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R Inagaki

Publications and source records attributed to R Inagaki.

14 recordsLinked to original sources

Rapid acid extrusion response triggered by alpha(1) adrenoceptor in CHO cells.

1. Using a microphysiometer with synchronized valve switching, we investigated real-time acid extrusion from Chinese hamster ovary (CHO) cells in which human alpha(1) adrenoceptor (AR) is stably expressed, in response to noradrenaline (NA). 2. In the cells expressing alpha(1a) AR, the time course of extracellular acidification after stimulation had two phases; in the first phase it transiently reached a rate several times greater than the base rate with a peak at around 10 s, and in the second it increased to 2 times the base rate and reached a plateau in 2 min. Both phases showed a concentration-dependent increase of acidification rate in response to NA, but had distinct pEC(50) values; 5.6 for the transient phase and 7.2 for the steady phase. 3. In the cells expressing alpha(1b) AR, the transient phase was not detected but the steady phase was observed. The pEC(50) value was 7.1, although the magnitude of the response was much smaller than that with alpha(1a) AR. 4. Both 5-(N-ethyl-N-isopropyl)amiloride (EIPA) and HOE642 inhibited the acid extrusion response by either AR in a concentration-dependent manner. EIPA and HOE642 had high pIC(50) values (7.4 and 7.3, respectively) for inhibition of the transient phase response via alpha(1a) AR. In the inhibition of the steady phase response via alpha(1a) AR, both drugs revealed the presence of two components in the response; one had high pIC(50) values (8.1 and 8.2 for EIPA and HOE642, respectively) and the other had low pIC(50) values (5.6 and 6.0, respectively). In contrast, the steady phase response via alpha(1b) AR was inhibited by EIPA and HOE642 with low pIC(50) values (5.3 and 5.9, respectively). 5. As Ca2+ was depleted, the alpha(1a) AR-induced transient phase disappeared, while the steady phase was not affected. 6. These results suggest that alpha(1a) AR drives two acid extrusion systems in CHO cells upon stimulation; one elicits the transient response, which is largely mediated by an EIPA/HOE642-sensitive and Ca(2+)-dependent Na(+)-H(+) exchanger (NHE), presumably NHE1, and the other induces the steady acid extrusion that is mediated by NHE1 and another NHE which has low sensitivity to both EIPA and HOE642. alpha(1b) AR drives only the steady phase acid extrusion response, which is mainly mediated by NHEs other than NHE1.

Acids↗

Anticancer drugs inhibit induction of NO synthase in rat in vivo.

Nitric oxide (NO), synthesized by inducible NO synthase (iNOS) in immunoreactive cells, plays important roles in their activities such as bactericidal and tumoricidal functions. We examined the distribution of iNOS and evaluated the effects of anticancer drugs, 4'-epi-doxorubicin (EPI-DXR) and mitomycin C (MMC), on iNOS induction by lipopolysaccharide in rats. Ascites cells and bone marrow showed the highest induction of iNOS in the tested organs. Administration of EPI-DXR to rats strongly inhibited iNOS induction in lung, ascites, and bone marrow, but only slightly in liver and spleen. MMC administration inhibited the induction in the most immune reactive organs.

Animals↗

Microphysiometric analysis of human alpha1a-adrenoceptor expressed in Chinese hamster ovary cells.

1. The human recombinant alpha1a-adrenoceptor (AR) has been stably expressed in Chinese hamster ovary cells. Four stable clones, aH4, aH5, aH6 and aH7, expressing 30, 370, 940 and 2900 fmol AR mg(-1) protein, respectively, have been employed to characterize this AR subtype using radioligand binding and microphysiometry to measure extracellular acidification rates. 2. Noradrenaline (NA) gave concentration-dependent responses in microphysiometry with increasing extracellular acidification rates. The potency of NA increased as the receptor density increased; pEC50 values of NA for the clones aH4, aH5, aH6 and aH7 were 6.9, 7.5, 7.8 and 8.1, respectively. This increase of potency according to receptor density indicates the presence of spare receptor for NA. Methoxamine, phenylephrine, oxymetazoline and clonidine also gave concentration-dependent responses with various intrinsic activities. 3. Antagonists shifted concentration-response curves for NA rightward in a concentration-dependent manner. Schild analysis revealed that the affinity profile of this AR subtype to antagonists in the clone aH7 had a typical pattern for the alpha1a-AR; high affinity for prazosin and WB 4101, and low affinity for BMY7378 (pA2=9.5, 9.8 and 7.3, respectively). This profile is similar in the case of the clone aH4. These affinities were in good agreement with those obtained in binding experiments. 4. These results have demonstrated that (1) classical receptor theory can be applied in microphysiometry, and (2) microphysiometry is a useful tool to investigate the pharmacological characterization of alpha1a-AR.

Adrenergic alpha-Antagonists↗

[Two-phase responses of acid expulsion triggered by alpha-1a adrenoceptor in CHO cell].

Using microphysiometer, we have investigated acid expulsion from CHO cells expressing human alpha-1a adrenoceptor. Time course of extracellular acidification rate after noradrenaline stimulation had two phases; one with a peak within 10 s reached several folds of base rate, and another increased gradually to two folds of base rate and reached plateau around two min. Both phases showed concentration-dependent increase of acidification rates in response to noradrenaline but had distinct pEC50 values; 6.0 for rapid phase and 6.6 for late phase. Amiloride and its analogs inhibited both phases entirely, suggesting that Na/H exchanger mainly mediated these acid expulsion responses. Elimination of Ca by BAPTA/EGTA treatment resulted in extensive reductions of the rapid phase response but small decrease of the late phase response. Several Ca channel blockers, Ni and LOE908 also suppressed the rapid phase while nifedipine, verapamil, SKF96365 and omega-conotoxin GIVA did not. Repeated stimulation with noradrenaline enhanced inhibitory effect of blockers. These results indicate that Ca is one of the elements in the rapid phase but not in the late phase of acid expulsion from CHO cells in response to alpha-1 adrenoceptor stimulation and suggest that Ca from both intracellular storage and some type of Ca channel dominantly participates in the rapid phase.

Acetamides↗

Persistent release of noradrenaline caused by anticancer drug 4'-epidoxorubicin in rat tail artery in vitro.

Anthracycline derivatives including 4'-epidoxorubicin are known to cause cardiovascular side effects. In this study we examined the effects of 4'-epidoxorubicin on sympathetic nerves of rat tail artery in vitro. Treatment with 4'-epidoxorubicin at concentrations higher than 10 microM gradually increased the resting tension of the arterial strips, an effect which was greatly enhanced by subsequent addition of 10 microM cocaine. This increase of the resting tension by 4'-epidoxorubicin was prevented by prazosin, suppressed in the arterial strips of reserpine-pretreated rats, and reduced by superoxide dismutase. However, tetrodotoxin and histamine receptor antagonists (diphenhydramine and cimetidine) failed to influence it. The contractile response to electrical sympathetic stimulation was slightly attenuated by 30 microM 4'-epidoxorubicin. 4'-epidoxorubicin did not shift the concentration-response curve for noradrenaline. In the superfusion experiments, the basal release of noradrenaline was increased approximately five-fold by 30 microM 4'-epidoxorubicin, and this increase was not inhibited by 0.1 microM prazosin, 0.5 microM tetrodotoxin, 10 microM cocaine or Ca2+-free medium. Noradrenaline release evoked by electrical stimulation was gradually suppressed by 30 microM 4'-epidoxorubicin treatment. These results suggest that 4'-epidoxorubicin directly acts on the sympathetic nerve to cause persistent release of noradrenaline in rat tail artery.

Adrenergic alpha-Antagonists↗

CT-guided biopsy of pulmonary nodules less than 3 cm: usefulness of the spring-operated core biopsy needle and frozen-section pathologic diagnosis.

OBJECTIVE: The purpose of this study was to improve the diagnostic accuracy of CT-guided biopsy of small lung nodules with the aid of frozen-section histopathologic diagnosis. SUBJECTS AND METHODS: Since 1993, we have evaluated 52 lung nodules smaller than 3 cm with CT-guided transthoracic biopsy. Thirty-five lesions were malignant and 17 were benign. Biopsy always started with a 20-gauge spring-operated core biopsy needle. Tissue samples were sent to the pathology laboratory immediately after biopsy for histopathologic diagnosis of the frozen sections. RESULTS: In 47 (90%) of 52 lesions, sufficient material for histologic diagnosis was obtained, including 34 (97%) of 35 malignant lesions and 13 (76%) of 17 benign lesions. In the 13 benign lesions for which histologic sampling was successful, a specific diagnosis of benign was made for 10 lesions (77%). In three cases, the sample was too small to make a histologic specimen, but cytologic study using the same sample led to the correct final diagnosis: one as malignant and two as benign. In the remaining two cases, biopsy was unsuccessful. The lesions were both 1 cm in size and were found to be benign on follow-up studies. CONCLUSION: CT-guided biopsy with the aid of frozen-section specimens using small-bore spring-operated core needles is a feasible technique with good results in the histologic diagnosis of small lung lesions.

Biopsy, Needle↗

Percutaneous transhepatic lithotripsy using a choledochoscope: long-term follow-up in 14 patients.

OBJECTIVE: The purpose of our study was to estimate the long-term prognosis of patients with bile duct stones who undergo electrohydraulic lithotripsy guided by choledochoscopy. SUBJECTS AND METHODS: Since 1987, at our institution, 14 patients with bile duct stones have been treated using percutaneous electrohydraulic lithotripsy guided by choledochoscopy. The procedure was performed 5-7 days after biliary drainage using a 5-mm choledochoscope placed through an 18- to 20-French sheath. All patients underwent follow-up CT, sonography, or both every 6-12 months after treatment. RESULTS: No complications occurred in the 14 patients who underwent treatment. During a mean follow-up period of 4.8 years (range, 2-9 years), two (14%) of the 14 patients developed recurrent common bile duct stones, and another two (14%) developed recurrent small intrahepatic stones; all patients remained asymptomatic. CONCLUSION: Percutaneous electrohydraulic lithotripsy can be safely performed using a 5-mm choledochoscope. Recurrent calculi may be seen in 28% of patients.

Aged↗

US-guided left-sided biliary drainage: nine-year experience.

PURPOSE: The feasibility and safety of left-sided biliary drainage with ultrasound (US) guidance were studied prospectively. MATERIALS AND METHODS: From July 1987 to July 1996, 208 consecutive patients underwent US-guided biliary drainage; all were evaluated for left-sided drainage. Drainage procedure was begun with puncture of the hepatic duct branch of the lateral segment of the left lobe when the branch was well visualized with US; otherwise, a right-sided approach was used. When the hepatic duct branch diameter was greater than 3 mm, puncture was performed with an 18-gauge needle; smaller branches were punctured with 21-gauge needles. RESULTS: In 147 (71%) patients, the left hepatic duct branch was well visualized with US, and the branch diameter was greater than 3 mm. In these patients, left-sided drainage with use of an 18-gauge needle was successful. In 26 (12%) patients, the left hepatic duct branch diameter was less than 3 mm, and drainage was initiated with a 21-gauge needle. In six (23%) of these 26 patients, left-sided drainage was unsuccessful, but five of these patients underwent successful US-guided drainage from the right hepatic duct branch. Two patients died of septic shock within 72 hours of completed drainage. Three patients experienced severe hemobilia. CONCLUSION: US-guided left-sided biliary drainage is a highly successful and safe method when the left hepatic duct branch diameter is greater than 3 mm.

Adolescent↗

[CT-guided biopsy of small lung nodules: usefulness of frozen-section pathologic diagnosis].

PURPOSE: To improve the diagnostic accuracy of computed tomography (CT)-guided biopsy of small lung nodules. MATERIALS AND METHODS: The usefulness of fine-needle core biopsy combined with immediate frozen-section diagnosis by pathologists was prospectively studied. Forty-six biopsies of small lung nodules (less than 3 cm in greatest diameter) were performed under CT guidance in 46 patients with 31 malignant and 15 benign processes. Initial biopsy was always attempted with a 20 or 21G histological needle; tissue samples were sent to the pathology department immediately after biopsy for pathologic diagnosis of the frozen sections. RESULTS: In 41 of 46 lesions (89.1%), sufficient material was obtained for diagnosis, permitting a correct final diagnosis. For malignancy, the sensitivity was 100%, whereas 81.8% of the benign lesions were diagnosed as specifically benign. Pneumothorax occurred in 41.3%. CONCLUSION: Histological diagnosis using frozen sections is a useful adjunct for CT-guided biopsy of the chest.

Adenocarcinoma↗

Nonlinear geometric warping of the mask image: a new method for reducing misregistration artifacts in digital subtraction angiography.

PURPOSE: Misregistration artifact is the major cause of image degradation in digital subtraction angiography (DSA). The purpose of this study was to evaluate the efficacy of a newly developed nonlinear geometric warping method to reduce misregistration artifact in DSA. METHODS: The processing of the images was carried out on a workstation with a fully automatic computerized program. After making differential images with a lapracian filter, 49 regions of interest (ROIs) were set in the image to be processed. Each ROI of the live image scanned the corresponding ROI of the mask image searching for the best position to match itself. Each pixel of the mask image was shifted individually following the data calculated from the shifts of the ROIs. Five radiologists compared the images produced by the conventional parallel shift technique and those processed with this new method in 16 series of cerebral DSA. RESULTS: In 14 of 16 series (88%), more radiologists judged the images processed with the new method to be better in quality. Small arteries near the skull base and veins of low density were clearly visualized in the images processed by the new method. CONCLUSION: This newly proposed method could be a simple and practical way to automatically reduce misregistration artifacts in DSA.

Angiography, Digital Subtraction↗

Radiation exposure to interventional radiologists during manual-injection digital subtraction angiography.

PURPOSE: We investigated the relationship between the amount of radiation exposure to the operator during table-side manual-injection angiographic procedures including digital subtraction angiography (DSA) and the operator's position, as well as a simple means to decrease radiation exposure. METHODS: Measurement of radiation exposure was carried out with thermoluminescent dosimeters (TLDs) in nine abdominal angiographies. In the first study, radiation exposure during DSA or during fluoroscopy was measured using TLDs placed near the angiographic table. In the second study, radiation exposure to the interventional radiologist was measured during manual-injection DSA at a near and a far operator position. RESULTS: Radiation exposure to the operator received during manual-injection DSA accounted for more than 90% of the total procedural exposure. The exposure to the operator markedly decreased at the far position compared with that at the near position when performing DSA. CONCLUSION: Manual-injection DSA is the largest contributor to radiation exposure received by the interventional radiologist, therefore, the use of a power injector is always recommended when performing DSA. When manual-injection DSA is necessary, radiologists should position themselves as far away from the patient as possible.

Angiography, Digital Subtraction↗