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Biomedical subjects

K Ukai

Publications and source records attributed to K Ukai.

At least 37 records · Page 2Linked to original sources

Effects of Sho-seiryu-to on experimental allergic rhinitis in guinea pigs.

The effects of Sho-seiryu-to, an antiallergic Kampo medicine, on experimental allergic rhinitis were investigated in actively sensitized guinea pigs. The number of sneezes and scratches by the animals after a topical antigen challenge was significantly inhibited by pretreatment with Sho-seiryu-to (1000 mg/kg per os p.o.). The antigen-induced eosinophil infiltration in the nasal mucosa was significantly inhibited by Sho-seiryu-to (1000 mg/kg p.o.). Sho-seiryu-to (100 mg/kg p.o.) also reduced the increase in dye leakage to the nasal cavity induced by the antigen challenge and the antigen-induced decrease in volume of the nasal cavity was inhibited. Moreover, Sho-seiryu-to (1000 mg/kg p.o.) suppressed the volume change in the nasal cavity induced by leukotriene D4. These results demonstrate that Sho-seiryu-to inhibits experimental allergic rhinitis in guinea pigs, confirming that the agent may be beneficial for the treatment of allergic rhinitis.

Animals↗

Profiles of cytokines produced by CD4-positive T lymphocytes stimulated by anti-CD3 antibody in patients with chronic hepatitis C.

Helper T cells (Th) are classified as type 1 (Th1) and type 2 (Th2) according to the cytokines they produce; interferon-gamma is produced by Th1, and interleukin-4 by Th2. We counted the circulating CD4-positive Th cells that produce interferon-gamma or interleukin-4 with an enzyme-linked immunospot assay. CD4-positive T cells isolated from patients with chronic hepatitis B (n = 10), chronic hepatitis C (n = 16), and healthy subjects (n = 10) were stimulated with anti-CD3 antibody in vitro. The number of interferon-gamma-producing Th cells was significantly lower in patients with chronic hepatitis C than in healthy subjects (P = 0.0024), whereas in patients with chronic hepatitis B, the number was similar to that in healthy subjects (P = 0.8530). The number of interleukin-4-producing Th cells was significantly higher in patients with chronic hepatitis C (P = 0.0010) and chronic hepatitis B (P = 0.0089) than in healthy subjects. In chronic hepatitis C, the number of interferon-gamma-producing Th cells was increased after incubation of the cells with interferon-alpha (P = 0.008) or with recombinant interferon-gammala (P = 0.024), but not with interferon-beta (P = 0.051). The number of interleukin-4-producing Th cells was decreased after incubation with interferon-alpha (P = 0.0004), with interferon-beta (P = 0.003), and with recombinant interferon-gammala (P = 0.0004). Changes in the numbers of interferon-gamma- or interleukin-4-producing Th cells in vitro were more evident in sustained responders to interferon therapy than in non-responders. These results suggest that Th2 cells are the predominant cell type in chronic hepatitis C, and that their activity may be suppressed by the administration of interferon.

Adult↗

Nasal passage patency in patients with allergic rhinitis measured by acoustic rhinometry: nasal responses after allergen and histamine provocation.

We investigated nasal passage patency after allergen and histamine provocation in patients with allergic rhinitis by acoustic rhinometry. In total, 75 outpatients with allergic rhinitis were studied. The threshold of nasal hypersensitivity to histamine was measured by the 10 microliters instillation of serial 10-fold dilution in the ipsilateral nasal cavity. Nasal provocation testing to specific antigen was applied to the anterior part of inferior turbinate in bilateral sides in sitting position. Measurement of nasal patency by acoustic rhinometry was repeated three times in each nasal cavity. The minimal cross-sectional area and total volume of nasal cavity were measured in an individual subject. The minimal cross-sectional area and total volume in the histamine challenged-side significantly decreased on the 10(-2), 10(-1), 10(-0) of end point, and up to 30 min after challenge with the threshold dose, but not in the unchallenged side. This means acoustic reflection technique is sensitive at least 100-fold in comparison with classical method like findings by anterior rhinoscopy and symptom scores. Nasal passage patency after bilateral allergen provocation showed predominant in the unilateral side, suggesting the cross over-reflex effects. It was concluded that acoustic rhinometry is one of the highly quantitative and sensitive method which can observe the change of nasal congestion.

Adolescent↗

Expression of interferon-gamma, interleukin-4 and interleukin-5 mRNA in the nasal mucosal membrane of rats with allergic rhinitis.

The production of immunoglobulin E (IgE) antibody is largely dependent on the ratio between interleukin-4 (IL-4) (a T helper 2 (Th2)-type cytokine) and interferon-gamma (IFN-gamma) (a T helper 1 (Th1)-type cytokine). Interleukin-5 (IL-5) (also a Th2-type cytokine) is an important eosinophil differentiation factor and also co-stimulates B-cell growth and differentiation. The present study was designed to evaluate and compare the expression of IFN-gamma, IL-4 and IL-5 mRNA in the nasal mucosal membrane of sensitized Brown-Norway (BN) rats. Fourteen BN rats were divided into two groups: non-sensitized (control) and sensitized. The sensitized group was injected with ovalbumin (OA) intraperitoneally on three consecutive days. Twenty-one days later, rats were exposed to 1% OA aerosol. Twenty-four hours after exposure to aerosol, nasal mucosa was extracted from both groups and reverse transcriptase-polymerase chain reaction (RT-PCR) was performed. The densities of the bands of IL-4, IL-5 and IFN-gamma mRNA were expressed as percentages against beta-actin mRNA. Our results showed that the mean values for IL-4 and IL-5 mRNA were increased significantly in sensitized rats compared with control rats. In contrast, the mean value for IFN-gamma mRNA was significantly lower in sensitized rats compared with those of the control group. Our data therefore suggest that sensitization of rat nasal mucous membranes results in the predominant expression of Th2-type cytokines.

Airway Resistance↗

Effect of allergen-specific immunotherapy on interleukin-4, interleukin-5 and interferon-gamma mRNA expression in the nasal mucosa of rats with allergic rhinitis.

To elucidate the mechanism of immunotherapy, we tested the effect of ovalbumin and ovalbumin-pullulan conjugate immunotherapy on the expression of interleukin (IL)-4, IL-5 and interferon-gamma (IFN-gamma) mRNA in the nasal mucosa of sensitized rats. Forty-five rats were injected with ovalbumin intraperitoneally on three consecutive days and later were exposed to ovalbumin aerosol. The rats were injected intradermally, on six consecutive days, with saline, ovalbumin or ovalbumin-pullulan conjugate. Later, nasal mucosa was obtained and reverse transcription-polymerase chain reaction (RT-PCR) was performed. Nasal responses and specific immunoglobulin E (IgE) were measured. Although the immunotherapy significantly decreased nasal airway resistance, dye leakage and histamine content in nasal irrigation after allergen challenge, no significant difference was found in IL-4 and IL-5 mRNA expression or in specific IgE level among the three groups. We conclude that in this allergic model, the improvement of nasal responses after immunotherapy was the result of a mechanism other than decrease of T-helper 2 (Th2) cytokines.

Airway Resistance↗

Detection of thromboxane A2 receptor mRNA in the nasal mucosa of patients with allergic rhinitis.

Previous reports suggest that thromboxane (TX) A2 plays an important role in bronchial asthma, especially in the development of airway hypersensitivity. Similarly to asthmatic subjects, the nasal mucosa in patients with allergic rhinitis is hypersensitive to non-specific stimuli. Allergic rhinitis is mediated by chemical mediators released from inflammatory cells. However, the involvement of TXA2 in allergic rhinitis has been studied very little. Recently, TXA2 receptors from humans and mice have been characterized at the molecular level. We performed RT-PCR to examine whether TXA2 receptor mRNA expression is elevated higher in allergic rhinitis than in chronic sinusitis. We found that TXA2 receptor mRNA was expressed both in the nasal inferior turbinates with allergic rhinitis and in the maxillary sinus mucosa with chronic inflammation at a similar level. This result suggests that TXA2 receptor mRNA expression is not enhanced in allergic rhinitis.

Adolescent↗

[Epidemiological study of allergic rhinitis in different districts].

We investigated the morbidity of allergic rhinitis in downtown, rural area and fishing village by questionnaire in October, 1996. The morbidity rate of allergic rhinitis was 35.7% (370 subjects out of 1036) in downtown, 27.5% (266 out of 966) in rural area and 12.9% (273 out of 2112) in fishing village, and that of adult was 36.2% (314 out of 868) downtown, 28.9% (137 out of 474) in rural area and 12.07% (199 out of 1649) in fishing village, and that of child was 33.3% (56 out of 168) in downtown, 26.22% (129 out of 492) in rural area and 15.98% (74 out of 463) in fishing village. The morbidity of Japanese cedar pollinosis was 17.37% (180 out of 1036) in downtown, 13.77% (133 out of 966) in rural area and 2.60% (55 out of 2112) in fishing village. There was statistical difference (p < 0.001) between the each district respectively. It was proved that the morbidity of allergic rhinitis in downtown was higher than the rural area or fishing village, and that in fishing village was the lowest in these districts.

Adolescent↗

[Japanese cedar pollinosis in children in our allergy clinic].

Recently, it is pointed out that the incidence of Japanese cedar pollinosis has increased in children. We studied on the rate of sensitization and the onset of the disease in children under sixteen who visited allergy clinic in the Department of Otorhinolaryngology in Mie University Hospital. The percentage of positive rate of skin test and IgE antibodies of house dust mite was about 80 to 90% in 1981, 1991, and 1996. However, the percentage of positive rate of skin test and IgE antibodies of Japanese cedar pollen was 43% and 26%, respectively in 1981, but both increased to 58% in 1996. Most of Japanese cedar pollinosis patients also had house dust mite allergy. Among 115 pediatric patients who visited our allergy clinics in the past seven years, 32.2% were allergic to house dust mite alone, 8.6% were allergic to Japanese cedar pollen alone, 40.9% were allergic to both, and 6.1% were allergic to house dust mite, Japanese cedar pollen, and orchard grass pollen. 68% of the total 115 patients were boys, but significantly more girls had the pollinosis. 17.4% of those who are sensitized to the pollen were asymptomatic during the pollen season. Thus, it was confirmed that the rate of children sensitized to the pollen has apparently increased for the past twenty years. We should take care of those children who are sensitized to the pollen but asymptomatic during the pollen season.

Adolescent↗

Effects of dopaminergic agents on reversal of reserpine-induced impairment in conditioned avoidance response in rats.

Male Slc:Wistar, Std:Wistar, and Slc:F344/N rats had good acquisition of the conditioned avoidance response (CAR), while that of the male Slc:Wistar/ST, Jcl:Wistar, and Crj:Wistar rats was bad. Reserpine-induced impairment (RII) in CAR was observed 2-72 h after administration of dopaminergic (DAergic) agents in male Slc:Wistar rats. Amitriptyline (5-80 mg/kg, P.O.), imipramine, desipramine, cis-dosulepine, and trans-dosulepine at dose of 40 mg/kg, P.O. showed no antagonism against RII in CAR 20-23 h after reserpine injection (1 mg/kg, S.C.). However, the atypical antidepressive agents sibutramine (5-10 mg/kg, P.O.), bupropion (40 mg/kg, P.O.), and nomifensine (10-40 mg/kg, P.O.) exhibited antagonism against RII in CAR. The calcium channel antagonists flunarizine, nimodipine, and KP-840 at dose of 10 and 100 mg/kg, P.O., the cerebral improving agent indeloxazine (20-80 mg/kg, P.O.), the anticholinergic agent atropine (5-40 mg/kg, P.O.), 5-hydroxy-L-tryptophan (5-HTP) (40 mg/kg, I.P.), a precursor of 5-hydroxytryptamine (5-HT), and (+/-)-threo-dihydroxyphenylserine [(+/-)-threo-DOPS] (20-200 mg/kg P.O.), a norepinephrine (NE) precursor, showed no antagonism against RII in CAR. The DAergic agents methamphetamine (5 mg/kg, P.O.) and amantadine (50-250 mg/kg, P.O.), L-DOPA (200 mg/kg, P.O.), and the DAergic D1/D2 receptor agonist apomorphine (0.1-1 mg/kg, S.C.) showed marked antagonism against RII in CAR. Although the DAergic D1-receptor agonist KF-38393 (0.3-30 mg/kg, I.P.) and the DAergic D2-receptor agonist quinpirole (0.3-10 mg/kg, I.P.) induced only a weak recovery of RII in CAR when they were administered alone, in contrast to a potent synergistic recovery of RII in CAR, which was observed when SKF-38393 (1 mg/kg, I.P.) and quinpirole (1 mg/kg, I.P.) were administered together. These results suggest that the DAergic nervous system rather than the adrenergic or 5-HT nervous system is involved in RII in CAR, and that both the DAergic D1- and D2-mediated nervous systems play important roles in this process.

Animals↗

Induced pupillary hippus following near vision: increased occurrence in visual display unit workers.

Using a quasistatic method, it has been found previously that one-third of normal subjects retained pupillary constriction under empty-field conditions for a substantial period following a near-vision task. This pupil after-effect was dissociated from adaptation of tonic accommodation. In this paper, essentially the same method was used to investigate further the effects of near vision on pupil response in VDU (Visual Display Unit) workers with complaint of general fatigue and/or asthenopia. In some cases, large and slow pupillary oscillation accompanied by miosis was noted after near vision. Pupillary oscillation is a well-established phenomenon that has a broadly spread frequency spectrum with an occasional component 'hippus' at approximately 0.2 Hz. A proportion of subjects (30 out of 100) showed hippus, a consistent oscillation of 0.22 Hz (SD = 0.03 Hz) in VDU workers, while only one out of 24 normal subjects showed this. Occurrence of pupillary hippus following near vision increased in VDU workers. It was suggested that this hippus is concerned with cumulative asthenopia and/or general fatigue although the origin of hippus is still unknown.

Accommodation, Ocular↗

Effect of allergen immunotherapy on nasal responses in guinea-pigs with allergic rhinitis.

METHODS: We have investigated the effects of allergen immunotherapy on the nasal responses in the guinea-pigs with allergic rhinitis. Thirty-three male Hartley guinea-pigs with allergic rhinitis were divided into three groups; those receiving intradermal injection of saline (Group 1) or 0.1% ovalbumin (Group 2) 6 days after the last intranasal sensitization, and those injected with 0.1% ovalbumin intradermally once daily for 6 consecutive days from the next day after the last intranasal sensitization (Group 3). RESULTS: The dye leakage and histamine content into the nasal lavage significantly decreased at 30 min after antigen challenge in Group 3, compared with Group 1 or 2. We also observed the change of mast cell numbers in superficial nasal mucosa, lamina propria and injected dorsal skin. The number of mast cells in superficial nasal mucosa significantly decreased in Group 3 compared with Group 1 or 2, but not those in nasal lamina propria or dorsal skin. CONCLUSIONS: These results suggest that the improvements of nasal responses such as dye leakage and histamine content may be caused by the decrease of mast cell numbers in the superficial mucosal layer after the specific immunotherapy, which may be developing tolerance and one of the mechanisms underlying the beneficial effect of immunotherapy.

Administration, Intranasal↗

Incidence of hepatocellular carcinoma after interferon therapy in patients with chronic hepatitis C.

We examined the effect of interferon (IFN) therapy for chronic active hepatitis (CAH) C in 207 patients by estimating the incidence of hepatocellular carcinoma (HCC) after IFN therapy using the person-years method. Statistical analysis was performed using the Mantel-Haenszel chi-square test. No HCC was detected in patients with normal serum alanine aminotransferase (ALT) levels after IFN therapy (response-effect group), and in patients with both normal serum ALT levels and hepatitis C virus (HCV)-RNA clearance after IFN therapy (complete-responder group). The incidence per 100,000 person-years in the patients with elevated serum ALT level after IFN therapy (other-effects group) were 1968 and 1624, respectively. The incidence in control patients who did not achieve IFN therapy was 901. No statistically significant differences were observed between the other-effects group, non-responder group, and the control group. Our results so far suggest that normalization of the serum ALT levels and/or HCV clearance might reduce the incidence of HCC.

Adult↗

Giant hepatic angiomyolipoma associated with disseminated intravascular coagulation.

We report a case of giant hepatic angiomyolipoma in a 68-year-old woman who had an increase in the fibrinolytic activity concomitant with disseminated intravascular coagulation (DIC). The presence of the tumor was confirmed by ultrasound (US), computed tomography (CT) and magnetic resonance imaging (MRI) of the abdomen and the selective arteriography of the liver via the superior mesenteric artery. Following treatment with heparin and gabexate mesilate, abnormal hemostatic values were corrected. Furthermore, the surgical removal of the huge hepatic angiomyolipoma completely normalized the alternations of the clotting system. These findings suggest that giant hepatic angiomyolipoma was profoundly associated with DIC.

Aged↗

Amount of defocus is not used as an error signal in the control system of accommodation dynamics.

Usually defocus is considered as the error signal in the negative feedback system of accommodation control. However it is difficult to estimate the amount of defocus from the contrast reduction of a retinal image because both defocus and the spatial structure of the target determine the contrast. To investigate whether the accommodation control system can perceive the amount of error signal (defocus) from the contrast reduction of a retinal image, step responses for various amplitudes of stimuli were measured. The traces were analysed using an exponential curve fitting method in which not only time constant, but also final value of the curve, could be estimated from a portion of the exponential curve. The near-to-far (or -intermediate) step responses have a common path and show that the curve initially goes towards a certain position around the dark focus of the subject and is suddenly clipped around the correct focus position. The time constant and the destination of the curve are independent from the stimulus step amplitude (amount of error). This fact suggests that the accommodative control system does not refer to the amount of error signal when error is large, and that the system monitors only whether retinal blur exists or not. When the system judges the retinal image to be no longer blurred during the preprogrammed fast movement, accommodative response is stopped suddenly and the control is transferred to the other mechanism to hold correct focusing.

Accommodation, Ocular↗

[Effects of topical application of adrenergic agents on refraction and accommodation].

In an attempt to clarify the functional role of adrenergic receptors on accommodation, effects of various adrenergic agents on the state of accommodation were studied. Fifty-two emmetropic normal subjects (age: 19-28 y) participated in this study. We examined the effect of the alpha agonist phenylephrine hydrochloride (5%), the alpha 1 antagonist adrenergic bunazosin hydrochloride (0.1%), the beta antagonist timolol maleate (0.5%), the beta 2 antagonist betaxolal hydrochloride (0.5%), and the beta agonist isoproterenol hydrochloride (3%). Using an infrared optometer, the refraction, far point and near point of accommodation, resting point of accommodation (empty-field accommodation and dark focus of accommodation), and accommodative adaptation were measured before and after topical application of various adrenergic agents. Application of bunazosin slightly but significantly decreased the near point of accommodation. Isoproterenol evoked a hyperopic shift on the far point of accommodation. None of the agents had any effect on the resting point of accommodation. Accommodative adaptation was increased by timolol and betaxolol, and decreased by isoproterenol. We surmised that beta adrenergic agents exerted an indirect influence on the parasympathetic nervous system. The activation of beta receptors produced a hyperopic shift on the far point of accommodation and decreased accommodative adaptation, which suggests that activation of adrenergic receptors may reduce parasympathetic activity, hence affecting the state of accommodation.

Accommodation, Ocular↗

General pharmacological profile of the novel cholecystokinin-A antagonist loxiglumide.

The general pharmacological properties of a novel cholecystokinin-A antagonist, loxiglumide ((+/-)-4-(3,4-dichlorobenzamido)-N-(3-methoxypropyl)-N-pentylgl utaramic acid, CR 1505, CAS 107097-80-3) on central nervous system, autonomic nervous system, cardio-respiratory system, gastrointestinal system, hematological and miscellaneous systems were investigated in experimental animals. 1. Central nervous system: At a dose of 30 mg/kg, i.v. loxiglumide showed ptosis in one of 6 mice, but at doses of 3 and 10 mg/kg, i.v. no change on gross behavior in mice. Loxiglumide had no effect on locomotor activity and thiopental-induced hypnosis, anti-convulsive activity, analgesic activity in mice and rectal temperature changes in rats. 2. Autonomic nervous system: In vitro, loxiglumide at concentrations of 10(-4) and 3 x 10(-4) mol/l slightly inhibited agonist-induced contractions in the isolated guinea pig ileum and spontaneous rhythmic contractions in the isolated non-pregnant rat uterus. But loxiglumide had no effect on oxytocin-induced contraction in isolated non-pregnant rat uterus. 3. Cardio-respiratory system: Loxiglumide had no effect on heart rate and electrocardiogram in anesthetized dogs. But it slightly increased blood pressure and decreased the frequency of respirations at a dose of 30 mg/kg, i.v. Furthermore, loxiglumide slightly decreased femoral arterial blood flow at doses of more than 3 mg/kg, i.v. On the other hand, it had no effect on contractile force or contraction rate in the isolated guinea pig atrium and resting tension in the isolated rabbit aorta. 4. Gastrointestinal system: Loxiglumide increased bile secretion at doses of 10 and 30 mg/kg, i.v. in anesthetized rats and at doses of 3, 10 and 30 mg/kg, i.v. in anesthetized dogs. However, total bile acid output was not affected by loxiglumide. On the other hand, loxiglumide had no effect on pancreatic secretion, gastric secretion and gastric emptying in rats and intestinal transport activity in mice. 5. Hematology: In vitro, in the case of samples without bovine serum albumin, at concentrations of more than 1.9 x 10(-3) mol/l loxiglumide showed hemolysis, while in the case of samples with bovine serum albumin, at concentrations of more than 6.9 x 10(-3) mol/l loxiglumide showed hemolysis, and its maximal potency was weak compared to albumin-free conditions. On the other hand, in vivo, loxiglumide had no effect on hemolysis. In addition, it had no effect on platelet aggregation, prothrombin time and activated partial thromboplastin time. 6. Miscellaneous pharmacological actions: Loxiglumide had no effect on local anesthetic activity in guinea pigs and renal function in mice. These results suggest that loxiglumide seems to produce no serious side effects on the central nervous system, autonomic nervous system, cardio-respiratory system, gastrointestinal system, hematological and miscellaneous systems at pharmacologically effective doses.

Animals↗