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Biomedical subjects

F Inoue

Publications and source records attributed to F Inoue.

At least 19 recordsLinked to original sources
PubMed2000

Calcium associated resistance to H(2)O(2) in Chinese hamster V79 cells.

To investigate whether the difference in cellular sensitivity of Chinese hamster V79 and their H(2)O(2)-resistant variant cells (Hpr-4) to H(2)O(2) relates to the difference in intracellular Ca(2+) concentration in these cells, we measured Ca(2+) concentration by calcium ion analysis after loading these cells with Fura-2/AM. Intracellular Ca(2+) concentration increased in both Chinese hamster V79 and Hpr-4 cells as extracellular Ca(2+) concentration increased. However, the increase in intracellular Ca(2+) concentration in response to extracellular H(2)O(2) was more pronounced in Hpr-4 than V79 cells. H(2)O(2) cytotoxicity of Hpr-4 but not V79 cells was also decreased in response to the increase in extracellular Ca(2+) concentration. In parallel with the decrease in cytotoxicity in response to increasing extracellular Ca(2+) concentration, the frequency of mitochondrial DNA single strand breaks (SSB) in Hpr-4 cells also decreased without producing observable nuclear DNA SSB. Use of permeabilized V79 and Hpr-4 cells exposed to H(2)O(2) showed that mitochondrial DNA SSB decreased when extramitochondrial Ca(2+) concentration increased. These findings indicate that elevated intracellular Ca(2+) concentration may protect against H(2)O(2)-induced mitochondrial damage and cytotoxicity in these cells.

Animals↗
PubMed2000

Autoimmune pancreatitis detected as a mass in the tail of the pancreas.

A mass in the tail of the pancreas was detected in a 62-year-old male patient who had hypergammaglobulinaemia, and was positive for antinuclear antigen and anti-SS-A antibody. Endoscopic retrograde pancreatography revealed focal irregular narrowing of the main pancreatic duct in the tail of the pancreas. Dynamic computed tomography showed swelling of the pancreatic tail, which was enhanced on delayed phase. Autoimmune pancreatitis was suspected and corticosteroid therapy was commenced. This led to significant resolution of the pancreatic stricture. It is important to recognize this clinical entity as corticosteroid therapy may avoid unnecessary surgery.

Autoantibodies↗
PubMed2000

Low-dose cytarabine and aclarubicin in combination with granulocyte colony-stimulating factor (CAG regimen) for previously treated patients with relapsed or primary resistant acute myelogenous leukemia (AML) and previously untreated elderly patients with AML, secondary AML, and refractory anemia with excess blasts in transformation.

We used the CAG regimen (low-dose cytarabine [10 mg/m2 per 12 hours, days 1-14], aclarubicin [14 mg/m2 per day, days 1-4], and granulocyte colony-stimulating factor [200 micrograms/m2 per day, days 1-14]) for the treatment of patients with primary resistant acute myelogenous leukemia (AML) and previously untreated elderly patients with AML, secondary AML, and refractory anemia with excess blasts in transformation (RAEB-T) in addition to relapsed AML. Forty-three of 69 (62%) patients achieved complete remission (CR), including 29 of 35 (83%) patients with relapsed AML, 1 of 8 patients with primary resistant AML, 5 of 8 elderly patients with previously untreated AML, and 8 of 18 patients with previously untreated secondary AML or RAEB-T. Ten of 22 (45%) patients > or = 65 years old achieved CR. The patients who achieved CR received at least 1 course of modified CAG therapy as the first consolidation therapy, followed by various second consolidation and intensification therapies. The median disease-free survival and overall survival were 8 and 15 months, respectively, for relapsed AML; 11 and 8 months for the elderly patients; and 8 and 17 months for secondary AML and RAEB-T. Myelosuppression was mild to moderate, and other than fever, severe nonhematologic toxicity was rare. CAG as the induction therapy seems promising for the treatment of various categories of poor-prognosis AML.

Aclarubicin↗
PubMed2000

Glucocorticoid-induced apoptotic pathways in eosinophils: comparison with glucocorticoid-sensitive leukemia cells.

Glucocorticoids are known to promote apoptosis of eosinophils, normal and neoplastic lymphoid cells, and blastic cells in some patients with acute myeloid leukemia. We investigated the biochemical signal transduction pathways, in particular, the generation of reactive oxygen species (ROS) and activation of caspases in dexamethasone (DEX)-induced apoptosis of eosinophils, and we compared them with those in DEX-sensitive myeloid and lymphoid leukemia cell lines. The GC-receptor antagonist completely abolished DEX-induced apoptosis of eosinophils and leukemia cells. Among inhibitors related to the ROS system, diphenylene iodonium (DPI), a nicotinamide adenine dinucleotide diphosphate (NADPH) oxidase inhibitor, strongly inhibited both spontaneous and DEX-induced apoptosis of eosinophils at concentrations as low as 0.2 to 2 mumol/L, while promoting apoptosis of leukemia cells in a dose-dependent manner. Apocynin, another NADPH oxidase inhibitor, and antioxidants did not affect the apoptosis of eosinophils or leukemia cells. DEX treatment did not change intracellular production of O2- and H2O2, and it decreased the extracellular release of O2- in both cells. These results suggest little or no involvement of ROS generation in DEX-induced apoptosis of both cells. Although among peptide-based caspase inhibitors, only z-VAD-FMK, a broad caspase inhibitor, partially inhibited the apoptosis of eosinophils and leukemia cells, DEX treatment increased the activities of caspases 2-, 3-, 6-, and 8-like proteases assessed by colorimetry in both cells, suggesting the involvement of a similar caspase activation pathway in DEX-induced apoptosis in both cells. DPI markedly reduced caspase 3-like activity in eosinophils, while augmenting the activity in leukemia cells, indicating that DPI acts upstream of caspase 3 activation opposingly in both cells. Thus, the action of DPI in eosinophils seems peculiar in respect to apoptosis induction, and DPI appears to exert an influence on unknown targets rather than those involved in NADPH oxidase inhibition.

Apoptosis↗
PubMed1999

Measurement of carnitine precursors, epsilon-trimethyllysine and gamma-butyrobetaine in human serum by tandem mass spectrometry.

Methods using tandem mass spectrometry for measurement of epsilon-trimethyllysine and gamma-butyrobetaine in human serum are described. Precursor ion scan analysis of a methylated sample was applied for gamma-butyrobetaine measurement. However, for epsilon-trimethyllysine measurement, homoarginine interfered with the methylated sample during precursor ion scan analysis. To overcome this interference, the sample was propylated and acetylated prior to precursor ion scan analysis. The obtained values resembled those obtained by enzymatic or HPLC measurement. Using tandem mass spectrometry, all members of the carnitine family, free carnitine, acylcarnitines, gamma-butyrobetaine, epsilon-trimethyllysine can be analyzed in 0.1 ml of serum. Thus, the proposed method appears to be suitable for clinical application, especially in the pediatric field.

Betaine↗
PubMed1999

Effect of sports activity on carnitine metabolism. Measurement of free carnitine, gamma-butyrobetaine and acylcarnitines by tandem mass spectrometry.

The effects of sports activity on carnitine metabolism were studied using mass spectrometry. Serum levels of free carnitine, acylcarnitines (acetylcarnitine, propionylcarnitine, C4-, C5- and C8-acylcarnitine) and gamma-butyrobetaine, a carnitine precursor, were determined by tandem mass spectrometry in liquid secondary ion mass ionization mode. The coefficients of variation at three different concentrations were 2.8-7.9% for gamma-butyrobetaine, and 1.2 to approximately 6.7% for free carnitine. The recoveries added to serum were 109.1% for gamma-butyrobetaine, 89.3% for free carnitine. Sports activity caused increased serum levels of gamma-butyrobetaine, acetylcarnitine, C4- and C8-acylcarnitines and decreased serum levels of free carnitine. This method requires a small amount of sample volume (20 microl of serum) and short total instrumental time for the analysis (1 h for preparation, 2 min per sample for mass spectrometric analysis). Therefore, this method can be applied to study carnitine metabolism under various conditions that affect fatty acid oxidation.

Betaine↗
PubMed1999

L-2-hydroxyglutaric aciduria: two Japanese adult cases in one family.

We report two adult Japanese sisters with L-2-hydroxy-glutaric aciduria (acidemia), both of whom were much older (aged 57, 47 years old) than previously reported patients (from neonate to 44 years old), and who presented with differing severity. Magnetic resonance imaging revealed typical subcortical white matter lesions in both cases and showed brainstem atrophy and thickness of the calvarium in the elder sister. L-2-Hydroxyglutaric acid levels were increased in urine, plasma, and cerebrospinal fluid. These cases suggest that organic acid analysis is necessary even in elderly patients who seem to have neurodegenerative disorders.

Brain↗
PubMed1999

Management of acute metabolic decompensation in maple syrup urine disease: a multi-center study.

BACKGROUND: Therapeutic modalities in acute metabolic decompensation in maple syrup urine disease (MSUD) are variable, and outcomes of each therapeutic measure have been known only individually. Factors that affect neurological outcome are not clear. METHODS: A questionnaire was sent throughout Japan to each pediatrician treating any of the 42 MSUD patients. RESULTS: Necessary information was available for 13 patients through the questionnaire, and through a publication for one patient. In nine of the 14 patients episodes of metabolic decompensation developed in the neonatal period. In the other five, the onset of disease was delayed until infancy or later. In the nine patients with neonatal onset, a pretreatment level of plasma leucine greater than 40 mg/100 mL or a duration of altered level of alertness longer than 10 days was associated with a poor neurological outcome. The therapeutic measures employed included intravenous infusion of glucose and electrolyte solution or hypertonic glucose and electrolyte solution, exchange transfusion, peritoneal dialysis, a large dose of thiamine and intravenous hyperalimentation. All patients had survived the episodes and were alive at the time of the survey. Five of the nine patients with neonatal onset have developed neurological sequelae to varying degrees. Episodes of metabolic decompensation in infancy or thereafter did not affect, or only minimally affected, the neurological outcome. CONCLUSION: Therapeutic goals to improve neurological outcome are to shorten the duration of the altered level of consciousness, and to minimize the peak plasma leucine level as much as possible.

Acute Disease↗
PubMed1999

Carnitine import to isolated hepatocytes and synthesis are accelerated in pivalate-treated rats.

To investigate the effect of pivalate on carnitine import and carnitine synthesis in the liver, we measured carnitine uptake in isolated rat hepatocytes with L-[(14)C] carnitine and concentrations of free carnitine, gamma-butyrobetaine and acylcarnitines using tandem mass spectrometry. Hepatocytes from rats treated with 20 mmol/L of pivalate for 4 wk had greater L-[(14)C] carnitine uptake than those of unsupplemented rats after 5, 10, 30 and 90 min. Addition of 1 mmol/L of pivalate or 1 mmol/L of pivaloylcarnitine to control cell suspensions did not affect L-[(14)C] carnitine uptake. The K(m) values for L-[(14)C] carnitine uptake for pivalate-treated rats were significantly lower than control (2.9 +/- 0.7 mmol/L for pivalate-treated rats, 6.2 +/- 1.1 mmol/L for controls). The concentration of free carnitine was not reduced in the liver of pivalate-treated rats, whereas the concentrations of acetylcarnitine and gamma-butyrobetaine were significantly lower than controls. In the heart and muscle the concentration of free carnitine was significantly lower and that of gamma-butyrobetaine was higher than controls. These results suggest that carnitine transport from plasma into the liver and synthesis in the liver are accelerated in rats with secondary carnitine deficiency induced by the administration of pivalate.

Animals↗
PubMed1999

[A case of bronchogenic in situ carcinoma originating in fourth order bronchi].

A case of bronchogenic in situ carcinoma originating in forth order bronchi was reported. Sputum cytology showed class IV in lung cancer mass screening in a 69-year-old male, although X-ray was negative. Bronchofiber scopy was repeated twice, and fine granular change of spur between Blai and ii was found in the second time. Right upper lobectomy was underwent, and post-surgical histology was in situ squamous cell carcinoma. The literature on early lung cancer was reviewed, and implication for management of bronchofiberscopic early lung cancer in general rule for clinical and pathological record of lung cancer was discussed.

Aged↗
PubMed1999

[Bacteria isolated from surgical infections and their susceptibilities to antimicrobial agents: special references to bacteria isolated between July 1996 and June 1997].

The annual multicenter studies on isolated bacteria from infections in general surgery and their antimicrobial susceptibility have been conducted in 20 facilities in Japan since July 1982. This paper describes the results obtained during period from July 1996 to June 1997. The number of cases investigated as objectives was 217 for one year. A total of 406 strains were isolated from 177 cases (81.6% of total cases). From primary infections 162 strains were isolated, and from postoperative infections 244 strains were isolated, respectively. From primary infections, anaerobic bacteria were predominant, while from postoperative infections, aerobic Gram-positive bacteria were predominant. Among aerobic Gram-positive bacteria, the isolation rate of Enterococcus spp. was the highest. In postoperative infections, the majority of them were Enterococcus faecalis, while in primary infections, many of them were Enterococcus avium. The isolation rate of Staphylococcus spp., especially from postoperative infections, followed that of Enterococcus spp. Among anaerobic Gram-positive bacteria, Peptostreptococcus spp. and Streptococcus spp. were commonly isolated from both types of infections. Among aerobic Gram-negative bacteria, Escherichia coli was the most predominantly isolated from primary infections, followed by Klebsiella pneumoniae and Pseudomonas aeruginosa in this order, and from postoperative infections, P. aeruginosa was the most predominantly isolated, followed by E. coli and Enterobacter cloacae. Among anaerobic Gram-negative bacteria, Bacteroides fragilis group was the majority of isolates from both types of infections. The isolation rate of aerobic Gram-negative bacillus has decreased with time, while those of anaerobes like B. fragilis group and of aerobic Gram-positive bacteria have gradually increased in both types of infections. We found vancomycin-resistant strains of neither Staphylacoccus aureus nor Enterococcus spp.; however, the MIC of arbekacin for one of strains of S. aureus was 100 micrograms/ml. Both the MIC90's of meropenem and imipenem/cilastatin against P. aeruginosa isolated in this term were 25 micrograms/ml, which were higher than those against the strains isolated in the previous years. Compared with the isolated strains in the year 1995, progress of resistance against carbapenem antibiotics was confirmed.

Anti-Bacterial Agents↗
PubMed1998

The sensitivity to DNA single strand breakage in mitochondria, but not in nuclei, of Chinese hamster V79 and variant cells correlates with their cellular sensitivity to hydrogen peroxide.

To investigate whether a relation exists between the level of DNA damage by and cytotoxicity of hydrogen peroxide, we measured the initial level of H2O2-induced nuclear and mitochondrial DNA single strand breaks in Chinese hamster V79 and H2O2-resistant variant cells (Hpr-4) with an alkaline elution technique and a quantitative Southern blot technique, respectively. The frequency of DNA single strand breaks in mitochondrial DNA induced by H2O2 was more than one hundred times that of nuclear DNA in the parent V79 cells. While a similar frequency of nuclear DNA single strand breaks was generated in V79 and Hpr-4 cells at an equidose of H2O2, a lower number of mitochondrial DNA single strand breaks were generated in Hpr-4 cells than in V79 cells by H2O2 in the range of 100 microM to 5 mM. The sensitivity to mitochondrial DNA single strand break-induction correlated with the cellular sensitivity to H2O2 in Chinese hamster V79 and variant cells.

Alkalies↗
PubMed1998

Estimation of coronary flow reserve by intracoronary administration of nicorandil: comparison with intracoronary administration of papaverine.

We investigated the usefulness of the intracoronary administration of nicorandil (NIC) compared with that of papaverine (PAP) in the evaluation of coronary flow reserve (CFR) in 17 patients, including 10 patients with old myocardial infarction and 7 patients with angina pectoris. CFR was measured with a Doppler guidewire inserted into the distal site of the left anterior descending coronary artery during intracoronary administration of 10 mg PAP, and of 0.5 mg, 1.0 mg, 2.0 mg, and 3.0 mg NIC. We examined the changes in heart rate (HR), mean blood pressure (mBP), the total score of QTc interval on a 12-lead electrocardiogram (sigma QTc), and ST-T segment, before and after drug administration. CFR was significantly lower during administration of 0.5 mg (1.9 +/- 0.9) and 1.0 mg (2.2 +/- 0.9) NIC than during administration of PAP (2.6 +/- 1.1) (P < 0.01). There was no significant difference in the CFR during administration of 2.0 mg (2.6 +/- 1.0) or 3.0 mg (2.5 +/- 1.0) NIC and that observed during administration of PAP. The CFR during administration of PAP was significantly correlated with that during administration of 2.0 mg NIC (r2 = 0.72, P < 0.0001) and 3.0 mg NIC (r2 = 0.70, P < 0.0001). PAP, but not NIC, significantly altered the HR, mBP, and sigma QTc. Inverted T waves were observed in 14 patients, and elevation of the ST segment was observed in 4 patients during administration of PAP (including 1 patient with ventricular tachycardia). The administration of 0.5 mg to 2.0 mg NIC was not associated with ST-T segment changes, except in 1 patient, but inverted T waves were observed in 2 patients and depression of the ST segment was observed in 2 patients during administration of 3.0 mg NIC. Intracoronary administration of NIC is useful and safe for evaluating the CFR. The appropriate dose for measuring CFR is 2.0 mg nicorandil.

Angina Pectoris↗
PubMed1998

Mature and immature myeloid cells decrease the granulocyte colony-stimulating factor level by absorption of granulocyte colony-stimulating factor.

We studied the effects of polymorphonuclear neutrophils (PMN) and immature myeloid cells on the granulocyte colony-stimulating factor (G-CSF) level in vitro to better understand the regulatory mechanisms of neutropoiesis. Intact normal PMN decreased the G-CSF level after incubation with recombinant human (rh) G-CSF in a time- and dose-dependent manner. The percent reduction decreased as the concentration of rhG-CSF increased. However, the cell-free PMN-conditioned medium (PMN-CM) did not decrease the G-CSF level. The intact PMN also decreased the granulocyte-macrophage (GM)-CSF level after culture with rhGM-CSF, but did not affect the monocyte (M)-CSF level after culture with rhM-CSF. Normal bone marrow (BM) immature neutrophilic cells and G-CSF-dependent acute myeloid leukemic cells (OCI/AML la) also decreased the G-CSF level, whereas K-562 cells, which have no detectable G-CSF receptors, did not affect it. Phenylarsine oxide (PhAsO), an inhibitor of endocytosis of ligand receptor complex, abrogated this decreasing effect of intact PMN and OCI/AML la cells. These findings suggest that mature and immature myeloid cells negatively regulate neutropoiesis by, at least in part, decreasing the G-CSF level probably through receptor-mediated continual absorption and metabolism of G-CSF.

Absorption↗