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Biomedical subjects

T Kanzaki

Publications and source records attributed to T Kanzaki.

At least 19 recordsLinked to original sources
PubMed2000

Enhanced expression of cyclooxygenase (COX)-2 in human skin epidermal cancer cells: evidence for growth suppression by inhibiting COX-2 expression.

Cyclooxygenase (COX)-2 is one of the rate-limiting enzymes in the conversion of arachidonic acid to prostaglandins and other eicosanoids. Recent studies have shown enhanced expression of COX-2 in cancer cells of several tissues. We investigated the expression of COX-2 and prostaglandin (PG) E((2)) production in two human skin epidermal cancer cell lines: cutaneous squamous cell carcinoma, HSC-5, and eccrine carcinoma, EcCa. Both COX-2 expression and PGE((2)) production were significantly enhanced in cancer cell lines compared with the non-tumorigenic human keratinocyte cell line, HaCaT. In order to determine the role of COX-2 in the proliferation of HSC-5 and EcCa, the growth of untreated cells and cells transfected with COX-2 antisense oligonucleotide was compared using the MTT assay. Transfection with the antisense oligonucleotide suppressed COX-2 protein expression and significantly inhibited cell growth. The effect of a selective inhibitor of COX-2, NS398, was compared with the effect of the antisense oligonucleotide in order to see whether COX-2 expression and prostaglandins have selective effects on cell growth. COX-2 expression was unchanged by NS398 treatment, whereas NS398 inhibited cell growth to a certain extent. The degree of growth inhibition was greater with the antisense oligonucleotide than with NS398. Our findings indicate that COX-2 protein expression is enhanced in skin epidermal cancer cells and that COX-2 plays a pivotal role in regulating cell growth. Furthermore, inhibition of COX-2 expression had a more significant effect on growth suppression than inhibition of COX-2 catalytic activity, suggesting the existence of two different signal pathways via COX-2 in regulating cell growth.

Catalysis↗
PubMed2000

Involvement of extracellular signal-regulated protein kinase in gliosis induced during recovery from metabolic inhibition.

Brain reperfusion may be of particular importance in the etiology of periventricular leukomalacia, of which the common findings are gliosis and ventricular dilatation. To investigate the mechanism of this pathogenesis, we used a metabolic inhibition (MI) model using cyanide plus deoxyglucose treatment of cultured glia isolated from fetal rat brain and examined the activity of extracellular signal-regulated protein kinase (ERK) during MI and also during the recovery from MI of 30 min. ERK activation was stimulated during MI and the recovery from MI. The time course and extent of activation of ERK during MI and the recovery from MI, however, were distinctly different. Activation of ERK was stimulated within 5 min of MI and declined thereafter. Activation of ERK was sustained during the recovery phase from MI and the extent of the activation was much greater than that during MI. Pretreatment with EGTA to eliminate extracellular Ca(2+), or with APV, an NMDA receptor antagonist, to inhibit Ca(2+) influx through the NMDA receptor, attenuated the activation of ERK. Moreover, pretreatment with PMA to downregulate PKC abolished the activation of ERK. PD98059, an inhibitor of ERK kinase, attenuated the cell proliferation induced by MI followed by recovery from MI. These results suggest that ERK is involved in gliosis during the recovery phase from MI and may play a role in the etiology of periventricular leukomalacia.

2-Amino-5-phosphonovalerate↗
PubMed2000

Fabry disease: ultrastructural lectin histochemical analyses of lysosomal deposits.

Fabry disease is an X-linked inborn error of glycosphingolipid catabolism resulting from a deficiency of lysosomal alpha-galactosidase activity. Globotriaosylceramide accumulates predominantly in lysosomes of various tissues. Former studies have clarified the nature of this disease, and the accumulated materials in the lysosomes have been analyzed using biochemical techniques. In the present study, transmission electron microscopy was used to reveal the fine structure of these lysosomal deposits, and sugar residues in the lysosomal deposits in Fabry disease were examined by lectin histochemistry combined with enzyme digestion. This is the first report to describe the lysosomal sugar residues in Fabry disease analyzed using lectin histochemistry at the ultrastructural level. With these techniques, we were able to detect alpha-galactosyl, beta-galactosyl and glucosyl sugar residues in the lysosomal deposits. The experimental procedures used in this study have considerable potential for use in investigations of glycolipid and glycoprotein storage diseases without the need for complex methodology and expensive materials.

Adolescent↗
PubMed2000

Increased atherogenesis in Otsuka Long-Evans Tokushima fatty rats before the onset of diabetes mellitus: association with overexpression of PDGF beta-receptors in aortic smooth muscle cells.

The mechanism of diabetic macroangiopathy was studied from the view point of phenotypic change of arterial smooth muscle cells (SMC). Otsuka Long-Evans Tokushima fatty (OLETF) rat, an animal model of non-insulin dependent diabetes mellitus (NIDDM), develops spontaneous persistent hyperglycemia after the age of 18 weeks. Medial SMC in OLETF rats expressed more platelet-derived growth factor (PDGF) beta-receptor and fibronectin at the protein level than those from control, Long-Evans Tokushima Otsuka (LETO) rats, not only after but also before the onset of diabetes mellitus. Cultured SMC from OLETF rats more strongly responded specifically to the mitogenic stimuli of PDGF-AB and PDGF-BB and also expressed PDGF beta-receptor more intensely compared with those from LETO rats. PDGF is known to be the main contributor to the intimal thickening induced by balloon catheter injury, which is one of several forms of arterial injuries. Intimal thickening of carotid arteries in OLETF rats after balloon catheter injury increased compared with that in LETO rats before the onset of diabetes mellitus. In in vitro culture system, fibronectin synthesis was stimulated by transforming growth factor-beta1(TGF-beta1) in SMC from OLETF rats, but not in those from LETO rats, suggesting that SMC from OLETF rats respond to TGF-beta1. These results indicate that overexpression of PDGF beta-receptor and fibronectin in medial SMC plays an important role in the accelerated intimal thickening before the onset of diabetes mellitus in OLETF rats.

Animals↗
PubMed2000

A case of pseudogout.

We report a 56-year-old Japanese male with a gout-like acute attack of synovitis and panniculitis in his right wrist without hyperuricemia. Calcium pyrophosphate dihydrate (CPPD) crystals were found in the synovial fluid of the affected joint. A diagnosis of pseudogout was made. The attack subsided two days after medication with 30 mg of predonisolon. Although this is a relatively common disease in elderly people, we rarely encounter such case reports in dermatological journals.

Calcium Pyrophosphate↗
PubMed2000

Dimeric inhibin A as a fourth marker for Down's syndrome maternal serum screening in native Japanese women.

OBJECTIVE: This study was conducted to assess the usefulness of dimeric inhibin A as a fourth marker for Down's syndrome screening in addition to AFP, hCG and uE3 markers for native Japanese women. METHODS: Serum specimens from 367 native Japanese women in the second trimester were assayed for dimeric inhibin A levels. Day specific dimeric inhibin A medians were established for gestational ages 15.0-21.9. Weekly median values for the native Japanese were compared with those of a U.S. population. Selected Japanese specimens from 15 diagnosed Down's syndrome and 3 trisomy 18 cases were also assayed for dimeric inhibin A. RESULTS: Dimeric inhibin A levels did not vary greatly over the gestational age range as expected. Median value comparison showed that native Japanese dimeric inhibin A medians are higher than the U.S. population medians by an average of 7.95%. Native Japanese dimeric inhibin A median values in this study are 1.77 times higher in Down's syndrome cases than in unaffected pregnancies. Trisomy 18 dimeric inhibin A levels show no significant difference from the unaffected pregnancies. CONCLUSIONS: This report shows for the first time that dimeric inhibin A can be informative as a fourth marker for Down's syndrome screening in native Japanese women. We expect the addition of dimeric inhibin A to a triple marker protocol will increase the accuracy of predicted risk for all pregnancies screened and increase the detection rate of Down's syndrome affected pregnancies.

Biomarkers↗
PubMed2000

Three cases of pityriasis rubra pilaris successfully treated with cyclosporin A.

BACKGROUND: Pityriasis rubra pilaris (PRP) is reported to respond poorly to cyclosporin A (CsA). OBJECTIVE: We attempted to determine the efficacy of CsA in the treatment of classic adult-type PRP. METHODS: Three patients with classic adult-type PRP were treated with 5 mg/kg/day CsA. RESULTS: A sustained clinical response was achieved within 2-4 weeks of therapy. Relapses were noted when the CsA dose was decreased to 1.2 mg/kg/day. CONCLUSION: CsA should be considered in the treatment of classical adult-type PRP.

Adult↗
PubMed2000

Scleroderma en coup de sabre with central nervous system involvement.

We describe a patient with scleroderma en coup de sabre and central nervous system symptoms. She presented with a linear scleroderma on her left paramedian forehead and scalp and suffered from headaches and dizziness. Axial T2-weighted MRI showed a 1 cm, high intense signal abnormality in the medial aspect of the left frontal lobe.

Adolescent↗
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↗