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Biomedical subjects

T Shimizu

Publications and source records attributed to T Shimizu.

At least 145 records · Page 8Linked to original sources

Anti-Mycobacterium tuberculosis activities of new fluoroquinolones in combination with other antituberculous drugs.

OBJECTIVES: Studies were undertaken in order to assess the anti- Mycobacterium tuberculosis (MTB) activities of newly developed fluoroquinolones in combination with other antituberculous drugs. METHODS: A new C-8-methoxyl fluoroquinolone, gatifloxacin (GFLX), and a new C-8-chloro fluoroquinolone, sitafloxacin (STFX), in combination with other drugs were examined for their activities against extracellular growing MTB organisms and those replicating in RAW264.7 macrophages (RAW-M phis s). RESULTS: STFX but not GFLX potentiated the activities of rifampin and rifalazil against extracellular MTB. Both GFLX and STFX exhibited combined activities against intramacrophage MTB, when used in combination with rifampin, rifalazil, isoniazid, pyrazinamide, ethambutol, streptomycin, or clofazimine. CONCLUSIONS: Although the observed combined effects varied to some extent from case to case depending on drug combinations, the present findings suggest the usefulness of these new fluoroquinolones in multi-drug regimens for tuberculosis patients.

Animals↗

Effects of n-3 polyunsaturated fatty acids on dermatitis in NC/Nga mice.

The administration of n-3 polyunsaturated fatty acids (PUFAs) is known to be effective against allergic diseases by suppressing the production of eicosanoids derived from arachidonic acid. To investigate the mechanisms and efficacy of n-3 PUFA treatment in patients with atopic dermatitis (AD), we administered four different formulas of alpha-linolenic acid for 6 weeks in an AD model using NC/Nga mice. According to the doses of alpha-linolenic acid given, the levels of alpha-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid in the red blood cell membranes increased while the levels of linoleic acid and arachidonic acid decreased. However, there was no significant difference among the four dose groups in clinical skin severity score, histopathological findings of skin lesions, or levels of total plasma IgE. Moreover, there was no significant difference in the production of leukotriene B(4) and Leukotriene C(4) from skin lesions after stimulation with A23187 among the groups, although the production of prostaglandin E(2) (PGE(2)) was significantly reduced and skin blood flow in the ear was significantly higher in the group given the highest dose of alpha-linolenic acid. Our results suggest that the administration of alpha-linolenic acid can change the fatty acid composition, PGE(2) production, and skin blood flow but may not prevent the development of dermatitis in NC/Nga mice.

Animals↗

Late onset of right Bochdalek's hernia with strangulation of the omentum.

UNLABELLED: We report a case of bloody pleural effusion and infarction of the greater omentum caused by a non-traumatic diaphragmatic hernia with a late presentation. A 15-y-old boy with Down's syndrome developed abdominal pain and vomiting, as well as an elevated serum level of C-reactive protein. Chest roentgenograms showed a right-sided pleural effusion and computed tomography revealed a right diaphragmatic hernia. Barium enema confirmed the diagnosis. An operation revealed a right Bochdalek's hernia with strangulation of the greater omentum in the right pleural cavity. CONCLUSION: Diaphragmatic hernia should be considered in patients with pleural effusion, abdominal pain and vomiting.

Abdominal Pain↗

Th1/Th2 balance in childhood idiopathic nephrotic syndrome.

AIMS: In view of the conflicting evidence of helper T cell type 1 (Th1) or type 2 (Th2) pattern of cytokine synthesis in childhood idiopathic nephrotic syndrome (INS) this study examined the balance of Th1 and Th2 which are characterized by intracellular cytokine production of interferon-gamma (IFNgamma) and interleukin-4 (IL-4), respectively. SUBJECTS AND METHODS: Sixteen children with steroid-sensitive INS (mean age 9.0 years) were included in this study, together with 15 healthy normal children (mean age 7.9 years) for the control group. Intracellular production of both IFNgamma and IL-4 in helper T cell (CD4+ cell) was investigated by a 3-color flow cytometry. RESULTS: The cross-sectional data showed no significant differences of percentages of Th0 (IFNgamma+ IL-4+ CD4+ cell), Th1 (IFNgamma+ lL-4- CD4+ cell) and Th2 (IFNgamma- IL-4+ CD4+ cell) in CD4+ cells (p > 0.05). The Th1/Th2 ratio during nephrotic relapse did not differ from those during nephrotic remission and in normal healthy children (p > 0.05). CONCLUSION: We conclude that there is no significant skew of Th1/Th2 balance in childhood INS and that the cardinal immunological abnormality does not lie in helper T cells but in other cells, such as suppressor/cytotoxic T cells, natural killer cells or monocytes/macrophage. To clarify the pathogenesis of INS, comprehensive studies for these cells would be worthwhile.

Case-Control Studies↗

[Strategy for preventing recurrence after video-assisted thoracoscopic surgery for spontaneous pneumothorax; efficacy of talc pleurodesis and absorbable mesh covering].

Video-assisted thoracoscopic surgery (VATS) has been widely used in the treatment of spontaneous pneumothorax. The unexpectedly high increase of the recurrence rate is the most important problem. We examined the interaction between recurrence, clinical features and patient's backgrounds. The main causes of recurrence were oversight of bullae and the emphysematous changes at the periphery of the site where an autosuture device was used. 90% of the recurrence occurred in the patients with type III small diffuse bullae. Introduction of the regional talc pleurodesis and covering stapled line with absorbable mesh were extremely useful to lower the recurrence rate after VATS for spontaneous pneumothorax.

Absorbable Implants↗

Critical role of the neuronal nitric-oxide synthase heme proximal side residue, Arg418, in catalysis and electron transfer.

Nitric oxide (NO) is synthesized from L-Arg in the P450-type heme active site of nitric-oxide synthase (NOS). The internal axial ligand of the heme, Cys415, may hydrogen-bond to the side chain of the conserved Arg418 residue in neuronal NOS (nNOS). To understand the role of Arg418, we generated the nNOS mutants, Arg418Ala and Arg418Leu. NO formation activities with the mutants using both L-Arg and NHA as substrates were less than 0.1 nmol/min/nmol heme, in contrast to rates of 34-35 nmol/min/nmol heme with the wild-type enzyme. The heme reduction rate of the mutants was very slow, less than 10(-2) min(-1), in contrast with that (more than 10 min(-1)) of the wild type. The backbone amide group of Arg418 interacts with the Cys415 thiolate through van der Waals contact, whereas the carbonyl oxygen of Cys415 and the guanidino N(epsilon) atom of Arg418 form a tight hydrogen bond. The results suggest that Arg418 is critical in preserving the heme proximal structure and thus, is indirectly involved in both catalysis and electron transfer from the reductase domain to the heme.

Amino Acid Sequence↗

Mouse homologue of coq7/clk-1, longevity gene in Caenorhabditis elegans, is essential for coenzyme Q synthesis, maintenance of mitochondrial integrity, and neurogenesis.

coq7/clk-1 was isolated from a long-lived mutant of Caenorhabditis elegans, which showed sluggish behavior and an extended life span. Mouse coq7 is homologous to Saccharomyces cerevisiae coq7/cat5 that is required for biosynthesis of coenzyme Q (CoQ), an essential cofactor in mitochondrial respiration. Here we generated COQ7-deficient mice to investigate the biological role of COQ7 in mammals. COQ7-deficient mouse embryos failed to survive beyond embryonic day 10.5, exhibiting small-sized body and delayed embryogenesis. Morphological studies showed that COQ7-deficient neuroepithelial cells failed to show the radial arrangement in the developing cerebral wall, aborting neurogenesis at E10.5. Electron microscopic analysis further showed the enlarged mitochondria with vesicular cristae and enlarged lysosomes filled with disrupted membranes, which is consistent with mitochondriopathy. Biochemical analysis demonstrated that COQ7-deficient embryos failed to synthesize CoQ(9), but instead yielded demethoxyubiquinone 9 (DMQ(9)). Cultured embryonic cells from COQ7-deficient mice were rescued by adding bovine fetal serum in vitro, but exhibited slowed cell proliferation, which resembled to the phenotype of clk-1 with delayed cell divisions. The result implied the essential role of coq7 in CoQ synthesis, maintenance of mitochondrial integrity, and neurogenesis in mice.

Animals↗

Unsaturated thiacrown ethers: synthesis, physical properties, and formation of a silver complex.

The 6-, 9-, 12-, 15-, 18-, 21-, 24-, and 27-membered unsaturated thiacrown ethers 1-8 were formed by reaction of cis-1,2-dichloroethylene with sodium sulfide in acetonitrile. Crystal structures of 4-8 were determined by X-ray crystallography, and it was found that all sulfur atoms of 5-8 direct to the inside of the ring (endodentate). All of the ORTEP drawings show that there are cavities in these molecules, and the cavity sizes in 4-8 were 1.76, 2.34, 3.48, 4.43, and 5.36 A, respectively. The UV spectra of 4-8 showed absorption maximums at the range of 255-276 nm in acetonitrile, and the absorption maximums of 4-8 were found to shift to longer wavelengths by changing the solvent from acetonitrile to cyclohexane. The cyclic voltammograms of 4-8 indicate that the larger unsaturated thiacrown ethers were oxidized more easily than the smaller systems, and unsaturated thiacrown ethers were oxidized more easily than corresponding saturated systems. The reaction of 4 with silver trifluoroacetate in acetone afforded the colorless complex Ag(I)(C2H2S)5(CF3COO) 9. The crystal structure of 9 was determined by X-ray analysis, and it was found that three of the five sulfur atoms bonded to the silver atom.

Journal Article↗

Solid state optical activity of dichalcogenides: isolation by chiral crystallization and determination of absolute configuration.

[reaction--see text] Optically active diphenyl dichalcogenides were isolated in bulk for the first time by chiral crystallization. The absolute configuration of the P-helical enantiomer of diphenyl disulfide was determined by X-ray crystallography. On the basis of this determination and considering the similarities of the Cotton effects of diphenyl diselenide and ditelluride, the absolute configuration of optically active diphenyl dichalcogenides could be assigned. Furthermore, stereochemistry of chiral crystallization could be controlled by using an optically active crystal as a seed crystal.

Chalcone↗

Fractures of the posterior part of the body and unilateral spinous process of the axis: a case report.

STUDY DESIGN: A case report and review of the literature. OBJECTIVES: To present a case of the fractures of the posterior part of the body and unilateral spinous process of the axis. SUMMARY OF BACKGROUND DATA: A few authors have described fractures involving the body of the axis. Fractures of the posterior part of the body and unilateral spinous process of the axis are extremely rare. METHODS: A fracture of the posterior part of the body and unilateral spinous process was treated nonsurgically by a halo and a Philadelphia brace. The relevant literature was reviewed. RESULTS: Solid bony union was shown by plain radiographs and computed tomography. The patient was free of pain and obtained a full range of motion. CONCLUSION: The presumed mechanism of injury in the fracture described here was flexion and axial rotation.

Aged↗

Total sleep deprivation induces an acute and transient increase in NK cell activity in healthy young volunteers.

STUDY OBJECTIVES: To investigate the effects of one night's total sleep deprivation (TSD) on NK cell activity, with rigorous control of circadian phase of sampling points as well as physical exercise level in association with sleep deprivation. DESIGN: The mean sleep onset time of each subject before starting the study was defined as his 0000 h. This study was composed of a Sleep-Sleep session (sleep times, 00:00 h - 08:00 h and 24:00 h - 32:00 h) and a Sleep-Wake session (sleep time, 00:00 h - 08:00 h) with TSD (24:00 h - 32:00 h) placed in a cross-over design with 2-week interval between each session. In each session, the subjects were rested in the supine position under dim light from - 06:00 h to 36:00 h (for 42 hours). SETTING: University-based sleep and chronobiology laboratory PARTICIPANTS: 10 healthy adult men (mean age, 20.9 y; age range, 19-23 y) INTERVENTIONS: NA. MEASUREMENTS AND RESULTS: NK cell activity was measured every 4 hours from 12:00 h. NK cell activity during TSD (at 28:00 h) has been revealed to significantly increase (p=0.01) compared with the corresponding value in the Sleep-Sleep session. This effect was weaker at their usual waking time 32:00 h (p=0.07), and disappeared until 36:00 h (4 hours after awakening). The circadian rhythm phases (dim light melatonin onset time) were coincident between the 2 sessions. CONCLUSIONS: The present findings suggest that one night TSD induces an acute and transient increase in NK cell activity that is not influenced by the effects of circadian rhythm or the amount of physical exercise undertaken during TSD.

Adult↗

Extensor musculature of the cervical spine after laminoplasty: morphologic evaluation by coronal view of the magnetic resonance image.

STUDY DESIGN: A radiographic study in 22 patients using magnetic resonance imaging was conducted. OBJECTIVE: To describe the relation between postoperative cervical alignment and morphologic evaluation of the cervical extensor musculature, especially semispinalis cervics in laminoplasty. SUMMARY OF BACKGROUND DATA: Cervical laminoplasty has been widely accepted as a treatment for cervical myelopathy. Posterior procedures, however, involve the extensor musculature of the cervical spine. METHODS: In this study, 22 patients who underwent laminoplasty for repair of the extensor musculature were reviewed prospectively. The semispinalis cervics was evaluated by coronal view of the magnetic resonance image 1 month, 12 months, and 24 months after surgery. Cervical alignment at last follow-up assessment was compared with preoperative alignment using the lateral view of cervical radiographs. RESULTS: In 18 patients (82%), morphologic repair of semispinalis cervics had been maintained (Group A), but in 4 patients (18%), but it had not been maintained at the last follow-up assessment (Group B). Cervical alignment in Group A had been maintained, but maximum loss of cervical lordosis occurred in Group B. Moreover, Group B consisted of elderly women. CONCLUSIONS: The findings from this magnetic resonance imaging study suggest that the degree of semispinalis cervics repair affects postoperative cervical alignment, and significant loss of cervical lordosis tends to occur in elderly women who undergo laminoplasty.

Adult↗

Interleukin-10 promotes the maintenance of antitumor CD8(+) T-cell effector function in situ.

Interleukin-10 (IL-10) is a multifunctional cytokine that can exert suppressive and stimulatory effects on T cells. It was investigated whether IL-10 could serve as an immunostimulant for specific CD8(+) cytotoxic T cell (CTL) in vivo after vaccination and, if so, under what conditions. In tumor prevention models, administration of IL-10 before, or soon after, peptide-pulsed primary dendritic cell immunization resulted in immune suppression and enhanced tumor progression. Injection of IL-10, however, just after a booster vaccine significantly enhanced antitumor immunity and vaccine efficacy. Analysis of spleen cells derived from these latter animals 3 weeks after IL-10 treatment revealed that the number of CD8(+) CD44(hi) CD122(+) T cells had increased and that antigen-specific proliferation in vitro was enhanced. Although cytotoxicity assays did not support differences between the various treatment groups, 2 more sensitive assays measuring antigen-specific interferon-gamma production at the single-cell level demonstrated increases in the number of antigen-specific responder T cells in animals in the vaccine/IL-10 treatment group. Thus, IL-10 may maintain the number of antitumor CD8(+) T cells. In adoptive transfer studies, the ability of IL-10 to maintain CTL function could be enhanced by the depletion of CD4(+) T cells. This suggests that IL-10 mediates contrasting effects on both CD4(+) and CD8(+) T cells that result in either immune dampening or immune potentiation in situ, respectively. Appreciation of this dichotomy in IL-10 immunobiology may allow for the design of more effective cancer vaccines designed to activate and maintain specific CD8(+) T-cell effector function in situ.

Animals↗

Single nucleotide polymorphism of human platelet-activating factor receptor impairs G-protein activation.

Various proinflammatory and vasoactive actions of platelet-activating factor (PAF) are mediated through a specific G-protein-coupled PAF receptor (PAFR). We identified a novel DNA variant in the human PAFR gene, which substitutes an aspartic acid for an alanine residue at position 224 (A224D) in the putative third cytoplasmic loop. This mutation was observed in a Japanese population at an allele frequency of 7.8%. To delineate the functional consequences of this structural alteration, Chinese hamster ovary cells were stably transfected with constructs encoding either wild-type or A224D mutated PAFR. No significant difference was observed in the expression level of the receptor or the affinity to PAF or to an antagonist, WEB2086, between the cells transfected with wild-type and mutant PAFR. Chinese hamster ovary cells expressing A224D mutant PAFR displayed partial but significant reduction of PAF-induced intracellular signals such as calcium mobilization, inositol phosphate production, inhibition of adenylyl cyclase, and chemotaxis. These findings suggest that this variant receptor produced by a naturally occurring mutation exhibits impaired coupling to G-proteins and may be a basis for interindividual variation in PAF-related physiological responses, disease predisposition or phenotypes, and drug responsiveness.

Adenylate Cyclase Toxin↗