Biomedical subjects

S Okuyama

Publications and source records attributed to S Okuyama.

At least 37 records · Page 2Linked to original sources

PubMed1999

Binding characteristics of [3H]DAA1106, a novel and selective ligand for peripheral benzodiazepine receptors.

Here, we investigated the binding characteristics of [3H]N-(2,5-dimethoxybenzyl)-N-(5-fluoro-2-phenoxyphenyl)acetamide ([3H]DAA1106), a potent and selective ligand for peripheral benzodiazepine receptors, in mitochondrial fractions of the rat brain. [3H]DAA1106 bound to the mitochondrial fraction of the rat brain in a saturable manner. The dissociation constant (Kd) and maximal number of binding sites (Bmax) obtained from Scatchard plot analysis of the saturation curve of [3H]DAA1106 binding were 0.12 +/- 0.03 nM and 161.03 +/- 5.80 fmol/mg protein, respectively. [3H]DAA1106 binding to mitochondrial preparations of the rat cerebral cortex was inhibited by several peripheral benzodiapine receptor ligands, and DAA1106 was the most potent inhibitor in inhibiting [3H]DAA1106 binding among the peripheral benzodiazepine receptor ligands we tested. The binding of [3H]DAA1106 was not affected by several neurotransmitter-related compounds, including adrenoceptor, gamma-aminobutyric acid (GABA), dopamine, 5-hydroxytryptamine (5-HT), acetylcholine, histamine, glutamate and central benzodiazepine receptor ligands even at a concentration of 10 microM. In the cerebral cortex of rhesus monkeys, DAA1106 and 1-(2-chlorophenyl)-N-methyl-(1-methylpropyl)-3-isoquinoline carboxamide (PK11195) potently inhibited [3H]DAA1106 binding, while 7-chloro-5-(4-chlorophenyl)-1-methyl-1,3-dihydrobenzo[e][1,4]diazepin -2-one (Ro5-4864) did not. The highest [3H]DAA1106 binding was observed in the olfactory bulb, followed by the cerebellum. In autoradiographic studies, practically the same results were obtained, in that the highest binding of [3H]DAA1106 was in the olfactory bulb. Potent labeling was also noted in ventricular structures such as the choroid plexus. Thus, [3H]DAA1106 is a potent and selective ligand for peripheral benzodiazepine receptors and should prove useful for elucidating the physiological relevance of events mediated through peripheral benzodiazepine receptors.

Acetamides↗

PubMed1999

In vitro pharmacological profile of nonpeptide CRF1 receptor antagonists, CRA1000 and CRA1001.

We investigated pharmacological properties of CRA1000 (2-(N-(2-methylthio-4-isopropylphenyl)-N-ethylamino-4-(4-(3-fluoro phenyl)-1,2,3,6-tetrahydropyridin-1-yl)-6-methylpyrimidine) and CRA1001 (2-( N-(2-bromo-4-isopropylphenyl)-N-ethylamino-4-(4-(3-fluorophenyl)-1 ,2,3,6-tetrahydropyridin-1-yl)-6-methylpyrimidine), novel and selective antagonists for the corticotropin-releasing factor1 (CRF1) receptor. Both CRA1000 and CRA1001 inhibited [125I]ovine CRF binding to membranes of COS-7 cells expressing the rat CRF1 receptor with IC50 values of 30 and 38 nM, respectively, without affecting [125I]sauvagine binding to membranes of COS-7 cells expressing the rat CRF2alpha receptor. CRF elicited intracellular cyclic AMP (cAMP) accumulation in AtT-20 cells which express the CRF1 receptor but not the CRF2 receptor, and COS-7 cells expressing CRF1 or CRF2alpha receptors. The CRF-induced cAMP accumulation was inhibited by both CRA1000 and CRA1001, concentration-dependently, in AtT-20 cells and COS-7 cells expressing the CRF1 receptor, while these compounds did not attenuate the CRF response in COS-7 cells expressing the CRF2alpha receptor. CRF increased adrenocorticotropin (ACTH) secretion from AtT-20 cells, and CRA1000 and CRA1001 inhibited CRF-induced ACTH secretion, concentration-dependently, as did other CRF1 receptor antagonists. These results show that both CRA1000 and CRA1001 are potent and selective CRF1 receptor antagonists.

Adrenocorticotropic Hormone↗

PubMed1999

Design, synthesis, structure-activity relationships, and biological characterization of novel arylalkoxyphenylalkylamine sigma ligands as potential antipsychotic drugs.

sigma Receptor antagonists may be effective antipsychotic drugs that do not induce motor side effects caused by ingestion of classical drugs such as haloperidol. We obtained evidence that 1-(2-dipropylaminoethyl)-4-methoxy-6H-dibenzo[b,d]pyran hydrochloride 2a had selective affinity for sigma receptor over dopamine D2 receptor. This compound was designed to eliminate two bonds of apomorphine 1 to produce structural flexibility for the nitrogen atom and to bridge two benzene rings with a -CH2O- bond to maintain the planar structure. In light of the evidence, N, N-dipropyl-2-(4-methoxy-3-benzyloxylphenyl)ethylamine hydrochloride 10b was designed. Since compound 10b had eliminated a biphenyl bond of 6H-dibenzo[b,d]pyran derivative 2a, it might be more released from the rigid structure of apomorphine 1 than compound 2a. The chemical modification of compound 10b led to the discovery that N, N-dipropyl-2- [4-methoxy-3-(2-phenylethoxyl)phenyl]ethylamine hydrochloride 10g (NE- 100), the best compound among arylalkoxyphenylalkylamine derivatives 3, had a high and selective affinity for sigma receptor and had a potent activity in an animal model when the drug was given orally. We report here the design, synthesis, structure-activity relationships, and biological characterization of novel arylalkoxyphenylalkylamine derivatives 3.

Animals↗

PubMed1999

Cloning and characterization of a short variant of the corticotropin-releasing factor receptor subtype from rat amygdala.

We have identified and characterized a cDNA encoding a novel isoform of the corticotropin-releasing factor (CRF) receptor, referred to as CRF2alpha-tr, from the rat amygdala cDNA library. The nucleotide sequence of the cloned cDNA has a structure of an alternatively spliced form of the CRF2alpha receptor, which contains unspliced introns 6 and 7 in the message, and encodes a 236-amino-acid truncated protein that comprises three unique transmembrane domains. Northern blot analysis shows that the CRF2alpha-tr receptor is more strongly expressed in the rat amygdala, thalamus, and hypothalamus than the intact CRF2alpha receptor. Western blot analysis also reveals that the CRF2alpha-tr protein can be expressed in transfected COS-7 cells as well as CRF2alpha. Furthermore, this receptor binds rat/human CRF with almost the same low affinity (Kd = 12.7 nM) as the CRF2alpha and without accumulation of intracellular cAMP. Interestingly, it does not bind sauvagine or rat urocortin. These findings suggest that this truncated CRF receptor is the major isoform of CRF2alpha receptor mRNA transcripts in the amygdala and would mediate some functions of CRF pathways in the central nervous system.

Alternative Splicing↗

PubMed1999

Effects of targeted disruption of the mouse angiotensin II type 2 receptor gene on stress-induced hyperthermia.

1. We have previously reported that brain angiotensin II type 2 receptors (AT2) contribute to immunological stress-induced hyperthermia (fever) in rats. Now, in mice, we report the effect of AT2 gene disruption on the hyperthermia induced by immunological (interleukin-1 (IL-1) injection) and non-immunological (saline injection or cage switch) stress. 2. AT2-deficient and control mice both showed typical circadian rhythmicity in body temperature and physical activity. During the latter half of the dark period, AT2-deficient mice exhibited a lower body temperature than the controls. 3. By comparison with the controls, AT2-deficient mice exhibited: (i) a significantly smaller hyperthermia after intraperitoneal (i.p.) injection of IL-1beta; (ii) significantly greater increases in body temperature and physical activity after i. p. saline; and (iii) a significantly greater hyperthermia (but a similar increase in activity) during cage-switch stress. 4. These results suggest that AT2, presumably in the brain, plays important roles in stress-induced hyperthermia in mice.

Animals↗

PubMed1999

Anxiety-like behavior in mice lacking the angiotensin II type-2 receptor.

The main biological role of angiotensin II type 2 receptor (AT2) has not been established. We made use of targeted disruption of the mouse AT2 gene to examine the role of the AT2 receptor in the central nervous system (CNS). AT2-deficient mice displayed anxiety-like behavior compared with wild-type mice. However, AT2-deficient mice showed no depressant-like activity and no change in hexobarbital-induced sleeping time as compared with findings in wild-type mice. Both noradrenergic and corticotropin-releasing factor (CRF) neuronal systems appear to be involved in this anxiety-like behavior. Diazepam, captopril (angiotensin I converting enzyme inhibitor), prazosin (alpha1 antagonist) reversed the anxiety-like behavior in these AT2-deficient mice, whereas yohimbine (alpha2 antagonist), phenylephrine (alpha1 agonist), clonidine (alpha2 agonist), isoproterenol (beta1/beta2 agonist), propranolol (beta1/beta2 antagonist) and alpha-helical CRF9-41 (CRF receptor antagonist) has no apparent effects on anxiety-like behavior in AT2-deficient mice. In addition, concentrations of plasma adrenocorticotropic hormone (ACTH) and corticosterone in AT2-deficient mice did not differ from these in wild-type mice, hence, there are probably no endocrine abnormalities involving the hypothalamic-pituitary-adrenal axis (HPA). The amygdala appears to play an important role in many of the responses to fear and anxiety. The number of [3H]prazosin but not [125I]CRF binding sites in the amygdala was significantly reduced in AT2-deficient mice. These findings indicate that the noradrenergic system is involved in mediating the anxiety-like behavior in AT2-deficient mice.

Adrenocorticotropic Hormone↗

PubMed1999

Amino acid residues in the transmembrane domain of the type 1 sigma receptor critical for ligand binding.

The type 1 sigma receptor expressed in Xenopus oocytes showed binding abilities for the sigma-1 ligands, [3H](+)pentazocine and [3H]NE-100, with similar kinetic properties as observed in native tissue membranes. Amino acid substitutions (Ser99Ala, Tyr103Phe and di-Leu105,106di-Ala) in the transmembrane domain did not alter the expression levels of the type 1 sigma receptor as determined by immunoblot analysis using an anti-type 1 sigma receptor antiserum. By contrast, ligand binding was significantly suppressed by the substitutions. These findings provide evidence that the transmembrane domain of the type 1 sigma receptor plays a critical role in ligand binding of this receptor.

Amino Acids↗

PubMed1999

Reduction of depressive-like behavior in mice lacking angiotensinogen.

We made use of targeted disruption of the mouse angiotensinogen (ATN) gene to examine the functional role of the ATN in the central nervous system. Both male and female ATN-deficient mice displayed the reduction of depressive-like behavior in the behavioral despair swim tests and spontaneous locomotor activity diminished. However, both male and female ATN-deficient mice showed no anxiogenic-like or memory-deficit behavior and there was no change in the pain threshold. We propose that endogenous ATN in the central nervous system may regulate the depressant state in the brain.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1999

Functional properties of two bombesin-like peptide receptors revealed by the analysis of mice lacking neuromedin B receptor.

The neuromedin B-preferring receptor (NMB-R) is one of the members of the bombesin (BN)-like peptide receptor subfamily in mammals. Previously, we have generated and characterized mice with targeted disruption of the two other BN-like peptide receptors, bombesin receptor subtype-3 (BRS-3) and gastrin-releasing peptide-preferring receptor (GRP-R). Here we describe the generation and analysis of NMB-R-deficient mice to investigate how NMB-R differs from BRS-3 and GRP-R. Compensation for NMB-R deficiency by overexpression of GRP-R and/or BRS-3 was not detected. Although the hypothermic effect of NMB was reduced by 50% in NMB-R-deficient mice, the effect of GRP infusion was comparable to the wild-type mice. In contrast, fundic smooth muscle contraction on stimulation with NMB or GRP was normal in NMB-R-deficient mice. Administration of GRP but not NMB suppressed glucose intake in both normal and NMB-R-deficient mice. These results suggest that the NMB-R has an essential role in thermoregulation, but not for smooth muscle contraction of the fundus or for the suppression of feeding behavior. In addition, the behavioral phenotypes of GRP-R-deficient mice were not observed in NMB-R-deficient mice. These data show that the functions of NMB-R and GRP-R are distinct, with only partial overlap.

Animals↗

PubMed1999

Neuropharmacological profile of peripheral benzodiazepine receptor agonists, DAA1097 and DAA1106.

Receptor binding and behavioral profiles of N-(4-chloro-2-phenoxyphenyl)-N-(2-isopropoxybenzyl)acetamide (DAA1097) and N-(2,5-dimethoxybenzyl)-N-(5-fluoro-2-phenoxyphenyl)acetamide (DAA1106), novel, selective agonists for the peripheral benzodiazepine receptor (PBR) were examined. DAA1097 and DAA1106 inhibited [3H]PK 11195 binding to crude mitochondrial preparations of rat whole brain, with IC50 values of 0.92 and 0.28 nM. Likewise, DAA1097 and DAA1106 inhibited [3H]Ro 5-4864 binding to the same mitochondrial preparation, with IC50 values of 0.64 and 0.21 nM. In contrast, DAA1097 and DAA1106 did not inhibit [3H]-flunitrazepam, the central benzodiazepine receptor (CBR) ligand, binding to membranes of rat whole brain (IC50>10,000nM). Oral administration of DAA1097 and DAA1106 had anxiolytic effects in the mouse light/dark exploration test and in the rat elevated plus- maze test. Oral administration of DAA1106, diazepam and buspirone but not DAA1097 significantly increased sleeping time in hexobarbital-induced anesthesia in mice. The order of potency of potentiation of hexobarbital anesthesia was diazepam> buspirone> DAA1106> DAA1097. Oral administration of DAA1097 and DAA1106 but not diazepam and buspirone did not affect spontaneous locomotor activity in mice. These findings indicate that DAA1097 and DAA1106 are PBR selective ligands with potent anxiolytic-like properties, in laboratory animals.

Acetamides↗

PubMed1999

A selective dopamine D4 receptor antagonist, NRA0160: a preclinical neuropharmacological profile.

NRA0160, 5 - [2- ( 4- ( 3 - fluorobenzylidene) piperidin-1-yl) ethyl] - 4 -(4-fluorophenyl) thiazole-2-carboxamide, has a high affinity for human cloned dopamine D4.2, D4.4 and D4.7 receptors, with Ki values of 0.5, 0.9 and 2.7 nM, respectively. NRA0160 is over 20,000fold more potent at the dopamine D4.2 receptor compared with the human cloned dopamine D2L receptor. NRA0160 has negligible affinity for the human cloned dopamine D3 receptor (Ki=39 nM), rat serotonin (5-HT)2A receptors (Ki=180 nM) and rat alpha1 adrenoceptor (Ki=237 nM). NRA0160 and clozapine antagonized locomotor hyperactivity induced by methamphetamine (MAP) in mice. NRA0160 and clozapine antagonized MAP-induced stereotyped behavior in mice, although their effects did not exceed 50% inhibition, even at the highest dose given. NRA0160 and clozapine significantly induced catalepsy in rats, although their effects did not exceed 50% induction even at the highest dose given. NRA0160 and clozapine significantly reversed the disruption of prepulse inhibition (PPI) in rats produced by apomorphine. NRA0160 and clozapine significantly shortened the phencyclidine (PCP)-induced prolonged swimming latency in rats in a water maze task. These findings suggest that NRA0160 may have unique antipsychotic activities without the liability of motor side effects typical of classical antipsychotics.

Animals↗

PubMed1999

Effects of selective dopamine D4 receptor blockers, NRA0160 and L-745,870, on A9 and A10 dopamine neurons in rats.

Extracellular single-unit activities of dopamine neurons were recorded using chloral hydrate anaesthetized rats. We examined the reversal effects of the selective dopamine D4 receptor blockers, NRA0160 (2-Carbamoyl-4-(4-fluorophenyl)-5-[2-[4-(3-fluorobenzylidene) piperidin-1-yl] ethyl] thiazole) and L-745,870 (3-[[4-(4-chlorophenyl) piperazin-1-yl] methyl]-1H-pyrrolo [2,3-b] pyridine), on dopamine agonists induced inhibition of dopamine neural activity. The firing rates of the substantia nigra pars compacta (A9) and the ventral tegmental area (A10) dopamine neurons were inhibited by methamphetamine (MAP: 1 mg/kg, i.v.) and apomorphine (APO: 40 microg/kg, i.v). NRA0160 dose-dependently reversed the inhibitory effects of MAP and APO on both A9 and A10 dopamine neurons. NRA0160 was more potent in reversing the inhibitory effects of both MAP and APO on A10 than A9 dopamine neurons. L-745,870 failed to reverse the inhibition produced by MAP on A9 and A10 dopamine neurons, whereas L-745,870, at the highest dose used, significantly reversed APO-induced inhibition of A10 but not A9 dopamine neurons. These results suggest that NRA0160 has different electrophysiological profiles on dopaminergic neural activity compared to L-745,870 and may have atypical antipsychotic effects.

Animals↗

PubMed1999

In vivo receptor occupancy of NRA0045, a putative atypical antipsychotic, in rats.

We have previously reported that (R)-(+)-2-amino-4-(4-fluorophenyl)-5-[1-[4-(4-fluorophenyl)-4-oxobutyl]+ ++pyrrolidin-3-yl]thiazole (NRA0045) is a novel antipsychotic agent with affinities for dopamine D4, 5-hydroxytryptamine 2A (5-HT2A) and alpha1 receptors. In the present study, in vivo receptor occupancy of 5-HT2A, alpha1, dopamine D2 and D3 receptors by NRA0045 was assessed, based on in vivo and ex vivo receptor binding, and findings were compared to reference antipsychotic drugs (haloperidol, risperidone, clozapine). Intraperitoneal administration of haloperidol highly occupied the dopamine D2 receptor in the striatum and nucleus accumbens, and alpha1 adrenoceptors in the frontal cortex. Occupation of the 5-HT2A receptor in the frontal cortex and the dopamine D3 receptor in the nucleus accumbens and islands of Cajella was moderate. By contrast, atypical antipsychotics such as risperidone and clozapine dose-dependently occupied the 5-HT2A receptor in the frontal cortex, with moderate to negligible occupancy of the D2 receptor in the striatum and the nucleus accumbens. Clozapine and risperidone also occupied the alpha1 adrenoceptor in the frontal cortex, and clozapine did not occupy the dopamine D3 receptor. As seen with other atypical antipsychotics, intraperitoneal administration of NRA0045 dose-dependently occupied the 5-HT2A receptor and the alpha1 adrenoceptor in the frontal cortex, while it was without effect on dopamine D2 and D3 receptors in the striatum, nucleus accumbens and islands of Cajella. Thus, the strong occupancy of 5-HT2A and alpha1 receptors is involved in the pharmacological action of NRA0045.

Animals↗

PubMed1999

Effects of NRA0045, NRA0160, and NRA0215 on regional Fos-like immunoreactivity in the rat brain.

Pharmacological characteristics of NRA compounds, novel atypical antipsychotics, were compared with those of clozapine and haloperidol, in regard to modification of Fos-like immunoreactivity (FLI) in rats. (R)-(+)-2-Amino-4-(4-fluorophenyl)-5-[1-[4-(4-fluorophenyl)-4-oxobutyl] pyrrolidin-3-yl] thiazole (NRA0045) and 2-carbamoyl-4-phenyl-5-[2-[4-(4-fluorobenzylidene) piperidin-1-yl] ethyl] thiazole (NRA0215) have a high affinity for dopamine D4 receptors, serotonin2A receptors, and the alpha1 adrenoceptor. 2-Carbamoyl-4-(4-fluorophenyl)-5-[2-[4-(3-fluorobenzylidene) piperidin-1-yl] ethyl] thiazole (NRA0160) has a selective and high affinity for dopamine D4 receptors. NRA0045 and clozapine (10 and 30 mg/kg, IP) produced significant increases in FLI in both the nucleus accumbens (N. Acc.) and the medial prefrontal cortex (mPFC) but not in the dorsolateral striatum (DLS). In contrast, NRA0160 and NRA0215 (10 and 30 mg/kg, IP) significantly increased FLI in the mPFC but not in the N. Acc. and the DLS. Haloperidol (0.1 and 1 mg/kg, IP) significantly produced FLI in the N. Acc., the DLS, and the mPFC. These data indicate that the antagonistic effects of dopamine D4 receptors may contribute, at least in part, to the actions of NRA0045, NRA0160, and NRA0215 in the mPFC.

Animals↗

PubMed1999

Chemical modification of apomorphine to discover sigma ligands: 6H-dibenzo[b,d]pyran and carbazole analogues.

It seems that many sigma ligands have been designed from known sigma ligands. We focused on a difference in structural flexibility between haloperidol and apomorphine, and studied chemical modification of apomorphine, a compound with high affinity for dopamine D2 receptors but not for sigma receptors, for discovery of sigma ligands. The first modification yielded good results with 6H-dibenzo[b,d]pyran analogues with weak affinity for sigma receptors but not D2 receptors. Furthermore, carbazole analogues, compounds designed from 6H-dibenzo[b,d]pyran analogues, potentially acted at sigma receptors with high selectivity. This paper describes the design, synthesis and sigma/D2 selectivity of 6H-dibenzo[b,d]pyran and carbazole analogues.

Animals↗

PubMed1999

[Atypical antipsychotic profiles of sigma receptor ligands].

This is a review on the recent results of research on sigma-receptor antagonists. NE-100, a selective sigma1-receptor antagonist, shows improvement of abnormal behaviors and cognitive dysfunction induced by phencyclidine (PCP). However, NE-100 does not inhibit dopamine agonist-induced behaviors nor induces catalepsy. The mode of action of NE-100 is estimated to be the indirect modulation of the NMDA/PCP-receptor ion channel complex and the modulation of dopamine release from the dopaminergic nerve terminals. The recently reported MS-355/MS-377, which is also a selective sigma1-receptor antagonist, has a similar pharmacological profiles as NE-100, but in addition, MS-355/MS-377 inhibits methamphetamine-induced formation of reversal tolerance and also inhibits apomorphine-induced climbing behavior like dopamine D2-receptor antagonists. The report on clinical trial targeting schizophrenia shows results on rimcazole, remoxipride, BMY 14802, panamesine (EMD 57445) and SL 82.0715. Rimcazole was effective in the open study, but the double blind trial was discontinued due to seizure induction. Remoxipride showed efficacy different from those of dopamine D2-receptor antagonists (less extrapyramidal adverse effects), but the trial was discontinued due to occurrence of aplastic anemia. Panamesine and SL 82.0714 showed favorable efficacy in the open studies, but BMY 14802 showed no efficacy in clinical trials.

Animals↗

PubMed1999

Role of the angiotensin II type-2 receptor in the mouse central nervous system.

There are two known major angiotensin II receptor subtypes, type 1 (AT1) and type 2 (AT2), both of which are present in the brain. AT1 and AT2 receptors occur in characteristic distributions that are highly correlated with the distribution of angiotensin II-like immunoreactivity in nerve terminals. Acting through the AT1 receptor in the central nervous system, angiotensin II has effects on fluid and electrolyte homeostasis, neuroendocrine systems, autonomic pathways regulating cardiovascular function and behavior. While the role of the AT2 receptor in the brain is less well understood, recent knockout studies point to their involvement in behavioral and cardiovascular functions. We discuss here evidence regarding the function of the AT2 receptor in the brain, determined using mice lacking the AT2 receptor.

Angiotensin II↗

PubMed1999

[Management of mycobacteriosis in general hospital without isolation ward for tuberculosis patients. 2. The problems of management of the patients diagnosed pulmonary tuberculosis after admission to the respiratory ward of university hospital having no an isolation ward for the tuberculous patients].

The management of 28 patients, diagnosed pulmonary tuberculosis by bacteriological or pathologic findings after the administration to the Koshigaya Hospital of Dokkyo university school of Medicine from January 1994 through September 1997, which had no an isolation ward for tuberculosis patients was analyzed. The mean age of the patients was 50.6 +/- 16.7 (18-85), and the number of male and female patients was 22 and 6 respectively. The underlying diseases found in 10 patients were gastric cancer, breast cancer, osteochondrosarcoma, collagen disease, diabetes mellitus, liver cirrhosis, pneumoconiosis, and bronchial asthma. Two patients were complicated by a lung cancer. Six of 28 patients showed smear-positive and culture-positive specimens and 22 of 28 patients showed smear-negative and culture-positive specimens. The detection of mycobacterial DNA in the samples after amplification by the polymerase chain reaction (PCR) used in 15 patients and was positive for 7 of 15 patients. The pathological study of the specimens obtained by Transbronchial lung biopsy was performed for 14 patients. The pathological findings were compatible with tuberculosis in 7 of 14 patients. The chief complaints of the 11 patients admitted to the hospital with in 3 days after first visit, were fever in all patients and in 5 patients with pleural effusion. A few patients showed smear-negative and PCR positive specimens and complicated by lung cancer or other malignancy, were treated in non isolation ward in the particular case of emergency evacuation before admission, careful examination such as a tuberculin test, bacterial examination, and PCR of sputum should be performed in the patients suspected of having pulmonary tuberculosis. The patients isolating tubercule bacilli after administration should be transferred to the hospital with isolated ward for tuberculosis or isolated room in general hospital in the particular case of emergency evacuation with the greatest care.

Adolescent↗