigs. We examined the effects of human recombinant IL-1beta (0.05-100 ng/ml), IL-8 (2-256 ng/ml), and TNF-alpha (0.625-80 ng/ml) on acid secretion stimulated by three secretagogues (10(-4) M histamine, 10(-4) M carbachol, and 10(-5) M tetragastrin) and on basal acid secretion from isolated parietal cells, which was measured by the aminopyrine accumulation method. None of three cytokines showed any significant effects on stimulated or basal acid secretion from isolated guinea pig parietal cells. We concluded that inflammatory cytokines induced by Helicobacter pylori infection may affect acid secretion through mechanisms other than direct actions on parietal cells.

Aminopyrine↗

Hydrazine-conjugated cellulose for adsorption of glycated proteins.

Glycated proteins and advanced glycation end-products are postulated to play an important role in the development of complications due to diabetes mellitus or renal failure. The purpose of this study was to assess the ability of hydrazine-conjugated cellulose to adsorb glycated albumin. The samples used for adsorption test were artificially glycated albumin or the serum from patients with diabetes mellitus. The hydrazine-conjugated cellulose adsorbed more than 20% of the albumin glycated artificially over 77 days. The serum concentrations of glycated albumin in patients with diabetes mellitus (39.6 +/- 2.5% (mean +/- SEM), n = 14) were not decreased by incubation with cellulose alone (postincubation level, 39.7 +/- 2.5%) whereas they were significantly (p < 0.0001) reduced to 38.0 +/- 2.4% after incubation with hydrazine-conjugated cellulose. There was a significant correlation (r = 0.75, p < 0.01) between the preincubation levels of glycated albumin and the degree of adsorption. The hydrazine-conjugated cellulose has a higher affinity for albumin with greater glycation.

Adsorption↗

[A case report of male alcoholics treated the left replacement prosthesis on account of the idiopathic avascular necrosis of the left femoral head].

Idiopathic necrosis of the femoral head is already described associated with alcoholism. However, it is unusual to meet alcoholic patient with idiopathic necrosis of the femoral head in psychiatric hospital. In this report, we describe about the psychiatric treatment of an alcoholic male patient who complicated idiopathic necrosis of the femoral head. He begun drinking a large amount of alcohol at the age of 20. After 32 years old, he repeated admission to psychiatric hospitals for the treatment against alcohol dependence. At the age of 35, he felt left hip pain. At 36 years old, the illness was diagnosed as idiopathic necrosis of the femoral head and osteotomy was performed. After the operation, he did not keep the direction to keep a rest and not to drink. At last, total replacement arthroplasty was undergone. All through the treatment, we supported the patient to participate in group therapy and Alcoholics Anonymous, and approached directively and supportively to gain an insight about problems of drinking. As a result, after the last operation he hoped psychiatric treatment of his own will and began to gain insight gradually about his own alcoholic problems. This case emphasizes the necessity of psychotherapeutic approach and treatment programs for alcohol dependence and its physical complications.

Adult↗

[Mental and physical symptoms in alcoholics after alcohol withdrawal--comparing with involutional melancholia patients].

As a factor of recurrence of drinking in patients with alcoholic dependence, emotional disorders accompanied by alcohol dependence has been noted in many reports. Particularly, it is noted to be very likely that depression after abstinence is an incentive to re-start drinking. In this study, we investigated depressive feeling in aspects of psychiatric and physical subjective symptoms after abstinence in patients with alcohol dependence, and compared the symptoms with those in patients with involutional depression. On analysis of the major component of psychiatric subjective symptoms, a sense of alienation, emotional instability, anxiety, and aggressiveness were observed. In involutional depression, depressive feeling, somnipathy, anxiety, self accusation/sense of guilt, delusion of culpability were observed. On analysis of the major component of physical subjective symptoms, autonomic nervous symptoms accompanied by feebleness, hysterical neurosis-like autonomic nervous symptoms, reduced sexual libido, anorexia, hydrodipsia/sweating were observed. Similarly, in patients with involutional depression, hysterical neurosis-like autonomic nervous symptoms, anorexia, elevation of tonus, general malaise, and hydrodipsia were noted. Differences in status were emphasized in comparison between the two groups in both analyses. Unlike involutional depression that exhibits the current features of depression, patients with alcohol dependence showed a sense of alienation, emotional instability, anxiety, and aggressiveness, reflecting self-uncertainty and loss of self-respect. Drinking may be re-started to relieve or reduce tension and frustration in such conditions.

Alcoholism↗