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Biomedical subjects

F Inoue

Publications and source records attributed to F Inoue.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1998

[Molecular therapy for human cancer with tumor suppressor p53 gene transfer].

Molecular level approaches have demonstrated that tumor suppressor p53 gene, which is the most commonly mutated gene yet described in human cancers, plays an important role in the pathway of apoptosis triggered by DNA-damaging agents. In addition, defects in apoptosis caused by the inactivation of p53 resulted in resistance to treatment. Human gene therapy has become a reality with the development of effective techniques for delivering the gene to the target cells. These findings suggested a novel approach to cancer therapy with the direct delivery of wild-type p53 gene construct to cancer cells by using an adenoviral vector system. Restoration of wild-type p53 function markedly enhanced the antitumor effect of a common chemotherapeutic agent, cisplatin, in human non-small cell lung cancer cells as well as human colon cancer cells. The application of this technology to human cancer therapy is now in progress.

Apoptosis↗
PubMed1998

[A clinical study on the cases of ischemic colitis: comparison of clinical images based on time from onset of the disease to detection of bloody stool].

A study was performed on 28 cases of ischemic colitis. The patients were divided into three groups: Group A (9 cases with bloody stool detected within 2 hours after the onset of abdominal pain), Group B (7 cases with bloody stool detected in 2 to 6 hours), and Group C (12 cases with bloody stool detected after more than 6 hours). These cases were comparatively studied. Variables used were as follows: (1) age, (2) sex, (3) constipation, (4) vomiting, (5) peak value of WBC count (/microliter) after admission, (6) peak value of log CRP (microgram/dl), (7) presence of ulcerative lesion in endoscopic findings in acute stage. Using Group A B and C as classification variables, canonical discriminant analysis was performed. As a result, clear linearity was recognized in Group A-->B-->C, and the values (5), (6) and (7) were extracted as the corresponding variables. For these variables, significant difference was also noted in multivariate analysis of covariance. These results suggest that it is possible to predict the severity of the disease to some extent as represented by objective markers of inflammation by finding the time from onset of abdominal pain to detection of bloody stool.

Adolescent↗
PubMed1997

Total absence of protein 4.2 and partial deficiency of band 3 in hereditary spherocytosis.

Unlike previously reported cases with total protein 4.2 deficiency due to mutations in the EPB42 gene, we describe a total deficiency in protein 4.2 with normal EPB42 alleles. Hereditary spherocytosis (HS) was observed in a Japanese woman (unsplenectomized) and her daughter (splenectomized). The mother showed a partial deficiency in band 3 and a proportional reduction in protein 4.2. She was heterozygous for a novel allele of the EPB3 gene, allele Okinawa, which contains the two mutations that define the Memphis II polymorphism (K56E, AAG-->GAG, and P854L, CCG-->CTG) and, additionally, the mutation: G714R, GGG-->AGG, located in a highly conserved position of transmembrane segment 9. The latter change was responsible for HS. In trans to allele Okinawa, the daughter displayed allele Fukuoka: G130R, GGA-->AGA, an allele known to alter the binding of protein 4.2 to band 3. The daughter presented with a more pronounced decrease of band 3, and lacked protein 4.2, resulting in aggravated haemolytic features. Although the father was not available for study, heterozygosity for allele Fukuoka has been documented in another individual who showed no clinical or haematological signs, and a normal content of band 3. We suggest that band 3 Okinawa binds virtually all the protein 4.2 in red cell precursors, band 3 Fukuoka being unable to do so, and that the impossibility of band 3 Okinawa incorporation into the membrane leads to degradation of the band 3 Okinawa protein 4.2 complex. In contrast, band 3 Fukuoka, free of bound protein 4.2, could then incorporate normally into the bilayer. Thus, protein 4.2 would not appear in the daughter's red cell membrane.

Amino Acid Substitution↗
PubMed1997

The effect of carnitine on ketogenesis in perfused livers from juvenile visceral steatosis mice with systemic carnitine deficiency.

Juvenile visceral steatosis (JVS) mice have been reported to have systemic carnitine deficiency, and the carnitine concentration in the liver of JVS mice was markedly lower than that of controls (11.6 +/- 2.6 versus 393.5 +/- 56.4 nmol/g of wet liver). To evaluate the role of carnitine in mitochondrial beta-oxidation in liver, we examined the effects of carnitine on ketogenesis in perfused liver from control and JVS mice. In control mice, ketogenesis was increased by the infusion of 0.3 mM oleate, but not by L-carnitine. In contrast, although ketogenesis in JVS mice was not increased by the infusion of oleate, it was increased 2.5-fold by the addition of 1000 microM L-carnitine. Addition of 50, 100, and 200 microM L-carnitine increased ketogenesis in a dose-dependent manner. The infusion of 0.3 mM octanoate or butyrate increased ketogenesis in a carnitine-independent fashion in both control and JVS mice. These findings suggest that endogenous long chain fatty acids from accumulated triglycerides may be used as substrates in the presence of carnitine in JVS mice. The relationship between ketogenesis and free carnitine concentration was examined in livers from JVS mice. Ketogenesis increased as free carnitine levels increased until concentrations exceeded about 100 nmol/g of wet liver (340 microM). The free carnitine concentration required for half-maximal ketone body production in liver of JVS mice was 45 microM (13 nmol/g of wet liver), which corresponds to a K(m) value of carnitine palmitoyltransferase I. We conclude that carnitine is a rate-limiting factor for beta-oxidation in liver only when the carnitine level in liver is very low.

Animals↗
PubMed1997

Absence of myocardial 123I-BMIPP uptake in the presence of a normal coronary angiogram and normokinetics on a left ventriculogram.

We present the case of a 44-year-old man with abnormal myocardial fatty acid metabolism who exhibited no myocardial uptake of 123I-beta-methyl- iodophenyl pentadecanoic acid (123I-BMIPP). This patient presented to our hospital with an ECG abnormality detected during a medical check-up. He felt no chest discomfort, but a 12-lead ECG at rest showed flat T-waves in leads I, V5, and V6 with no marked ischemic changes during exercise. A left ventriculogram and coronary angiograms were normal. Thallium-201 single photon emission computed tomography imaging revealed a normal myocardial uptake, but 123I-BMIPP imaging showed no such uptake. However, 18F-labelled fluorodeoxyglucose positron emission tomography imaging after an overnight fast showed a marked increase in myocardial uptake. It appears that myocardial uptake of 123I-BMIPP was totally lacking and that energy production by the myocardium during fasting depended on the metabolism of glucose rather than of fatty acids.

Adult↗
PubMed1997

[Human gene therapy for lung cancer].

Lung cancer is one of the leading causes of cancer death in the world. The high mortality rate for lung cancer results from the absence of standard therapeutic strategies. Recent advances in molecular biology have demonstrated that multistep genetic alterations are involved in the carcinogenesis of human lung cancer. Human gene therapy has become a reality with the development of effective techniques for delivering the gene to the target cells. The efficacy of gene therapy for various types of genetic disease now being evaluated in clinical trials. These findings led us to develop a novel gene therapeutic strategy for human lung cancer that could either inhibit the oncogene expression or replace the tumor suppressor gene by using recombinant, replication-defective viral vectors. The article reviews recent highlights in this rapidly evolving field.

Adenoviridae↗
PubMed1996

Pivalate affects carnitine status but causes no severe metabolic changes in rat liver.

To investigate the carnitine deficiency induced by pivalate, rats had free access to drinking water with or without pivalate. Consumption of 20 mmol/L pivalate for 1 wk decreased the levels of both free and total carnitine in plasma to approximately 20% of levels before treatment. After 4 wk, the concentrations of free carnitine in the liver, heart and muscle of pivalate-treated rats were approximately 60-80% of the control, and in the kidney, 26% of the control. Fractional excretion of free carnitine (FEFC) in pivalate-treated rats was measured; however, the treatment for 3 or 8 d did not affect the values relative to those obtained before treatment. Treatment with pivalate for 4 wk did not affect plasma concentrations of glucose, ammonia and free fatty acids (FFA) in the rats; however, the concentration of 3-hydroxybutyrate (3-OHB) was higher, and the FFA/3-OHB ratio was lower than those of controls. In a liver perfusion study, ketogenesis from oleate and gluconeogenesis from lactate and pyruvate in rats treated with pivalate for 4 wk were not different from controls. These results suggest that administration of pivalate did not induce the excessive excretion of free carnitine in urine, and secondary carnitine deficiency induced by intake of 20 mmol/L pivalate for 4 wk did not cause severe metabolic changes in rat liver.

3-Hydroxybutyric Acid↗
PubMed1996

Inverse relation of serum Helicobacter pylori antibody titres and extent of intestinal metaplasia.

AIMS: To clarify the relation between the serum titre of anti-Helicobacter pylori (H pylori) antibody and the extent of intestinal metaplasia of the gastric mucosa. METHODS: The serum anti-H pylori IgG titres of 95 asymptomatic individuals (mean age 65 years) undergoing an annual health examination were measured and compared with the extent of intestinal metaplasia (absent, moderate, or extensive), determined by examination of multiple endoscopic mucosal biopsy specimens. Serum pepsinogen I (PGI) levels, as a marker for gastric atrophy, were also measured. RESULTS: The prevalence of seropositivity for H pylori antibody was high (> 80%), regardless of the extent of metaplasia. However, there was a negative association between the extent of metaplasia and the anti-H pylori titre: 75% of the subjects in the group without metaplasia had high (3+) antibody levels, as did 43% with moderate, and 37% with extensive metaplasia (absent v extensive). The inverse relation between the titre and the extent of metaplasia was evident when examined in those with normal PGI (> 30 ng/ml), whereas no such relation was apparent in subjects with low PGI (< or = 30 ng/ml). CONCLUSIONS: The anti-H pylori titre correlates inversely with the extent of intestinal metaplasia, particularly in subjects with less marked gastric atrophy.

Aged↗
PubMed1996

Case report: malignant haemobilia detected in the gallbladder--retrograde cholangiographic findings.

Haemobilia caused by gallbladder cancer is a rare condition and cholangiography rarely detects gallbladder haemorrhage because cancer cells or blood clots obstruct the cystic duct. We describe a patient with haemobilia caused by gallbladder cancer, in whom retrograde cholangiography showed a cast-like filling defect in the common bile duct and, in addition, several string-like defects in the gallbladder. The string-like defects appeared to be streams of clotted blood flowing towards the common bile duct in this case of relatively minor haemorrhage.

Adenocarcinoma↗
PubMed1996

The production of colony-stimulating factors by thyroid carcinoma is associated with marked neutrophilia and eosinophilia.

Cancers producing colony-stimulating factors and associated with marked leukocytosis are relatively rare. We report here a case of a thyroid cancer producing both granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF). A 72-year-old woman had a thyroid carcinoma with significant neutrophilia and eosinophilia without any evidence of infection. The serum concentrations of both G-CSF and GM-CSF were elevated significantly in this patient, which might have induced the leukocytosis. Furthermore, the G-CSF concentrations in thyroid tumor tissue and metastatic lesions in the lung and skin examined at autopsy also were extremely high.

Aged↗
PubMed1996

[A case of rheumatoid arthritis associated with multiple myeloma].

Previous reports have stressed the association between autoimmune disease and lympho-proliferative neoplasm. Here we report a patient in whom multiple myeloma developed about 30 years after the onset of rheumatoid arthritis. A 79 year-old woman with an about 30-year history of rheumatoid arthritis was admitted because of lumbago in December, 1993. Laboratory findings revealed M-proteinemia (IgA 2,380 mg/dl, IgG 728 mg/dl, IgM 51 mg/dl) and serum immunoelectrophoresis showed monoclonal IgA with lambda type light chain. Bone marrow aspirate contained 66.0% plasma cells. Serological tests of rheumatoid factor were positive. X-ray findings revealed radiolucent myelomatous foci in the skull and typical destructive changes of rheumatoid arthritis in multiple joint. From these findings, IgA lambda-type multiple myeloma with rheumatoid arthritis was diagnosed. Although the pathogenesis of the association between rheumatoid arthritis and multiple myeloma is unknown, prolonged antigenic stimulation manifested by rheumatoid arthritis is considered to be a possible pathogenetic factor in the development of multiple myeloma.

Aged↗
PubMed1996

Mitochondrial biosynthesis controls the sensitivity of Chinese hamster cells to hydrogen peroxide.

The mechanism of H2O2-resistance of Hpr-4, a variant of Chinese hamster V79 cells, was investigated. The effect of H2O2 on the mitochondria of the parental and Hpr-4 cells was compared. First, both biochemical and ultrastructural results showed that mitochondria in the parental cells were damaged by exposure to H2O2, while those in Hpr-4 cells recovered from the damage. Second, the H2O2-resistance of Hpr-4 cells was reversibly reduced or recovered by the addition or removal of inhibitors of mitochondrial biosynthesis, respectively. Third, the parental cells were auxotrophic to pyruvate after exposure to H2O2. Fourth, H2O2-sensitivity of the parental cells was also enhanced by the inhibition of mitochondrial biosynthesis. From these results, it was concluded that the mitochondria of Hpr-4 cells apparently had a greater resistance to H2O2 than those of the parental cells and that functional mitochondria were involved in the recovery of Chinese hamster V79 cells from H2O2-induced damage.

Adenosine Triphosphate↗
PubMed1995

Changes of erythrocyte ouabain maximum binding after birth in neonates--in relation to erythrocyte sodium and potassium concentrations.

Erythrocyte ouabain maximum binding (Vmax level) represents the number of molecules of Na-K ATPase on the erythrocyte membrane. Erythrocyte Vmax levels and sodium potassium concentrations were studied in 38 mature and 57 premature infants, including 40 very low birth weight infants, 41 children and 16 adults, in order to clarify the development of erythrocyte Na-K ATPase related to mineral balance and thermogenesis. Vmax levels were the highest (22.9 +/- 8.9 nmol/l cells) for premature infants; correlated negatively with gestational age (r = -0.77, P < 0.01). Vmax levels correlated positively with the ratio of erythrocyte potassium to sodium concentration (IC-K/Na) at < 20 nmol/l cells of Vmax levels (r = 0.72, P < 0.01), but not at > or = 20 nmol/l cells (r = 0.23). Vmax levels in very low birth weight infants, especially < 28 weeks postconception, decreased gradually with postnatal days. Ln(Vmax) levels correlated negatively with postconceptional age (r = -0.75, P < 0.01). Under 28 weeks postconception, Vmax levels were high, but not correlated with IC-K/Na. It is probable that individual Na-K ATPase molecules may be less active, and the large numbers of Na-K ATPase molecules may compensate for the individual lower activity.

Adolescent↗