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M Kitada

Publications and source records attributed to M Kitada.

At least 37 records · Page 2Linked to original sources

[Comparison of microwave coagulation using a new type electrode with radiofrequency ablation in the liver of living animals].

In the present study, we compared microwave coagulation using a new type of electrode, a teflon-coated electrode that was developed in order to increase the area of coagulation, with radiofrequency ablation using a Radionics Cool-tip electrode inserted into the pig liver. Two Landrace male pig were put under general anesthesia. A microwave electrode (insulated area: 6 mm, teflon-coated electrode 16 G) and a radiofreqency (RF) electrode (Cool-tip RF single electrode 17 G) were passed through the surface of the livers of the pig. A thermometer was placed 1 cm from the tip of the electrode in order to measure the changes in the temperature of the area surrounding the electrode. In this study, the microwave setting was 80 W, and the RF pulse was set automatically. The coagulated and ablated areas of the liver were measured after 2.5, 5, and 10 minutes of energy delivery (n = 4). The diameter of the coagulated area of the liver following 2.5, 5 and 10 minutes of microwave exposure was 23.5 +/- 4.8 mm, 29.5 +/- 5.2 mm and 32.5 +/- 6.4 mm, respectively. On the other hand, the diameter of the ablated area of the liver following 2.5, 5 and 10 minutes of RF exposure was 18.5 +/- 4.1 mm, 24 +/- 7.8 mm and 28 +/- 4.9 mm, respectively. The mean temperature of the liver 1 cm from the microwave and RF electrodes (measured time: 2 minutes) was 69.6 degrees C and 56.3 degrees C. respectively (n = 12). Thus, the temperature of the area surrounding the microwave electrode was significantly higher than the temperature of the area surrounding the RF electrode (p = 0.0065). The teflon-coated microwave electrode achieved superior results to the Radionics Cool-tip electrode with respect to the diameter of the coagulated area and the temperature of the area in which the electrode was inserted, at the specified times.

Animals↗

[A case of carcinosarcoma of the lung].

A 63-year-old man was admitted to our hospital because of cough and slight fever up. A tumor shadow in right S6 and obstructive pneumonia was detected by X-ray and CT. Bronchoscopic study showed that right B6 bronchous was occluded by the tumor and in which malignant cell (squamous cell carcinoma suspect) were detected. Therefore right middle and lower lobectomy was performed. Histological examination of the resected specimen showed that the tumor was composed of poorly differentiated squamous cell carcinoma and abnormal spindle cell component. Both components of the tumor were mixed each other in part. Immunohistologically, malignant cell of sarcomatous elements were positively stained by vimentin and actine, but was not found such as osteosarcoma or rabdomyosarcoma. He was diagnosed as so-called carcinosarcoma of the lung.

Carcinosarcoma↗

Simple method for determination of the active metabolite of the inotropic drug pimobendan in rat liver microsomes.

A rapid and sensitive high-performance liquid chromatographic method for quantitation of the O-demethylated active metabolite formed in a liver microsomal assay system has been developed. The metabolite was separated on an Inertsil ODS-2 column and quantitated by fluorescence detection (excitation at 338 nm, emission at 405 nm). The retention times for pimobendan and its metabolite were 5.6 and 2.8 min, respectively. The intra- and inter-assay relative standard deviations in the measurement of pimobendan O-demethylase activity at the substrate concentrations of 1 microM and 500 microM were 2.0%, 6.8%, 2.1% and 5.6%, respectively, and the limit of detection was 0.1 ng for the demethylated metabolite.

Animals↗

Species difference in enantioselectivity for the oxidation of propranolol by cytochrome P450 2D enzymes.

We examined and compared enantioselectivity in the oxidation of propranolol (PL) by liver microsomes from humans and Japanese monkeys (Macaca fuscata). PL was oxidized at the naphthalene ring to 4-hydroxypropranolol, 5-hydroxypropranolol and side chain N-desisopropylpropranolol by human liver microsomes with enantioselectivity of [R(+)>S(-)] in PL oxidation rates at substrate concentrations of 10 microM and 1 mM. In contrast, reversed enantioselectivity [R(+)<S(-)] in PL 5-hydroxylation and N-desalkylation rates at the same substrate concentrations was observed in monkey liver microsomes, although the selectivity was the same for PL 4-hydroxylation between the two species. All oxidation reactions of the PL enantiomers in human liver microsomes showed biphasic kinetics, i.e. the reactions could be expressed as the summation of a low-K(m) phase and a high-K(m) phase. Inhibition studies using antibodies and characterization of CYP2D6 enzymes expressed in insect cells or human lymphoblastoid cells indicated that the enantioselectivity of PL oxidation, especially the ring 4- and 5-hydroxylations reflected the properties of CYP2D6 in human liver microsomes. In monkey liver microsomes, all of the oxidation reactions of S(-)-PL showed biphasic kinetics, whereas ring 4- and 5-hydroxylations were monophasic and side chain N-desisopropylation was biphasic for R(+)-PL. Similarly, from the results of inhibition studies using antibodies and inhibitors of cytochrome P450 (P450), it appears that the reversed selectivity [R(+)<S(-)] of PL oxidation rates is catalyzed by CYP2D enzyme(s) in monkey liver at low substrate concentrations. These results indicate that different properties of P450s belonging to the 2D subfamily cause the reversed enantioselectivity between human and monkey liver microsomes.

Animals↗

Optimal therapeutic range for oral anticoagulants in Japanese patients with prosthetic heart valves: a preliminary report from a single institution using conversion from thrombotest to PT-INR.

The thrombotest (TT) technique has been widely used in Japan for monitoring oral anticoagulant therapy (OAT). The therapeutic range was originally recommended to be 10%-25%. However, the International Committee for Standardization in Hematology/International Committee on Thrombosis and Hemostasis (ICSH/ICTH) recommended using the international normalized ratio of prothrombin time (PT-INR) for monitoring OAT. It is necessarv to use a universal standard measure for monitoring OAT in accordance with the ICSH/ISTH recommendation. We simultaneously measured TT and PT in blood samples from 1,157 patients on long-term warfarin therapy, and studied the correlation between TT and PT-INR. An excellent linear correlation was obtained between TT-INR and PT-INR with the regression equation PT-INR = 1.0420 TT-INR - 0.0987 (r = 0.905, P < 0.001). We also examined the correlation between the incidence of thromboembolism in 170 patients receiving warfarin therapy after prosthetic valve replacement; 50.5% received concomitant antiplatelet therapy. Thromboembolism occurred in 9 of 170 patients during a mean follow-up period of 2.44 years. The average TT values in patients with and without thromboembolism were 26.4% (PT-INR: 1.53) and 21.1% (1.73), respectively (P < 0.01). The incidence of thromboembolism did not differ significantly between patients on warfarin alone (average TT: 22.2%) and those on warfarin and antiplatelet agent (average TT: 20.9%). Our results suggest that the incidence of thromboembolism is low in Japan despite a less intensive regimen having been adopted.

Administration, Oral↗

The Na+/H+ antiporter of alkaliphilic Bacillus sp.

The Na+/H+ antiporter, which appears to predominantly contribute to the alkaliphily of Bacillus halodurans C-125, was studied in an alkali-sensitive mutant of this strain and a transformant with restored alkaliphily. The alkali-sensitive mutant, strain 38154, which has lost the ability to grow above pH 9.5, was found to lack electrogenic Na+/H+ antiport activity driven by deltapsi (membrane potential, interior negative), and it showed defective regulation of intracellular pH under alkaline conditions. On the other hand, a transformant carrying a 2.0-kb DNA fragment from the parental genome that complemented this defect was able to maintain an intracellular pH lower than that of the external milieu, and it was found to have recovered the Na+/H+ antiport activity driven by deltapsi. Sequence analyses found that a 5.1-kb DNA region contained four open reading frames (ORF-1 to ORF-4). Direct sequencing of the corresponding region in mutant 38154 revealed a G-to-A substitution, which resulted in an amino acid substitution from Gly-393 to Arg in the putative ORF-1 product. It has been recently found that a region homologous to the DNA fragment responsible for the alkaliphily of strain C-125 exists in the genomes of Bacillus subtilis, Sinorhizobium (Rhizobium) meliloti, and Staphylococcus aureus. These homologues are present as a cluster of seven ORFs in each case. The shaA gene product of B. subtilis shows significant similarity to the ORF-1 product of strain C-125. Disruption of the shaA gene resulted in a decrease in Na+/H+ antiport activity, and growth of the shaA-disrupted strain was impaired when the external Na+ concentration was increased. We conclude that the shaA gene encodes a Na+/H+ antiporter, which plays an important role in extrusion of cytotoxic Na+.

Alkalies↗

Choroid plexus ependymal cells enhance neurite outgrowth from dorsal root ganglion neurons in vitro.

The epithelial cells of the choroid plexus are a continuation of the ventricular ependymal cells and are regarded as modified ependymal cells. The present study was carried out to determine the influence of choroid plexus ependymal cells (CPECs) on axonal growth in vitro. Choroid plexuses were dissected from the fourth ventricle of postnatal day-1-10 mice, mechanically dissociated, and plated in fibronectin-coated culture dishes. CPECs had spread into monolayers with few endothelial cells in 3-week cultures. Some macrophages were scattered on the monolayer of CPECs. Dorsal root ganglia (DRG) were excised from mouse fetuses of 14-day gestation, dissociated with trypsin and cocultured on the CPEC monolayers. For comparison, dissociated DRG neurons were cocultured on astrocyte monolayers or cultured on laminin-coated plates. After 4.5 h culturing, the cultures were fixed and immunohistochemically double-stained for neurites and CPECs using antibodies against beta-tubulin III and S-100 beta, respectively. It was demonstrated that neurons extended many long neurites with elaborate branching on the surface of S-100-stained CPECs. In contrast, DRG neurons cultured on the astrocytes and on the laminin-coated plates had much shorter primary neurites with fewer branches than those cultured on the CPECs. The total length of neurites including primary neurites and their branches, of a single DRG neuron was 285 +/- 14, 395 +/- 15 and 565 +/- 12 microM on the laminin-coated plates, on astrocytes and on CPECs, respectively. Scanning electron microscopy revealed extension of neurites with well-developed growth cones on the ependymal cells. These results suggest that CPECs have a great capacity to promote neurite outgrowth from DRG neurons in vitro.

Animals↗

Catalytic activity of three variants (Ile, Leu, and Thr) at amino acid residue 359 in human CYP2C9 gene and simultaneous detection using single-strand conformation polymorphism analysis.

This study evaluated the catalytic activity of three variants (Ile, Leu, and Thr) at codon 359 of CYP2C9 enzymes expressed in a yeast cDNA expression system, and then established single-strand conformation polymorphism (PCR-SSCP) analysis for simultaneous detection as a screening method. Diclofenac was used for the in vitro experiment, and its hydroxy metabolite (4'-hydroxydiclofenac) was measured by HPLC. To discuss the in vivo effect of the Thr359 variant on the pharmacokinetics of phenytoin, a case report is presented. The efficiency of the SSCP method was evaluated by analyzing DNA samples from a homozygote for Ile359 and a heterozygote for Leu359 or Thr359. To evaluate the interaction between the P450 level and reductase activity, two batches of the Thr359 variant with a different P450:reductase activity ratio (1:4.0 and 1:1.4) were used. The in vitro study revealed that recombinant Ile359, Leu359, and Thr359 (2 batches) possessed a mean Km of 2.0, 16.5 and (3.8 and 2.9) micromol and Vmax of 12.4, 17.9 and (4.4 and 5.1) nmol/min/nmol P450, respectively. Although the magnitude of the change in catalytic efficiency for the Thr359 variant was close to that of the Leu359 variant, the effect of the two variants on diclofenac 4'-hydroxylation appears to be different because Leu359 variant was associated with a high Km, and Thr359 with a low Vmax. No significant differences in the kinetic data were observed between the two Thr359 enzymes, suggesting that low reductase activity in the Thr359 enzyme was not a major determinant in the present in vitro experiment. Estimated pharmacokinetic parameters of phenytoin obtained by the Bayesian method in an epileptic patient who was a heterozygote carrier for Thr359 variant were: Km = 6.45 microg/mL, Vmax = 5.77 mg/kg/d, and Vmax/Km = 0.89 L/kg/day. The Vmax/Km value in this patient was similar to the population mean value (0.90 L/kg/day) in Japanese heterozygotes for the Leu359 variant. Results for PCR-SSCP were in complete agreement with those obtained using established methods. Thus, the PCR-SSCP approach is useful for identifying these three variants of the CYP2C9 gene.

Adult↗

Function of a principal Na(+)/H(+) antiporter, ShaA, is required for initiation of sporulation in Bacillus subtilis.

ShaA (sodium/hydrogen antiporter, previously termed YufT [or NtrA]), which is responsible for Na(+)/H(+) antiporter activity, is considered to be the major Na(+) excretion system in Bacillus subtilis. We found that a shaA-disrupted mutant of B. subtilis shows impaired sporulation but normal vegetative growth when the external Na(+) concentration was increased in a low range. In the shaA mutant, sigma(H)-dependent expression of spo0A (P(S)) and spoVG at an early stage of sporulation was sensitive to external NaCl. The level of sigma(H) protein was reduced by the addition of NaCl, while the expression of spo0H, which encodes sigma(H), was little affected, indicating that posttranscriptional control of sigma(H) rather than spo0H transcription is affected by the addition of NaCl in the shaA mutant. Since this mutant is considered to have a diminished ability to maintain a low internal Na(+) concentration, an increased level of internal Na(+) may affect posttranscriptional control of sigma(H). Bypassing the phosphorelay by introducing the sof-1 mutation into this mutant did not restore spo0A (P(S)) expression, suggesting that disruption of shaA affects sigma(H) accumulation, but does not interfere with the phosphorylation and phosphotransfer reactions of the phosphorelay. These results suggest that ShaA plays a significant role at an early stage of sporulation and not only during vegetative growth. Our findings raise the possibility that fine control of cytoplasmic ion levels, including control of the internal Na(+) concentration, may be important for the progression of the sporulation process.

Bacillus subtilis↗

Interaction of drugs and Chinese herbs: pharmacokinetic changes of tolbutamide and diazepam caused by extract of Angelica dahurica.

The inhibitory effects of Angelica dahurica root extract on rat liver microsomal cytochrome P450 and drug-drug interactions were studied. The 2alpha- and 16alpha-hydroxylase activity of testosterone were most strongly inhibited, with 17.2% and 28-5% of their activity remaining, respectively, after oral administration of A. dahurica extract at a 1 g kg(-1) dose. 6beta-Hydroxylase activity was also inhibited, with 70% of its activity remaining, under the same conditions. In addition, treatment with the extract inhibited the metabolism of tolbutamide, nifedipine and bufuralol. These results showed that the extract inhibited the various isoforms of cytochrome P450 such as CYP2C, CYP3A and CYP2D1. The A. dahurica extract delayed elimination of tolbutamide after intravenous administration at a 10 mg kg(-1) dose to rats. Thus, the extract altered the liver intrinsic clearance. It had little effect, however, on the pharmacokinetic parameters of diazepam after intravenous administration at 10 mg kg(-1). Since diazepam showed high clearance, it underwent hepatic blood flow rate-limited metabolism. Therefore, the change of intrinsic clearance had little effect on hepatic clearance. However, the Cmax value after oral administration of diazepam with extract treatment was four times that with non-treatment. It was suggested that the first-pass effect was changed markedly by the extract. High-dose (1 g kg(-1)), but not low dose (0.3 g kg(-1)), administration of A. dahurica extract increased significantly the duration of rotarod disruption following intravenous administration of diazepam at 5 mg kg(-1). It was concluded that administration of A. dahurica extract has the potential to interfere with the metabolism, by liver cytochrome P450, of other drugs.

Administration, Oral↗

Undefined complications of parathyroid adenoma, parathyroid hyperplasia (primary hyperparathyroidism), thyroid follicular adenoma, thyroid papillary carcinoma, temporal astrocytoma, cerebellar meningioma, and hemangioma of external auditory meatus and oral papilloma.

A 59-year-old woman who had parathyroid adenoma, parathyroid hyperplasia, thyroid follicular adenoma, thyroid papillary carcinoma, astrocytoma of the right temporal lobe, cerebellar meningioma, capillary hemangioma of the left external auditory meatus and papilloma of the left upper gingiva is reported. Dynamic magnetic resonance imaging, computed tomography with contrast-enhancement and gastrofiberscopy revealed no remarkable findings in the pituitary, pancreas, adrenals, stomach or duodenum. Similar lesions were not found in any family members. Defect of the causative genes of multiple endocrine neoplasia types I and IIa, MENIN and RET was not detected. Further follow-up of this patient and family members is needed.

Adenoma↗

Identification of cytochrome P-450 isoform(s) responsible for the metabolism of pimobendan in human liver microsomes.

Pimobendan, 4, 5-dihydro-6-(2-(4-methoxyphenyl)-1H-benzimidazol-5-yl)-5-methyl-3( 2-H )-pyridazinone, is a new inotropic drug that augments Ca(2+) sensitivity and inhibits phosphodiesterase in cardiomyocytes. Pimobendan is well absorbed after oral administration and is metabolized in the liver to the O-demethyl metabolite, which is also active. This study was conducted to identify the cytochrome P-450 (CYP) isoform(s) responsible for the pimobendan O-demethylation in human liver microsomes. Pimobendan O-demethylase activity in human liver microsomes was significantly correlated with phenacetin O-deethylase activity. CYP1A2 antibody and specific inhibitors of CYP1A2 strongly inhibited the metabolism of pimobendan. CYP1A2 was the only one of 10 recombinant human CYP isoforms tested that catalyzed pimobendan O-demethylation at the substrate concentration of 1 microM. At a high substrate concentration (100 microM), recombinant CYP3A4 also catalyzed the reaction, and antibody to CYP3A4 partially inhibited the activity in human liver microsomes. The contribution of CYP1A2 to pimobendan O-demethylation in human liver microsomes varied in the range of 18 to 76%, whereas CYP3A4 accounted for less than 10%, as calculated using the relative activity factor method. We conclude that CYP1A2 is one of the major enzymes responsible for the O-demethylation of pimobendan and CYP3A may make a minor contribution at clinically relevant concentrations of the drug.

Adolescent↗

[Concomitant surgical treatment of valvular heart disease and coronary artery disease].

Concomitant valvular surgery and coronary artery bypass grafting were performed in 24 patients. Aortic valve replacement was carried out in 18 cases (A group), and mitral valve surgery (M group) was done in 6 cases (replacement in 3, and plasty in 3). There were two hospital deaths (11.1%) in the A group, and two (33.3%) in the M group of mitral valve replacement with Hancock II. One late death was observed in the M group. Aortic valve replacement with coronary revascularization resulted in satisfactory outcome. However, surgical management of concomitant mitral valve and coronary artery disease may need to be improved.

Aged↗

[Assessment of colorectal cancer patients exhibiting bilobular multiple hepatic metastases].

We assessed 23 patients who underwent surgical therapy of hepatectomy or microwave coagulation therapy (MCT) for bilobular multiple hepatic metastatic foci following curative resection of the primary lesion of colorectal cancer. Hepatectomy was the first surgical therapy for 10 patients, and 6 of them received combined intra-arterial chemotherapy. All 13 patients in the MCT group received intra-arterial chemotherapy, and 8 of them underwent combined hepatectomy. The two-year survival rate of the hepatectomy group, classified according to the first surgical therapy, was 40% against 52% in the MCT group. In comparison with the H2 (2-5 foci) patients in the hepatectomy group, there were 7 H2 patients in the MCT group, and the two-year survival rate of these 7 patients was 50%. No significant difference was observed between hepatectomy and the MCT as the first surgical therapy. The survival rates of the 5 patients who received treatment for recurrence after the first surgery and of the 18 patients without any recurrence treatment were 80% and 40%, respectively. No significant difference existed between the two groups, but a p value of 0.06 was noted. MCT was considered to be useful local therapy for cancer as the first therapy and as a therapy following recurrence.

Antineoplastic Agents↗

[A case report of intra-thoracic biliary fistula after percutaneous microwave coagulation therapy].

Among the locoregional therapies for hepatic malignant tumor, percutaneous microwave coagulation therapy (PMCT) has spread widely as a minimally invasive therapy. We performed PMCT on 40 patients under hepatic blood flow interruption with the aim of improving the radical treatment and expanding the coagulation area by single microwave delivery. A patient with a 2.5 cm lesion in S5 of the liver under PMCT transdiaphragmatically, but he developed a postoperative biliary fistula with consequent development of an intra-thoracic abscess through the diaphragm. Biliary fisture and liver abscess disappeared with open drainage under thoracotomy and laparotomy. Liver abscess has occasionally been reported as a PMCT complication, whereas there have been no reports, to the authors' knowledge, about intra-thoracic abscess as a PMCT complication, as in our case. It should be kept in mind that the penetration of the diaphragm as a route for PMCT may result in a biliary fistula flowing into the thorax, leading to a very serious condition.

Abscess↗

[Transcatheter arterial chemo-embolization using degradable starch microspheres (DSM) markedly effective for post-hepatectomy intra-hepatic recurrence in a patient with cholangioma].

Transcatheter arterial chemo-embolization (TACE) using degradable starch microspheres (DSM) was performed for multiple recurrence after hepatectomy in a patient with cholangiocarcinoma. The patient was a 68-year-man. He received treatment for hepatitis type C starting in 1996 at a nearby hospital. In November 1997, an increased AFP level was noted and a CT scan of the abdomen revealed an abnormal shadow in the liver. On May 21, 1998, imaging results led to the diagnosis of cholangiocarcinoma or a mixed type of hepatocellular carcinoma with cholangioma. Hepatic S7 sub-sequential resection was performed. The lesion was found to be a tumor-forming type, measuring 2.2 x 2.0 cm in diameter, diagnosed histopathologically as cholangiocarcinoma, tw (-), but Stage III since a nodule suggesting intrahepatic metastasis was noted in the cut surface of the resected liver. CT scan after a month revealed multiple metastatic lesions in the liver. TACE was performed by administering 450 mg of DSM, 10 mg of MMC and 30 mg of FARM, given in three divided doses on October 30, 1998, and February 9, 1999, according to Seldinger's method. A CT scan on January 31, 2000 revealed nearly complete remission of the hepatic SOL. Accordingly, TACE was considered to be useful therapy in combination with DSM, MMC and FARM for intrahepatic recurrence of cholangiocarcinoma.

Aged↗

[Three long surviving patients with gastric cancer metastasizing to the liver under interdisciplinary therapy].

In 30 patients with gastric cancer metastasizing to the liver over the past 15 years at our hospital the primary foci in the stomach could be resected in a curative manner. The authors report herein three long surviving patients in this series. [Case 1] A 49-year-old male. Distal gastrectomy was performed in November 1984. Metastasis to the liver occurred in June 1986. The right lobe of the liver was resected in November 1987 after transcatheter arterial embolization (TAE). Although hepatic arterial infusion chemotherapy was conducted, the cancer metastasized to the whole body, and the patient died in December 1991. [Case 2] A 65-year-old female. Distal gastrectomy was performed in July 1994. The left hepatic lobe and segment 5 in the right lobe were resected in June 1995. Although TAE was performed six times starting in December 1996, the patient died of hepatic failure in July 1999. [Case 3] A 73-year-old male. This patient simultaneously received distal gastrectomy and extended resection of the posterior hepatic segments in September 1997. Cancer recurred in the remaining liver in July 1998. Although microwave coagulation therapy (MCT) and TAE were performed, the patient died of hepatic failure in January 2000. In these patients who survived for a long period, the primary focus was well-differentiated adenocarcinoma under sufficient local control with metastasis limited to the nearest regional lymph nodes (group 1 lymph nodes). The patients could undergo interdisciplinary therapy, including hepatectomy, MCT, TAE, and hepatic arterial infusion chemotherapy.

Adenocarcinoma↗

Analyses of a Bacillus subtilis homologue of the Na+/H+ antiporter gene which is important for pH homeostasis of alkaliphilic Bacillus sp. C-125.

Bacillus subtilis was revealed to have a homologous region to the DNA fragment responsible for alkaliphily of alkaliphilic Bacillus sp. C-125 on the genome, as reported previously [1]. The yufT gene on the B. subtilis genome showed a significant similarity with ORF1 of Bacillus sp. C-125, which is related to membrane potential (DeltaPsi)-driven Na+/H+ antiport activity and is important for pH homeostasis in an alkaline condition. Disruption of the yufT gene resulted in the decrease of Na+/H+ antiport activity, and the growth of the yufT disrupted strain was impaired with an increase in the external Na+ concentration. We conclude that the yufT gene encodes a Na+/H+ antiporter, which has a dominant role in the extrusion of cytotoxic Na+.

Bacillus subtilis↗