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Biomedical subjects

T Noguchi

Publications and source records attributed to T Noguchi.

At least 523 records · Page 29Linked to original sources

Hippocalcin: a calcium-binding protein of the EF-hand superfamily dominantly expressed in the hippocampus.

Hippocalcin is a recently identified Ca(2+)-binding protein with three EF-hand structures, dominantly expressed in the hippocampal pyramidal layer. The complete amino acid sequence of hippocalcin deduced from the cDNA is composed of 195 residues, has a calculated molecular mass of 22,574 daltons, and has a striking sequence homology to those of visinin, recoverin, S-modulin, neurocalcins and neural visinin-like proteins. Hippocalcin binds 3 mol of Ca2+ per mol of protein at submicromolar Ca2+ levels, and associates the plasma membrane in a Ca(2+)-dependent manner. Hippocalcin is myristoylated at its NH2-terminal glycine residue, and this modification is a key event in terms of its membrane-association property.

Amino Acid Sequence↗

A 15N-1H nuclear magnetic resonance study on the interaction between isoleucine tRNA and isoleucyl-tRNA synthetase from Escherichia coli.

Imino 15N and 1H resonances of Escherichia coli tRNA(lIle) were observed in the absence and presence of E coli isoleucyl-tRNA synthetase. Upon complex formation of tRNA(lIle) with isoleucyl-tRNA synthetase, some imino 15N-1H resonances disappeared, and some others were significantly broadened and/or shifted in the 1H chemical shift, while the others were observed at the same 15N-1H chemical shifts. It was indicated that the binding of tRNA(lIle) with IleRS affect the following four regions: the anticodon stem, the junction of the acceptor and T stems, the middle of the D stem, and the region where the tertiary base pair connects the T, D, and extra loops. This result is consistent with those of chemical footprinting and site-directed mutagenesis studies. Taken together, these three independent results reveal the recognition mechanism of tRNA(lIle) by IleRS: IleRS recognizes all the identity determinants distributed throughout the tRNA(lIle) molecule, which induces changes in the secondary and tertiary structures of tRNA(lIle).

Base Sequence↗

Estrogen productivity of endometrium and endometrial cancer tissue; influence of aromatase on proliferation of endometrial cancer cells.

Aromatase, estrone (E1) sulfatase and E1 sulfotransferase activities were examined in endometrium and endometrial cancer tissue preparations. Aromatase and E1 sulfatase activities in endometrial cancer tissues were found to be significantly higher than in normal endometrial tissues. However, E1 sulfotransferase activity did not differ between benign and malignant tissue. We also examined the effect of testosterone (T) on aromatase activity and tritiated thymidine uptake (DNA synthesis) in various cultured cervical or corpus endometrial cancer cell lines (OMC-4, HHUA, Ishikawa, HEC-59). The results demonstrated that only the HEC-59 cell line had high aromatase activity and increased its DNA synthesis in response to T. This increase of DNA synthesis by T was not suppressed by simultaneous addition of cyproterone acetate, but was by tamoxifen. These data suggest that in situ estrogen production in endometrial cancer tissue is biologically important and that aromatase in cancer cells may contribute partially to cell proliferation if androgen substrate is provided.

Aromatase↗

Relationship between aromatase activity and steroid receptor levels in ovarian tumors from postmenopausal women.

Aromatase activity, as well as steroid receptors, exists in nonfunctional ovarian tumors. Steroid receptor status has been reported to be related to prognosis in ovarian cancer patients. We determined aromatase activity and progesterone receptor (PR) and estrogen receptor (ER) levels in 43 ovarian tumors obtained from postmenopausal women. Aromatase activity was detected in 35 tumors (81%), PR in 21 tumors (49%) and ER in 13 tumors (30%). Eighty-three percent (10/12) of mucinous cystadenoma tissues showed positive PR with high aromatase activity, while 93% (13/14) of malignant tumors showed negative PR and low aromatase activity. Aromatase activity was detected in 95% (20/21) of PR-positive tumors, being greater than in PR-negative tumors (P < 0.002). There was a positive correlation between aromatase activity and PR (rs = 0.49, P < 0.001). However, there was no correlation between aromatase activity and ER. In 17 patients (43%), the serum estradiol level was higher than 30 pg/ml and there was a positive correlation among estradiol, estrone, androstenedione and testosterone. However, serum steroid levels were not correlated with aromatase activity, PR or ER. Aminoglutethimide inhibited aromatase activity of benign and malignant ovarian tumors, uterine myoma, choriocarcinoma cells and purified human placental P-450arom in a similar manner. These results suggest that aromatase activity is correlated with PR in ovarian tumors of postmenopausal women. In addition to steroid receptor status, aromatase activity may be a useful prognostic factor in ovarian cancers.

Adult↗

Growth suppression of MCF-7 human breast cancer cells by aromatase inhibitors: a new system for aromatase inhibitor screening.

In our previous study we found that MCF-7 cells possess aromatase activity and stimulate estrogen receptor-mediated growth. The pathways through which androgens are converted to estrogens by aromatase and estrogens interact with estrogen receptors contribute significantly to growth stimulation. The administration of aromatase inhibitor results in suppression of growth stimulation by androgens. This system enabled us to assess directly the biological activities of aromatase inhibitors. Aromatase activity was inhibited in a dose-dependent manner by the addition of aminoglutethimide and CGS 16949A, competitive inhibitors, and of 14 alpha-hydroxy-4-androstene-3,6,17-trione and 4-hydroxy-androstenedione, mechanism-based inhibitors. After preincubation with mechanism-based inhibitors, aromatase activity was significantly suppressed, whereas after preincubation with competitive inhibitors, it was adversely increased. These effects were concentration- and time-dependent. Preincubation with competitive inhibitors resulted in augmentation of subsequent androgen stimulation of thymidine incorporation, while preincubation with mechanism-based inhibitors resulted in diminished stimulation by subsequent androgen administration. These results suggest that in MCF-7 cells competitive inhibitors adversely induce aromatase and accelerate the subsequent androgen stimulation of DNA synthesis. Suicide inhibitors are more effective than competitive inhibitors. This system will be useful for aromatase inhibitor screening.

Aminoglutethimide↗

Effect of protein nutrition on the mRNA content of insulin-like growth factor-binding protein-1 in liver and kidney of rats.

Effect of quantity and nutritional quality of dietary proteins on the content of mRNA of insulin-like growth factor-binding protein-1 (IGFBP-1) was studied in rat liver and kidney. IGFBP-1 mRNA content per unit RNA increased in liver and kidney of rats fed on a protein-free diet and in those of fasted rats compared with that in the rats fed on a casein diet. When rats were given a gluten diet for 7 d, IGFBP-1 mRNA content in liver did not change significantly but that in kidney increased considerably compared with that in those organs of the rats fed on the casein diet. Because IGFBP-1 mRNA has been demonstrated both in liver parenchymal and non-parenchymal cells (Takenaka et al. 1991), the effect of the protein-free diet on these two types of cells has been studied. An increase in IGFBP-1 mRNA content under protein deprivation was observed in both liver parenchymal and non-parenchymal cells, suggesting that these two types of cells are regulated in a similar mode as far as IGFBP-1 mRNA content is concerned. The physiological and nutritional significance of the previously stated results on protein anabolism are discussed when considered together with our previous observations on the plasma concentrations of IGF-1 (Takahashi et al. 1990) and IGFBP (Umezawa et al. 1991) and insulin-like growth factor-1 mRNA content in liver (Miura et al. 1991).

Animals↗

Increased plasma level of interleukin-6 in disseminated intravascular coagulation.

Plasma interleukin-6 (IL-6) was higher in patients with disseminated intravascular coagulation (DIC) than in those without DIC. Levels of IL-1 beta and TNF alpha were also significantly higher in patients with DIC. Plasma IL-6 was highest in patients with underlying sepsis and was also high in those with advanced solid cancer. Levels were high in some patients with acute promyelocytic leukaemia and were significantly higher in patients with organ failure than in those without this complication. Plasma IL-6 was higher in DIC patients showing a poor response to therapy than in those with a good response. Incubation with IL-6 caused significant increases in tissue factor activity in mononuclear cells and release of plasminogen activator-1 antigen from human umbilical vein endothelial cells. As increases in IL-6 might give rise to hypercoagulable and hypofibrinolytic states, this may be a cause of DIC and be related to prognosis and organ failure.

Disseminated Intravascular Coagulation↗

Presence of tetrodotoxin and tetrodotoxin-producing bacteria in freshwater sediments.

The occurrence of tetrodotoxin (TTX) in sediment from Lake Suwa, Japan, was confirmed by a tissue culture assay, high-performance liquid chromatography, and gas chromatography-mass spectrometry. Altogether, 17 TTX-producing bacteria belonging to five genera were isolated from Lake Suwa and Pond Inokasira. Our results indicate that TTX and TTX-producing bacteria occur even in freshwater environments.

Journal Article↗

Structure, mapping, and expression of erp, a growth factor-inducible gene encoding a nontransmembrane protein tyrosine phosphatase, and effect of ERP on cell growth.

We have characterized a growth factor-inducible gene, erp, and demonstrated that it encodes a 367-amino-acid nontransmembrane tyrosine phosphatase protein with significant similarity to the vaccinia virus H1 protein. Immunoprecipitation analyses show that the erp protein, ERP, is rapidly induced following serum stimulation of quiescent fibroblasts. ERP has been expressed as a fusion protein with glutathione S-transferase and shown to have tyrosine as well as serine protein phosphatase activity. The enzymatic activity of ERP depends on the presence of reducing agents such as dithiothreitol, and its tyrosine phosphatase activity is inhibited by sodium vanadate, a potent inhibitor of protein tyrosine phosphatases. The number of stable NIH 3T3 clones obtained after transfection with a vector expressing the complete ERP protein is reduced more than 90% compared with that after transfection with a vector expressing a mutated inactive ERP protein. The remaining ERP-expressing clones present a significant increase in the proportion of bi- and multinucleated cells and a decrease in proliferation rate. Studies on the genomic structure reveal that the erp transcription unit is 2.8 kbp long and split into four exons. The erp gene maps to the 17A2-17C region of the murine genome. Our results demonstrate that the protein product of the immediate-early gene erp has a negative effect on cell proliferation.

3T3 Cells↗

Intraportal US with 20-MHz and 30-MHz scanning catheters. Work in progress.

Intraportal ultrasonography (US) with scanning catheters was attempted in nine patients with various biliary tract diseases, to evaluate the portal venous system for tumor invasion. Intraportal US was performed successfully in seven patients. Intraportal US scans were compared with images obtained with arterial portography, direct portography, and intraoperative US. Intraportal and intraoperative US revealed cancer invasion into the wall of the portal venous trunk in two patients. Negative findings for cancer invasion with intraportal US were verified with intraoperative US and laparoscopic examination in five cases. Arterial portography was unable to delineate the fine portal venous wall configuration in six of the seven patients, and direct portographic images were not fully diagnostic of tumor invasion in three cases. The improved detection of tumor invasion to the portal venous system with intraportal US was helpful in determining the appropriate treatment for biliary tract disease in these patients.

Adult↗

The stability of a novel carbapenem antibiotic, meropenem (SM-7338), in a solid state formulation for injection.

A formulation of meropenem, a novel carbapenem antibiotic for injection, was developed as a vial filled with a mixture of meropenem and dried sodium carbonate. During the design phase, we studied the effect of water in the formulation on the stability of meropenem in the solid state. Meropenem is obtained as trihydrate, whose moisture content is 12.35% and is nonhygroscopic. Dehydrated meropenem, whose moisture content was 3.4%, took up moisture quickly even under low humidity (33% RH). Also, the chemical stability of dehydrated meropenem was poor compared with that of untreated meropenem, which is quite stable. Degradation of meropenem by free water was considered as a possible cause of the poor stability. Degradation of meropenem due to liberation of its crystal water to free water was also observed when meropenem was micronized by pneumatic pulverization. Crystal water of meropenem was found to stay bound and to be almost inert in the formulation. Thus, meropenem injection formulation is stable for long time at room temperature.

Chemistry, Pharmaceutical↗

The influence of endocrine factors on the serum concentrations of insulin-like growth factor-I (IGF-I) and IGF-binding proteins.

Serum insulin-like growth factor-I (IGF-I) levels in lit (isolated GH deficiency), dw (panhypopituitarism), hyt (hypothyroidism) and cog (congenital goiter) mutant mice were found to be significantly lower than in control mice. In addition, liver and kidney IGF-I concentrations in mutants were also found to be significantly reduced compared with controls. These differences in IGF-I concentration were not observed in pg (genetic IGF receptor or post-receptor defect?) mice. These results indicated that serum IGF-I production is induced by thyroid hormones as well as by GH. Western blot analysis of serum IGF-binding protein (IGFBP) fractions revealed the following differences among the five mutants: the triplet of IGFBP-3 (42, 45 and 49 kDa) and IGFBP-4 (24 kDa) levels were significantly reduced. IGFBP-2 (32 kDa) levels were also reduced in the lit, hyt and cog mice, although the level in serum of dw mice was found to be greatly elevated. No differences in serum IGFBP levels were found in the pg mouse. Consequently, the ratio of IGFBP-3%: IGFBP-2% (the percentage of IGFBP-3 fraction of total IGFBP (IGFBP-3%) divided by that of IGFBP-2 (IGFBP-2%)) was decreased in GH-deficient mice but increased in hypothyroid mice, suggesting that IGFBP-3 and IGFBP-2 production in the liver is induced by GH and thyroid hormones respectively.

Animals↗

Hereditary complete thyroxine-binding globulin deficiency: identification by T3 resin uptake test and DNA analysis.

Complete thyroxine-binding globulin deficiency (TBG-CD) was uncovered in a subject receiving a comprehensive health examination. The subject had an abnormally high T3 resin uptake. A family study showed that the TBG abnormality had been inherited by X-chromosome linkage. Genetic analysis revealed single nucleotide deletion, common among Japanese with TBG-CD, from the allele specific amplification of the TBG genes of the family.

DNA Mutational Analysis↗

Vestibular neuronitis: epidemiological survey by questionnaire in Japan.

An epidemiological survey on vestibular neuronitis in Japan was conducted by means of a questionnaire filled in by major neuro-otology clinics (otolaryngologists) during 1988-1990 (3 years). The diagnostic criteria of vestibular neuronitis settled on in 1986 by the Standardization Committee of the Japan Society of Equilibrium Research were applied. Gross analysis of questionnaire answers showed that i) there was no sexual difference, ii) the peak of age distribution was between 40-50 years, iii) about 30% of all cases had had common colds prior to the disease, the rate being highest among children below 10 years, iv) disappearance of positional and positioning nystagmus appeared in about 60% of all cases within 3 months, and that v) caloric CP was observed in about half of the cases at the follow-up test. Progress was not as favorable when compared to previous studies.

Adolescent↗

Studies on cell growth stimulating substances of low molecular weight. Part 2. Exfoliazone and lavanducyanin, potent growth promoting substances of rat liver cell line, RLN-8, produced by Streptomyces exfoliatus and Streptomyces aeriouvifer.

Exfoliazone and lavanducyanin isolated from Streptomyces exfoliatus BT-38 and Streptomyces aeriouvifer CL-190, respectively, showed strong growth promoting activities to liver cell RLN-8 established from normal Donryu rat. When RLN-8 cells were cultured in Eagle's minimal essential medium containing 1% fetal bovine serum, exfoliazone significantly stimulated the growth of RLN-8 cells. However, no effect was observed under serum-free conditions. Effective dose of exfoliazone was at the range of 0.004-0.1 microgram/ml. Cell proliferation was confirmed by MTT assay and by the increases of cell number and DNA synthesis. Lavanducyanin also stimulated the growth of RLN-8 cells in the same medium. It showed growth promoting activity at lower concentrations than exfoliazone and the effective dose was at the range of 0.0001-0.06 microgram/ml. Analogous compounds of exfoliazone and lavanducyanin also promoted the growth of RLN-8 cells. In addition, exfoliazone and lavanducyanin enhanced the growth of NIH 3T3 and T601 cells. These results indicate that exfoliazone, lavanducyanin and their related compounds seem to be a new type of growth promoting substances with low molecular weight produced by microorganisms, and that they can partially substitute for functions of serum. Since 12-O-tetradecanoylphorbol-13-acetate (TPA) did not show the growth promoting activities under the same conditions, the action mechanism(s) of exfoliazone and lavanducyanin are different from that of TPA.

Animals↗

[The alteration of right ventricular performance in patients with pneumonectomy and pulmonary lobectomy].

Elevation of right ventricular afterload associated with the decrease of pulmonary vascular bed is a serious problem immediately after pneumonectomy. We studied the alteration of right ventricular performance and hemodynamics by using an RVEF thermodilution catheter, and compared them among 6 patients after pneumonectomy and 8 patients after pulmonary lobectomy. Results demonstrate that 1) PVRI increased significantly immediately after the pneumonectomy, and recovered to the preoperative level on the 1st postoperative day. On the other hand, in the lobectomy patients, PVRI showed no significant change throughout the operation, because the decrease of pulmonary vascular bed after pneumonectomy was larger than that after pulmonary lobectomy. 2) In the pneumonectomy group, CI and RVEF were preserved and right ventricular works (RCWI and RSWI) increased in spite of an increase of right ventricular afterload after the ligation of the pulmonary artery. We considered that immediately after pneumonectomy the increase of right ventricular afterload associated with decreased pulmonary vascular bed was compensated by increasing right ventricular work. 3) On the 1st postoperative day, CI and RVEF did not change, but mRAP decreased significantly, and PVRI and right ventricular works recovered to the preoperative level in the pneumonectomy patients. From the above results, we considered that after the pneumonectomy, increased right ventricular afterload was compensated by the decreased circulating blood volume.

Hemodynamics↗