Studies on the alkaloids of Pachysandra terminalis Sieb. et Zucc. (7). Structure of pachysantermine-A, a novel intramolecular ester alkaloid.
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Biomedical subjects
Publications and source records attributed to T Kikuchi.
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We have developed a microplate photon counting system based on a cooled charge-coupled device (Lumi Box U-800 II) jointly with Maikurotekku Nition Company (Chiba, Japan). The system makes it possible to quantify chemiluminescence (CL) in a 96-well microplate automatically and simultaneously in a single experiment. We studied the measurement conditions for a luminol-dependent CL assay from neutrophils stimulated with opsonized zymosan (OZ) using this system. Parameters examined included the effect of OZ dose per well, mixing speed, mixing time and detection time on CL responses. The results indicated that this system allows the measurement of CL from phagocytes on a large number of samples using small amounts of sample and regents.
In normal hematopoiesis, stem cell factor (SCF) stimulates survival, proliferation and differentiation of hematopoietic progenitors. Although SCF acts synergistically with a variety of cytokines, the mechanism of growth factor-cooperation remains to be determined. To analyze the synergism between SCF and granulocyte-macrophage colony-stimulating factor (GM-CSF), we established a new megakaryoblastic cell line, HML-2, by culture in the presence of both SCF and GM-CSF. While SCF alone or GM-CSF alone supported modest cell growth, SCF and GM-CSF together induced substantial growth of this cell line. SCF alone tyrosine-phosphorylated several bands including the 145 kDa subunit of c-kit. GM-CSF alone did not cause the tyrosine phosphorylation of the 145 kDa subunit, but markedly up-regulated the expression of the 145 kDa subunit of c-kit. The combination of SCF and GM-CSF resulted in a synergistic increase in tyrosine phosphorylation of the 145 kDa subunit of c-kit. Several proliferation inhibitors which removed the two-factor interaction on the growth of the HML-2 cells down-regulated the 145 kDa subunit of c-kit. Thus, a synergistic increase in tyrosine phosphorylation of the 145 kDa subunit of c-kit may be one possible mechanism underlying the cooperation of SCF and GM-CSF on the HML-2 cell growth.
Two new cytotoxic chromene derivatives, butyrylmallotochromene [10] and isobutyrylmallotochromene [11], were isolated from the pericarps of Mallotus japonicus. The new derivatives were identified as 5,7-dihydroxy-6-(2',4'-dihydroxy-3'-acetyl-5'-methyl-6'-methoxybenzyl)-8 - butyryl-2,2-dimethylchromene [10] and 5,7-dihydroxy-6-(2',4'-dihydroxy-3'-acetyl-5'-methyl-6'-methoxybenzyl)-8 - isobutyryl-2,2-dimethylchromene [11] by means of spectral data. These compounds and their respective acetylation and methylation products were found to be cytotoxic against KB cell lines.
Interleukin-18 (IL-18) exhibits antitumor activity in various laboratory models. In the current study, brain tumors in naive mice regressed after an intratumoral injection of a single dose of recombinant IL-18 (rIL-18). Intraperitoneal rIL-18 substantially delayed the growth of subcutaneously inoculated gliomas but not gliomas located in the brain. Efficacy was reduced when studies were performed in mice depleted of natural killer cells. Although intracerebral administration of rIL-18 increased the serum interferon-gamma concentration, the antitumor effect of IL-18 was not mediated by interferon-gamma. These data suggest the therapeutic potential for control of tumor growth by intratumoral administration of rIL-18 in patients with glioma.
Anti-hepatitis C virus (HCV) immunoglobulin M antibody titres were measured by an enzyme-linked immunosorbent assay method in 16 patients with non-A, non-B acute hepatitis (NANB AH), 13 with non-A, non-B fulminant hepatitis (NANB FH) and nine with type C chronic hepatitis. Anti-HCV IgM was positive in one of the 16 patients with NANB AH, six of the 13 with NANB FH, and five of the nine with type C chronic hepatitis. Anti-HCV IgG was positive in eight of the 16 patients with NANB AH and eight of the 13 with NANB FH. Either anti-HCV IgM or anti-HCV IgG were positive in 10 of the 13 patients with NANB FH. All of the five anti-HCV IgM positive patients with type C chronic hepatitis were undergoing an exacerbation of the diseases, while all of the anti-HCV IgM negative patients were in a remission stage which had lasted for more than 6 months. The findings of this study suggest that anti-HCV IgM is useful for the early diagnosis of type C FH and may be a useful marker of diseases activity in type C chronic hepatitis.
BACKGROUND: Atrioventricular (Bjork) connection used for the correction of tricuspid atresia has become of little more than historical interest. However, the optimal form of management of patients undergoing this repair still requires continued assessment of the long-term outcome. We review our experience with valveless atrioventricular connection focusing on the morphological changes seen in the heart chambers. METHODS: Between October 1978 and March 1986, seven patients with tricuspid atresia having concordant ventriculoarterial connection underwent atrioventricular connection. Configuration of the surgical connection included Dacron extracardiac conduit without valve insertion. End-diastolic volumes were calculated in the respective heart chambers. A group of patients undergoing atriopulmonary connection was used as control subjects. RESULTS: The diminutive right ventricle showed conspicuous growth at 1.1 +/- 1.1 years after the initial repair, with the end-diastolic volume index increasing from 25.0 +/- 8.7% of normal value at a preoperative state to 80.4 +/- 31.1% of normal value postoperatively. Further operation was done in three patients because of the obstructive atrioventricular pathway. At reoperation, reconstruction of the connection with an addition of either atriopulmonary or cavopulmonary anastomosis afforded clinical improvement in our series. CONCLUSIONS: This study suggests that volume load resulting from the widely patent atrioventricular connection combined with backward regurgitation affects the development of young heart muscle of the right ventricle. The optimal choice of surgical strategy should be made at reintervention through recognition of the particular postsurgical anatomy.
Susceptibility patterns of methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus faecium obtained from various hospitals of the Tohoku district were documented. MICs of 6 antimicrobial agents against a total of 480 strains (380 strains were MRSA and 100 were E. faecium) were estimated. All MRSAs were susceptible to vancomycin, teicoplanin and quinupristin/dalfopristin, but all of them were resistant to ampicillin and benzylpenicillin. None of the E. faecium strains were found to be resistant to vancomycin, teicoplanin and quinupristin/dalfopristin. Excluding these, almost all strains of E. faecium were resistant to the remaining drugs. These data suggest that despite the emergence of vancomycin resistance to E. faecium in Europe and in the United States, vancomycin, teicoplanin and quinupristin/dalfopristin will nevertheless provide effective bactericidal activity in the Tohoku area of Japan.
The activity of S-4661, a new parenteral carbapenem antibiotic, was evaluated against 202 recent clinical isolates of respiratory pathogens. S-4661 was similar to or 2 times more active than imipenem, meropenem, and biapenem, and 8-128 times more active than ceftazidime against gram-positive bacteria. Against gram-negative bacteria, S-4661 was slightly less active than meropenem, but 2-8 times more active than the other agents. In particular, against Pseudomonas aeruginosa S-4661 showed the most potent activity. Thus it was found that S-4661 possesses a potent and well-balanced activity against respiratory pathogens.
OBJECTIVE: Examination of the utility of (99m)Tc-hexamethylpropylene amine oxide ((99m)Tc-HM-PAO) SPECT hippocampal image to diagnose early stages of Alzheimer's disease (AD) using semiquantitative analysis. SUBJECTS: 10 early-stage AD patients and 8 normal sex-matched elderly controls. SETTING: Outpatient division of the Ehime University Hospital. METHOD: We performed (99m)Tc-HM-PAO SPECT perfusion imaging in each subject. A semiquantitative method of assessing regional variation was used. The regions of interest for temporal regions were set at images parallel to the long axis of the hippocampal formation which were reconstructed at 30 degrees negative to the orbitomeatal line and those for other regions were set on ordinary transaxial images. RESULTS: The regional cerebral blood flow ratio of the bilateral medial temporal lobe at the hippocampal image was significantly lower in the AD subjects than in the normally aged controls without any other differences in ordinary transaxial images. CONCLUSION: This study suggests that (99m)Tc-HM-PAO SPECT hippocampal images might be a helpful tool for the diagnosis of very-early-stage AD.
Levels of circulating intercellular adhesion molecule-1 (cICAM-1) were measured by ELISA in the sera of 21 patients with unexplained cardiac dysfunction. By evaluating the biopsy or autopsy specimens, they were classified into two groups: a myocarditis group (n = 8) and a nonmyocarditis group (n = 13). Levels of cICAM-1 were significantly higher in the myocarditis group (p < 0.01). Increased levels of cICAM-1 (> 2 SD above the control mean) were detected in 6 of 8 patients in the myocarditis group. Therefore, the detection of increased levels of cICAM-1 could be a useful marker for myocarditis.
In 8.0 gestation-day embryos, a central cilium and microvilli were present on the apical surface of the cells of the presumptive otic placode and other ectoderm regions as well. The cilium at this stage lacked a central pair of fibres and was regarded as a primitive cilium with 9+0 composition. The microvilli gained in length and density of distribution as soon as the otic placode began to invaginate in 8.5-d. embryos. With further development in 9.5-11.0-d. embryos, they took on a regular distribution pattern. Narrowing and concomitant bulging out appeared in the cells along the neck of the otic invagination in 8.5-d. embryos. Marked regional differences also occurred in the apical-surface structures of the cells, particularly in the relatively more advanced form of the embryos. Kinocilia of the adult vestibular sensory cells were found to lack a continuous central pair of fibres, resembling the apical cilia of the otic placode. This finding seems to suggest that a vestibular kinocilium represents a direct descendant from the primordial cilium, which generally emerges from the primordial ectodermal cells and is entirely lost from the keratinizing ectoderm in the later development.
The fine structure of the utricular kinocilium of the guinea pig was examined with transmission electron microscopy after treatment with tannic acid to enhance resolution of internal morphology. The utricular kinocilium was devoid of inner dynein arms and a central pair of microtubules, while a set of outer dynein arms and radial spokes was found. This supports the hypothesis that the vestibular kinocilium is non-motile. Internal electron-dense particles at the attachment sites of the stereo-kinociliar bonds were situated in the immediate periphery of the outer dynein arms, although no visible connection existed between these structures. Findings obtained in the present study seem to give insight on the mechanism of mechanosensory transduction in the vestibular sensory cells.
The authors studied antitumor immunity conferred by fusions of dendritic and glioma cells in a mouse brain tumor model. Previous immunization with fusion cells (FCs) prevented tumor formation on challenge with glioma cells in the flank or in the brain. Efficacy was decreased when studies were performed in mice depleted of CD8+ cells. In a treatment model, FCs were injected subcutaneously after tumor development in the brain. The administration of FCs alone had limited effects on survival of mice bearing brain tumors. Importantly, however, administration of FCs and recombinant interleukin-12 (rIL-12) remarkably prolonged the survival of mice with brain tumors. Cytotoxic T lymphocyte activity against glioma cells from immunized mice was also stimulated by coadministration of FCs and rIL-12 compared with that obtained with FCs or rIL-12 alone. These data support the therapeutic efficacy of combining FC-based vaccine therapy and rIL-12.
To evaluate the effects of a traditional Chinese herbal medicine, Hochu-ekki-to [Bu-zong-yi-qi-tang], on the bone loss induced by ovariectomy in rats, ovariectomized female rats of the Sprague-Dawley strain at age 35 weeks were daily given Hochu-ekki-to and/or 17 alpha-ethynylestradiol for 8 weeks by gastric tube and, subsequently, the serum hormone levels and the tibial bone mineral density were measured. Hochu-ekki-to treatment suppressed the ovariectomy-induced reduction of the bone mineral density in the whole and metaphysis of tibia with a slight increase of serum levels of estradiol and progesterone, maintaining bone mineral density values similar to that in the estradiol treated ovariectomized rats, as well as the intact control rats. Hochu-ekki-to is suggested to elevate the serum levels of ovarian hormones slightly and prevent bone loss in ovariectomized rats.
A gas chromatographic-mass spectrometric method using selected ion monitoring mode for simultaneous determination of 6 sulfonamides in egg and edible animal tissues has been developed. Sulfonamides are extracted from a sample with acetonitrile. The extract is passed through a silica cartridge column and concentrated. Diazomethane in ether is added to methylate sulfonamides. After evaporation, the residue is dissolved in methylene chloride and cleaned up by silica gel column chromatography. The methylene chloride eluate containing sulfonamide-methyl derivatives is evaporated to dryness, redissolved in ether and partitioned between 6N hydrochloric acid. The acid phase is made alkaline, extracted with ether, and the ether solution, after concentration, is analyzed by gas chromatography-mass spectrometry in selected ion monitoring mode. Average recoveries from egg and silver salmon fortified at 1 and 0.2 ppm levels with 6 sulfonamides are 99.2 and 84.3%, respectively; coefficients of variation are 7.03 and 11.20%, respectively. Detection limits are 0.01-0.05 ppm.