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Biomedical subjects

M Yoshikawa

Publications and source records attributed to M Yoshikawa.

At least 253 records · Page 14Linked to original sources

Growth arrest associated with 12-o-tetradecanoylphorbol-13-acetate-induced hematopoietic differentiation with a defective retinoblastoma tumor suppressor-mediated pathway.

The retinoblastoma tumor suppressor (Rb) gene product plays an essential role in cell-cycle regulation. However, its role in terminal differentiation of hematopoietic cells is speculative. Here we show a model of 12-o-tetradecanoylphorbol-13-acetate (TPA)-induced hematopoietic differentiation and growth arrest with a defective Rb-mediated pathway. TPA treatment arrested the cell cycle of a human hematopoietic cell line, MEG-01s, at the G1-S boundary and induced expression of p21/SDI1/WAF1/CIP1 and p27/KIP1. Both of these proteins were present in cyclin E-associated complexes, the histone H1 and Rb kinase activities of which were then inactivated. However, MEG-01s cells lacked the intact Rb protein and the Rb-mediated pathway was defective. This model raises a question about the role for Rb in terminal differentiation of hematopoietic cells.

Blotting, Northern↗

Usefulness of the hydrogen--deuterium exchange method in the study of drug metabolism using liquid chromatography-tandem mass spectrometry.

The usefulness of the hydrogen-deuterium (H-D) exchange method in the study of drug metabolism was investigated. Metabolite samples of denopamine and promethazine prepared in vitro were introduced to a triple stage quadrupole tandem mass spectrometer via a high performance liquid chromatography (HPLC) system using a deuterated mobile phase. Mass spectra by various ionization modes and collisionally induced dissociation (CID) mass spectra were obtained. A metabolite of denopamine was observed to have a shift of 7 mass units by the H-D exchange method, and this shift proved to be a glucuronidated metabolite. Discrimination between N- or S-oxide formation and hydroxylation observed in the metabolism of promethazine was also easily accomplished by this method. In this manner, the structures of the metabolites were elucidated unequivocally by determining the number of labile hydrogen atoms by the use of the H-D exchange method, since various reactions in drug metabolism are accompanied by an increase or a decrease in the number of labile hydrogen atoms. Additional information on the structures was obtained by analysis of the CID spectra of the molecular ion species. Thus, the combination of the H-D exchange method and tandem mass spectrometry was found to be very useful for the study of drug metabolism.

Animals↗

Mode of action of escins Ia and IIa and E,Z-senegin II on glucose absorption in gastrointestinal tract.

We examined the mode of action of escins Ia (1) and IIa (2) and E,Z-senegin II (3) for the inhibitory effect on the increase in serum glucose levels in oral glucose-loaded rats. Although 1-3 inhibited the increase in serum glucose levels in oral glucose-loaded rats, these compounds did not lower serum glucose levels in normal or intraperitoneal glucose-loaded rats, or alloxan-induced diabetic mice. Furthermore, 1-3 suppressed gastric emptying in rats, and also inhibited glucose uptake in the rat small intestine in vitro. These results indicated that 1-3 given orally have neither insulin-like activity nor insulin-releasing activity. Compounds 1-3 inhibited glucose absorption by suppressing the transfer of glucose from the stomach to the small intestine and by inhibiting the glucose transport system at the small intestinal brush border.

Animals↗

Antinociceptive and anti-inflammatory activities of limonin isolated from the fruits of Evodia rutaecarpa var. bodinieri.

Antinociceptive and anti-inflammatory effects of limonin isolated from the dried fruits of Evodia rutaecarpa var. bodinieri were investigated. Oral administration of 30 or 100 mg/kg limonin significantly decreased the frequency of licking and biting behavior within a unit of time at the late phase without affecting that of the early phase in the formalin test. Limonin inhibited the rise of vascular permeability induced by acetic acid and the increase of paw edema induced by carrageenin. Limonin also showed inhibitory effects on bradykinin-induced paw edema and arachidonic acid-induced ear swelling. These results suggest that limonin possesses an antinociceptive effect and the effect may be accompanied by an anti-inflammatory action, and that the antinociceptive activity in Evodiae Fructus is partially attributable to limonin.

Analgesics↗

An image analyzing system using an artificial neural network for evaluating the parenchymal echo pattern of cirrhotic liver and chronic hepatitis.

To objectively evaluate the parenchymal echo pattern of cirrhotic liver and chronic hepatitis, we applied an image analyzing system (IAS) using a neural network. Autopsy specimens in a water tank (n = 13) were used to examine the relationship between the diameter of the regenerative nodule and the coarse score (CS) calculated by IAS. CS was significantly correlated with the diameter of the regenerative nodule (p < 0.0001, r = 0.966). CS is considered to be useful for evaluating the coarseness of the parenchymal echo pattern.

Hepatitis, Chronic↗

Cyclin D1 overexpression detected by a simple competitive reverse transcription-polymerase chain reaction assay for lymphoid malignancies.

t(11;14)(q13;q32) observed in B-cell malignancies is associated with cyclin D1 (bcl-1, PRAD1, CCND1) overexpression. We devised a simple competitive reverse transcription-polymerase chain reaction (RT-PCR) assay for rapid detection of cyclin D1 overexpression. Sharing a single upstream primer derived from a homologous sequence in cyclins D1, D2 and D3, each PCR product serves as a competitor and cyclin D1 overexpression is determined by comparing the intensities of the three amplified products. We analyzed cyclin D1 in clinical specimens from 104 patients with lymphoid malignancies. Cyclin D1 overexpression was evident in 13 of 104 (7/72 non-Hodgkin's lymphomas, 0/6 adult T-cell lymphoma/leukemias, 0/4 Hodgkin's diseases, 0/11 acute lymphoblastic leukemias, 3/4 multiple myelomas, 1/2 Waldenström's macroglobulinemias, 1/2 prolymphocytic leukemias and 1/3 chronic lymphocytic leukemias). Among 72 patients for whom cytogenetic studies had been done, all 7 patients with t(11;14) were positive. The relative expression levels of D-type cyclins altered dramatically in the presence of t(11;14). Thus, this RT-PCR assay can identify tumors with cyclin D1 overexpression. Cyclin D1 overexpression was frequent in extranodal specimens (11 out of 32 vs. 2 of 72 lymph nodes) and was restricted to specific types of lymphoid malignancies, as observed using other methods. This reliable assay should be suitable to provide clinical guidance for the diagnosis and management of lymphoid malignancies, especially in the case of extranodal involvement.

Adolescent↗

Expression of cellular adhesion regulatory molecule in hepatocellular carcinoma.

Cellular adhesion regulatory molecule (CMAR) enhances the adhesiveness of cells to collagen and laminin and is considered to be a candidate anti-oncogene. The purpose of the present study was to investigate the relationship between the expression of CMAR and clinical features of hepatocellular carcinoma (HCC). Small amounts of liver tissue were obtained from HCC and non-cancerous portions of the liver in 29 patients and from normal liver in seven patients with metastatic liver tumour by biopsy under ultrasound guidance. RNA was extracted with acid guanidinium thiocyanate-phenol-chloroform. Expression of CMAR was assessed by quantitative PCR using beta-actin as an internal standard. A 4 b.p. insertion polymorphism at nucleotide 241 of the CMAR coding region was then investigated using extracted RNA to assess the relationship between the expression of variant mRNA of CMAR and HCC carcinogenesis. The relative expression of CMAR was significantly reduced in HCC compared with non-cancerous and normal livers and had a relationship with certain clinical background factors. The reduced expression of CMAR was thought to be closely associated with the progression of HCC. However, the 4 b.p. insertion polymorphism pattern of CMAR was the same between HCC and non-cancerous liver in all cases in which it was found. These results suggest that progression of HCC may be predicted based on the relative expression of CMAR.

ATPases Associated with Diverse Cellular Activitie↗

Antiproliferative effect of calcitriol on human prostatic cancer cell lines: unrelated to the expression of major histocompatibility complex antigens or intercellular adhesion molecule-1 (ICAM-1).

BACKGROUND: In addition to its role in calcium and phosphorus metabolism, calcitriol (1,25-dihydroxyvitamin D3; 1,25-D3) demonstrates multiple effects on cell proliferation/differentiation by expressing major histocompatibility complex (MHC) antigens and intercellular adhesion molecule-1 (ICAM-1). It has recently been reported that 1,25-D3 inhibits the growth of prostatic cancer (PCa) cells. In this study we examined the effect of 1,25-D3 on both the growth and expression of HLA-ABC, HLA-DR and ICAM-1 antigens in PCa cells. METHODS: Four human PCa cell lines (PC-3, PPC-1, ALVA-41 and ALVA-101) were examined. The cell numbers were enumerated, and the effects of interferon-y (IFN-gamma) and 1,25-D3 on the expression of HLA-ABC, HLA-DR and ICAM-1 were quantitated by flow cytometry. RESULTS: A dose-dependent antiproliferative effect of 1,25-D3 was found in all PCa cells lines except ALVA-41.1,25-D3 was approximately 10 times as potent as its analogue 24,25-dihydroxyvitamin D3 in inhibiting the growth of PC-3 cells. Also, the relative inhibitory ability of these compounds paralleled the strength of their binding affinities for the 1,25-D3 receptor, indicating that the antiproliferative effect may require a receptor-ligand interaction. HLA-ABC was expressed in PC-3, ALVA-41 and ALVA-101, but not in PPC-1 cells, while HLA-DR was not expressed on any of the tested cells. IFN-gammacould enhance or induce HLA-ABC but not HLA-DR expression in the tested cells. ICAM-1 was expressed in all cells and slightly upregulated by IFN-gamma. CONCLUSION: In this study 1,25-D3 had an antiproliferative effect on 3 of the 4 examined PCa cell lines.

24,25-Dihydroxyvitamin D 3↗

Effect of cytokinin 4PU30 on organ differentiation and dihydroisocoumarin production in amacha callus cultures.

Effect of a suitable combination of 1-naphthaleneacetic acid (NAA) and cytokinin N-(2-chloro-4-pyridyl)-N'-phenylurea (4PU30) concentrations, regarding organ differentiation and dihydroisocoumarin production, was examined in Hydrangea macrophylla var. thunbergii callus cultures. The callus cultured in a Linsmaier-Skoog medium containing 10(-5) M NAA and 10(-5) M 4PU30 under a light condition gave the highest level for callus growth, shoot formation, and phyllodulcin 8-O-glucoside content.

2,4-Dichlorophenoxyacetic Acid↗

Studies on Kochiae Fructus. V. Antipruritic effects of oleanolic acid glycosides and the structure-requirement.

We examined the antipruritic effects of various oleanolic acid glycosides from natural medicines such as Kochiae Fructus (the fruit of Kochia scoparia SCHRAD.) and Momordicae Radix (the roots of Momordica cochinchinensis SPRENG.) using a compound 48/80-induced pruritic model in mice. Oleanolic acid 3-O-monodesmosides showed an antipruritic effect, while oleanolic acid 3,28-O-bisdesmosides and their common sapogenol oleanolic acid lacked the activity. This evidence indicated that the 3-O-glycoside moiety and the 28-carboxyl group in oleanolic acid glycosides were essential for exhibiting the antipruritic effect. Furthermore, it was found that the 3-O-glucuronides showed more potent activity than the corresponding 3-O-glucosides.

Animals↗

Studies on Alismatis Rhizoma. II. Anti-complementary activities of methanol extract and terpene components from Alismatis Rhizoma (dried rhizome of Alisma orientale).

A methanol extract (TMe-ext) from the dried rhizome of Alisma orientale was screened for anti-complementary activity in experimental models. In the animal models, it was found that TMe-ext inhibits zymosan-induced hind paw edema in rats and zymosan-activated rat serum (ZAS)-induced vascular permeability in mice. TMe-ext showed an inhibitory effect on complement-induced hemolysis through both the classical pathway and the alternative pathway. And TMe-ext inhibited hypotonic shock-induced hemolysis, but this effect was weak compared with the anti-complementary activities of TMe-ext. Four triterpenes (alisol A, alisol A monoacetate, alisol B and alisol B monoacetate) isolated from the rhizome also inhibited the complement-induced hemolysis through the classical pathway, but two sesquiterpenes (alismol and alismoxide) were ineffective. These results indicate that Alismatis Rhizoma shows anti-complementary activity, and its anti-complementary components are partially attributable to the terpene components mentioned above.

Animals↗

Development of bioactive functions in Hydrangeae Dulcis Folium. VII. Immunomodulatory activities of thunberginol A and related compounds on lymphocyte proliferation.

Immunomodulatory activities of constituents isolated from Hydrangeae Dulcis Folium and their related compounds on lymphocyte proliferation were investigated using splenocytes and lymph node cells. Thunberginol A (TA) significantly suppressed B lymphocyte proliferation stimulated by lipopolysaccharide (LPS) at 10(-5) M. However TA at a lower concentration (10(-6) M) and the other compounds, except hydrangenol and 3'-hydroxyhydrangeaic acid, tended to potentiate B lymphocytes proliferation (10(-5) M). On the other hand, thunberginol A significantly suppressed T lymphocyte proliferation stimulated by concanavalin A (Con A), but did not suppress phytohemagglutinin (PHA). Hydrocortisone and cyclosporin A strongly suppressed T lymphocyte proliferation induced by both Con A and PHA. These results suggest that thunberginol A acts on both B and T lymphocytes and may have a suppressive mechanism different from the known immunosuppressants. The cytotoxicity of TA for splenocytes seemed weaker than known immunosuppressants resulting from viability tests using MTT assay and the measurement of lactate dehydrogenase (LDH) released in the medium. Moreover, TA suppressed antigen-specific T lymphocyte proliferation in mice lymph node cells immunized with keyhole limpet hemocyanin (KLH). Thus, these findings show that TA has a suppressive effect on lymphocyte activation, and this inhibitory effect of TA seems to contribute to its suppressive effect on type IV allergies.

Animals↗

Medicinal foodstuffs. XIV. On the bioactive constituents of moroheiya. (2): New fatty acids, corchorifatty acids A, B, C, D, E, and F, from the leaves of Corchorus olitorius L. (Tiliaceae): structures and inhibitory effect on NO production in mouse peritoneal macrophages.

Following the characterization of the glycosidic constituents in a medical foodstuff "moroheiya," the leaves of Corchorus olitorius L., four higher fatty acids with a trienone function, corchorifatty acids, A, B, C, and D, an undecanoic acid, corchorifatty acid E, and a trihydroxyfatty acid, corchorifatty acid F, were isolated from the less polar fraction of "moroheiya". The structures and optical purity of corchorifatty acids were determined on the basis of chemical and physicochemical evidence. Corchorifatty acids A, B, and C showed an inhibitory effect on lipopolysaccharide-induced NO production in cultured mouse peritoneal macrophages.

Animals↗

Antidiabetic principles of natural medicines. II. Aldose reductase and alpha-glucosidase inhibitors from Brazilian natural medicine, the leaves of Myrcia multiflora DC. (Myrtaceae): structures of myrciacitrins I and II and myrciaphenones A and B.

The methanolic extract and ethyl acetate-soluble portion from a Brazilian natural medicine, the leaves of Myrcia multiflora DC., which has been used as a specific medicine against diabetes, were found to show inhibitory activities on aldose reductase and alpha-glucosidase and on the increase of serum glucose level in sucrose-loaded rats and in alloxan-induced diabetic mice. From the ethyl acetate-soluble portion, new flavanone glucosides, myrciacitrins I and II, and new acetophenone glucosides, myrciaphenones A and B, were isolated together with several known compounds such as five flavonol glycosides, myricitrin, mearnsitrin, quercitrin, desmanthin-1, and guaijaverin. The structures of new compounds were determined on the basis of physicochemical and chemical evidence. The principal components of this natural medicine including new glucosides, myrciacitrin I and myrciaphenone B, were found to show potent inhibitory activities on aldose reductase and alpha-glucosidase.

Acetophenones↗

Kotalanol, a potent alpha-glucosidase inhibitor with thiosugar sulfonium sulfate structure, from antidiabetic ayurvedic medicine Salacia reticulata.

A potent natural alpha-glucosidase inhibitor called kotalanol has been isolated from an antidiabetic traditional Ayurvedic medicine, the roots and stems of Salacia reticulata Wight, through bioassay-guided separation. The structure of kotalanol was elucidated on the basis of chemical and physicochemical evidence to be the inner salt comprised of 1-deoxyheptosyl-3-sulfate anion and 1-deoxy-4-thio-D-arabinofuranosyl sulfonium cation. Kotalanol was found to show more potent inhibitory activity against sucrase than salacinol and acarbose.

Animals↗

Antidiabetic principles of natural medicines. III. Structure-related inhibitory activity and action mode of oleanolic acid glycosides on hypoglycemic activity.

We examined the structure-related activity of oleanolic acid glycosides with respect to their inhibitory effect on the increase in serum glucose in oral glucose-loaded rats and their mechanism of action using oleanolic acid 3-O-glucuronide and momordin Ic. Both the 3-O-monodesmoside structure and 28-carboxyl group were confirmed to be essential for such activity, and the 3-O-glucuronide was more potent than 3-O-glucoside. On the other hand, the 28-ester glucoside moiety and 6'-methyl ester of the glucuronide moiety reduced such activity. Oleanolic acid 3-O-glucuronide and momordin Ic, both of which inhibited the increase in serum glucose in oral glucose-loaded rats, did not lower serum glucose in normal or intraperitoneal glucose-loaded rats, or alloxan-induced diabetic mice. These glycosides were found to suppress gastric emptying in rats, and also inhibit glucose uptake in the rat small intestine in vitro. These results indicate that oleanolic acid 3-O-glucuronide and momordin Ic, given orally, have neither insulin-like activity nor insulin releasing-activity. They exhibit their hypoglycemic activity by suppressing the transfer of glucose from the stomach to the small intestine and by inhibiting glucose transport at the brush border of the small intestine.

Administration, Oral↗

Bioactive saponins and glycosides. XII. Horse chestnut. (2): Structures of escins IIIb, IV, V, and VI and isoescins Ia, Ib, and V, acylated polyhydroxyoleanene triterpene oligoglycosides, from the seeds of horse chestnut tree (Aesculus hippocastanum L., Hippocastanaceae).

New acylated polyhydroxyoleanene triterpene oligoglycosides, escins IIIb, IV, V, and VI and isoescins Ia, Ib, and V, were isolated from the seeds of horse chestnut tree (Aesculus hippocastanum L.). Their structures were elucidated on the basis of chemical and physicochemical evidence.

Carbohydrate Sequence↗