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Biomedical subjects

I Tsujino

Publications and source records attributed to I Tsujino.

At least 19 recordsLinked to original sources
PubMed2006

Promoter polymorphism in the macrophage migration inhibitory factor gene is associated with obesity.

OBJECTIVE: To explore the association of promoter polymorphisms of macrophage migration inhibitory factor (MIF) gene with obesity. SUBJECTS: In total, 213 nondiabetic Japanese subjects. They were divided into three groups according to World Health Organization definitions: lean (body mass index (BMI) <25 kg/m2), overweight (25 < or = BMI < 30 kg/m2) and obese (BMI> or = 30 kg/m2). METHODS: We examined two polymorphic loci in the MIF gene in the subjects: a single-nucleotide polymorphism at position -173 (G/C) and a CATT-tetranucleotide repeat polymorphism at position -794, which both can affect promoter activity in different cells. RESULTS: We detected four alleles: 5-, 6-, 7- and 8-CATT at position -794. Genotypes without the 5-CATT allele (X/X, X refers to 6-, 7- or 8-CATT alleles) were more common in obese subjects than in lean or overweight groups (P = 0.013). The X-CATT allele was more frequent in obese subjects than in lean or overweight subjects (P = 0.030). In contrast, -173G/C was not associated with obesity. Among the haplotypes of the two promoter polymorphisms, G/5-CATT ((-173G/C)/(-794[CATT](5-8))) was associated with a decreased risk of obesity (P = 0.025) and G/6-CATT with an increased risk of overweight (P=0.028). CONCLUSION: Promoter polymorphism in the MIF gene is linked with obesity.

Adult↗
PubMed2001

Application of hypothermia to autologous stem cell purging.

Autologous stem cell transplantation is used widely after high-dose chemotherapy for treating hematological and other malignancies. Bone marrow harvested for autologous bone marrow transplantation may contain residual malignant cells even when the cancer is judged to be in remission. Attempts to purge marrow of its putative residual malignant cells may delay hemopoietic reconstitution and are of uncertain efficacy. In this report, we demonstrate the possibility of applying hypothermia to autologous stem cell purging. Using clonogenic assay, we compared the surviving fraction of human leukemia (HL60, K562) and human small cell lung cancer (H69) cell lines with that of normal human bone marrow CFU-GM and BFU-E cells after incubation at 4 +/- 0.1 degrees C for 24 and 48 h. Hypothermia decreased the surviving fraction of HL60, H69, and K562 cells. In contrast, the surviving fractions of stem cells were not affected by the temperature shift. The surviving fraction of HL60 cells at 4 degrees C cooling was significantly lower than that at 22 degrees C cooling. These findings suggest that in vitro hypothermia may selectively purge residual malignant cells in stored remission bone marrow and may be applicable before autologous bone marrow transplantation. In addition, the method is very simple and cost effective.

Bone Marrow Purging↗
PubMed2001

Postirradiation hyperthermia selectively potentiates the merocyanine 540-sensitized photoinactivation of small cell lung cancer cells.

Lung cancer has long been considered a disease that might benefit from the dose escalation of radio/chemotherapy afforded by a stem cell transplant. However, the clinical experience with high-dose chemotherapy and autologous bone marrow transplantation in lung cancer has been disappointing, with most trials showing little or no improvement in long-term survival. Unfortunately, lung cancer has a tendency to metastasize to the bone marrow, and lung cancer cells are known to circulate in the peripheral blood. Therefore, there is concern that autologous stem cell grafts from lung cancer patients may reinoculate recipients with live tumor cells. Photochemical purging of stem cell grafts with Merocyanine 540 (MC540) is highly effective against a wide range of leukemia and lymphoma cells and is well tolerated by normal hematopoietic stem and progenitor cells. Most solid tumor cells (including lung cancer cells), however, are only moderately sensitive or refractory to MC540-mediated photodynamic therapy (PDT). We report here that postirradiation hyperthermia (< or = 42 degrees C, 3 h) potentiates the MC540-mediated photoinactivation of both wild-type (H69) and cisplatin-resistant mutant (H69/CDDP) small cell lung cancer cells by several orders of magnitude, while only minimally enhancing the depletion of normal human granulocyte/macrophage progenitor cells. Our data suggest that postirradiation hyperthermia provides a simple and effective means of extending the utility of MC540-PDT to the purging of stem cell grafts contaminated with lung cancer and possibly other solid tumor cells.

Bone Marrow Purging↗
PubMed2000

Non-ionic detergent Tween 80 modulates VP-16 resistance in classical multidrug resistant K562 cells via enhancement of VP-16 influx.

The non-ionic detergent Tween 80, which is used as a solvent for lipophilic drugs such as VP-16 and Taxotere, was found to reverse VP-16 resistance of the P-glycoprotein-associated multidrug resistance phenotype via increasing VP-16 influx. In adriamycin-resistant human chronic myelogenous leukemia K562 cells (K562/ADM), which overexpress mdr1 mRNA, the accumulation of VP-16 was only about 10% that in wild-type K562 cells. Tween 80 enhanced VP-16 accumulation in K562/ADM cells but did not influence VP-16 accumulation in parental K562 cells. VP-16 efflux was rapid and similar in both sensitive and resistant cell lines and was not blocked by Tween 80 or verapamil. Under glucose-free conditions, VP-16 accumulation in K562/ADM cells was only half of that in K562 cells. Tween 80 increased VP-16 accumulation in K562/ADM cells in glucose-free medium. In growth inhibition assay, Tween 80 reversed K562/ADM sensitivity to VP-16 without cell damage. Taken together, Tween 80 reverses VP-16 sensitivity in multidrug-resistant K562 cells by increasing influx, which is considered to be the primary mechanism of VP-16 resistance in K562/ADM cells.

Antineoplastic Agents, Phytogenic↗
PubMed2000

A case of idiopathic constrictive bronchiolitis in a middle-aged male smoker.

When one sees a middle-aged male smoker who presents with progressive exertional dyspnoea and irreversible airflow obstruction, the most likely clinical diagnosis is pulmonary emphysema or chronic obstructive pulmonary disease (COPD). We report a 45-year-old male smoker who was initially suspected to have such a disease but was eventually diagnosed as having idiopathic constrictive bronchiolitis by lung biopsy, clinical history, and laboratory findings. A finding on lung computed tomography of diffuse hyperinflation but few low attenuation areas and relatively well-preserved diffusing capacity of carbon monoxide seems to be the key for suspecting this rare clinical entity. The pathological difference between this bronchiolitis and small airway disease observed in COPD will be also discussed.

Biopsy↗
PubMed2000

Exhaled nitric oxide--is it really a good marker of airway inflammation in bronchial asthma?

BACKGROUND: The concentration of exhaled nitric oxide ([NO]) has been reported to reflect the inflammatory process of airways in patients with bronchial asthma, particularly when they are steroid naive. However, it is not fully understood whether it equally reflects the degree of airway inflammation in patients receiving inhaled corticosteroids, but whose symptoms are not necessarily well controlled. OBJECTIVE: To examine whether the exhaled [NO] really reflects airway inflammation in patients with bronchial asthma, regardless of treatment with inhaled steroids. METHODS: Exhaled [NO] was measured in patients with bronchial asthma (43 steroid treated and 32 steroid naive), chronic obstructive pulmonary disease (COPD) (n = 36), bronchiectasis (n = 10) and in control subjects (n = 26). We examined in each asthmatic group whether the exhaled [NO] correlated with parameters reflecting airway inflammation. RESULTS: Exhaled [NO] was significantly correlated with symptom score, clinical severity, circulating eosinophil count, and the percentage of eosinophils in induced sputum in the steroid-naive asthmatics, but not in the steroid-treated asthmatics, although airway inflammation in this group was not well controlled, as evidenced by clinical symptoms and the higher percentage of eosinophils in induced sputum. Exhaled [NO] from the patients with COPD (6.2 +/- 0. 7 ppb) or bronchiectasis (5.4 +/- 1.3 ppb) was not significantly increased compared with the controls (6.0 +/- 1.0 ppb), and was significantly lower than in the asthmatic patients as a whole (19.0 +/- 2.0 ppb). CONCLUSIONS: Although exhaled [NO] is a useful marker of airway inflammation for differential diagnosis and evaluation of severity in steroid-naive patients with bronchial asthma, it may not be as useful in steroid-treated patients.

Adrenal Cortex Hormones↗
PubMed2000

Genetic variability in the response of normal murine hematopoietic progenitor cells to extracorporeal photochemotherapy.

Normal hematopoietic progenitor cells from 129S6/SvEv mice are substantially less sensitive to Merocyanine 540 (MC540)-mediated photodynamic therapy (PDT) than hematopoietic progenitors from sex- and age-matched C57BL/6 mice. When exposed to a combination of MC540 and light commonly used for the extracorporeal purging of hematopoietic stem cells, granulocyte/macrophage progenitors (CFU-GM) from C57BL/6 mice are depleted 7.9-fold whereas CFU-GM from 129S6/SvEv and (C57BL/6 x 129S6/SvEv) F1 mice are depleted 1.4- and 2-fold, respectively. The same rank order of sensitivity is also found with regard to unipotent progenitors of granulocytes and macrophages and with regard to early and late erythroid progenitors. The resistance of hematopoietic progenitors from 129S6/SvEv mice to MC540-PDT appears to be the result of reduced dye binding rather than the result of high levels of intracellular glutathione. These findings have practical implications for the design of preclinical tests of PDT in animal models. They may also provide a useful tool for future investigations into the molecular determinants of sensitivity to MC540-PDT.

Animals↗
PubMed2000

[Hypoxemia and tissue hypoxia in sleep apnea syndrome].

Hypoxemia is defined as abnormally reduced oxygenation of the blood, whereas tissue hypoxia indicates inadequate oxygen supply against oxygen demand in the integrity of cellular metabolic processes. Thus, the presence of tissue hypoxia may not be predicted by the level of hypoxemia alone. Obstructive sleep apnea syndrome is characterized by periodic apnea/hypopnea, which is often associated with severe hypoxemia. In this chapter, we discussed how tissue hypoxia should be assessed in this syndrome, and also what is the clinical usefulness and/or limitations of such assessment.

Adenosine Triphosphate↗
PubMed1999

Effect of Tween-80 on cell killing by etoposide in human lung adenocarcinoma cells.

PURPOSE: The non-ionic detergent Tween-80, a surface-active agent, has been shown to modulate the cytocidal effect of certain antitumor agents. In the present study, we sought to determine whether or not Tween-80 could enhance the antitumor effect of etoposide (VP16) in human lung cancer cells in vitro. METHODS: Survival fractions were measured by growth inhibiton assays of PC14, H69, KB, and PC14/CDDP (the corresponding cisplatin-resistant subline of PC14) cells. An in vitro clonogenic assay of PC14 and PC14/CDDP cells was undertaken after incubation for 10-12 days in RPMI-1640 medium with 20% fetal calf serum and 1.72% methyl cellulose, plus continuous exposure to VP16 with Tween-80. We also investigated the direct toxicity of Tween-80 to PC14 and PC14/CDDP cells using a clonal assay. The intracellular accumulation of VP16 was further analyzed using [3H]VP16 in PC14, PC14/CDDP, A549, KB and H69 cells, and compared with that of daunorubicin (DNR), a hydrophilic anti-cancer agent, using [3H]DNR in PC14, A549 and KB cells. RESULTS: It was found that PC14/CDDP had collateral sensitivity to VP16 and Tween-80 markedly enhanced the killing effect of VP16 not only of PC14 cells but also of PC14/CDDP cells while exerting little cytotoxic effect. Moreover, Tween-80 increased the intracellular accumulation of VP16 in PC14, PC14/CDDP and A549 cells, and not in KB and H69 cells. Tween-80 did not increase the intracellular DNR levels in PC14, A549 and KB cells. CONCLUSIONS: Tween-80 was shown to potentiate the cytotoxicity of VP16 against several human lung adenocarcinoma cells by increasing the accumulation of VP16 in vitro. Tween-80-mediated sensitization of lung adenocarcinoma cells to VP16 is considered to be related to both the characteristics of the cell membrane in adenocarcinoma cells and the lipotropic properties of VP16. These results suggest that this combination might have the potential to improve the therapeutic index of VP16 in human lung adenocarcinoma.

Adenocarcinoma↗
PubMed1999

Measurement of exhaled nitric oxide concentration using nasal continuous negative pressure.

Contamination of nasal nitric oxide (NO) is a major obstacle when one needs to sample exhaled NO originating only from the lungs. To eliminate nasal NO, we used the nasal continuous negative pressure (nasal CNP) technique which, we verified, caused closure of the vellum. Exhaled gas was sampled from six healthy volunteers into fraction 1 (initially exhaled 200 mL) and fraction 2 (remainder of the gas) under three conditions; while subjects were wearing a noseclip, using nasal CNP at -5, -10 and -20 cm H2O, and under endotracheal intubation. Exhaled NO concentration ([NO]) obtained with nasal CNP was significantly lower, regardless of the pressure applied, than that measured with a noseclip, and was similar to and closely correlated to that obtained under intubation (F1, r = 0.90; F2, r = 0.88; P < 0.05). Real-time recorded [NO] obtained with nasal CNP of -5 cm H2O was again lower than that measured with a noseclip at any expiratory flow rate examined, indicating nasal NO contamination was eliminated irrespective of the flow rate. In conclusion, because a nasal CNP of -5 cm H2O was easily tolerated without any discomfort, this technique is a simple, easy and effective technique to eliminate nasal NO which should be widely applicable for the measurement of exhaled [NO].

Adult↗
PubMed1999

Plasma concentration of adenosine during normoxia and moderate hypoxia in humans.

Adenosine, a purine nucleoside, plays a variety of roles in cardiovascular and ventilatory control, and may be a marker of tissue hypoxia. There is, however, no direct evidence of an increase in plasma or in tissue levels of adenosine during moderate hypoxia in humans. We measured the plasma concentrations of adenosine in an artery and the median cubital vein simultaneously in 12 normal volunteers, and also in the internal jugular vein in seven of them during normoxia and moderate hypoxia (SaO2 = 80%, 20 min) with or without dipyridamole (0.6 mg/kg) pretreatment. Dipyridamole was expected to block reuptake of adenosine by red blood cells and vascular endothelial cells so that the plasma level of adenosine would more likely reflect the tissue level. Blood was sampled with an appropriate stopping solution, and adenosine was measured with a high-pressure liquid chromatographic (HPLC)-fluorometric technique. The plasma concentration of adenosine did not rise either in the artery or in the vein at any phase of hypoxia without the dipyridamole pretreatment. However, when subjects were pretreated with dipyridamole, the plasma concentration of adenosine increased significantly and markedly in a time-dependent manner during hypoxia in the vein, but not in the artery. The adenosine level rose from 20. 7 +/- 2.5 nM (mean +/- SE) during normoxia to 50.7 +/- 10.7 nM at 20 min of hypoxia, and returned to the baseline level in the recovery phase. The plasma concentration of adenosine in the jugular vein did not change during hypoxia either with or without dipyridamole pretreatment. These data provide evidence that in humans, the local production of adenosine increases during moderate hypoxia in forearm tissue, although this is not reflected in plasma unless the subject is pretreated with dipyridamole.

Adenosine↗
PubMed1999

Effects of inhaled bronchodilators on pulmonary hemodynamics at rest and during exercise in patients with COPD.

INTRODUCTION: Inhaled anticholinergic drugs are often recommended for use as a first-line therapy for patients with COPD because they provide similar or more effective bronchodilating actions, as well as fewer side effects. It is not known, however, which class of bronchodilators is more advantageous for pulmonary hemodynamics, particularly during exercise. OBJECTIVES: To compare the effects of oxitropium and fenoterol on pulmonary hemodynamics in patients with COPD at rest and during exercise. PATIENTS: The study participants consisted of 20 consecutive male patients with stable COPD, a mean (+/- SD) age of 68+/-8 years old, and an FEV1/FVC ratio of 47.5+/-10.0%. METHODS: Eleven patients inhaled two puffs of oxitropium, and nine patients inhaled two puffs of fenoterol. Seven members of each group performed incremental exercise using a cycle ergometer. The hemodynamic measurements with right heart catheterization were performed by taking the average of three consecutive respiratory cycles before and after the administration of inhaled bronchodilators at rest and during exercise. RESULTS: At rest, despite a similar improvement of spirometric data with the two drugs, fenoterol, not oxitropium, caused significant increases in heart rate and cardiac output, a decrease in pulmonary vascular resistance, and a deteriorated Pao2. During exercise, however, both drugs similarly attenuated elevations in the mean pulmonary arterial pressure (40+/-12 to 38+/-10 mm Hg by oxitropium, and 41+/-9 to 36+/-9 mm Hg by fenoterol), the mean pulmonary capillary wedge pressure, and the mean right atrial pressure. CONCLUSION: Our findings indicate that both classes of bronchodilators are equally beneficial in the attenuation of right heart afterload during exercise in patients with COPD.

Administration, Inhalation↗
PubMed1999

[Chronic pulmonary thromboembolism diagnosed on the basis of characteristic mosaic patterns on lung computed tomograms].

We report on a 59-year-old woman who presented with characteristic findings on lung computed tomographic (CT) scans and was therefore suspected to have chronic pulmonary thromboembolism. She visited our hospital because of worsening exertional dyspnea over the preceding year, and because she was dissatisfied with an earlier diagnosis made by another institution. Chest roentgenograms disclosed nonhomogeneous hyperlucency in both lungs associated with linear and bundle shadows, dullness of the right costophrenic angle, and dilatation of the descending branch of the right pulmonary artery. The patient experienced moderate hypoxemia even at rest. Pulmonary function tests demonstrated a restrictive ventilatory pattern associated with reduced diffusion capacity. The lung CT scans disclosed a mosaic pattern of attenuation in the lung parenchyma, which probably reflected scattered areas of low perfusion. The unique characteristics of such CT findings drew our attention to chronic pulmonary thromboembolism as a possible diagnosis. We eventually confirmed the diagnosis on the basis of enhanced CT scans, pulmonary perfusion and ventilation scintigrams, and digital subtraction angiography. In our view, chronic pulmonary thromboembolism should be kept in mind as a possible differential diagnosis of the mosaic patterns of attenuation on lung CT scans.

Chronic Disease↗
PubMed1996

Production of nitric oxide (NO) in intrathoracic airways of normal humans.

To gain insight into the source of exhaled nitric oxide (NO) in normal humans, we examined the effects of respiratory pattern on the concentration of NO in exhaled air while subjects were wearing a noseclip and then under endotracheal intubation, using a specially designed gas sampling system to separate exhaled air into two fractions: the initially exhaled 200 ml (Fraction 1; F1), and the remainder (Fraction 2; F2). We also examined the effect of hypoxic gas inhalation (F(I)O2 = 0.1, 3 min) on the concentration of exhaled NO. The concentration of exhaled NO measured with a chemiluminescence NO analyzer was significantly lower with intubation, by 59.2 +/- 10.6% (mean +/- SD) (F1) and 54.4 +/- 8.0% (F2), than without intubation. The concentration of NO in F1 was consistently higher than that in F2 with or without intubation. With breath holding, the concentration of NO increased markedly only in F1. In contrast, prolongation of the expiratory phase slightly but significantly increased the concentration of NO only in F2. Inhalation of hypoxic gas did not cause any significant change in NO concentration in either fraction. These data indicate that in normal humans wearing a noseclip, about 40 to 45% of NO in exhaled air originates from the lungs, particularly from intrathoracic airways. The concentration of exhaled NO collected from subjects wearing a noseclip is not affected by hypoxic gas inhalation.

Adult↗
PubMed1995

[Effects of inhaled oxitropium bromide, an anticholinergic drug, on pulmonary hemodynamics in patients with chronic obstructive pulmonary diseases].

We studied the effects of the inhaled anticholinergic agent oxitropium bromide (Ox) on pulmonary hemodynamics in eleven patients with chronic obstructive pulmonary disease. All the patients underwent right heart catheterization and seven of them underwent an incremental ergometer exercise test while in the supine position. Pulmonary hemodynamics and arterial blood gases were measured at rest and during maximal exercise, before and 30 minutes after inhalation of 2 puffs (200 micrograms) of Ox. Inhalation of Ox did not significantly change pulmonary hemodynamics at rest. The mean pulmonary arterial pressure and the mean pulmonary capillary wedge pressure during exercise decreased significantly (from 40.3 +/- 4.6 to 37.7 +/- 3.9 mmHg, and from 20.4 +/- 3.5 to 17.1 +/- 2.7 mmHg, respectively, mean +/- SE). However, neither cardiac output nor pulmonary vascular resistance changed with inhalation of the drug, at rest or during exercise. We therefore conclude that this commonly used dose of Ox does not directly affect the pulmonary vascular system. The small but significant decreases in pulmonary arterial pressure and pulmonary capillary wedge pressure with Ox may have been indirect effects, caused by bronchodilation.

Administration, Inhalation↗
PubMed1993

[Involvement of the intraabdominal lymph nodes in a case of subacute necrotizing lymphadenitis].

A 40-year-old woman was admitted to our hospital because of fever, polyposia and polyuria in October 1990. The fasting blood sugar level was 471mg/dl and abdominal CT showed enlargement of the liver, kidneys, and intraabdominal lymph nodes. Although severe diabetes mellitus was controlled with insulin, intraabdominal lymph node swelling continued. Lymph node biopsy was performed under laparotomy. Four from intraabdominal lymph nodes, in addition to one from the left axillary lymph nodes. Four showed findings of non specific lymphadenitis, but one specimen obtained from near the right kidney demonstrated focal necrosis and invasion of macrophages and immunoblasts, which were compatible with the features of subacute necrotizing lymphadenitis (SANL). In SANL, lymphadenopathy is usually observed in the cervical region of young female and the involvement of intraabdominal lymph nodes is quite rare. This patient is the second case of SANL involving an intraabdominal lymph node reported in Japan, and it is suggested that SANL should be considered as a causative disorder of intraabdominal lymphadenopathy.

Abdomen↗