Biomedical subjects

Tadashi Abe

Publications and source records attributed to Tadashi Abe.

16 recordsLinked to original sources

PubMed2006

Phase I and pharmacologic study of irinotecan and amrubicin in advanced non-small cell lung cancer.

PURPOSE: We conducted a Phase I trial of irinotecan (CPT-11), a topoisomerase I inhibitor, combined with amrubicin, a topoisomerase II inhibitor. The aim was to determine the maximum tolerated dose (MTD) of amrubicin combined with a fixed dose of CPT-11 as well as the dose-limiting toxicities (DLT) of this combination in patients with advanced non-small cell lung cancer. PATIENTS AND METHODS: Eleven patients with stage IIIB or IV disease were treated at 3-week intervals with amrubicin (5-min intravenous injection on days 1-3) plus 60 mg/m2 of CPT-11 (90-min intravenous infusion on days 1 and 8). The starting dose of amrubicin was 25 mg/m2, and it was escalated in 5 mg/m2 increments until the maximum tolerated dose was reached. RESULTS: The 30 mg/m2 of amrubicin dose was one dose level above the MTD, since three of the five patients experienced DLT during the first cycle of treatment at this dose level. Diarrhea and leukopenia were the DLT, while thrombocytopenia was only a moderate problem. Amrubicin did not affect the pharmacokinetics of CPT-11, SN-38 or SN-38 glucuronide. Except for one patient, the biliary index on day-1 correlated well with the percentage decrease of neutrophils in a sigmoid Emax model. There were five partial responses among 11 patients for an overall response rate of 45%. CONCLUSION: The combination of amrubicin and CPT-11 seems to be active against non-small cell lung cancer with acceptable toxicity. The recommended dose for Phase II studies is 60 mg/m2 of CPT-11 (days 1 and 8) and 25 mg/m2 of amrubicin (days 1-3) administered every 21 days.

Anthracyclines↗

PubMed2006

[Recurrent pulmonary edema associated with obstructive sleep apnea syndrome].

A 70-year-old non-obese man with no history of cardiopulmonary disease presented 4 times to the emergency room because of sudden onset of seizure during sleep. Each time he recovered within a few hours without any medication. Nocturnal polysomnographic recording revealed severe obstructive sleep apnea syndrome (OSAS, AHI 52.4/Hr). Nasal continuous positive airway pressure (n-CPAP) therapy was performed with 10cmH2O of pressure. His symptoms of severe daytime sleepiness and seizure were diminished. CPAP was decreased from 10cmH2O to 6 cmH2O later, because the patient complained with its high pressure. He then felt daytime sleepiness and suffered seizures during sleep again, and was re-admitted to our hospital. Chest roentgenogram taken at this admission showed remarkable pulmonary edema. We found that the pulmonary edema was recognized every time on his chest roentgenogram taken when he complained seizure. In addition, subsequesnt roentgenograms also showed that the pulmonary edema was diminished soon. On the other hand, his AHI was high (24.7/hr) even when he was under 6cmH2O of n-CPAP. We concluded that incompletely treated OSAS might lead not only to pulmonary edema, but also to seizures in this patient.

Aged↗

PubMed2005

Drug interaction between gefitinib and warfarin.

Gefitinib is a synthetic, oral anilinoquinazoline specifically designed to inhibit the epidermal growth factor receptor tyrosine kinase, and is the first targeted drug to demonstrate reproducible activity in non-small cell lung cancer patients who do not respond to platinum-based chemotherapy. In this report, we present two cases of an interaction between gefitinib and warfarin which has not been reported previously. Because of the potentially serious consequences of this interaction, close monitoring of the International Normalized Ratio and warfarin dosage adjustment are recommended for patients receiving warfarin together with gefitinib.

Aged↗

PubMed2005

[Effect on duration of antibiotic therapy and drug cost by introducing critical pathway for patients with CAP in Japan].

The aim of this study was to assess whether Marrie's critical pathway is an effective approach to reduce the duration of antibiotic intravenous therapy and drug cost in patients with community-acquired pneumonia (CAP) in Japan. We conducted a retrospective cohort study in patients with CAP who were admitted to a community hospital or a university hospital. We collected clinical and economic data from medical records and medical fee receipts and estimated drug cost for switching the dosage form using Marrie's critical pathway. Outcomes of this study were change in duration of intravenous therapy and drug cost. Fifty patients with CAP were selected from two hospitals. Actual days of antibiotic intravenous therapy were 9.5+/-4.2 days; in contrast, estimated days were 1.2+/-3.0 days (p<0.001). Actual drug cost was 37148+/-28791 yen; in contrast, estimated drug cost was 8364+/-18356 yen (p<0.001). Average reduction of days of therapy and drug cost were 8.3 days and 28704 yen, respectively. This study suggests that the implementation of Marrie's critical pathway may be an effective approach to reduce medical resources used for CAP treatment in Japan.

Adult↗

PubMed2005

[Assessment of dihydropyrimidine dehydrogenase and thymidylate synthase expression in gastric carcinoma and colonic carcinoma].

We measured DPD activity and TS content in cancer and normal mucosa obtained from 23 patients with colorectal carcinoma and 7 patients with gastric carcinoma. DPD activity in colorectal carcinoma cases was significantly decreased in cancer tissues compared to those in adjacent normal mucosa (p<0.001), while TS content was significantly increased in cancer tissues (p<0.01). No significant correlation was found between cancer and adjacent normal mucosa in DPD activity and TS content of gastric carcinoma cases. Immunohistochemically, DPD and TS overexpression were found in 11 out of 23 patients (47.8%) and 3 out of 23 patients (13%) in colorectal carcinoma cases, respectively. In gastric carcinoma cases, DPD and TS overexpression were found in 3 out of 7 patients (42.9%) and 3 out of 7 patients (42.9%), respectively. No significant correlation was found between quantitative measurement and immunohistochemical overexpression in colorectal and gastric carcinoma cases. DPD and TS protein were partially overexpressed in some cases. Heterogeneity of the tumor is thought to be one of the reasons for the discrepancy between quantitative measurement and immunohistochemical overexpression.

Aged↗

PubMed2004

The stimulatory action of amphiphysin on dynamin function is dependent on lipid bilayer curvature.

Amphiphysin is a major dynamin-binding partner at the synapse; however, its function in fission is unclear. Incubation of large unilamellar liposomes with mice brain cytosol led to massive formation of small vesicles, whereas cytosol of amphiphysin 1 knockout mice was much less efficient in this reaction. Vesicle formation from large liposomes by purified dynamin was also strongly enhanced by amphiphysin. In the presence of liposomes, amphiphysin strongly affected dynamin GTPase activity and the recruitment of dynamin to the liposomes, but this activity was highly dependent on liposome size. Deletion from amphiphysin of its central proline-rich stretch dramatically potentiated its effect on dynamin, possibly by relieving an inhibitory intramolecular interaction. These results suggest a model in which maturation of endocytic pits correlates with the oligomerization of dynamin with either amphiphysin or other proteins with similar domain structure. Formation of these complexes is coupled to the activation of dynamin GTPase activity, thus explaining how deep invagination of the pit leads to fission.

Animals↗

PubMed2004

Interactive simulation system for artificial ventilation on the internet: virtual ventilator.

OBJECTIVE: To develop an interactive simulation system "virtual ventilator" that demonstrates the dynamics of pressure and flow in the respiratory system under the combination of spontaneous breathing, ventilation modes, and ventilator options. The simulation system was designed to be used by unexperienced health care professionals as a self-training tool. METHODS: The system consists of a simulation controller and three modules: respiratory, spontaneous breath, and ventilator. The respiratory module models the respiratory system by three resistances representing the main airway, the right and left lungs, and two compliances also representing the right and left lungs. The spontaneous breath module generates inspiratory negative pressure produced by a patient. The ventilator module generates driving force of pressure or flow according to the combination of the ventilation mode and options. These forces are given to the respiratory module through the simulation controller. RESULTS: The simulation system was developed using HTML, VBScript (3000 lines, 100 kB) and ActiveX control (120 kB), and runs on Internet Explorer (5.5 or higher). The spontaneous breath is defined by a frequency, amplitude and inspiratory patterns in the spontaneous breath module. The user can construct a ventilation mode by setting a control variable, phase variables (trigger, limit, and cycle), and options. Available ventilation modes are: controlled mechanical ventilation (CMV), continuous positive airway pressure, synchronized intermittent mandatory ventilation (SIMV), pressure support ventilation (PSV), SIMV + PSV, pressure-controlled ventilation (PCV), pressure-regulated volume control (PRVC), proportional assisted ventilation, mandatory minute ventilation (MMV), bilevel positive airway pressure (BiPAP). The simulation system demonstrates in a graph and animation the airway pressure, flow, and volume of the respiratory system during mechanical ventilation both with and without spontaneous breathing. CONCLUSIONS: We developed a web application that demonstrated the respiratory mechanics and the basic theory of ventilation mode.

Computer Simulation↗

PubMed2004

Analysis of the oligosaccharide chain of human serum immunoglobulin g in patients with localized or metastatic cancer.

A quantitative imbalance between matrix metalloproteinases produced by cancer cells and tissue inhibitors of metalloproteinases produced by fibroblasts and other types of cells has been demonstrated to be a causative factor in invasion and metastasis of cancer cells. On the other hand, it is reported that sugar chains of adhesion molecules such as integrins and CD44 also influence the metastasis of cancer cells. Here, alterations of serum IgG oligosaccharide chain structure were investigated during tumor progression using the new method of fluorophore-assisted carbohydrate electrophoresis (FACE). The structure of serum IgG oligosaccharide chains from 22 cancer patients (11 localized cancer, 11 metastatic cancer) and 10 healthy controls was evaluated by FACE. It was clearly demonstrated that serum IgG oligosaccharide chains without galactose (agalactosyl IgG oligosaccharide) significantly increased with tumor progression of lung and gastric cancers. It is concluded that a marked increase of agalactosyl IgG oligosaccharide in these cancer patients is associated with carcinogenesis and metastasis. Therefore, the analysis of serum IgG oligosaccharide chain structure by FACE may be useful for evaluating diagnosis and prognosis in patients with these carcinomas.

Aged↗

PubMed2003

Respiratory muscle electromyogram and mouth pressure during isometric contraction.

When extra-diaphragmatic muscles are activated progressively under approximately isometric conditions, we expect a corresponding increase in respiratory muscle output. Therefore, we examined relative recruitment shown as the latency to onset of EMG activity, and the relationship between mouth pressure and electromyogram activity of the neck accessory and transversus abdominis (TRANS) muscles during respiratory maneuvers against occlusion. Fine wire electrodes were inserted into the scalene (SCLN), sternocleidomastoid (STERNO), trapezius (TRAPZ) and TRANS in six awake, healthy subjects. Mouth pressure, raw and moving average EMG signals were recorded during gradual production of expiratory or inspiratory mouth pressure to maximum (MPmax) at FRC in the standing posture. Group mean linear regression lines of EMG activity versus mouth pressure were strongly significant for SCLN and TRANS, less for STERNO, and least for TRAPZ. The SCLN and STERNO showed EMG activities with low, and TRAPZ showed EMG activity only with high, mouth pressure. At 90% MPmax, TRAPZ was much less active compared with TRANS, SCLN, or STERNO. These results suggest that over a wide range of respiratory effort there is a significant difference in the relationship between mouth pressure and EMG activity in the accessory muscles, with differential recruitment of individual respiratory muscles.

Adult↗

PubMed2003

Characterization of hydrogen peroxide removal reaction by hemoglobin in the presence of reduced pyridine nucleotides.

Hydrogen peroxide removal rates by hemoglobin were enhanced in the presence of reduced pyridine nucleotides. The species which had the activity to oxidize pyridine nucleotides was purified from human blood and identified as hemoglobin A. Hydrogen peroxide removal rates by hemoglobin A without reduced pyridine nucleotides at 0.2 mM hydrogen peroxide were 0.87+/-0.11 micromol/s/g hemoglobin, and the removal rates using 0.2 mM NADH and NADPH were 2.02+/-0.20 and 1.96+/-0.31 micromol/s/g hemoglobin, respectively. We deduced that the removal reaction by hemoglobin included formations of methemoglobin and the ferryl radical and reduction of the latter with pyridine nucleotides. The hydrogen peroxide removal ability by hemoglobin was less than that by catalase but was larger than that by glutathione peroxidase-glutathione reductase system at 0.2 mM hydrogen peroxide. Under acatalasemic conditions, it was suggested that NAD(P)H were important factors to prevent the oxidative degradation of hemoglobin.

Acatalasia↗

PubMed2003

Formation of S-[2-carboxy-1-(1H-imidazol-4-yl) ethyl]glutathione, a new metabolite of L-histidine, from cis-urocanic acid and glutathione by the action of glutathione S-transferase.

Exposure of the skin to sunlight results in an increase of the content of epidermal trans-urocanic acid, a key metabolite of L-histidine, and also in occurrence of the isomerization of trans-urocanic acid to the cis isomer. S-[2-Carboxy-1-(1H-imidazol-4-yl)ethyl]glutathione (GS(CIE)), an adduct of urocanic acid and glutathione, is a presumed origin of a urinary compound S-[2-carboxy-1-(1H-imidazol-4-yl)ethyl]-L-cysteine (Cys(CIE)). The formation of GS(CIE) is stimulated by exposing the skin to sunlight irradiation. In this study we investigated an enzymatic formation of GS(CIE) from glutathione and cis-urocanic acid by incubation with rat liver extract that contained glutathione S-transferase (GST) at high activity. The formation of GS(CIE) was suppressed significantly when a liver extract depleted of GST activity was used. Enzymatic degradation of GS(CIE) with gamma -glutamyl transpeptidase resulted in the formation of N-[S-[2-carboxy-1-(1H-imidazol-4-yl)ethyl]-L-cysteinyl]glycine, a metabolic intermediate between the glutathione adduct and Cys(CIE). A hydrolyzed product of GS(CIE) by HCl was identical with the urinary Cys(CIE). Compounds were analyzed by high-voltage paper electrophoresis, capillary electrophoresis, and fast atom bombardment mass spectrometry. From these results, we suggest that GS(CIE) formed from cis-urocanic acid and glutathione is an origin of the urinary compound Cys(CIE) and that the formation reaction is catalyzed mostly by the action of GST.

Animals↗

PubMed2003

Formation of meso, N-diphenylprotoporphyrin IX by an aerobic reaction of phenylhydrazine with oxyhemoglobins.

Administration of phenylhydrazine to rabbits resulted in the denaturation of hemoglobins in erythrocytes, causing the formation of intracellular precipitates known as Heinz bodies, severe hemolytic anemia, and reticulocytosis. To elucidate the molecular mechanism of the destabilization, we allowed human oxyhemoglobins to react aerobically with phenylhydrazine. After treatment with acetic acid/HCl and H2SO4/methanol, the chloroform extract contained blue-green pigments of major products accompanied by different minor products. Each product was isolated by column chromatography. By fast-atom-bombardment mass spectrometry (FAB-MS) and proton nuclear magnetic resonance (1H-NMR) spectrometry, dimethyl esters of N-phenylprotoporphyrin IX and meso, N-diphenylprotoporphyrin IX were determined. Other major products also were determined to be dimethyl esters of triphenyl-and tetraphenyl-substituted protoporphyrins by FAB-MS. The formation of meso, N-diphenylprotoporphyrin indicated that the addition of a phenyl radical to the meso-carbon atom of the protoporphyrin ring occurred. Triphenyl and tetraphenyl adducts also indicated the formation of phenyl radicals in the aerobic reaction of phenylhydrazine with oxyhemoglobins. From these results, we suggest that the formation of phenyl radicals and the replacement of heme with phenyl-substituted protoporphyrins cause the destabilization of hemoglobins to induce Heinz bodies and hemolytic anemia with phenylhydrazine.

Anemia, Hemolytic↗

PubMed2003

[Electromyographic activity of human triangularis sterni muscles during thoracic rotation].

The triangularis sterni muscles (TS) have been recognized as expiratory muscles, but there is no information on their postural activity or their phasic electromyographic (EMG) activity during thoracic rotation. We examined the EMG activity of the right TS using fine-wire electrodes, in 5 healthy male subjects. With subjects breathing through a mouthpiece, airflow, raw and moving-averaged EMG signals were sampled with a computer during thoracic rotation and resting, accompanied by breathing with or without voluntary thoracic rotation. Maximum EMG (EMGmax) was defined as the greatest moving-averaged EMG activity recorded from each subject during the slow expiratory maneuver from functional residual capacity to residual volume. With leftward thoracic rotation without breathing, the tonic EMG activity of the right TS was observed in all subjects. During resting breathing without thoracic rotation, there were respiration-related phasic activities on TS EMG during expiration in all subjects. With leftward thoracic rotation, the respiration-related phasic activities on TS EMG significantly increased from 8.2 +/- 3.5 (mean +/- SE) %EMGmax to 15.2 +/- 6.1 %EMGmax. On the other hand, with rightward thoracic rotation, it decreased to 3.0 +/- 1.0 %EMGmax. We concluded that 1) TS has a postural function like that of the intercostal muscles, and that 2) the respiratory function of TS is affected by thoracic rotation.

Adult↗

PubMed2003

[Case report of pulmonary epithelioid hemangioendothelioma].

A 45-year-old man was admitted to our hospital because of multiple nodular shadows in the right upper field of a chest radiogram taken at a regular medical checkup. He underwent open lung biopsy. The lung tumor found was diagnosed histologically as pulmonary epithelioid hemangioendothelioma. The tumor cells showed positive staining for CD34 and factor VIII-related antigen. Pulmonary epithelioid hemangioendothelioma (PEH) is a rare lung tumor, of which only 40 cases, including the present case, were reported between 1983 and 2002 in Japan. PEH is a progressive, low-grade malignant tumor that originates from hemangioendothelial cells. In chest radiography or CT scanning, PEH is usually discovered incidentally as multiple nodular shadows. Many cases of PEH are diagnosed by open lung biopsy or thoracoscopic biopsy. No standard therapy for PEH has yet been established, other than resection of a solitary lesion. The present patient has been followed without treatment for five-and-a-half years, and is still alive with no symptoms.

Hemangioendothelioma, Epithelioid↗

PubMed2002

Phosphatidylinositol 4,5-bisphosphate stimulates vesicle formation from liposomes by brain cytosol.

As a step toward the elucidation of mechanisms in vesicle budding, a cell-free assay that measures cytosol-induced vesicle generation from liposomes was established. This assay then was used to explore the role of phosphoinositides in vesicle formation. Liposomes incubated with brain cytosol in the presence of ATP and GTP massively generated small vesicles, as assessed both quantitatively and qualitatively by a dynamic light-scattering assay. Both ATP and GTP were required. Vesicle formation was inhibited greatly by the immunodepletion of dynamin 1 from the cytosol, indicating a major contribution of this GTPase in this reaction and suggesting that it mimics endocytic vesicle fission. Increasing the concentration of l-alpha-phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] but not of l-alpha-phosphatidylinositol 4-monophosphate or l-alpha-phosphatidylinositol in the lipid membranes enhanced vesicle formation. Lipid analysis revealed rapid degradation of PtdIns(4,5)P2 to l-alpha-phosphatidylinositol during the incubation with the reaction reaching a maximum within 5 sec, whereas vesicle formation proceeded with a longer time course. PtdIns(4,5)P2 degradation was independent of vesicle formation and occurred also in the presence of guanosine 5'-O-(thiotriphosphate), where few vesicle formations occurred. These results suggest that PtdIns(4,5)P2 plays a critical role in the early step of vesicle formation, possibly in the recruitment of coats and fission factors to membranes.

Adenosine Triphosphate↗

PubMedDate not supplied

Relationship between N-linked oligosaccharide chains of human serum immunoglobulin G and serum tumor markers with non-small cell lung cancer progression.

BACKGROUND: It has been demonstrated that increased expression of the sialyl Le(x) sugar chains on cancer cells influences cellular adhesion to vascular-endothelial cells. Therefore, it was thought that alterations in the sugar chain structure of E-cadherin, a calcium dependent adhesion molecule, influence the metastasis of cancer cells. MATERIALS AND METHODS: In this study, N-linked oligosaccharides of human serum immunoglobulin G (IgG) were analyzed in 12 patients with non-small cell lung cancer (NSCLC) (6 localized cancer: 3 adenocarcinomas and 3 squamous cell carcinomas; 6 metastatic cancer: 3 adenocarcinomas and 3 squamous cell carcinomas) and 10 healthy controls using fluorophore-associated carbohydrate electrophoresis (FACE). The relationship between changes in sugar chain structure and serum concentrations of carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA21-1) were evaluated. CEA levels in the sera were determined using an enzyme immunoassay, and CYFRA21-1 levels were determined using an enzyme chemiluminescent immunoassay. RESULTS: Fri (monogalactosyl IgG oligosaccharides) and Fr2 (digalactosyl IgG oligosaccharides) decreased, while Fr4 (agalactosyl IgG oligosaccharides) significantly increased (p < 0.01-0.05) with NSCLC progression. The Fr4/Fr1+Fr2 ratio increased with NSCLC progression, and the ratios in localized and metastatic NSCLC were significantly higher than in healthy controls (p < 0.01 and p < 0.01, respectively). There was a strong correlation between serum CEA levels and Fr4 (r = 0.91) and a significant correlation between serum CEA levels and the Fr4/Fr1+Fr2 ratio (r = 0.83, p < 0.05) in patients with lung adenocarcinoma. There was a significant correlation between serum CYFRA21-1 levels and Fr4 (r = 0.88, p < 0.001) and a positive correlation between serum CYFRA21-1 levels and the Fr4/Fr1+Fr2 ratio (r = 0.38) in patients with lung squamous cell carcinoma. CONCLUSION: The analysis of serum IgG N-linked oligosaccharide chain structures by FACE may be an auxiliary indicator of serum tumor markers for monitoring NSCLC progression.

Aged↗