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Biomedical subjects

Y Tezuka

Publications and source records attributed to Y Tezuka.

At least 19 recordsLinked to original sources

[Prognosis of patients after resection for lung cancer with intrapulmonary metastasis in different lobes].

BACKGROUND: The prognosis of lung cancer patients with intrapulmonary metastasis in different lobes (pm2) is poor. However, some patients achieve long-term survival. We retrospectively investigated the prognosis of resected primary lung cancer patients with pm2. METHOD: Among 845 patients with primary lung cancer who underwent complete resection from 1984 to 2003, 14 cases that had lung cancer with pm2 were evaluated about prognostic factors. RESULTS: The overall 5-year survival rate was 9.5%. The analysis of survival curve based on clinicopathological factors (surgical procedure, histology, tumor size, lymph nodal metastasis, pleural invasion, pleural dissemination and number of pm2) revealed that bronchioloalveolar carcinoma (BAC), the absence of pleural invasion and the absence of pleural dissemination are better prognostic factors. CONCLUSION: Lung cancer patients with pm2 whose lesions show BAC histology, the absence of pleural invasion or pleural dissemination may achieve long-term survival and could be candidates for surgical treatment.

Adenocarcinoma, Bronchiolo-Alveolar↗

Hypoglycemic effects of the wood of Taxus yunnanensis on streptozotocin-induced diabetic rats and its active components.

Hypoglycemic effects of the H(2)O and MeOH extracts of the wood of Taxus yunnanensis were examined in streptozotocin (STZ)-induced diabetic rats. The H(2)O extract significantly lowered the fasting blood glucose level by 33.7% at a 100mg/kg dose on intraperitoneal administration. From the active H(2)O extract of the wood, three lignans, i.e., isotaxiresinol (1), secoisolariciresinol (2) and taxiresinol (3), were isolated as major components. These lignans were further tested for their hypoglycemic effects on the same experimental model. At a dose of 100mg/kg (i.p.), isotaxiresinol (1) reduced the fasting blood glucose level of diabetic rats by 34.5%, while secoisolariciresinol (2) and taxiresinol (3) reduced by 33.4% and 20.9%, respectively. The blood glucose lowering effects of 1 and 2 were stronger than the mixture of tolbutamide (200mg/kg) and buformin (1mg/kg) used as a positive control, which lowered fasting blood glucose level by 24.0%.

Animals↗

In vivo anti-osteoporotic activity of isotaxiresinol, a lignan from wood of Taxus yunnanensis.

Isotaxiresinol, the main lignan isolated from the water extract of wood of Taxus yunnanensis, was investigated for its effect on bone loss, on serum biochemical markers for bone remodeling and on uterine tissue, using ovariectomized (OVX) rats as the model of postmenopausal osteoporosis. After oral administration of isotaxiresinol (50 and 100mg/kg/d) for 6 weeks, bone mineral content (BMC) and bone mineral density (BMD) in total and cortical bones were increased as compared to those of OVX control rats, and decreases of three bone strength indexes induced by OVX surgery were prevented. Serum biochemical markers for bone remodeling revealed that isotaxiresinol slightly increased bone formation and significantly inhibited bone resorption without side effect on uterine tissue. These results suggest that isotaxiresinol may be useful for treatment of postmenopausal osteoporosis, especially for prevention of bone fracture induced by estrogen deficiency.

Animals↗

CYP3A4 and CYP2D6 inhibitory activities of Indonesian medicinal plants.

Thirty samples of Indonesian medicinal plants were analyzed for their capacity to inhibit in vitro metabolism by human cytochrome P450 3A4 (CYP3A4) and CYP2D6 with a radiometric assay. The MeOH-soluble fractions of 25 samples, prepared from water extracts, demonstrated inhibitory activity more than 50% on the metabolism mediated by CYP3A4, and 21 samples on the metabolism mediated by CYP2D6. Among the MeOH-soluble fractions, Piper nigrum leaf showed the highest inhibitory activity against CYP3A4 (91.7%), and Punica granatum against CYP2D6 (98.1%). The water extracts of which MeOH-soluble fraction showed inhibitory activity more than 70% were fractionated with EtOAc. From the EtOAc-soluble fractions, Curcuma heyneana (67.0%), Pi. cubeba (75.0%), Pi. nigrum fruit (84.0%), Pi. nigrum leaf (85.8%), and Zingiber aromaticum (75.3%) demonstrated inhibitory activity more than 50% on the metabolism mediated by CYP3A4, but only Pi. nigrum fruit (72.8%) and Pi. nigrum leaf (69.1%) showed strong inhibitory activity against CYP2D6. For samples that showed more than 70% inhibition, their IC(50) values were determined. The most potent inhibitory activity against CYP3A4 (IC(50) value of 25 microg/ml) was found for the extract of Pi. nigrum leaf, while that of Catharanthus roseus showed the most potent inhibitory effect against CYP2D6 (IC(50) value of 11 microg/ml). These results should indicate once more the possibility of potential medicinal plant-drug interactions.

Cytochrome P-450 CYP2D6↗

Inhibition of IL-6 overproduction by steroid treatment before transsternal thymectomy for myasthenia gravis: does it help stabilize perioperative condition?

Overproduction of interleukin (IL)-6 plays an important role in the pathophysiology of myasthenia gravis (MG), and thymectomy can cause myasthenic crisis because of surgically induced overproduction of IL-6. Preoperative steroid therapy is beneficial in preventing MG crisis during the perioperative period. The purpose of this study was to clarify the effect of preoperative steroid therapy on proinflammatory mediators during the perioperative period of transsternal thymectomy for MG. The study group comprised 20 consecutive MG patients undergoing transsternal thymectomy during the period March 2002 through March 2004. Seventeen of these patients received dose-escalated steroid therapy before thymectomy (steroid treatment group) and three did not (non-steroid treatment group). Serum concentrations of C-reactive protein (CRP) and IL-6 were determined during the perioperative period; clinical outcomes were reviewed, and the results were compared between the two groups. Peak serum IL-6 and CRP concentrations were significantly lower in the steroid treatment group than in the non-steroid treatment group. Amongst perioperative variables subjected to multiple regression analysis, preoperative steroid treatment were found to be the most significant independent predictor of inhibited IL-6 production on postoperative day 1. No postoperative respiratory failure occurred in the steroid treatment group, but it did occur in the non-steroid treatment group. Preoperative steroid therapy can ameliorate IL-6 overproduction and may help stabilize the patient's postoperative condition.

Aged↗

[Clinicopathologic features of small-sized peripheral lung cancer; is intentional limited resection appropriate for selected patients?].

We sought to determine the eligibility of patients with early peripheral lung cancer for intentional limited resection. The clinicopathologic features of 103 patients who underwent lobectomy and mediastinal nodal dissection for early stage peripheral lung cancer measuring 2 cm or less in maximum dimension between 1992 and 2002 were examined retrospectively. The lymph node metastasis and residual cancer after thoracoscopic partial resection were analyzed by the following categories. Three groups were divided by maximum dimension of the primary lesion in the resected specimen; 10 mm or less (n = 11), 15 mm or less (n = 33), and 20 mm or less (n = 59). Two groups were divided by lesion histology; bronchioloalveolar adenocarcinoma (BAC) [n = 42] and invasive lung cancer (n = 61). Residual cancer was found in the residual lobe after thoracoscopic partial resection in 3 of 43 patients who had no diagnosis preoperatively. Their maximum dimensions were 15 mm or less. No lymph node metastasis was detected in the patients with tumor measuring 10 mm or less, and BAC. Intentional limited resection without mediastinal nodal dissection is appropriate for patients with tumor measuring 10 mm or less and BAC. Further investigation associated with partial resection is necessary.

Adenocarcinoma, Bronchiolo-Alveolar↗

Topological polymer chemistry: systematic classification of nonlinear polymer topologies.

Nonlinear polymer topologies composed of cyclic and branched polymer segments are systematically classified by reference to constitutional isomerism in a series of alkanes (CnH2n+2), monocycloalkanes (CnH2n), and polycycloalkanes (CnH2n-2, CnH2n-4, etc). Thus, the total number of chain ends (termini) and of branch points (junctions) are maintained as invariant parameters, as well as the number of branches at each junction and the connectivity of junction. On the other hand, the distance between two adjacent junctions and that between the junction and terminus are taken as variant parameters. On the basis of the classification of polymer topologies, a novel synthetic strategy by an "electrostatic self-assembly and covalent fixation" technique has been proposed to construct a variety of topologically unique polymer architectures.

Journal Article↗

Molecular cloning of POEM: a novel adhesion molecule that interacts with alpha8beta1 integrin.

Cell adhesion molecules are involved in a number of biological functions, such as cell survival, cell differentiation, tissue repair, and development. A novel molecule, POEM (preosteoblast epidermal growth factor-like repeat protein with meprin, A5 protein, and receptor protein-tyrosine phosphatase mu domain), was isolated by reverse transcription-polymerase chain reaction using a set of degenerate primers designed after other known epidermal growth factor (EGF)-like motifs. From its structure, POEM was suggested to be a novel adhesion molecule with five EGF-like domains, an Arg-Gly-Asp (RGD) cell binding motif, and a meprin, A5 protein, and receptor protein-tyrosine phosphatase mu (MAM) domain. By in situ hybridization using embryonic day 16.5 (E16.5) mouse embryos, strong expression of POEM mRNA was observed in developing kidney renal tubules, parathyroid and thyroid glands, developing bone, tooth germ, and endocrine organs of the brain. The inner ear, skeletal muscle, smooth muscle (except for the vascular system), and skin were also positive for POEM expression. Bacterial recombinant POEM protein containing the RGD sequence and MAM domain showed strong cell adhesion, spreading, and survival-promoting activities. By mutating the RGD sequence to RGE, the cell spreading and survival activities were significantly decreased, but the MAM domain was shown to contribute only to cell adhesion and not to cell spreading and survival-promoting activities. The distribution of POEM in several tissues was close to that of alpha(8)beta(1) integrin. Therefore, we conducted cell adhesion assays using KA8 cells, a K562 leukemia clone stably expressing alpha(8) integrin. Parental K562 cells, which expressed alpha(5)beta(1) integrin, bound to fibronectin but not to POEM. On the other hand, KA8 cells showed strong binding and spreading on both fibronectin and POEM. These results suggest that POEM is a novel ligand for alpha(8)beta(1) integrin and that POEM may be involved in the development and function of various tissues, such as kidney, bone, muscles, and endocrine organs.

Amino Acid Sequence↗

Recent progress in pharmacological research of propolis.

Propolis is a resinous hive product collected by honeybees from various plant sources. It is a popular folk medicine possessing a broad spectrum of biological activities. It has also been used as a health drink in various Asian, European and American countries. Several groups of researchers have focused their attention on the biological activity of propolis and its active principles. Many scientific articles are published every year in different international journals related to the pharmacological properties of propolis. This review article compiles recent findings (since 1995) on the pharmacological properties of propolis focusing on its antihepatotoxic, antitumour, antioxidative, antimicrobial and antiinflammatory properties. The possible mechanism of action of propolis as well as the active compounds are discussed.

Anti-Infective Agents↗

Screening of Chinese herbal drug extracts for inhibitory activity on nitric oxide production and identification of an active compound of Zanthoxylum bungeanum.

Sixty-eight water and methanol extracts from 34 Chinese herbal drugs, most of which are used for inflammatory diseases, were screened for their inhibitory effects on nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated J774.1 macrophages and in LPS/interferon (IFN)-gamma-stimulated mouse peritoneal exudate macrophages. Among the extracts, methanol extracts of Myristica fragrans, Plantago asiatica, Rubia cordifolia, and Zanthoxylum bungeanum showed significant inhibition in J774.1 macrophages, while in mouse peritoneal exudate macrophages, water extracts of Ru. cordifolia and Scutellaria baicalensis and methanol extracts of Angelica megaphylla, My. fragrans, and Z. bungeanum inhibited the NO production. Among them, inhibition of water extract of Sc. baicalensis was found to be mainly due to direct scavenging of NO radicals, through an examination of its scavenging activity on PAPA NONOate-generated NO radicals, while water extract of Ru. cordifolia and methanol extracts of An. megaphylla, My. fragrans, P. asiatica, and Z. bungeanum showed inhibition on iNOS mRNA expression. At last, an inhibitory compound on iNOS mRNA expression was isolated from a methanol extract of Z. bungeanum and identified as 4-O-beta-D-glucopyranosyldihydroferulic acid by NMR spectral analyses and chemical synthesis.

Animals↗

Triterpene saponins from Vietnamese ginseng (Panax vietnamensis) and their hepatocytoprotective activity.

The methanol extract of Vietnamese ginseng (Panax vietnamensis) was found to possess hepatocytoprotective effects on D-galactosamine (D-GalN)/tumor necrosis factor-alpha (TNF-alpha)-induced cell death in primary cultured mouse hepatocytes. Further chemical investigation of the extract afforded two new dammarane-type triterpene saponins, ginsenoside Rh(5) (1) and vina-ginsenoside R(25) (2), as well as eight known dammarane-type triterpene saponins, majonoside R(2) (3), pseudo-ginsenoside RT(4) (4), vina-ginsenosides R(1) (5), R(2) (6), and R(10) (7), ginsenosides Rg(1) (8), Rh(1) (9), and Rh(4) (10), and a known sapogenin protopanaxatriol oxide II (11). Their structures were elucidated on the basis of spectral analysis. In addition, by the using LC-electrospray ionization (ESI)-MS method, five known saponins, ginsenosides Rb(1), Rb(2), Rc, Rd, and Re (12--16), were also identified in the extract. Among the compounds isolated, majonoside R(2) (3), the main saponin in Vietnamese ginseng, showed strong protective activity against D-GalN/TNF-alpha-induced cell death in primary cultured mouse hepatocytes. This demonstrates that the hepatocytoprotective effect of Vietnamese ginseng is due to dammarane-type triterpene saponins that have an ocotillol-type side chain, a characteristic constituent of Vietnamese ginseng.

Animals↗

Three new triterpenes from the seeds of Combretum quadrangulare and their hepatoprotective activity.

Three new triterpenes of the lupane type, 2alpha,6beta-dihydroxybetulinic acid (1) and 6beta-hydroxyhovenic acid (2), and an oleanane type, 6beta-hydroxyarjunic acid (3), together with several known compounds, have been isolated from the MeOH extract of the seeds of Combretum quadrangulare. The structures of these compounds were elucidated on the basis of spectroscopic analysis, and their hepatoprotective activities were tested for D-GalN/TNF-alpha-induced cell death in primary cultured mouse hepatocytes.

Asia↗

Eleven novel diarylheptanoids and two unusual diarylheptanoid derivatives from the seeds of Alpinia blepharocalyx.

An EtOH extract of the seeds of Alpinia blepharocalyx afforded 11 novel diarylheptanoids, named deoxycalyxin A (1), epicalyxin F (2), calyxin K (3), epicalyxin K (4), calyxin I (5), epicalyxin I (6), calyxin J (7), epicalyxin J (8), and calyxin L (9), an epimeric mixture of calyxin M (10) and epicalyxin M (11), and two unusual diarylheptanoid derivatives, named neocalyxins A (12) and B (13), together with four known calyxins, calyxins A (14), F (15), E (16), and G (17). Structures were elucidated by spectroscopic techniques including 2D NMR spectroscopy. All compounds were examined for cytotoxicity toward murine colon 26-L5 carcinoma and human HT-1080 fibrosarcoma cells. Diarylheptanoids 2, 3, and 5 were cytotoxic against both cell lines, while 4 and 6-8 were cytotoxic against human fibrosarcoma cells.

Animals↗

Blepharocalyxins C--E, three new dimeric diarylheptanoids, and related compounds from the seeds of Alpinia blepharocalyx.

Three novel diarylheptanoids, blepharocalyxins C--E (5--7), together with four new (1--4) and one known (8) diarylheptanoids bearing a tetrahydropyran ring were isolated from the residual fraction of an EtOH extract of the seeds of Alpinia blepharocalyx. The structures and the stereochemistry at the chiral centers of the new diarylheptanoids were elucidated by spectroscopic techniques including 2D NMR spectroscopy. Blepharocalyxins C--E (5--7) have a novel carbon framework and are dimeric diarylheptanoids consisting of two diarylheptanoid units. Blepharocalyxin D (6) showed potent antiproliferative activity against murine colon 26-L5 carcinoma cells (ED(50), 3.61 microM), while against human HT-1080 fibrosarcoma cells, blepharocalyxin E (7) showed potent activity (ED(50), 9.02 microM).

Animals↗

Six new diarylheptanoids from the seeds of Alpinia blepharocalyx.

Chromatographic separation of part of an EtOH extract of the seeds of Alpinia blepharocalyx resulted in the isolation of six new (1-6) and two known (7, 8) diarylheptanoids together with 12 known compounds. The structures of the new compounds, including their absolute stereochemistry, were elucidated by spectroscopic and chemical methods as (3S,5S)- (1) and (3S,5R)-3-hydroxy-5-methoxy-1-(4-hydroxyphenyl)-7-phenyl-6E-heptene (2), (3S,5S)- (3) and (3S,5R)-3-hydroxy-5-ethoxy-1-(4-hydroxyphenyl)-7-phenyl-6E-heptene (4), (3S)-methoxy-1,7-bis(4-hydroxyphenyl)-6E-hepten-5-one (5), and 1,7-bis(4-hydroxyphenyl)hepta-4E,6E-dien-3-one (6). Among the isolated compounds, 5, (3S,5S)-3,5-dihydroxy-1,7-bis(4-hydroxyphenyl)heptane (8), 4'-hydroxy-5,6-dehydrokawain (14), and/or phloroglucinol (20) showed significant antiproliferative activity against murine colon 26-L5 carcinoma (ED(50): 5, 5.2 microM; 8, 12.8 microM; 14, 20.7 microM; 20, 26.4 microM) and human HT-1080 fibrosarcoma (ED(50): 5, 10.1 microM; 14, 20.1 microM; 20, 20.9 microM) cells.

Cell Division↗

Five novel highly oxygenated diterpenes of Orthosiphon stamineus from Myanmar.

Five novel highly oxygenated diterpenes, orthosiphols K (1), L (2), M (3), and N (4) and norstaminone A (5), were isolated from the aerial part of Orthosiphon stamineus, together with three known diterpenes, orthosiphols A (6) and B (7) and neoorthosiphol A (8). Orthosiphol L (2) is an isopimarane-type diterpene with a hydroxyl group at C-12, which supports the biogenesis of staminane-type diterpenes, i.e., migration of a vinylic group from C-13 of isopimarane to C-12. Norstaminone A (5) has a staminane carbon framework and supports the biosynthetic pathway from staminols to norstaminols via staminolactones. All the isolated compounds showed mild to weak antiproliferative activities toward highly liver metastatic colon 26-L5 carcinoma and human HT-1080 fibrosarcoma cell lines.

Antineoplastic Agents, Phytogenic↗

New spirostanol steroids and steroidal saponins from roots and rhizomes of Dracaena angustifolia and their antiproliferative activity.

The MeOH extract of Nam ginseng (roots and rhizomes of Dracaena angustifolia) afforded nine new compounds, including three spirostanol sapogenins, named namogenins A-C (1-3), four spirostanol saponins, named namonins A-D (4-7), a furostanol saponin, named namonin E (8), and a pregnan glycoside, named namonin F (9), along with another eight known steroidal saponins (10-17). Their structures were determined on the basis of spectral analyses and chemical methods. All compounds were tested for their antiproliferative activity against murine colon 26-L5 carcinoma, human HT-1080 fibrosarcoma, and B-16 BL6 melanoma cells. Compounds 4, 5, and 10 showed potent antiproliferative activity against HT-1080 fibrosarcoma cells, having IC(50) values of 0.2, 0.3, and 0.6 microM, respectively, comparable to that of doxorubicin.

Animals↗

Dimeric aporphine alkaloids of Phoenicanthus obliqua from Sri Lanka.

A new dimeric aporphine alkaloid, phoenicanthusine (1), and six known alkaloids were isolated from the stem bark of Phoenicanthus obliqua. The structure of 1 was elucidated by 1D ((1)H, (13)C) and 2D ((1)H-(1)H COSY, HMQC, HMBC, and NOESY) NMR and HRMS studies. Phoenicanthusine represents the first example of a N-6--C-4' and C-7--C-5' linked dimeric aporphine alkaloid.

Annonaceae↗