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Biomedical subjects

M Natsume

Publications and source records attributed to M Natsume.

At least 37 records · Page 2Linked to original sources

Preparation of alkyl-substituted indoles in the benzene portion. Part 15. Asymmetric synthesis of (+)-duocarmycin SA using novel procedure for preparation of hydroxyindoles.

An asymmetric total synthesis of natural (+)-duocarmycin SA (1) starting from L-malic acid (7) was achieved as shown in Chart 5, establishing firmly the absolute configuration of 1. In order to find suitable reaction conditions for the key step, i.e., the formation of an alkoxyindole derivative, model compounds 9 and 40 were synthesized and two acetalization conditions using i) 2-ethyl-2-methyl-1,3-dioxane and boron trifluoride etherate, and ii) 1,3-bis(trimethylsilyloxy)propane and trimethylsilyl triflate were found to be effective. The former conditions were successfully applied to total synthesis and 49b was prepared from 48 in 54% yield. Further elaborations including i) Curtius rearrangement of 53b to 56, and ii) cleavage of the primary benzyloxy group in the presence of the secondary one in its close vicinity (56-->57) led to the relay compound 62, whose conversion to 1 has already been accomplished.

Alkylation↗

The antioxidative substances in cacao liquor.

The antioxidative substances contained in cacao liquor, which is one of the major ingredients of chocolate, were separated by column chromatography and high-performance liquid chromatography. Three major compounds were purified and two of them were identified by 1H, 13C NMR and mass spectra as (-)-epicatechin (EC) and (+)-catechin (CA). Their antioxidative activity was measured by monitoring the peroxide value of linoleic acid and the thiobarbituric acid-reactive substance values of erythrocyte ghost membranes and microsomes. EC and CA had strong antioxidative effects in all three methods, but one unidentified peak was found to be less effective. Additionally, we analyzed the polyphenol concentration of cacao liquor extractions produced in several countries. The total polyphenol concentration was 7.0 to 13.0%, catechin concentration was 0.31 to 0.49%, and epicatechin concentration was 0.35 to 1.68% in the extractions. It is believed that chocolate is stable against oxidative deterioration on account of the presence of these polyphenolic compounds, and it is also expected to have a protective role against lipid peroxidation in living systems.

Alcoholic Beverages↗

Alleviation of monocrotaline-induced pulmonary hypertension by antibodies to monocyte chemotactic and activating factor/monocyte chemoattractant protein-1.

Administration of monocrotaline (MCT) causes pulmonary vascular lesions consisting of monocyte/macrophage infiltration in the early phase and medial thickening in pulmonary arteries and arterioles associated with pulmonary hypertension (PH) in the later phase. However, the molecular mechanism of monocyte/macrophage infiltration and its roles remain elusive. Herein, we have evaluated the role of a potent monocyte chemotactic and activating chemokine/monocyte chemoattractant protein-1 (MCAF/MCP-1) in MCT-induced PH in rats. A single injection of MCT induced PH at Day 21, as evidenced by increases in the ratio of right ventricular to left ventricular and septum weights (RV/LV+S) and right ventricular systolic pressure (RVSP). A significant increase in macrophage number in lungs started at Day 14, reaching a maximum at Day 21. MCAF/MCP-1 levels in bronchoalveolar lavage fluids were elevated significantly at Day 14 and remained high until Day 28, whereas plasma MCAF/MCP-1 levels increased at Day 7, returning to normal levels by Day 21. Immunoreactive MCAF/MCP-1 proteins were mainly detected in macrophages in alveoli and in perivascular regions of pulmonary arterioles and venules. Intravenous administration of anti-MCAF/MCP-1 antibodies with MCT significantly decreased macrophage infiltration and eventually reduced the increases in RV/LV+S and RVSP, as well as medial thickening of pulmonary arterioles. Thus, MCAF/MCP-1 is essentially involved in MCT-induced PH by recruiting and activating macrophages.

Animals↗

Characterization of a water-soluble polysaccharide fraction with immunopotentiating activity from Bifidobacterium adolescentis M101-4.

The soluble and insoluble fractions obtained after sonication and centrifugation of Bifidobacterium adolescentis M101-4 cells were examined, and both of these fractions exhibited mitogenic activity in an assay of murine splenocytes and Peyer's patch cells in vitro. The soluble fraction was further treated by a 6-step procedure involving proteinase K-treatment, ultrafiltration with a 50-kDa cut-off molecular-sieving membrane, anion-exchange chromatography, dialysis, ultrafiltration through a 6-kDa cut-off membrane filter, and gel-filtration to yield a soluble high molecular weight fraction (SHF) which was effective for stimulating the proliferation of murine splenocytes. Almost three quarters of this fraction by weight was found to consist of carbohydrates containing glucose and galactose as major constituents, and the average molecular weight was estimated to be between 60,000 and 2,460,000, with the main peak at 1,550,000 Da, by the retention time of gel permeation chromatography. A structural analysis by 1H- and 13C-nuclear magnetic resonance and methylation indicated that SHF contained polysaccharides consisting of -4Galp1-, -4Glcp1-, and -6Glcp1- as the major residues, and Galf1- and -6Galf1- as the minor residues. Immunopotentiating SHF was found to contain galactofuranosyl residues as characteristic constituents which had not been previously detected in other soluble fractions from Gram-positive bacteria.

Adjuvants, Immunologic↗

Intracellular fate of 2-NBDG, a fluorescent probe for glucose uptake activity, in Escherichia coli cells.

A fluorescent derivative of D-glucose, 2-NBDG, which was previously developed for the evaluation of glucose uptake activity by living cells, was used on Escherichia coli cells and its fate after incorporation in the cells was investigated. 2-NBDG was converted to another fluorescent derivative (2-NBDG metabolite) immediately after it was taken by E. coli cells. This 2-NBDG metabolite was then decomposed to non-fluorescent forms. 2-NBDG metabolite was decomposed into the original 2-NBDG by G6Pase with concurrent liberation of inorganic phosphate. Furthermore, FAB/MS analysis showed that its molecular weight was 420, the same value as that of 2-NBDG 6-phosphate. These indicate 2-NBDG metabolite should be 2-NBDG 6-phosphate. Based on these results, the feasibility of 2-NBDG as a fluorescent non-toxic probe for glucose uptake activity and its application to viability assessment of various living systems are discussed.

4-Chloro-7-nitrobenzofurazan↗

Structure-activity relationship of pamamycins: effects of alkyl substituents.

Nine new pamamycin homologues were isolated from the culture broth of Streptomyces alboniger IFO 12738 using a combination of ODS and NH2 HPLCs, and their structures determined by GC-MS. The structural differences in these homologues are in the numbers and positions of methyl and ethyl groups. The aerial mycelium-inducing and growth-inhibitory activities in S. alboniger of these homologues and their antibiotic activity against Bacillus subtilis were examined. The effects of the alkyl substituents on these activities are discussed.

Antifungal Agents↗

Isolation and characterization of alginate-derived oligosaccharides with root growth-promoting activities.

Lytic digestion of poly(mannuronate), poly(guluronate), and alginate with an alginate lyase from Alteromonas macleodii was used to prepare mixtures of unsaturated oligosaccharides. Four oligosaccharides isolated from the alginate lyase-lysate by anion-exchange chromatography on Q-Sepharose were found to be the major components of the root growth-promoting lysate. The oligosaccharides were analyzed by NMR and SIMS and identified as di- and tri-saccharides having O-(4-deoxy-L-erythro-hex-4-enopyranosyluronic acid)-1--> at the nonreducing terminus. The trisaccharides from the lysate were found to have root growth-promoting activity in a barley bioassay.

Alginates↗

Total synthesis of a frog poison, (+/-)-epibatidine, a potent non-opioid analgesic.

A non-opioid analgesic, epibatidine (1), isolated from Ecuadoran poison frogs was synthesized in the racemic form starting from a readily available compound 2. A partial Curtius rearrangement product 5 of 2 was converted into 12c by way of the ketone 3 and its condensation product with the pyridine moiety 9c, and catalytic hydrogenation of 12c was specifically conducted in hydrochloric acid-containing 2-propanol for the preferential formation of an exo-product 15b. Conversion of the substituent from 15b to 15a in a single operation using the Vilsmeier reagent, followed by deprotection of the p-toluenesulfonyl group with hydrobromic acid completed an eight-step synthesis of (+/-)-1 from 2.

Analgesics↗

Pendolmycin, a new tumor promoter of the teleocidin A class on skin of CD-1 mice.

Pendolmycin, isolated from Nocardiopsis, is a compound structurally similar to teleocidin A, one of the 12-O-tetradecanoylphorbol-13-acetate (TPA)-type tumor promoters. Pendolmycin has a C5 dimethyl allyl group attached to C-7 of (-)-indolactam-V, whereas teleocidin A has a C10 linalyl group attached to the molecule. The structure-activity relationships of a hydrophobic moiety attached to (-)-indolactam-V were studied in four compounds, (-)-indolactam-V, pendolmycin, teleocidin A and newly synthesized 7-(nerolidyl)-(-)-indolactam-V in tests on inhibition of the specific [3H]TPA binding to a particulate fraction of mouse skin, activation of protein kinase C and induction of both adhesion of HL-60 cells and ornithine decarboxylase in mouse skin. The potencies of the compounds for these activities increased mainly depending on the length of the hydrophobic group. Pendolmycin had a tumor-promoting activity on mouse skin initiated with a single application of 7,12-dimethyl-benz[a]anthracene, and its potency was just between those of (-)-indolactam-V and teleocidin A. The role of the hydrophobic moiety is discussed with particular emphasis on the results obtained with 7-(nerolidyl)-(-)-indolactam-V.

Alkaloids↗

Calcium ion regulates aerial mycelium formation in actinomycetes.

Ca2+ induced the formation of aerial mycelia in Streptomyces ambofaciens. Its effect was inhibited by ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid, a Ca2+ specific chelating agent. A survey of 36 strains of actinomycetes showed that Ca2+ regulated aerial mycelium formation in 21 (58%) of them. The Ca2+ concentration required for aerial mycelium formation in the culture medium ranged from 0.1 to 1.5 mM.

Actinomycetales↗

[The method for stress assessment of workers (Part 1). Stress score by self-rating method].

In order to evaluate the grade of reaction to stressors, especially those on occupational life of workers, the following stress survey was conducted. Eighteen new items of occupational life stressors were proposed in addition to the social readjustment rating scale (S.R.R.S.) prepared by Holmes. Furthermore, two items, "own stress tolerance" and "own stress at present," were designed in addition to the foregoing 65 stressors. Marriage is given a score of 50 in reference-standard of stress strength. These 67 items of 1,630 workers were evaluated by the self-rating method ranging in score from 0 to 100. The results can be summarized as follows: 1. As for each item, we examined the average value of the total sample and analyzed them by sex, age, kind of occupation, position, and length of service. We named these stress scores and analyzed the ranking of 65 stress scores. The item with the highest score was "death of spouse (score 82.7)" and the item with the lowest one was "income increase (score 24.7)." The scores of 27 out of 65 items were higher than 50. Next, 65 items were classified into 4 groups, that is, individual life, family life, occupational life, and social life. 2. Scores of the newly designed items to examine the ability to adjust oneself to place of work were "own stress tolerance (score: 73.7)" and "own stress at present (48.8)," respectively. 3. We examined the difference by sex, age, kind of occupation, position, and length of service based on the average value of stress score by t-test and the following results were obtained. 1) Scores of those in the thirties were higher than those in the twenties. 2) Section heads and leaders were under greater stress than division heads. In the same way, the differences among the four groups were analyzed and the following results were observed. 1) The only significant difference was seen in the occupational life stress group. 2) In the occupational life stress group, the scores of those in the thirties, forties, and fifties were higher than those in the twenties. Section heads and leaders were under greater stress than the staff. Workers in service for more than 21 years had higher scores than workers in service for less than 10 years. 4. The practical uses of our stress survey are also discussed in this report.

Adult↗

Isolation, physico-chemical properties and biological activity of pamamycin-607, an aerial mycelium-inducing substance from Streptomyces alboniger.

Pamamycin-607, which showed aerial mycelium-inducing activity, has been isolated from Streptomyces alboniger IFO 12738. At 0.1 microgram/disc it induces aerial mycelia in the aerial mycelium-negative strain of S. alboniger but inhibits growth of the substrate mycelia at 10 micrograms/disc. It also acts as an antibiotic against some fungi and bacteria. When KMnO4 was partitioned with pamamycin-607 between benzene and water, MnO4- but no K+ was transferred from the water to the benzene layer; pamamycin-607 was thus shown to be a novel anion-transfer antibiotic.

Anti-Bacterial Agents↗

[Studies on the occupational maladjustment syndrome. (Part 3). In reference to the therapeutic system for the OMA syndrome and the industrial physician's roles].

In order to ascertain the effects of the newly-devised therapeutic system (described later) and clarify the industrial doctor's roles, a study was made on 96 patients with O.M.A.S. (34 in core group, 26 in dropout group, 15 in other group, 13 in transient reaction group and 8 in special job maladjustment group) whom we had directly treated. The subjects of the present study were 54 patients with O.M.A.S. who were treated in the clinic (our clinic) at the Dept. of Mental Health, Osaka Prefectural Institute of Public Health during the past 19 years and 42 patients who were examined in the company's clinic (this company consists of 15,000 employees) where we have practiced mental hygiene of industrial medicine during the past 15 years. Two typical cases in respect of the therapeutic system are presented. We developed a newly-devised therapeutic system of O.M.A.S. (I. Medical examination, II. Counselling for the patients and their family, III. Psychiatric rehabilitation, and IV. Therapeutic advices for their colleagues or superiors in their working place). Of the 96 patients, 81 were reinstated to their office and are at work by using the therapeutic system. Of 96 patients it was necessary for 59 to accept the therapeutic advices. In 49 of 59 patients (Accepted group), doctor's therapeutic advices were accepted by their colleagues or superiors in their working place. In the remaining 10 patients (Refused group) treated by our clinic, the therapeutic advices were refused. Accepted group was observed to be more adaptable to their jobs than refused group. As to the therapeutic content we manipulated their conditions as follows: therapeutic transposition in 27 patients, reduction of duty and guidance of work in 18 patients, and therapeutic preliminary reappointment in 13 patients. It is considered that the industrial doctor of mental hygiene plays an important role in order to establish the therapeutic system of O.M.A.S.

Adaptation, Psychological↗

[Studies on the occupational maladjustment syndrome (Part 2). In reference to relationship between psychophysiological characters and clinical features].

In a previous report (Natsume et al., Jpn. J. Ind. Health, Vol. 24) on the occupational maladjustment syndrome (O.M.A.S.), on the basis of clinical data, we classified patients with O.M.A.S. into 5 subcategories; core, drop-out, transient reaction, special job maladjustment and other. The core and drop-out types are typical of O.M.A.S. In order to test our hypothesis regarding the clinical and psychophysiological character of patients with O.M.A.S., 39 subjects (25 core type and 14 drop-out type) were studied by polygraphic techniques such as EEG, EMG of facial muscles and electrooculogram, and the results were compared with those of 16 normal subjects. We were specifically interested in their behavior in mental arithmetic and at rest. The results are summarized as follows: At rest, less frequent irregular rapid eye movement (especially "r-type") and smaller amplitudes of the corrugator supercilii muscle characterized the patients compared to the normals. During mental arithmetic these two indicators showed a greater tendency to increase in the core type than in the normals, but they remained unchanged in the drop-out group. In the core type subjects, the increased levels in these indicators persisted briefly after the arithmetic sessions. We discuss the relationship between the clinical character of the two types and the above results. We consider that the psychophysiological character of the two types may play an important role in the pathogenetic mechanism of O.M.A.S.

Adjustment Disorders↗