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T Tsujimura

Publications and source records attributed to T Tsujimura.

At least 55 records · Page 3Linked to original sources
PubMed1994

Cushing's syndrome with cortisol hypersecretion from one of bilateral adrenocortical adenomas: report of a case.

We report herein the case of a 40-year-old man with Cushing's syndrome, diagnosed by clinical manifestations and endocrinological studies, who was found to have bilateral adrenocortical adenomas, one of which hypersecreted cortisol. The Cushing's syndrome was therefore attributed to primary adrenocortical disease, and the right adrenal tumor was resected and histologically diagnosed as a so-called black adenoma. After resection of the right tumor, the left adrenal tumor showed no signs of cortisol hypersecretion for the 23 months of follow-up until the patient died of peritonitis subsequent to the rupture of a duodenal ulcer. The left adrenal tumor was examined at autopsy and found to be a cortical adenoma. These data imply that the adrenal adenomas developed primarily from the adrenal gland itself, and that one of the tumors was well differentiated and secreted excess hormones, while the other remained in cell proliferation without hypersecretion.

Adrenal Gland Neoplasms↗
PubMed1994

Tyrosine hydroxylase indicates cell differentiation of catecholamine biosynthesis in neuroendocrine tumors.

The intracellular localization of tyrosine hydroxylase (TH), which is the rate limiting enzyme in catecholamine (CA) biosynthesis, and its activity in various adrenal and other neuroendocrine tumors was studied. TH was strongly localized in adrenal medulla, pheochromocytoma, and paraganglioma, but was scatteredly expressed in neuroblastoma. TH was not detected in adrenocortical tumors, ganglioneuroma, and other neuroendocrine tumors. Neuron specific enolase (NSE) was found in all neuroendocrine tumors, but Grimelius staining showed only the secreting granules of the tumor cells. TH activity was significantly high in pheochromocytoma and paraganglioma as compared with that in normal adrenal gland, whereas TH activity was low in a neuroblastoma and was undetectable in other tumors. These findings indicate that TH correlates well with the biosynthetic function of CA in the tumor cell and, thus, both the immunostaining of TH and the measurement of its activity in adreno-medullary and related tumors may provide some information about the process of cell differentiation in these tumors.

Adrenal Gland Neoplasms↗
PubMed1994

Different effects of antidepressants on dissociation of 3H-imipramine from solubilized binding sites of rat brain.

1. The effects of several antidepressants and 5-hydroxytryptamine on dissociation of 3H-imipramine from solubilized binding sites were investigated. 2. Binding sites were solubilized from rat brain membranes and gelfiltrated on a column of Sephacryl S-300. 3. Most of the agents used allowed biphasic dissociation with 1mM of displacing agent and without using dilution-induced dissociation. This biphasic dissociation without nonspecific effects of membranes may be due to the existence of low-affinity binding sites. 4. Dissociation of up to 40 min followed first-order kinetics. The dissociation half-life of 3H-imipramine with the various displacing agents was calculated at from 15.0 to 25.0 min, and the differences among the agents were not so significant as the attenuation or the acceleration of the dissociation was indicated. The lower concentration of the displacing agents may obscure the modulation of the dissociation.

Animals↗
PubMed1994

Efficacy of interferon therapy in patients with chronic hepatitis C. Comparison between non-drinkers and drinkers.

BACKGROUND: Alcohol has been reported to be an important factor that modulates the development and prognosis of chronic viral hepatitis; however, little is known about interaction of alcohol intake and chronic hepatitis C. The aim of this study was to examine whether alcohol drinking affects the effectiveness of interferon (IFN) therapy for chronic hepatitis C. METHODS: Thirty-nine patients with chronic hepatitis C were divided into three groups on the basis of the amount of alcohol intake before IFN therapy: group I (n = 15), non-drinkers; group II (n = 14), less than 70 g/day; and group III (n = 10), more than 70 g/day of ethanol intake for at least 10 years. The IFN (total dose, 330 +/- 206 MU) was administered daily for 2 weeks and then intermittently. Drinkers stayed abstinent for at least 1 month before, during, and after IFN therapy. The sustained responder was defined as the patient who showed normal alanine aminotransferase (ALAT) levels continuously for more than 6 months after the therapy. The liver histology (HAI score) and serum hepatitis C virus (HCV) RNA were also examined before and after the therapy. RESULTS: There was no significant difference among the three groups in the level of ALAT before IFN therapy, age, total dose of IFN, and liver histology. The rates of sustained responders in groups I, II, and III were 53.3%, 42.9%, and 0%, respectively, resulting in a significantly lower rate in group III than in groups I (p < 0.01) and II (p < 0.01). The serum HCV-RNA turned negative after the therapy in 58.3%, 20.0%, and 12.5% of groups I, II, and III, respectively, leading to a significantly lower rate of disappearance of HCV-RNA in group III than in group I (p < 0.05). CONCLUSION: The IFN therapy for chronic hepatitis C was less effective in heavy drinkers than in non-drinkers.

Alanine Transaminase↗
PubMed1994

Wn mutation of c-kit receptor affects its post-translational processing and extracellular expression.

The W locus of mice encodes the c-kit receptor tyrosine kinase. Recently, we characterized a novel mutant allele, Wn, and demonstrated that the c-kit protein synthesized in Wn/Wn cultured mast cells (CMC) was reduced in size and not expressed on their surface (Tsujimura et al., 1993). In this study, we further examined biochemical nature of the mutant form of c-kit protein, by using Wn/Wn CMC and 293T cells transfected with Wn-type c-kit cDNA (c-kitWn). The c-kit product synthesized in Wn/Wn CMC was truncated almost all cytoplasmic domain and was less glycosylated. In c-kitWn-transected cells, both glycosylation and extracellular expression of c-kit protein was also impaired, however, no truncation was detected. These results indicate that Wn-mutant form of c-kit product is insufficient in maturation, which is associated with impairments in the transport to the plasma membrane, and retention of the mutant protein in endoplasmic reticulum is suggested. This is the first demonstration of the c-kit mutation affecting posttranslational processing its product.

Alleles↗
PubMed1994

Activating mutations of the c-kit proto-oncogene in a human mast cell leukemia cell line.

The c-kit proto-oncogene encodes a receptor tyrosine kinase that is known to play a crucial role in mast cell growth and differentiation. In a human mast cell leukemia cell line (HMC-1), KitR was found to be constitutively phosphorylated on tyrosine, activated and associated with phosphatidylinositol 3-kinase (P13K) in the absence of autocrine production of SCF. Sequencing of c-kit cDNA revealed that c-kit genes of HMC-1 cells were composed of a normal, wild-type allele and a mutant allele with two point mutations in codon 560 and codon 816, resulting in intracellular amino acid substitutions of Gly-560 for Val and Val-816 for Asp, respectively. Murine c-kit mutants encoding Gly-559 and/or Val-814, corresponding to human Gly-560 and/or Val-816, were constructed by site-directed mutagenesis and expressed in cells of a human embryonic kidney cell line (293T). In the transfected cells, KitR (Gly-559 + Val-814) and KitR (Val-814) were strikingly phosphorylated on tyrosine and activated in the absence of SCF, whereas tyrosine phosphorylation and activation of KitR (Gly-559) or wild-type KitR was modest or little, respectively. These results suggest that constitutive activation of KitR in HMC-1 results from the activating mutations of c-kit gene, and raise the possibility that the activating mutations, particularly at codon 814 of murine c-kit or at codon 816 of human c-kit, may participate in oncogenesis of mast cells.

Humans↗
PubMed1994

Cell type-specific deficiency of c-kit gene expression in mutant mice of mi/mi genotype.

The mi locus of mice encodes a novel member of the basic-helix-loop-helix-leucine zipper protein family of transcription factors (hereafter called mi factor). In addition to microphthalmus, osteopetrosis, and lack of melanocytes, mice of mi/mi genotype are deficient in mast cells. Since the c-kit receptor tyrosine kinase plays an important role in the development of mast cells, and since the c-kit expression by cultured mast cells from mi/mi mice is deficient in both mRNA and protein levels, the mast cell deficiency of mi/mi mice has been attributed at least in part to the deficient expression of c-kit. However, it remained to be examined whether the c-kit expression was also deficient in tissues of mi/mi mice. In the present study, we examined the c-kit expression by mi/mi skin mast cells using in situ hybridization and immunohistochemistry. Moreover, we examined the c-kit expression by various cells other than mast cells in tissues of mi/mi mice. We found that the c-kit expression was deficient in mast cells but not in erythroid precursors, testicular germ cells, and neurons of mi/mi mice. This suggested that the regulation of the c-kit transcription by the mi factor was dependent on cell types. Mice of mi/mi genotype appeared to be a useful model to analyze the function of transcription factors in the whole-animal level.

Animals↗
PubMed1994

[Thoracic solitary neurenteric cyst--case report].

A 61-year-old man presented with repeated back pain and progressive anesthesia of both lower limbs. MR images and myelography showed an intradural, extramedullary tumor at the Th8-9 level. Surgery revealed a thin membrane containing xanthochromic cerebrospinal fluid behind the spinal cord. Microscopically, the excised lesions contained columnar epithelium with goblet cells. Spinal neurenteric cysts are a rare anomaly, especially solitary cysts located in the thoracic spine. The neurenteric canal transiently develops in the lumbosacral region during the 3rd week of gestation. Thus, it is difficult to claim that the neurenteric cyst in our case originated in a remnant of the neurenteric canal. As Bentley and Smith (1960) suggested, thoracic solitary neurenteric cysts may develop from a remnant of adhesion between ectoderm and endoderm during the 3rd week of gestation as a result of splitting of the notochord.

Humans↗
PubMed1993

Mast cell number in the skin of heterozygotes reflects the molecular nature of c-kit mutation.

The W locus of mice encodes the c-kit receptor tyrosine kinase. Heterozygous WJic/+ and Wn/+ mice and homozygous Wf/Wf mice were similar in appearance; all of them have large depigmented areas lacking any well-defined pattern. The WJic, Wn, and Wf mutant alleles were characterized and their molecular nature was correlated with the mast cell differentiation in the skin and the biologic features of cultured mast cell (CMC). All WJic, Wn, and Wf were point mutations at the tyrosine kinase domain, and c-kit mRNA was normally transcribed from all of them. The mature 145-Kd form of the c-kit protein was produced from the WJic and Wf alleles, but not from the Wn allele. c-kit proteins produced by the WJic or Wf allele were expressed on the surface of CMCs, but those of the Wn allele were not. When double heterozygous mice were produced between W and WJic and between W and Wn, both W/WJic and W/Wn mice lacked skin mast cells. W/WJic CMCs and W/Wn CMCs did not survive in the coculture with fibroblasts. W/WJic CMCs normally attached to fibroblasts, but W/Wn CMCs did not. The defect of W/Wn CMCs in the attachment was attributed to the deficient extracellular expression of the c-kit protein. The number of skin mast cells was compared among WJic/+, Wn/+, Wf/+, and Wf/Wf mice. Mast cells decreased in WJic/+ and Wf/Wf mice, but not in Wn/+ and Wf/+ mice. Although the Wn was a point mutation at the kinase domain, the biologic effect of the Wn was comparable with that of the W mutant allele, which produces truncated c-kit protein without the transmembrane domain. The weak phenotype of Wn/+ mice may be explained by the deficient extracellular expression of c-kit proteins produced by the Wn allele. When WJic/WJic, Wn/Wn, and Wf/Wf CMCs were stimulated by the recombinant c-kit ligand, autophosphorylation activity was observed only in Wf/Wf CMCs. This result was consistent with the weak biologic effect of the Wf mutant allele.

Adenosine Triphosphate↗
PubMed1993

Enhancement of DNA polymerase beta activity in the pituitary gland by hormonal feedback.

The activity of DNA polymerase beta (beta-enzyme) in bovine and rat pituitary glands was remarkably higher in the anterior than in the posterior lobe. In sucrose gradient centrifugation, the activity in the anterior lobe of the bovine pituitary gland appeared at the sedimentation constant, 3.3 S, while that of rat pituitary gland appeared at 3.3 S, 7.3 S and 12 S, respectively. The activity in each fraction increased in the anterior lobes of rat pituitaries that were stimulated to release TSH by decreased thyroid hormone levels induced by an antithyroid drug. These results suggest that the activity of the beta-enzyme is high in the cells of the anterior lobe which are hyperfunctioned to produce pituitary thyreotrophic hormone and may be controlled by hormonal feedback regulation.

Animals↗
PubMed1993

Identification of mutations in the coding sequence of the proto-oncogene c-kit in a human mast cell leukemia cell line causing ligand-independent activation of c-kit product.

The c-kit proto-oncogene encodes a receptor tyrosine kinase. Binding of c-kit ligand, stem cell factor (SCF) to c-kit receptor (c-kitR) is known to activate c-kitR tyrosine kinase, thereby leading to autophosphorylation of c-kitR on tyrosine and to association of c-kitR with substrates such as phosphatidylinositol 3-kinase (PI3K). In a human mast cell leukemia cell line HMC-1, c-kitR was found to be constitutively phosphorylated on tyrosine, activated, and associated with PI3K without the addition of SCF. The expression of SCF mRNA transcript in HMC-1 cells was not detectable by means of PCR after reverse transcription (RT-PCR) analysis, suggesting that the constitutive activation of c-kitR was ligand independent. Sequencing of whole coding region of c-kit cDNA revealed that c-kit genes of HMC-1 cells were composed of a normal, wild-type allele and a mutant allele with two point mutations resulting in intracellular amino acid substitutions of Gly-560 for Val and Val-816 for Asp. Amino acid sequences in the regions of the two mutations are completely conserved in all of mouse, rat, and human c-kit. In order to determine the causal role of these mutations in the constitutive activation, murine c-kit mutants encoding Gly-559 and/or Val-814, corresponding to human Gly-560 and/or Val-816, were constructed by site-directed mutagenesis and expressed in a human embryonic kidney cell line, 293T cells. In the transfected cells, both c-kitR (Gly-559, Val-814) and c-kitR (Val-814) were abundantly phosphorylated on tyrosine and activated in immune complex kinase reaction in the absence of SCF, whereas tyrosine phosphorylation and activation of c-kitR (Gly-559) or wild-type c-kitR was modest or little, respectively. These results suggest that conversion of Asp-816 to Val in human c-kitR may be an activating mutation and responsible for the constitutive activation of c-kitR in HMC-1 cells.

Amino Acid Sequence↗
PubMed1993

Stem cell factor induces outgrowth of c-kit-positive neurites and supports the survival of c-kit-positive neurons in dorsal root ganglia of mouse embryos.

The c-kit receptor tyrosine kinase is highly expressed by about 10% of the neurons in the dorsal root ganglia (DRGs) of mouse embryos. We investigated the in vitro effect of stem cell factor (SCF), the ligand for c-kit receptor, on DRGs. Recombinant murine SCF (rmSCF) induced the outgrowth of c-kit-positive neurites from DRGs of normal (+/+) embryos. The effect of SCF was dose dependent and completely abolished by anti-c-kit ACK2 monoclonal antibody (mAb). Some neurites whose outgrowth was induced by nerve growth factor (NGF) were c-kit-positive, but anti-NGF mAb did not inhibit the rmSCF-induced neurite outgrowth. rmSCF did not induce neurite outgrowth from DRGs of W/W embryos that did not express c-kit receptors on the cell surface and of W42/W42 mutant embryos that expressed c-kit receptors without tyrosine kinase activity. rmSCF also had a trophic effect on c-kit-positive neurons in the culture of dissociated DRG cells. Most c-kit-positive neurons appeared to respond to NGF as well, and the SCF-responsive subpopulation represented about 10% of NGF-responsive neurons. rmSCF did not support the survival of DRG neurons from embryos of W/W and W42/W42 genotypes. These results suggest that the stimulus through the c-kit receptor tyrosine kinase has an important role in development of the peripheral nervous system.

Animals↗
PubMed1993

Localization of Cu/Zn and Mn superoxide dismutase in various thyroid disorders.

The intracellular localization of Cu/Zn- and Mn-superoxide dismutase (SOD), which catalyze the dismutation of superoxide radicals (O2-) to O2 and H2O2, was studied in the thyroid tissue of various thyroid disorders by an immunohistochemical technique. The concentrations of both SODs in those tissues were measured also by a sandwich enzyme immunoassay technique. Copper/zinc-SOD in thyroid tissues were identified by immunocytochemical staining in most cases of papillary carcinoma and in some cases of other thyroid disorders. In normal follicular cells this enzyme is localized in the perinuclear cytoplasm, whereas in thyroid tumor or hyperplastic follicular cells it exists homogeneously in cytoplasm. Manganese-SOD stained strongly in papillary carcinoma and papillary-growing cells in the thyroid tissue of adenoma and Graves' disease. The concentrations of Cu/Zn-and Mn-SOD in thyroid tumor tissues and hyperplastic follicular disorders were significantly higher than those in normal thyroid tissue when they were compared as a function of protein or deoxyribonucleic acid contents. The ratio of Mn-SOD to Cu/Zn-SOD was significantly higher only in papillary carcinoma, except for other thyroid disorders as compared with that in the normal thyroid. In conclusion, SOD seems to be related to cell proliferation and differentiation in the thyroid follicular cell because Cu/Zn-SOD changes its localization in tumor and hyperplastic follicular cells and because the Mn-SOD concentration is increased in papillary carcinoma or papillary-growing cells.

Humans↗
PubMed1993

[Study of the localization and the concentration of superoxide dismutase in various thyroid disorders].

The localization of Cu/Zn and Mn superoxide dismutase (SOD), which catalyzes the dismutation of superoxide radicals (O2-) to O2 and H2O2, in various thyroid disorders was studied by an immunohistochemical technique in 20% formalin fixed paraffin embedded thin sections using anti-human Cu/Zn and Mn-SOD antibodies. The concentrations of both SODs in those tissues were also measured by a sandwich enzyme immunoassay technique. Cu/Zn SOD was immunocytochemically stained in most of papillary carcinoma, and some of other disorders. In the normal follicular cells it localized in the perinuclear cytoplasm, whereas in the tumor or hyperplastic cells it was in the cytoplasm homogeneously. Mn SOD was strongly stained in papillary carcinoma and papillary growing cells in adenoma and Graves' disease. The concentrations of Cu/Zn and Mn SOD in every thyroid disorder were higher than those in normal thyroid, and it was much higher in the malignant tumors. The ratio of the concentration of Mn SOD against Cu/Zn SOD in the tissues was higher only in papillary carcinoma compared with that in normal thyroid. In conclusion, SOD seems to be relating to the cell proliferation and differentiation in the thyroid since both SODs increased in tumors and hyperplastic disorders, and Cu/Zn SOD changed its localization and Mn SOD existed predominantly in papillary carcinoma or papillary growing cells.

Carcinoma, Papillary↗
PubMed1993

Deficient differentiation of mast cells in the skin of mi/mi mice. Usefulness of in situ hybridization for evaluation of mast cell phenotype.

The staining property of skin mast cells changed from Alcian blue+/berberine sulfate- to Alcian blue+/berberine sulfate+ in the skin of normal (+/+) and Wv/Wv mice. In contrast, this change did not occur in the skin of mi/mi mice. Heparin content and histamine content per a mi/mi skin mast cell were estimated to be 34% and 18% those of a +/+ skin mast cell, respectively. The low heparin content of mi/mi skin mast cells seemed to be consistent with the Alcian blue+/berberine sulfate- staining property. Expression of genes encoding mast cell-specific proteolytic enzymes was examined by Northern blotting and in situ hybridization. Messenger RNA of mast cell carboxypeptidase A was expressed most of all by +/+, Wv/Wv, and mi/mi skin mast cells, but mRNA of mouse mast cell protease (MMCP)-6 was expressed by approximately a half of +/+ and Wv/Wv skin mast cells and by only 3% of mi/mi skin mast cells. A significant amount of MMCP-2 mRNA was not expressed in the skin of all +/+, Wv/Wv and mi/mi mice. This shows the presence of at least three phenotypes in skin mast cells of mice: berberine sulfate+/MMCP-6+, berberine sulfate+/MMCP-6-, and berberine sulfate-/MMCP-6-. The in situ hybridization of mRNA of mast cell-specific proteolytic enzymes seemed to be useful to describe abnormalities of mast cell differentiation in the skin of mi/mi mice.

Animals↗
PubMed1993

[Surgical stress induces the secretion of alpha human atrial natriuretic peptide].

The changes in plasma alpha-hANP level and the factors affecting its secretion were studied in 35 patients treated by surgery for gastrointestinal disease (laparotomy group, 17) and (non-laparotomy group, 18). They did not have any particular complication during the study period. alpha-hANP, catecholamine (CA), antidiuretic hormone (ADH), aldosterone and plasma renin activity (PRA) were determined serially before and after the surgery. Plasma alpha-hANP level elevated on the post-operative day 1 and dropped to the upper limit of the normal range by the day 3, then gradually recovered to the level of before surgery. This early elevation of alpha-hANP was more marked in the laparotomy group than in the non-laparotomy group. These change in alpha-hANP level correlated well to those of CA, but not to those of ADH, aldosterone, and PRA. Age, sex, duration of surgery, bleeding and infusion volume during surgery did not affect the difference in alpha-hANP secretion between the two groups. In conclusion, the early elevation of plasma alpha-hANP level was correlated well to the surgical stress, and that this alpha-hANP secretion might be induced by CA secretion.

Adult↗