Biomedical subjects

T Koide

Publications and source records attributed to T Koide.

At least 91 records · Page 5Linked to original sources

PubMed1998

Expression of Tamm-Horsfall protein in stone-forming rat models.

OBJECTIVES: To examine the expression of Tamm-Horsfall protein (THP) and calcium oxalate deposition in three rat models to clarify whether THP plays an active role in crystal formation or whether crystals induce the secretion of this protein. MATERIALS AND METHODS: A stone-forming rat model (model 1) with marked tubular dilatation in an entire kidney was produced by rendering Wistar rats (aged 8 weeks) hyperoxaluric and hypercalciuric, through compulsorily feeding with 0.12 mL of 5% ethylene glycol (in two doses daily) and 0.5 microgram of vitamin D3 every other day. Two other rat models were also produced. Model 2 comprised stone-forming rats with minimal tubular dilatation, achieved by giving rats the same dose of ethylene glycol once daily, and model 3 comprised stone-free rats with marked tubular dilatation achieved by unilateral ureteric ligation. The rats' kidneys were resected after 4 weeks and all resected kidneys immunohistochemically stained with an antibody to THP. Simultaneously, the location of calcium oxalate (CaOx) crystals was established with von Kossa staining. The relation between crystals and the secretion of THP was also assessed in vitro. Cultured renal epithelial cells (NRK-52E) were stained with an antibody to THP after they had been cultured for 72 h in a medium containing CaOx crystals. RESULTS: In model-1 kidneys with both tubular dilatation and many crystals, there was local and intense expression of THP in many renal tubules. CaOx crystals and the intense expression of THP tended to occur in the same renal tubules. In model 2 kidneys with little tubular dilatation, only a few renal tubules expressed THP strongly and the location of the crystals rarely coincided with that of THP expression. In model 3 kidneys with marked tubular dilatation but no crystals, THP was expressed strongly in many renal tubules. The expression of THP in cultured NRK-52E cells was not stimulated by CaOx crystals. CONCLUSIONS: The results from the in vivo models suggest that THP did not initiate crystal formation and the strong expression of THP was induced not by crystals but by renal tubular damage caused by tubular dilatation. From the close association of THP and crystals in model 1 kidneys, this protein might play a secondary role as an adhesive, promoting stone formation.

Adjuvants, Immunologic↗

PubMed1998

Trypanocidal effects of gallic acid and related compounds.

Gallic acid (3,4,5-trihydroxybenzoic acid) is a naturally abundant plant phenolic compound and it is well known as a component of hydrolyzable tannins. We report here that gallic acid and related compounds have trypanocidal activity against Trypanosoma brucei brucei (GUTat 3.1) in both the long slender bloodstream forms and the procyclic forms, in vitro. LD50 values of gallic acid are 46.96 +/- 1.28 microM for bloodstream forms and 30.02 +/- 3.49 for procyclic forms, respectively. A study of structurally related compounds suggested that the pyrogallol moiety could be responsible for this activity.

Animals↗

PubMed1998

Inhibition of cell growth in culture by quinones.

Quinones were studied for their growth inhibitory effect on cultured malignant cells. HCT-15 cells derived from human colon carcinoma were used for these experiments. Quinones used were arbutin in the benzoquinone group, juglone and lawsone in the naphthaquinone group, alizarin, emodin, 1,8-dihydroxyanthraquinone, and anthraquinone in the anthraquinone group, and xanthone. Cultured cells were incubated with various concentrations of the quinones for four days in a 5% CO2 incubator, after which cell numbers were counted and significance of differences was analyzed by Student's t test. Anthraquinones and naphthaquinones used in these experiments were more effective than the monocyclic quinone. The 50% suppression dose was less than 12.5 micrograms/ml for them. The number of OH groups seemed to play an important role in the degree of the cell growth inhibition: anthraquinones with 2 or 3 OH groups were more effective than those with no OH group like, 9,10-dioxoanthracene and xanthone. In fact, anthraquinones with no OH group and xanthone were not significantly effective. Flow cytometric histograms revealed a specific pattern; that is, lawsone and juglone in the naphthaquinone group and alizarin and 1,8-dihydroxy-anthraquinone in the anthraquinone group blocked mainly the S phase, and emodin in the anthraquinone group blocked the G1 to S phase of the cell cycle.

Anthraquinones↗

PubMed1998

Antitumor effect of gold as revealed by growth suppression of cultured cancer cells.

Gold agents have been widely used for the treatment of rheumatoid arthritis. We studied the growth inhibiting effect of such an agent on malignant cells in vitro. HCT-15, AGS cells derived from a human malignancy, and Meth/A cells from a malignant lymphoma of Balb/C mice were cultured separately with gold agent at concentrations of 2 micrograms/ml. Four days after the cultures had been incubated in a 5% CO2 incubator at 37 degrees C, cell counts were made; and significance of differences was analyzed by Student's t test. Additionally, HCT-15 cells were cultured with gold for two days, and then the cells were analyzed by flow cytometry. The growth of HCT-15, AGS, and Meth/A cells was suppressed by gold. Fifty percent suppression was observed at a concentration between 50 micrograms/ml and 10 micrograms/ml for HCT-15 cells, between 125 micrograms/ml and 50 micrograms/ml for AGS cells, and between 125 micrograms/ml and 50 micrograms/ml for Meth/A cells. Fifty percent suppression of HCT-15 cell growth by cisplatinum was found between 50 micrograms/ml and 10 micrograms/ml. Flow cytometric findings showed a significant rise in the tetraploid peak, a mild rise in the resion between diploid and tetraploid peaks, and an increase in cells with a ploidy greater than four. These data suggest that gold blocks the S phase, G2 to M phase, and M phase as well. To observe the cytotoxicity of gold, each of 10 of 4 week-old Balb/C mice was injected s.c. at a dose of 10 mg/kg or 2 mg/kg every other day for a total of 3 injections, or was administered the gold at 30 mg/kg/day p.o. for 10 days. All mice were still alive after 20 days of observation. Cisplatinum at a dose of 10 mg/kg was also injected s.c. one time into each of 10 mice, and 60% of the animals died within 10 days after the injection.

Animals↗

PubMed1998

Effect of gold on survival of tumor-bearing mice.

Sodium aurothiomalate (monogold monosodium mono-hydrogen sulfidobutanedioate), an anti-rheumatoid gold agent, was injected s.c. every other day for three times or given in drinking water daily for two weeks to Balb/C mice that were inoculated with syngeneic Meth/A cells i.p. As the control, cisplatinum was injected s.c. Survival curve was then observed and significance was determined by Wilcoxon's method. Statistically significant effects on survivals was obtained by 30 mg/kg/day s.c. or 75 mg/kg/day p.o. of gold. A dose of less than 12.5 mg/kg/day s.c. adversely affected the survival. Cisplatinum was significantly effective at the dose of 12.5 mg/kg/day, but markedly toxic at the dose of 125 mg/kg and adversely effective at 6 mg/kg/day s.c. The range of dose effectiveness of cisplatinum on survival was narrower than that of gold. Gold was effective when given s.c. or p.o. No significant toxicity of gold was observed at doses up to 125 mg/kg/day.

Administration, Oral↗

PubMed1998

Anti-tumor effect of methanol extracts from red and white wines.

Crude methanol extracts of red and white wines were added to diethyl ether in order to divide them into the anthocyanin fraction (insoluble in diethyl ether) and fractions containing other flavonoids and their derivatives (soluble in diethyl ether). However, the white wine did not contain anthocyanins (all of the methanol extract was soluble in diethyl ether). When HCT-15 cells, derived from human colon cancer or AGS cells, derived from human gastric cancer, were cultured with these fractions, the anthocyanin fraction from the red wine and the non-anthocyanic substances extracted from red and white wines suppressed the growth of the cells, and the suppression rate by the anthocyanin fraction was significantly higher than that of the other fractions. Thin-layer chromatographic analysis revealed mostly delphinidin in the anthocyanin fraction. The other fractions contained mostly flavonoids and their derivatives. The sugars in all fractions were mainly glucose, fucose, and fructose. Flow cytometric study suggested that the anthocyanin fraction blocked mostly S, G2, and M phase, and the non-anthocyanic flavonoids also blocked these phases, although the histographic pattern varied depending on the fractions. Methanol insoluble but water soluble fractions (mostly free sugars) of red and white wines did not show such suppressive effects.

Anthocyanins↗

PubMed1998

Non-synchronous double adenoma of the parathyroid gland.

A 46-year-old female underwent an excision of a parathyroid adenoma diagnosed as recurrent primary hyperparathyroidism 24 years after the initial excision of a parathyroid adenoma. We report a case of non-synchronous double adenomas of the parathyroid glands documented histopathologically.

Adenoma↗

PubMed1998

Investigation of the possible role of sialic acid in calcium oxalate urolithiasis.

OBJECTIVE: It is considered that sialic acid in urine comprises two different types of sialic acid, that is, the free sialic acid and the bound one which exists as a basic component of urinary macromolecules. The present studies were performed to clarify the role of sialic acid in urine and compare the excretion and concentrations of sialic acid in urine between calcium oxalate (CaOx) stone formers and healthy subjects. METHODS: First, we prepared the crystal surface binding substances from whole human urine. The crystal surface binding substances were digested with sialidase and both the inhibitory activity on CaOx crystal growth and concentrations of sialic acid before and after sialidase digestion were measured. The inhibitory activity of free sialic acid in ultrafiltered urine was also measured. The excretion and concentration of sialic acid in urine from patients with CaOx urolithiasis and healthy controls were determined and compared. RESULTS: The inhibitory activity of crystal surface binding substances on CaOx crystal growth did not show any significant difference before and after sialidase digestion. The free sialic acid had also no effect on CaOx crystal growth. There was no statistically significant difference between CaOx stone formers and healthy controls on the excretion and concentration of sialic acid in urine. The free:bound sialic acid ratio in urine was considered 1:0.97 and 1:1.33 for healthy controls and CaOx stone formers respectively (p = NS). CONCLUSIONS: It is suggested that neither the free sialic acid nor the bound one in urine has a significant inhibitory effect on CaOx crystal growth.

Calcium Oxalate↗

PubMed1998

Disruption of primary imprinting during oocyte growth leads to the modified expression of imprinted genes during embryogenesis.

Parthenogenetic embryos, which contained one genome from a neonate-derived non-growing oocyte and the other from a fully grown oocyte, developed to day 13.5 of gestation in mice, 3 days longer than previously recorded for parthenogenetic development. To investigate the hypothesis that disruption of primary imprinting during oocyte growth leads to the modified expression of imprinted genes and this parthenogenetic phenotype, we have examined Peg1/Mest, Igf2, Peg3, Snrpn, H19, Igf2r and excess p57KIP2. We show that paternally expressed genes, Peg1/Mest, Peg3 and Snrpn, are expressed in the parthenotes, presumably due to a lack of maternal epigenetic modifications during oocyte growth. In contrast, the expression of Igf2, which is repressed in a competitive manner by transcription of the H19 gene, was very low. Furthermore, we show that the maternally expressed Igf2r and p57KIP2 genes were repressed in the alleles of the non-growing oocyte indicating maternal modifications during oocyte growth are necessary for its expression. Thus, our results show that primary imprinting during oocyte growth exhibits a crucial effect on both the expression and repression of maternal alleles during embryogenesis.

Animals↗

PubMed1998

Importance of sialic acid in recombinant thrombomodulin in terms of pharmacokinetics and separation of desialyzed glycoprotein.

Recombinant glycosaminoglycan-modified urinary thrombomodulin (GAG-UTM) expressed in mouse C-127 cells has potent antithrombotic activity available as an anticoagulant. GAG-UTM, a glycoprotein with sialic acid, was investigated regarding the influence of the terminal sialic acid on its pharmacokinetics upon rapid intravenous injection in rat. Asialo GAG-UTM desialated by neuraminidase was cleared rapidly from plasma. Sialyzed GAG-UTM, a sialyzed asialo GAG-UTM with alpha-2, 6-sialyltransferase, containing sialic acid similarly to native sialo GAG-UTM, had only a short half-life in plasma, suggesting that the binding site of sialic acid on galactose was not only sialyzed with alpha-2, 6-sialyltransferase but also with 2, 3-sialyltransferase. Asialo GAG-UTM with oxidized terminal galactose, however, had a long half-life. These results suggest that terminal sialic acid may be important to the pharmacokinetics of GAG-UTM; therefore, an analysis of asialo GAG-UTM became significant for quality control. In order to analyze sialo- and asialo-types in the early stage of purification, we investigated separation and analysis methods for both types and found a suitable sample of each: RCA-120-Agarose column for separation and ELISA using anti-thrombomodulin antibody and RCA lectin for analysis.

Animals↗

PubMed1998

Formation of reactive oxygen intermediates might be involved in the trypanocidal activity of gallic acid.

We investigated the mechanism of the trypanocidal activity of gallic acid (GA). GA-induced trypanocidal activity was significantly reduced by pretreatment with superoxide dismutase (SOD) and/or catalase. The ESR technique with 5,5-dimethyl-1-pyrroline N-oxide (DMPO) as a spin trapping agent revealed that a DMPO-OH adduct was detected in culture medium containing GA. The intensity of ESR signals of the DMPO-OH adduct was increased in a time dependent manner. SOD also inhibited the formation of GA-induced DMPO-OH adducts. Furthermore, GA enhanced DNA single-strand breaks induced by Fenton reagent. These results suggest the possibility that GA acts as pro-oxidant for trypanocidal activity.

Animals↗

PubMed1998

Trypanocidal effects of curcumin in vitro.

During the course of study searching for the antiparasitic agents from natural compounds, we found that curcumin showed cytotoxicity against African trypanosomes in vitro. The LD50 values of curcumin were 4.77 +/- 0.91 microM for bloodstream forms and 46.52 +/- 4.94 microM for procyclic forms of Trypanosoma brucei brucei (GUTat 3.1 clone).

Animals↗

PubMed1998

Insulin-like growth factor-I potentiates protein synthesis induced by thyrotropin in FRTL-5 cells: comparison of induction of protein synthesis and DNA synthesis.

In FRTL-5 cells, we and others have shown that TSH and insulin-like growth factor-I (IGF-I) stimulate DNA synthesis synergistically. The present study was undertaken to determine whether interaction between TSH and IGF-I also affects protein synthesis in this cell line, and if so by what mechanism. Quiescent cells were treated with TSH and/or IGF-I and [3H]valine incorporation into the acid-insoluble fraction was measured as a parameter of protein synthesis. Similar to their effects on cell proliferation, TSH or IGF-I alone induced protein synthesis only slightly, but treatment with a combination of TSH and IGF-I (or insulin with about a 100-fold higher concentration than IGF-I) greatly increased protein synthesis. The presence of IGF-I potentiated a TSH-concentration-dependent increase in protein synthesis and in DNA synthesis. In addition, we observed this potentiation when the cells were treated with other cAMP-generating agents and cAMP analogues instead of TSH. We have shown that priming with TSH potentiated DNA synthesis induced by IGF-I, whereas pretreatment with IGF-I enhanced protein synthesis induced by TSH. This observation suggested that protein synthesis and DNA synthesis were potentiated through different mechanisms. From an analysis of cAMP production, it appears that the potentiation of protein synthesis may be explained by an IGF-I-dependent increase in cAMP production induced by TSH at least in part. On the other hand, IGF-I and TSH stimulated (alpha-aminoisobutyric acid (AIB) uptake synergistically, but RNA synthesis induced by IGF-I was depressed by TSH. From these results, we concluded that in FRTL-5 cells, IGF-I potentiated protein synthesis induced by TSH by means of complex mechanisms and the interaction between IGF-I and cAMP-dependent pathways may also have a physiological meaning in regulating protein anabolism.

Animals↗

PubMed1998

Effect of acarbose (alpha-glucosidase inhibitor) on disaccharase activity in small intestine in KK-Ay and ddY mice.

The hypoglycemic effect and the alpha-glucosidase activity inhibition of acarbose (AC:alpha-glucosidase inhibitor) were investigated in normal and KK-Ay mice, an animal model of noninsulin-dependent diabetes mellitus (NIDDM). AC improved hyperglycemia after an oral administration of maltose or sucrose, dose dependently in normal mice (1, 10, and 50mg/kg body weight) and in KK-Ay mice (50mg/kg). Furthermore, AC (50mg/kg) significantly inhibited maltase and sucrase activities in the small intestines of normal and KK-Ay mice (inhibitory efficacy: sucrase > maltase). The enzymatic inhibition in KK-Ay mice is stronger than in normal mice. However, AC (50 mg/kg) did not suppress the blood glucose in oral lactose tolerance and did not inhibit the lactase activity in either normal or KK-Ay mice. These findings indicate that the AC effect on the inhibition of alpha-glucosidase activity is selective for sucrase and maltase in normal and NIDDM mice.

Acarbose↗

PubMed1998

Continuous growth of bloodstream forms of Trypanosoma brucei brucei in an axenic culture system containing a low concentration of serum.

An effective axenic culture system for bloodstream forms of Trypanosoma brucei brucei GUT at 3.1 containing a low concentration of serum is described. Bloodstream forms routinely maintained in Iscove's modification of Dulbecco's medium supplemented with 100 microM hypoxanthine, 30 microM thymidine, 40 microM adenosine, 1 mM sodium pyruvate, 50 microM L-glutamine, 100 microM 2-mercaptoethanol and 20% FBS for more than one year were grown in the same medium supplemented with 5% FBS without reducing their growth rate. Then culture adapted trypanosomes in the culture medium containing 5% FBS were transferred into the modified medium supplemented with 0.5% FBS. For the constant growth of bloodstream forms in the medium containing 0.5% FBS, the culture medium was further supplemented with 200 microM L-alanine, 100 microM glycine, 10 microM L-oruithine hydrochloride and 10 microM L-citrullin. The trypanosomes propagated in this culture system for one year retained their infectivity for mice. This culture system was also shown to be useful for cloning of T.b. brucei GUT at 3.1 which is important for separation of mutants.

Animals↗

PubMed1998

Antitrypanosomal effects of traditional Chinese herbal medicines on bloodstream forms of Trypanosoma brucei rhodesiense in vitro.

The antitrypanosomal activity of traditional Chinese herbal medicines and these crude drug ingredients were determined using axenic cultured bloodstream forms of Trypanosoma b. rhodesiense which is one of the two causative agents of African sleeping sickness in man. The drugs tested were 8 traditional Chinese herbal medicines and these 14 crude drug ingredients. Of these traditional Chinese medicines examined, san'o-shasin-to and oren-gedoku-to showed most potent antitrypanosomal effect. The minimal effective concentration (MEC) which killed all bloodstream form populations within 24 hours of both drug exposure was 125 microg/ml. The 50% effective concentration (EC50) of san'o-shashin-to and oren-gedoku-to was 63 and 74 microg/ml, respectively. In the crude drug ingredients tested, Scutellaria baicalensis G. and Coptis japonica M. which are the main components of san'o-shasin-to and oren-gedoku-to, showed the most powerful antitrypanosomal activity. The MEC and EC50 value of these crude drug ingredients were 30 and 60 microg/ml, and 20 and 36 microg/ml.

Animals↗

PubMed1998

[Effect of chorei-to and gorei-san on calcium oxalate crystallization in human urine].

The inhibitory effect of two kinds of Kampou medicine, Chorei-to and Gorei-san, on calcium oxalate crystallization in human urine, was examined. Chorei-to or Gorei-san was administered to 15 healthy male volunteers for three consecutive days under normal dietary conditions and 24-hour urine samples were collected before and after the administration. Urinary parameters including calcium, phosphorus, uric acid, oxalate and citrate were measured on each sample obtained. The inhibitory effect on calcium oxalate crystallization was examined using part of the collected 24-hour urine. There was no significant difference in urinary parameters before and after Chorei-to administration. Gorei-san administration significantly increased magnesium excretion in urine. A significant inhibitory effect on calcium oxalate crystallization in human urine was recognized when Gorei-san was administered, whereas Chorei-to had no inhibitory effect on calcium oxalate crystallization in urine.

Adult↗

PubMed1998

[Fleroxacin treatment for acute uncomplicated cystitis in women: comparison of 3-day and 7-day therapy].

The clinical efficacy of fleroxacin (FLRX), a new fluoroquinolone, for acute uncomplicated cystitis (AUC) in women was assessed. Two regimens, 3-day and 7-day courses of FLRX, 200 mg once a day, were compared. Clinical and bacteriological efficacy were evaluated after the therapy, and recurrence rate was evaluated 1 week and 4 weeks after termination of the therapy. Of 136 registered subjects, 35 in the 3-day group and 47 in the 7-day group were evaluated. According to the criteria of Japanese UTI Committee (3rd edition), the rate of excellent results was significantly higher in the 7-day group (78.9%) than in the 3-day group (48.6%), but the overall clinical efficacy rate was similar being 100% and 97.9%, respectively. Although no recurrence was seen 1 week after the therapy in either group, recurrence was seen in 14.3% and 7.4% of the cases in the 3-day and 7-day groups, respectively, 4 weeks after the therapy. Adverse reactions were observed in 2 and 3 cases in the 3-day and 7-day groups, respectively. Both 3-day and 7-day regimens of FLRX treatment showed good efficacy. Although the 7-day treatment was superior to the 3-day treatment as to high rate of excellent results and low rate of recurrence, the 3-day treatment was concluded to be sufficient for AUC.

Adult↗