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Biomedical subjects

Y Komatsu

Publications and source records attributed to Y Komatsu.

At least 145 records · Page 8Linked to original sources
PubMed1998

Oral administration of a Kampo (Japanese herbal) medicine Juzen-taiho-to inhibits liver metastasis of colon 26-L5 carcinoma cells.

We have investigated the inhibitory effect of oral administration of Juzen-taiho-to, a Kampo Japanese herbal medicine, on liver metastasis by the inoculation of a liver-metastatic variant (L5) of murine colon 26 carcinoma cells into the portal vein. Oral administration of Juzen-taiho-to for 7 days before tumor inoculation resulted in dose-dependent inhibition of liver tumor colonies and significant enhancement of survival rate as compared with the untreated control, without side effects. We also found that liver metastasis of L5 cells was enhanced in BALB/c mice pretreated with anti-asialo GM1 serum or 2-chloroadenosine, and in BALB/c nu/nu mice, compared to normal mice. This indicates that NK cells, macrophages, and T-cells play important roles in the prevention of metastasis of tumor cells. Juzen-taiho-to significantly inhibited the experimental liver metastasis of colon 26-L5 cells in mice pretreated with anti-asialo GM1 serum and untreated normal mice, whereas it did not inhibit metastasis in 2-chloroadenosine-pretreated mice or T-cell-deficient nude mice. Oral administration of Juzen-taiho-to activated peritoneal exudate macrophages (PEM) to become cytostatic against the tumor cells. These results show that oral administration of Juzen-taiho-to inhibited liver metastasis of colon 26-L5 cells, possibly through a mechanism mediated by the activation of macrophages and/or T-cells in the host immune system. Thus, Juzen-taiho-to may be efficacious for the prevention of cancer metastasis.

2-Chloroadenosine↗
PubMed1998

In vivo adenovirus-mediated prodrug gene therapy for carcinoembryonic antigen-producing pancreatic cancer.

In gene therapy for malignancy, the herpes simplex virus thymidine kinase (HSVtk)-ganciclovir (GCV) system has been widely used. For pancreatic cancer targeting, we estimated the therapeutic efficacy of gene transduction by an adenovirus-carrying HSVtk gene under the control of a carcinoembryonic antigen (CEA) promoter (AdCEAtk) followed by systemic administration of GCV. Four cell lines, CEA-producing Su.86.86. BxPC-3 (pancreatic cancer cells), MKN45 (gastric cancer cells) and CEA-nonproducing HeLa, were used for analysis of GCV sensitivity induced by adenoviral gene transduction. To evaluate the therapeutic efficacy of AdCEAtk and GCV administration in human CEA-positive pancreatic cancer in vivo, a subcutaneously implanted tumor-bearing nude mouse model was used. When the HSVtk gene was transduced with a ubiquitous promoter into these cells, increase of the GCV sensitivity was independent of CEA-production. In contrast, when the cells were transduced with a CEA promoter, the cell-killing effect of GCV was increased in only CEA-producing cells. For in vivo analysis, AdCEAtk was delivered into subcutaneously established tumors of Su.86.86 cells. Immunohistochemical staining of the tumor showed that HSVtk protein was expressed only in tumor cells, and tumor growth was markedly suppressed by administration of GCV. These results suggest that the adenovirus-mediated transfer of HSVtk gene with CEA promoter specifically increases the GCV sensitivity of CEA-producing pancreatic cancer cells in vitro and in vivo. This strategy may provide a useful tool for treating pancreatic cancer, especially CEA-producing tumor cells.

Adenoviridae↗
PubMed1998

Evidence for the interplay between trehalose metabolism and Hsp104 in yeast.

Disruption of the HSP104 gene in a mutant which cannot accumulate trehalose during heat shock treatment caused trehalose accumulation (H. Iwahashi, K. Obuchi, S. Fujii, and Y. Komatsu, Lett. Appl. Microbiol 25:43-47, 1997). This implies that Hsp104 affects trehalose metabolism. Thus, we measured the activities of enzymes involved in trehalose metabolism. The activities of trehalose-synthesizing and -hydrolyzing enzymes are low in the HSP104 disruption mutant during heat shock. This data is correlated with intracellular trehalose and glucose levels observed in the HSP104 disruption mutant. These results suggest that during heat shock, Hsp104 contributes to the simultaneous increase in both accumulation and degradation of trehalose.

Fungal Proteins↗
PubMed1998

Anti-inflammatory effects of mao-bushi-saishin-to in mice and rats.

Effects of Mao-Bushi-Saishin-to (MBS) on anti-inflammatory activities were examined in mice and rats. MBS significantly inhibited the increase in vascular permeability induced by acetic acid, the ear edema induced by arachidonic acid and phorbol ester, and the cutaneous extravasation induced by bradykinin and histamine. MBS, however, was not effective against the serotonin-induced cutaneous permeability increase in mice. MBS significantly inhibited carrageenin-induced hind foot edema and cotton pellet-induced granulation tissue growth in rats. These results show that MBS may exert anti-inflammatory effects through the underlying mechanism(s) of preventing mediator release from mast cells and macrophages.

Acetic Acid↗
PubMed1998

Regulation of endothelial production of C-type natriuretic peptide by interaction between endothelial cells and macrophages.

We demonstrated endothelial production of C-type natriuretic peptide (CNP), the third member of the natriuretic peptide family, and its regulation by cytokines, including tumor necrosis factor-alpha (TNF alpha). We thus proposed that CNP can control vascular tone and growth as an endothelium-derived relaxing peptide. We also revealed the marked elevation of plasma CNP concentration in patients with septic shock, in which TNF alpha plays a significant part. As the interaction between endothelial cells (EC) and monocytes-macrophages plays a pivotal role in the pathogenesis of atherosclerosis, we investigated the effect of coculture of EC and macrophages on endothelial production of CNP. We used a human monocytic leukemia cell line, THP-1, which differentiates into macrophages when treated with phorbol 12-myristate 13-acetate. The coculture of EC and THP-1-derived macrophages enhanced CNP secretion by more than 10-fold compared with the single culture of EC or the coculture of EC and THP-1 without phorbol 12-myristate 13-acetate treatment. Prevention of direct contact between EC and THP-1-derived macrophages did not attenuate the increase in CNP secretion. Northern blotting revealed the augmentation of CNP messenger RNA expression in EC in the coculture. We detected TNF alpha in the conditioned medium from the coculture of EC and THP-1-derived macrophages. Furthermore, anti-TNF alpha antibody inhibited the stimulation of CNP secretion in the coculture. CNP at a concentration of 1 nM did not stimulate cGMP production in EC or THP-1-derived macrophages, but it elevated cGMP production significantly in vascular smooth muscle cells. These results indicate that endothelial production of CNP is stimulated mainly by TNF alpha released from THP-1-derived macrophages in the coculture. Endothelial CNP at the enhanced level may be one of the vascular mediators to regulate local vascular tone and growth through cGMP production by vascular smooth muscle cells, suggesting the potential significance of endothelial CNP in atherosclerosis.

Animals↗
PubMed1998

Primary position upbeat nystagmus increased on downward gaze: clinicopathologic study of a patient with multiple sclerosis.

We describe a patient with multiple sclerosis who had primary position upbeat nystagmus that increased in amplitude on downward gaze. Pathologic examination revealed demyelinating foci with macrophage infiltration in the lower medulla, involving the perihypoglossal nuclei (the intercalatus nuclei). A lesion of this region may be responsible for upbeat nystagmus.

Autopsy↗
PubMed1998

Effects of Hange-shashin-to on cholera toxin-induced fluid secretion in the small intestine of rats.

The effects of Hange-shashin-to (TJ-14) on cholera toxin-induced intestinal fluid secretion were studied to elucidate the mechanism by which this kampo medicine manifests antidiarrheal effects. TJ-14 suppressed the intestinal fluid secretion induced by cholera toxin (1 microg/rat) in a dose-dependent manner at doses between 125 and 1000 mg/kg. It also inhibited the luminal prostaglandin E2 (PGE2) level. On the other hand, serotonin (5-HT) release was not affected by TJ-14. Subcutaneous injection of indomethacin at 10 mg/kg or ondansetron at 100 microg/kg significantly suppressed intestinal secretion. The luminal PGE2 level was also inhibited by indomethacin (10 mg/kg, s.c.). TJ-14, even at 10(-4) g/ml, had little effect on the phasic contraction of isolated guinea pig ileum induced by 5-HT (2 x 10(-6) g/ml), while ondansetron suppressed the phasic contraction caused by 5-HT. These results indicate that TJ-14 is useful in suppressing cholera toxin-stimulated intestinal fluid secretion, and that this effect is partially due to its suppressive action on the PGE2 level.

Animals↗
PubMed1998

Mechanisms by which Hange-shashin-to reduces prostaglandin E2 levels.

To determine the mechanisms by which Hange-shashin-to (TJ-14) reduces prostaglandin E2 (PGE2) levels, the effects on blood corticosterone levels were examined in vivo and the effects on cyclooxygenase (COX) activity in vitro assessed. TJ-14, orally administered to rats at dose levels between 125 and 1000 mg/kg, caused a dose-dependent increase in blood corticosterone levels. We also showed that Glycyrrhizae Radix and Ginseng Radix, constituents of TJ-14, are involved in the increase in blood corticosterone. The activity of COX-1 was not inhibited by TJ-14 even at a dose of 1000 microg/ml, while COX-2 was inhibited at dose levels between 10 and 1000 microg/ml. The constituents Scutellariae Radix, Glycyrrhizae Radix and Coptidis Rhizoma were believed to be involved in COX-2 inhibition. These results suggest that the effect of TJ-14 in decreasing PGE2 is partially mediated by corticosterone and inhibition of COX-2.

Animals↗
PubMed1998

New antidiabetic compounds, mangiferin and its glucoside.

Mangiferin (MF) and its glucosides (mangiferin-7-O-beta-glucoside) (MG) isolated from Anemarrhena asphodeloides Bunge rhizome, were tested for their antidiabetic activity in KK-Ay mice, an animal model of non-insulin-dependent diabetes mellitus (NIDDM). MF and MG lowered the blood glucose level of KK-Ay mice after oral administration. However, no affect on the blood glucose level in normal mice was seen, indicating that MF and MG are useful in treating NIDDM. In addition, MF or MG improved hyperinsulinemia in KK-Ay mice. From these findings, it seems likely that MF and MG exert their its antidiabetic activity by increasing insulin sensitivity.

Animals↗
PubMed1998

Expression of the anti-metastatic effect induced by Juzen-taiho-to is based on the content of Shimotsu-to constituents.

We investigated the inhibitory effect of oral administration of Juzen-taiho-to, a Kampo Japanese herbal medicine, and its related formulations on the experimental liver and lung metastasis of tumor cells in vivo. Oral administration of Juzen-taiho-to for 7 d before tumor inoculation significantly reduced the number of liver metastatic colonies of colon 26-L5 carcinoma cells and attenuated the increase of liver weight in a dose-dependent manner ranging from 4 to 40 mg/d. Its oral administration for this same period before tumor inoculation also significantly inhibited lung metastasis of B16-BL6 melanoma cells. Juzen-taiho-to originally consisted of 8 crude drugs derived from Shimotsu-to and Shikunshi-to prescriptions together with two crude drugs (Cinnamomi Cortex and Astragali Radix). Oral administration of Shimotsu-to as well as Juzen-taiho-to for 7 d before tumor inoculation resulted in a significant reduction in the number of metastatic colonies and the liver weight as compared with the control, whereas Shikunshi-to did not exhibit such an inhibitory effect. Unsei-in containing four Shimotsu-to constituents was also active in inhibiting liver metastasis. Toki-shakuyaku-san and Ninjin-yoei-to, which include all Shimotsu-to constituents except Rehmanniae Radix and Cnidii Rhizoma, respectively, did not show a significant anti-metastatic effect. Rikkunshi-to and Ninjin-yoei-to, which contain Shikunshi-to constituents, did not affect the inhibition of liver metastasis. Hochu-ekki-to treatment before tumor inoculation also led to a significant inhibition of liver metastasis, probably through an inhibitory mechanism different from Juzen-taiho-to. These results suggest that the anti-metastatic effect of Juzen-taiho-to is partly associated with its Shimotsu-to-derived constituents.

Animals↗
PubMed1998

Inhibitory effect of Coptidis Rhizoma and Scutellariae Radix on azoxymethane-induced aberrant crypt foci formation in rat colon.

This study was conducted to obtain effective cancer chemopreventive agents with low toxicity from medicinal herbs. The effect of aqueous extracts from 9 medicinal herbs with antiinflammatory effect were examined on the formation of azoxymethane (AOM)-induced aberrant crypt foci (ACF), putative preneoplastic lesions of the colon. Male F344 rats were treated with 15 mg/kg body weight of AOM once a week for two weeks. Herbal extract consisting of 2% of the diet was administered from 1 d prior to the first carcinogen treatment. The number of AOM-induced ACF per colon was counted at 4 week. Extracts of Coptidis Rhizoma and Scutellariae Radix significantly inhibited AOM-induced ACF formation. The number of ACF was decreased to 54% and 78% of that of the control by 2% Coptidis Rhizoma and Scutellariae Radix extract in the diet, respectively. Berberine and Baicalin, major ingredients of Coptidis Rhizoma and Scutellariae Radix, inhibited ACF formation at a dose equivalent to the amount in each herbal extract. Therefore, to investigate the mechanisms of action of berberine and baicalein which is the active substances of orally administered baicalin, their effects on cyclooxygenase 1 and 2 activities were studied. Berberine was found to inhibit cyclooxygenase 2 activity without inhibition of cyclooxygenase 1 activity, and baicalein inhibited cyclooxygenase 1 activity. Thus, Coptidis Rhizoma and Scutellariae Radix suppressed experimental colon carcinogenesis, and their chemopreventive effects were explained from the inhibition of berberine on cyclooxygenase 2 activity and baicalein on cyclooxygenase 1 activity.

Animals↗
PubMed1998

Effect of Gosha-jinki-gan, a Kampo medicine, on enhanced platelet aggregation in streptozotocin-induced diabetic rats.

We evaluated the effects of Gosha-jinki-gan on platelet aggregation in streptozotocin-induced diabetic rats. Enhanced ADP (2 microM)-induced aggregation of platelets obtained from diabetic rats was inhibited by a single treatment with Gosha-jinki-gan (0.3, 1.5 g/kg, p.o.). The anti-platelet aggregatory effect of Gosha-jinki-gan (1.5 g/kg, p.o.) was attenuated by simultaneous administration of atropine (1 mg/kg, i.p.) and was abolished by combination of atropine with Hoe 140 (250 microg/kg x 2, i.p.), a bradykinin B2 receptor antagonist or L-NAME (10 mg/kg, i.p.), an inhibitor of nitric oxide-synthase. These results suggested that Gosha-jinki-gan could improve platelet aggregation in diabetes through increased production of nitric oxide via bradykinin B2-receptors and muscarinic acetylcholine receptors.

Adenosine Diphosphate↗
PubMed1998

Effects of intravenously administered C-type natriuretic peptide in humans: comparison with atrial natriuretic peptide.

We have previously reported that C-type natriuretic peptide (CNP), the third member of the natriuretic peptide family, is produced in vascular endothelial cells and suggested that CNP might be a local regulator of vascular tone and growth. To evaluate the biological actions of CNP as compared with human atrial natriuretic peptide (hANP), we intravenously administered synthetic CNP (0.43 nmol/kg) and alpha-hANP (0.43 and 0.043 nmol/kg) to healthy humans. The experiments were done on different days in the same five healthy volunteers (31+/-1 yr old). CNP injection caused a transient but significant decrease in both systolic and diastolic blood pressure (-4.3+/-1.3, -4.1+/-1.0 mmHg) with a significant increase in heart rate (+7.6+/-2.6 bpm), and exerted significant diuretic and natriuretic activities (+130+/-80%, +160+/-100% over the basal level). These effects of CNP (0.43 nmol/kg) were comparable to, or less than, those of alpha-hANP (0.043 nmol/kg). CNP injection also significantly suppressed aldosterone secretion (22% reduction as compared with the basal level). Our results demonstrate that intravenously-administered CNP acts as a natriuretic peptide with less potency than ANP.

Adult↗
PubMed1998

Effects of gosha-jinki-gan, a kampo medicine, on peripheral tissue blood flow in streptozotocin-induced diabetic rats.

We examined the effects of Gosha-jinki-gan on peripheral tissue blood flow in streptozotocin-induced diabetic rats and its mechanism. The decrease in peroneal muscular blood flow in diabetic rats was dose-dependently improved by treatment with Gosha-jinki-gan (0.1-1 g/kg/day, p.o.) for 4 weeks. Investigation of the time course of blood flow in the hind paws revealed that single-dose of Gosha-jinki-gan (0.3, 1.5 g/kg, i.d.) increased peripheral blood flow. Peripheral blood flow-increasing effects of Gosha-jinki-gan (1.5 g/kg, i.d.) were reduced in combination with atropine (1 mg/kg, i.v.), and disappeared by pretreatment with NG-nitro-L-arginine methyl ester (10 mg/kg, i.v.). Levels of aortic guanosine 3',5'-cyclic monophosphate were dose-dependently increased by administration of Gosha-jinki-gan (0.3, 1.5 g/kg, p.o). These results suggest that Gosha-jinki-gan has vasodilating effects via increases in nitric oxide production. Gosha-jinki-gan may be useful for treating peripheral circulation disorders in the diabetic state.

Animals↗
PubMed1998

Protective effect of oral administration of a traditional medicine, Juzen-Taiho-To, and its components on lethal Candida albicans infection in immunosuppressed mice.

Protective effects of a kampo medicine, Juzen-taiho-to (TJ-48) and its herbal components against experimental candidiasis in cyclophosphamide-induced immunosuppressive mice were investigated. ICR mice were immunosuppressed by intraperitoneal treatment with cyclophosphamide (day-4) and were orally given TJ-48 or one of its 10 herbal components for 4 consecutive days (day-4--1). They were then challenged intravenously with a lethal dose of Candida albicans (day 0). An oral dose of 1 g/kg/day of TJ-48 prolonged their life span. A similar protective effect was obtained by treatment with its component drugs Ginseng radix, Glycyrrhizae radix, Atractylodis lancea rhizoma or Cnidii rhizoma. These herbal components were suggested to have a main role in the protective effect of Juzen-taiho-to against Candida infection.

Adjuvants, Immunologic↗
PubMed1998

Binding properties of indocyanine green in human blood.

PURPOSE: Binding properties of indocyanine green (ICG) to human plasma proteins were identified using electrophoresis and a fundus video system. METHODS: Blood samples were obtained from three healthy volunteers after intravenous administration of ICG. The resulting plasma samples were fractionated by agarose gel immunoelectrophoresis and polyacrylamide gel DISC electrophoresis. In the former, antisera, anti-apolipoprotein (Apo)-A, and anti-Apo-B antibodies were used to identify all classes of plasma proteins, high-density lipoprotein (HDL), and low-density lipoprotein (LDL), respectively. In the latter method, plasma samples could be separated into chylomicron, very low-density lipoprotein, LDL, and HDL. The electrophoretic pattern obtained by each method was observed with an ICG fundus video system. Furthermore, we studied the affinity of ICG for lipids that were common molecular components of HDL and LDL. Four kinds of ICG solutions mixed with phospholipid, free cholesterol, esterified cholesterol, and triacylglycerol were observed with the ICG fundus video system. RESULTS: Both electrophoretic studies showed that ICG bound intensely to HDL and moderately to LDL, and only the solution with phospholipid fluoresced brightly when observed with the ICG fundus video system. CONCLUSIONS: These findings indicated low vascular or tissue permeability of ICG, which is caused by the larger molecular size of HDL and LDL. Also noted was that the ICG fluorescence observed in the angiogram may be equivalent to the hemodynamics of HDL alone or in combination with LDL in the bloodstream. This biochemical consideration may be a basis for the further understanding of ICG angiography.

Blood Proteins↗