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Biomedical subjects

A Nagai

Publications and source records attributed to A Nagai.

At least 109 records · Page 6Linked to original sources
PubMed1998

Erythromycin inhibits ATP-induced intracellular calcium responses in bovine tracheal epithelial cells.

Erythromycin (EM) therapy is known to decrease airway secretion in chronic inflammatory airway diseases such as diffuse panbronchiolitis. Airway secretion is regulated by intracellular Ca2+ concentration ([Ca2+]i). To elucidate the intracellular site of action of EM in airway epithelium, we examined the effect of EM on Ca2+ dynamics in cultured bovine tracheal epithelial cells using fura-2. EM per se did not cause any change in [Ca2+]i. Adenosine triphosphate (ATP; 10(-4) M) induced a biphasic [Ca2+]i increase, consisting of a transient response followed by a sustained response. Pretreatment of cells with EM had little effect on the ATP-induced transient Ca2+ response but substantially reduced the sustained response in a dose-dependent manner. Clarithromycin, another 14-membered ring macrolide, likewise showed the inhibitory effect, but ampicillin and cephasolin did not. Uridine triphosphate (UTP; 10(-4) M) induced a biphasic [Ca2+]i increase similar to ATP, and the UTP-induced sustained Ca2+ response was also inhibited by EM. In Ca2+-deficient medium (1 mM ethyleneglycol-bis-(beta-aminoethyl ether)-N, N'-tetraacetic acid [EGTA]) or in the presence of La3+, the sustained Ca2+ response disappeared, suggesting that EM may inhibit Ca2+ influx induced by P2u purinoceptor stimulation. In single-cell Ca2+ image analysis, low concentration of ATP (10(-6) M) induced Ca2+ oscillations, which were also inhibited by EM. The disappearance of [Ca2+]i oscillations after addition of EM was similar to that after addition of EGTA. These results suggest that EM may decrease Ca2+-dependent airway secretion by inhibiting agonist-stimulated Ca2+ influx.

Adenosine Triphosphate↗
PubMed1998

[Thirteen-week intravenous repeated dose toxicity study of T-3762, a novel parenteral quinolone antimicrobial agent, and four-week recovery test in cynomolgus monkeys].

A thirteen-week intravenous repeated dose toxicity study of T-3762, parenteral quinolone antimicrobial agent, and four-week recovery test was carried out in male and female cynomolgus monkeys at dosages of 26, 52 and 104 mg/kg. The following results were obtained. 1) There was no death of animals during administration period at any dose levels. In general signs, there was no abnormality at any dose levels. 2) In appetite, body weights and ophthalmological examination, there was no abnormality attributable to the treatment. 3) In urinalysis, hematological examination and biochemical examination, there was no abnormality attributable to the treatment. 4) In organ weights, macroscopic findings and histopathological findings, there was no abnormality attributable to the treatment. 5) From these results in this study, no-toxic dose level of T-3762 for cynomolgus monkeys is considered over 104 mg/kg.

Animals↗
PubMed1998

[Encephalopathy induced by fleroxacin in a patient with Machado-Joseph disease].

Convulsive seizure with unconciousness is an adverse effect of new quinolone antibiotics including fleroxacin. A block of GABA receptor in CNS has been reported as pathomechanism. A 48-year-old female patient with Machado-Joseph disease (MJD) had encephalopathy induced by fleroxacin. She revealed unconsciousness after the administration of fleroxacin (200mg/day) for three days. Electroencephrogram (EEG) showed diffuse slow waves. The administration was discontinued and her consciousness became clear after a day. The abnormal findings on EEG disappeared gradually. The concentrations of fleroxacin were within normal limits in serum and cerebrospinal fluid. The patient with MJD might have a tendency to develop encephalopathy by fleroxacin, because the GABA-ergic nervous system could be involved in MJD.

Anti-Infective Agents↗
PubMed1998

[A case manifested overlapping neuropathologic features of both progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD)].

A 62-year-old man developed clumsiness, vertical ophthalmoplegia, right-side dominant parkinsonism, pyramidal signs, limb-kinetic apraxia and dementia. His brain MRI and SPECT revealed mild fronto-parietal atrophy and hypoperfusion predominately on the right side. At the age of 65, the patient died of sepsis. The duration of his illness was approximately 3 years. Clinical diagnosis was corticobasal degeneration (CBD). On neuropathological examination, there was no neuronal loss and many neurofibrillary tangles (NFTs) in the cerebral cortices. Basal ganglia and substantia nigra showed moderate to severe neuronal loss. And there were many NFTs and argyrophillic threads (threads) in the subthalamic nucleus and nuclei of the brainstem. These findings were almost compatible to those of PSP. However, the following findings were atypical for PSP, 1) mild atrophy and absence of gliosis in the tegmentum of the brain stem, 2) Mild neuronal loss in the subthalamic nucleus and the dentate nucleus without grumose degeneration. Furthermore, characteristic findings were noted on modified Gallyas-Braak stain. Numerous threads and many astrocytic plaques (AP) were shown in cerebral cortices, which were particular to CBD cases. So this case demonstrated neuropathological findings of both PSP and CBD. Therefore, it was difficult to classify this case as either PSP or CBD, and we diagnosed this case as a neuropathological overlapping case of both PSP and CBD.

Aged↗
PubMed1998

Regulation of adrenergic nerve-mediated contraction of canine pulmonary artery by K+ channels.

The aim of the present study was to investigate the role of certain subtypes of K+ channels in nerve-evoked contractions of pulmonary artery in vitro. The lobar or segmental pulmonary arteries were dissected from dogs, cut into ring segments, and the contractile responses to electrical field stimulation (EFS) and noradrenaline were measured under isometric conditions. Addition of iberiotoxin, a big conductance Ca2+-activated K+ channel blocker, and apamin, a small conductance Ca2+-activated K+ channel blocker, did not change the resting tension but augmented the contractile responses to EFS, so that the electric stimulus frequency required to produce a half-maximal contraction (ES50) was decreased from 18.2+/-3.5 to 7.4+/-2.3 Hz (p<0.01) and from 16.8+/-2.2 to 11.4+/-2.0 Hz (p<0.05), respectively, whereas glibenclamide, an adenosine triphosphate (ATP)-sensitive K+ channel blocker, had no effect. In contrast, none of the K+ channel blockers altered the contractile response to noradrenaline. Incubation of tissues with iberiotoxin and apamin increased the release of 3H-noradrenaline evoked by EFS. We conclude that big conductance Ca2+-activated K+ channels and small conductance Ca2+-activated K+ channels may play a role in the regulation of adrenergic neurotransmission in the pulmonary artery, probably by inhibiting the exocytotic release of noradrenaline from the adrenergic nerve terminals.

Animals↗
PubMed1998

[A case of pulmonary eosinophilic granuloma undergoing spontaneous remission].

A case of pulmonary eosinophilic granuloma that underwent spontaneous remission is presented. A 23-year old man presented with dry cough and fever. Chest X-ray film revealed diffuse reticulo-nodular infiltrates in the middle and upper lung fields. Chest CT and HRCT showed multiple cystic lesions with thick walls and small nodules predominantly in the inner zone. Based on radiographic findings, pulmonary eosinophilic granuloma was suspected. Bronchoalveolar lavage cell data showed lymphocyte and eosinophil alveolitis with no increase of CD 1 lymphocytes. The symptoms and radiographic findings improved markedly within 4 months after the onset of symptoms without treatment and upon cessation of smoking. Chest CT and HRCT showed that the cystic walls were thinner and that the small nodules had decreased. Thoracoscopic lung biopsy revealed granulomatous lesions consisting of CD 1 and S-100 protein positive histiocytes with infiltration of eosinophils and fibrous lesions. Pulmonary eosinophilic granuloma was diagnosed. There has been no recurrence for 1 year.

Adult↗
PubMed1998

[Effect of adenosine and its analogues on microvascular leakage in the rat trachea].

We examined the effects of adenosine and its analogues on vascular permeability in rat trachea using Evans blue dye as a marker for plasma leakage. Inhalation of N6-2-(4-aminophenyl) ethyladenosine (APNEA), a specific A 3 receptor agonist, increased microvascular leakage in a dose-dependent manner, but adenosine, [R]-N6-(1-Methyl-2-phenylethyl) adenosine (R-PIA), aspecific A 1 receptor agonist, and 5'-(N-ethyl-carboxamide) adenosine (NECA), a specific A 2 receptor agonist, had no effect. Inhalation of capsaicin increased vascular permeability in a dose-dependent manner. Pretreatment with NECA (10-1000 nmol/kg, i.v.) but not adenosine (100 nmol/kg i.v.), R-PIA (100 nmol/kg, i.v.) or APNEA (100 nmol/kg, i.v.) inhibited microvascular leakage produced by capsaicin aerosol (3 x 10(-5) M) in a dose-dependent manner. However, NECA (10-100 nmol/kg, i.v.) failed to inhibit substance P aerosol (10(-4) M)-induced extravasation of the dye. These findings suggest that stimulation of adenosine A 3 receptors produces airway vascular permeability, and that A 2 receptors inhibit neurogenic plasma extravasation, presumably by inhibiting the release of tachykinins from sensory nerves.

Adenosine↗
PubMed1998

[Effect of salbutamol on proliferation of human bronchial epithelial cells: role of MAP kinase].

To determine whether stimulation of beta-adrenoceptors affects proliferation of airway epithelial cells and, if so, whether activation of mitogen-activated protein kinase (MAPK) is involved, we studied cultured human bronchial epithelial (16-HBE) cells in vitro. The 16-HBE cells were grown to subconfluence in 96-well plates, and their growth was inhibited by incubation in serum-free medium for 72 h. The cells were ten incubated in the presence of saltbutamol (SAL, 10(-7) M), a specific beta(2)-adrenoceptor agonist. Proliferation of the cells was evaluated by MTT assay and total DNA content, and activation of MAPK was assessed by immunocytochemistry and Western blotting for phosphorylated MAPK (phospho-MAPK). Immunocytochemistry and immunoblots demonstrated that phospho-MAPK was expressed within minutes of SAL exposure. This effect of SAL was as potent as that of 10% serum, and was greatly inhibited by treatment with propranolol. These results suggest that SAL is a potent mitogen of airway epithelial cells and that its effect may be exerted by beta(2)-adrenocepter-mediated activation of MAPK.

Adrenergic beta-2 Receptor Agonists↗
PubMed1998

[Relaxation of canine pulmonary arteries caused by stimulation of atypical beta-adrenergic receptors].

To examine possible contributions of beta(3)-adrenoceptors to catecholamine-induced pulmonary vasodilation, we studied isolated canine pulmonary arterial segments under isometric conditions. Addition of beta-adrenoceptor agonists produced a concentration-dependent relaxation of tissues precontracted with 50 mM KCl; the rank order of potency was isoproterenol (ISO, 1) > salbutamol (SAL, 0.97) > selective beta(3)-adrenoceptor agonists CL 316243 (CL, 0.87) and BRL 37344 (BRL, 0.86). Relaxant responses to SAL were competitively antagonized by the beta(2)-adrenoceptor antagonist ICI 118551 and the pA2 value was 6.67 +/- 0.21 (mean +/- SE), whereas the response to CL was weekly antagonized only by a high concentration of ICI 118551 (10(-5) M) and the apparent pA2 value was 5.24 when alpha-and beta(1)-adrenergic receptors were blocked. By contrast, the atypical beta-adrenoceptor antagonist cyanopindolol antagonized CL-induced relaxation in a competitive manner; the pA2 value was 6.71 +/- 0.12, which was lower than that with salbutamol (p < 0.05). Intracellular cyclic AMP levels were increased in a contraction-dependent manner by CL. These results suggest that beta(3)-adrenoceptors may exist in canine pulmonary arterial smooth muscle and that stimulation of this atypical receptor causes vasodilation through a cyclic AMP-dependent pathway.

Adrenergic beta-Agonists↗
PubMed1998

[Effect of heparin on airway goblet cell secretion in sensitized guinea pigs].

Heparin and related proteoglycans are released from mast cells and possess anti-inflammatory and anti-complement activities. To elucidate whether heparin affects goblet cell secretion in asthmatic airways and, if so, what the mechanism of action is, we studied guinea pigs sensitized with ovalbumin (OVA) by determining the mucus score (MS) of tracheal goblet cells stained with Alcian blue and PAS. Inhalation of OVA caused a rapid decrease in MS in a dose-dependent manner, with the maximal decrease being from 545 +/- 26 to 192 +/- 35 (p < 0.001), indicating an increase in goblet cell mucus discharge. This effect was selectively inhibited by the histamine H2 receptor blockade with cimetidine. Prior inhalation of heparin inhibited OVA-induced goblet cell secretion in a dose-dependent fashion, but had no effect on histamine-induced goblet cell secretion. The OVA-induced histamine release from the tracheal tissue was likewise inhibited by heparin. These results suggest that allergic challenge stimulates airway goblet cell secretion mainly through the release of histamine and the concomitant activation of histamine H2 receptors on goblet cells, and that heparin protects against this effect by inhibiting the histamine release from mast cells.

Animals↗
PubMed1998

[Single dose intravenous toxicity studies of T-3762, a novel parenteral quinolone antimicrobial agent, in rats, dogs and monkeys].

Single dose intravenous toxicity studies of T-3762, a novel parenteral quinolone antimicrobial agent, were conducted in rats, dogs and monkeys. The following results were obtained. 1. In the rat study, all males and females given 260 mg/kg survived and all males and 3 of 5 females given 391 mg/kg died. Approximate lethal doses in male and female rats were between 260 and 391 mg/kg. In survived animals, decrease in locomotor activity and irregular respiration were observed. These clinical signs were recovered within 1 hour after dosing. In female rats given 260 mg/kg, no abnormalities were observed in general signs. In dead animals, decrease in locomotor activity, irregular respiration, staggering gait and tonic convulsion were observed and died within about 90 minutes after dosing. Macroscopic examinations in dead animals showed dark red discoloration in lung and had white foamy liquid in trachea. In histopathological examinations of dead animals, congestion, hemorrhage and edema were observed in lung. 2. In the dog study, 2 animals given 260 mg/kg survived and 2 animals given 521 mg/kg died. Approximate lethal dose in dogs was between 260 and 521 mg/kg. In the 260 and 521 mg/kg groups, decrease in locomotor activity, lateral position, vomiting, salivation and decrease in body temperature were observed. In the 521 mg/kg group, one animal died at 4 minutes and another 7 days after dosing. Histopathological examinations in 2 dead animals showed congestion or hemorrhage in heart, lung, liver, kidney, spleen and digestive tract. Erosion and necrosis at cartilage layer and cluster of chondrocyte were observed in scapular fossa and head of humerus in the 260 and 561 mg/kg groups. 3. In the monkey study, 2 animals given 260 mg/kg survived and 2 animals given 520 mg/kg died. Approximate lethal dose in monkeys was between 260 and 520 mg/kg. In the 260 mg/kg group, soft feces was observed. In the 520 mg/kg group, paleness mucosa of oral cavity, muscle weakness, mydriasis and dyspnea were observed and animals died within 4 minutes after dosing. Macroscopic and histopathological examinations in 2 dead animals showed congestion in lung, liver and kidney.

Alanine Transaminase↗
PubMed1998

[Three months intravenous repeated dose toxicity study of T-3762 in rats].

A three months intravenous repeated dose toxicity study of T-3762, a novel parenteral quinolone antibacterial agent, was carried out in rats at dose levels of 4, 13, 39, 130 mg/kg. Fifteen rats of each sex were used in each group. Out of these, 5 rats of each sex were used for the recovery study. The following results were obtained. 1. There were no death caused by T-3762 within the study period. In clinical signs, the squeaks during injection in 130 mg/kg group were observed, but they decreased day by day. In body weight changes, a tendency to very slight decrease of weight gain in male 130 mg/kg group were seen, but there was no significant difference from control group. In food and water consumption, there was no abnormality. 2. There were no abnormality caused by T-3762 in urinalysis, hematological examination and ophthalmological examination. 3. In blood chemistry examinations, increase of A/G ratio was seen in 13, 39 and 130 mg/kg groups, but it showed tendency of recovery after withdrawal period. 4. In macroscopic and histological findings, erosion and cavitation of the articular cartilage were seen in 3 of 20 rats in 130 mg/kg group and 1 of 20 rats in 39 mg/kg group. 5. Non-toxic dose levels is estimated to 13 mg/kg, that showed no abnormality in the articular cartilage in this study.

Alanine Transaminase↗
PubMed1997

Case report of rec(7)dup(7q)inv(7)(p22q22) and a review of the recombinants resulting from parental pericentric inversions on any chromosomes.

We report a rare case of duplication for 7q22 --> 7qter and deletion for 7p22 --> 7pter, resulting from a meiotic recombination of a paternal pericentric inversion, inv(7)(p22q22). The newborn boy had the 7q trisomy syndrome. In addition, the diagnosis of chondrodysplasia punctata was made from lumbar and hand X-ray films taken soon after birth. Only two cases of rec(7)dup(7q), both in a single family, have been reported previously. We review 133 offspring with recombinations resulting from pericentric inversions on any chromosomes reported between 1981 and 1995. Of the 133 cases, 110 had a long-arm duplication and short-arm deletion, while only 23 had a short-arm duplication and long-arm deletion. In 85 of the 133 cases, the mother was an inversion carrier (five carriers had two affected offspring), and in 46, the carrier was a father (one carrier had three affected offspring). Kaiser [Hum Genet 1984;68:1-47] reviewed 63 offspring with recombinations derived from a parental pericentric inversion reported between 1972 and 1981. In both surveys, recombinations resulting from pericentric inversions of chromosomes 1, 12, 19, and Y were not found.

Chromosome Aberrations↗
PubMed1997

Sudden unexpected death due to Fournier's gangrene.

A 43-year-old Japanese male vagrant collapsed suddenly in a police station. The man was resuscitated in hospital but died about 13 h later. An autopsy revealed necrotizing fasciitis in the genitalia and lower abdominal wall. The man was considered to have died from endotoxic shock following on Fournier's gangrene.

Adult↗