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Biomedical subjects

Y Kitamura

Publications and source records attributed to Y Kitamura.

At least 397 records · Page 22Linked to original sources

Inhibition of attachment between cultured mast cells and fibroblasts by phorbol 12-myristate 13-acetate and stem cell factor.

Cultured mast cells (CMC) derived from the bone marrow of mice express the receptor encoded by the W (c-kit) locus (W receptor), and the WCB6F1(+/+)-3T3 fibroblasts express the ligand encoded by the Sl locus (stem cell factor [SCF]). CMC attach to the fibroblasts through the W receptors and cell-bound SCF. We investigated the effect of phorbol 12-myristate 13-acetate (PMA) and recombinant murine SCF (rmSCF) on the attachment. PMA induced both the internalization and shedding of W receptors, whereas rmSCF induced only the internalization. Moreover, both PMA and rmSCF reduced the expression of c-kit mRNA levels in CMC. Addition of either PMA or rmSCF to the coculture of CMC and fibroblasts resulted in the inhibition of attachment. Since the magnitude of the attachment between CMC and fibroblasts may be manipulated by changing the doses of either PMA or rmSCF, the present experimental system may be useful as a model for the attachment between blood cells and stromal cells.

3T3 Cells↗

Enhanced expression of CD34 messenger RNA by developing endothelial cells of mice.

BACKGROUND: Immunohistochemical studies have demonstrated that CD34 antigen is present on the surface of vascular endothelial cells and hematopoietic cells. Roles of CD34 for angiogenesis and its function as a homophilic adhesion molecule between endothelial and hematopoietic cells have been speculated. EXPERIMENTAL DESIGN: Northern blotting was used to examine the expression levels of CD34 mRNA, and in situ hybridization was used to localize CD34 mRNA. First, we investigated changes in CD34 mRNA expression in developmental processes of mice. Second, we investigated the changes in skin tissues of adult mice in the process of wound healing and tumor growth. RESULTS: CD34 mRNA was strongly expressed by most of the vascular endothelial cells in developing organs. The magnitude of the expression decreased after birth but increased again in the process of wound healing and tumor growth. Although CD34 mRNA signals were observed in hematopoietic cells in the yolk sac and fetal liver, the endothelial cells of these tissues did not express CD34 mRNA signals. CD34 mRNA signals were detectable in neither hematopoietic nor endothelial cells of the bone marrow. In tissues other than hematopoietic ones, however, blood cells within the vessels did not express CD34 mRNA, although the endothelial cells expressed CD34 mRNA. CONCLUSIONS: The expression pattern of CD34 mRNA suggested its significant role in development of blood vessels not only in embryos but also in adults. Although CD34 mRNA was expressed both by endothelial cells and hematopoietic cells, the expression did not occur within the same organ, suggesting that the CD34 molecule may not be used as a homophilic adhesion molecule between endothelial and hematopoietic cells.

Animals↗

[Usefulness of rapid detection of plasma insulin levels during resection of insulinoma].

Insulinoma is one of the causes of hypoglycemia and can be cured by surgery. Using the enzyme immunoassay kit (ERUMOTEC INSULIN, Mochida Pharmacy Co.), immunoreactive insulin (IRI) can be measured within one hour. Curative operation was confirmed by normalized IRI level. A 58-year-old man had an episode of loss of consciousness. His blood glucose was below, and his IRI was above, normal. These and other examinations revealed that he was suffering from insulinoma. Tumor resection under general anesthesia was scheduled. Glucose was continuously administered intravenously to prevent hypoglycemia until the end of tumor resection. Frequent blood glucose measurement showed that he had no hypoglycemic episodes. Using the enzyme immunoassay kit, IRI was found to be 704 microU.ml-1 during manipulation of the tumor. At 30 minutes after the tumor resection, it decreased to 9.8 microU.ml-1 (within normal ranges). These data suggested that the operation was curative and that no further hypoglycemic attacks by remnant insulinomas would be anticipated.

Anesthesia, General↗

[Renal cell carcinoma with regional lymph node metastasis].

A follow up study of 20 cases of renal cell carcinoma with regional lymph node metastasis at the department of urology in Niigata Cancer Center Hospital from 1979 to 1993 is presented. During this period, we treated 249 patients with renal cell carcinoma with or without lymph node metastasis. Lymph node metastasis could be estimated in 188 out of 249 patients. Histologically, lymph node metastasis was classified as pN1 in 8 cases, pN2 in 7 cases, and pN3 in 5 cases. The 3- and 5-year survival rates of 20 patients with lymph node metastasis were 45.0% and 16.4%, respectively. Nine of the 20 cases had no distant metastasis and 11 cases had distant metastasis. Three of the 9 patients with distant metastasis had no recurrence. Two of these 3 patients are still alive after 10 years and 3 years and 1 patient died because of acute heart failure. These 3 patients had pN1 metastasis smaller than 1 cm lymph node. Four of the 11 patients with distant metastasis had more than a two-year survival. However, 3 patients died due to renal cell carcinoma although primary and metastatic regions were resected and IFN with chemotherapy were given. Only one patient is still alive without recurrence after 3 years. This case detected as right renal cell carcinoma with pN2 metastasis and bilateral pulmonary metastasis was treated with radical nephrectomy with regional lymph node dissection and administered Methotrexate, VP16 and CisPlatinum chemotherapy and IFN.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[Definition of early renal cell carcinoma--from the study of pathological and clinical findings according to tumor size].

In this study we tried to define the term "early renal cell carcinoma" from the study of pathological and clinical findings of renal cell carcinoma according to tumor size. During the 33 years from 1961 to 1993, 288 patients with renal cell carcinoma were treated in Niigata Cancer Center Hospital. In 250 of the 288 cases, tumor size was measurable. The average tumor size was 6.9 +/- 3.4 cm (from 1.5 cm to 17 cm). First we divided renal cell carcinoma into four group according to tumor size; under 2.5 cm (n = 32), 2.5-5 cm (n = 67), 5-10 cm (n = 108) and over 10 cm (n = 43). The 5-year survival rate was 89.2, 71.4, 54.3 and 33.2% respectively. The survival rate for tumors under 5 cm in size was significantly higher than that for tumors over 5 cm in size (p < 0.01). Then the tumors under 5 cm were analyzed for every centimeter in tumor size. The survival rate was 89.9% for tumors under 2 cm (n = 22), 94.1% for 2-3 cm (n = 18), 85.2% for 3-4 cm (n = 25) and 61.8% for 4-5 cm (n = 32). None of the patients with tumors under 3 cm died of renal cell carcinoma. One patient with distant metastasis and another patient with regional lymph node metastasis were found among the patients with tumors under 3 cm in size but these two patients are now free from the disease. Recurrence was not found in the patients with tumors under 3 cm in size. There was little vein involvement in the cases under 3 cm (2/37). From these findings, we define the early renal cell carcinoma as the cases in which the tumor is under 3 cm in size and without distant or lymph node metastasis.

Adult↗

Expression of osteopontin messenger RNA in the rat kidney on experimental model of renal stone.

We investigated the expression of osteopontin (OPN) messenger (m) RNA in the rat kidney under the experimental models of several conditions that are considered to be risk factors of human renal stones. In the renal stone formation model administrated glyoxylic acid and 1,25-dihydroxyvitamin D3, pyelonephritis model and hydronephrosis model the expression of OPN mRNA in the distal convoluted tubule of the kidney was enhanced compared with the control which was sporadically positive utilizing in situ hybridization and northern blot analysis. The expression of OPN mRNA was markedly inhibited in the renal stone formation model by concominant administration of estradiol and/or progesterone.

Animals↗

Mechanisms of eosinophilia in mice infested with larval Haemaphysalis longicornis ticks.

Infestation of larval Haemaphysalis longicornis ticks induced a threefold increase of eosinophils in the peripheral blood of normal WBB6F1- +/+ mice 2 days after tick infestation. In genetically mast cell-deficient WBB6F1- W/Wv mice, a threefold increase of blood eosinophils was observed 6 days after the tick infestation. However, marked infiltration of eosinophils was detected in the tick infestation sites of the WBB6F1- +/+ mice but not the WBB6F1- W/Wv mice. When the mast cell deficiency of WBB6F1- W/Wv mice had been rescued locally by intradermal injections of WBB6F1- +/+ mouse-derived cultured mast cells, a rapid increase of blood eosinophils and tissue infiltration of eosinophils were revealed following tick infestation. The intravenous (i.v.) injection of immune spleen or lymph node cells obtained from WBB6F1- +/+ mice 10 days after tick infestation led to significant eosinophilia in naive recipient mice. Treatment with anti-Thy-1.2 or anti-CD4 monoclonal antibody (mAb) and complement (C) completely abolished the eosinophilia; the early response (2 days after tick challenge) is dependent on mast cells at the feeding site, and the late response (6 days after tick challenge) is dependent on T lymphocytes. Since amplified interleukin-5 (IL-5) cDNA was detectable in the spleen cells 4 days after tick infestation, the late response might be mediated by IL-5. The infiltration of eosinophils at the feeding site of skin appeared to be dependent on mast cells.

Animals↗

Expression of bone matrix protein messenger ribonucleic acids in human breast cancers. Possible involvement of osteopontin in development of calcifying foci.

BACKGROUND: Development of calcifying foci is a fairly common finding in human breast cancers, and the deposition of calcium phosphate is observed in such foci. The calcium phosphate is a physiologic component of bones and teeth. Since the expression of messenger (m) RNAs of osteopontin (OPN), osteocalcin (OC), osteonectin (ON), and matrix gla protein (MGP) has been described in bones and teeth, we examined the mRNA expression of OPN, OC, ON, or MGP in the calcifying foci that were observed in human breast cancers. EXPERIMENTAL DESIGN: Cell types expressing mRNAs of OPN, ON or MGP were identified with combination of in situ hybridization and immunohistochemistry. RESULTS: The OPN mRNA-expressing cells clustered around the necrotic foci within cancer cell nests, and the examination with anti-OPN antibody revealed that OPN protein was localized in such necrotic foci where calcium phosphate deposited. The OPN mRNA-expressing cells were identified as macrophages by staining the adjacent section with the anti-CD68 PG-M1 monoclonal antibody which specifically recognizes macrophages. Neither ON mRNA-expressing cells nor MGP mRNA-expressing cells appeared to correlate with the deposition of calcium phosphate. CONCLUSIONS: The OPN protein produced by macrophages appeared to play a significant role for development of calcifying foci within necrotic area of breast cancers.

Antibodies, Monoclonal↗

Functional role of nerve-derived nitric oxide in isolated dog ophthalmic arteries.

PURPOSE: To determine if nitric oxide (NO) is involved in the relaxant response to nerve stimulation by nicotine and electrical pulses in dog external ophthalmic arteries (EOA) and internal ophthalmic arteries (IOA). METHODS: Changes in isometric tension were recorded in helical strips of the arteries, and the presence of perivascular nerve containing NADPH diaphorase was histochemically demonstrated. RESULTS: Nicotine (10(-4) M, EOA and IOA) and transmural electrical stimulation (5 Hz, EOA) produced a slight or no contraction followed by a moderate relaxation in the strips contracted with prostaglandin F2 alpha. The contraction was abolished by alpha-adrenoceptor antagonists. The relaxation was abolished and the contraction was potentiated by NG-nitro-L-arginine (L-NA), a nitric oxide (NO) synthase inhibitor; the relaxation was reversed by L-arginine. Contractile response in L-NA-treated EOA was greater than in the IOA, and the relaxation was less in nontreated EOA. NO-induced relaxation and norepinephrine-induced contraction were not influenced by L-NA. There were plenty of nerve fibers visualized by NADPH diaphorase staining method in the adventitia of EOA and IOA, indicating the presence of NO synthase-containing nerves. CONCLUSIONS: The neurogenic relaxation appears to be mediated by NO released from the vasodilator nerve in EOA and IOA. There is a reciprocal innervation in vasodilator nitroxidergic and vasoconstrictor noradrenergic nerves; functionally, the latter is more predominant in EOA than in IOA.

Animals↗

[Clinical and pathological studies of renal cell carcinoma with vein involvement].

To clarify the meaning of vein involvement, the clinical and pathological findings of the patients with renal cell carcinoma were examined. Out of 288 patients treated for renal cell carcinoma-from 1961 to 1993 at Niigata Cancer Center Hospital, 238 patients were examined for vein involvement. Tumor stages were evaluated according to the general rules for clinical and pathological studies on renal cell carcinoma (2nd edition). In 154 patients, the stage was pV0, in 41 pV1a, in 23 pV1b and in 20 pV2. The 5-year survival rate was 72.2% in pV0, 60.1% in pV1a, 51.9% in pV1b and 30.0% in pV2. Histological findings as grade, tumor size, regional lymph node metastasis and distant metastasis were proportional to vein involvement. The difference in the survival rate and histological findings of primary tumor between pV1a and pV1b group was small but the difference between pV0 and pV1a was significant. Therefore, the histological and clinical studies of the cases with pV1a must be done carefully. The 5-year survival rate of the patients with pV2 and without distant metastasis was 50.0%. However, the prognosis of the patients with pV2 and with distant metastasis was poor. Therefore aggressive treatment was not recommended for these patients.

Aged↗

[The evaluation of surgical management for metastatic lesions of renal cell carcinoma].

The clinical experience with 29 renal cell carcinoma patients who underwent resection of their metastatic lesions was reviewed. Fourteen patients had no metastatic lesions when nephrectomy was performed initially (initial M0 group) and 15 patients already had detected metastases at diagnosis of their renal tumors (initial M1 group). The final point of follow-up was May 31, 1994. Eighteen patients (M0 9, M1 9) were curatively resected and 11 (M0 5, M1 6) underwent non-curative resection. In the curatively resected group, 7 patients (3 lung, 2 adrenal gland, 1 brain, 1 bone metastasis) were alive with no recurrence followed from 50 to 174 months. Eight died from tumor recurrences, 1 was alive with tumor recurrence and 2 died from other diseases. The 3-year and 5-year survival rates in the curatively resected group (16 patients, excluding 2 who died from other diseases) were 87.5% and 61.9%, respectively, according to the Kaplan-Meier method. On the other hand, the 3-year and 5-year survival rate in the non-curatively resected group were 36.4% and 27.3%, respectively. Between the curatively resected group and non-curatively resected group, a significant difference was shown concerning the survival rate (3 year: P = 0.0018, 5 year: P = 0.003, generalized Wilcoxon method). We concluded that curative resection was the most important prognostic factor in the treatment of metastatic lesions.

Aged↗

Expression of vascular endothelial growth factor and its receptor mRNA in angiosarcoma.

BACKGROUND: Vascular endothelial growth factor (VEGF), a specific mitogen for endothelial cells in vitro, can be angiogenic factor in vivo. VEGF is known to be produced by several tumor cells and plays an important role for neovascularization in tumor tissue. Recently, tyrosine kinase encoded by the flt gene was identified as a receptor for VEGF. Angiosarcoma (AS) is a rare malignant tumor that arises from endothelium. At present, little is known about a mechanism of proliferation of the AS. EXPERIMENTAL DESIGN: In an immunohistochemical study of 99 cases of AS, 11 cases showing a positive reaction for anti-VEGF Ab were selected for the present study. In these cases, expression of VEGF and its receptor (flt) mRNA was examined by in situ hybridization: sense and antisense probes for VEGF and flt mRNA were used. RESULTS: In situ hybridization study with antisense probes revealed that the VEGF mRNA was expressed in AS cells and mononuclear cells in all but one case. Intensity of VEGF staining by immunohistochemistry correlated well with VEGF mRNA expression. The flt mRNA was expressed in AS cells in all 10 cases that were positive for VEGF mRNA. Sense probe for VEGF and flt mRNA gave no positive reactions. CONCLUSIONS: These findings suggest a presence of paracrine or autocrine mechanism of proliferation in AS through VEGF and its receptor flt.

Aged↗

Loss of DNA binding ability of the transcription factor encoded by the mutant mi locus.

The mi locus of mice encodes a novel member of the basic-helix-loop-helix-leucine zipper protein family of transcription factors (MITF). Mutant mice of the mi/mi genotype have the deletion of an arginine in the basic domain and show the abnormality in development of eyes, melanocytes, osteoclasts and mast cells. The expression of the mast cell protease 6 (MMCP-6) gene is markedly reduced in mi/mi mice. We examined the in vitro binding ability of the normal and mutant MITF to a hexameric motif (CACATG) located in the 5'-flanking sequence of the MMCP-6 gene. The normal MITF bound the hexameric motif but the mutant MITF did not, suggesting that the MITF directly regulated the expression of the MMCP-6 gene.

Animals↗

Binding of serum amyloid P component to heparin in human serum.

It has been proposed that the function of serum amyloid P component (SAP) may closely relate with its binding to polysaccharides, especially glycosaminoglycans. We employed a quantitative immunoelectrophoresis (QIE) method and a native polyacrylamide gel electrophoresis (PAGE) method to characterize the SAP-heparin binding in soluble state. The SAP-heparin binding showed positive cooperativity. The apparent numbers of heparin molecules bound to SAP varied with the calcium concentration with a ratio of 1:1 (SAP/heparin), a Kd of 2.06 x 10(-7) M at 0.1 mM CaCl2 and a ratio of 1:1.6 (SAP/heparin), a Kd of 3.91 x 10(-7) M at 2 mM CaCl2, when estimated by the QIE method. No binding between SAP and heparin was observed in the absence of calcium. Magnesium and barium failed to induce the formation of SAP-heparin complex. Furthermore, they showed inhibitory effects on the calcium-mediated complex formation. We propose that heparin might be a regulator to modulate the anticoagulant activity of SAP and a useful drug to prevent SAP deposition on amyloid deposits.

Barium↗

Poor response of cultured mast cells derived from mi/mi mutant mice to nerve growth factor.

Decreased numbers of mast cells and abnormalities in the phenotype of mast cells are observed in the skin of mi/mi mutant mice. Recently, the mi locus was identified to encode a novel member of the basic-helix-loop-helix-leucine zipper protein family of transcription factors. Since nerve growth factor (NGF) has been reported to influence the proliferation and the phenotype of cultured mast cells (CMCs), we compared the effect of NGF between mi/mi and control normal (+/+) CMCs. Addition of NGF to the suboptimal dose of recombinant murine interleukin-3 (rmIL-3) increased the plating efficiency of +/+ CMCs, but not of mi/mi CMCs. Although +/+ CMCs were berberine sulfate-negative when cultured with rmIL-3 alone, +/+ CMCs became berberine sulfate-positive when cultured in the presence of both rmIL-3 and NGF, which suggests increased heparin content. In contrast, NGF did not influence the phenotype of mi/mi CMCs. +/+ CMCs significantly bound 125I-NGF, but mi/mi CMCs did not, which suggests a defect of NGF receptors in mi/mi CMCs. Both p75 and p140 molecules are known to be involved in the formation of NGF receptors. Although the expression of p140 messenger (m)RNA was comparable between +/+ and mi/mi CMCs, the expression of p75 mRNA was significantly lower in mi/mi CMCs than in +/+ CMCs. Taken together, the poor response of mi/mi CMCs to NGF appeared to be attributable to the impaired transcription of the p75 gene.

Animals↗