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Biomedical subjects

N Higashi

Publications and source records attributed to N Higashi.

At least 37 records · Page 2Linked to original sources
PubMed2000

Migration of dermal cells expressing a macrophage C-type lectin during the sensitization phase of delayed-type hypersensitivity.

Dermal cells expressing a macrophage C-type lectin (mMGL) were previously suggested to migrate to regional lymph nodes during the sensitization phase of delayed-type hypersensitivity (DTH). The migration seemed to be induced by the solvent used to dissolve the antigen, and the DTH response was significantly enhanced by the migration. In this study, immunohistochemical analysis of skin after epicutaneous application of one of such solvents, a mixture of acetone and dibutylphthalate (AD), revealed a transient decrease in the number of mMGL-positive cells in the dermis. A similar decrease in this cell population was also observed in an ex vivo assay with skin explants excised from AD-treated sites. Conditioned medium from organ culture of AD-treated skin induced a similar decrease of mMGL-positive cells in untreated dermis, indicating the involvement of soluble factors. mMGL-positive cells seemed to represent a unique subpopulation of F4/80-positive dermal cells.

Acetone↗
PubMed1999

Effects of Helical Sense and Macrodipole on Helix Interaction in Poly(glutamic acid) Monolayers at the Air-Water Interface.

The effect of the helical sense and the helical macrodipole moment of poly(glutamic acid) (PGA) amphiphiles on miscibility in their binary surface monolayers was examined by means of the surface pressure-area isotherm and spectroscopic measurements. Four types of PGA amphiphiles, having different chirality (l or d) and two long alkyl chains at the C- or N-terminus (1 or 2), were successfully prepared by polymerization of the corresponding NCAs. In acidic solutions, these amphiphiles were found to take right-handed or left-handed helical conformation, depending upon the chirality of the glutamic acid unit, and are dispersed in water molecularly without aggregation. On the other hand, the binary mixed monolayer of 1L and 1D provided a marked positive deviation from an ideal mixing curve, while that of the combination of 1L and 2L gave a much smaller negative deviation, suggesting that helical sense would play a more important role in monolayer miscibility. Copyright 1999 Academic Press.

Journal Article↗
PubMed1999

Role of Rho small GTP binding protein in the regulation of actin cytoskeleton in hepatic stellate cells.

BACKGROUND/AIMS: In the fibrotic response to liver injury, hepatic stellate cells are activated, leading to the myofibroblastic cell shape, with actin cytoskeletal reorganization and increased extracellular matrix production. The reorganization of actin cytoskeleton suggests that the small GTP binding protein Rho might modulate the process of this myofibroblastic change. The aim of this study was to investigate the role of Rho in the phenotypic changes of hepatic stellate cells. METHODS: The phenotypic changes were investigated by the overexpression of Rho regulator, Rho GDI or dominant negative mutant of Rho in mouse hepatic stellate cell line, GRX cells. In activated rat hepatic stellate cells, the effects of microinjection of Botulinus toxin C3, which is the specific inhibitor for Rho, were analyzed. Furthermore, the effect of C3 on the type I collagen accumulation in hepatic stellate cells was investigated. RESULTS: Overexpression of Rho GDI or the dominant negative mutant of Rho caused the shrinkage cell shape and suppressed stress fiber formation. Microinjection of toxin C3 caused a markedly distorted cell shape and the disappearance of stress fibers in rat stellate cells. In addition, C3 strongly suppressed collagen accumulation in activated stellate cells. CONCLUSIONS: These results suggest that Rho regulates the actin cytoskeletal reorganization, and may be implicated in the collagen accumulation in activated stellate cells. These findings provide evidence for the role of Rho in the myofibroblastic phenotype in hepatic stellate cells.

Actins↗
PubMed1999

Effects of Yokuinin on the therapeutic efficacy of a new benzoxazinorifamycin KRM-1648 against Mycobacterium avium infection.

The Chinese traditional medicine, Yokuinin, which has anti-inflammatory effects and anti-human papilloma virus activity, was examined for its effects on the therapeutic efficacy of a benzoxazinorifamycin KRM-1648 (KRM) against Myobacterium avium infection in mice. Reverse transcription-PCR analysis revealed that Yokuinin increased the mRNA expression of all test cytokines in lung tissues of infected ice at week 8, in the order transforming growth factor-beta (TGF-beta) > IFN-gamma > TNF-alpha > IL-10. Mice given Yokuinin in combination with KRM had higher levels of TFG-beta mRNA expression than did mice given KRM alone, indicating that TGF-beta plays an important role in the expression of the anti-inflammatory effect of Yokuinin in vivo. Yokuinin reduced IL-10 production by M. avium-infected macrophages ph. (M phis) but did not affect M phi TFG-beta production. Although Yokuinin significantly modified cytokine expression in M. avium-infected mice, this drug did not influence the therapeutic efficacy of KRM against M. avium infection, suggesting that administration of Yokuinin in combination with KRM to the patients with M. avium infection does not cause severe disadvantages.

Animals↗
PubMed1999

Effects of the Chinese traditional medicine mao-bushi-saishin-to on therapeutic efficacy of a new benzoxazinorifamycin, KRM-1648, against Mycobacterium avium infection in mice.

The Chinese traditional medicine mao-bushi-saishin-to (MBST), which has anti-inflammatory effects and has been used to treat the common cold and nasal allergy in Japan, was examined for its effects on the therapeutic activity of a new benzoxazinorifamycin, KRM-1648 (KRM), against Mycobacterium avium complex (MAC) infection in mice. In addition, we examined the effects of MBST on the anti-MAC activity of murine peritoneal macrophages (M phi s). First, MBST significantly increased the anti-MAC therapeutic activity of KRM when given to mice in combination with KRM, although MBST alone did not exhibit such effects. Second, MBST treatment of M phi s significantly enhanced the KRM-mediated killing of MAC bacteria residing in M phi s, although MBST alone did not potentiate the M phi anti-MAC activity. MBST-treated M phi s showed decreased levels of reactive nitrogen intermediate (RNI) release, suggesting that RNIs are not decisive in the expression of the anti-MAC activity of such M phi populations. MBST partially blocked the interleukin-10 (IL-10) production of MAC-infected M phi s without affecting their transforming growth factor beta (TGF-beta)-producing activity. Reverse transcription-PCR analysis of the lung tissues of MAC-infected mice at weeks 4 and 8 after infection revealed a marked increase in the levels of tumor necrosis factor alpha, gamma interferon (IFN-gamma), IL-10, and TGF-beta mRNAs. KRM treatment of infected mice tended to decrease the levels of the test cytokine mRNAs, except that it increased TGF-beta mRNA expression at week 4. MBST treatment did not affect the levels of any cytokine mRNAs at week 8, while it down-regulated cytokine mRNA expression at week 4. At week 8, treatment of mice with a combination of KRM and MBST caused a marked decrease in the levels of the test cytokines mRNAs, especially IL-10 and IFN-gamma mRNAs, although such effects were obscure at week 4. These findings suggest that down-regulation of the expression of IL-10 and TGF-beta is related to the combined therapeutic effects of KRM and MBST against MAC infection.

Animals↗
PubMed1998

Hyperglycaemia due to insulin resistance caused by interferon-gamma.

Marked hyperglycaemia (30.9 mmol l(-1)) during interferon-gamma (IFN-gamma) therapy for asymptomatic recurrent renal cancer as multiple lung metastases in a 52-year-old man is described. Although the involvement of IFN-gamma has been reported in the development of autoimmune diabetes, in this case, antibodies against pancreatic beta-cells including anti-islet cell antibody (ICA) and anti-glutamic acid decarboxylase (GAD) antibody were negative. Moreover, serum level of immunoreactive insulin (IRI) (11 microU ml(-1) at fasting) and urinary excretion of C-peptide (108 microg day(-1), reference range: 20-130) suggested insulin resistance, supported by results of insulin tolerance tests. With insulin therapy and cessation of IFN-gamma, fasting blood glucose concentration returned to 6.2 mmol l(-1), and insulin therapy was discontinued. The injection of IFN-gamma may cause hyperglycaemia because of insulin resistance, rather than beta-cell injury.

Adenocarcinoma, Clear Cell↗
PubMed1998

Pharmacokinetics and pharmacodynamics of FK143, a nonsteroidal inhibitor of steroid 5 alpha-reductase, in healthy volunteers.

The pharmacokinetics and pharmacodynamics of FK143, a new nonsteroidal inhibitor of steroid 5 alpha-reductase, were investigated in healthy volunteers, with use of plasma FK143 concentrations and serum dihydrotestosterone levels as an index for pharmacologic effects. The area under the plasma concentration-time curve from zero to infinity [AUC(0-infinity)] and maximum plasma concentration [Cmax] were increased dose proportionally after oral administration (100 to 500 mg) while subjects were in the fed state. The AUC(0-infinity) and Cmax after 500 mg oral administration during fed conditions were significantly larger than those during the fasted state, suggesting an increase of the absorption of FK143. Dihydrotestosterone concentrations after a single administration of FK143 (100 to 500 mg) during fed conditions decreased to about 65% of predose values and thereafter slowly recovered to the same levels as predose values at 168 hours. A combined pharmacokinetic-pharmacodynamic model was constructed with use of changes in dihydrotestosterone concentrations. The pharmacokinetic-pharmacodynamic profiles of FK143 after repeated administration were predictable with use of the pharmacokinetic-pharmacodynamic parameters obtained after a single administration of FK143.

5-alpha Reductase Inhibitors↗
PubMed1998

A novel monoclonal antibody that recognizes apical membrane of frog taste cells.

We established a hybridoma clone 1N1 that produced a monoclonal antibody to stain the apical portion of frog taste cells, by directly immunizing taste discs of the bullfrog (Rana catesbeiana) without any dispersion procedure of the taste organ. The antibody stained discrete regions on the surface of the taste discs, but did not stain the epithelium sheet of the tongue devoid of taste discs. The antibody stained approximately 93% of the taste discs tested (172/184) derived from nine frogs, showing that distribution of the antigen was common to most of the taste discs. The following observations strongly suggested that the antibody recognized a certain antigen on the apical membrane of the taste cells. (i) The antibody selectively stained cross points of intermucus areas on the surface of the taste disc. Neither the mucus cells nor the wing cells that mainly cover the surface were stained with the antibody. (ii) Dispersed taste cells were prepared by calcium ion chelating and subsequently by collagenase treatment to avoid digestion of the antigen. The antibody stained the apical end of the taste cells.

Animals↗
PubMed1998

[Topical treatment of onychomycosis by occlusive dressing using bifonazole cream containing 40% urea].

Topical treatment with an antifungal agent was performed in 70 cases of onychomycosis (69 cases of tinea unguium and 1 case of Candida onychomycosis). The patients were treated every night by occlusive dressing using bifonazole cream containing 40% urea, and then by simple application of 1% bifonazole solution in the morning. During the treatment period, the softened affected nails were removed as completely as possible with nail clippers and files. The nails were observed every two weeks, and the efficacy was evaluated after 12 weeks. Two cases were excluded and 28 cases dropped out leaving 40 cases for efficacy evaluation. Among the 40 patients, 20 appeared to be mycologically negative (mycological cure rate: 50.0%). Clinical response was judged by the changes in opacity and thickness of the nails. Nine patients were evaluated as showing "marked improvement" and 16 as showing "improvement" (improvement rate: 62.5%). Erosion was noted as an adverse reaction in 2 patients. In one patient, treatment was stopped and the lesion was improved by antibiotic ointment, and in another, treatment was resumed when erosion was cured by discontinuation of the treatment. These results suggest that the topical treatment of onychomycosis by occlusive dressing is a useful method for those patients who have difficulties in or do not wish to be treated with oral antifungal agents.

Administration, Topical↗
PubMed1998

[Nonrotation of the midgut with abnormality of the superior mesenteric artery].

This report describes an anomalous case of nonrotation of the midgut with two superior mesenteric arteries in a 74 year-old Japanese female cadaver at the anatomical laboratory of Kanazawa Medical University. The characteristics of this nonrotation case were as follows: all the small bowel shifted to the right side and all the large bowel to the left side of the abdomen; cecum and appendix vermiform were situated to the left lower abdomen; and ligament of Treiz was absent. There were three arteries originating from the abdominal aorta for blood supply of abdominal organs: 1) the celiacomesenteric trunk with the first superior mesenteric artery, 2) the second superior mesenteric artery, 3) the inferior mesenteric artery. This case had two superior mesenteric arteries. The first one arose from the celiacomesenteric trunk. The second one arose from the left wall of the abdominal aorta about 95.0 mm below the origin of the celiacomesenteric trunk and 23.0 mm above the origin of the inferior mesenteric artery. The first superior mesenteric artery with five branches supplied the inferior portion of the duodenum and the superior portion of the small bowel. The second superior mesenteric artery had five small intestinal arteries supplying the inferior portion of the small bowel, and five large intestinal arteries supplying the cecum, the ascending colon, the transverse colon and the superior portion of the descending colon. The authors believe that the existence of the two superior mesenteric arteries caused the malformation in the nonrotation of the intestinal tracts in this cadaver.

Abdomen↗
PubMed1998

Biodistribution and kinetics of holmium-166-chitosan complex (DW-166HC) in rats and mice.

UNLABELLED: The fate of 166Ho-chitosan complex, a radiopharmaceutical drug for cancer therapy, was determined by studying its absorption, distribution and excretion in rats and mice. METHODS: Holmium-166-chitosan complex [0.75 mg of Ho(NO3)3 x 5H2O and 1 mg chitosan/ head] was administered intrahepatically to male rats. Radioactive concentrations in blood, urinary and fecal excretion and radioactive distribution in tissues were examined. To determine the effects of chitosan in 166Ho-chitosan complex, 166Ho alone [0.75 mg of Ho(NO3)3 x 5H2O/head] was intrahepatically administered to male rats, and radioactive concentrations in blood, urinary and fecal excretion and radioactive distribution were examined. In B16 melanoma-transplanted nude mice, radioactive distribution after intratumoral administration of 166Ho-chitosan complex [0.075 mg of Ho(NO3)3 x 5H2O and 0.10 mg chitosan/head] was investigated also. RESULTS: After administration of 166Ho-chitosan complex, the radioactive concentrations in blood were low, and cumulative urinary and fecal excretions over a period of 0-72 hr were 0.53% and 0.54%, respectively. The radioactive concentrations in tissues and the whole-body autoradiography images showed that most of the administered radioactivity was localized at the administration site, and only slight radioactivity was detected from the liver, spleen, lungs and bones. On the other hand, results of intrahepatic administration of 166Ho alone showed high radioactive concentrations in the blood, and the whole-body autoradiographs showed that the administered radioactivity was distributed in many organs and tissues. These results strongly suggest that 166Ho is retained at the administration site only when it forms a chelate complex with chitosan. Autoradiographs after intratumoral administration of 166Ho-chitosan complex showed that radioactivity was localized at the site of administration without distribution to the other organs and tissues. CONCLUSION: Administered 166Ho-chitosan complex is retained at the administration site after either intrahepatic or intratumoral administration to rats or tumor-transplanted nude mice.

Animals↗
PubMed1997

Surface Monolayers of Poly(l-glutamic Acid)-Functionalized Amphiphiles: Effect of Attachment of Spiropyran to the Polymer Segment

A novel poly(l-glutamic acid)-functionalized amphiphile (2) containing spiropyran groups in the side chain was successfully prepared. Surface monolayers of 2 were affected by isomerization of the spiropyran group; i.e., 2sp, which is in the spiro form, gave an expanded monolayer comparable with that of the spiropyran-free 1, while 2mc in the cyanine form gave a well-condensed monolayer similar to the 1 monolayer. CD measurements for these deposited monolayers onto quartz plates showed that the helix content was higher for the 2sp monolayer than for the 2mc monolayer. Upon isomerization from the cyanine to the spiro form, the 2mc monolayer had a tendency to expand gradually. When d-tryptophan was added into the subphase, such a monolayer expansion was completely suppressed due to electrostatic interactions between zwitterions, whereas no effect of the addition of l-tryptophan on the monolayer was observed. This result suggests that the assembled structure of alpha-helical poly(l-glutamic acid) would provide a suitable site for capturing alpha-amino acid enantioselectively.

Journal Article↗
PubMed1996

Fusion between Jurkat cell and PEO-lipid modified liposome.

Direct fusion between Jurkat cell and a liposome modified with poly(ethylene oxide)-bearing lipid (PEO-lipid) was examined using diphtheria toxin fragment A (DTA) as the probe. Only the DTA-loaded liposome modified with PEO-lipid(n = 32) (n is the number of ethylene oxide units) exerted significant cytotoxicity against Jurkat cells, while liposomes lacking either the PEO-lipid or DTA did not. Liposomes modified by the PEO-lipid with shorter PEO chain(n = 5 or 15) did not show any cytotoxicity, irrespective of their DTA-loading. The cytotoxicity was observed even in the presence of cytochalasin B, an inhibitor of endocytosis. Judging from these results, we concluded that the PEO-lipid(n = 32)-modified liposome directly fused with plasma membrane of Jurkat cell.

Cell Survival↗