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Biomedical subjects

N Shigematsu

Publications and source records attributed to N Shigematsu.

At least 145 records · Page 8Linked to original sources

Abolishment of inhibitory effects of 3'-deazaadenosine on superoxide generation of guinea pig phagocytes by pre-exposure to phorbol myristate acetate.

Superoxide generation by guinea pig macrophages and polymorphonuclear leukocytes induced by wheat germ agglutinin, immune complexes or formyl-methionyl-leucyl-phenylalanine was inhibited considerably by 3'-deazaadenosine. The pre-exposure of the 3'-dezazaadenosine-treated cells to a small amount of phorbol myristate acetate abolished the inhibitory effect of 3'-deazaadenosine on the generation of superoxide.

Animals↗

Suppressive effect of Escherichia coli on adjuvant-induced arthritis in germ-free rats.

Our previous finding, that germ-free F344 rats develop severe adjuvant-induced arthritis, whereas specific pathogen-free rats develop mild disease, prompted us to investigate the role of bacterial flora in promoting the development of this disease. Germ-free rats given Escherichia coli experienced disease suppression. Germ-free rats treated with 3 strains of Lactobacillus experienced an enhancement of the disease, although it was not significant. Germ-free rats treated with a combination of E coli and lactobacilli had disease suppression similar to that of E coli monoassociated rats. Thus, these findings suggest that E coli may play a dominant role in modulating the development of the disease in this particular strain of F344 rats, possibly through its lipopolysaccharide (as evidenced by positive results on limulus tests). These findings also suggest that microflora play an important role in modifying the development of joint disease.

Animals↗

[Combined effects of radiation and 5-FU derivatives].

The combined effects of X-ray irradiation and 5-FU derivatives (5-FU, tegafur, HCFU) treatment were investigated in mouse adenocarcinoma-755. Mice were given a single irradiation 5 Gy or 10 Gy of 6-MV X-rays and orally administered 5-FU derivatives at the time of pre- or post-irradiation. Under these conditions, antitumor activity and survival time were compared between pre- and post-irradiation. Under these conditions, antitumor activity and survival time were compared between pre- and post-irradiation, in combination with 5-FU, tegafur or HCFU. The antitumor effects and survival time were greater for pre-irradiation treatment than for post-irradiation. Among 5-FU derivatives, the highest combination effect was shown by HCFU, followed by 5-FU and tegafur. The concentration of 5-FU in the tumor was correlated with the antitumor effect of each drug.

Adenocarcinoma↗

Acute and chronic polyarthritis induced by an aqueous form of 6-O-acyl and N-acyl derivatives of N-acetylmuramyl-L-alanyl-D-isoglutamine in euthymic rats and athymic nude rats.

The analogs of N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP), 6-O-stearoyl-MDP (L18-MDP), and N-(N-acetylmuramyl-L-alanyl-D-isoglutaminyl)-N-stearoyl-L-lysine (MDP-Lys-L18) and N-(2-tetradecylhexadecanoyl)-MDP (B30-MDP) induced acute polyarthritis in both euthymic rats and in athymic nude rats after a single or multiple systemic administrations of their aqueous forms; water-in-oil emulsions did not induce acute polyarthritis. MDP and the adjuvant-active analogs MDP-O-nBu (MDP butyl ester), N-(3-hydroxy-2-docosylhexacosanoyl)-MDP (BH48-MDP) and the adjuvant-inactive analogs [L18-MDP (L)] or MDP-Lys-L18 (L), which is 6-O-stearoyl-N-acetylmuramyl-L-alanyl-L-isoglutamine, or N-(N-acetylmuramyl-L-alanyl-L-isoglutaminyl)-N-stearoyl-L-lysine, did not induce disease, at the dosages used. Histological examination of the acute exudative inflammatory reactions around joints revealed hypertrophy of both synovial villi and tendon sheath, infiltration of polymorphonuclear leukocytes (PMN) and fibrin deposition of the affected joint spaces. Most of these lesions rapidly subsided after cessation of the adjuvant injections. During multiple systemic injections of acyl-MDPs, this acute arthritis became chronic in euthymic rats but not in athymic nude rats; the chronic polyarthritis consisted of mononuclear cell infiltration and proliferation of the connective tissue growth and severe new bone formation of the shaft of the bone. It remains uncertain whether chronic polyarthritis results from the repeated flare of acute inflammatory reactions to the continuing stimulation of the adjuvants or whether it may require some immunologic process to such exogenous substances as bacterial fragments or autoantigens modified by exogenous substances such as type II collagen.

Acetylmuramyl-Alanyl-Isoglutamine↗

Peritoneal macrophages of guinea pig possibly lack LTC4 synthetase.

Peritoneal cells and adherent cells of mice and rats synthesized LTC4 and LTB4 when stimulated with A23187 in vitro. On the other hand, neither peritoneal cells nor adherent cells of guinea pigs generated LTC4, D4, and E4, but did the lower amounts of LTB4. Only generation of LTB4 was potentiated by simultaneous addition of 10 microM A.A. in this species. Enzyme solutions which were extracted from peritoneal cells of these three species were capable of converting DNCB to a colored product in the presence of glutathione and then these potencies were in the following order; guinea pig greater than mouse greater than rat. On the other hand, the potencies of converting LTA4 to LTC4 in the presence of glutathione were in the following order; mouse greater than rat much greater than guinea pig approximately equal to 0. These results suggest that macrophages of guinea pigs lack "LTC4 synthetase" and also this enzyme is different from usual GSH S-transferases.

Animals↗

Influences of salts on high-performance liquid chromatography of leukotrienes.

The effects of concentrations and kinds of salts on the resolution of leukotrienes (LT) C4, D4, E4, and B4 were investigated by two kinds of reversed-phase high-performance liquid chromatography columns (muBondapak C18 and Novapak C18). When a mobile phase (acetonitrile/methanol/water) with a lower concentration of acetic acid (0.02-0.1%) at pH 5.6 was used, LTC4 and LTD4 were not eluted from the muBondapak column. On the Novapak column, LTC4 and LTD4 were eluted, but they were poorly resolved. When the concentration of acetic acid in the mobile phase was raised to 1.0% and adjusted to pH 5.6 with ammonium hydroxide or triethylamine, excellent resolution of LTs was obtained. Sodium hydroxide was, to some extent, useful for the pH adjustment of the mobile phase. Sodium chloride could not be substituted for acetic acid-ammonium hydroxide or -triethylamine salt. The resolution of LTC4, LTD4, and LTE4 was affected more strongly than that of LTB4 by changes of concentrations and kinds of salts. When the acetonitrile/methanol/water/acetic acid solvent system adjusted to pH 5.6 with triethylamine was applied to the analysis of the leukotrienes produced from rat peritoneal cells with stimulation of calcium ionophore A23187, de novo-synthesized LTC4, LTD4, LTB4, and isomers were clearly separated. This solvent system may be useful for the investigation of variations in the synthesis of subclasses of LTs with different stimuli and under different circumstances.

Animals↗

Prognostic factors influencing relapse of squamous cell carcinoma of the maxillary sinus.

In 95 surgically staged patients with squamous cell carcinoma of the maxillary sinus, multivariate regression analyses were employed to identify prognostic factors. Possible prognostic factors for local control were TNM stage and type of surgical procedures: T2 or T3 tumors and use of total maxillectomy showed better local control rates (P less than 0.01). High radiation doses of 40 Gy or more also seemed to be of prognostic significance: P less than 0.2 for 40 to 60 Gy, and P less than 0.1 for 60 Gy or more. The risk of cervical relapse increased when the cheek or alveolus was grossly involved (P less than 0.2). However, since cervical relapse frequently accompanied uncontrollable primary recurrence or distant spread, and since cervical relapse alone was frequently salvaged by radical neck dissection, prophylactic irradiation to the neck is not recommended. Sex, age, nodal state, addition of chemotherapy, total doses of bleomycin or 5-fluorouracil (5-FU), or intra-arterial administration of chemotherapeutic agents did not appear to be of prognostic significance.

Adult↗

Reverse effect of gram-positive bacteria vs. gram-negative bacteria on adjuvant-induced arthritis in germfree rats.

Germfree (GF) F344 rats developed severe adjuvant-induced arthritis with a 100% incidence after a single intradermal injection of heat-killed Mycobacterium bovis (BCG). Specific pathogene-free (SPF) rats developed less severe arthritis with a lower incidence. The rats colonized with Escherichia coli or Bacteroides developed mild disease comparable to that in SPF rats. The rats colonized with Bifidobacterium, Propionibacterium acnes, Lactobacillus casei, L. fermentum, L. murini, and L. acidophilus developed more severe disease than that in GF rats. Furthermore, the rats colonized with a mixture of E. coli and the above lactobacilli developed very mild disease similar to that in SPF rats. These results suggest that gram-negative bacteria, such as E. coli and Bacteroides, may suppress the disease, possibly through their lipopolysaccharides, and may be responsible for the lower susceptibility of SPF rats; gram-positive bacteria, such as Bifidobacterium, P. acnes, and lactobacilli, may enhance the disease, possibly through their peptidoglycans; and E. coli may play a dominant role in modulating the development of adjuvant-induced arthritis.

Animals↗

Granuloma formation by muramyl dipeptide associated with branched fatty acids, a structure probably essential for tubercle formation by Mycobacterium tuberculosis.

Muramyl dipeptide, which does not induce epithelioid granuloma when injected alone dissolved in phosphate-buffered saline, could induce extensive granulomas in guinea pigs when chemically conjugated with branched, but not linear, fatty acids. Peptidoglycan fragments of Staphylococcus epidermidis could evoke epithelioid granulomas when incorporated in a water-in-oil emulsion. These findings suggest the importance of a lipid bound to muramyl dipeptide for granuloma formation. In view of the fact that mycobacteria uniquely contain large amounts of branched fatty acids, it was proposed that the complex of muramyl dipeptide and branched fatty acids, mostly mycolic acids, is a structure in tubercle bacilli responsible for tubercle formation.

Acetylmuramyl-Alanyl-Isoglutamine↗

Respiratory involvement and immune status in yusho patients.

Clinical and experimental studies on respiratory involvement and alterations in immune status were carried out. Respiratory distress occurring in these patients has improved gradually for 14 years but still remains. Copious expectoration at an early stage of the disease may be related to the fact that a number of discrete polychlorinated biphenyls (PCBs) are distributed throughout the lung parenchyma. For accumulation in the bronchial mucosa, structural requirements and specific dose dependence of PCBs have been clearly shown; however, pathological and physiological studies have indicated that respiratory involvement in yusho is mainly small airway disease that may be caused by involvement of cellular component (Clara cells) in bronchioles and/or associated infection. Respiratory distress is often exacerbated by viral or bacterial infection. Changes in the immune status in PCB and polychlorinated dibenzofuran (PCDF) poisoning are as follows: IgA and IgM in the serum are decreased at an early stage of the disease and then return to normal; suppression of cellular immunity was reported in Taiwanese patients and some may remain in the later stages of the disease, as shown in our patients. PCDFs now appear to be the main causal agents in yusho. Rats given PCDFs showed necrosis of the Clara cells in bronchioles and marked thymus atrophy, while few such changes were noted in rats given PCBs. Therefore, further examination is needed for the difference of the toxic effects between two compounds.

Animals↗

Biphenomycins A and B, novel peptide antibiotics. II. Structural elucidation of biphenomycins A and B.

The structures of biphenomycins A and B, novel peptide antibiotics produced by a strain of Streptomyces, have been established as 1 and 2, respectively, on the basis of spectroscopic and chemical evidence. They are unique in that they are cyclic peptides containing a biphenyl moiety included in a 15-membered ring and show potent antibacterial activities especially against Gram-positive bacteria.

Anti-Bacterial Agents↗

Determination of methylthio and methylsulphone polychlorinated biphenyls in tissues of patients with 'yusho'.

The liver, lung and mesenteric adipose tissue of three patients with 'yusho', polychlorinated biphenyl (PCB) poisoning, and two control persons were analysed for methylthio and methylsulphone metabolites of PCBs by gas chromatography with electron capture detection, gas chromatography-mass spectrometry and mass fragmentography. The tissues were shown to contain two congeners of methylthio PCBs with four chlorine atoms, and 16 congeners of methylsulphone PCBs with three, four, five or six chlorine atoms. The concentrations of methylthio PCBs in the liver, lung and adipose tissue of the yusho patients were 0.1-0.5, 0.2-1.4 and 0.5-1.0 micrograms/kg, respectively, and those of methylsulphone PCBs were 0.3-0.7, 1.0-2.5 and 0.7-1.0 micrograms/kg, respectively. The concentration ratios of methylthio and methylsulphone PCBs to unchanged PCBs were 1-2% in the liver, 4-8% in the lung and 0.1-0.2% in the adipose tissue for yusho patients, indicating that these metabolites accumulate slightly more in the lung and liver than in the adipose tissue, relative to PCBs. The tissue levels of the PCB metabolites in control persons were about one tenth of those in yusho patients.

Adipose Tissue↗