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Biomedical subjects

K Koike

Publications and source records attributed to K Koike.

At least 163 records · Page 9Linked to original sources

New triterpenoid saponins and sapogenins from Saponaria officinalis.

Five new triterpenoid saponins, named saponariosides I-M, were isolated from the whole plants of Saponario officinalis. Their structures were established as saponarioside I (1) 3-O-beta-D-xylopyranosyl-16 alpha-hydroxygypsogenic acid 28-O-alpha-D-galactopyranosyl-(1-->6)-beta-D- glucopyranosyl-(1-->3)[-beta-D-glucopyranoside[, saponarioside J (3) 3-O-beta-D-xylopyranosylolean-11,13(18)-diene-23,28-dioic acid 28-O-beta-D-glucopyranosyl-(1-->3)-beta-D-glucopyranosyl-(1-->6)[- beta-D-glucopyranoside[, saponarioside K (4) 3,4-seco-16 alpha-hydroxygypsogenic acid 28-O-beta-D-glucopyranosyl- (1-->3)-beta-D-glucopyranosyl-(1-->6)[-beta-D-glucopyranoside[, saponarioside L (5) 3-O-beta-D-xylopyranosylgypsogenic acid 28-O-beta-D-glucopyranosyl-(1-->3)-beta-D-glucopyranosyl-(1-->6)[-beta- D- glucopyranoside[, and saponarioside M (6) 3-O-beta-D-glucopyrano-sylgypsogenic acid 28-O-beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranosyl-(1--6)-beta-D- glucopyranoside[ by NMR studies and chemical degradations. The aglycons of saponariosides J (3) and K (4) are new sapogenins.

Fabaceae↗

Treatment of intracranial nongerminomatous germ-cell tumor by high-dose chemotherapy and autologous stem-cell rescue.

Nongerminomatous germ-cell tumor (NGGCT) in the central nervous system (CNS) is still highly lethal. The present study evaluated the outcome of high-dose chemotherapy followed by autologous stem-cell rescue (ASCR). The patients included three cases of choriocarcinoma, two cases of embryonal carcinoma and one case of yolk sac carcinoma. High-dose cisplatin (200 mg/m2), etoposide (1250 mg/m2) and ACNU (150 mg/m2) were administrated in combination with ASCR to patients at complete remission as a result of surgical removal, irradiation, and from four to seven courses of induction chemotherapy. All the patients treated with this therapy were alive from one to seven years after the diagnosis, living with good performance status. The patients have not required any additional treatments after ASCR. The myelosuppression period, characterized by fewer than 500/microl peripheral neutrophils, ranged from 8 to 15 days (median, 11.5 days). Within seven days of ASCR, high fever was found in four patients. Although mild liver dysfunction was found in all patients, renal dysfunction was not observed. Hearing disturbance was found in 50% of the patients. This treatment regime will improve long-term survival for patients with NGGCT.

Adolescent↗

Enhanced inhibition of experimental metastasis by the combination chemotherapy of Cu-Zn SOD and adriamycin.

We previously reported that reactive oxygen species (ROS) enhance tumor cell metastasis, and by administration of recombinant human superoxide dismutase (rh SOD), an enzyme which scavenges O2- successfully reduced lung metastasis of mouse MethA sarcoma and Lewis lung carcinoma. These observations suggested that rh SOD suppressed tumor cell invasion by eliminating O2- the primary source of ROS. However, for the clinical application of the drug as an anti metastatic agent, rh SOD needs to be administered in combination with other cytotoxic agents, since SOD by itself has no cytotoxic activity. In this paper, we investigated the effectiveness of the combination chemotherapy of rh SOD and adriamycin (ADR), an anti-cancer agent against the experimental metastasis of highly metastatic clone, MH-02, which was derived from murine Meth A sarcoma. The present metastasis experiment clearly indicates that the administration of rh SOD enhances the antimetastatic effect of ADR. On the other hand, we found that the inhibition rate of metastasis exhibited by the combination chemotherapy of rh SOD and a certain dose (5 mg/ml) of ADR was inferior to that of rh SOD. This apparent paradoxical phenomenon was presumably explained by our finding that tumor cells themselves augment their invasive capacity and platelet aggregation, both of which are causative factors for metastasis formation, by generation of O2- when they were treated with ADR. Nevertheless, the combination chemotherapy of SOD with anticancer drugs such as ADR can be a practical anti-metastasis strategy.

Animals↗

Allogeneic hematopoietic stem cell transplantation for patients with hemophagocytic syndrome (HPS) in Japan.

Seventeen cases (age at onset, 1 month to 18 years; M/F, 9/8) of hemophagocytic syndrome which received allogeneic hematopoietic stem cell transplantation (SCT) in Japan during the period 1988-1998 are reported. The patients consisted of six familial inheritance-proven erythrophagocytic lymphohistiocytosis (FEL), five familial inheritance-unknown and infective agents-unknown HLH (of which two were highly likely to have been FEL with characteristic CNS signs), and six aggressive Epstein-Barr virus (EBV)-related HLH (of which two were natural killer cell-type large granular leukemia/lymphoma-associated hemophagocytic syndrome, EBV-NK-LGLL-HPS). All cases were treated intensively with immuno-chemotherapy, or with chemotherapy before SCT. As sources of SCT, 12 cases received bone marrow cells (sibling six, father one, URD five), two cord blood, two purified CD34-positive cells, and one PBSC. SCTs were successful in all 17 cases, apart from one receiving CD34-positive SCT. Following SCT, four patients relapsed and five died with a median follow-up of 23 months. Among the relapsed cases, the two EBV-NK-LGLL-HPS previously published as successfully transplanted were included. Among the fatal cases, three patients died from relapsed active disease and the remaining two from fatal post-SCT EBV-positive T cell lymphoma and extensive chronic GVHD, respectively. As of the end of September 1998, 10 patients are alive without disease for 3.5 months to 147 months, while two post-SCT patients are still having therapy for residual/recurrent disease. The Kaplan-Meier analysis showed a 2-year event-free survival after SCT as 54.0+/-13.0%.

Adolescent↗

Insulin-induced hypoglycemia activates a chemokinergic neuronal pathway in the hypothalamo-pituitary system.

Recently, we found the presence of cytokine-induced neutrophil chemoattractant (CINC) neuronal pathway in the hypothalamo-pituitary system. This observation prompted us to investigate the effect of insulin-induced hypoglycemia on CINC neuronal pathway in the hypothalamo-pituitary system. An insulin injection decreased the plasma glucose level, which followed a prompt rise in plasma ACTH level and an increase in serum CINC level. Before the insulin injection, the signal for CINCmRNA was undetectable in the paraventricular hypothalamic nucleus (PVN). The hypoglycemic challenge induced strong hybridization signals of CINC mRNA in the parvocellular and magnocellular subdivision of the PVN within 30 min, and reached the peak within 3 h. No change was observed in the supraoptic nucleus after the hypoglycemic challenge. These studies demonstrate the presence of a hypoglycemia-sensitive chemokinergic neuronal pathway in the hypothalamo-neurohypophysial system and this newly described pathway will provide novel information for understanding pathophysiology of hypoglycemia.

Acute Disease↗

A comparative study on commercial, botanical gardens and wild samples of the roots of Platycodon grandiflorum by HPLC analysis.

Thirteen commercial samples of Platycodi radix of Platycodon grandiflorum, were collected from China (5 kinds), Korea (5 kinds), and Japan (3 kinds) along with 8 kinds of botanically cultivated Platycodi radix, 3 kinds of wild Platycodi radix collected from different places in Japan. HPLC analysis showed that the commercial botanical and wild samples of P. radix all contained platycodins and a total of twelve peaks were identified by co-HPLC anlaysis with authentic samples isolated earlier from this laboratory. The peak purity and identify were checked with a PDA. The contents of the major saponins, platycodins A, C, D were determined and the peak-area ratios of platycodins A, C, D were shown to be correlated with their sources of origin. The commercial samples from China and Korea each gave a distinct HPLC pattern with peak-area ratio of platycodins A, C, D at 1:2:3 and 2:4:1, respectively. HPLC analysis showed that those on the Japanese market were either imported from China or Korea based upon their HPLC patterns while the Japanese botanical garden or wild type samples gave a higher total saponin content with the peak-area ratio of platycodins A, C, D at 1:2:1.

Carbohydrate Sequence↗

Regiospecific internal desaturation of aliphatic compounds by a mutant Rhodococcus strain.

A mutant Rhodococcus strain lacking the ability to utilize 1-chlorohexadecane was found to cis-desaturate aliphatic compounds, such as 1-chlorohexadecane, n-hexadecane, and heptadecanonitrile, yielding corresponding products with a double bond mainly at the ninth carbon from the terminal methyl groups. A new oxidative pathway involving the cis-desaturation step was suggested for alkane utilization by Rhodococcus spp.

Alkanes↗

Impairment of transalveolar fluid transport and lung Na(+)-K(+)-ATPase function by hypoxia in rats.

We examined whether hypoxic exposure in vivo would influence transalveolar fluid transport in rats. We found a significant decrease in alveolar fluid clearance of the rats exposed to 10% oxygen for 48 h. Terbutaline did not stimulate alveolar fluid clearance, and alveolar fluid cAMP levels were lower than those determined in normoxia experiment. Hypoxia did not influence the alveolar fluid lactate dehydrogenase levels, Evans blue dye fluid-to-serum concentration ratio, or lung wet-to-dry weight ratio, indicating no significant change in the permeability of alveolar-capillary barrier. Histological examination showed no significant fluid accumulation into the interstitium and the alveolar space. Hypoxia did not reduce lung ATP content; however, we found significant decrease in Na(+)-K(+)-ATPase hydrolytic activity in lung tissue preparations and isolated alveolar type II cells. Our data indicate that hypoxic exposure in vivo impairs transalveolar fluid transport, and this impairment is related to the decrease in alveolar epithelial Na(+)-K(+)-ATPase hydrolytic activity but is not secondary to the alteration of cellular energy source.

Adenosine Triphosphate↗

Pharmacological analysis of atypical beta-adrenoceptors in the guinea pig gastric fundus using the beta(3)-adrenoceptor antagonist bupranolol.

Atypical beta-adrenoceptor-mediated relaxations to catecholamines (isoprenaline, noradrenaline and adrenaline) and beta(3)-adrenoceptor agonists, BRL37344 [(R*, R*)-(+/-)-4-[2-[(2-(3-chlorophenyl)-2-hydroxyethyl)amino]-propyl]phen oxyacetic acid sodium salt] and CGP12177A [(-)-4-(3-t-butylamino-2-hydroxy- propoxy)benzimidazol-2-one] in guinea pig gastric fundus were investigated. The five agonists induced concentration-dependent relaxation of the gastric fundus. In the presence of both atenolol and butoxamine only small rightward shifts of the concentration-response curves to these agonists were observed. Under this condition, however, bupranolol caused a concentration-dependent rightward shift of the concentration-response curve to catecholamines and beta(3)-adrenoceptor agonists. Schild plot analyses of bupranolol against these agonists gave pA(2) values of 6.08 (isoprenaline), 6. 04 (noradrenaline), 5.90 (adrenaline), 6.50 (BRL37344) and 5.80 (CGP12177A), respectively. These results clearly suggest that the existence of functional atypical beta-adrenoceptors in the guinea pig gastric fundus and the relaxation of these agonists in this tissue are mediated via atypical beta-adrenoceptors.

Adrenergic beta-Agonists↗

Prognostic value of nucleolar protein p120 in patients with resected lung adenocarcinoma.

PURPOSE: In this study we investigated the prognostic significance of proliferation-associated nucleolar protein p120 in primary resected lung adenocarcinoma because it reflects tumor growth fractions in vitro. PATIENTS AND METHODS: Expression levels of p120 in tumors were assessed by immunohistochemistry in 74 patients who underwent radical resection. With clinical follow-up data, the prognostic significance of p120 calculated by labeling indices was evaluated using the Cox proportional hazards model. RESULTS: p120 protein was clearly detected in nucleoli of adenocarcinoma cells. Its expression levels widely varied in each sample from 8.5% to 67. 2%, with a mean +/- SD of 35.2% +/- 15.1%. No significant correlation was found between expression levels of p120 and clinicopathologic factors. However, the expression levels of p120 were negatively correlated with the tumor doubling time calculated with retrospective chest roentgenograms. Using a cutoff value of 35% in the labeling index of p120, patients with high expression of p120 experienced early recurrence and shorter survival compared with those who had low expression of p120. Multivariate analysis showed that p120 served as an independent, as well as the strongest, prognostic factor for resected lung adenocarcinoma. CONCLUSION: This report provides the first evidence that expression levels of p120 in tumor tissues can be used as an independent and powerful prognostic marker for resected lung adenocarcinoma.

Adenocarcinoma↗

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↗

Nematocidal activity of picrodendrins against a species of diplogastridae.

To develop parasiticides, the nematocidal activity of 22 picrotoxane terpenoids, picrodendrins isolated from the Euphorbiaceae plant Picrodendron baccatum (L.) KLUG et URBAN, was measured using a species of Diplogastridae (Nematoda). Picrodendrin P displayed the most potent nematocidal activity with a minimum lethal concentration (MLC) value of 4.4 x 10(-3) M. The nematocidal activity of picrodendrin P was 9-fold more potent than that of kainic acid (4.0 x 10(-2) M) and santonin (4.0 x 10(-2) M) and 6-fold more potent than that of diethylcarbamazine citrate (3.0 x 10(-2) M). Thus, picrodendrin P may eventually be used as a leading parasiticide. In light of the relationship between the structure of picrodendrins and their nematocidal activities, potent nematocidal activity was found to require the following elements within the picrotoxane skeleton: the gamma-lactone that bridges C-3 and C-5, the epoxide group that bridges between C-6 and C-8, a cis-OCH3 group and a trans-CH2OH group related to carbonyl at alpha-methylene-gamma-lactone ring (C-18), and the absence of 4- and 8-hydroxyl groups. These results are the first demonstration of nematocidal activity for these terpenes and thus are important in furthering our understanding.

Animals↗

Improvement in the turnover rate of the stratum corneum in false aged model rats by the administration of geniposidic acid in Eucommia ulmoides Oliver Leaf.

We earlier reported that collagen synthesis in false aged model rats was stimulated by the administration of a methanol extract from the leaves of Eucommia ulmoides OLIVER. When the methanol extract was fractionated to n-hexane, ethyl acetate, acetone and methanol fractions by silica gel chromatography, we discovered that geniposidic acid and aucubin, contained in the acetone fraction, were the active ingredients. In the current study, we set out to examine if active compounds found in the Eucommia ulmoides OLIVER leaf (EUOL) improved the low turnover rate in the stratum corneum of false aged model rats. The turnover rate in the stratum corneum in rats was measured as 50% dansyl chloride clearance day. In the first experiment, administration of a 2.4% water soluble methanol extract (WSME) of EUOL, along with an 11% protein diet, led to a 20% higher turnover rate in the stratum corneum (p<0.05, Mann-Whitney) than the control value. The WSME mainly contained iridoid mono-glycosides such as geniposidic acid. In the second experiment, treatment with geniposidic acid similarly caused a higher turnover rate in the stratum corneum, increasing turnover by 23% (p<0.05, Mann-Whitney) compared to the control value. In this paper we reveal that the WSME contains compounds effective against aging, and one of them is geniposidic acid.

Aging↗

Changes in lactate dehydrogenase and 3-hydroxyacetyl-CoA dehydrogenase activities in rat skeletal muscle by the administration of Eucommia ulmoides OLIVER leaf with spontaneous running-training.

We examined the effect of Eucommia ulmoides OLIVER leaf on rat skeletal muscles together with spontaneous running-training in terms of the isozyme profile and specific activity of lactate dehydrogenase (LDH; EC 1.1.1.27) and 3-hydroxyacetyl-CoA dehydrogenase (HAD; EC 1.1.1.35). On the twenty-ninth day of the experimental period, a mandatory endurance running exercise (treadmill, 7 degrees grade) was conducted. Twenty-four hours later, the rats were sacrificed and the skeletal muscles and other organs were dissected. Due to the training, the HAD specific activity in the skeletal muscles had increased and a more oxidative metabolism had developed, which was further enhanced by the administration of the leaf. In soleus (SOL) muscle in the Eucommia leaf treated running-training group (ET), the LDH specific activity in the skeletal muscle was significantly higher than in the sedentary control group (SC). The isozyme profile of the group ET was significantly different when compared with the group SC. The changes in the LDH isozyme profile were larger in the SOL than that in extensor digitorum longus (EDL) muscle. The results show that mechanical training and the use of the leaf cooperatively increase the ability to avoid lactate accumulation in skeletal muscle. This effect is supported by the group where 67% of rats accomplished the endurance running exercise. Theses results suggest that the administration of Eucommia ulmoides OLIVER leaf along with light intensity training enhances the ability of a muscle to resist fatigue.

3-Hydroxyacyl CoA Dehydrogenases↗

New saponins from the seeds of Aesculus chinensis.

Eight new acylated polyhydroxyoleanene triterpenoidal saponins, aesculiosides A-H (1-8), along with four known ones, have been isolated from the seeds of Aesculus chinensis. On the basis of extensive NMR studies, the structures of the new compounds were determined to be 21-O-tigloylprotoaescigenin 3-O-[beta-D-glucopyranosyl-(1-->2)][beta-D-glucopyranosyl-(1-->4)]- beta-D-glucuronopyranosyl acid (1), 21-O-angeloylprotoaescigenin 3-O-[beta-D-glucopyranosyl- (1-->2)][beta-D-glucopyranosyl-(1-->4)]-beta-D-glucuronopyranosyl acid (2), 21,22-O-ditigloylprotoaescigenin 3-O-[beta-D-glucopyranosyl-(1-->2)][beta-d-glucopyranosyl- (1-->4)]-beta-D-glucuronopyranosyl acid (3), 21-O-tigloyl-22-O-angeloylprotoaescigenin 3-O-[beta-D-glucopyranosyl- (1-->2)][beta-D-glucopyranosyl-(1-->4)]-beta-D-glucuronopyranosyl acid (4), 21,22-O-ditigloylprotoaescigenin 3-O-[beta-D-glucopyranosyl- (1-->2)][beta-D-glucopyranosyl-(1-->4)]-methyl beta-d-glucuronopyranosate (5), 21-O-tigloyl-22-O-angeloylprotoaescigenin 3-O-[beta-D-glucopyranosyl-(1-->2)-[beta-D-glucopyranosyl-(1-->4)]-methy l beta-D-glucuronopyranosate (6), 21-O-tigloyl-28-O-acetylprotoaescigenin 3-O-[beta-D-glucopyranosyl-(1-->2)][beta-D-glucopyranosyl-(1-->4)]-methy l beta-D-glucuronopyranosate (7) and 21-O-angeloyl-28-O-acetylprotoaescigenin 3-O-[beta-D-glucopyranosyl-(1-->2)][beta-D-glucopyranosyl-(1-->4)]-methy l beta-D-glucuronopyranosate (8).

Carbohydrate Conformation↗

Triterpenoidal saponins acylated with two monoterpenic acids from Gleditsia sinensis.

The isolation and characterization of three new oleanane-type triterpenoidal saponins, called gleditsiosides E-G, along with two known ones, from the anomalous fruits of Gleditsia sinensis LAM. are described. Their structural details were unambiguously determined by using a combination of modern NMR techniques, including distortionless enhancement by polarization transfer (DEPT), double-quantum filtered 1H-1H correlated spectroscopy (DQF-COSY), homonuclear hartmann-hahn (HOHAHA), 1H-13C heteronuclear correlation (HET-COR), heteronuclear multiple-bond connectivity (HMBC) and rotating-frame overhauser enhancement spectroscopy (ROESY) experiments as well as some chemical methods. The five bisdesmosidic triterpenoidal saponins consisting of the same sugar sequence were all acylated with two different or identical monoterpenic acids to the C-2 and C-3 positions of rhamnose moiety.

Carbohydrate Sequence↗

Minor triterpenoid saponins from Ardisia crenata.

Two minor triterpenoid saponins, ardisicrenoside G [3 beta-O-{alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranosyl-(1-->4)- [beta-D-glucopyranosyl-(1-->2)]-alpha-L-arabinopyranosyl}-16 alpha,28-dihydroxyolean-12-en-30-oic acid] and ardisicrenoside H [3 beta-O-{beta-D-xylopyranosyl-(1-->2)-beta-D- glucopyranosyl-(1-->4)-[beta-D-glucopyranosyl-(1-->2)]-alpha-L- arabinopyranosyl}-16 alpha,28-dihydroxyolean-12-en-30-oic acid] were isolated from the roots of Ardisia crenata. Structural assignments are based on NMR, MS and chemical reactions.

Carbohydrate Sequence↗