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Biomedical subjects

T Kanzaki

Publications and source records attributed to T Kanzaki.

At least 19 recordsLinked to original sources
PubMed1999

The effect of a thymidine phosphorylase inhibitor on angiogenesis and apoptosis in tumors.

Thymidine phosphorylase (TP) is an enzyme involved in the reversible conversion of thymidine to thymine and is identical to an angiogenic factor, platelet-derived endothelial cell growth factor. TP is expressed at higher levels in a wide variety of solid tumors than in the adjacent nonneoplastic tissues. Patients with TP-positive colon and esophageal tumors have a poorer prognosis than those with TP-negative tumors. We have recently synthesized a new TP inhibitor (TPI), 5-chloro-6-[1-(2-iminopyrrolidinyl) methyl] uracil hydrochloride. We investigated the effect of TPI on angiogenesis in KB cells transfected with platelet-derived endothelial cell growth factor cDNA, KB/TP, and a mock transfectant, KB/CV, using the mouse dorsal air sac assay model. We found that KB/TP cells had a higher angiogenic ability than KB/CV cells and that TPI completely suppressed angiogenesis by KB/TP. Furthermore, at a dose of 50 mg/kg/day, TPI considerably decreased the growth rate of KB/TP cells xenografted into nude mice. Microvessel density in KB/TP tumors was higher than that in KB/CV tumors, and TPI did not significantly change the density in either of the tumors. The apoptotic index in KB/TP tumors was significantly lower than that in KB/CV tumors, and TPI significantly increased the apoptotic index in KB/TP tumors but not in KB/CV tumors. These findings, taken together with previous reports, suggest that the expression of TP plays an important role in tumor growth and that TPI suppresses tumor growth by increasing the proportion of apoptotic cells and probably inhibiting angiogenesis.

Animals↗
PubMed1999

N-cadherin expressed on malignant T cell lymphoma cells is functional, and promotes heterotypic adhesion between the lymphoma cells and mesenchymal cells expressing N-cadherin.

Cadherins are Ca2+-dependent cell-cell adhesion molecules, and are involved in the formation and maintenance of the organocellular architecture. Using a combination of molecular biologic and biochemical methods, we analyzed cadherins expressed on cultured human malignant lymphoma cell lines (adult T cell lymphomas, human T cell leukemia virus type 1-negative T cell lines, and thymus-derived lymphoma cell lines), and obtained evidence that N-cadherin is the major cadherin expressed on these cells. These cells were found to form cell aggregates in a Ca2+-dependent manner, and more importantly to coaggregate and adhere with cells expressing N-cadherin, suggesting that N-cadherin on lymphoma cells is functionally active. Therefore, N-cadherin expressed on lymphoma cells could underlie the frequent invasion of these cells into the mesenchymal tissue in the skin and the central nervous system.

Cadherins↗
PubMed1999

A novel point mutation affecting the tyrosine kinase domain of the TRKA gene in a family with congenital insensitivity to pain with anhidrosis.

A nerve growth factor receptor encoded by the TRKA gene plays an important part in the formation of autonomic neurons and small sensory neurons in dorsal root ganglia and in signal transduction through its intracytoplasmic tyrosine kinase domain. Recently, three mutations in the tyrosine kinase domain of TRKA have been reported in patients with congenital insensitivity to pain with anhidrosis, which is an autosomal recessive disorder characterized by recurrent fever due to absence of sweating, no reaction to noxious stimuli, self-mutilating behavior, and mental retardation. We examined the TRKA gene in five generations of a large Japanese family with many consanguineous marriages who live in a small remote island of the southern part of Japan. We found a novel point mutation at nucleotide 1825 (A-->G transition) resulting in Met-581-Val in the tyrosine kinase domain. Two of the three affected patients were homozygous for this mutation; however, the third affected patient was heterozygous. Further analysis revealed that the third patient was a compound heterozygote with the Met-581-Val mutation in one allele and with a single base C deletion mutation at nucleotide 1726 in exon 14 in the other allele, resulting in a frameshift and premature termination codon.

Adult↗
PubMed1999

Adenocarcinoma with signet ring cells of the axilla showing apocrine features: a case report.

A 74-year-old Japanese man developed a reddish, indurated plaque composed of multiple nodules on his right axilla. Histopathologic examination showed a solid tumor that extended from the upper dermis into the subcutis, with both inter- and intracellular lumen formation, cellular arrangement in single files, a fibrotic reaction around the tumor cells, and the presence of mucinous material in the cytoplasm. There was both nuclear and cytoplasmic pleomorphism. Both lysozyme and GCDFP-15 were identified in the tumor cells. Electron microscopic examination showed periluminal condensation of the cytoplasm. Because thorough clinical and laboratory examinations were unremarkable, we regarded this to be a case of primary adenocarcinoma with signet ring cells of the axilla. The neoplasm might have differentiated toward the apocrine sweat glands or the mammary glands. Radiation therapy was effective to some degree. This seems to be the first reported case in which adenocarcinoma with signet ring cells of the skin affected a site other than the eyelids.

Aged↗
PubMed1999

Differentiation of malignant lymphoma and non-lymphoma by an occlusive dressing method employing bromodeoxyuridine.

Although lymphoma cells can proliferate in skin tissue, lymphocytes which have infiltrated the skin due to inflammatory changes are generally unable to do so. It may be possible to differentiate malignant lymphomas from benign lymphocytic infiltrations in skin tissue by detection of cell cycle-related antigens. We developed a novel in vivo method for studying the cell kinetics of human skin using bromodeoxyuridine (BrdU) with an occlusive dressing. Following the application of BrdU, BrdU-labeled lymphoid cells were counted in the dermis. The patients studied included 22 with various types of lymphomas (lymphoma group) and 22 with different forms of inflammatory skin disease (non-lymphoma group). Skin specimens were obtained after applying occlusive adhesive plasters containing 2% BrdU dissolved in 0.9% sodium chloride solution and were then immunostained with anti-BrdU monoclonal antibody. The average percentages of labeled cells were 15.9 +/- 7.6% for the lymphoma group and 4.7 +/- 2.6% for the non-lymphoma group. This difference was statistically significant (p < 0.0001). Using this method, malignant lymphomas and benign lymphocytic infiltrations of the skin could be differentiated by counting BrdU-labeled lymphoid cells, and this method could help in determining a prognosis.

Biopsy↗
PubMed1999

A case of sarcoidosis involving the tongue.

Sarcoidosis is a systemic granulomatous disorder which commonly affects the skin. Involvement of the tongue is rare; a review of the previous literature over the last 30 years revealed only six cases of sarcoidosis affecting the tongue. We studied a case of sarcoidosis involving the tongue in a 32-year-old Japanese woman with characteristic clinical and pathological findings. She visited our department with a complaint of a tongue lesion of which she had been aware for a month. A diagnosis of sarcoidosis was made for the lesion by clinical and pathological examinations. Oral involvement by sarcoidosis is rare, however this disorder should be considered as a possible cause of intraoral granulomatous lesions.

Adrenal Cortex Hormones↗
PubMed1999

Two cases of gigantic dystrophic calcinosis cutis caused by subcutaneous and/or intramuscular injections.

We describe two female patients with gigantic dystrophic calcinosis cutis caused by a large number of subcutaneous and/or intramuscular injections which they received when they were much younger. Laboratory data and physical examinations were generally within normal limits, and we detected no disease which might induce cutaneous calcification. There are many reports of dystrophic calcinosis cutis caused by injection of several kinds of drugs. However, we found no previous report describing a patient with calcinosis cutis induced by local tissue injury from a large number of injections and with extraordinarily widespread calcification at the injection sites. Because we do not know the exact drugs injected, it is difficult to say if a specific ingredient in the injections was related to this condition. We do know that a large number of subcutaneous or intramuscular injections were frequently administered to patients who had difficulty in maintaining venous infusions in the past, so there may be similar cases of dystrophic calcinosis cutis which have not been reported.

Aged↗
PubMed1999

Mitogen-activated protein kinase cascade is involved in endothelin-1-induced rat puerperal uterine contraction.

The regulation of mitogen-activated protein (MAP) kinase by endothelin-1 (ET-1) in cultured rat puerperal uterine myometrial cells was investigated. ET-1 caused the rapid stimulation of MAP kinase activity. ET-1-induced MAP kinase activation is neither extracellular Ca2+- nor intracellular Ca2+-dependent. ET-1 stimulation also led to an increase in phosphorylation of son-of-sevenless (SOS), and transfection of dominant negative SOS attenuated the ET-1-induced MAP kinase activity. Phorbol-12-myristate 13-acetate (PMA) also induced the MAP kinase activity, but pretreatment of the cultured cells with PMA, to down-regulate protein kinase C (PKC), did not abolish the activation of MAP kinase by ET-1. In addition, down-regulation of PKC had no effect on ET-1-induced SOS phosphorylation. Pertussis toxin, which inactivates Gi/Go proteins, blocked the ET-1-induced MAP kinase activation but not the PMA-induced MAP kinase activation. The results suggested that MAP kinase is acutely activated by ET-1 through a pertussis toxin-sensitive G protein and SOS, not through the PMA-sensitive PKC. In addition, although reverse-transcriptase PCR assays detected messenger RNA for both ET- 1 receptor subtypes in cultured rat puerperal uterine myometrial cells, ET-1-induced MAP kinase activity and uterine contraction were blocked by treatment with BQ485, an antagonist selective for an ET type A receptor (but not by BQ788, an ET type B receptor antagonist). Ritodrine, which is known to relax uterine muscle contraction, attenuated ET-1-induced MAP kinase activity. We further examined the role of MAP kinase pathway in uterine contraction using an inhibitor of MEK activity, PD098059. This inhibitor completely inhibited the ET-1-induced MAP kinase activation and partially, but significantly, inhibited the ET-1-induced uterine contraction. These results indicate that ET-1-induced MAP kinase signaling cascade may play an important role in the ET-1-induced uterine contraction.

Animals↗
PubMed1998

Role of latent TGF-beta 1 binding protein in vascular remodeling.

Transforming growth factor-beta (TGF-beta) is secreted as a latent, high molecular weight complex, which is composed of TGF-beta, a latency associated peptide (LAP) and a latent TGF-beta binding protein (LTBP). In this study, we report on the role of LTBP in vascular remodeling. 0.01-5 ng/ml of LTBP stimulated the migration activities of cultured rat arterial smooth muscle cells (SMC) about 4-7 fold compared with control in vitro. The maximal activity of SMC migration by LTBP was 75% of that by 10 ng/ml of PDGF-BB. A checker board analysis showed that the migration by LTBP was chemotactic, not chemokinetic. By cross-linking experiment, LTBP associated with 80-120 kd cell surface protein of SMC, suggesting that a part of LTBP can bind with SMC. Furthermore, LTBP was more strongly expressed in the intimal layer than in the medial layer of BCI artery. These results suggest that LTBP plays an important role in the initial stage of arterial intimal thickening through the acceleration of SMC migration from the medial to intimal layer and is one of the essential factors influencing vascular remodeling.

Animals↗
PubMed1998

Autocrine inhibition of leptin production by tumor necrosis factor-alpha (TNF-alpha) through TNF-alpha type-I receptor in vitro.

The aim of this study was to find factors which regulate m-leptin secretion during pregnancy. Mouse parametrial adipocytes from day 13 of pregnancy were cultured with or without mouse placental lactogen (mPL)-I, mPL-II, or mouse tumor necrosis factor-alpha (mTNF-alpha) and mouse-leptin (m-leptin) concentration in the medium was assessed by RIA. Up to four days of mPL-I or mPL-II treatment did not affect m-leptin secretion. However, mTNF-alpha, which is produced by adipocytes, significantly inhibited m-leptin secretion in a dose- and time-dependent manner. Antibody to mTNF-alpha completely blocked the inhibitory effect of mTNF-alpha on m-leptin secretion. mTNF-alpha significantly inhibited the expression of m-leptin messenger RNA. Agonistic polyclonal antibody directed against the mTNF-type-I receptor (mTNF-RI) significantly inhibited m-leptin secretion, but the anti-mTNF-RII antibody did not change m-leptin secretion. Moreover, human TNF-alpha (h-TNF-alpha) also inhibited human-leptin (h-leptin) secretion by cultured human adipocytes collected from the subcutaneous fat of pregnant women. These results suggest that TNF-alpha, which is secreted by adipocytes, inhibits m-leptin secretion through mTNF-RI and suggest the presence of an autocrine or paracrine regulation of leptin secretion in human and mouse adipose tissue in vivo.

Adipocytes↗
PubMed1998

An atherogenic midband lipoprotein: a risk factor for coronary artery disease in diabetes mellitus with hyperlipidemia.

On polyacrylamide gel (PAG) disc electrophoresis of serum lipoproteins, the band(s) which migrates between pre beta- and beta-lipoproteins was more frequently observed in hyperlipidemics with diabetes mellitus (73%), than in those without diabetes mellitus (37%) (P < 0.01). Those bands were seen at three positions between pre beta- and beta-lipoproteins. A higher incidence of coronary artery disease (CAD) was observed in patients with midband as a shoulder of beta-lipoproteins (44%), than in those without midband (11%) (P < 0.05) after the matching of other risk factors. These results suggest that midband as a shoulder of beta-lipoproteins may be a risk factor for CAD in diabetes mellitus with hyperlipidemia.

Coronary Disease↗
PubMed1998

Effects of nicotine on peripheral cutaneous blood flow and skin temperature.

We hypothesized that if nicotine was used in a form that was not adulterated with other hazardous substances found in tobacco, it would increase cutaneous blood flow (CBF) resulting in an increase in skin temperature. The effects of nicotine on CBF was investigated in 80 healthy volunteers and 6 patients with peripheral circulation disturbances. Each subject was required to chew nicotine gum (containing 2 mg nicotine) for 15 min and the CBF was then measured with laser blood flowmetry. Skin temperature of 35 volunteers was measured with thermography before and after chewing the gum for 15 min. A control study was performed using ordinary gum without nicotine. Increased CBF (> or = + 1 ml/min/100 g) was observed in 55 of 86 subjects (64%, 33.7-38.6 ml/min/100 g, P < 0.01). An elevation in skin temperature (> + 0.1 degree C) was also observed with nicotine gum in 26 of 35 healthy subjects (74%, + 0.62 +/- 0.96 degree C, P < 0.001). The increase in CBF was greater in subjects in which the initial CBF was lower than in others (P < 0.01). Nicotine gum was found to increase CBF (55/86) and elevate skin temperature (26/35). The smaller the initial CBF value, the greater was the increase in CBF. Nicotine or nicotine derivatives might prove to be useful agents for the treatment of peripheral circulation disturbances.

Adult↗
PubMed1998

Morphological, biochemical and molecular biological characteristics of a granulocyte colony-stimulating factor-producing human eccrine carcinoma cell line.

We describe here a newly established cell line from an eccrine carcinoma which produced an abundant amount of granulocyte colony-stimulating factor (G-CSF). An eccrine carcinoma of the scalp of a 69 year-old-Japanese female had metastasized to the pleura. Clinically, she had marked neutrophilia (up to 60,000/mm3), and a high level of G-CSF (38.7 x 10(3) pg/ml) was detected in the pleural effusion, as determined by enzyme-linked immunosorbent assay (ELISA). We established a cell line in vitro and maintained the cells in culture for 30 months in 90 subcultures. We investigated whether these tumor cells were able to produce G-CSF in culture and found that they were. We also found that the amount of G-CSF produced paralleled the rise in cell number (26.5 x 10(3) pg/ml at confluency). When culture media were administered to rabbits (25 ml/rabbit), the amount of circulating neutrophils increased until the number was equal to or greater than that resulting from injection of recombinant human G-CSF (rhG-CSF)(75 micrograms). This effect persisted for 7 days. When tumors were induced in SCID and nude mice by injecting cultured cells (1 x 10(7) cells/mouse), the number of circulating neutrophils also correlated well with tumor size in these mice (200,000/mm3, 3 cm tumor). After tumor removal, the neutrophil number returned to normal within 30 days. G-CSFmRNA in cultured, cells was detected by RT-PCR. Based on these results, it was confirmed that the marked neutrophilia observed in the patient was caused by the tumor-generated G-CSF. This is the first G-CSF-producing cell line developed from a cancer of the skin.

Adenocarcinoma↗
PubMed1998

Search for human T-lymphotropic virus type I carriers among northeastern Chinese.

Human T-lymphotropic virus type I (HTLV-I) is thought to be the causative agent of adult T-cell leukemia/ lymphoma (ATL). This virus infection is endemic in southwestern Japan, parts of Africa and the Caribbean Islands. We examined sera of 1645 subjects of Liaoning province, northeastern China to detect HTLV-I carriers in an effort to reveal the migratory route taken by the early Japanese (Jomon people). As a result, all sera were found to be negative as tested by particle-agglutination (PA), immunofluorescence (IF), enzyme-linked immunoabsorbent (ELISA) and Western blotting methods. This suggests that the Jomon people, who are thought to have brought HTLV-I to the Japan archipelago tens of thousands of years ago, did not come from northeast China.

Adult↗