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Biomedical subjects

Y Miyamoto

Publications and source records attributed to Y Miyamoto.

At least 361 records · Page 20Linked to original sources

Expression and protein kinase C-dependent regulation of peptide/H+ co-transport system in the Caco-2 human colon carcinoma cell line.

The characteristics of the transport of the dipeptide glycylsarcosine were studied in the human colon carcinoma cell line Caco-2 grown as a monolayer on impermeable plastic support. Transport of glycylsarcosine in these cells was found to be Na(+)-independent, but was stimulated by an inwardly directed H+ gradient. This H(+)-dependent transport of glycylsarcosine was inhibited by di- and tri-peptides and also by the beta-lactam antibiotic cephalexin, but was unaffected by the amino acids glycine and leucine. The transport system exhibited a Michaelis-Menten constant (Kt) of 1.1 +/- 0.1 mM for glycylsarcosine. The specific activity of the transport system in this cell line was found to be maximal when the cultures were confluent. Treatment of the cells with phorbol esters which activate protein kinase C resulted in a significant inhibition of the transport system. This inhibition was specific and could be blocked if treatment was done in the presence of staurosporine, an inhibitor of protein kinase C. Kinetic analysis revealed that the inhibition was associated with a decrease in the maximal velocity, the Kt remaining unaffected. The phorbol-ester-induced inhibition of the peptide-transport system was not prevented by co-treatment with cycloheximide, an inhibitor of cellular protein synthesis. In addition, there was no change in the intracellular pH following treatment with the phorbol ester, suggesting that the effect was not due to alterations in the transmembrane pH gradient. It is concluded that the peptide/H+ co-transport system, which is known to exist in the normal intestine, is expressed in Caco-2 cells and that the function of the transport system is under the regulatory control of protein kinase C.

Alkaloids↗

Relation of impaired left ventricular function in mitral regurgitation to left ventricular contractile state after mitral valve replacement.

To reevaluate the postoperative contractile state and survival, 34 patients (19 men and 15 women; average age 45 years, range 23 to 65) undergoing conventional mitral valve replacement between 1980 and 1990 were studied. There were 5 cardiac deaths (2 early and 3 late). Four of 5 deaths occurred in patients who had a preoperative left ventricular end-systolic volume index > 100 ml/m2. Sixteen patients with an end-systolic volume index < 100 ml/m2 (group I), and 5 with an index > 100 ml/m2 (group II) underwent repeat catheterization 8 months (range 4 to 17) after surgery. The ratio of end-systolic wall stress to end-systolic volume index increased significantly after surgery in group I, whereas it remained reduced in group II. The postoperative end-systolic wall stress/volume index ratio correlated significantly with the preoperative end-systolic volume index (p < 0.001). In the relation between end-systolic wall stress and ejection fraction, all patients in group II had values that were less than the 95% confidence limits for the normal relation. In conclusion, patients with a preoperative end-systolic volume index > 100 ml/m2 appeared to be at high risk of incurring irreversible depressed myocardial contractility, with a high postoperative mortality.

Adult↗

A new attempt to solve the scale-up problem for granulation using response surface methodology.

Scale-up from lab to production is always problematic for the development of pharmaceuticals. In granulation, an optimal formulation of binder solution determined in a lab scale is often different than that in a production scale. A new mathematical procedure to solve this scale-up problem is assessed. Granules were prepared in the two manufacturing scales (2- and 5-kg scale) by using a high-speed mixer granulator. In the manufacturing process, the binder solution plays an essential role in the formation of granules with desired physical properties, in close conformity with the manufacturing scale. A computerized optimizing technique based on a response surface methodology was developed to study the scale-up problem in the manufacturing of granules. For this purpose, a new mathematical function was introduced for the first time, which is namely an integrated optimization function. A universal optimal formulation unaffected by manufacturing scale could be obtained by minimizing the integrated optimization function. Predicted values such as yield, mean granule size, and uniformity of granule size agreed well with experimental ones on both scales. Furthermore, the optimized characteristics measured at the production scale coincided well with those obtained at laboratory scale, suggesting that this approach could be very useful in minimizing scale-up problems.

Drug Compounding↗

Treatment of tuberculous empyema with multiple fistulae by reexpansion of the affected lung and restoration of its function: report of a case.

We report herein the case of a patient in whom a calcified tuberculous empyema with multiple fistulae was successfully treated by a new surgical approach. Reexpansion of the affected lung which had calcified over 30 years was achieved by covering the multiple bronchial fistulae using the omentum without obliterating the empyema cavity. Although the patient presented with severe aspiration pneumonia, he made a complete recovery and is now leading a better quality of life than before. This new operative method is less invasive and can therefore be performed much more easily on critically ill patients than conventional methods.

Bronchial Fistula↗

One hundred and one cases of bronchoplasty for primary lung cancer.

The results of 101 consecutive bronchoplasties performed between 1979 and 1993, including 8 cases of pneumonectomy, 88 cases of lobectomy, 3 cases of segmentectomy, and 2 cases of bronchial resection, are herein reported. Squamous cell carcinoma was the most common disease (59%) followed by adenocarcinoma (30%) and other diseases (11%). Anastomosis was satisfactory in 96 cases. Among the five stenosed cases, local recurrence was found in two cases, and there were three benign strictures. Two of the three benign strictures were treated with bouginage. The pulmonary artery was concomitantly reconstructed in seven cases with satisfactory results. Preoperative chemoradiotherapy was performed in 15 advanced cases and was followed by acceptable surgical results. The 5-year survival rate, according to the postoperative staging of the 86 patients without induction therapy, was 86% in stage I (19 patients), 49% in stage II (21 patients), and 27% in stage IIIA (40 patients). The overall survival rate was 46% at 5 years. There were two indications for this procedure i.e., a positive resection margin in 59 cases and positive hilar nodes in 42 cases. Better survival was noted in patients with squamous cell carcinoma, stage I, and surgery was thus selected for a positive resection margin, and not for a positive node.

Bronchi↗

Hepatic encephalopathy due to congenital splenorenal shunts: report of a case.

A 76-year-old Japanese woman with hepatic encephalopathy was successfully treated for congenital splenorenal shunts by surgical intervention. The flow volume of the splenorenal shunts was 800 ml/min with a shunt pressure of 9.8 mmHg. The portal pressures before and after the shunt resection were 9 mmHg and 12 mmHg, respectively. The portal flows before and after the shunt resection were 230 ml/min and 470 ml/min, respectively. Therefore, both the hepatic sinusoid and the portal vein might provide good compliance for an increased portal flow volume load after shunt resection.

Aged↗

Participation of opioid receptor types on post-tetanic twitch inhibition in isolated guinea-pig ileal longitudinal muscle.

The participation of opioid receptor types in the inhibition of the twitch (0.1 Hz, 0.5 msec duration, maximum intensity) following high frequency stimulation (10 Hz, 0.5 msec duration, maximum intensity for 1 min) (post-tetanic twitch inhibition) was investigated in isolated guinea-pig ileal longitudinal muscle using highly selective mu, kappa and delta opioid receptor antagonists. The mu antagonist, beta-funaltrexamine (beta-FNA), produced a concentration-dependent twitch inhibition, which disappeared with thorough washing. The concentration-response curve of the twitch inhibition for morphine was shifted rightward about 10-20-fold by beta-FNA pre-exposure, whereas that for dynorphin 1-13 inhibition remained unchanged. However, after thorough washing of beta-FNA the twitch inhibition of morphine continued during the post-tetanic twitch inhibition for as long as it was tested. The post-tetanic twitch inhibition was partially antagonized by beta-FNA pretreatment and further antagonized by additional exposure to naloxone (NLX). In the presence of nor-binaltorphimine (nor-BNI), a kappa antagonist, which has no effect on the twitch inhibition of morphine, the concentration-response curve of the twitch inhibition of dynorphin 1-13 was shifted rightward approx 100-fold. The post-tetanic twitch inhibition was antagonized by nor-BNI, and no further antagonism was produced by NLX. (Allyl)2-Tyr-Aib-Aib-Phe-Leu (ICI 174,864), a delta antagonist, did not affect the post-tetanic twitch inhibition. These results suggest that both mu and kappa opioid receptors participate in post-tetanic twitch inhibition in isolated guinea-pig ileal myenteric plexus-longitudinal muscle (MPLM).

Amino Acid Sequence↗

Parietal pleural invasion of lung masses: evaluation with CT performed during deep inspiration and expiration.

PURPOSE: To determine whether respiratory phase shift of lung masses at computed tomography (CT) indicates the absence of parietal pleural invasion. MATERIALS AND METHODS: Helical CT was performed during deep inspiration and expiration in 17 patients with peripheral lung tumors in contact with the chest wall. Changes in the location of the tumor relative to a chest wall marker were noted. RESULTS: Six of 10 lesions in the middle or lower lobes showed substantial respiratory phase shift; all were proved at surgery not to have invaded the parietal pleura. Three of the 10 showed no respiratory phase shift and were found at surgery to have invaded the parietal pleura. CT findings for tumors in the upper lobe did not correlate with the surgical findings. CONCLUSION: The presence of respiratory phase shift is a reliable indicator of the lack of parietal pleural invasion for tumors in the middle or lower lobes.

Adult↗

Effect of some peptidase inhibitors on exogenous and endogenous opioid actions in guinea-pig ileum.

Met-enkephalin concentration-dependently and transiently inhibited the ileal twitch contraction and this inhibition gradually recovered with time. Bacitracin, phosphoramidon, thiorphan and captopril did not influence the twitch inhibition of met-enkephalin, but bestatin increased the twitch inhibitory potency of met-enkephalin and terminated it in a manner which almost paralleled that of untreated tissue. Transient inhibition of twitch contraction after tetanic stimulation (post-tetanic twitch inhibition) was obtained. Bestatin increased the potency of met-enkephalin and this was terminated within 2 min. Phosphoramidon tended to increase the potency and delayed the termination of post-tetanic twitch inhibition. Bacitracin, thiorphan and captopril did not influence either the potency or the termination of post-tetanic twitch inhibition. Morphine-induced twitch inhibition was not influenced by bacitracin, bestatin or phosphoramidon. These results suggest that bestatin-sensitive aminopeptidase and phosphoramidon-sensitive enkephalinase take part in post-tetanic twitch inhibition, acting in a different mode of action, and have an important role in the termination of the pharmacological action of endogenous opioids (post-tetanic twitch inhibition) in MPLM. This different mode of response of bestatin and phosphoramidon upon post-tetanic twitch inhibition may underlie that aminopeptidase is a more soluble enzyme and enkephalinase is membrane-bound in myenteric plexus-longitudinal muscle (MPLM).

Aminopeptidases↗

Effects of a mixture of peptidase inhibitors (amastatin, captopril and phosphoramidon) on Met-enkephalin-, beta-endorphin-, dynorphin-(1-13)- and electroacupuncture-induced antinociception in rats.

The effects of a mixture of three peptidase inhibitors (PIs), amastatin, captopril and phosphoramidon, on methionine-enkephalin (Met-enk)-, beta-endorphin (beta-end)-, dynorphin-(1-13) (Dyn)- and electroacupuncture (EA)-induced antinociception were compared in rats. EA was performed by passing electric pulses (3 Hz, 0.1-msec duration, for 45 min) through acupuncture needles inserted into the Hoku-point. The antinociceptive effect was estimated by the hind paw pressure test. The antinociceptive effects of Met-enk and beta-end injected i.c.v. or i.t. and of Dyn injected i.t. were clearly potentiated by the PIs pretreated by the same administration routes as used for the injection of opioid peptides. The antinociceptive effects of Met-enk, beta-end and Dyn injected i.c.v. were also potentiated significantly by i.t.-PIs. PIs injected into the periaqueductal gray (PAG) potentiated EA antinociception. However, the EA effect was not affected by i.t.-PIs and was rather attenuated by i.c.v.-PIs. These results suggest that: i) Met-enk hydrolyzing enzymes are involved in the degradation of not only Met-enk but also beta-end and Dyn in the rat central nervous system; ii) Met-enk and beta-end act on both supraspinal and spinal sites, while Dyn acts only on the spinal site; iii) EA antinociception is mediated by supraspinal Met-enk and/or beta-end; and iv) an anti-opiate peptide system may be activated by EA stimulation, being susceptible to Met-enk hydrolyzing enzymes.

Acupuncture Analgesia↗

Atypical bronchoplasty to lung cancer and benign bronchial disease.

Twenty-one cases of atypical bronchoplasty were selected from a series of 125 tracheobronchoplastic procedures by the same surgeon between 1979 and 1993 and were reviewed to assess the indications and technical problems. The procedures were classified as follows: Type A (3 cases) was anastomosis between the right main and lower bronchi with upper and middle lobe resection. Type B (4 cases) was anastomosis between the left main and upper segmental bronchi with resection of the lower lobe and lingula or between the left main bronchus and the basal bronchus with resection of the upper lobe and superior segment of the lower lobe. Type C (5 cases) was resection of the right lateral wall of the trachea with various types of lung resection. Type D (4 cases) was sleeve segmentectomy. Type E (2 cases) was bronchial reconstruction without lung resection. Type F (3 cases) was miscellaneous procedures. All these procedures except one achieved favorable results. It is emphasized that lung-preserving surgery must always be considered under strict observation using frozen section study, even if an unusual procedure is required. If lung tissue has to be resected, as little as possible should be removed.

Adult↗

Effect of work rate on cardiorespiratory response to rhythmic-static exercise.

Influence of work rate (30 and 30 rpm) on exercise hyperpnoea, respiratory entrainment and cardiovascular system was studied in 9 healthy men performing rhythmic-static exercise (RSE). Respiratory frequency (f), tidal volume (VT), minute ventilation (VE), heart rate (HR), stroke volume (SV), and cardiac output (Q) were continuously measured. RSE was performed in upright position on a special motor-driven cycloergometer with an intensity of 40% VO2max for 5 min. The subjects opposed the flywheel movement by pressing the pedal alternately with left and right leg. It was found that in both work rates respiratory frequency followed the rhythm of exercise. The increases in f (28v35 breaths/min. p < 0.05) were associated with decreased VT (1.3v1.0L, p < 0.05) but they did not influence VE which was 33 and 36 1/min (NS). Accelerations of f and VE were faster for 30 than 60 rpm reaching respective values of 2.70v0.75 breaths/min/s (p < 0.05), and 0.59v0.31 1/min/s (p < 0.05). Cardiac response and its kinetics were found to be similar for both exercise rhythms. It is concluded that breathing entrainment does not affect either ventilation or the cardiac response during the RSE exercise. Since changes in acceleration of ventilation were not accompanied by appropriate changes in cardiac output acceleration the cardiodynamic hypothesis of exercise hyperpnoea does not seem to be valid for rhythmic-static exercise.

Adult↗

[A successful use of VAS for bridge to heart transplantation after oversea transportation in a 18-year-old patient with dilated cardiomyopathy].

An 18-year-old boy with dilated cardiomyopathy developed a relatively rapid deterioration and went into severe congestive heart failure. After short-while use of percutaneous cardiopulmonary support system (PCPS) and IABP, LVAS was indicated because of persisting low cardiac output syndrome and deterioration of organ functions. An LVAS (TOYOBO) was implanted on June 26, 1992 in a fashion of left atrium to ascending aorta bypass. Satisfactory circulatory support (flow rates of 4-5 L/min) was achieved resulting in complete recovery of the organ functions. After two months of LVAS support, the patient was transported to U.S.A.. The LVAS system was working well without any problems during 17 hrs flight under low atmospheric pressure (0.8 atm) in the plane. The patient successfully underwent heart transplantation (HTx) at Texas Heart Institute after 119 days support of LVAS. The patient is doing well enjoying active life after HTx. This is the first case of successful bridge use of extracorporeal LVAS to HTx in Japan.

Adolescent↗

[A case of Churg-Strauss syndrome associated with severe leg pain and necrotizing skin lesions].

A 68-year-old woman with bronchial asthma and a history of drug hypersensitivity came to our hospital because of severe pain, swelling, and ecchymoses in the lower extremity. The eosinophil count was 53.5%, therefore Churg-Strauss syndrome was diagnosed and she was given prednisolone (PSL) (30 mg/day). A skin specimen taken the next day showed tissue eosinophilia, acute and subacute necrotizing vasculitis. Immunofluorescence staining showed IgG in the blood vessels. After one month of PSL, biopsy specimens of muscle fiber revealed atrophy of type IIb fibers, and myxomatous degeneration of neuron-fibers. Eosinophilia decreased rapidly after administration of PSL, but the necrotizing lesions of the skin, muscle, and nerve were so severe that she needed orthopedic shoes.

Aged↗

Na(+)-dependent glutamate transporter in human retinal pigment epithelial cells.

PURPOSE: To characterize glutamate uptake in the human retinal pigment epithelial (HRPE) cell line 165 and to determine the feasibility of using this cell line as an experimental model for glutamate transport studies. METHODS: Confluent monolayers of the HRPE cells cultured in 35-mm petri dishes were used to study glutamate uptake with regard to its ion dependence, substrate specificity, and kinetics. The radioactivity associated with the cells was measured by a liquid scintillation counter. RESULTS: Glutamate uptake was noticeably stimulated by the presence of Na+ in uptake buffer. Acidic amino acids (100 microM; L-glutamate, L-aspartate, D-aspartate, and L-cysteate) and glutamate transporter inhibitors (100 microM; dihydrokainic acid, DL-threo-beta- hydroxyaspartic acid, and L-trans-pyrrolidine-2,4-dicarboxlic acid) interacted with uptake of radiolabeled glutamate. The activity of glutamate uptake depends on Na+ concentration. Glutamate uptake in the presence of Na+ does not have anion dependence. The uptake of glutamate was enhanced by external acidic environment and inhibited by 0.5 mM DIDS: Glutamate receptor antagonists (100 microM; [+/-]-2-amino-4-phosphonobutyric acid and 6-cyano-7- nitroquinoxaline-2,3-dione) did not inhibit glutamate uptake. Kinetic analysis shows that this transporter consists of at least two saturable systems. CONCLUSIONS: The results of the present study demonstrate that a glutamate transporter is expressed in the HRPE cells. Its characteristics are similar to those of glutamate transporters observed in the RPE of laboratory animals. The human cell line 165 will be a useful tool for characterization of glutamate transport in the RPE. This study also provides clear evidence for the presence of a glutamate transporter in the human RPE.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

Expression of the c-met protooncogene in human hepatocellular carcinoma.

The c-met protooncogene is a growth factor receptor with tyrosine kinase activity. Recently the hepatocyte growth factor was identified as the ligand for this receptor. Because the hepatocyte growth factor is a most potent mitogen in hepatocytes, possible involvement of c-met expression in hepatocarcinogenesis is suspected. In this study, we examined c-met expression in 23 hepatocellular carcinoma cases by means of Northern-blot analysis and an immunohistochemical study. Northern-blot analysis revealed c-met mRNA expression in the tumors of 6 of 19 patients (31.6%); in the immunohistochemical study, c-met protein was detected in 16 of 23 patients (69.6%). With both methods, c-met was found to be overexpressed in hepatocellular carcinoma compared with the surrounding normal liver. Comprehensive analysis showed that c-met protein expression was correlated with poor-to-moderate differentiation of cancer cells (p < 0.05). Tumor proliferative activity of hepatocellular carcinoma was evaluated by means of Ki-67 labeling index. All cases with increased tumor proliferative activity showed c-met protein expression, although the elevation of proliferative activity in the c-met-positive group was not statistically significant. These data suggest that the overexpression of c-met plays an important role in the development of hepatocellular carcinoma.

Adult↗