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Biomedical subjects

J Tsuji

Publications and source records attributed to J Tsuji.

At least 19 recordsLinked to original sources

Effect of TYB-2285 on peritoneal anaphylaxis in passively sensitized rats.

1. The effect of TYB-2285, a novel anti-inflammatory drug, was investigated on passive peritoneal anaphylaxis in rats, and compared with disodium cromoglycate (DSCG), amlexanox, ketotifen fumarate and tranilast. 2. As parameters of passive peritoneal anaphylaxis, histamine release into the peritoneal cavity and capillary permeability elicited by ascitis were measured. 3. TYB-2285 (10 mg/kg), when given intraperitoneally at 0.5, 1 and 2 min before antigen challenge, inhibited anaphylactic histamine release by 36.2%, 57.5% and 52.6%, respectively. TYB-2285 also inhibited capillary permeability by 20.9%, 57.6% and 49.0%, respectively. 4. DSCG (10 mg/kg), given intraperitoneally 0.5 min before challenge, inhibited histamine release and capillary permeability by 79.6% and 57.6%, respectively. 5. Amlexanox (10 mg/kg), given intraperitoneally 0.5 min before challenge, inhibited histamine release and capillary permeability by 85.6% and 74.8%, respectively. 6. A time-course study showed that TYB-2285 (30 mg/kg) was effective for 30 min after oral administration. A dose-response study suggested that the inhibitory effect of TYB-22585 (postoperatively) on histamine release during PPA reached a plateau at 10 mg/kg. 7. In passive peritoneal anaphylaxis in vitro, TC-1121 and TC-1122, metabolites of TYB-2285, inhibited antigen-induced histamine release at 10(-7) to 10(-5) M in a dose-dependent manner, whereas TYB-2285 itself and other major metabolites of TYB-2285, TC-286 and TC-326, did not inhibit histamine release, even at 10(-4) M.

Anaphylaxis

Intracellular labeling of auditory nerve fibers in guinea pig: central and peripheral projections.

Auditory-nerve fibers (ANFs) in the cat have been subdivided according to spontaneous rate (SR), with high-SR fibers showing the lowest thresholds. Cochlear terminals of the three SR groups differ in caliber and synaptic position around the inner hair cell (Liberman [1982b] Science 216:1239-1241); central terminals differ in degree of branching and in which subregions of the cochlear nucleus (CN) are targeted (Liberman [1991] J. Comp. Neurol. 313:240-258). The present study investigates whether these SR-based differences in ANF connections are unique to the cat. Thirty ANFs from 15 guinea pigs were intracellularly labeled after measuring characteristic frequency, threshold, and SR. Labeled cochlear projections showed significant SR-based differences in axonal caliber, with low- and medium-SR fibers 20-40% thinner than those of high-SR fibers for both peripheral and central (modiolar) axons. Spatial segregation in the inner hair cell area could not be assessed; however, the peripheral axons in the osseous spiral lamina showed the same SR-based organization reported for the cat (Kawase and Liberman [1992] J. Comp. Neurol. 319:312-318). Labeled central projections also showed significant SR-based differences. Low- and medium-SR fibers: 1) were more highly branched, 2) sent significantly more terminals to the small-cell cap region of the CN, and 3) produced endbulb terminals (on spherical cells) that were significantly more complex than high-SR fibers. All of these SR-based trends for both central and peripheral projections are analogous to those reported in the cat, and, thus, may represent a fundamental organizational principle of the mammalian ear.

Animals

Effect of TYB-2285 on passive cutaneous anaphylaxis in rats.

1. TYB-2285 (1-30 mg/kg p.o.) inhibited ovalbumin (OA)- and dinitrophenyl-Ascaris (DNPAs)-induced passive cutaneous anaphylaxis (PCA) in a dose-dependent manner. 2. The ED50 of TYB-2285 and ketotifen fumarate on OA-induced PCA were 0.5 and 3.9 mg/kg, respectively. The ED50 of TYP-2285 and amlexanox on DNP-As-induced PCA were 3.5 and 0.9 mg/ kg, respectively. 3. TYB-2285 (3-30 mg/kg p.o.) inhibited histamine consumption at the PCA site. 4. Unlike cyproheptadine or amlexanox, TYB-2285 (30 mg/kg p.o.) did not inhibit histamine-, serotonin-, ascites-, 48/80-, or A23187-induced capillary permeability. It inhibited dextran-induced capillary permeability slightly. 5. These results demonstrate that TYB-2285 inhibits PCA by inhibiting histamine release, although it does not inhibit capillary permeability.

Animals

Effect of TYB-2285 on lung anaphylaxis in actively sensitized rats.

1. We examined the effect of TYB-2285 on the acute phase and the late phase of lung anaphylaxis in rats. 2. TYB-2285 (3-30 mg/kg PO) inhibited antigen-induced bronchoconstriction and TxB2 production during the acute phase of lung anaphylaxis in a dose-dependent manner. 3. Ketotifen fumarate (30 mg/kg p.o.) inhibited bronchoconstriction and TxB2 production less potently than TYB-2285. 4. TYB-2285 (30 mg/kg p.o.) inhibited the accumulation of neutrophils during the late phase of lung anaphylaxis significantly without a significant change in total cells. 5. Hydrocortisone acetate (100 mg/kg p.o.) inhibited the accumulation of total cells as potent as neutrophils.

Anaphylaxis

Effects of TYB-2285 on the accumulation of eosinophils in the airway induced by antigen exposure in actively sensitized brown Norway rats.

1. The effect of TYB-2285 on the antigen-induced accumulation of eosinophils into the airway was investigated in two models (inhalant sensitization and noninhalant sensitization) using Brown Norway (BN) rats. 2. In the method of inhalant sensitization, BN rats were sensitized by weekly exposure to ovalbumin (OA). The accumulation of eosinophils was inhibited by the oral administration of TYB-2285 for the first 2 days of each sensitization in a dose-dependent manner. 3. With noninhalant sensitization, BN rats were sensitized by i.m. injection of OA and i.p. injection of killed Bordetella pertussis. The accumulation of eosinophils was inhibited by TYB-2285 in a dose-dependent manner, when TYB-2285 is given p.o. 5 mm before and 5 hr after the antigen exposure. Moreover, this accumulation of eosinophils was inhibited by a single administration of TYB-2285 5 hr after the antigen exposure, presumably when the mast cell degranulation was already finished. 4. In the method with noninhalant sensitization, the accumulation of eosinophils was not inhibited by mast cell stabilizers such as ketotifen, tranilast, or DSCG. 5. The present study demonstrates that TYB-2285, unlike other mast cell stabilizers, inhibits the antigen-induced accumulation of eosinophils into the airway. It also suggests that this drug might be effective in asthmatic patients.

Animals

Effect of TYB-2285 on antigen-induced accumulation of eosinophils into the peritoneal cavity of rats sensitized with Ascaris suum extract.

1. The present study was carried out to investigate the effect of 3,5-bis-(acetoxyacetylamino)-4-chloro-benzonitrile (TYB-2285) on the accumulation of eosinophils in the peritoneal cavity of Wistar rats sensitized with Ascaris suum extract (Asc). 2. Rats were sensitized by IP injection of Asc on day 0 and were challenged by IP injection of Asc on day 7. Antigen challenge caused a specific, delayed infiltration of eosinophils into the peritoneal cavity that was inhibited by PO administration of TYB-2285, but not ketotifen fumarate, in a dose-dependent manner (3-30 mg/kg). 3. TYB-2285 inhibited the infiltration of eosinophils when during the induction phase, but not during the effector phase. The inhibitory effect of TYB-2285 when during the induction phase was stronger than any other antiallergic drugs, such as tranilast, azelastine, ibudilast, repirinast, tazanolast, oxatomide, or pemirolast. 4. Transfer of lymphocytes, but not serum, from sensitized rats to intact rats provoked a remarkable infiltration of eosinophils after the antigen challenge. In the experiment of adoptive transfer in rats, TYB-2285 was effective when given to donor rats. 5. These results demonstrate that TYB-2285 inhibits the accumulation of eosinophils presumably by inhibiting antigen recognition.

Adoptive Transfer

The effects of TYB-2285 and its metabolites on lymphocyte responses in vitro.

1. We examined the effects of TYB-2285 and its metabolites (TC-286 and TC-326) on antigen-induced lymphocyte proliferation, allogeneic mixed lymphocyte reaction (MLR) and mitogen-induced lymphocyte proliferation. 2. Splenic lymphocytes from C57BL/6 strain mice sensitized with human serum albumin were cultured with the antigen in the presence of TYB-2285 or its metabolites (10(-7)-10(-4) M). The lymphocyte proliferation enhanced by antigen was inhibited by TYB-2285 and its metabolites in a dose-dependent manner. 3. Splenic lymphocytes collected from C57BL/6 and Balb/C strain mice were cocultured in the presence of TYB-2285 and its metabolites (10(-7)-10(-4) M). Allogeneic MLR was inhibited by TYB-2285 and its metabolites in a dose-dependent manner. 4. Splenic lymphocytes from C47BL/6 strain mice were cultured with concanavalin A (Con A) in the presence of TYB-2285 and its metabolites (10(-7)-10(-4) M). TYB-2285 and its metabolites did not affect Con A-induced lymphocyte proliferation. Cyclosporin A showed an inhibitory effect on Con A-induced lymphocyte proliferation that was as strong as the inhibitory effect on antigen-induced lymphocyte proliferation and allogeneic MLR at a lower concentration.

Albumins

Characteristics of DPOAE audiogram in tinnitus patients.

To investigate cochlear activity in tinnitus, the DPOAE (distortion product otoacoustic emission) audiograms (DP-gram) of tinnitus patients were measured. Nine tinnitus patients (15 ears) with normal hearing and 55 tinnitus patients (75 ears) with hearing impairment were included in this study. Significant decreases in DPOAE amplitude over a limited frequency range were observed in 93.3% of the normal hearing tinnitus group and in 96% of the hearing-impaired tinnitus group. The averaged DP-gram of the normal hearing tinnitus group was significantly different from that of the normal subject (repeated-measures ANOVA, P < 0.01). These results imply that tinnitus may be evaluated objectively by DPOAE.

Adult

The effect of intravenous lidocaine injection on hearing thresholds.

The effect of intravenous injection of lidocaine on hearing thresholds was studied in normal subjects. Continuous and intermittent tones at 1, 4 and 8 kHz were used as stimuli and the threshold change with lidocaine injection was measured using a self-recording audiometer (Békésy audiometer). Both increases and decreases in the threshold were observed. The former occurred more frequently than the latter. In cases of a threshold increase, lidocaine injection exhibited a frequency specific effect; the higher the frequency, the more often the threshold was increased by lidocaine injection. There was no significant difference in threshold changes between continuous and intermittent tones. The present results suggest that lidocaine may act on the inner ear hair cells.

Adult

Multiple expression of Ly-6C and accumulation of a Ly-6C pre-mRNA in activated macrophages involved in rejection of an allografted tumor.

We established a monoclonal antibody against a surface antigen of activated macrophages (Møs) involved in the rejection of an allografted mouse tumor, Meth A. Bacteria-elicited Møs also expressed the antigen but resident or inflammatory Møs, or other leukocytes, did not. The antigen was identified as Ly-6C by isolation of cDNA clones encoding it. Two-dimensional immunoblotting revealed that Ly-6C of the Møs exists in multiple forms with a similar size but with different isoelectric points. A Ly-6C pre-mRNA also accumulated abundantly in the Møs. Thus, the multiple expression of Ly-6C and the accumulation of the pre-mRNA are the features of allograft- and bacteria-elicited Møs.

Amino Acid Sequence

Purification of (+)-delta-cadinene synthase, a sesquiterpene cyclase from bacteria-inoculated cotton foliar tissue.

A sesquiterpene cyclase whose activity is induced in a glandless, bacterial blight-resistant line of cotton (Gossypium hirsutum L.) catalyses the conversion of (E,E)-farnesyl diphosphate to (+)-delta-cadinene. This enzyme was purified by a combination of salt-induced phase separation, hydroxylapatite fractionation, hydrophobic interaction and strong anion-exchange chromatography, and denaturing polyacrylamide gel electrophoresis, followed by renaturation with Tween 80. The purified enzyme has a molecular weight of 64-65 kDa, and exhibited a single silver-staining band following electrophoresis in analytical denaturing polyacrylamide gels. Amino acid sequences of three tryptic peptides from the enzyme have been determined and are similar to known sequences in other terpene cyclases from plants.

Amino Acid Sequence

A similarity and a difference between two models of late eosinophil accumulation into the airway induced by antigen exposure in actively sensitized brown Norway (BN) rats.

1. Exposure of sensitized Brown Norway (BN) rats to ovalbumin aerosol induced a remarkable and a sustained accumulation of eosinophils into broncho-alveolar lavage (BAL) fluid. 2. When male BN rats, sensitized by i.m. injection of ovalbumin and i.p. injection of killed Bordetella pertussis, were exposed to the antigen on day 14, eosinophils accumulated into BAL fluid, maximal 48 hr after antigen exposure. This accumulation of eosinophils was inhibited completely by administration of cyclosporin A (Cs A, 50 mg/kg/day) during induction phase, whereas it was inhibited slightly by administration of CsA (50 mg/kg) during the effector phase. 3. When BN rats were sensitized by weekly exposure of ovalbumin, eosinophils accumulated into BAL fluid, maximal 48 hr after the third exposure of antigen. The accumulation of eosinophils by this method was observed only in female rats and was inhibited completely by administration of CsA (50 mg/kg) during induction phase, whereas it was inhibited slightly by administration of CsA (50 mg/kg) during effector phase. 4. The present study demonstrates similarities and differences between two models of eosinophilia and also suggests increased function of T cells in BN rats.

Aerosols

The transition of alpha-helix to beta-structure of poly(L-lysine) induced by phosphatidic acid vesicles and its kinetics at alkaline pH.

Static and dynamic circular dichroism (CD) measurements were carried out for poly(L-lysine) in suspensions of dilauroylphosphatidic acid (DLPA) vesicles at alkaline pH (8-11.5). The static experiments demonstrated that the alpha-helix of poly(L-lysine) induced by deprotonation in alkaline solutions is transformed to beta-structure by the addition of DLPA vesicles. Stopped-flow CD measurements for such order-to-order transition revealed that the rate determining step is the unfolding process of alpha-helix to random coil. Previously, we have reported the conformational change of poly(L-lysine) induced by DLPA vesicles at neutral pH, where the beta-structure transition from random coil was observed. Thus two types of transition of poly(L-lysine) are observed depending on bulk pH, i.e., from random coil to beta-structure and from alpha-helix to beta-structure. So far the phospholipid-induced conformations of poly(L-lysine) were interpreted in terms of counterbalance between the positively charged terminals of the lysyl chains and the negative headgroups of the phospholipid in vesicle. However, present work indicates the direct interaction other than electrostatic interaction between the lysyl chain and phosphate groups of the lipid.

Circular Dichroism

Effect of caloric stimulation on primary vestibular fibers originating from otolith organs in the guinea pig.

The influence of caloric stimulation on the primary vestibular fibers originating from the otolith organ was investigated in the guinea pig. Firing rates were recorded from single vestibular neurons in the superior vestibular (Scarpa's) ganglion which were identified physiologically as originating from the otolith organs, mainly from the utricles. Eighty-six percent of the neurons responded to caloric stimulation. Neurons with a high coefficient of variation of firing regularity reacted more sensitively to tilting and also had a tendency to react more sensitively to caloric stimulation. There was a tendency for neurons with increased firing rates in response to ipsilateral tilting to have increased firing rates to warm stimulation, while neurons whose rates increased to contralateral tilting had increased firing rates to cold stimulation. These results indicate that the otolith organs have the same unidirectional tendency to caloric simulation with results comparable to optimal tilting directions.

Action Potentials

Reliability of the promontory stimulation test for the preoperative evaluation of cochlear implants: a comparison with the round window stimulation test.

The electrical stimulatory threshold of the preoperative promontory stimulation test (PST) was compared with the postoperative threshold of the electrode following cochlear implantation. Postoperative results from warble-tone audiometry, the vowel recognition test, the consonant recognition test, and the speech tracking test, which employed a speech processor, were similarly evaluated. In certain patients who responded insufficiently to the PST, an exploratory tympanotomy under local anesthesia was performed prior to cochlear implantation, and stimulatory threshold was measured with an electrode placed directly on the round window [round window stimulation test (RWST)]. No correlation was found between the PST results and the postoperative performance of the cochlear implant. The RWST was determined to be better than the PST in the evaluation of cochlear implant performance.

Adult

Effects of rIL-7 on murine bone marrow NK precursor cells.

We recently demonstrated that functional NK cells are produced from their precursors in murine long-term bone marrow cultures without the addition of exogenous growth factors. Because IL-7 is known to be produced by bone marrow stromal cells and is a proliferation factor for some immature cells of the B and T cell lineages, we tested whether rIL-7 could support the proliferation or maturation of NK precursor cells. By itself, rIL-7 did not induce NK lytic activity in cultures of unseparated bone marrow cells (BMC), but it did augment the response of unseparated BMC to 50 U rIL-2/ml, with a maximal enhancement at 10 ng IL-7/ml. Depletion experiments demonstrated that the IL-7-induced increase in cytotoxicity was not due to NK precursors, however, but to mature T and NK cells. IL-7 preferentially increased the number of CD8+ cells. Preculture of NK 1.1-depleted BMC with IL-7 did not increase the total number of NK 1.1+ cells or the lytic activity generated from NK precursor cells. However, IL-2-responsive NK lineage cells survived better in IL-7-supplemented medium than in medium alone. Thus, soluble rIL-7 did not expand the NK precursor cell population in vitro but it maintained the viability and subsequent responsiveness to IL-2 of NK precursors.

Animals

Efferent vestibular fibers to otolith organs in guinea pigs.

The origins of efferent vestibular fibers to the otolith organs in guinea pigs, examined with the use of retrograde transport of HRP were: i) the bilateral lateral portions of the facial genu and ii) the ipsilateral reticular nucleus at the level of the facial nucleus. These origins are almost the same as those of the efferent fibers to the three semicircular canals which we have previously identified in cats; however, they differ in certain respects.

Animals

[Computerized database system for pure tone audiometry].

The management and storage of pure tone audiometry data creates a major problem for otolaryngological clinics. We have devised a new computerized database system to overcome this problem. The hardware involved includes multiple audiometers and computers interfaced with a glassfiber local area network (Pi-Net). The software used is database 3 plus, a popular database language and utility software package. Programs were written for data entry, data transfer, reference, entry of patient ID, and evaluation of tympanoplasty. The following benefits of the system are noted. 1) Data entry is possible at every terminal (audiometer and computer). 2) Storage capacity is sufficient for more than 10 years of operation. 3) All data can be retrieved rapidly at any terminal. Evaluations of pre- and post-tympanoplasty hearing loss are facilitated by this system. This system is very effective for follow up of hearing disorders.

Audiometry, Pure-Tone