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Biomedical subjects

K Ito

Publications and source records attributed to K Ito.

At least 19 recordsLinked to original sources
PubMed1992

Peculiar nuclear clearing composed of microfilaments in papillary carcinoma of the thyroid.

BACKGROUND: Papillary carcinoma of the thyroid frequently occurs in young women. Four cases of papillary carcinoma were found in women in their 20s, and the disease was characterized by unusual morphologic and clinical features. METHODS: Four cases were analyzed clinically, grossly, microscopically, ultrastructurally, and immunohistochemically and compared with control cases of papillary carcinoma. RESULTS: The tumors histologically showed various appearances with trabecular, solid cribriform, follicular, and papillary patterns. A striking finding was that stratified cancer cell nests with prominent nuclear clearings were scattered in the tumors. Ultrastructurally, the nuclear clearings were composed of fine thread-like fibrils, and they were bound unselectively to various antibodies against hormones and intermediate filaments. The four patients also had common clinicopathologic features as follows: they were all women in their 20s and their preoperative serum thyroglobulin levels were all normal despite the large size of their thyroid tumors. The tumors were grossly well encapsulated, and there was no lymph node metastasis, except in one patient who had only one positive node. CONCLUSIONS: The peculiar nuclear features were distinct from intranuclear cytoplasmic inclusions or ground-glass nuclei, and these have not been reported previously to the authors' knowledge in conventional thyroid neoplasms. These tumors might represent another subtype of papillary thyroid carcinoma.

Actin Cytoskeleton↗
PubMed1992

Adenosine A2 receptor antagonist facilitates the reversal of long-term potentiation (depotentiation) of evoked postsynaptic potentials but inhibits that of population spikes in hippocampal CA1 neurons.

The effects of the adenosine A2 receptor antagonist CP-66713 on the reversal of long-term potentiation (LTP) were studied in CA1 neurons of guinea pig hippocampal slices. Reduction of LTP (depotentiation, DP) was effected by delivering a train of low-frequency afferent stimuli (depotentiation stimulation, DPS) which was given 20 min after tetanus (100 Hz, 100 pulses). DPS (1 Hz, 1000 pulses) was applied during perfusion of CP-66713 (10 microM). In the presence of CP-66713, DPS reduced the potentiated component of the slope of the field EPSP (S-EPSP) and the amplitude of the population spike (A-PS) by 101.7% and 19.1% of the potentiated amount, respectively (mean, n = 8). The reduction of LTP of the S-EPSP was significantly larger than the control (68.5% (mean, n = 6)) while that of the A-PS was significantly smaller than the control (80.1% (mean, n = 6)). Based on these results, we conclude that the inhibition of DP in the EPSP, the facilitation of DP in the PS, and the consequent attenuation in the EPSP-PS relationship follow from activation of adenosine A2 receptors.

Animals↗
PubMed1992

Manganese-mediated oxidative damage of cellular and isolated DNA by isoniazid and related hydrazines: non-Fenton-type hydroxyl radical formation.

The mechanism by which hydrazines induce damage to cellular and isolated DNA in the presence of metal ions has been investigated by pulsed-field gel electrophoresis (PFGE), DNA sequencing methods, and the ESR spin-trapping technique. For the detection of single-strand breaks by PFGE, an experimental procedure with alkali treatment has been designed. Isoniazid, hydrazine, and phenylhydrazine induced DNA single- and double-strand breaks in cells pretreated with Mn(II), whereas iproniazid did not. With isolated 32P-DNA, isoniazid produced DNA damage in the presence of Cu(II), Mn(II), or Mn(III). Iproniazid damage isolated DNA only in the presence of Cu(II). The Cu(II)-mediated DNA damage by isoniazid or iproniazid is due to active oxygen species other than hydroxyl free radical (.OH), presumably the Cu(I)-peroxide complex. Cleavage of isolated DNA by isoniazid plus Mn(II) occurred without marked site specificity. The DNA damage was inhibited by .OH scavengers and superoxide dismutase (SOD) but not by catalase, suggesting the involvement of .OH formed via O2- but not via H2O2. Consistently, in ESR experiments .OH formation was observed during Mn(II)-catalyzed autoxidation of isoniazid, and the .OH formation was inhibited by SOD, but not by catalase. Iproniazid plus Mn(II) produced no or little .OH. We propose a reaction mechanism for the .OH formation without a H2O2 intermediate during manganese-catalyzed autoxidation of hydrazine. The present and previous data raise the possibility that hydrazines plus Mn(II)-induced cellular DNA damage may occur, at least in part, through the non-Fenton-type reaction.

Autoradiography↗
PubMed1992

In vitro catalysis of oxidative folding of disulfide-bonded proteins by the Escherichia coli dsbA (ppfA) gene product.

It was shown previously that the Escherichia coli gene ppfA (dsbA) encodes a periplasmic protein, and its inactivation leads to a deficiency in disulfide bond formation of envelope proteins (Kamitani, S., Akiyama, Y., and Ito, K. (1992) EMBO J. 11, 57-62; Bardwell, J. C. A., McGovern, K., and Beckwith, J. (1991) Cell 67, 581-589). The DsbA/PpfA protein was overproduced, purified, and examined for its activities in vitro. Its abundance in a wild-type cell was estimated to be about 850 molecules which probably exist as homodimers as suggested by size exclusion chromatography. Purified DsbA markedly stimulated disulfide bond formation of E. coli alkaline phosphatase, either in vitro synthesized or purified and denatured, as well as of reduced bovine ribonuclease A. The DsbA-catalyzed rapid disulfide bond formation occurred after a lag period which appeared to be determined by the redox state of the reaction mixture and concentration of DsbA. Inclusion of higher concentrations of oxidized glutathione or DsbA shortened the lag period. We propose that DsbA, which proved to directly catalyze disulfide bond formation, may also have a role in maintaining the bacterial periplasm oxidative.

Alkaline Phosphatase↗
PubMed1992

[Change in serum G-CSF levels in patients with Graves' disease by treatment with methimazole].

We evaluated the determination of serum G-CSF in the diagnosis of granulocytopenia due to methimazole (MMI) in 54 patients with Graves' disease, while they were being treated with MMI, by way of measuring WBC counts and serum levels of G-CSF, thyroid hormones, IgE, and interleukin-2. Serum TSH was measured by immunoradiometric assay, serum G-CSF was done by enzyme immunoassay, thyroid hormones and IgE were done by radioimmunoassay, and serum Interleukin-2 was done by enzyme-linked immunosorbent assay. The population whose G-CSF levels were higher than the minimum detectable level (30pg/ml) was 6 (30%) in normal subjects, 4 (22%) in patients with untreated Graves' disease, 2 (12%) in patients with treated euthyroid Graves' disease, 3 (23%) in patients with Graves' disease who had gone through agranulocytosis, and 2 (33%) in patients with Graves' disease complicated with granulocytopenia. There was no significant change in WBC counts for 4 weeks, but there was a significant difference between WBC counts before treatment and those at 8 weeks after treatment. We observed no significant change of serum G-CSF levels in patients with Graves' disease under treatment. However, there were significantly high levels of serum G-CSF and significantly low counts of WBC in patients with Graves' disease complicated with granulocytopenia induced by MMI, compared with those in normal subjects, patients with untreated Graves' disease, patients with treated euthyroid Graves' disease, and patients with euthyroid Graves' disease who had gone through agranulocytosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Effects of the chaperonin GroE on the refolding of tryptophanase from Escherichia coli. Refolding is enhanced in the presence of ADP.

The refolding of the tetrameric enzyme tryptophanase was facilitated by the chaperonin GroE. Maximum refolding yield of tryptophanase molecules (about 80%) was attained in the presence of a 15-fold excess of GroE 21-mer over tryptophanase monomer. The GroEL subunit was required for this improvement in refolding yield, whereas the GroES subunit was not. Light scattering experiments of the refolding reaction revealed that GroE bound to tryptophanase folding intermediates and suppressed their aggregation. The presence of ATP was required for the efficient dissociation of tryptophanase from GroEL. However, our experiments indicated that tryptophanase dissociated readily from GroEL in the presence of not only ATP, but also in the presence of non-hydrolyzable ATP analogues such as ATP gamma S (adenosine 5'-O-(3-thiotriphosphate)) and AMP-PNP (adenyl-5'-yl imidodiphosphate) as well. Surprisingly, the release of tryptophanase from GroEL was facilitated in the presence of ADP as well. We concluded that the binding of nucleotides such as ATP and ADP changed the conformation of GroEL and facilitated the dissociation of tryptophanase molecules. The conformation formed in the presence of ADP was distinct from the conformation formed in the presence of ATP, as shown by the selective dissociation of various folding proteins from the two conformations.

Adenine Nucleotides↗
PubMed1992

Energy aspects of oil/water partition leading to the novel hydrophobic parameters for the analysis of quantitative structure-activity relationships.

Partition properties, that is partition coefficients and enthalpies (delta Hp degree) and entropies (delta Sp degree) of partition, have been measured for 50 benzoic acids in the 1-octanol/water system, and their role in QSAR (quantitative structure-activity relationship) analysis examined. The novel hydrophobic parameters have been introduced as a result of the separation of the Gibbs free energy term into the corresponding enthalpy and entropy terms. Application of these novel parameters to some available biological activity data supported the usefulness of these parameters in QSAR analysis. Relative contributions of the enthalpy and entropy terms are also discussed.

Benzoates↗
PubMed1992

Analysis of thyroid carcinoma based on material registered in Japan during 1977-1986 with special reference to predominance of papillary type.

BACKGROUND: As geographic differences have been observed in the characteristics of thyroid carcinoma, an analysis was made on thyroid carcinoma in the iodine rich country of Japan. METHODS: A total of 10,973 patients with histologically confirmed thyroid carcinoma registered in Japan from 1977-1986 were analyzed. Cases detected incidentally at autopsy and cases of nonepithelial tumor were excluded. This series included approximately 27% of all thyroid carcinoma cases in Japan. RESULTS AND CONCLUSIONS: Histologic distribution showed that papillary carcinoma accounted for 78.4% of cases, follicular carcinoma accounted for 17.2%, medullary carcinoma for 1.4%, squamous cell carcinoma for 0.3%, and anaplastic carcinoma for 2.7%. There is a tendency in Japan to diagnose papillary carcinoma as follicular carcinoma and to diagnose malignant lymphoma as anaplastic carcinoma. It was considered that the percentage of papillary carcinoma was higher and the percentage of follicular carcinoma and anaplastic carcinoma was lower than foregoing values. The characteristics of thyroid carcinoma in Japan were described, and the low incidence of nonpapillary carcinoma compared with papillary carcinoma was discussed in relation to iodine excess as an etiologic factor.

Adolescent↗
PubMed1992

Proliferative activity in thyroid tumors.

To clarify the proliferative activity of papillary thyroid carcinoma, the bromodeoxyuridine (BrdU) labeling index (LI) of 61 various thyroid tumors was investigated using an in vitro labeling technique and immunohistochemical staining with anti-BrdU monoclonal antibody. The mean LI (+/- standard deviation) of 31 papillary carcinomas, 12 adenomas, 10 adenomatous goiters, 3 follicular carcinomas, and 2 medullary carcinomas were 1.2% (+/- 1.3%), 0.6% (+/- 0.3%), 0.7% (+/- 0.6%), 1.5% (+/- 2.2%), and 0.7% (+/- 0.6%), respectively. The LI of the papillary carcinomas ranged from 0.1% to 4.6%, and approximately 66% of these showed less than a 1% similarity with almost all benign tumors. However, the LI of the two malignant lymphomas and the one anaplastic carcinoma were more than 13%. When the LI of the papillary carcinomas was compared with their various prognostic factors, there was no correlation with tumor size, nodal status, or morphologic features. However, the patients who were 50 years of age or older tended to have relatively high LI, and the LI of the papillary carcinomas correlated with patient age. According to these results, the biologic characteristics of papillary carcinomas vary with age and high proliferative activity may contribute to the poor prognosis of this tumor in elderly patients.

Adenoma↗
PubMed1992

Stem cell factor has histamine releasing activity in rat connective tissue-type mast cells.

Stem cell factor (SCF) was documented to be involved in the growth of mast cells controlled by fibroblasts. We tested the effect of recombinant rat SCF on degranulation from rat peritoneal mast cells (connective tissue-type mast cells: CTMC). SCF induced histamine release (approximately 20% of total histamine content) in a dose-dependent fashion. The release response was relatively rapid and reached a maximum within 5 min. The release showed total dependence on the presence of extracellular phosphatidylserine (PTS). These results reveal that SCF has histamine releasing activity in CTMC.

Animals↗
PubMed1992

Inhibition of IgE-mediated histamine release by myosin light chain kinase inhibitors.

Wortmannin, a specific inhibitor of myosin light chain kinase (MLCK) blocked IgE mediated histamine release from rat basophilic leukemia cell (RBL-2H3) and human basophils dose-dependently. Its IC50 was 20 nM for RBL-2H3 cells and 30 nM for human basophils. There was complete inhibition at the concentration of 1 microM. Wortmannin inhibited partially the A23187 induced histamine release from RBL-2H3 cells (40% inhibition at 1 microM). This inhibition was not accompanied by any significant effect on cytosolic free calcium concentration [( Ca2+]i). KT5926, another MLCK inhibitor, inhibited histamine release comparably with wortmannin and blocked to some degree the increase of [Ca2+]i in RBL-2H3 cells. Thus, the phosphorylation of myosin seems to be involved in signal transduction through Fc epsilon RI.

Alkaloids↗
PubMed1992

Comparison of the modes of action of a Vero toxin (a Shiga-like toxin) from Escherichia coli, of ricin, and of alpha-sarcin.

The modes of action of a Vero toxin (VT2 or Shiga-like toxin II) from Escherichia coli, of ricin, and of alpha-sarcin were compared. Elongation factor 1 (EF1) and GTP-dependent Phe-tRNA binding to ribosomes in the presence of poly(U) was inhibited by these three toxins, but EF1 and guanylyl (beta, gamma-methylene)-diphosphate-dependent Phe-tRNA binding was inhibited by alpha-sarcin only. EF1- and Phe-tRNA-dependent GTPase activity was inhibited by these toxins, but nonenzymatic binding of Phe-tRNA was not. The turnover rate of EF1 binding to ribosomes during Phe-tRNA binding was also decreased by these three toxins. The addition of EF1 recovered the inhibition of Phe-tRNA binding to ribosomes by VT2 and ricin but not by alpha-sarcin. The formation of and EF2- and GTP-dependent puromycin derivative of phenylalanine was inhibited slightly by the three toxins, indicating that translocation is not influenced significantly by them. EF2-dependent GTPase activity was stimulated by these toxins, and especially by VT2 and ricin. In contrast, the binding of EF2 to ribosomes was inhibited strongly by VT2 and ricin, and slightly by alpha-sarcin. The stimulation of EF2-dependent GTPase activity by the toxins may compensate for the decrease of EF2 binding to ribosomes which they caused during translocation. In total, these results indicate that VT2 and ricin inhibit protein synthesis through the disturbance of the turnover of EF1 binding to ribosomes during aminoacyl-tRNA binding to ribosomes, and that alpha-sarcin inhibits the synthesis through the inhibition of the binding of the complex of Phe-tRNA, EF1, and GTP to ribosomes.

Animals↗
PubMed1992

Identification and characterization of an Escherichia coli gene required for the formation of correctly folded alkaline phosphatase, a periplasmic enzyme.

Tn5 insertion mutations of Escherichia coli were isolated that impaired the formation of correctly folded alkaline phosphatase (PhoA) in the periplasm. The PhoA polypeptide synthesized in the mutants was translocated across the cytoplasmic membrane but not released into the periplasmic space. It was susceptible to degradation by proteases in vivo and in vitro. The wild-type counterpart of this gene (named ppfA) has been sequenced and shown to encode a periplasmic protein with a pair of potentially redox-active cysteine residues. PhoA synthesized in the mutants indeed lacked disulfide bridges. These results indicate that the folding of PhoA in vivo is not spontaneous but catalyzed at least at the disulfide bond formation step.

Alkaline Phosphatase↗
PubMed1992

Correlation between the prostatic vein and vertebral venous system under various conditions.

In dogs, the venous blood from the prostate gland was observed under X-ray fluoroscopy to drain into the vertebral venous system under conditions of abdominal compression, the addition of various intraabdominal pressures, and occlusion of the inferior vena cava by a balloon catheter. Pressure in the inferior vena cava and abdominal cavity were measured simultaneously. The venous blood draining from the prostate gland started to flow from the inferior vena cava into the vertebral veins at more than 25 mmHg of intraabdominal pressure with the animal in the supine position. The average pressure of the inferior vena cava draining into the vertebral veins was 12.8 +/- 1.3 mmHg in the supine position and 21.1 +/- 2.7 mmHg in the standing position. The average intraabdominal pressures were 35.5 +/- 3.9 mmHg and 30.1 +/- 2.8 mmHg, respectively. Under conditions of abdominal compression and balloon occlusion of the inferior vena cava, the materials flowed into the vertebral venous system from various routes, such as the internal iliac vein, common iliac vein, and inferior vena cava. It was suggested that the inferior vena caval blood easily enters the vertebral venous system in the standing position by adding high intraabdominal pressure, and that the vertebral venous system may be useful for experimental study of drug administration in bone metastasis of prostate cancer.

Animals↗
PubMed1992

The simultaneous measurement of the redox state of cytochrome oxidase in heart and brain of rat in vivo by NIR.

The mutual relationship of the redox state of cytochrome oxidase in both cardiac and brain tissues were examined by the simultaneous optical measurement. The oxygenation states of cardiac and brain tissues behaved in a same manner during progressive hypoxia. We concluded that the oxygenation state of brain completely depends on the oxygenation state of cardiac tissue which determines the cardiac output.

Animals↗