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Biomedical subjects

T Morikawa

Publications and source records attributed to T Morikawa.

At least 73 records · Page 4Linked to original sources
PubMed2000

Synthesis of a potent aminocyclitol alpha-mannosidase inhibitor, 1L-(1,2,3,5/4)-5-amino-4-O-methyl-1,2,3,4-cyclopentanetetrol.

Demethylthio-, de-S-methyl-, and ethylthio-derivatives of the alpha-mannosidase inhibitor, mannostatin A, have been synthesized and evaluated for their inhibition of Jack bean alpha-mannosidase in order to elucidate the roles of the methylthio group. All derivatives had lowered inhibitory potentials. However, a mannostatin A analogue with a methoxyl instead of the methylthio, exhibited about 2-fold enhancement of the activity, indicating an importance for the methyl group rather than the sulfur atom.

Biochemistry↗
PubMed2000

Inhibitory effects of sesquiterpenes from bay leaf on nitric oxide production in lipopolysaccharide-activated macrophages: structure requirement and role of heat shock protein induction.

The methanolic extract from the leaves of Laurus nobilis (bay leaf, laurel) was found to inhibit nitric oxide (NO) production in lipopolysaccharide (LPS)-activated mouse peritoneal macrophages. Through bioassay-guided separation, fourteen known sesquiterpenes were isolated from the active fraction and were examined for ability to inhibit the NO production. Seven sesquiterpene lactones (costunolide, dehydrocostus lactone, eremanthine, zaluzanin C, magnolialide, santamarine and spirafolide) potently inhibited LPS-induced NO production (IC50 = 1.2 approximately 3.8 microM). Other sesquiterpene constituents also showed the inhibitory activity (IC50 > or = 21 microM), but their inhibitory activities were less than those of sesquiterpene lactones. Alpha-methylene-gamma-butyrolactone also showed inhibitory activity (IC50 = 9.6 microM), while mokko lactone and watsonol A etc., reductants of the alpha-methylene-gamma-butyrolactone moiety by NaBH4 or DIBAL, and a 2-mercaptoethanol adduct of dehydrocostus lactone showed little activity (IC50 > or = 18 microM). These results indicated that the alpha-methylene-gamma-butyrolactone moiety is important for the activity. Furthermore, costunolide and dehydrocostus lactone inhibited inducible nitric oxide synthase (iNOS) induction in accordance with induction of heat shock protein 72 (HSP 72). These results suggested that, as one of their mechanisms of action, sesquiterpene lactones induce HSP 72 thereby preventing nuclear factor-kappaB activation followed by iNOS induction.

Animals↗
PubMed2000

Effects of stilbene constituents from rhubarb on nitric oxide production in lipopolysaccharide-activated macrophages.

Two new anthraquinone glucosides [chrysophanol 8-O-beta-D-(6'-galloyl)-glucopyranoside, aloe-emodin 1-O-beta-D-glucopyranoside] together with various known stilbenes and their glucosides, anthraquinone glucosides, and a naphthalene glucoside were isolated from the rhizome of Rheum undulatum L. Three stilbenes (rhapontigenin, piceatannol, resveratrol), a naphthalene glucoside (torachrysone 8-O-beta-D-glucopyranoside), and two stilbene glucoside gallates (rhaponticin 2''-O-gallate, rhaponticin 6''-O-gallate) showed inhibitory activity of NO production in lipopolysaccharide-activated macrophages, (IC50 = 11-69 microM). The oxygen functions (-OH,-OCH3) at the benzene ring were found to be essential to show the activity. Whereas, the glucoside moiety reduced the activity, while the alpha,beta-double bond did not affect the activity. Furthermore, the active stilbenes (rhapontigenin, piceatannol, resveratrol) inhibited iNOS induction.

Anthraquinones↗
PubMed2000

Glial pathology in development of cerebellar dysplasia in the hereditary cerebellar vermis defect (CVD) rat.

The cerebellar vermis defect (CVD) rat is a new neurological mutant characterized by a cerebellar vermis defect and dysplasia in the cerebellum, especially at the cerebellopontine junctions. In this study, the cytokinetics of glia in terms of the development of cerebellar dysplasia in the CVD rat was investigated using glial fibrillary acidic protein (GFAP) and vimentin immunohistochemistry. In the cerebellar hemispheres, dislocation of the Bergmann glia was observed from postnatal day 5 (P5) in lesions with abnormally aggregated external granule cells (EGCs). Rearranging Bergmann glia were often seen around the EGCs penetrating into the white matter. In the cerebellopontine junctional areas, Bergmann glia were induced after penetration of the Purkinje cells, identified with calbindin immunohistochemistry, and EGCs into the pons from P10. Bergmann fibers were frequently arranged perivascularly. In the clusters of Purkinje cells without EGC settlement in the pons, a small number of Bergmann fibers were observed and their alignment was completely disturbed. These findings suggest that morphological changes in the Bergmann glia depend on their contact with Purkinje cells, but that the orientation of their processes may be influenced by EGC settlement. These glial fibers in the CVD rat may play an important role in the aberrant migration of EGCs, resulting in the development of cerebellar dysplasia.

Animals↗
PubMed2000

Reconstruction after total pharyngolaryngoesophagectomy. Comparison of elongated stomach roll with microvascular anastomosis with gastric pull up reconstruction or something like that.

BACKGROUND: We have performed total pharyngolaryngoesophagectomy in case of double cancer, head-neck and thoracic esophageal cancer, or cervical esophageal cancer that extended down to the level of aortic arch. The procedure is very challenging. METHODS: From April 1984 to May 1998, 14 patients underwent the procedures for double cancer of head-neck and thoracic esophagus (n=10), hypopharyngeal or cervical esophageal cancer (n=3), and synchronous esophageal cancer (n=1). The grafts used were whole stomach (n=6), elongated stomach roll (n=5), and stomach roll with free jejunum (n=3). The routes of reconstruction were posterior mediastinum (n=10), antesternal (n=3), and retrosternal (n=1). RESULTS: Elongated stomach roll with microvascular anastomoses was long enough for reconstruction and the blood supply of the graft was sufficient. There was no fatal complication in this procedure. Oral feeding was achieved in 13 (93%) patients. CONCLUSIONS: The elongated stomach roll with microvascular anastomosis is efficient and the placement of the conduit in the posterior mediastinum is recommended to allow a better alimentary comfort in total pharyngolaryngoesophagectomy.

Adult↗
PubMed2000

Nonfunctioning endocrine tumor of the pancreas with extrapancreatic growth and cyst formation: report of a case.

We report a case of nonfunctioning endocrine tumor of the pancreas with extrapancreatic growth and cyst formation. A 48-year-old woman was admitted to our hospital with an upper abdominal mass, which was detected during a routine medical checkup. The preoperative diagnosis was a solid cystic tumor of the pancreas. The tumor, which measured about 7cm in diameter, arose from the head of the pancreas and had a thin stalk, measuring about 1 cm in diameter. The histopathological diagnosis was a malignant nonfunctioning endocrine tumor of the pancreas. Cyst formation occurred in 67% of the reported cases with extrapancreatic growth in Japan. It is speculated that the cyst formation in this disease is related to the large size of the tumor and to the extrapancreatic growth.

Abdominal Pain↗
PubMed2000

Alcohol absorption inhibitors from bay leaf (Laurus nobilis): structure-requirements of sesquiterpenes for the activity.

Through a bioassay-guided separation using inhibitory activity on blood ethanol elevation in oral ethanol-loaded rat, various sesquiterpenes having an alpha-methylene-gamma-butyrolactone moiety, costunolide (1), dehydrocostus lactone (2), zaluzanin D (3), reynosin (4), santamarine (5), 3alpha-acetoxyeudesma-1,4(15),11(13)-trien-12,6alpha-+ ++olide (6) and 3-oxoeudesma-1,4,11(13)-trien-12,6alpha-olide (7), were isolated as the active principle from the leaves of Laurus nobilis (bay leaf, laurel). In order to characterize the structure requirement for the activity, several reduction products (2a-2d) and amino acid adducts (2e, 2f) of the alpha-methylene-gamma-butyrolactone moiety were synthesized from 2 and the inhibitory activities of these sesquiterpenes, together with alpha-methylene-gamma-butyrolactone (12) and its related compounds (13-16), were examined. These results indicated that the gamma-butyrolactone or gamma-butyrolactol moiety having alpha-methylene or alpha-methyl group was essential for the inhibitory activity on ethanol absorption. Since 1, 2 and 12 showed no significant effect on glucose absorption, these sesquiterpenes appeared to selectively inhibit ethanol absorption. In addition, the acute toxicities of 1 and 2 in a single oral administration were found to be lower than that of 12.

4-Butyrolactone↗
PubMed2000

Targeted killing of carcinoembryonic antigen (CEA)-producing cholangiocarcinoma cells by polyamidoamine dendrimer-mediated transfer of an Epstein-Barr virus (EBV)-based plasmid vector carrying the CEA promoter.

The present study reports a novel nonviral method to efficiently and specifically target carcinoembryonic antigen (CEA)-producing cholangiocarcinoma (CC) cells in vitro. Epstein-Barr virus (EBV)-based and conventional plasmid vectors were constructed that possess the beta-galactosidase (beta-gal) or herpes simplex virus-1 (HSV-1) thymidine kinase (Tk) genes as well as tandem repeats of the human genomic sequence -82 to -42 bp from the transcriptional start site of the CEA gene. The plasmids were transfected by means of polyamidoamine dendrimer into CEA-positive (HuCC-T1) or -negative cell lines. Transfection of the conventional plasmid vector with the CEA promoter and beta-gal gene resulted in a very low or undetectable level of marker gene expression even in the CEA-positive cell line. Transferring the HSV-1 Tk gene by conventional plasmid did not affect the susceptibility of HuCC-T1 cells to ganciclovir. In marked contrast, strong beta-gal expression was specifically obtained in HuCC-T1 cells by transfecting the EBV-based plasmid in which the CEA promoter and a ubiquitous promoter (SRalpha) are employed to drive the EBV-encoded nuclear antigen 1 (EBNA1) and beta-gal genes, respectively (pTES.beta). Furthermore, CEA-positive but not -negative tumor cells were rendered highly susceptible to ganciclovir when transfected with the EBV-based vector that carries the CEA promoter-EBNA1 and SRalpha-HSV-1 Tk genes (pTES.Tk). These results strongly suggest that the EBV-based plasmid vector/cationic polymer system (EBV/polyplex) equipped with the CEA promoter provides an efficient nonviral method for the targeted gene therapy of CEA-producing malignancies.

Carcinoembryonic Antigen↗
PubMed2000

5-day vs. 7-day triple therapy with rabeprazole, clarithromycin and amoxicillin for Helicobacter pylori eradication.

AIM: To determine whether a 5-day regimen with rabeprazole, clarithromycin and amoxicillin (RCA) was as effective as a 7-day regimen. METHODS: A total of 139 H. pylori-infected patients were randomized to receive either a 5-day or 7-day course of rabeprazole 10 mg b.d., clarithromycin 400 mg b.d. and amoxicillin 750 mg b.d. Eradication was assessed by CLO test, histology and 13C-urea breath test. RESULTS: On the intention-to-treat basis, eradication rates were 66% (46 out of 70) and 84% (58 out of 69) for the 5- and 7-day regimens, respectively (P < 0.05). Using per protocol analysis, eradication rates were 70% (46 out of 66) and 91% (58 out of 64) for the 5- and 7-day regimens, respectively (P < 0.01). Adverse events, which were observed in 14 patients from each group, caused discontinuation of treatment in only two patients, resulting in excellent compliance. CONCLUSIONS: Our 5-day regimen of RCA yielded inferior results, whereas the 7-day regimen achieved an eradication rate exceeding 90% on the per protocol basis. Therefore, treatment regimens of less than 7 days for proton pump inhibitor-clarithromycin-amoxicillin therapies cannot be recommended.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2000

Psychological effect of the Nagasaki atomic bombing on survivors after half a century.

In 1997 a mental health survey using a 30-item General Health Questionnaire (GHQ-30) and an interview survey of an atomic bombing experience were conducted in survivors of the Nagasaki atomic bombing. Overall psychological distress measured on the basis of the GHQ-30 was greater in the atomic bombing survivors than in the controls. As for the contents of psychological distress, those concerning emotion such as anxiety and depression were milder in survivors than in the controls, but those related to social activities such as apathy, disturbance of human relations, loss of enjoyment of living were more severe. Furthermore, recurring and distressing recollection of the experience of the atomic bombing, suspicion over the relationship between the atomic bombing and an unhealthy physical condition, and the experience of witnessing death or severe injury of close relatives due to the atomic bombing were significantly related to the degree of psychological distress of the survivors.

Aged↗
PubMed2000

Promotion of skin carcinogenesis by dimethylarsinic acid in keratin (K6)/ODC transgenic mice.

Dimethylarsinic acid (DMA) is a major metabolite of inorganic arsenicals in mammals, and arsenic exposure is associated with tumor development in a wide variety of human tissues, particularly the skin. Transgenic mice with ornithine decarboxylase (ODC) targeted to hair follicle keratinocytes are much more sensitive than littermate controls to carcinogens. In this study we investigated the promoting effect of DMA on skin carcinogenesis in such K6 / ODC transgenic mice. The back skin of female C57BL / 6J K6 / ODC transgenic mice, 10 to 14 weeks old, was initiated with topical application of 7, 12-dimethylbenz[alpha]anthracene (DMBA) at a dose of 50 microg or acetone alone on day 1 of the experiment, followed by treatment with 3.6 mg of DMA, 5 microg of 12-O-tetradecanoylphorbol-13-acetate (TPA) or neutral vehicle (control) twice a week for 18 weeks. Mice were killed 1 week after the end of the treatment. Induction of skin tumors was significantly accelerated in the DMA-treated group, as well as in the TPA-treated group, indicating that DMA has a promoting effect on skin tumorigenesis in K6 / ODC transgenic mice.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2000

Superoxide dismutase in alveolar macrophages from patients with diffuse panbronchiolitis.

BACKGROUND: Diffuse panbronchiolitis (DPB) is characterized by chronic neutrophil-mediated inflammation of the airway mediated by oxygen radical production. DPB can be controlled with low-dose and long-term erythromycin therapy based on its anti-inflammatory effect. OBJECTIVE: In this study, the antioxidant levels were analyzed as an anti-inflammatory effect of erythromycin in the patients. METHODS: We investigated the activity and protein level of an antioxidant enzyme, Cu, Zn-superoxide dismutase (SOD) in alveolar macrophages (AMs) of patients with DPB before and after erythromycin therapy. AMs were obtained from bronchoalveolar lavage fluid. RESULTS: There was no significant difference in the activity of Cu, Zn-SOD between normal subjects and untreated patients. Erythromycin therapy (600 mg/day) significantly increased the activity of the enzyme relative to that before therapy and normal subjects [18.2 units/10(6) cells (9.2-26.2) vs. 4.4 units/10(6) cells (1.1-9.3), p < 0.01 and 10.4 units/10(6) cells (2.4-20.6), p < 0.05, respectively]. Furthermore, the protein level of Cu, Zn-SOD in AMs in treated patients was significantly higher than in the other two groups [69.4 ng/10(6) cells (34.2-147.1) vs. 20.1 ng/ 10(6) cells (16.9-39.8) for untreated patients, p < 0.01 and 43.2 ng/10(6) cells (32.6-68.2) for normal subjects, p < 0.01], but the levels in the latter groups were not different. CONCLUSION: Our results suggest that one of the anti-inflammatory effects of erythromycin in DPB may be, in part, mediated by enhancement of antioxidant activity in AMs.

Adult↗
PubMed2000

Isolation of the antiulcer compound in essential oil from the leaves of Cryptomeria japonica.

Essential oil from the leaves of Tateyamasugi (Cryptomeria japonica) exhibited strong inhibitory activity on ulceration induced by HCl/ethanol, HCl/aspirin, water-immersion stress and pylorus-ligation. We separated the antiulcer compounds from cedar essential oil by use of distillation and chromatography. As a result, terpinen-4-ol, a monoterpene, and elemol, a sesquiterpene, were isolated as active compounds. The antiulcer activity of the former was more potent than that of the latter. Terpinen-4-ol was a mixture of optical isomers and each possessed potent antiulcer activity. Secretion of gastric juice and output of acid and pepsin activity were lowered by terpinen-4-ol. These results suggest that terpinen-4-ol isolated from cedar essential oil could be a valuable antiulcer agent.

Acetaldehyde↗
PubMed2000

Medicinal flowers. II. Inhibitors of nitric oxide production and absolute stereostructures of five new germacrane-type sesquiterpenes, kikkanols D, D monoacetate, E, F, and F monoacetate from the flowers of Chrysanthemum indicum L.

The methanolic extract and ethyl acetate-soluble portion from the flowers of Chrysanthemum indicum L., Chrysanthemi Indici Flos, were found to show inhibitory activity against nitric oxide (NO) production in lipopolysaccharide-activated macrophages. Five new germacrane-type sesquiterpenes, kikkanols D, D monoacetate, E, F, and F monoacetate, were isolated from the ethyl acetate-soluble portion. Their absolute stereostructures were elucidated on the basis of chemical and physicochemical evidence, which included application of the modified Mosher's method. The effects of fifteen principal components from the ethyl acetate-soluble portion of this medicinal flower against NO production were examined and, among them, acetylenic compounds and flavonoids were found to show potent inhibitory activity.

Animals↗
PubMed2000

Intergenomic translocations of polyploid oats (genus Avena) revealed by genomic in situ hybridization.

Wild and cultivated hexaploid oats share the same genomes (AACCDD) and display a considerable level of interspecific variation in both plant and chromosome morphology. The GISH was utilized to detect the interspecific genomic compositions in four hexaploid and two tetraploid oats using total genomic DNA of Avena eriantha (a C-genome diploid) as probe. Intergenomic translocations between A/D and C-genome chromosomes were frequently observed in hexaploid and tetraploid species. In the hexaploid, two pairs of A/D genome segments on C-genome chromosome (A/D-C) translocation and four to six pairs of C-genome segments on A/D genome chromosome (C-A/D) translocation were clearly identified whilst the number of A/D-C translocations was constant among species. In the tetraploid A. maroccana (AACC), a pair of A-C and four pairs of C-A translocations were observed. Moreover, the A/D translocation segments on chromosome 5C was detected only in A. byzantina and A. maroccana, whilst A/D-C translocations were observed on the 1C and 7C of A. sativa, A. fatua and A. sterilis. A. byzantina did however also carry the 1C rearrangement. This result shows that A. byzantina has retained a similar genomic constitution to the tetraploid ancestor of hexaploid oats, A. maroccana. Three pairs of A-C translocations were detected only in A. murphyi (AACC), and two pairs of those were the 1C and 7C as well as the three hexaploid species except A. byzantina.

Avena↗
PubMed2000

Embolic cerebellar infarction caused by spontaneous dissection of the extracranial vertebral artery--two case reports.

Spontaneous dissection of the extracranial vertebral artery (VA) may cause ischemic stroke in the posterior circulation. A 22-year-old female and a 38-year-old male presented with sudden onset of vertigo and nausea without trauma. Angiography was initially interpreted as normal, but retrospective examination disclosed extracranial VA dissection in the V3 segment in both cases. Arterial dissection resulting in embolic stroke in the territory of the ipsilateral posterior inferior cerebellar artery was highly suspected. Both patients were treated conservatively without sequelae. Careful angiographic interpretation is important for the diagnosis of extracranial VA dissection. Spontaneous extracranial VA dissection should be suspected in young patients presenting with ischemic stroke but without predisposing risk factors or associated trauma.

Adult↗
PubMed2000

Observation of the abluminal surface of the atrioventricular endothelium which undergoes transition into cardiac cushion mesenchymal cells in the chick embryo.

In the developing chick heart, endothelial cells in the atrioventricular canal (AV) undergo a series of morphological changes and transform into cushion mesenchymal cells. In the present scanning electron microscopic study, we examined the abluminal surface features of the AV endothelium through an artificial window in the myocardial wall. The AV endothelial cell at stages 12 or earlier had a smooth, flattened basal surface with only a few blebs. In the successive stages, the abluminal surface exhibited remarkable changes; 1) the number of blebs increased, 2) elongated microvillous projections emerged, and 3) a thick filopodium, or a migratory appendage developed. It appeared, however, that these changes do not occur synchronously within the entire AV endothelium but were initially observed mostly in the proximity of the endothelial "crease" which was a limited invagination of the endothelial sheet towards the underlying acellular matrix. In addition, even in the proximity of the crease, endothelial cells with flattened basal surfaces were also observed next to endothelial cells that showed apparent morphological indications of transition into mesenchymal cells. These findings suggest that AV endothelial cells are possibly heterogeneous in the competency of transformation into mesenchymal cells and such heterogeneity would be important for maintaining the continuity of the AV endothelium.

Animals↗