Biomedical subjects
Publications and source records attributed to Masami Tanaka.
Three benzoyl p-terphenyl derivatives named thelephantins A, B and C were isolated from the ethyl acetate extract of fruit bodies of the Thelephoraceous Basidiomycete Thelephora aurantiotincta. Their structures were elucidated by analysis of high-resolution 2D NMR, MS, IR and UV spectra.
Five p-terphenyl derivatives named thelephantins D-H (1-5) together with nine known compounds, thelephantins A-C (6-8), ganbajunin E (9), p-hydroxylbenzoic acid (10), ganbajunin C (11), thelephorin A (12), 2-O-methylatromentin (13) and atromentin (14), were isolated from the methanolic extract of fruit bodies of the Thelephoraceous Basidiomycete Thelephora aurantiotincta. Their structures were elucidated by high-resolution MS, 2D NMR, IR and UV spectroscopic analysis.
Four p-terphenyl derivatives named curtisians E-H (1-4) were isolated from the methanolic extract of fruit bodies of the Basidiomycete Paxillus curtisii by a combination of Sephadex LH-20, silica gel column chromatography and preparative reversed phase HPLC. The relative stereochemistries of the curtisians were elucidated by 2D NMR, MS, IR and UV spectroscopy with the absolute configurations at C(3a-3d) of the side chains being established as S by GC-MS on a chiral column previously used for separation of authentic standards.
Four p-terphenyl derivatives named curtisians I-L (1-4) were isolated from the MeOH extract of the fruit bodies of Paxillus curtisii. Their structures were elucidated by 2D NMR, MS, IR and UV spectroscopy and chemical reaction. The absolute configurations of curtisians were determined by GC-MS on a chiral column of the hydrolyzed products with authentic samples. Their antioxidative activities were also estimated by examination of the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging effect.
Five novel p-terphenyl derivatives called curtisians M-Q (1-5) were isolated from the methanolic extract of fruit bodies of the Basidiomycete Paxillus curtisii. Their structures were elucidated by two dimensional (2D) NMR, MS, IR, and UV spectroscopy, and chemical reaction. Their antioxidative activities were also investigated.
Phytochemical examination of the methanol extract of the fruit bodies of the Japanese fungus Tyromyces fissilis led to the isolation of two new lanostane derivatives called tyromycic acids F (1) and G (2), together with two known compounds, tyromycic acid (3) and trametenolic acid B (4). Their structures were identified by 2D NMR, IR, and UV spectroscopy.
Two novel butenolides, isoravenelone (1) and ravenelone (2), and a large amount of a known compound, vulpinic acid (3), were isolated from the methanolic extract of the Japanese fungus Pulveroboletus ravenelii (Boletales). These structures were elucidated by two dimensional (2D) NMR, MS, IR and UV spectra, and X-ray crystallographic analysis.
We report a 70-year-old woman with bilateral optic atrophy, external ophthalmoplegia, bilateral blepharoptosis, and sensory ataxic neuropathy. She had a visual disturbance since childhood. She had dysarthria and gait disturbance at 28 years old. She had bilateral blepharoptosis, marked gait disturbance and dysphagia at 50. On neurological examination, external ophthalmoplegia, bilateral blepharoptosis, mild weakness and muscular atrophy of promixal muscles, hyporeflexia, positive Romberg sign, glove and stocking type sensory disturbance including hypesthesia, hypalgesia, and bathyhypesthesia were found. She did not show pigmented retinopathy, cognitive dysfunctions, hearing loss, cerebellar ataxia, Hoffman reflex nor Babinski sign. She did not show increased lactic acid nor pyruvic acid in the cerebrospinal fluid but mild increase of pyruvic acid (1.0 mg/dl) in her serum. The conduction velocity and amplitude of CMAP of tibial nerve was 37.4 m/sec and 2.9 mV, respectively. The SNAP of ulner and sural nerve were not evoked. Brain MRI showed no pathological findings. Muscle biopsy from the biceps muscle showed many ragged-red fibers (5.3%) and some fibers with decreased or absent COX activity. Sural nerve biopsy showed a marked loss of large myelinated fibers with thin myelinated fibers, and onion-bulb formation. The clinical findings of our patient is similar to that of SANDO (the triad of sensory ataxic neuropathy, dysarthria, and ophthalmoparesis), however, large mtDNA deletion reported by Fadic in patients with SANDO was not found in our patient. It might be possible that her mtDNA deletion is small or point mutation is existed.
Half of all patients with limbic encephalitis and small cell lung carcinoma (SCLC) have anti-Hu antibodies that react with all of central and peripheral nervous system neuronal nuclei in immunohistochemical studies and 35- to 40-kDa reactive bands on western blots of extracts from isolated central nervous system neurons. The roles of anti-Hu antibodies in neuronal damage, however, have yet to be shown. Evidence of infiltration of CD8-positive T cells to tumors and affected nervous tissues and limited use of the T cell receptor repertoire in the central nervous system suggests that CD8-positive cytotoxic T cells (CTL) cause neuronal loss. We found the HLA B7 supertype in all of seven Japanese patients with anti-Hu syndrome. We identified HLA class I-restricted, CD 8-positive cytotoxic T cell activity in peripheral blood from three patients with anti-Hu syndrome for five peptides with binding motifs for the HLA B7 supertype in the amino acid sequence of the Hu protein. This study support the involvement of CD8-positive cytotoxic T cells in the development of paraneoplastic neurological syndrome with anti-Hu antibodies.
Three neogrifolin derivatives, 3-hydroxyneogrifolin, 1-formylneogrifolin and 1-formyl-3-hydroxyneogrifolin along with grifolin and neogrifolin were isolated from the Japanese mushroom Albatrellus ovinus belonging to Scutigeraceae. Their structures were established by a combination of two-dimensional NMR spectroscopic analyses and by chemical synthesis. 3-Hydroxyneogrifolin and 1-formyl-3-hydroxy-neogrifolin showed more potent antioxidative activity properties than either alpha-tocopherol or BHA.
Four iridoid glucosides, three of which are dimeric were isolated from the methanol extract of roots of Vietnamese Paederia scandens (Lour) Merrill together with the five known glucosides, paederoside, asperuloside, paederosidic acid, asperulosidic acid and geniposide. Seven sulfur-containing iridoid glucosides were also isolated. The structures of the iridoid glucosides were determined by a combination of high-resolution NMR, MS, IR and UV spectra, and chemical reaction such as acetylation.
Three squalene-type triterpenoids named concentricols B, C and D (1-3) were isolated from the ethyl acetate extract of fruiting bodies of the xylariaceous ascomycete Daldinia concentrica. Their absolute structures were elucidated by analysis of 2D NMR, MS, IR and UV spectra, and the modified Mosher's method.
Four compounds, daldinone A (1), daldinone B (2), daldiniapyrone (4-methoxy-5-carbomethoxy-6-pentyl-2H-pyran-2-one, 3), and daldinialanone (22R-hydroxylanosta-7,9(11),24-trien-3-one, 4), were isolated from an ethyl acetate extract of fruit bodies of Daldinia concentrica collected in Europe. In addition, 11 known compounds, 4:5:4':5'-tetrahydroxy-1:1'-binaphthyl (5), 3,4,5-trihydroxy-1-tetralone (6), (+)-orthosporin (7), curuilignan D (8), (22E)-cholesta-4,6,8(14),22-tetraen-3-one (9), 3beta,22-dihydroxylanosta-7,9(11),24-triene (10), concentricol (11), concentricol B (12), concentricol C (13), concentricol D (14), and phenochalasin B (15), were obtained. The structures of the new compounds were elucidated by 2D NMR, MS, IR, and UV spectra and by X-ray crystallographic analysis. The absolute configurations of 1 and 4 were determined by CD spectroscopy and the modified Mosher's method, respectively. The chemotaxonomic relevance of the compounds obtained in this investigation is discussed.
Ebselen is a seleno-organic compound that inhibits oxidative stress by lipid peroxidation through a glutathione peroxidase-like activity. We studied the effect of ebselen on the expression of hepatic drug-metabolizing enzymes in rats with deoxycholic acid-induced liver injury. Hydrophobic bile acids, such as deoxycholic acid, are known to cause cholestatic liver injury, and it was reported that expression of hepatic cytochrome P-450 (CYP) was reduced by deoxycholic acid administration in rats. Hydrophobic bile acids induce lipid peroxidation in the liver, and this may be one mechanism of the development of liver injury. In the present study, we investigated the effect of ebselen (30 mg/kg/day for 10 days) on rats ingesting deoxycholic acid (1% of diet for 10 days). Deoxycholic acid decreased levels of CYP1A1, 2B1, 2E1 and 3A2 to 34, 58, 62 and 37% of control values, respectively, and increased serum alkaline phosphatase (ALP) and alanine aminotransferase (ALT) activities to 1.8 and 8.6 times the levels of controls, respectively. Administration of ebselen with deoxycholic acid prevented the decreases in levels of CYP1A1 and 3A2 (86 and 65% of control, respectively) and the increases in serum ALP and ALT activities (1.4 and 1.9 times of control, respectively) caused by deoxycholic acid. These results indicate that ebselen may have a protective effect against hydrophobic bile acid-induced liver injury.
A notable proportion of patients with taste disorders complain of xerostomia and when zinc is prescribed the xerostomia is often improved in conjunction with the taste disorder. To study the relationship between taste disorders, zinc deficiency and xerostomia, we measured salivary gland function and zinc levels in 93 patients with hypogeusia and/or xerostomia and 60 patients with unilateral acute peripheral facial palsy who served as controls. We then prescribed zinc for patients with low serum zinc levels and evaluated xerostomia and taste sensation after 6 months of this treatment. The salivary gland secretory ratio (SGSR), determined by dynamic salivary 99mTc scintigraphy, was found to be an objective measure of salivary gland function and was reduced in patients with xerostomia. Patients with salivary gland dysfunction also had abnormal morphology of the papillae of the tongue. No significant relation was found between the severity of taste disorders and SGSR values, but low SGSR values were found in patients with zinc deficiency. Patients with taste disorders and/or xerostomia who were treated with zinc had relief of symptoms at 6 months, indicating that both taste disorders and xerostomia are among the symptoms of zinc deficiency.
In 96 patients who visited our hospital with glossodynia, we conducted gustatory tests, measured serum zinc and copper levels, examined lingual papillae using biomicroscopy, conducted psychological tests and investigated the effectiveness of treatments directed at the cause of dysgeusia. Gustatory test results showed that 43 (44.8%) of the patients had dysgeusia, which was mild in 62.8%, moderate in 30.2% and severe in 7.0%. By giving higher priority to treatment of dysgeusia than to glossodynia, pain disappeared or was relieved and gustatory sensation improved in 27 (62.8%) of these 43 patients. Overall, pain disappeared or was improved in 65 (67.7%) cases. When treating glossodynia, it is important to diagnose the cause of pain and to give higher priority to treating that cause. The clinical efficacy of treatment for glossodynia will be improved when the presence or absence of dysgeusia is diagnosed early in the course of treatment.
The objectives of this study were to produce acid soluble, polyvinylacetal diethylaminoacetate (AEA) microspheres containing trimebutine (as maleate), using a water-in-oil-in-water (w/o/w) emulsion solvent evaporation method, to characterize their in-vitro release properties, and to evaluate the taste-masking potential of this formulation in human volunteers. The pH of the external aqueous phase was the critical factor in achieving a high loading efficiency for trimebutine in the microencapsulation process; nearly 90% (w/w) loading efficiency was obtained at above pH 10. Trimebutine was completely released from AEA microspheres within 10 min in a dissolution test at pH 1.2, simulating conditions in the stomach, whereas at pH 6.8, the pH in the mouth, only small quantities of trimebutine were released in the initial 1-2 min. The results of a gustatory sensation test in healthy volunteers confirmed the taste-masking effects of the AEA microspheres. Finally, an attempt was made to encapsulate the salts of other basic drugs (lidocaine, imipramine, desipramine, amitriptyline, promethazine and chlorpheniramine) into AEA microspheres using the w/o/w emulsion evaporation method. The loading efficiencies were ranked in almost inverse proportion with the solubility of the drugs in the external aqueous phase. This study demonstrated the possibility of masking the taste of salts of basic drugs by microencapsulation with AEA using a w/o/w emulsion solvent evaporation method.
A 43-year-old Japanese woman presented hypertension, hypokalemia and typical Cushingoid signs. Autonomous secretion of both aldosterone and cortisol was shown. Abdominal computed tomography demonstrated a single tumor in the right adrenal gland, which established the diagnosis of combined primary aldosteronism and Cushing's syndrome. The resected tumor was a golden yellow-colored adenoma (diameter 4.3 cm) which expressed P450(aldo) and P450(11beta), causing oversecretion of both hormones from this adenoma. After tumor resection, overproduction of both hormones disappeared and she developed adrenal insufficiency, suggesting the strong suppression of normal adrenal function. This case was complicated by Hashimoto's thyroiditis.