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Biomedical subjects

Y Nakai

Publications and source records attributed to Y Nakai.

At least 145 records · Page 8Linked to original sources
PubMed1998

Intravenous glucose tolerance test-derived glucose effectiveness in strength-trained humans.

The effect of long-term strenuous resistance training on glucose effectiveness (SG) was examined by comparing 11 strength-trained and 20 sedentary males by a minimal model approach. Lean body mass (LBM) was measured by hydrostatic weighing. The LBM in strength-trained subjects (65.7 +/- 3.1 kg) was significantly larger than in sedentary subjects (56.6 +/- 1.2 kg, P < .01). The glucose disappearance constant ([KG] 3.07% +/- 0.45% min(-1)) and insulin sensitivity ([SI] 17.5 +/- 2.0 x 10(-5) x min(-1) x pmol/L(-1)) in strength-trained subjects were significantly higher than in sedentary subjects (2.06% +/- 0.14% x min(-1) and 10.3 +/- 1.2 x 10(-5) x min(-1) x pmol/L(-1), P < .05). SG in strength-trained subjects (0.024 +/- 0.003 min(-1)) was significantly higher than in sedentary subjects (0.018 +/- 0.001 min(-1), P < .05). These results thus suggest that the improved glucose tolerance in strength-trained subjects was due to increased SG and SI.

Adult↗
PubMed1998

An electron microscopic observation of the vesicular acetylcholine transporter-immunoreactive fibers in the rat dorsal raphe nucleus.

By using immunocytochemistry with an antibody directed against the vesicular acetylcholine transporter, many cholinergic neuronal processes were found to be immunopositive in the dorsal raphe nucleus. At the electron microscopic level, most of these processes were found to be axons. The immunopositive axon terminals made synapses on immunonegative dendrites and their spines whereas rare synapses were found between the immunopositive axon terminals and the immunonegative neuronal perikarya. Occasionally, the dendrites postsynaptic to an immunopositive axon terminal also received a synapse from an immunonegative axon terminal. The synapses made by the immunopositive axon terminals were usually symmetric and had a short active zone. Fewer immunostained dendrites were found, and they usually received asymmetric synapses from nonimmunostained axon terminals. The existence of cholinergic axon terminals and the synapses made by these terminals support the physiological data indicating that acetylcholine plays a role in the pain inhibition system in the dorsal raphe nucleus.

Animals↗
PubMed1998

Influence of absorption enhancers (bile salts) and the preservative (benzalkonium chloride) on mucociliary function and permeation barrier function in rabbit tracheas.

Effects of bile salts and benzalkonium chloride on the ciliary beat activity (frequency) and the mucociliary transport rate of tracheas, and permeabilities of 6-carboxyfluorescein (6-CF; Mw 376) and FITC-dextrans (FD-4; Mw 4300) as hydrophilic compounds through trachea were investigated for intratracheal delivery of drugs. Ciliary beat activity was measured by an in vitro photoelectric method by using excised rabbit tracheas. Transport rate was determined by an in vivo endoscopic method in rabbit tracheas. Permeation test was carried out by using excised rabbit tracheas. The ciliary beat activities and mucociliary transport rates were not significantly affected by 1, 10 and 20 mM sodium glycocholate, while they were significantly decreased by 1 and 10 mM sodium taurodeoxycholate and immediately halted after application of 20 mM taurodeoxycholate. They were not significantly affected by 0.02% of benzalkonium chloride, whereas they were completely halted by 0.05% of benzalkonium chloride. The apparent permeability coefficients (Papp) of 6-CF and FD-4 were 2.35x10(-7) and 2.22x10(-8) cm/s, respectively. One mmol of glycocholate did not significantly increase the Papp of 6-CF and FD-4, while, 10 mM of glycocholate and 1 and 10 mM of taurodeoxycholate significantly increased the Papp. Benzalkonium chloride (0.01%) did not significantly increase the Papp of 6-CF, whereas 0.03% significantly increased the Papp of 6-CF. Benzalkonium chloride (0.01 and 0.03%) slightly increased the Papp of FD-4. Therefore, sodium glycocholate may be a safe and useful absorption enhancer for intratracheal delivery of drugs.

Animals↗
PubMed1998

Effect of high molecular mobility of poly(vinyl alcohol) on protein stability of lyophilized gamma-globulin formulations.

The protein stability of lyophilized serum gamma-globulin (BGG) formulations containing poly(vinyl alcohol) (PVA) and dextran was studied in relation to the molecular mobility as determined by proton NMR. The critical temperature, Tmc, at which the Lorentzian relaxation process due to liquid polymer protons appears in these lyophilized formulations was lower than the glass transition temperature, Tg. Above Tmc, protein aggregation in the formulations was related to the Tmc according to the Williams-Landel-Ferry equation by replacing Tg with Tmc. Protein aggregation appears to occur substantially in a "rubbery-like" state even below Tg, if the formulations become microscopically liquidized above Tmc. Lyophilized BGG formulations containing PVA with a lower water content were less stable than those containing dextran with a higher water content. The difference in stability can be explained by the difference in the Tmc of these formulations. Tmc that is determined by NMR relaxation measurement appears to be a useful parameter for the characterization of protein formulations, for which the Tg cannot generally be determined by standard calorimetric techniques. Furthermore, Tmc appears to be more closely related to protein stability than does Tg.

Calorimetry, Differential Scanning↗
PubMed1998

The clinical role of specific IgE and IgG4 antibodies in patients having immunotherapy for seasonal allergic rhinitis.

This study was designed to investigate the clinical role of specific IgG4 and IgE responses in patients during immunotherapy for seasonal allergy. The study included 109 patients with seasonal allergic rhinitis due to Japanese cedar pollens. They were divided into the control group and the immunotherapy group. Serum samples were obtained at the start of immunotherapy, before the pollen season and during the season, to determine serum specific IgE and IgG4. In the control group specific IgE was significantly increased, but specific IgG4 was not changed during the pollen season. In the immunotherapy group specific IgE was not significantly increased, but specific IgG4 was significantly increased during the season. In the patients having immunotherapy for 2 years or less, the seasonal increase in specific IgG4 related to the magnitude of the clinical effect. In the patients having immunotherapy for 3 years or more, the seasonal increase in specific IgE related to the magnitude of the clinical effect. In conclusion, the specific IgG4 response and specific IgE response during the pollen season make a significant contribution to the clinical effect of immunotherapy. However, modulation of specific IgE and IgG4 responses out of the pollen season was unlikely to be an important phenomenon related to the clinical effect of immunotherapy.

Adolescent↗
PubMed1998

Soluble adhesion molecules in middle ear effusions from patients with chronic otitis media with effusion.

Soluble forms of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) have been identified in the peripheral blood and other body fluids. These soluble adhesion molecules have been reported to reflect the upregulation of cell surface ICAM-1 and VCAM-1 expression in inflammatory diseases. The levels of soluble ICAM-1 and soluble VCAM-1 in 37 middle ear effusions from 37 patients with chronic otitis media with effusion (OME) were quantitatively determined with enzyme-linked immunosorbent assays. The levels of soluble ICAM-1 in mucoid effusions were significantly higher than those in serous effusions, but the levels of soluble VCAM-1 did not differ significantly between the two types of effusion. The levels of soluble VCAM-1 in effusions from atopic patients were significantly higher than those from non-atopic patients, whereas the levels of soluble ICAM-1 in samples from atopic patients were significantly lower than those from non-atopic patients. Therefore, our data suggest that an increase in soluble VCAM-1 plays a more important role in the pathogenesis of OME in atopic patients than in non-atopic patients. In addition, soluble ICAM-1 is likely to play a more important role in the pathogenesis of OME in nonatopic patients than soluble VCAM-1.

Adult↗
PubMed1998

Ten-year follow-up study of allergen-specific immunoglobulin E and immunoglobulin G4, soluble interleukin-2 receptor, interleukin-4, soluble intercellular adhesion molecule-1 and soluble vascular cell adhesion molecule-1 in serum of patients on immunotherapy for perennial allergic rhinitis.

Recent double-blind placebo-controlled trials for perennial allergic rhinitis have all clearly shown the efficacy of immunotherapy. Although several mechanisms for the clinical efficacy of immunotherapy have been proposed, the exact mechanisms related to the clinical effect still remain unclear. Since immunotherapy is a form of systemic treatment and its clinical benefit is likely to be, at least in part, a consequence of its systemic effects on different phases of immunological events, our study focused exclusively on several immunological parameters in serum. A total of 47 patients with perennial allergic rhinitis due to Dermatophagoides farinae enrolled in this prospective study. Venous blood was collected for determination of specific immunoglobulin (Ig)E, specific IgG4, soluble interleukin-2 receptor (IL-2R), interleukin-4 (IL-4), soluble intercellular adhesion molecule-1 (ICAM-1) and soluble vascular cell adhesion molecule-1 (VCAM-1), six times from 20 untreated patients and 27 patients on immunotherapy, at enrolment, and 1, 2, 3, 5, and 10 years after enrollment. No specific IgE, IgG4, soluble IL-2R, IL-4 and soluble ICAM-1 levels changed significantly for a span of 10 years in the untreated patients. By contrast, immunotherapy affected serum levels of specific IgE, specific IgG4, soluble IL-2R, IL-4 and soluble ICAM-1, but not of soluble VCAM-1. The rates of increase in specific IgG4 and the rates of decrease in soluble IL-2R were correlated with the rates of decrease in symptom scores during the first 3 years, but not 5 and 10 years after the course of immunotherapy. On the other hand, the rates of decrease in specific IgE, IL-4 and soluble ICAM-1 were significantly correlated with the rates of decrease in symptom scores at 5 and 10 years, but not during the first 3 years. Each immunological modulation by immunotherapy was likely to be involved in the working mechanism related to clinical efficacy at different phases of immunotherapy.

Adolescent↗
PubMed1998

Allergen-induced synthesis of interleukin-5, but not of IgE, is a key mechanism linked to symptomatic episodes of seasonal allergic rhinitis in sensitized individuals.

Some individuals with detectable levels of Japanese cedar (Criptomeria japonica) pollen-specific immunoglobulin (Ig)E in serum have no apparent nasal symptoms during the pollen season. The response of CD4+ T-helper (Th) cells to the pollen allergen might differ fundamentally between asymptomatic and symptomatic individuals who are already sensitized to the pollen. The aim of this study was to discern the possible differences in responses of peripheral blood mononuclear cells (PBMCs) to the pollen allergen between asymptomatic and symptomatic subjects who have been sensitized to the pollen. This study included 20 non-atopic healthy volunteers (non-atopic group) and 48 patients who had detectable levels of the pollen-specific IgE before the pollen season in 1997. In the review of nasal symptoms during the pollen season 1997, 24 patients had typical symptoms of seasonal allergic rhinitis (symptomatic group), and the remainder had no seasonal aggravation of nasal symptoms (asymptomatic group). Peripheral blood mononuclear cells (1.0 x 10(7) cells/well) were obtained from each individual during the pollen season and cultured in the absence or presence of 12.5 microg of Cry j 1 for 4 days. The concentrations of IgE, interleukin-5 (IL-5), and interferon-gamma (IFN-gamma) in the culture supernatants were measured. The levels of IgE produced by Cry j 1-stimulated PBMCs of the asymptomatic and symptomatic groups were significantly higher than those of the non-atopic group, but did not differ between the asymptomatic and symptomatic groups. The levels of IL-5 produced by Cry j 1-stimulated PBMCs did not differ significantly between the non-atopic group and the asymptomatic group, but the levels of IL-5 were significantly higher in the symptomatic group than in the asymptomatic group as well as the non-atopic group. The levels of IFN-gamma produced by Cry j 1-stimulated PBMCs did not differ significantly among the three groups. In conclusion, our study has suggested that Japanese cedar pollen-induced synthesis of IL-5, but not of IgE or IFN-gamma, is likely to be a key mechanism linked to the symptomatic episode of seasonal allergic rhinitis in individuals sensitized to the pollen.

Adolescent↗
PubMed1998

Immunotherapy suppresses both Th1 and Th2 responses by allergen stimulation, but suppression of the Th2 response is a more important mechanism related to the clinical efficacy of immunotherapy for perennial allergic rhinitis.

Increased attention has recently been directed at the possibility that the clinical efficacy of immunotherapy might be elaborated by alteration of T-cell reactivity. However, there is no general agreement among different investigators regarding the effect of immunotherapy on Th-cell reactivity. Peripheral blood mononuclear cells (PBMCs) from 15 nonatopic subjects and 76 patients with perennial allergic rhinitis (18 untreated patients and 58 patients on immunotherapy) were cultured in the absence and in the presence of a major Dermatophagoides farinae allergen, Der f 1, and the levels of IgE, interleukin-5 (IL-5), interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) in the culture supernatants were determined. The difference between the absence and presence of Der f 1 was calculated to consider the Der f 1-dependent synthesis of IgE, IL-5, IFN-gamma and TNF-alpha. The levels of Der f 1-dependent synthesis of IgE, IL-5 and TNF-alpha were significantly higher in the untreated group than in the nonatopic group, whereas Der f 1-dependent synthesis of IFN-gamma was significantly lower in the untreated group than in the nonatopic group. Immunotherapy decreased the enhanced Der f 1-dependent synthesis of IgE, IL-5 and TNF-alpha, and further decreased the suppressed Der f 1-dependent synthesis of IFN-gamma as the therapy proceeded. The levels of Der f 1-dependent synthesis of IgE and IL-5 did not differ between nonatopic individuals and patients whose duration of immunotherapy was 10 or more years. The levels of Der f 1-dependent synthesis of IgE and IL-5, but not of IFN-gamma and TNF-alpha, were correlated significantly with the levels of symptom scores. In addition, the levels of Der f 1-dependent synthesis of IgE and IL-5, but not of IFN-gamma and TNF-alpha, differed significantly between good and poor responders. In conclusion, immunotherapy for perennial allergic rhinitis may possibly work via induction of tolerance or anergy of both Th1- and Th2 cells. However, our study is likely to support a view that the mechanisms responsible for the clinically beneficial effects of immunotherapy principally involve the tolerance of Th2- rather than Th1 cells. In addition, suppression of IgE synthesis is also likely to be linked to the clinical efficacy of immunotherapy for perennial allergic rhinitis.

Allergens↗
PubMed1998

Dose-dependent response of vestibular hair cells of guinea pigs following streptomycin ototoxiation.

Although the involvement of apoptosis has been suggested in the loss of vestibular hair cells due to aminoglycosides, dose-dependent effects of aminoglycosides have not been determined. We therefore examined dose-dependent effects of streptomycin on the degeneration of hair cells of guinea pig ampullar cristae using TUNEL stain and Hoechst nuclear stain. Streptomycin induced apoptosis of hair cells in a dose-dependent manner. Even following high-dose applications, most of the affected cells showed apoptotic features. Apoptosis may therefore play a predominant role in the deletion of vestibular hair cells affected by aminoglycosides.

Animals↗
PubMed1998

Seasonal rise in interleukin-4 during pollen season is related to seasonal rise in specific IgE for pollens but not for mites.

Since IL-4 plays a key role in inducing and increasing the generation of not only primary polyclonal but also secondary specific IgE responses by B lymphocytes, a seasonal increase in IL-4 is likely to be involved in such seasonal rises in specific IgE in seasonal allergic rhinitis. The first aim of this study was to investigate the possible seasonal increase in serum IL-4 in patients with seasonal allergic rhinitis due to Japanese cedar pollens. If serum IL-4 increases in response to seasonal pollen exposure and is responsible for the seasonal increase in pollen-specific IgE in sera, this increase in IL-4 might theoretically affect specific IgE synthesis for other allergens. The second aim was to investigate the effect of natural pollen exposure on serum concentrations of house dust mite-specific IgE in patients who have seasonal allergic rhinitis and concurrent perennial allergic rhinitis due to house dust mites. This study included 55 adult patients with seasonal and perennial allergic rhinitis due to Japanese cedar pollens and Dermatophagoides farinae (D. farinae). Venous blood was collected twice from each patient, before and during the cedar pollen season 1996, to determine IL-4, cedar pollen-specific IgE and D. farinae-specific IgE in sera. Both IL-4 and pollen-specific IgE in sera were significantly increased during the pollen season, and the seasonal increase rate in pollen-specific IgE was significantly correlated with the seasonal increase rate in IL-4. By contrast, D. farinae-specific IgE was not changed during the pollen season in these patients. In conclusion, an elevation of IL-4 in sera during the pollen season may play an important part in the seasonal rise in pollen-specific IgE, and enhancement of specific IgE synthesis is likely to need not only an increase in IL-4 but also an increase in the number and/or capacity of specific IgE-secreting B cells.

Adolescent↗
PubMed1998

Soluble vascular cell adhesion molecule-1 in perennial allergic rhinitis.

Since the expression of vascular cell adhesion molecule-1 (VCAM-1) on endothelial cells plays a central part in the selective recruitment of eosinophils into allergic inflammatory lesions, VCAM-1 may be a key molecule in allergic inflammatory diseases. Soluble forms of VCAM-1 (sVCAM-1) have recently been identified in the circulation, but there is limited published information on levels of sVCAM-1 in the circulation. If the levels of sVCAM-1 vary between patients with allergic diseases and normal controls, this variance would be very useful to investigate the state of the allergic disease and underlying inflammation. This study investigated the serum sVCAM-1 level in patients with perennial allergic rhinitis (rhinitis group) in comparison with non-atopic healthy volunteers (control group). No significant difference in the serum sVCAM-1 level was seen between the two groups (p = 0.4342). However, the serum sVCAM-1 levels in the severe rhinitis group were significantly higher than those in both the control group (p = 0.0067) and the mild rhinitis group (p = 0.0015), whereas no significant difference was observed between the mild rhinitis group and the control group (p = 0.1113). In addition, the serum levels of sVCAM-1 were significantly correlated with the nasal symptoms in the rhinitis group (rs = 0.486, p < 0.0001). In conclusion, serum concentrations of sVCAM-1 are increased in patients with severe perennial allergic rhinitis, and measurement of sVCAM-1 concentrations in sera is likely to be a useful tool for investigation of the severity of allergic rhinitis and underlying inflammatory reactions.

Animals↗
PubMed1998

Role of amino acids in cochlear degeneration: deprivation of cystine induces death of cochlear hair cells of guinea pigs in vitro.

Redox regulation reportedly plays a role in maintaining cochlear homeostasis. However, little is known about the roles of oxidation-reduction systems in the cochlea. We examined the role of the cystine/cysteine oxidation-reduction system in survival of cochlea hair cells in vitro. The survival of hair cells was evaluated in cochlea specimens following incubation with the medium supplemented with various concentrations of cystine. Dying hair cells were detected by the trypan blue extrusion method. The rates of cell death for both outer and inner hair cells increased significantly with a decrease in the concentration of cystine. In addition, the rate of cell death of IHCs tended to be higher than that of OHCs. These findings suggest that the cystine/cysteine system might be required for maintenance of homeostasis in cochlear hair cells, especially in IHCs.

Animals↗
PubMed1998

Role of amino acids in cochlear degeneration: morphological changes in cochlear outer hair cells following glutamate application.

Glutamate is an excitatory neurotransmitter in the cochlea and has toxic effects on the organ of Corti in various pathological conditions. The toxic effects of glutamate have not been determined in detail. In this study, we examined morphological changes in the organ of Corti of guinea pigs following local application of glutamate. Morphological changes were noted in outer hair cells. Degeneration of outer hair cells was found 24 h after glutamate treatment. The extent of degeneration depended on exposure time. Inner hair cells did not exhibit any degeneration. In addition, no degenerative changes were detected in nerve endings attached to hair cells. These findings suggest that outer hair cells are the initial site of degeneration caused by application of excess glutamate to the inner ear.

Animals↗
PubMed1998

Time-dependent response of vestibular hair cells of guinea pigs following high-dose applications of streptomycin.

Apoptosis has been reported to occur in vestibular hair cells following aminoglycoside treatment and is suggested to play a predominant role in deletion of affected hair cells. However, the type of cell death occurring during an acute phase of vestibular damage following high-dose application of streptomycin has not yet been determined. Hence, in this study we examined the cell death mode of vestibular hair cells during the acute phase. The numbers of hair cell nuclei stained by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling (TUNEL) method and residual hair cells were quantitatively analysed. Hoechst nuclear staining was used for analysis of the nuclear morphology of affected hair cells. TUNEL staining of hair cell nuclei and lost hair cells began to appear 6 h after streptomycin treatment and increased with more exposure time. Apoptotic nuclear features could also be found from 6 h after streptomycin treatment. These findings support the thesis that apoptosis is a predominant cell death mode in degeneration of vestibular hair cells due to streptomycin ototoxicity.

Animals↗
PubMed1998

Cycloheximide blocks the toxic effect of streptomycin in guinea pig vestibular hair cells.

Apoptosis has been suggested to be a predominant cell death process for streptomycin-induced degeneration of vestibular hair cells. However, the biochemical aspects of this have not been studied. The purpose of this study was to examine the biochemical aspects of apoptosis of vestibular hair cells caused by streptomycin. Cycloheximide is a widely used protein synthesis inhibitor in studies of apoptosis. We therefore investigated cycloheximide effects on degeneration of vestibular hair cells following streptomycin applications. Supplements of cycloheximide significantly prevented DNA fragmentation in hair cell nuclei and reduced the loss of hair cells. This suggests that cycloheximide possibly inhibits apoptosis of hair cells and attenuates streptomycin-induced degeneration of the vestibular epithelium.

Animals↗