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Biomedical subjects

K Asakura

Publications and source records attributed to K Asakura.

At least 91 records · Page 5Linked to original sources
PubMed1997

Chlorpromazine reduces toxicity and Ca2+ uptake induced by amyloid beta protein (25-35) in vitro.

Amyloid beta protein (A beta), has been reported to be toxic to neurons in vitro. However, the molecular mechanism leading to neuronal death remains unknown. Here we report protective effects of phenothiazines, a class of neuroleptic agent, against A beta toxicity in primary cultures of rat cortical neurons and PC12 cells. beta(25-35), an active sequence of A beta, showed dose-dependent reduction of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide dye (MTT) reductivity, and chlorpromazine (CPZ), promethazine or trifluoperazine restored it at micromolar concentration. The significant increase in Ca2+ uptake by chronic treatment of beta(25-35) was reduced not only by nimodipine but also by CPZ. These results suggest that phenothiazines attenuate beta(25-35) toxicity possibly by reducing of Ca2+ influx through L-type Ca2+ channels.

Amyloid beta-Peptides↗
PubMed1997

The effects of NK1 receptor antagonists (FK224 and FK888) on agonist- and antigen-induced nasal microvascular leakage in guinea pigs.

OBJECTIVE: To study the inhibitory effects of two NK1 receptor antagonists on substance P (SP) and antigen-induced increase of nasal vascular permeability in ovalbumen (OA)-sensitized guinea pigs. MATERIAL: Male Dunkin-Hartley guinea pigs. TREATMENT: SP (100 mumol/l), FK224 (1-10 mumol/kg) and FK888 (0.2-2 mumol/kg). METHODS: The in vivo model of nasal microvascular leakage was used for nasal allergic challenge in ovalbumin (OA)-sensitized guinea pigs, or nasal stimulation with substance P (SP) in non-sensitized animals. Nasal microvascular leakage was measured by the accumulation of Evans Blue dye after intravenous injection. RESULTS: Following nasal stimulation with SP 100 microM, the concentration of dye in the nasal lavage fluid rapidly increased. NK1 receptor antagonists FK224 (10 mumol/kg i.v.) and FK888 (2 mumol/kg i.v.) inhibited SP-induced microvascular leakage. In OA-sensitized guinea pigs, exudation of dye into nasal lavage fluid was observed soon after topical antigenic stimulation and continued for over 60 min. Both NK1 receptor antagonists inhibited the immediate phase of the antigen-induced microvascular leakage. CONCLUSIONS: We conclude that the immediate change of vascular permeability during the nasal allergic response is mediated by activation of the NK1 receptor in the guinea-pig.

Animals↗
PubMed1997

Effects of a cysteinyl leukotriene antagonist, ONO-1078 (pranlukast), on total airway resistance after antigen challenge in sensitized guinea pigs.

OBJECTIVE AND DESIGN: To define the role of leukotriene (LT) in allergic rhinitis, we examined the effects of a cysteinyl (Cys) LT antagonist (ONO-1078, pranlukast). MATERIAL: Actively sensitized Dunkin-Hartley guinea pigs. TREATMENT: ONO-1078 (pranlukast), 3-100 mg/kg p.o. 1 h before antigen challenge. METHODS: Nasal symptoms (sneezing, nasal scratches), changes of total airway resistance (TAR by plethysmography) and eosinophil infiltration into the nasal mucosa were determined following topical antigen (OA) challenge. Dunnet's test (TAR and symptoms) and the Mann-Whitney U-test (eosinophils) were applied. RESULTS: Control animals showed bi-phasic nasal responses, peaking 10 min and 240 min after the topical antigen challenge, respectively. While the early-phase response was characterized by nasal symptoms of sneezing and scratching accompanied by the increase in TAR, the late-phase was characterized by an increase in TAR accompanied by eosinophil infiltration into nasal mucosa. The nasal symptoms (sneezing and scratching) were not inhibited by pretreatment with ONO-1078 at doses up to 100 mg/kg (p.o., n = 15). Although early peak responses of TAR were not affected with even the highest dose (30 mg/kg, p.o., n = 6), late-phase TAR peak response (control: 174.8 +/- 8.2%, n = 6) were significantly inhibited by 10 mg/ kg (142.7 +/- 15.8%; p < 0.05, n = 6) and 30 mg/kg (118.0 +/- 6.6%; p < 0.01, n = 6) of ONO-1078 (p.o.). In addition, the eosinophil infiltration induced by the antigen was not inhibited by ONO-1078 (30 and 100 mg/kg, p.o., n = 6). CONCLUSIONS: Our results suggest that Cys LT may play an important role in the late-phase increase in TAR in the guinea pig model of allergic rhinitis.

Administration, Topical↗
PubMed1997

Amyloid beta protein potentiates Ca2+ influx through L-type voltage-sensitive Ca2+ channels: a possible involvement of free radicals.

Amyloid beta protein (A beta), the central constituent of senile plaques in Alzheimer's disease (AD) brain, is known to exert toxic effects on cultured neurons. The role of the voltage-sensitive Ca2+ channel (VSCC) in beta (25-35) neurotoxicity was examined using rat cultured cortical and hippocampal neurons. When L-type VSCCs were blocked by application of nimodipine, beta (25-35) neurotoxicity was attenuated, whereas application of omega-conotoxin GVIA (omega-CgTX-GVIA) or omega-agatoxin IVA (omega-Aga-IVA), the blocker for N- or P/Q-type VSCCs, had no effects. Whole-cell patch-clamp studies indicated that the Ca2+ current density of beta (25-35)-treated neurons is about twofold higher than that of control neurons. Also, beta (25-35) increased Ca2+ uptake, which was sensitive to nimodipine. The 2', 7'-dichlorofluorescin diacetate assay showed the ability of beta (25-35) to produce reactive oxygen species. Nimodipine had no effect on the level of free radicals. In contrast, vitamin E, a radical scavenger, reduced the level of free radicals, neurotoxicity, and Ca2+ uptake. These results suggest that beta (25-35) generates free radicals, which in turn, increase Ca2+ influx via the L-type VSCC, thereby inducing neurotoxicity.

Amyloid beta-Peptides↗
PubMed1997

Effects of transforming growth factor-beta and platelet-derived growth factor on oligodendrocyte precursors: insights gained from a neuronal cell line.

Conditioned medium derived from a rat central nervous system neuronal cell line B104 (B104 CM) was shown previously to contain uncharacterized potent mitogen(s) for oligodendrocyte/type-2 astrocyte (O-2A) progenitor cells. In this study, we demonstrated that B104 cells produce and secrete platelet-derived growth factor (PDGF)-AA homodimer, but not PDGF-B chain. B104 cells did not express other known potent mitogens for O-2A progenitor cells, including fibroblast growth factor-2 and neurotrophin-3. Unexpectedly, B104 cells also expressed transcripts of transforming growth factor-beta1 (TGF-beta1) and -beta2 (TGF-beta2), which are known to regulate O-2A progenitor cell differentiation and proliferation, and secreted exclusively the 25-kDa active forms of TGF-beta1 and TGF-beta2. Neutralization of B104 CM with anti-PDGF-AA antibody decreased proliferation of O-2A progenitor cells, whereas neutralization with anti-TGF-beta antibodies had no effect. The combination of PDGF and TGF-beta on proliferation was not equivalent to the effect of B104 CM, indicating the possibility of an unidentified growth factor. B104 CM maintained a high expression of PDGF-alpha receptor in oligodendrocytes. The observation that both a stimulatory factor (PDGF-AA) and a regulatory factor (TGF-beta) for O-2A progenitor cell proliferation and differentiation are produced from a single neuronal cell line emphasizes the potential critical interaction between neurons and O-2A progenitor cells in myelination and possibly in remyelination.

Animals↗
PubMed1997

The immune system preferentially clears Theiler's virus from the gray matter of the central nervous system.

Infection of susceptible strains of mice with Daniel's (DA) strains of Theiler's murine encephalomyelitis virus (DAV) results in virus persistence in the central nervous system (CNS) white matter and chronic demyelination similar to that observed in multiple sclerosis. We investigated whether persistence is due to the immune system more efficiently clearing DAV from gray than from white matter of the CNS. Severe combined immunodeficient (SCID) and immunocompetent C.B-17 mice were infected with DAV to determine the kinetics, temporal distribution, and tropism of the virus in CNS. In early disease (6 h to 7 days postinfection), DAV replicated with similar kinetics in the brains and spinal cords of SCID and immunocompetent mice and in gray and white matter. DAV RNA was localized within 48 h in CNS cells of all phenotypes, including neurons, oligodendrocytes, astrocytes, and macrophages/microglia. In late disease (13 to 17 days postinfection), SCID mice became moribund and permitted higher DAV replication in both gray and white matter. In contrast, immunocompetent mice cleared virus from the gray matter but showed replication in the white matter of their brains and spinal cords. Reconstitution of SCID mice with nonimmune splenocytes or anti-DAV antibodies after establishment of infection demonstrated that both cellular and humoral immune responses decreased virus from the gray matter; however, the cellular responses were more effective. SCID mice reconstituted with splenocytes depleted of CD4+ or CD8+ T lymphocytes cleared virus from the gray matter but allowed replication in the white matter. These studies demonstrate that both neurons and glia are infected early following DAV infection but that virus persistence in the white matter is due to preferential clearance of virus from the gray matter by the immune system.

Animals↗
PubMed1997

Topical antigen provocation increases the number of immunoreactive IL-4-, IL-5- and IL-6-positive cells in the nasal mucosa of patients with perennial allergic rhinitis.

To evaluate the role of Th2-type cytokines in the nasal mucosa which has been repeatedly exposed to antigen, an immunohistological study for IL-4, IL-5 and IL-6 was performed in patients with perennial allergic rhinitis and non allergic rhinosinusitis. The numbers of immunoreactive (ir)-IL-4, ir-IL-5 and ir-IL-6-positive cells were significantly higher in allergic mucosa than in nonallergic mucosa. In allergic mucosa, the numbers of these ir-cytokine-positive cells were significantly higher in the antigen-challenged site than in the control site. When the patients were divided into an early group (4-6 h after challenge) and a later group (15-25 h after challenge), only the change of ir-IL-4-positive cells was remarkable in the former group, whereas those of the ir-IL-4, ir-IL-5 and ir-IL-6-positive cells were significant in the latter group. These results suggest that antigen-induced upregulation of IL-4, IL-5 and IL-6 is important in the pathogenesis of perennial allergic rhinitis.

Administration, Intranasal↗
PubMed1997

Induction of ST-segment elevation by regional myocardial stretch in normal canine hearts in vivo.

The purpose of this study was to evaluate ST-segment elevation induced by regional myocardial stretch without myocardial ischemia in canine hearts. A strain gauge arch (TH-601T) was sutured to the left ventricular epicardium, parallel to the short axis, to shorten the end-diastolic length of the myocardium beneath the arch (stretch zone; SZ) and to produce regional myocardial stretch in each of 6 dogs. An increase in preload caused by altering the height of a saline-filled reservoir affected prolongation or shortening of the myocardium both in the SZ and outside the arch (normal zone; NZ) to increase myocardial stretch. An epicardial electrocardiogram was recorded in both the SZ and the NZ. After suture of the strain gauge arch, the ST segment was elevated in the SZ. An increase in preload augmented stretch during systole in the SZ, resulting in additional ST-segment elevation. These results suggest that regional myocardial stretch itself plays an important role in ST-segment elevation.

Animals↗
PubMed1997

Prognostic factors and treatment outcome in non-Hodgkin's lymphoma of Waldeyer's ring.

Prognostic factors and treatment outcome of 71 patients with non-Hodgkin's lymphoma of Waldeyer's ring were analyzed retrospectively. In univariate analyses, unfavorable prognosis was associated with primary disease in the base of the tongue, stage III-IV diseases, B-symptoms, high-grade histology, T-cell phenotype, elevated serum LDH levels, decreased peripheral blood lymphocyte counts, and negative response on delayed type hypersensitivity skin reactions. Multivariate analysis showed that stage III-IV and T-cell phenotype were significant independent risk factors for death. In stage I-II lymphomas, patients with unilateral large or bilateral cervical lymph node involvement had a poorer prognosis. In stage I-II lymphomas with intermediate or high-grade histology, patients who had received radiotherapy with MTCOP-P chemotherapy (pirarubicin, cyclophosphamide, vincristine, methotrexate with leucovorin rescue, peplomycin, and predonisolone) showed significantly better 5-year disease-free survival rate compared with patients treated with radiotherapy alone.

Adolescent↗
PubMed1996

Application of a CdTe Solid-State Detector to Polarization-Dependent Total-Reflection Fluorescence XAFS Measurements.

A CdTe solid-state detector was applied to the measurement of polarization-dependent total-reflection fluorescence XAFS spectra. The data revealed that the detector has good sensitivity, and this, together with its compact size, make it appropriate for in-situ measurements and removal of X-ray Bragg diffraction. The detector efficiently recorded the high-energy K-edge XAFS spectra for molybdenum oxides supported on TiO(2) (110).

Journal Article↗
PubMed1996

Monoclonal autoantibody SCH94.03, which promotes central nervous system remyelination, recognizes an antigen on the surface of oligodendrocytes.

A monoclonal antibody SCH94.03, made in syngeneic mice by injection of spinal cord homogenate, promotes central nervous system remyelination when injected into SJL/J mice chronically infected with Theiler's virus. To elucidate the mechanism of antibody-mediated remyelination, SCH94.03 was investigated by immunocytochemistry, flow cytometry, immunoelectron microscopy, Western blotting, and immuno-thin layer chromatography. All cell types investigated in vitro showed strong cytoplasmic staining with a pattern resembling a cytoskeletal protein. In contrast, among the primary cultured cells studied, only oligodendrocytes showed strong surface reactivity. Other cell types, including astrocytes, microglia, Schwann cells, myoblasts, and T and B lymphocytes, were negative. Mouse and rat oligodendrocytes which showed strong surface reactivity exhibited a well-differentiated morphology, and approximately 50% expressed myelin basic protein. Since oligodendrocyte progenitors were negative for surface staining, the expression of the antigens recognized by this monoclonal antibody appears to be developmentally regulated, i.e., transiently expressed on younger, terminally differentiating oligodendrocytes. Among the cell lines studied, only two rat oligodendrocyte lineage cell lines showed surface reactivity with SCH 94.03. Western blotting of secondary isolated oligodendrocytes lysates revealed reactivity with multiple protein bands of 27, 32, 50, 100, and 106 kDa, whereas there was no reactivity to lipid antigens by immuno-thin layer chromatography. These results raise the possibility that SCH94.03 recognizes a novel oligodendrocyte-specific surface antigen, and may act directly on oligodendrocytes to promote remyelination.

Animals↗
PubMed1996

Traumatic cervical tracheal disruption: report of two cases.

We report herein the cases of two patients who suffered tracheal disruption, both of whom underwent successful surgical treatment. The first patient was a 48-year-old truck driver who suffered severe dyspnea after jamming his neck in a truck door. An endotracheal tube was unable to be inserted due to bleeding and thus, an emergency tracheostomy was performed. On admission massive subcutaneous emphysema was noted in the neck and anterior chest, and tracheal disruption was confirmed by a lateral neck X-ray, computed tomography (CT), and fiberscopy. An emergency end-to-end anastomosis of the trachea with insertion of a T-type silicon tube into the lower trachea was performed. The second patient was a 36-year-old man who suffered severe dyspnea after having his neck caught in a chain while driving a motorcycle. On admission, marked subcutaneous emphysema in the neck and paradoxical movement of the trachea were noted. Tracheal disruption was confirmed by a lateral neck X-ray and CT, and a similar operation to that of the first patient was performed. This type of injury is rare; however, lateral neck X-ray, CT, and fiberscopy proved extremely useful for making an accurate diagnosis following which successful emergency surgery was able to be performed, achieving good long-term results.

Adult↗
PubMed1996

A monoclonal autoantibody which promotes central nervous system remyelination is highly polyreactive to multiple known and novel antigens.

A monoclonal antibody (mAb), designated SCH94.03, which promotes central nervous system remyelination in susceptible mice infected with Theiler's virus, has been proposed to be a natural autoantibody based on its germline immunoglobulin sequence. To identify the potential antigens recognized by mAb SCH94.03, a rat brain lambda gtll cDNA expression library was screened with this antibody. Nine independent clones were identified. Five clones were identical or highly similar to known cDNAs or proteins (rat kinesin light chain, mouse thrombospondin 1, mouse oncofetal antigen, RNA polymerase beta subunit and nuclear phosphoprotein). Four clones, designated REM#1, REM#2, REM#3 and REM#4, contained open reading frames, but were not homologous to any known genes or proteins. The reactivity of SCH94.03 with all nine clones was specific in that all nine clones identified contained continuous open reading frames and none of nine control IgM mAbs showed reactivity with any of the nine cDNA clones. The precise specificity of binding of mAb SCH94.03 was demonstrated by the absence of reactivity to the identified clones with IgM Ab from B cell lymphoma (CH12) which has identical cDNA sequences with mAb SCH94.03, but differ only in the heavy chain CDR3 N region. Our studies support the hypothesis that highly polyreactive natural autoantibodies can play a role in promoting central nervous system remyelination.

Actins↗
PubMed1996

Retropharyngeal abscess after radiation therapy and cis-platinum, 5-fluorouracil treatment for nasopharyngeal carcinoma with collagen disease: report of two patients and a review of the literature.

Collagen disease are frequently associated with malignant tumors. Recently, radiotherapy combined with chemotherapy has been recommended for improving the efficacy of treatment for nasopharyngeal carcinoma. Two patients with nasopharyngeal carcinoma complicated by collagen diseases (dermatomyositis in one, and Sjögren's syndrome with mixed connective tissue disease in the other) were given radiotherapy combined with chemotherapy consisting of cis-platinum and 5-fluorouracil. Following this combination therapy, both patients developed retropharyngeal abscess and ulceration of the mucosal membrane on the posterior wall of the oropharynx; there was no tumor cell involvement. Because these injuries were more severe than would have been expected from radiotherapy alone, it is recommended that special attention be paid to combination therapy in patients with nasopharyngeal carcinoma complicated by collagen disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Central nervous system remyelination clinical application of basic neuroscience principles.

Studies in both humans and experimental animals have demonstrated that myelin repair in the CNS is a normal physiological response to myelin damage, similar to tissue injury elsewhere in the body. The unanswered question is why myelin repair is incomplete in multiple sclerosis patients. In this paper we review the morphological characteristics of remyelination, discuss the available animal models of CNS demyelination and their usefulness to identify the molecular, cellular, and morphological events involved in CNS myelin repair, examine the use of immunosuppression, immunoglobulins, protein growth factors, and glial cell transplantation at the primary experimental therapies designed to promote CNS remyelination, and address the potential electrophysiological and clinical benefits of myelin repair in the CNS.

Animals↗
PubMed1996

Effects of thromboxane A2 receptor antagonist (Bay u 3405) on nasal symptoms after antigen challenge in sensitized guinea pigs.

To define the role of thromboxane A2 (TxA2) in allergic rhinitis, we examined the effects of the TxA2 receptor antagonist Bay u 3405 (1, 3 and 10 mg/kg, orally) on nasal symptoms, changes in total airway resistance (TAR), histamine hypersensitivity and eosinophil infiltration into the nasal mucosa induced by topical antigen challenge in actively sensitized guinea pigs. Nasal symptoms (number of sneezes and scratches) were significantly inhibited by pretreatment with Bay u 3405, in a dose-dependent manner. We noted a biphasic increase in TAR after antigen challenge. The first peak response of TAR (177.5 +/- 6.1%, mean +/- SE) was partially but significantly inhibited by Bay u 3405 at 10 mg/kg (142.8 +/- 4.3%, p < 0.01). The second peak response of TAR (181.0 +/- 13.4%) was also inhibited by Bay u 3405 at 3 mg/kg (120.3 +/- 3.1%) and 10 mg/kg (125.2 +/- 9.4%) (both, p < 0.01). The histamine hypersensitivity induced by antigen was inhibited by Bay u 3405 at 15 mg/kg (p < 0.05). Moreover, the mean eosinophil infiltration into the nasal mucosa induced by antigen (644.1 +/- 202.6/both sides of the nasal septum) was inhibited to 137.8 +/- 69.0 by Bay u 3405 at 10 mg/kg (p < 0.05). In conclusion, our results suggest that TxA2 may play an important role in allergic rhinitis in guinea pig models.

Airway Resistance↗
PubMed1996

In vivo effects of monoclonal antibody against ICAM-1 and LFA-1 on antigen-induced nasal symptoms and eosinophilia in sensitized rats.

We applied anti-ICAM-1 and anti-LFA-1 monoclonal antibody (mAb) to ovalbumin-sensitized rats and examined the effects on nasal eosinophilia and nasal symptoms following topical antigen challenge. In a general and local immunization (GLI) group of rats, the mAbs were applied during the booster topical immunization period. In a general immunization group and a local immunization (LI) group of rats, the mAbs were applied during the immunization period. The number of sneezes and nasal scratching movements occurring soon after topical antigen (Ag) challenge was significantly suppressed in the GLI and LI group rats. Eosinophil infiltration into nasal mucosa 24 h after Ag challenge was also significantly suppressed in GLI and LI group rats. These findings suggest that the ICAM-1/LFA-1 system is important in topical allergic inflammation in rats.

Animals↗