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K Inui

Publications and source records attributed to K Inui.

At least 253 records · Page 14Linked to original sources
PubMed1995

Simulation for population analysis of Michaelis-Menten elimination kinetics.

A simulation study was conducted to compare the cost and performance of various models for population analysis of the steady state pharmacokinetic data arising from a one-compartment model with Michaelis-Menten elimination. The usual Michaelis-Menten model (MM) and its variants provide no estimate of the volume of distribution, and generally give poor estimates of the maximal elimination rate and the Michaelis-Menten constant. The exact solution to the Michaelis-Menten differential equation (TRUE) requires a precise analysis method designed for estimation of population pharmacokinetic parameters (the first-order conditional estimation method) and also considerable computational time to estimate population mean parameters accurately. The one-compartment model with dose-dependent clearance (DDCL), in conjunction with the first-order conditional estimation or Laplacian method, ran approximately 20-fold faster than TRUE and gave accurate population mean parameters for a drug having a long biological half-life relative to the dosing interval. These findings suggest that the well-known MM and its variants should be used carefully for the analysis of blood concentrations of a drug with Michaelis-Menten elimination kinetics, and that TRUE, in conjunction with a precise analysis method, should be considered for estimating population pharmacokinetic parameters. In addition, DDCL is a promising alternative to TRUE with respect to computation time, when the dosing interval is short relative to the biological half-life of a drug.

Computer Simulation↗
PubMed1995

Focal cytochrome c oxidase deficiency in the brain and dorsal root ganglia in a case with mitochondrial encephalomyopathy (tRNA(Ile) 4269 mutation): histochemical, immunohistochemical, and ultrastructural study.

This is the first report with histochemical and immunohistochemical techniques of an autopsy case with mitochondrial encephalomyopathy caused by the mitochondrial tRNA(Ile) (nt4269) A to G mutation showing focal cytochrome c oxidase (COX) deficiency of neuronal cells. The 18-year-old male patient had cardiomyopathy, hearing disability, mental retardation, and seizures. Muscle biopsy exhibited many ragged-red fibers and focal COX deficiency. A postmortem histochemical study on frozen sections of the cerebral cortex, cerebellum, brain stem, and dorsal root ganglia revealed a loss of COX activity in some neuronal cells. On immunohistochemical staining, COX was also defective in a mosaic pattern. Focal COX deficiency may cause variable neurological manifestations in mitochondrial encephalomyopathies.

Adolescent↗
PubMed1995

Surgical treatment of small cell carcinoma of the lung: advantage of preoperative chemotherapy.

To assess the effect of chemotherapy on postoperative survival of patients with small cell lung carcinoma (SCLC), 46 patients who underwent surgery at Kyoto University between 1976 and 1991 were retrospectively reviewed. Seventeen patients (37.0%) received chemotherapy prior to as well as after surgery (neoadjuvant therapy group), 23 (50.5%) received chemotherapy only after surgery (adjuvant therapy group), and the other six received no chemotherapy (non-chemotherapy group). The 5-year survival rate of patients with c-Stage I or II disease in the neoadjuvant therapy group was as high as 80.0%, which seemed to be higher, although with no statistical significance, than that in the adjuvant therapy group (37.7%, P = 0.10). The 5-year survival rate of patients with c-Stage III (IIIa or IIIb) disease in the neoadjuvant therapy group, although not satisfactory (10.0%), was significantly higher than that in the adjuvant therapy group (0.0%, P = 0.04). No patients in the non-chemotherapy group had survived 5 years. Moreover, multivariate analysis showed that failure to employ preoperative chemotherapy was the strongest prognostic factor causing a poor prognosis (P = 0.01). On the other hand, eight (30.8%) out of 26 patients with c-Stage I or II disease postoperatively proved to have mediastinal lymph node involvement (pN2-3), and two (7.7%) proved to have intrapulmonary metastasis (PM). Considering the advantage of preoperative chemotherapy and the discrepancy between c- and p-stage, sufficient chemotherapy prior to surgery should be employed, and may realize a good prognosis in patients with c-Stage I or II disease. In contrast, patients with c-Stage III disease are not appropriate as candidates for surgery even if preoperative chemotherapy is performed.

Aged↗
PubMed1995

Expression of adult T-cell leukemia-derived factor in bronchoalveolar lavage cells after canine lung transplantation.

Lung transplantation is now an accepted therapeutic option for patients with end-stage lung disease, and an early diagnosis of rejection is essential in the management of these patients. Adult T-cell leukemia-derived factor (ADF), known as a human homolog of thioredoxin, has been shown to be induced by a variety of stresses. In this study we examined ADF expression in lung tissues and bronchoalveolar lavage cells after canine lung transplantation to determine whether it could be induced by allogenic stimulations and could be used to diagnose early rejection. Allotransplantations were performed in adult mongrel dogs, and immunosuppression was performed from the day of operation to the fifth postoperative day. No immunosuppressant was given from the sixth to the tenth postoperative days. Animals were put to death on the tenth postoperative day. Bronchoalveolar lavage was performed on the fifth and tenth postoperative days, and the lavage cells and lung tissues were examined immunohistochemically with anti-ADF antibody. The grades of rejection were as follows: grade 1 in two animals, grade 2 in three animals, and grade 3 in two animals. The percentages of ADF high-producer cells in bronchoalveolar lavage cells on the fifth and tenth postoperative days were 4.29% +/- 2.65% and 26.6% +/- 3.99%, respectively (p < 0.01). The percentages of ADF high-producer cells in normal healthy dogs and in those with grade 1, grade 2, and grade 3 rejection were 3.00% +/- 1.64%, 20.5% +/- 9.00%, 25.5% +/- 6.06%, and 34.5% +/- 6.50%, respectively. The percentage in each rejection group was significantly higher than that in normal healthy dogs (p < 0.05). These results suggest that examination of bronchoalveolar lavage cells with ADF staining may be useful in the early diagnosis of rejection.

Animals↗
PubMed1995

Reliable cryopreservation of trachea for one month in a new trehalose solution.

We previously reported that trehalose, a reduced disaccharide, was effective in the preservation of lungs. In this study, we investigated the possibility of prolonged cryopreservation of tracheas in a preservative solution containing trehalose. Five rings of cervical trachea were removed and immersed in the preservative solution. The harvested tracheas were then cryopreserved and stored in a deep freezer at -85 degrees C. One month later, five rings of mediastinal trachea were removed. The cryopreserved cervical tracheas were thawed and autotransplanted in place of the excised mediastinal trachea (n = 6). The anastomotic site and graft were then covered with an omental pedicle. All six animals survived for more than 6 months. All grafts survived without any evidence of atrophy or stenosis. Microscopic examination of the grafts showed that the integrity of the tracheal tissues was maintained. Our findings show that consistent cryopreservation of the trachea for 1 month is possible in a preservative solution containing trehalose.

Animals↗
PubMed1995

Improved 20-hour canine lung preservation with a new solution--ET-Kyoto solution.

We developed a new solution, ET-Kyoto (ET-K) solution, and compared its efficacy in 20 h lung preservation with that of Euro-Collins (EC) solution in a canine left lung transplantation model. The lungs were flushed with ET-K solution (ET-K group, n = 5), with EC solution plus prostaglandin E1 (PGE1) pretreatment (EC + PGE1 group, n = 6) or with EC solution (EC group, n = 6), and were stored at 4 degrees C for 20 h. The function of left lung grafts was assessed 40, 70, and 130 min after transplantation. The arterial pressure of oxygen (PaO2) in the ET-K group was significantly greater than in the EC + PGE1 group (p < 0.05 or p < 0.01) and in the EC group (p < 0.01). The peak inspiratory pressure and wet to dry weight ratio in the ET-K group were significantly lower than in the EC + PGE1 group and in the EC group (p < 0.05 or p < 0.01). Pulmonary vascular resistance in the ET-K group 130 min after reperfusion was significantly lower than in the EC group (p < 0.05). All the transplanted lungs in the EC + PGE1 group and the EC group showed histological evidence of pulmonary edema, whereas all in the ET-K group showed no signs of edema. We concluded that ET-K solution is superior to EC solution with or without PGE1 pretreatment in 20 h canine lung preservation.

Animals↗
PubMed1995

Transport characteristics of ceftibuten, a new cephaloporin antibiotic, via the apical H+/dipeptide cotransport system in human intestinal cell line Caco-2: regulation by cell growth.

PURPOSE: The intestinal epithelial cell line Caco-2 possesses the H+/dipeptide cotransport system responsible for uptake of oral cephalosporins. In this study, the transport characteristics of ceftibuten were examined from the viewpoint of cell growth in the Caco-2 cells. METHODS: The uptake of cephalosporins by Caco-2 cell monolayers grown on plastic dishes was measured and analyzed kinetically. RESULTS: The uptake of ceftibuten was increased by lowering pH of the incubation medium and was inhibited by excess dipeptide. The transport activity of ceftibuten was dependent on the duration of analysis revealed that the development of ceftibuten uptake was due to not only a decrease in Km but also to an increase in Vmax value. CONCLUSIONS: The uptake of ceftibuten is mediated by the apical H+/dipeptide cotransport system which is regulated by cell growth and/or differentiation in the Caco-2 cells.

Aminopeptidases↗
PubMed1995

Endothelin-1 and endothelin B type receptor are induced in mesangial proliferative nephritis in the rat.

We studied whether endothelin-1 (ET-1) and its receptor subtypes (ETAR, endothelin A type receptor; and ETBR, B type receptor) were up-regulated in the glomerulus of a rat model of mesangial proliferative glomerulonephritis induced by anti-thymocyte serum (anti-Thy-1 GN). A marked increase in preproET-1 mRNA could be demonstrated in glomerular RNA 3 and six days after disease induction (4.1- and 4.9-fold vs. day 0, respectively), corresponding to the time of mesangial cell proliferation, to the time of macrophage infiltration into glomeruli, and also to the time of increase in glomerular PDGF B-chain mRNA expression. The localization of ET-1 protein in the mesangial area and along the inner aspect of the glomerular capillary wall was also demonstrated by immunohistochemistry from day 3 and maximal at day 6. The major source of the cells expressing ET-1 in glomeruli appeared to be mesangial cells, glomerular endothelial cells and monocyte/macrophages. Furthermore, both gene and protein expression of ET-1 were associated with increased urinary excretion of ET-1. There was no increase in the plasma ET-1 immunoreactivity. Glomerular expression of ETBR mRNA increased in anti-Thy-1 GN (1.5-fold vs. day 0 at day 3 after disease induction, 3.6-fold at day 6 and 2.7-fold at day 10), but there was minimal change in ETAR mRNA expression. These results suggest that preproET-1 mRNA, which is induced in anti-Thy-1 GN, is linked primarily with ETBR mRNA expression.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Endoscopic MRI: preliminary results of a new technique for visualization and staging of gastrointestinal tumors.

BACKGROUND AND STUDY AIMS: The principle of endoscopic ultrasonography--introducing the transducer of an external imaging method, such as ultrasonography, in combination with an endoscope into the gastrointestinal tract for higher-resolution imaging--has also been applied to magnetic resonance imaging (MRI). We report here on our preliminary experience with a new method of endoscopic MRI in the upper gastrointestinal tract. PATIENTS AND METHODS: Endoscopic MRI was performed in 32 patients with esophageal (n = 8) or gastric diseases (n = 24), mostly tumors (n = 26). Most cancers were at an advanced stage (T3/T4). A prototype MRI endoscope connected to a 1.5 tesla MRI scanner was used. The accuracy of endoscopic MRI in visualizing and staging gastrointestinal lesions was assessed. RESULTS: The normal gastrointestinal wall consisted of three layers, and tumors were visualized as having a low signal intensity on both T1- and T2-weighted sequences. Destruction of the wall layers was found to be characteristic of malignancy. Sufficient images were obtained in seven of eight esophageal cases (88%), but in only 14 of 24 gastric cases (58%). In patients in whom adequate visualization was achieved, the endoscopic MRI results of local and regional staging were consistent with surgical, histopathological, CT and/or EUS results in all six esophageal cancer cases and in 89% (T stage) and 56% (N stage) of the nine patients with gastric cancer. CONCLUSIONS: These preliminary results of endoscopic MRI are the first to be reported in the English literature. They show the potential of the method for local and regional staging, three-dimensional visualization of lesions being a potential advantage. Further technical improvements are expected.

Diagnosis, Differential↗
PubMed1995

Treatment of Pancoast tumors. Combined irradiation and radical resection.

Eighteen patients underwent combined preoperative irradiation and radical resection for a Pancoast tumor at the Department of Thoracic Surgery, Chest Disease Research Institute, Kyoto University between 1977 and 1993. Four patients were applied a full radiation dose of 50-70 Gy and fourteen patients were applied a reduced dose of 33-40 Gy preoperatively. Eleven of these fourteen were applied a supplemental dose postoperatively up to a total dose of at least 50 Gy. Fourteen lobectomies, three partial resections, and one pneumonectomy were performed with combined resection of chest wall or adjacent structures: rib in 14, vertebra in 4, brachiocephalic vein in 3, subclavian artery in 2, spinal nerve in 3, sympathetic truncus in 2, phrenic nerve in 2 cases. Chest walls were reconstructed with marlex mesh in 5 patients, and two subclavian arteries and one brachiocephalic vein were repaired with artificial grafts. In 13 patients complete resections were achieved, but in the other 5 only incomplete resections leaving residual tumor were achieved. Incomplete resections consisted of 4 positive stumps at the brachial plexus of the apex and one aortic involvement by a metastatic lymph node. There was one operative death. Median survival was 21.6 months and the 5-year-survival rate was 38.5% for all 18 patients. In the complete resection group 5-year-survival was 56.4%, but in the incomplete-resection group 0%, showing a significantly more favorable result for the complete resection group. It is considered that evidence of incomplete resection influences the prognosis and that particularly tumor invasion to the brachial plexus may serve as a limiting factor for surgery.

Adult↗
PubMed1995

Pulmonary metastasis of polymorphous low-grade adenocarcinoma of the minor salivary gland.

A surgical case of pulmonary metastases of polymorphous low-grade adenocarcinoma (PLGA) originating from the minor salivary gland in the soft palate in a 62-year-old woman is reported. PLGA has been to be a locally invasive carcinoma without distant metastases; thus our case is the first reported case with histologically-proven distant metastases to the lung. We emphasise that attention should be paid to distant metastases especially to the lung even in case of PLGA.

Adenocarcinoma↗
PubMed1995

Molecular defects in Krabbe disease.

Krabbe disease (globoid cell leukodystrophy) is an autosomal recessive neurodegenerative disorder that affects both the central and peripheral nervous systems due to an enzymatic defect of the galactocerebrosidase. In this study, molecular defects in Krabbe disease were investigated in 11 patients (seven Japanese and four non-Japanese) using cultured skin fibroblasts. A Japanese late infantile patient had a missense mutation of Pro at codon 302 to Ala and a non-Japanese patient had a missense mutation of Val at codon 550 to Gly. The reduced enzymatic activities expressed from the cDNAs with these missense mutations and from the previously reported nonsense mutation (E369X, Glu at codon 369 to stop codon) were confirmed. Genomic DNA analyses revealed that the P302A and E369X mutations were heterozygous and the V550G mutation was homozygous in these patients. A 12 base deletion with a 3 base insertion was found in three unrelated Japanese infantile patients, but not in 30 controls. The mutation was homozygous in two patients and heterozygous in one patient. We could not find any confirmed mutation in the coding region in the other six patients. These findings suggest that mutations in infantile and late infantile patients are relatively heterogeneous.

Amino Acid Sequence↗
PubMed1995

Attenuation of ischaemia reperfusion injury by human thioredoxin.

BACKGROUND: Active oxygen species are thought to play a part in ischaemia reperfusion injury. The ability of a novel agent, human thioredoxin (hTRX), to attenuate lung damage has been examined in a rat model of ischaemia reperfusion injury. METHODS: Twenty eight animals were studied. At thoracotomy the left main bronchus and the left main pulmonary artery were clamped for 75 minutes and the lung was then reperfused for 20 minutes. Phosphate buffered saline was administered intravenously to nine control animals and hTRX (30 micrograms/g body weight) was given intravenously to another group of nine animals. Two experiments were carried out. The first (Exp 1) was a time matched pair experiment (five treated, five controls), and the second (Exp 2) was performed under controlled conditions (four treated, four controls; temperature 25 degrees C, humidity 65%). In another 10 nonischaemic rats and those in Exp 1 biochemical measurements of lipid peroxide, superoxide dismutase, and glutathione peroxide levels were performed. RESULTS: In both experiments rats perfused with hTRX survived longer than controls. In Exp 1 the arterial oxygen tension (PaO2) on air in the hTRX group was higher at 20 minutes than at one minute after reperfusion. In Exp 2 PaO2 at 20 minutes was higher in the hTRX group than in the controls. Lipid peroxide, superoxide dismutase, and glutathione peroxide levels in the control group were higher than in the hTRX group and in the non-ischaemic groups. Histological examination showed less thickening and oedema of the alveolar walls in the hTRX group than in controls. CONCLUSIONS: These results suggest that hTRX is effective as a radical scavenger and can limit the extent of ischaemia reperfusion injury of the lungs of experimental animals.

Animals↗
PubMed1995

Local delivery of heparin inhibits neointimal hyperplasia in injured rabbit artery.

The efficacy of local delivery of an antithrombotic drug on neointimal hyperplasia was investigated in 17 rabbits. One rabbit iliac artery was injured by a balloon catheter as a control injured artery. The other iliac artery was also injured and treated by local delivery of 25 U/kg of heparin. One hour after the balloon injury, angioscopy demonstrated an occlusive or mural thrombus in all the controls, but few in the locally-treated arteries. Four weeks after balloon injury, the percent stenosis was 34 +/- 31% in the heparin treated group (n = 7, p < 0.005) vs control side 73 +/- 17%). Accumulation of FITC-labeled heparin at the injured site was confirmed by microscopy. The activated partial thromboplastin time and fibrinogen level did not change significantly. PDGF-B chain was prominent at the neointimal layer in all the controls, whereas it was less in the locally treated arteries. Thus local delivery of heparin can inhibit neointimal hyperplasia after balloon injury by reducing thrombus-related growth stimulation.

Angioscopy↗
PubMed1995

[A study of the relationship between nocturnal intragastric pH and sleep stages of peptic ulcer].

We studied the correlation of the gastric acid secretion and the depth of sleep at night with no medication in 32 cases (19 gastric ulcer, 6 duodenal ulcer patients and 7 healthy controls). Using Memory PH: Monitor intragastric pH values were consecutively measured without antiulcer drugs. The depth of sleep were monitored continuously by recording without any sleeping drugs. In healthy controls, the pH values of awake phase was significantly lower than that of sleep stage 1, 4 and rapid eye movement (REM) phases. The pH values of REM phases were significantly high rather than that of sleep stage 1 and 2 phases. In patients with gastric ulcer, the pH values of awake phases were significantly lower than that of sleep stage 1 and REM phases. The pH values of REM phases were significantly high rather than that of the other sleep stages. On the other hand, in patients with duodenal ulcer, the obvious changes of the pH values were not seen with sleep stages. The pH values of healthy controls and gastric patients were changed with sleep stages. But the pH of duodenal ulcer patients were not changed obviously. Therefore, it is suggested that the dysfunction of autonomous nervous system was influenced the nocturnal intragastric pH in the patients with duodenal ulcer and played one of the important role in the occurrence of duodenal ulcer.

Adult↗
PubMed1995

[Effects of combined aprotinin and prostagrandin E1 therapy on aortic arch replacement].

This study was undertaken to compare the effects of combined aprotinin and prostaglandin E1 therapy on aortic arch replacement. Twenty patients were divided into 2 groups with (group A; n = 10) or without (group B; n = 10) the treatment (200 KIU of aprotinin and 0.01-0.02 microgram/kg/min of prostaglandin E1 during cardiopulmonary bypass (CPB) and the first postoperative day. Preoperative evaluation of respiratory function and all parameters related to CPB procedure were revealed to be equal between the groups. Postoperative A-a DO2 and respiratory index (RI) as functional parameters of oxygenation capacity, dosage of dopamine were monitored at 0, 3, 6, 12, 18 and 24 hr after termination of CPB and at extubation period. Serum creatinine, platelet numbers and blood coagulation function (PT, APTT) were also assayed postoperatively. The recovery of respiratory and cardiac function were superior in group A with treatment, but renal and blood coagulation function showed no difference in the groups. We suggest the combined therapy with aprotinin and prostaglandin E1 for aortic arch replacement may emerge as a valuable treatment to save postoperative respiratory and cardiac function.

Alprostadil↗