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Biomedical subjects

K Inui

Publications and source records attributed to K Inui.

At least 217 records · Page 12Linked to original sources
PubMed1996

Surgical treatment for invasive thymoma, especially when the superior vena cava is invaded.

BACKGROUND: We analyzed the operative outcome of extensive surgery for invasive thymoma, especially in those with thymomas invading the superior vena cava, the left innominate vein, or both. METHODS: We treated 41 patients with invasive thymoma, including 34 stage III, 5 stage IVa, and 2 stage IVb thymomas. Thirty-eight patients received radiotherapy preoperatively or postoperatively. In 12 patients with invasion of the superior vena cava or innominate vein, we performed angioplasty, reconstruction, or both. RESULTS: The overall 5-year survival rate was 77% and the 10-year survival rate was 59%. In the stage III group, there was a significant difference between those with complete and those with incomplete resection. Ten of 12 patients who had angioplasty with or without reconstruction of the superior vena cava or innominate vein survived without recurrence of the tumors. CONCLUSION: Angioplasty and vascular reconstruction are recommended because successful treatment for invasive thymomas depends on complete resection of the tumors.

Adolescent↗
PubMed1996

A newly developed solution enhances thirty-hour preservation in a canine lung transplantation model.

Ischemia and reperfusion cause the production of oxygen free radicals. These damage grafts or disrupt normal vascular homeostatic mechanisms, with a parallel reduction in endothelial nitric oxide and adenosine 3',5'-cyclic monophosphate levels. We hypothesized that lung preservation failure may be related to these events. To improve lung preservation, we prepared a new ET-Kyoto solution, which contains N-acetylcysteine (a radical scavenger), nitroglycerin (to elevate the nitric oxide level), and dibutyryl adenosine 3',5'-cyclic monophosphate (to elevate the adenosine 3',5'-cyclic monophosphate level) and examined its efficacy in a canine single-lung transplantation model. Lungs were flushed with new ET-Kyoto solution (group I, n = 9), basal ET-Kyoto solution (group II, n = 6), basal ET-Kyoto solution plus ethanol and propylene glycol (solvents of nitroglycerin; group III, n = 6), or low-potassium dextran glucose solution (group IV, n = 6), and stored at 4 degrees C for 30 hours. After left single-lung transplantation, the right main bronchus and right pulmonary artery were ligated and the functions of the transplanted lung were assessed for 6 hours. Arterial oxygen tension was significantly higher in group I than in groups II, III, and IV (p < 0.05). Peak inspiratory pressure and wet-to-dry lung weight ratio were significantly lower in group I than in groups II and IV (p < 0.01). Histologic and ultrastructural studies showed better preservation in group I than in groups II, III, and IV. We conclude that the new ET-Kyoto solution provides enhanced 30-hour lung preservation.

Animals↗
PubMed1996

Split transplantation of the trachea: a new operative procedure for extended tracheal resection.

Before tracheal transplantation can be applied clinically, several problems must be solved: immunosuppression, blood supply to grafts, and reliable long-term preservation of grafts. We have conducted experiments on tracheal transplantation to solve these problems. In the present study, we tried a new operative procedure to accomplish reliable revascularization of transplanted tracheal grafts. It has been reported that transplantation of a 10-ring length of trachea is difficult even with omentopexy. Long tracheal allografts can be transplanted with use of direct revascularization, but this technique is extremely troublesome. Thus we developed a new operative procedure, "split tracheal transplantation," in which grafts are divided at the midportion and covered with omentum, after demonstrating that the blood supply to tracheal grafts can be reestablished around the suture lines. Two groups of dogs were used. In group A (control, n = 4), a 10-ring length of trachea was autotransplanted. The anastomotic sites and grafts were covered with omental pedicles. In group B (split tracheal transplantation, n = 10), tracheal grafts 10 rings long were autotransplanted. These grafts were divided at the midportion, a piece of omentum was inserted between the two halves, and the midportion was sutured. Grafts were observed regularly by bronchoscopy and examined histopathologically after the animals died or were killed. In some animals, microangiography of the bronchial circulation was done. In the control group, necrosis, stenosis, or malacia of the grafts was observed in three of the four animals. In the split transplantation group, all animals survived for at least 2 months, all grafts were incorporated, and none showed ischemia, stenosis, or malacia. Microscopic examination and microangiography revealed that neovascularization of the graft was promoted by omentum inserted at the midportion of the graft. Split transplantation of the trachea is an easy and reliable way to extend tracheal resection.

Anastomosis, Surgical↗
PubMed1996

Time trends and survival after operations for primary lung cancer from 1976 through 1990.

To assess the time trends and survivals after operations for primary lung cancer, the cases of 845 consecutive patients who underwent thoracotomy between 1976 and 1990 were retrospectively reviewed by groups corresponding to year of the operation (the early period was 1976 to 1980, n = 208; the middle period was 1981 to 1985, n = 291, and the late period was 1986 to 1990, n = 346). The 5-year survivals at the early, the middle, and the late periods were 31.5%, 39.0%, and 54.0%, respectively, with significant improvement particularly at the late period (p < 0.05 for the early period vs the middle period, p < 0.01 for the early or middle period vs the late period); the improvement was caused by increase in the ratio of patients with stage I disease (20.7% at the early period, 32.0% at the middle period, 44.2% at the late period), increase in the rates of complete tumor resection with lymph node dissection (57.2%, 68.0%, 74.3%, respectively), and decrease in the rates of operation-related death (3.8%, 3.4%, 0.9%, respectively). The postoperative prognosis of patients with stage II disease at the late period (5-year survival 74.8%) showed significant improvement compared with the other periods. Moreover, the prognosis of patients with stage IIIa, pN2 disease (5-year survival 41.5%) showed significant improvement, which was caused by the significant decrease in patients with pT3 N2 M0 disease and poor prognosis.

Adenocarcinoma↗
PubMed1996

Long-term cryopreservation can prevent rejection of canine tracheal allografts with preservation of graft viability.

We previously reported that cryopreservation of tracheas for 1 month was possible in a canine tracheal autotransplantation model with use of a preservative solution containing trehalose. Realizing that the allogenicity of many organs is decreased by freezing, we examined the possibility of immunosuppressant-free canine tracheal allotransplantation after long-term cryopreservation. Six to 10 rings of the trachea were removed from donor dogs (n = 12), immersed in the preservative solution, and cryopreserved in a deep freezer at -85 degrees C for 285 +/- 28 days (cryopreservation group). Five rings of the mediastinal trachea of recipient dogs were removed. The cryopreserved tracheas were thawed and transplanted to replace the excised mediastinal tracheas. In a control group (n = 6), the graft was preserved in Euro-Collins solution at 10 degrees C for 16 to 17 hours. Allotransplantation of tracheas was done as in the cryopreservation group. The anastomotic site and graft were covered with an omental pedicle in both groups. In the cryopreservation group, every animal, except one that was killed for pathologic examination, survived more than 2 months. All the grafts of this group were viable, and no stenosis or tracheomalacia was observed. In the control group, most of the animals died within 1 month of tracheal stenosis caused by rejection. These findings reveal that immunosuppressant-free canine tracheal allotransplantation was consistently possible after long-term cryopreservation of the graft in a preservative solution containing trehalose. This simple method could solve both donor shortage and immunosuppression problems.

Animals↗
PubMed1996

Extensive resection with selective cerebral perfusion for a lung cancer invading the aortic arch.

An extensive operation for lung cancer invading the aortic arch is reported. A 66-year-old man presented the recent onset of hoarseness. Chest computed tomography and magnetic resonance imaging demonstrated a tumor of the Botallo lymph node invading the aortic arch. Left pneumonectomy with combined resection of the aortic arch was performed with the use of brain-isolated cardiopulmonary bypass. The aortic arch was resected and replaced by an artificial graft. Pathological examination revealed a primary lesion of adenocarcinoma in the left upper lobe and contiguous lymph node involvement, pT4N2M0. He was discharged and followed as an outpatient, however he died of miswallowing 10 months later. Such an extensive operation may be of value in selected patients.

Adenocarcinoma↗
PubMed1996

Effect of cyclosporin analogues and FK506 on transcellular transport of daunorubicin and vinblastine via P-glycoprotein.

PURPOSE: P-glycoprotein-mediated transcellular transport of anticancer agents and the inhibitory effect of cyclosporin analogs and FK506 were investigated. METHODS: The transcellular transport of daunorubicin and vinblastine by monolayers of LLC-GA5-COL150 cells which overexpressed P-glycoprotein was measured in the presence and absence of cyclosporins or FK506. RESULTS: Cyclosporins and FK506 inhibited P-glycoprotein-mediated transport of daunorubicin and vinblastine in the order of cyclosporin D, dihydrocyclosporin D > cyclosporin A > FK506 > cyclosporin C, dihydrocyclosporin C. The intracellular accumulation of the anticancer agents was highly associated with the transporting function of P-glycoprotein. The inhibitory effect of cyclosporin D was concentration-dependent. The inhibitory effect of the modulators on P-glycoprotein was not correlated with the immunosuppressive activity, but was correlated with their lipophilicity. CONCLUSIONS: In the transcellular transport system, lipophilicity may be one of the determinants for the inhibitory effect of various multidrug resistance modulators on the P-glycoprotein-mediated transport.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Modulation of organic cation transport and lipid fluidity by benzyl alcohol in rat renal brush-border membranes.

PURPOSE: Organic cations are actively transported in renal brush-border membranes (BBM) by the H+/organic cation antiport system. In the present study, we investigated the relationship between membrane fluidity and organic cation transport in the BBM. METHODS: The effects of benzyl alcohol, a membrane fluidizing agent, on the organic cation tetraethylammonium (TEA) uptake were studied using renal BBM vesicles isolated from rat kidney. BBM fluidity was assessed by fluorescence polarization technique. RESULTS: H+ gradient-dependent uptake of TEA in BBM vesicles was inhibited by benzyl alcohol in a dose-dependent manner, with an apparent half inhibitory concentration of 18mM. The decrease in fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene in BBM, which represents the increase in membrane fluidity, was correlated with the decrease in TEA transport activity. The dissipation rate of H+ gradient, a driving force for organic cation transport in BBM, was increased by benzyl alcohol. In addition, H+ gradient-independent TEA-TEA exchange was also inhibited by benzyl alcohol. These findings indicate that benzyl alcohol inhibits the uptake of TEA by affecting the intrinsic activity of the organic cation transporter and the H+ gradient dissipation rate. CONCLUSIONS: The membrane fluidity should be an important determinant for organic cation transport in renal BBM.

Animals↗
PubMed1996

Molecular cloning and expression of cDNA for murine galactocerebrosidase and mutation analysis of the twitcher mouse, a model of Krabbe's disease.

The cDNA for a murine galactocerebrosidase was isolated from a murine testis cDNA library on the basis of its homology with the cDNA for human galactocerebrosidase and a PCR method was used to clone the 5' end. It has a 2,278-nucleotide sequence including a 2,004-nucleotide open reading frame, which encodes 668 amino acid residues. The identity between the human and murine amino acid sequences was very high, being calculated to be 84%. Sequencing of cDNA from liver of the twitcher mouse revealed a nonsense mutation at codon 339 (TGG-->TGA). The most abundant mRNA of the murine galactocerebrosidase gave a 3.6-kb band, which was not detected in twitcher mice. This suggests that the cDNA (2,278 bp) we characterized represents a minor species generated by an alternate poly(A) signal and that most of the mRNA has a much longer 3'-untranslated region. Genome analysis revealed that this mutation was homozygous in the twitcher and heterozygous in the carrier but was not present in normal mice. The normal mouse cDNA but not the mutant cDNA of the galactocerebrosidase transfected into COS1 cells gave rise to an increase in enzymatic activity. We concluded that this mutation results in the deficiency of galactocerebrosidase in the twitcher mouse.

Amino Acid Sequence↗
PubMed1996

Intercostal hemangioma.

Chest wall tumors are uncommon and there have been only a few reports of intercostal hemangioma during the past 20 years. We treated a 33-year-old man who presented with intercostal hemangioma. We resected tumor and surrounding muscles beyond the limits of the lesion without removing any bone or lung tissue. The patient is free of any recurrence 3 years after surgery.

Adult↗
PubMed1996

In-vivo clearance study of vancomycin in rats.

The renal handling of vancomycin in rats and the effects of various drugs (probenecid, cimetidine and quinidine) on urinary excretion of the antibiotic were investigated by in-vivo clearance. The vancomycin-to-inulin excretion ratio (ER) was greater than unity at various infusion rates of vancomycin. Quinidine, co-administered with vancomycin, significantly decreased the total, renal and net secretory clearance of the antibiotic. Cimetidine also decreased, though not significantly, the secretory clearance of vancomycin by about 20%, but probenecid did not. These results suggested that vancomycin is secreted in renal tubules in rats, and that quinidine decreases the total clearance of vancomycin partly by inhibiting its tubular secretion in the kidney.

Analysis of Variance↗
PubMed1996

A prejunctional mechanism in midbrain periaqueductal gray inhibition of vagal bradycardia in rats.

Stimulation of the dorsal part of the midbrain periaqueductal gray matter (dPAG) inhibits baroreflex vagal bradycardia (BVB) via a central mechanism. Here we report that the dPAG suppresses vagal bradycardia also by a peripheral mechanism. In chloralose-urethan-anesthetized, beta-blocked rats, the cervical vagus nerve was cut and the distal cut end was electrically stimulated to induce vagal bradycardia (VIB). Sustained electrical stimulation of the dPAG attenuated VIB in a duration-dependent manner but did not affect bradycardia induced by intravenous acetyl-choline (AIB). The dPAG inhibition of VIB was abolished by C1 transection. Intravenous norepinephrine (NE) reduced VIB but did not affect AIB. Both the dPAG and NE inhibitions of VIB were largely attenuated during intravenous prazosin, a selective alpha 1-receptor antagonist. In contrast, BVB provoked by aortic depressor nerve stimulation was remarkably inhibited by a shortly preceding dPAG stimulation, but this inhibition was not affected by C1 transection. Prazosin treatment did reduced the inhibition, but only moderately. In conclusion, the dPAG has a potential ability to suppress VIB by prejunctionally inhibiting acetylcholine release from cardiac vagus nerve terminals via alpha 1-receptors. However, dPAG stimulation first suppresses BVB largely at a central site, leaving a limited fraction of vagal outflow to be inhibited by a prejunctional mechanism operating with long latency.

Acetylcholine↗
PubMed1996

Regulation of p-aminohippurate transport by protein kinase C in OK kidney epithelial cells.

We studied the effect of phorbol 12-myristate 13-acetate (PMA), a phorbol ester which activates protein kinase C, on p-aminohippurate (PAH) transport in OK cells. PMA (10(-7) M) almost completely inhibited the transcellular transport of PAH across OK cell monolayers from the basal to the apical side, as well as the accumulation of PAH in the cells. The uptake of PAH across the basolateral membrane of OK cells was inhibited by PMA in a time-and dose-dependent fashion. Exposing the cells with other protein kinase C activators such as active phorbol esters and diacylglycerols also resulted in a significant inhibition of basolateral PAH uptake, but the inactive phorbol ester, 4 alpha-phorbol 12,13-didecanoate, had no effect. The inhibition of basolateral PAH uptake by PMA was blocked by staurosporine, an inhibitor of protein kinase C. Cycloheximide, actinomycin D, colchicine, and cytochalasin D did not affect the inhibitory effect of PMA on basolateral PAH uptake. These results suggested that the PAH transport system in OK cells is under the regulatory control of protein kinase C.

Animals↗
PubMed1996

The effect of alpha-linolenic acid-rich emulsion on fatty acid metabolism and leukotriene generation of the colon in a rat model with inflammatory bowel disease.

The purpose of this study was to investigate the efficacy of alpha-linolenic acid-rich perilla oil emulsion (POE) in a rat model with trinitrobenzenesulfonic acid (TNB)-induced inflammatory bowel disease. Three different isocaloric solutions, which are glucose solution (FF), soybean oil emulsion (SOE) and POE, were infused for 14 days after instillation of TNB. After infusion, total cholesterol and phospholipid concentration in the plasma in the POE group were significantly decreased compared with the FF and SOE groups. Arachidonic acid level in the colonic phospholipids was significantly decreased and eicosapentaenoic acid level was significantly increased in the POE group compared with the FF and SOE groups. Thickness, damage score and leukotriene B4 content in the colon in the POE group were the lowest among the infusion groups. These results suggest that alpha-linolenic acid suppresses the synthesis of leukotriene B4 in the colon by changing the fatty acid composition in the colonic phospholipids and that POE may be effective in the improvement of inflammation in the colon.

Animals↗
PubMed1996

The nutritional effect of a-linolenic acid-rich emulsion with total parenteral nutrition in a rat model with inflammatory bowel disease.

The purpose of this study was to investigate the nutritional effect of perilla oil emulsion (POE) in a rat model with inflammatory bowel disease (IBD) induced by 2,4,6-trinitrobenzenesulfonic acid. POE and soybean oil emulsion (SOE) were infused at 20% of nonprotein energy during 7 days' total parenteral nutrition (TPN). After infusion of test solutions, body weight gain and cumulative nitrogen balance in the POE group were significantly higher than those in the fat-free TPN (FF) group after infusion of test solutions. Moreover, those in the POE group were higher than those in the SOE group, but no significant difference was observed between the POE and SOE groups. In the POE group, total cholesterol and phospholipid concentration in the plasma was significantly decreased compared with the FF and SOE groups. Triglyceride concentration in the plasma did not significantly differ between the POE, SOE and FF groups. Plasma lipid peroxide concentration in the POE group was significantly lower than that in the SOE group, but it was not different from the FF group. In fatty acid composition in the plasma total lipids, linoleic acid in the POE and SOE groups and alpha-linolenic acid in the POE group were significantly increased compared with those in the FF group. Arachidonic acid (AA) in the POE and FF groups were significantly decreased compared with that in the SOE group. Otherwise, eicosapentaenoic acid (EPA) in the POE group was significantly increased compared with that in the SOE and FF groups. EPA/AA ratio in the POE group was significantly increased compared with the SOE group. The thickness and damage score of the colon were significantly depressed in the POE group compared with the SOE group. These results suggest that POE has a superior nutritional effect and improves inflammation in the IBD.

Animal Nutritional Physiological Phenomena↗
PubMed1996

Population pharmacokinetics of phenytoin in Japanese patients with epilepsy: analysis with a dose-dependent clearance model.

The population pharmacokinetic parameters of phenytoin were estimated using routine therapeutic drug monitoring data from 116 epileptic patients. The 531 serum concentration values at steady-state after repetitive oral administration were analyzed using a nonlinear mixed effects model (NONMEM) program designed for estimation of population pharmacokinetic parameters. A one-compartment model with dose-dependent clearance was used for the pharmacokinetic analysis of phenytoin. The volume of distribution (V) was estimated to be 1.231/kg in a typical 42-kg patient, assuming that the bioavailability of orally administered phenytoin is 100%. The maximal elimination rate (V(max)) and the Michaelis-Menten constant (K(m)) were 9.80 mg/d/kg and 9.19 micrograms/ml, respectively. The parameter of power function of weight to adjust V and V(max) was estimated to be 0.463. In addition, K(m) for phenytoin appeared to be 16% increased in patients receiving zonisamide concurrently. The population pharmacokinetic parameters of phenytoin will be useful for designing dosage regimens in epileptic patients.

Adolescent↗