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Biomedical subjects

T Yano

Publications and source records attributed to T Yano.

At least 415 records · Page 23Linked to original sources
PubMed1995

[Comparison of the clinical features of smear-positive and culture-positive tuberculous patients with smear-negative and culture-positive patients in an education hospital].

The clinical features of 27 smear-positive and culture-positive tuberculous patients (Group 1) were compared with those of 39 smear-negative and culture-positive patients (Group 2) experienced in our hospital. The proportion of the patients who have underlying diseases was lower in Group 1 than Group 2. Ninety-five % of the patients in Group 1 showed positive PPD skin reaction in comparison with 73% of the patients in Group 2. In most of the patients in Group 1, the chest X-ray findings were typical ones for pulmonary tuberculosis, but 36% of the patients in Group 2 showed atypical X-ray findings. Final diagnosis was more difficult for the patients in Group 2 than Group 1. Almost all patients in Group 1 could be diagnosed within a few days and were referred to a tuberculosis hospital for the treatment of tuberculosis. On the contrary, by the patients in Group 2, the final diagnosis was delayed more than one month until the results of culture was available. Also, many patients in this group had underlying disease and only 8 patients could be transferred to a tuberculosis hospital.

Adolescent↗
PubMed1995

[Lysosomal membrane transport disorders--cystinosis and sialic acid storage disorders (Salla disease, ISSD)].

Cystinosis and sialic acid storage diseases (Salla disease, ISSD; infantile sialic acid storage disease) are lysosomal membrane disorders resulting from defective carrier-mediated transport of cystine and sialic acid across the lysosomal membrane. Both are rare autosomal recessively inherited disorders. The major clinical manifestations of cystinosis are renal failure and ocular damages. Sialic acid storage diseases are characterized by various degrees of psychomotor retardation. Salla disease patients trace a mild clinical course, and the life span is relatively long. While, in patients with ISSD follow a very severe progressive clinical course and often die in the first year of life. The genes responsible for each disease have not been isolated, the etiologies are not well known, and there is no specific treatment.

Biological Transport↗
PubMed1994

Synthesis of prostaglandin H synthase-2 by human alveolar macrophages in response to lipopolysaccharide is inhibited by decreased cell oxidant tone.

We previously demonstrated that lipopolysaccharide (LPS) increases expression of the prostaglandin H synthase-2 (PGHS-2) gene (Hempel, S.L., Monick, M.M., and Hunninghake, G.W. (1994) J. Clin. Invest. 93, 391-396). In this study, the expression of the PGHS-2 gene in response to changes in cell oxidant tone was studied. During LPS exposure, inhibition of synthesis of the free radical, NO., resulted in a small decrease in prostaglandin E2 synthesis that did not reach statistical significance. There was no effect on enzyme mass or mRNA. In contrast, incubation of alveolar macrophages in the presence of LPS plus the antioxidant pyrrolidine dithiocarbamate, the spin trap 5,5-dimethyl-1-pyrroline-N-oxide, or hypoxia, resulted in near complete inhibition of prostaglandin E2 synthesis, PGHS-2 enzyme synthesis, and gene transcription of PGHS-2 mRNA. There was no evidence of cytotoxicity. These results demonstrate that synthesis of PGHS-2 in response to LPS is inhibited by agents that decrease cell oxidant tone.

Amino Acid Oxidoreductases↗
PubMed1994

Vitamin E acts as a useful chemopreventive agent to reduce spontaneous lung tumorigenesis in mice.

The present study was designed to evaluate whether vitamin E could be a useful chemopreventive agent to reduce spontaneous lung tumorigenesis in mice. Starting at 6 weeks of age, groups were divided into three groups, i.e. A/J mice fed a control diet (A/J control), A/J mice fed a vitamin E-supplemented diet (A/J vitamin E) and ddY mice fed a control diet (ddY control). At the 28th experimental week, nuclear NADPH-driven active oxygen generation, thiobarbituric acid reactive substances (TBARS) and DNA single strand breaks (DNA-SSB) in A/J mice fed a control diet were significantly higher than those in the ddY control group. A/J mice fed Vitamin E for 28 weeks could decrease the levels of TBARS and DNA-SSB with a significant difference, as compared with those in A/J control mice. The nuclear alpha-tocopherol levels in A/J controls were significantly lower than those in ddY controls, on the contrary, the vitamin feeding to A/J mice increased nuclear alpha-tocopherol levels more than that in the ddY controls. At the 40th experimental week, lung tumor incidence and tumor multiplicity (percentage of mice with tumors) in A/J controls were reduced and brought close to those in ddY control mice by vitamin E. Then the alpha-tocopherol level in plasma of A/J controls was significantly lower than the level in plasma of ddY controls, and the level in tumor-bearing mice in A/J controls also showed a lower level with significant difference as compared to that in non-tumor-bearing mice of A/J controls. These results suggest that the difference in susceptibility to spontaneous lung tumorigenesis between A/J and ddY mice partly depends on the difference of oxidative stress on the pulmonary nuclei, and vitamin E can act as a useful chemopreventive agent to reduce spontaneous lung tumorigenesis in mice.

Animals↗
PubMed1994

NMR studies of 1H resonances in the 10-18-ppm range for aspartate aminotransferase from Escherichia coli.

We have recorded 500-MHz 1H NMR spectra in the 10-18-ppm range for aspartate aminotransferase from Escherichia coli and for three specific mutant forms. Histidine 143 has been replaced by either alanine or asparagine. In the third mutant, tryptophan 140 has been replaced by phenylalanine. The NMR spectrum of the native enzyme is very similar to that of porcine cytosolic aspartate aminotransferase in the most downfield region. However, the resonances of the proton on the ring nitrogen of the pyridoxal 5'-phosphate (peak A) and on the His-143 imidazole ring (peak B) of the E. coli enzyme are broader and more readily lost at low pH or higher temperatures than those of the porcine enzyme. The possible role of tautomerism in promoting such broadening is discussed. In the histidine mutant proteins, peak A of the pyridoxal 5'-phosphate form is too broad to see under most conditions but is clearly present in the pyridoxamine phosphate form. Peak B is missing in the 2 histidine mutants. Observation of nuclear Overhauser effects further confirms the identity of B as the resonance of HN epsilon 2 of His-143 and that of peak D at approximately 11.8 ppm as HN epsilon 2 of His-189. The mutant spectra also provide insight into electronic interactions between groups in and near the active site which confirm and supplement conclusions drawn from spectra of porcine cAspAT. While no clear loss of a peak was observed for the Trp-140 mutant in its free form, the spectrum of the succinate complex lacked a strong band at 11.26 ppm. This may represent the Trp-140 indole NH proton which has been shifted downfield by binding to a succinate carboxylate group. While our results confirm the basic similarity of cytosolic aspartate aminotransferase and E. coli aspartate aminotransferase 1H NMR spectra, they also point out differences that may be useful in identifying resonances. A large number of mutant proteins have been prepared for the E. coli enzyme. The present results provide essential information for future study of these mutants and for study of NMR spectra of isotopically labeled enzyme.

Alanine↗
PubMed1994

Identification of amino acid residues associated with the [2Fe-2S] cluster of the 25 kDa (NQO2) subunit of the proton-translocating NADH-quinone oxidoreductase of Paracoccus denitrificans.

In order to identify the ligand residues of the [2Fe-2S] cluster of the 25 kDa (NQO2) subunit of the proton-translocating NADH-quinone oxidoreductase of Paracoccus denitrificans, we mutated individually all seven cysteine residues (C61, C96, C101, C104, C113, C137, and C141) and one conserved histidine residue (H92) to Ser or Ala and expressed them in E. coli. After purification of the mutated 25 kDa subunits, the effect of mutations on the iron-sulfur cluster were characterized by chemical analyses and UV-visible and EPR spectroscopy. All mutated subunits, especially mutants of conserved cysteines, contained lower amounts of non-heme iron than wild-type. The subunits of three non-conserved cysteine residues (C61, C104, and C113) mutated to Ser and a histidine residue (H92) mutated to Ala exhibited essentially the same spectroscopic properties as those of the wild-type subunit. In contrast, mutation of the four conserved cysteine residues (C96, C101, C137, and C141) to Ser or Ala considerably altered the UV-visible and EPR spectra from the wild-type subunit. These results indicate that the four conserved cysteine residues coordinate the [2Fe-2S] cluster in the P. denitrificans 25 kDa subunit.

Amino Acids↗
PubMed1994

Properties of the iron-sulfur center in the 25-kilodalton subunit of the proton-translocating NADH-quinone oxidoreductase of Paracoccus denitrificans.

The 25-kDa subunit of the proton-translocating NADH-quinone oxidoreductase (NDH-1) of Paracoccus denitrificans has been expressed in Escherichia coli and purified to homogeneity. EPR studies of the reduced recombinant protein indicated that the expressed subunit contains a single [2Fe-2S] cluster (Yano, T., Sled', V. D., Ohnishi, T., and Yagi, T. (1994) Biochemistry 33, 494-499). In this report, the electronic, magnetic, and vibrational properties of the [2Fe-2S]2+,+ center have been investigated by the combination of absorption, circular dichroism, variable-temperature magnetic circular dichroism, electron paramagnetic resonance, and resonance Raman spectroscopies and compared with a range of simple [2Fe-2S]-containing proteins. The results are consistent with coordination by two cysteinyl residues at both the reducible and nonreducible iron sites and reveal a striking similarity between the properties of the [2Fe-2S] cluster in the P. denitrificans NDH-1 25-kDa subunit and those of the subclass of ferredoxin-type [2Fe-2S] centers typified by Clostridium pasteurianum 2Fe ferredoxin. The four cyteines residues involved in cluster ligation in these proteins have been tentatively identified based on sequence homology considerations.

Amino Acid Sequence↗
PubMed1994

Inhibition of growth of OV-1063 human epithelial ovarian cancer xenografts in nude mice by treatment with luteinizing hormone-releasing hormone antagonist SB-75.

Female athymic nude mice bearing xenografts of OV-1063 human epithelial ovarian cancer cell line were treated with potent luteinizing hormone (LH)-releasing hormone (LH-RH) antagonist SB-75 (Cetrorelix; [Ac-D-Nal(2)1, D-Phe(4 CI)2, D-Pal(3)3, D-Cit6, D-Ala10]LH-RH in which Ac-D-Nal(2) = N-acetyl-3-(2-naphthyl)-D-alanine, D-Phe(4CI) = 4-chloro-D-phenylalanine, D-Pal(3) = 3-(3-pyridyl)-D-alanine, and D-Cit = D-Citrulline) or with the agonist [D-Trp6]LH-RH. In the first experiment, SB-75 and [D-Trp6]LH-RH were administered in the form of microcapsules releasing 60 and 25 micrograms/day, respectively. In the second study, the analogs were given by daily s.c. injections in doses of 100 micrograms/day. In both experiments, tumor growth, as measured by reduction in tumor volume, percentage change in tumor volume, tumor burden, and increase in tumor doubling time, was significantly inhibited by treatment with SB-75 but not with [D-Trp6]LH-RH. Uterine and ovarian weights were reduced and serum LH levels decreased by administration of either analog. Chronic treatment with SB-75 greatly reduced the concentration of receptors for epidermal growth factor and insulin-like growth factor I in tumor cell membranes, a phenomenon that might be related to tumor growth inhibition. It is possible that the antitumoral effects of SB-75 on OV-1063 ovarian cancers are exerted not only through the suppression of the pituitary-gonadal axis, but also directly. In view of its strong inhibitory effect on the growth of OV-1063 ovarian cancers in vivo, the potent LH-RH antagonist SB-75 might be considered for possible hormonal therapy of advanced epithelial ovarian carcinoma.

Animals↗
PubMed1994

Mutations in the coding region of c-MYC in AIDS-associated and other aggressive lymphomas.

Our previous studies of the translocated MYC gene in Burkitt's lymphoma showed the existence of clustered somatic mutations located in the transcriptional activation domain. We now report that aggressive lymphomas arising in the acquired immunodeficiency syndrome (AIDS) contain similar mutations and that the presence of mutations is correlated with the rearrangement of the oncogene. Mutations were also found in other de novo non-AIDS, non-Burkitt's aggressive lymphomas with MYC rearrangements. An unusual asparagine to serine mutation at codon 11 was identified in several transformed follicular lymphomas without MYC rearrangement but not in normal tissues from patients with this mutation. These findings indicate that AIDS-associated and other de novo aggressive lymphomas with the MYC gene rearrangement are subject to the same mutation and selection process that affects Burkitt's lymphomas.

Amino Acid Sequence↗
PubMed1994

Additive effects of cepharanthin in CDDP/hyperthermia combination therapy against transplantable human esophageal cancer in nude mice.

PURPOSE: Additive effects of cepharanthin in CDDP/hyperthermia combination therapy were evaluated. METHODS AND MATERIALS: Nude mice bearing a transplantable human esophageal cancer (ES0-2), classified histologically as a moderately differentiated squamous cell carcinoma, were treated with cepharanthin (20 mg/kg IP) in addition to cis-diamminedichloroplatinum(II) (CDDP; 4 mg/kg IP) and/or hyperthermia at 42 degrees C for 30 min, to determine the additive effects of cepharanthin. Furthermore, effects of cepharanthin on intratumoral concentration of CDDP were evaluated. RESULTS: Cepharanthin itself did not have an anti-tumor effect. This agent did not enhance the anti-tumor effect of CDDP alone, but enhanced the anti-tumor effects of both 42 degrees C hyperthermia alone, and combination therapy with CDDP and 42 degrees C hyperthermia. The concentration of CDDP in the tumors treated by 42 degrees C hyperthermia was slightly higher than in nonheated tumors. Cepharanthin did not affect the intratumoral concentration of CDDP, irrespective of whether hyperthermia was applied. CONCLUSION: Cepharanthin enhanced the effect of CDDP/hyperthermia combination therapy through thermoenhancing effect.

Alkaloids↗
PubMed1994

Inhibition of growth of MKN45 human gastric-carcinoma xenografts in nude mice by treatment with bombesin/gastrin-releasing-peptide antagonist (RC-3095) and somatostatin analogue RC-160.

Nude mice bearing xenografts of the gastrin-responsive human gastric carcinoma MKN45 cell line were treated for 4 to 5 weeks with bombesin/gastrin-releasing-peptide(GRP) antagonist (RC-3095), somatostatin analogues RC-160 and SMS 201-995, or the combination of RC-3095 and RC-160. Tumor volumes and weights were reduced significantly to a similar extent by RC-160 and SMS 201-995, administered by daily s.c. injections at a dose of 100 micrograms/day. Bombesin/GRP antagonist RC-3095, given s.c. at a dose of 20 micrograms/day, had the greatest inhibitory effect on tumor growth. The combination of RC-3095 with RC-160 did not further potentiate the suppression of tumor growth. Histologically, the number of mitotic cels decreased significantly in the groups treated with RC-160 or the combination of RC-3095 with RC-160. Serum gastrin levels were significantly diminished in all treated groups. Therapy with RC-160 or the combination also significantly decreased levels of serum growth hormone. Receptor assays on tumor membranes showed that bombesin was bound to 2 classes of receptor sites, one with high affinity and low capacity, the other with low affinity and high capacity. Binding sites for epidermal growth factor (EGF) were down-regulated in tumor cells after treatment with RC-3095, RC-160 or the combination of RC-3095 with RC-160. In studies in vitro, both RC-160 and RC-3095 significantly inhibited the proliferation of MKN45 cells in culture as measured by cell number. These data demonstrate, for the first time, that the growth of human gastric cancer in nude mice can be inhibited not only by somatostatin analogues, but also by administration of modern bombesin/GRP antagonists, such as RC-3095.

Adenocarcinoma↗
PubMed1994

Inhibition of human epithelial ovarian cancer cell growth in vitro by agonistic and antagonistic analogues of luteinizing hormone-releasing hormone.

In this study, we investigated the effects of luteinizing hormone-releasing hormone (LH-RH) agonist [D-Trp6]LH-RH, LH-RH antagonist [Ac-D-Nal(2)1,D-Phe(pCl)2,D-Pal(3)3,D-Cit6,D-Ala10]LH-RH (SB-75), and estradiol on the growth of human epithelial ovarian cancer cell line OV-1063. Cells were cultured under estrogen-deprived conditions. Estradiol inhibited cell proliferation, as measured by cell number at 10(-9)-10(-7) M and [3H]thymidine incorporation into DNA at 10(-13)-10(-8) M. Both LH-RH analogs inhibited cell growth dose dependently in the range 10(-8)-10(-5) M, but SB-75 induced a greater growth inhibition than [D-Trp6]LH-RH. In OV-1063 cells, 125I-labeled [D-Trp6]LH-RH was bound to one class of specific, saturable binding sites with high affinity (Kd = 1.4 +/- 0.3 nM) and low capacity (4000 binding sites per cell). 125I-labeled [D-Trp6]LH-RH could be displaced by unlabeled [D-Trp6]LH-RH and SB-75, suggesting that both analogs are bound to the same receptor on OV-1063 cells. Ligand binding was dependent on time and temperature. Receptor internalization assay showed that the ligand-receptor complex was internalized at 37 degrees C, which indicates the presence of biologically active LH-RH receptors on OV-1063 cells. These results suggest that estradiol and LH-RH analogs can suppress the growth of OV-1063 human epithelial ovarian cancer cells by a direct action and that the inhibitory effect of LH-RH analogs is mediated through the high-affinity LH-RH receptors.

Cell Division↗
PubMed1994

Inhibitory effect of bombesin/gastrin-releasing peptide antagonist RC-3095 and luteinizing hormone-releasing hormone antagonist SB-75 on the growth of MCF-7 MIII human breast cancer xenografts in athymic nude mice.

BACKGROUND: The results of several clinical trials using various luteinizing hormone-releasing hormone agonists for treatment of advanced breast cancer are encouraging. However, only about 30% of breast cancers are estrogen-dependent and can be treated by hormonal manipulation. New therapeutic approaches combining estrogen ablation therapy with other compounds must be explored. Various studies suggest that bombesin or gastrin-releasing peptide acts as an autocrine growth factor and may play a role in the initiation and progression of some cancers, including that of the breast. METHODS: Female athymic nude mice bearing xenografts of the MCF-7 MIII human breast cancer cell line were treated for 7 weeks with bombesin/gastrin-releasing peptide antagonist (D-Tpi6, Leu13 psi[CH2NH]-Leu14) bombesin(6-14) (RC-3095) injected subcutaneously daily at a dose of 20 micrograms and luteinizing hormone-releasing hormone antagonist SB-75 (Cetrorelix) administered biweekly in the form of microgranules releasing 45 micrograms/day. RESULTS: After 2 weeks of treatment, a significant inhibition of tumor volume was observed in the groups treated with RC-3095 alone or in combination with SB-75 but not in those treated with SB-75 as a single agent. After 7 weeks, tumor growth as measured by tumor volume and percentage changes in tumor volume and tumor weight was greatly inhibited in all of the treated groups. Uterine and ovarian weights were reduced and serum luteinizing hormone levels decreased by administration of SB-75 alone or in combination with RC-3095. Histologically, a significant decrease in argyrophilic nucleolar organizer region count in tumor cell nuclei was observed in all of the treated groups, indicating a lower proliferation of these cells. High-affinity binding sites for bombesin were detected in cultured MCF-7 MIII cells. Chronic treatment with RC-3095 caused a significant down-regulation of epidermal growth factor receptors in tumor cell membranes, which might be related to tumor inhibition. In studies in vitro, SB-75 inhibited proliferation of MCF-7 cells in culture but not proliferation of MCF-7 MIII cells. CONCLUSIONS: Because previously we demonstrated that RC-3095 inhibits the proliferation of MCF-7 MIII cells in vitro, it appears that the major antitumoral effect of RC-3095 on the MCF-7 MIII cancer line is direct, whereas that of SB-75 is indirect, and that it is mediated by suppression of the pituitary-gonadal axis. In view of its immediate and powerful inhibitory effect on MCF-7 MIII tumors, bombesin/gastrin-releasing peptide antagonist RC-3095 might be considered as a possible new agent for the treatment of breast cancer.

Animals↗
PubMed1994

Expression of the 25-kilodalton iron-sulfur subunit of the energy-transducing NADH-ubiquinone oxidoreductase of Paracoccus denitrificans.

The energy-transducing NADH-ubiquinone (Q) oxidoreductase of Paracoccus denitrificans is composed of 14 dissimilar subunits and contains at least four iron-sulfur clusters [Yagi, T. (1993) Biochim. Biophys. Acta 1141, 1-17]. The complete DNA sequence of the gene cluster encoding the energy-transducing NADH-Q oxidoreductase of P. denitrificans has been determined. This paper reports the expression of the 25-kilodalton (kDa) (NQO2) subunit of the P. denitrificans enzyme complex in Escherichia coli and the characterization of the iron-sulfur cluster bound to the expressed subunit. The 25-kDa subunit was expressed in the cytoplasmic phase but not in the membrane fraction of E. coli cells and then purified using an affinity nickel chelation column. The purified subunit contains 1.44 mol of non-heme iron and 1.33 mol of acid-labile sulfide/mol of subunit. EPR analysis of the reduced form of this subunit indicates that the expressed subunit contains a single binuclear [2Fe-2S] cluster. This cluster exhibits a spectrum of rhombic symmetry with g values of gx,y,z = 1.913, 1.942, and 1.996, which is very similar to the spectrum of the [2Fe-2S] cluster in the resolved flavoprotein II subfraction (subunit 24 + 9 kDa) of bovine heart complex I [Ragan, C. I., Galante, Y. M., Hatefi, Y., & Ohnishi, T. (1982) Biochemistry 21, 590-594; Ohnishi, T., Ragan, C. I., & Hatefi, Y. (1985) J. Biol. Chem. 260, 2782-2788]. The assignment of the binuclear iron-sulfur cluster of the 25-kDa subunit to an EPR-visible iron-sulfur cluster in the Paracoccus NADH-Q oxidoreductase in situ is discussed.

Amino Acid Sequence↗
PubMed1994

Resistance to the anti-proliferative effect of IL-1 on human melanoma cell line is associated with endogenous production of IL-1 and IL-6.

A human melanoma cell line (A375-6) became resistant to the anti-proliferative effect of human IL-1 after a long period of culture. Two stable resistant sub-clones were obtained, and the mechanism of the IL-1 resistance was investigated. Resistant cells, but not sensitive cells, appeared to produce constitutively IL-1 activity. The activity was neutralized by anti-IL-1 alpha antibody but not by anti-IL-1 beta antibody. Resistant cells expressed IL-1 alpha but not IL-1 beta mRNA. Therefore, the resistant cells appeared to produce IL-1 alpha mRNA for IL-1 receptor antagonist (IL-1Ra) was not detected in resistant cells, indicating that the resistance is not attributable to IL-1Ra. These resistant cells were also resistant to the anti-proliferative effect of human IL-6, but not to that of human TNF. Resistant cells appeared to produce constitutively IL-6 more than sensitive cells, and IL-6 production both in sensitive and in resistant cells was augmented by exogenous IL-1. Furthermore, constitutive production of IL-6 in resistant cells was inhibited by IL-1Ra. Type I IL-1 receptor (IL-1R) mRNA was expressed equally in resistant and sensitive cells. These data indicate that the resistance is not the result of loss of functional IL-1R and that IL-1 induces IL-6 in an autocrine manner. It is, therefore, conceivable that endogenous IL-1 and IL-6 contribute to IL-1 resistance.

Cell Division↗